Basic Paediatric Management

Transcription

Basic Paediatric Management
Edited by
Daniel K. Ng, MD, M Med Sc
Yuen Yu Lam, FHKAM(Paed)
Lettie C. Leung, FHKAM(Paed)
Sharon W. Cherk, FHKAM(Paed)
Eric Y. Chan, FHKAM(Paed)
Fourth Edition
Published in 2014
Printed in Hong Kong SAR, China
Disclaimer: Considerable care has been taken to see that the information is accurate. Nevertheless
the user is advised to exercise clinical judgment. The authors shall not be responsible for any errors.
Opinions expressed by the contributors do not necessarily reflect that of the Department of
Paediatrics, Kwong Wah Hospital.
I
Preface to Fourth Edition
2014 is a special year for the Department of Paediatrics, Kwong Wah Hospital as it
was founded 85 years ago in the delivery rooms of this hospital. We are privileged to
work with the excellent staff of this department. To make their works simpler, we
publish this White book nearly 10 years ago in 2005. We receive a lot of suggestions
for improvement since the third edition in 2010. The main focus for this issue is to
simplify without losing the essential information that allows the front line doctors
practical application of the information to save the sick children. We hope this White
book does make a difference for that doctor in treating that particular child as every
child counts dearly in our hearts.
Daniel K. Ng
Yuen-yu Lam
Lettie C. Leung
Sharon W. Cherk
Eric Y. Chan
December 2014
DK Ng, dkkng@gmail.com
Department of Paediatrics
Kwong Wah Hospital
Waterloo Road
Hong Kong SAR, China
II
Preface to Third Edition
The major change in this edition sees the appointment of section editors to improve
on each section. I express my deepest gratitude to my colleagues, Dr. YY Lam
(Neonatology, Endocrinology), Dr. PY Chow (Respirology), Dr. KL Kwok
(Cardiology), Dr. S Cherk (Neurology), Dr. WF Lau (Gastroenterology) and Dr. L
Leung (Nephrology) who put in tremendous effort to make this small book useful for
the newcomers to paediatrics. I hope this book will provide that extra little help in the
daily works of paediatricians.
DK Ng
MT Soo
April 2010
Kwong Wah Hospital
Waterloo Road
III
Preface to Second Edition
We are much encouraged by the enthusiastic response to the first edition of the
manual. A lot of comments were received by the editors. The comments are now
incorporated into the second edition together with a number of new chapters that we
believe are important for the basic delivery of paediatric care in this department.
Daniel K. Ng, danielkkng@gmail.com
Ka-li Kwok
Pok-yu Chow
Man-ting Soo
Kwong Wah Hospital
Waterloo Road
Summer 2007
IV
Preface to First Edition
In the last few years we have been seeing an increasing number of medical staff on
short rotation for 3 months in this department. We perceive the need to equip them
with essential information during the first week of duty in the department so as to
allow them to manage common diseases. This book for the common diseases
encountered in the paediatric wards or clinics is intended to meet this need. The book
is set out in short note form to allow easy reading. To keep the size to a minimum,
references are not included in the text. The preparation of this pocket guide has
involved many people of this department. Each topic is prepared by at least one
specialist staff based on the available literature and personal experience as well as
biases. As such, the book should not be followed slavishly and clinical judgement
should always be exercised. Comments are welcome from the readers and should be
directed to the lead editor. We thank the contributors for giving their time, knowledge
and experience to help us prepare this book. We acknowledge Annie Young for her
great help in preparing the manuscripts of each chapter.
Daniel K. Ng, danielkkng@gmail.com
Ka-li Kwok
Pok-yu Chow
Kwong Wah Hospital
Waterloo Road
October 2005
V
List of contributors:
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
陳建平)
陳廣達)
Dr Chan Mei-ching (陳美貞)
Mr Chan Ping-shu Paul (陳平舒)
Dr Chan Yat-tung Eric (陳日東)
Dr Cherk Wan-wah Sharon (卓蘊樺)
Dr Choi Mui-sum Kathy (蔡梅心)
Dr Fung Tsui-hang Sharon (馮翠姮)
Dr Ho Che-shun Jackson (何誌信)
Ms Ho Mang-ying Emily (何孟瑩)
Dr Kwok Ka-li (郭嘉莉)
Dr Lam Yuen-yu (林琬瑜)
Dr Lau Wing-fai (劉永暉)
Dr Leung Chuk-kwan Lettie (梁竹筠)
Ms Leung Nga Shan Phillis (梁雅珊)
Dr Leung Ping Maurice (梁平)
Dr Ng Kwok-keung Daniel (吳國強)
Dr Pau Chee-kit Benjamin (包志傑)
Mr Poon Man Hong Freddie (潘文康)
Dr Soo Man-ting (蘇文庭)
Dr Tse Wing-sze Cindy (謝詠詩)
Dr Wong Chin-pang Jeff (黃展鵬)
Dr Wong Lai Yin (黃麗燕)
Ms Wong Siu-fong (黃少芳)
Dr Yip Yuen Fong Ada (葉遠芳)
Dr Yuen Chi-lap Angus (袁志立)
Dr Yu Pui Tak (余佩德)
Mr Chan Kin Ping (
Dr Chan Kwong-tat (
Pathology
Resident Specialist
Associate Consultant
Deputy Department Manager (Pathology)
Consultant
Deputy Consultant
Private Practice
Honorary Consultant
Pharmacist
Senior Medical Officer
Consultant
Consultant
Senior Medical Technologist
Honorary Consultant
Consultant
Pharmacist
Consultant Microbiologist
Consultant
Ward Manager
Resident Specialist
Resident Trainee
VI
Contents
Preface
List of contributors
Section 1. Neonatology
1. Anaemia in neonates
2. Congenital syphilis
3. Feeding regime for VLBW (<1,500 gm) babies
4. Inborn errors of metabolism (A clinical approach)
YY Lam
MC Chan
YY Lam
MT Soo, J Wong, DK Ng,
F Poon
5. Big baby (Macrosomia)
YY Lam
6. Maternal thyroid disorders
YY Lam, E Chan
7. Neonatal jaundice
B Pau, YY Lam
8. Patent ductus arteriosus in preterm infant
MC Chan, E Chan,
KL Kwok, YY Lam
9. Persistent pulmonary hypertension of neonate (PPHN) MC Chan, E Chan, YY Lam
10. Management of neonates with risk factors of early onset MT Soo
neonatal infection
11. Necrotizing enterocolitis (NEC)
MT Soo, YY Lam, E Chan
12. Neonatal parenteral nutrition
YY Lam, Freddie Poon
13. Transpyloric tube feeding in neonate
E Chan, YY Lam
14. Surfactant therapy
B Pau, YY Lam
15. Hypoxic-ischaemic encephalopathy
B Pau, S Cherk
16. Brain death in the neonate
S Cherk
17. Neonatal hypocalcaemia
MC Chan, L Leung
18. Neonatal bacterial meningitis
MT Soo, C Tse, YY Lam,
F Poon
19. Paramortem studies for inborn error of metabolism
MT Soo, L Leung,
Phyllis Leung, KP Chan
20. Bronchopulmonary dysplasia (BPD)
MT Soo, YY Lam
21. High frequency oscillation
DK Ng
22. Neonatal narcotic withdrawal
YY Lam
23. Normal Range of Neonatal Haematological Values
MT Soo
Section 2. Respiratory system
24. Allergic rhinitis
DK Ng
25. Bacterial tonsillitis
E Chan
26. Common cold (URI)
E Chan, DK Ng
27. Childhood pneumonia
E Chan
28. Chronic cough
E Chan, DK Ng
29. Acute asthma
E Chan, DK Ng
30. Ambulatory care of asthma
E Chan, DK Ng
31. Acute bronchiolitis
E Chan, DK Ng
32. Sleep-disordered breathing (SDB)
DK Ng, E Chan
33. Parapneumonic effusion and empyema
E Chan, DK Ng
34. Pulmonary function tests in children
E Chan, J Wong, DK Ng
VII
II
VI
10
11
13
17
20
28
29
31
39
42
45
48
50
53
54
56
62
64
66
69
72
76
77
81
83
84
85
86
87
89
91
95
99
102
106
109
35. Bronchoscopy
36. Preparation for endoscopy
37. Positive Mantoux test
38. Pulmonary tuberculosis
39. Primary spontaneous pneumothorax in adolescents
40. Modified bronchoalveolar lavage
41. Skin prick test
42. Primary ciliary dyskinesia and non-CF bronchiectasis
43. Nasal lavage
44. Reflux laryngitis
45. Normal values
Section 3. Cardiovascular system
46. Ambulatory management of hypertension
47. Management of severe hypertension
48. Management of Kawasaki disease
49. Treadmill (Exercise stress test)
50. Treatment regime for patients with heart diseases that
mandate prophylactic antibiotics
51. ECG criteria for LVH & RVH & prolonged QT interval
Section 4. Central nervous system
52. Acute management of post-neonatal convulsion
53. Generalized convulsive status epilepticus
(excluding neonates)
54. Febrile convulsion
55. Approach to a child with decreased conscious level
56. EEG
57. Sedation
58. Normal neuro-developmental milestones
59. Childhood epilepsy natural history (counselling)
60. Therapeutic hypothermia in paediatric patients
61. Tics and Tourette’s syndrome in childhood
62. Global developmental delay/ Intellectual Disability
(Mental retardation) – diagnostic approach
63. Anti-convulsants use in children with epilepsy
64. Migraine
65. Neonatal seizure
66. Screening/quick reference : Cerebral Palsy
67. Screening/quick reference : Special note on
management of various types of cerebral palsy
Section 5. Gastrointestinal system
68. Acute gastroenteritis
69. Gastro-oesophageal reflux
VIII
E Chan, DK Ng
E Chan, DK Ng
E Chan, DK Ng
DK Ng
KL Kwok, DK Ng
E Chan, DK Ng
E Chan, A Yip
E Chan, A Yip, DK Ng
A Yip, DK Ng
E Chan
E Chan, DK Ng
L Leung
L Leung
KL Kwok, Maurice Leung
YM Fu, KL Kwok
KL Kwok
115
116
117
118
119
123
124
125
128
130
131
132
133
140
144
150
152
S Cherk
S Cherk
154
157
158
159
MS Choi, S Cherk
S Cherk
161
163
CS Ho
DK Ng, CS Ho
MS Choi
KK Chan, S Cherk
S Cherk
166
167
169
172
174
TH Fung, S Cherk
S Cherk
176
178
TH Fung, S Cherk, CL Yuen
CL Yuen, S Cherk
TH Fung, S Cherk,
CL Yuen
LY Wong, S Cherk
LY Wong, S Cherk
183
186
189
193
197
PT Yu, L Leung, MC Chan
MC Chan
198
199
203
70. 24 hours oesophageal pH monitoring and
pH-impedance monitoring (MII-pH)
71. Helicobacter pylori infection
72. Recurrent abdominal pain
73. Cow’s milk protein allergy
74. Management of Idiopathic constipation in children
Section 6. Renal system
75. Urinary tract infection in children 2-24 months
76. Monosymptomatic nocturnal enuresis
77. Nephrotic syndrome
78. Fluid and electrolytes therapy
79. Systemic lupus erythematosus
80. Postnatal management of antenatal hydronephrosis
81. Systemic corticosteroids therapy
82. Intravenous cyclophosphamide
83. Formulae related to Nephrology
84. Normal Urine values
Section 7. Endocrinology, growth & nutrition
85. Nutritional assessment in children
86. Management of obesity
87. Diabetic ketoacidosis
88. Normal values
Section 8. Miscellaneous
89. Management of eczema
90. Infantile scabies
91. Fever of unknown origin
92. Medical management of phimosis using topical
corticosteroids
93. Dental service for children
94. Antibiogram
95. Megavitamin Cocktail Regimen
96. Immune Thrombocytopenia (ITP)
97. Haemphilia
98. Management of Haemangioma with Propranolol
IX
MC Chan
208
MC Chan,WF Lau
WF Lau
DK Ng
MC Chan, L Leung
210
211
213
214
218
219
224
226
230
233
235
238
241
242
245
247
248
250
251
254
256
257
258
259
260
L Leung
PH Chan, L Leung
L Leung
B Pau, L Leung, DK Ng
L Leung, A Yuen
PH Chan, L Leung
E Ho, YY Lam, L Leung
L Leung
L Leung
L Leung
YY Lam
YY Lam
YY Lam
YY Lam
DK Ng
KT Chan, F Poon, DK Ng
DK Ng, C Tse
MT Soo, DK Ng
S Cherk
C Tse
F Poon
KL Kwok, TH Fung,
MT Soo, E Chan
TH Fung, MT Soo, E Chan
KT Chan, L Leung
262
263
265
266
269
274
Section 1: Neonatology
10
Chapter 1 - Anaemia in neonates
YY Lam
Definition:
- Hb value less than 12g/dL in the first week or less than 10g/dL later in infancy
- Premature infants have slightly lower Hb, higher MCV and reticulocyte counts compared with
term infants
Causes:
Physiological anaemia
- Term: Hb unchanged till 3rd week of life trough 11g/dL at 8-12 weeks
- Preterm: more profound drop in Hb reaching 7-9g/dL at 4- 8 weeks
- Mechanisms: decreased RBC mass / iatrogenic blood loss / shorter life span of RBC /
erythropoietin deficiency / rapid body growth
Haemorrhagic anaemia
- Antenatal: APH (placenta praevia / anomalies of umbilical cord / placental tissue), twin-twin
transfusion
- Postnatal: fetal-placental haemorrhage, obstetrical trauma
- Neonatal: enclosed haemorrhage e.g. cephalhaematoma / ICH / subaponeurotic haemorrhage,
coagulation defect: sepsis / congenital lack of coagulation factor / haemorrhagic disease of
newborn (Vit K deficiency) / thrombocytopenia
Haemolytic anaemia
- to be considered if jaundice occurs in the first 24 hours of life
- immune / non-immune causes
Congenital erythrocyte defect
- G6PD deficiency / PK deficiency / thalassaemia / red cell membrane defects
Nutritional deficiency
- Iron deficiency
Systemic diseases
- Infection / metabolic diseases / congenital condition (Diamond-Blackfan syndrome)
Investigations:
Depends on the suspected causes
- CBC smear and D/C, reticulocyte count
- Direct Coombs test
- Kleihauer test
- Clotting profile
- Sepsis work-up / TORCH studies as indicated
11
Management:
- Treat the underlying cause
- Minimise blood taking (in ELBW, document amount of blood loss due to blood taking)
- Transfusion dose: 10-20ml/kg of packed cells over 4 hours
- Request CMV -ve and leucocyte depleted RBC minipack cells on the request form for preterm
babies less than 1.5kg
- For babies with PDA, transfusion of packed cells preferably ≤ 10ml/kg over at least 4 hours, if
repeated transfusion is indicated, preferably at least 24-48 hours apart.
Guidelines for transfusion in preterm neonates
1) Breathing spontaneously
- in room-air: T/F if Hb < 7g/dL
- with oxygen: T/F if Hb < 8g/dL
2) CPAP
- < 28 days: T/F if Hb < 10g/dL
- ≥ 28 days: T/F if Hb < 8g/dL
3) IPPV
- < 28 days: Hb < 11g/dL if FiO2 < 30%
Hb < 12g/dL if FiO2 ≥ 30%
- ≥ 28 days: T/F if Hb < 10g/dL
Guidelines for transfusion in term neonates
Treat underlying causes
Stable neonate with Hb 8-10g/dL with no evidence of acute bleeding observe
(Likely to be due to chronic / acute-on-chronic fetal-maternal or twin-twin transfusion)
Transfusion in patients with symptomatic anaemia or underlying diseases
Symptomatic anaemia, e.g. unexplained breathing disorders / unstable vitals / poor growth /
diminished activity:
- Maintain Hg > 8 g/dL
Underlying disease:
- Maintain Hct > 13 g/dL for severe cardiopulmonary disease
- Maintain Hct > 10 g/dL for moderate cardiopulmonary disease
(Severity depends on ventilator settings / FiO2)
- Maintain Hct > 10 g/dL for major surgery
- In case of severe bleeding with evidence of heart failure single volume ET
12
Chapter 2 - Congenital syphilis
MC Chan
Background:
- Treponema pallidum: thin, motile spirochaete and extremely fastidious
- Majority of infections occur by transplacental passage of Treponema pallidum
- Infection by contact with an active genital lesion at time of delivery possible
- Risk of transmission in untreated primary syphilis is 70-100%, 40% for early latent and 10% for
late latent disease
- High risk mother: low socioeconomic levels, HIV mother, poor antenatal care, pregnant women
with primary syphilis or illness of unknown duration, higher VDRL titre (>1:16) at treatment or
at delivery, < 4 weeks between treatment and delivery, women treated with non-penicillin
antibiotics, women received no or inadequate treatment (dose unknown, inadequate, or
undocumented)
Clinical presentation:
- Over 50% infected infants are asymptomatic at time of diagnosis. If not treated, symptoms
develop within first 5 weeks of age.
- Subtle and non-specific signs in symptomatic infants
Early manifestation (< 2 years of age)
Late manifestation (> 2 years of age)
Skeletal: osteochondritis, periostitis, SGA
Skeletal: frontal bossing, short maxilla,
saddle nose, scaphoid scapula, painless
arthritis of the knees
CNS: aseptic meningitis
CNS : sensorineural deafness, mental delay,
convulsion, paralysis
Mucocutaneous: maculopapular rash,
palmar / plantar bullae, mucous patches,
rhinitis, petechiae, jaundice
Mucocutaneous: rhagades, palatal
perforation; Hutchinson teeth, mulberry
molars
Ocular: uveitis, chorioretinitis, glaucoma
Ocular: interstitial keratitis, glaucoma,
corneal scarring, optic atrophy
Renal: nephritis, oedema, ascites
GI: hepatosplenomegaly, enteritis,
pancreatitis
Generalised nontender lymphadenopathy
13
Classification of Congenital Syphilis:
(Adapted from Center for Disease Control and Prevention 2014)
1 Confirmed case
T. pallidum is identified by dark microscopy, fluorescent antibody or specific stains in specimens
from lesions, placenta, umbilical cord, or autopsy material
2 Probable case
1. Mother with untreated or inadequately treated syphilis at delivery, regardless of signs or
symptoms in the infant
OR
2. Infant with a reactive treponemal test and any one of the following
a. Evidence of congenital syphilis on physical examination
b. Evidence of congenital syphilis on long bone x-ray
c. Reactive CSF VDRL
d. Elevated CSF cell count or protein (without other causes)
Inadequate treatment is defined by:
- non-penicillin therapy or any therapy (including penicillin) given less than 1month before
delivery
- undocumented therapy
- sub-therapeutic or undocumented treatment response (<4 fold decline in non-treponemal
antibody titers after treatment)
- inappropriate dose for maternal stage of disease
- maternal non-treponemal antibody titers suggest reinfection or relapse (i.e. 4 fold increase)
Investigation:
Full evaluation for congenital syphilis if mother’s RPR(or VDRL) and FTA-ABS are positive plus
one or more of the following conditions:
- Syphilis untreated or inadequately treated
- Syphilis during pregnancy treated with non-penicillin regime (e.g. erythromycin)
- Syphilis treated less than 1 month before delivery
- Syphilis during pregnancy treated with penicillin regimen but the expected decrease in RPR (or
VDRL) after therapy did not occur
- Syphilis treated before pregnancy, but with insufficient serological follow-up to assess the
response to treatment and current status
N.B. Serum RPR is tested at Kwong Wah Hospital and VDRL is tested at social hygiene clinic, they
are different non-treponemal tests and titer can be different for same individual
Full investigation of any suspected newborn infants for congenital infection:
1. CBP, D/C, R/LFT, RPR, FTA-ABS, blood culture
2. Cerebrospinal fluid: VDRL, R/M, dark field microscopy, biochemistry and culture
3. Babygram
4. Cranial ultrasound, ophthalmological examination or auditory brain stem evoked potential as
clinically indicated in proven or highly probable congenital syphilis
14
Treatment: (refer to the flowchart)
Treatment 1: Penicillin G 50,000 unit/kg/dose (given every 12 hours in the first week of age and
then every 8 hours in the second week of age onwards) intravenously for 10 days.
(If therapy is missed more than or equal to 24 hours, the entire course must be restarted.)
Treatment 2: Benzathine penicillin G 50, 000 unit/kg, IMI, single dose.
Isolation procedures: contact precaution for all infants with suspected or proven congenital
syphilis until therapy has been given for 24 hours.
Follow up:
- 3, 6 and 12 months of age for those treated as congenital syphilis
- Repeat RPR at 3, 6 and 12 months until it becomes non-reactive or shows a 4 fold decrease
- RPR should decline by 3 months of age and should be non-reactive by 6 months if baby is not
infected or adequately treated
- If RPR is stable or increases after age 6–12 months, the child should be evaluated (including
CSF examination) and treated with a 10-day course of parenteral penicillin G.
- Congenital neurosyphilis with initially positive CSF VDRL / abnormal CSF should undergo
clinical evaluation and repeat CSF examinations at 6 month intervals until normal
Retreatment should be considered when
- Clinical signs or symptoms of syphilis persist or recur
- Sustained 4 fold increase in the titer of RPR
- Initially high RPR fails to decrease 4 fold within a year
- A reactive CSF VDRL at 6 months
- If CSF WBC still abnormal at 2 years or not decreasing
- If 24 or more hours of therapy is missed, the entire course must be restarted.
Basic evaluation for asymptomatic infants born to mothers who were adequately treated
1. CBP, D/C, R/LFT, RPR, FTA-ABS
2. Further evaluation is warranted for any abnormal result
15
Algorithm:
Reactive maternal RPR/ VDRL
Nonreactive maternal treponemal
test (i.e.FTA-ABs)
False-positive reaction:
no further evaluation
Reactive maternal treponemal
test (i.e. AFB-ABs)
Maternal treatment:
-None, OR
-Undocumented, OR
- ≤ 4wk before delivery, OR
-Nonpenicillin drug, OR
-Maternal evidence of
reinfection/ relapse (≥4 fold
increase in maternal titers)^
Maternal penicillin
treatment during pregnancy
AND >4wks before
delivery, AND no evidence
of maternal reinfection or
relapse
Adequate maternal
treatment before pregnancy
with stable low titer
(i.e. RPR 1:4 or less or VRDL titer
1:2 or less beyond 1 year after
successful treatment),
AND infant exam normal
Full evaluate
Infant physical
exam normal;
evaluation normal;
infant RPR ≤ 4 fold
the maternal RPR
titer^
Infant physical
exam abnormal; OR
evaluation abnormal
or incomplete; OR
infant RPR at least 4
fold greater than
maternal RPR titer^
Infant RPR ≤ 4 fold
the maternal RPR No evaluation
No treatment
titer^
or basic
evaluation if
in doubt
Infant physical
Infant physical
exam normal
exam abnormal
Infant RPR 4 fold
or greater than
maternal RPR titer^
infant
exam
abnormal
full
evaluation
and
treatment
Basic evaluation;
Treatment 2
Treatment 1
Treatment 1
Full evaluation
and treatment 1
^ e.g a titer of 1:64 is fourfold greater than a titer of 1:16, and a titer of 1:4 is fourfold lower than a titer of 1:16
(Ref : CDC 2014, Red Book 2012, Up-to-Date)
16
Chapter 3 - Feeding regime for Premature and VLBW (<1.5kg) babies
YY Lam
Principles:
Immature gut has
- Decreased cell mass and enzyme activity
- Disordered/ immature motility
- Increased permeability and susceptibility to NEC
- Early enteral feeding (trophic feeding) stimulates maturation of gut and improves motility,
decreases TPN-related cholestasis, increases gut hormones, decreases risk of catheter-related
sepsis and does not increase NEC
Importance of human milk in enteral feeding
- Improves gut maturation, immunity and normal microbial formation
- Protects against NEC (dose dependent effect)
Initiation of trophic feeding (Minimal Enteral Nutrition) in VLBW
- Start trophic feeding as early as D1 for stable VLBW > 1 kg with no abnormal abdominal signs
and symptoms
- ELBW babies are usually more unstable: keep NPO during the first few days; trophic feeding
can be considered when haemodynamically stable with no inotropic drugs and preferably no
UAC in situ
- Human milk is preferred; if not available, use premature formula (C20)
- Trophic feeding duration and volume
●
< 20ml/kg/day during the period of trophic feeding, not counted in the daily fluid
●
For ELBW: (<1kg) start with around 10ml/kg/day, can increase gradually to < 20ml/kg/day,
for a total of 5-10 days
●
For > 1 kg and <1.5kg babies: start with 10-20ml/kg/day for a duration of 3-7 days; start
with the lower volume if baby is close to 1 kg
Increment of feeding volume after trophic feeding
- 10-20ml/kg/day increment, starting with the lower range for the ELBW; the volume will be
counted in the daily fluid
- If enteral feeding is tolerated well at 100-120ml/kg/day, off TPN/PPN
- Add Human Milk Fortifier (HMF) to breast milk if feeding volume is around 100ml/kg/day;
increase to 22 Kcal/oz first; keep volume of feeding same after adding HMF for at least 1 day
before advancing volume; increase to 24 Kcal/oz if feeding tolerance satisfactory on 22 Kcal/oz
for 2-3 days
- Full feeding is achieved at around 150ml/kg/day; higher volume or > 24 Kcal/oz formula can be
considered in individual case after discussion with neonatologist in charge
Monitoring during feeding in VLBW
- gastric residue: amount and character
- abdominal girth at baseline, then consider measuring regularly 2-4x/day before feed
- any abnormal stool
Feeding for premature babies ≥1.5kg
- for babies <32 weeks and ≥ 1.5 kg follow same regime for <1.5kg
- for babies ≥ 32 weeks and < 34 weeks, start with 20ml/kg/day and increase feeding by
20-30ml/day
17
Residual in gastric aspirate
Gastric residue is commonly found in VLBW especially during initial few days of trophic feeding.
It may persist longer in ELBW and may appear green initially. < 2ml aspirate can be regarded as
physiological if no accompanying abnormal physical findings (see below). Residue usually
decreases with increase in feeding, but is seldom > 50% of total enteric feeding if > 50ml/kg/day
milk is given, and is usually < 25% of total feeding volume. Assessment and monitoring of the
trend is more important than the amount of aspirate.
Abnormal physical signs or clinical findings that warrant assessment before continuation of
feeding
- Abnormal gastric aspirate: bile-stained or bloody
- Acute increase in the amount of aspirate in a baby with previously minimal aspirate
- Abdominal distension
- Abdominal signs: tenderness, erythema or ileus
- Bloody stool
Withhold feeding and inform doctor if abnormal abdominal signs or residues:
Doctors need to be informed for assessing the baby before deciding to resume feeding, augment the
feeding regime or proceed to further investigations and management.
Supplements of folic acid, vitamins and Ferrum with full enteral feeding
Enteral intake recommendations
for preterm infants
AAP-CON
Nutrients
(Reasonable nutrient
(unit)
intake by Tsang)*
Folate : 40 (25-50)
mcg/kg/day
Vit D : 400 IU/day
Folate
(mcg)
Vit D (IU)
Nutritional contents in milk#
Mature
Mature HM + 24 Kcal/oz
human
4 pkts
premature
milk(HM) (Enfamil)
formula
HMF
(Enfamil)
unit/dL
unit/dL
unit/dL
4.8
30
32
Neosure
20 Kcal/oz
Enfamil
Lipil
unit/dL
19
unit/dL
10.8
2
52
41
150
195
Iron : 2-3 mg/kg/day
Iron (mg)
0.03
1.44
1.5
1.3
1.22
Vit E : >1.3 (6-12)
Vit E (IU) 0.4
5
5.2
2.7
1.35
IU/kg/day
# Human milk composition varies; ingredients in formula serve as a reference: composition changes with
different brands and needs to be rechecked when accurate calculation is needed
* AAP-CON: AAP Committee on Nutrition, Pediatric Nutrition Handbook 2004
Tsang RC: Nutritional Needs of the Premature Infants 2005
Nutritional supplement when full enteral feeding:
Folic acid: 0.05mg PO daily until 40 weeks gestation if not on enriched formula
Vit D: supply in multivitamin to provide at least 400 units if demand not met in formula, especially
in purely breast fed babies
Ferrum: until 6 months of age if formula feeding, or 12 months of age if breast feeding, to provide
adequate supplement to prevent iron deficiency anaemia; hemolysis can occur if iron is
supplemented without adequate vit E, thus give vit E at least 5 IU for preterm on exclusive breast
milk feeding with Fe supplement
- < 1kg (birth weight): 4mg/kg/day elemental iron
- 1-1.5kg (birth weight): 3mg/kg/day elemental iron
- 1.5-2.5kg (birth weight): 2mg/kg/day elemental iron
- Total supplemented dose depends on the iron supply from milk feeding
- Maximal absolute dose 15mg daily
18
Content in Multivitamin drop (1 ml) :
Vit A
1500 IU
Vit B1
Vit B2 0.6mg
Vit B6
Vit B12 2mcg
Vit C
Vit D
400 IU
Vit E
Niacin 8mg
0.5mg
0.4mg
35mg
5 IU
19
Chapter 4 - Inborn errors of metabolism (A clinical approach)
MT Soo, J Wong, DK Ng, F Poon
Introduction:
Inborn errors of metabolism (IEM) are rare disorders in Hong Kong. The incidence was estimated
to be around 1 per 4,000 live births in 2013. In the US, the incidence is estimated to be between 1
in 1,400 and 1 in 5,000 live births. Early diagnosis and treatment of IEM can be life-saving and
may sometimes result in full recovery. A high index of suspicion is often required in making the
diagnosis.
Clinical presentation:
IEM can present in various ways, depending on the types of defects, the underlying
pathophysiology, age of patient and triggering factors. Based on the pathophysiology, it can be
divided into 3 main groups:
a) Disorders involving complex molecules:
- abnormality of synthesis or degradation of large, complex molecules
- present at any age, often after enough time for significant accumulation of substances
- permanent progressive organomegaly, bone deformities, organ dysfunction
- examples: mucopolysaccharidoses; glycogen storage diseases; gangliosidoses;
peroxisomal disorders
b) Disorders resulting from intoxication:
- damage due to acute or progressive intoxication from accumulation of small molecules
such as substrates of deficient enzyme, precursors or metabolites arising from minor
pathways
- symptom-free interval after birth
- present as lethargy, irritability, ataxia, slurred speech, seizures, coma
- examples: aminoacidopathies; organic acidaemias; urea cycle defects
c) Disorders involving energy metabolism:
- deficient production or utilization of energy
- symptoms may present right after birth (or even antenatally)
- present as failure to thrive, hypoglycaemia, hyperlacticacidaemia, hypotonia, myopathy,
cardiomyopathy, ALTE, liver failure
- examples: mitochondrial disorders; fatty acid oxidation defects; glycogen storage disorders
Clinical Evaluation:
- History: Chronicity, age of onset, periodicity, triggers, diet, any similar family history, past
history of unexplained deaths or neurologic problems, consanguinity etc
- Physical examination: including urine colour and odour
●
Dysmorphic features, organomegaly and neurological abnormalities
20
Basic workup:
- Complete blood count with differential count
- Urinalysis
- Blood gas (Anion gap: Na+ + HCO3- - Cl-, normal range: 12 ± 4)
- Serum electrolytes
- Blood glucose
- Plasma ammonia (send fresh in ice, contact lab before hand)
- Urine reducing substances
- Urine ketones if acidosis or hypoglycaemia present
- Plasma and urine amino acids, quantitative
- Urine organic acids
- Plasma lactate / pyruvate
- Dried blood spot test (contact lab for kit and attend to the collection method)
Interpretation:
Correct interpretation of the results can help to narrow down the list of differential diagnoses.
a. Hyperammonaemia: see Figure 1
Measuring serum ammonia level is always the first step in evaluating patients with IEM
especially those presenting with coma. By understanding the differential diagnoses,
appropriate measures can help to minimize the toxic effects due to accumulation of ammonia.
b. Metabolic acidosis: see Figure 2
c. Lactic acidosis: see Figure 2
d. Hypoglycaemia: see Figure 3
Management:
General measures:
- Stabilize the patient with appropriate supportive care
●
Monitor mental status (ICP)
●
Provide adequate calories to prevent catabolism and maintain glucose level above
5.5mmol/L
- Removal of toxic compounds or targeted treatment
●
Maintain good renal output
●
Avoid known precipitant food if any (e.g. galactose, fructose)
●
Avoid protein for no more than 1-2 days
●
Limit fat intake if fatty acid oxidation is suspected
●
Give carnitine empirically if suggestive clinical scenario
●
Consider haemodialysis (if hyperammonaemia or renal failure) or exchange transfusion
●
Consider cocktails of cofactors and antioxidants (see below)
●
Use specific scavengers when appropriate (e.g. for hyperammonaemia, see below)
Specific measures:
Specific measures depend on the likely diagnosis / group of diagnoses.
21
Megavitamin Cocktail Regimen:
Megavitamin cocktail therapy should be considered in patients who present with an acute severe
illness of unknown aetiology in which IEM is highly suspected. This may be in the form of
emergencies such as encephalopathy, seizures, liver failure, metabolic acidosis, shock or others.
Therapy should be directed to reduce the formation or enhance the secretion of toxic metabolites,
provide adequate calories and prevent catabolism, and to provide co-factors empirically if a specific
diagnosis is not established. Appropriate immediate treatment improves survival and reduces the
chance of neurodevelopmental sequelae.
Daily dose
Route
Availability in
KWH
Thiamine
50mg
IV/PO
Formulary drug
mitochondrial disorders, MSUD, PDH deficiency,
complex I deficiency
Riboflavin
100mg 300mg
PO
Formulary drug
glutaric aciduria type I/II, mild variants of ETF,
ETF-DH, complex I deficiency (congenital lactic
acidosis)
Biotin
10mg
PO
Non-formulary drug
multiple carboxylase deficiency (biotinidase,
holocarboxylase synthetase)
Pyridoxine
100mg
IV
Formulary drug
pyridoxine dependency with seizures,
homocystinuria, primary hyperoxaluria type I
Vitamin B12
1mg
IM/SC/PO
Formulary drug
methylmalonic academia, homocystinuria
Ascorbic acid
100mg/kg
PO
Formulary drug
tyrosinaemia III, transient tyrosinaemia of the
newborn, glutathione synthase deficiency,
abetalipoproteinaemia
25mg/kg Q6H
PO
Formulary drug
organic acidaemia, carnitine deficiency
Co-enzyme
Q10
5mg/kg
PO
Formulary drug
respiratory chain defects
Pyridoxal
phosphate
20mg/kg
PO
Non-formulary drug
PO
hereditary orotic aciduria, methionine synthase
deficiency, cerebral folate transporter deficiency,
Non-formulary drug
hereditary folate malabsorption, Kearns-Sayre
syndrome
Carnitine
Folinic acid
20mg
Examples of related conditions
PNPO deficiency: pyridoxal phosphate responsive
seizures
For non-formulary drugs, please contact pharmacist on duty and fill in a “non-formulary drug request form”;
stock kept in pharmacy for emergency.
22
Treatment of acute hyperammonaemia:
Ammonul (10% sodium phenylacetate and 10% sodium benzoate) intravenous injection is available
for the treatment of acute hyperammonaemia, and must be diluted by 1/10 with 10% dextrose to at
least 25ml/kg *(Dilution is not fixed for >20kg patient) before infusion via central venous catheter.
Arginine HCl injection may be mixed in the same container as Ammonul, and is an essential
component of therapy for patients with suspected urea cycle defects e.g. carbamyl phosphate
synthetase (CPS), ornithine transcarbamylase (OTC), argininosuccinate synthetase (ASS) or
argininosuccinate lyase (ASL) deficiency. Loading dose infused over 90-120 minutes should be
followed by maintenance infusion over 24 hours. Monitoring of electrolytes is needed because of
theoretical risks of hypokalaemia, hypernatraemia and fluid overload.
Start extracorporeal detoxification if ammonia > 500 µmol/L - use haemodiafiltration if available;
otherwise use haemofiltration or haemodialysis. Contact renal centre if the above treatment is
needed. Peritoneal dialysis is not efficient. Exchange transfusion may increase protein and
ammonia load, and is considered ineffective.
Patients 0 to 20 kg:
Patient Population
Components of Infusion Solution
AMMONUL must be diluted with
sterile 10% Dextrose Injection at ≥
25 mL/Kg before administration.
Arginine HCl
AMMONUL
Injection, 10%
Dosage Provided
Sodium
Phenylacetate
Sodium
Benzoate
Arginine
HCl
250 mg/kg
250 mg/kg
200 mg/kg
250 mg/kg
250 mg/kg
600 mg/kg
5.5 g/m2
5.5 g/m2
200 mg/kg
5.5 g/m2
5.5 g/m2
600 mg/kg
CPS and OTC Deficiency
Dose
Loading: over 90 to 120 minutes
Maintenance: over 24 hours
2.5mL/kg
2 mL/kg
ASS and ASL Deficiency
Dose
2.5 mL/kg
6 mL/kg
Patients > 20 kg:
CPS and OTC Deficiency
Dose
55 mL/m2
2 mL/kg
ASS and ASL Deficiency
Dose
55 mL/m2
Contact on duty pharmacist if the above drugs are needed.
6 mL/kg
(Ref : Ammonul (R) drug insert)
* For Ammonul infusion:
e.g 1) for 20kg child with dose 2.5ml/kg; drug dilute to 10x with D10, final volume 25 ml/kg for infusion.
2) for > 20kg child with BSA 1m2, 55ml/m2, if child weighs 27.5kg, drug given 2ml/kg; dilute 12.5x to
final volume of 25 ml/kg, i.e. add at least 632.5ml D10.
23
(Ref : Image from internet - http://drmhanna.com/urea-cycle-defects/)
24
Figure 1
Hyperammonaemia (ammonia > 170 µmol/L)
Symptoms in first 24hrs of life
Preterm
Transient
hyperammonaemia
of newborn
Symptoms after first 24hrs of life
Full Term
IEM
Acidosis
No acidosis
Organic
acidaemias
↑ citrulline (>1,000 µmol/L)
Citrullinaemia
Urea cycle
disorders
Normal citrulline (50-100 µmol/L)
↑ Arginine
↓ citrulline (undetectable)
↓ Arginine
Argininaemia
(ARG deficiency)
+ve urinary ASA
-ve urinary ASA
Urinary Orotic Acid
+ve
Argininosuccinic aciduria
(ASL deficiency)
Plasma Ornithine
Increased
HHH
Normal
Ornithine transcarbamoylase
(OTC) deficiency
Decreased
LPI
Key: ASA = Argininosuccinic acid
LPI = Lysinuric protein intolerance (reabsorption defect of the dibasic amino acids: lysine,
arginine, and ornithine, leading to interruption of urea cycle)
HHH = hyperammonaemia-hyperornithinaemia-homocitrullinaemia syndrome (disorder of
ornithine transport between cytoplasm and mitochondrion)
25
Carbamyl
phosphate
synthetase
(CPS)
deficiency
-ve
Figure 2
Metabolic acidosis (pH < 7.3, HCO3 < 15, BE more –ve than -6)
Normal Anion Gap
e.g. 12 ± 4
Increased Anion Gap
e.g. > 16
Abnormal loss of bicarbonate
e.g. diarrhoea, renal
tubular acidosis
Accumulation of fixed acid
↑ β-hydroxybutyrate
↑ acetoacetate
↑ lactate
Lactic acidosis
Ketoacidosis
abnormal a.a.
abnormal o.a.
Organic acidaemias
Rule out acquired causes of ↑lactate e.g. hypoxia, shock,
congestive heart failure, liver failure, intoxication e.g. ethanol
Primary lactic acidosis
normal or ↓pyruvate
↑ lactate/ pyruvate ratio (i.e. >25)
↑ pyruvate
normal (15-20) or ↓ lactate/pyruvate ratio (e.g. <10)
- Respiratory chain defects
- Pyruvate carboxylase deficiency type B
Hypoglycaemia
Gluconeogenesis defects e.g.
- Glycogen storage disease type 1
- Fructose 1,6-diphosphatase deficiency
- Phosphenolpyruvate carboxykinase
deficiency
Hyperglycaemia
Normoglycaemia
Diabetes mellitus
- Pyruvate dehydrogenase deficiency
- Pyruvate carboxylase deficiency type A
26
Figure 3
Hypoglycaemia
Rule out severe systemic illness, sepsis, SGA
+ve urinary reducing substance
-ve urinary reducing substance
- Galactosaemia
- Tyrosinaemia
- Hereditary fructose intolerance
check a.a. and o.a.
Low urinary ketones
Low free fatty acid
- Organic acidaemias
- Amino acidaemias
High urinary ketones
↑ free fatty acid
Hepatomegaly?
Hyperinsulinism
Fatty acid oxidation defects
Present
↑ lactate
- Glycogen storage disease type 1
- Fructose 1,6-diphosphatase deficiency
Absent
normal lactate
β
Consider endocrinopathies
e.g. hypopituitarism, hypocortisolism
Consider -ketothiolase
deficiency
Ref : Figures 1-3 reproduced with minor modification from Basic Paediatric Management 3rd
edition, Chapter 4
27
Chapter 5 - Big baby (Macrosomia)
YY Lam
Definition:
> 4,000gm baby or BW > 90th percentile
Problems:
- Increased risk of shoulder dystocia, birth trauma
- Associated with maternal diabetes
- Associated with syndromal disorders (e.g. Beckwith-Wiedemann syndrome, Sotos syndrome)
Management:
P/E:
1. To look for syndromal disorder
1.1 Beckwith-Wiedemann syndrome: macroglossia, linear fissures in lobule of external ear,
indentations on posterior rim of helix, large kidneys, hepatomegaly, omphalocoele,
hemihypertrophy
1.2 Sotos syndrome: large hands and feet, macrocephaly, prominent forehead, downslanting
palpebral fissures, hypertelorism, prognathism and coarse-looking facies
2.
Infant of diabetic mothers
RDS, polycythaemia, hypocalcaemia, hypoglycaemia
Look for congenital anomalies (6-9%)
CNS: anencephaly, meningocoele, holoprosencephaly
Cardiac: especially hypertrophic cardiomyopathy, conotruncal malformation
Skeletal: vertebral and caudal regression syndrome (sacral agenesis)
Renal: renal vein thrombosis
GI: small left colon syndrome
3.
Look for evidence of birth trauma (fracture clavicle, Erb’s palsy)
Investigation:
Monitor for polycythemia, hypocalcaemia or hypoglycaemia
- Monitor H’stix Q1H x 3 or till stable, then Q4H for 1 day
- Manage hypoglycaemia accordingly
- Check CBP, calcium
- X-Ray clavicle (if indicated)
28
Chapter 6 - Maternal thyroid disorders
YY Lam, E Chan
Background:
- Graves’ disease complicates 1/1,000 pregnancies
- PTU, iodine and TSI can cross placenta
- Baby may develop goitre, hyperthyroidism or hypothyroidism
- PTU may suppress thyroid function in the first few days of life
- TSI has a half life of 12 days; delayed hyperthyroidism may occur in 2nd week
- Maternal TSI level (if available) can predict occurrence of neonatal hyperthyroidism ( > 5x
upper limit suggests high risk of neonatal thyrotoxicosis)
- Other risk factors for neonatal thyrotoxicosis include: +ve family history of TSH receptor
mutation, mother on anti-thyroid drug or clinically thyrotoxic in 3rd trimester, evidence of foetal
thyrotoxicosis.
Protocol:
- All babies born with maternal thyrotoxicosis should be assessed for neonatal thyroid disease by
paediatrician and monitored for related signs and symptoms.
- P/E to look for signs and symptoms of hyperthyroidism, hypothyroidism, goitre and upper
airway obstruction
- Monitor in ward for 24 to 48 hours for any signs and symptoms of hyper- or hypothyroidism
(irritability, feeding, heart rate, BP)
- Trace cord blood TSH result (screening lab, fax no 27763795), babies with neonatal
thyrotoxicosis may have a suppressed TSH.
- If result is normal, patient can be discharged home. Babies with abnormal TSH/FT4
(suppressed or elevated) need to be reassessed for fitness for discharge.
- If result is not available, baby can be discharged if clinically fit after 24 to 48 hours.
- Advise mother / caretaker about signs and symptoms of thyrotoxicosis or hypothyroidism
before discharge, so early medical advice can be sought if needed. (Fact sheet available in
ward)
- 1st follow up between 1-2 weeks of age and repeat TSH and FT4 (KWH lab). If patient has been
recalled for TFT from Clinical Genetic Service, trace the result instead of repeating blood test
unless baby has signs or symptoms suggestive of abnormal thyroid function.
- 2nd follow up at around 2 to 4 weeks with TSH and FT4 repeated
- No further follow up if baby is well and results are normal. If abnormal result is found, discuss
with endocrine team colleagues for further management.
- Ward FU arrangement
Thyroid FU arranged at 9:00am
BW measured by HCA, check other parameters (e.g. growth parameters, blood pressure,
temperature) as clinically indicated and ordered by doctor.
Seen by doctor and blood test by phlebotomist afterwards
Doctor will review results and examine babies to decide if further follow up needed or case
closed.
29
Figure 1 - Flow chart of management in babies of mothers with thyroid disease
Assess babies at risk of thyroid problems, cord blood for TFT sent
Observe 24 to 48 hours
1st FU at 7 to 14 days, repeat FT4, TSH, P/E
(earlier if high risk)
2nd FU at 14 to 28 days, repeat FT4, TSH, P/E
(earlier if high risk)
Normal TFT, no FU
Abnormal TFT
- Consider admission and treatment
- Consult Endocrine team
30
Chapter 7 - Neonatal jaundice
B Pau, YY Lam
Definition:
- Jaundice occurring in the first month of life.
Clinical features:
- Yellow skin
-
- Unconjugated: bright yellow
- Conjugated: greenish yellow
Lethargy
Poor feeding
Complication of severe jaundice: Kernicterus
- Hypotonia, hypertonia, irritability or lethargy
- Severe brain damage, athetoid cerebral palsy, deafness or severe MR
- Death
Causes of NNJ:
Early jaundice (especially within 1st 24 hours of life)
- Haemolytic disease of newborn (ABO, rhesus, minor blood group incompatibility)
- Concealed haemorrhage, polycythaemia
- TORCH, syphilis
- Sepsis
From D3-D4
Non-specific jaundice due to a combination of increased red cell turnover and
immature liver conjugation function
DDX- Septicaemia
Metabolic and liver diseases (esp if prolonged or conjugated)
Investigation for severe jaundice (Early and rapid rising or close to ET level):
CBP (Non-urgent request if blood group or film review required)
Reticulocyte count, blood film
Baby’s and mother’s blood group
Mother’s blood for anti-A or anti-B Ab (mother Gp O )
Coombs test
Trace G6PD level
Sepsis screen, CRP
Other Ix if clinically indicated:
Urine x RS, bilirubin, urobilinogen
Thyroid function test (trace Cord blood)
Metabolic work up
LFT with conjugated and unconjugated bilirubin
Hb pattern
TORCH
Check maternal VDRL/RPR status
31
Management of NNJ:
1. Treat underlying cause e.g. sepsis
2. General management: ensure adequate hydration, discontinue any medication which may
interfere with bilirubin metabolism or binding
3. PT (phototherapy) or ET (exchange transfusion): Refer to the Department NNJ treatment
flowchart for GA ≥ 35 weeks
4. Treatment thresholds in Preterms (< 35 wks), Refer to NICE guideline for gestation specific
threshold of PT and ET. Print out copy for charting patient’s SB according to time after birth,
same GA specific chart to be used till day 14
http://guidance.nice.org.uk/CG98/treatmentthresholdgraph/xls/English
5. Care of babies on phototherapy
- Expose as much surface area as possible
- Shield baby’s eyes: watch out for conjunctivitis
- Monitor baby’s temperature and watch out for hyperthermia
- Monitor I/O if indicated and check BW daily
- May require addition fluids to compensate for insensible loss, especially for babies on
multiple/intensive phototherapy. EBM is the choice for supplementary fluid if available.
- Monitor SB: see flow chart
6. Feeding during phototherapy
- Enteral feeding including breast feeding is continued. Short interruption for breast feeding
or baby care during PT is allowed.
- Breast feeding may be stopped during intensive PT. Lactation support to mother should be
continued and EBM collected.
- If supplementary fluid is clinically indicated, EBM is the choice for supplementary fluid if
available.
7. Exchange transfusion: SB level for exchange transfusion, please refer to the Department
NNJ treatment flowchart for >/= 35 week and NICE guideline for < 35 week GA babies.
Intensive Phototherapy:
(Please refer to department protocol for intensive phototherapy for details)
Multiple phototherapy and biliblanket with a higher irradiance of the light to be delivered over as
much of the body surface as possible. Intensive PT is used to reduce serum bilirubin in cases with
severe NNJ that may require ET.
For cases admitted with severe NNJ:
- Start Intensive Phototherapy & consent for Exchange Transfusion, cross match for ET.
- Repeat SB 2 hours later.
- If increasing trend or not satisfactory decline, then contact Blood Bank for obtaining blood
from Red Cross for exchange transfusion
- Repeat SB again 2hrs later (4hrs after Intensive Phototherapy). Proceed to ET if SB still
above ET threshold.
If SB at presentation is very high or exchange transfusion inevitable (e.g. signs of kernicterus).
Immediately contact blood bank to speed up cross match process as well as get blood from Red
Cross. Repeat SB when blood is available (maybe within 2 hours) and proceed to ET if SB still
above ET threshold.
32
Exchange Transfusion:
Aims:
Remove bilirubin
Remove haemolytic antibody
Correct anaemia (e.g Antenatal anaemia with hydrops)
Procedure (Informed consent should be obtained)
- Perform in intensive care setting with resuscitation equipment immediately available
- Continuous monitoring of baby’s vital signs and ECG monitoring
- Use fresh whole blood < 72 hours old
- Exchange twice the blood volume i.e. 2 x 80ml/kg
- Warm blood during exchange transfusion
- Full aseptic technique
- Umbilical vein catheterization( if single access, refer to diagram for connection) or arterial
line with peripheral vein
- OG or NG tube to aspirate all gastric content before procedure and kept in situ during
procedure
Start exchange with each cycle following the steps below:
- draw blood slowly from body – umbilical vein or arterial line
- push blood into wastage bag
- draw blood from donor pack
- slowly inject donor blood into umbilical vein over 1-2 min
- wait for ½ min and resume cycle
- recording of volume exchanged
- each cycle should take > 3 min
- aliquot volume should not exceed 10% of estimated blood volume
> 2,500gm = 20ml
1,801-2,500gm = 15ml
1,201-1,800gm = 10ml
< 1,200gm = 5ml
Set up for E.T.:
33
Complications of ET:
- Catheter related
o air emboli
o aortic or portal vein thrombosis,
o haemorrhage from umbilical stump, catheter
o NEC
- Haemodynamic complications
- Hypoglycaemia
- Hypocalcaemia: citrate in blood; observe for cardiac arrhythmia on ECG monitor
- Hyperkalaemia
- Acidaemia
- Tissue hypoxia: 2,3-DPG level high in banked blood
- Hypernatraemia
- Hypothermia
Investigations Pre and Post ET:
- Can use the 1st and last aliquot drawn from patient
Blood for SB, Na, K, Ca, glucose, LFT (conjugated and unconjugated bilirubin), Astrup,
CBP (urgent and d/c), blood culture
- Consider checking donor blood for Hct, Na, K, Astrup as indicated
Prolonged Jaundice:
Term > 1/52,
Preterm > 2/52
Persistent unconjugated hyperbilirubinaemia (Conjugated bilirubin <15% of total SB)
Causes:
- Breast milk jaundice (diagnosis by exclusion, ask mother for herbs and drugs history)
- Transient familial
o Gilbert Syndrome, Criggler-Najjar Syndrome
- Haemolytic
o ABO, G6PD, Hereditary spherocytosis, Drug induced haemolysis
- Intestinal obstruction
o Pyloric stenosis, Hirschsprung’s disease
- Metabolic
o Galactosaemia , Hypothyroidism
- Infection
o e.g. UTI
Conjugated Hyperbilirubinaemia (Conjugated bilirubin >15% of total SB)
- Dark urine, pale stool, +/- hepatosplenomegaly
Causes:
- Neonatal Hepatitis Syndrome
- Congenital infection
o TORCH
o Coxsackie
o Varicella Zoster
o Listeria, Syphilis
- Biliary obstruction
o Biliary atresia
o Choledochal cyst
34
-
-
Acquired infection
o Septicaemia / UTI / Meningitis
Metabolic
o Galactosaemia
o Fructosaemia
o α1-antitrypsin deficiency
o Cystic fibrosis
o Tyrosinaemia and other IEM
Others – TPN related
FU for severe NNJ (Max SB above ET range):
- Repeat CBC for late anaemia (2-4 weeks), in cases with significant haemolysis
- Screen for hearing (BAER)
- Follow up development, watch out for cerebral palsy
35
SB (μmol/L)
Jaundice Treatment Thresholds ( ≥ 38 wks)
450
400
350
300
250
200
150
100
50
0
0
12
SB (μmol/L)
24
36
48
60
72
Age in hours
Jaundice treatment Threshold
84
96
108
120
108
120
(35-37+6 wks)
350
300
250
200
150
100
50
0
0
Ref:
12
24
36
48
60
72
Age in hours
84
96
AMERICAN ACADEMY OF PEDIATRICS CLINICAL PRACTICE GUIDELINE Subcommittee on Hyperbilirubinemia.
Management of Hyperbilirubinemia in the Newborn Infant 35 or More weeks of Gestation Pediatrics 2004;114;297
36
37
Routine Care
Monitor SB as indicated
B
Box A
Yes
No/
only 1 SB available
Is SB rising > 8.5 μmol/l/hr?
< 24hrs?
Yes
No
Box A
Stop PT if SB ≥ 20
below PT. Repeat SB
in 12-24 hrs
Yes
SB Stable or falling?
Start Single PT
Repeat SB in 12-24hrs
SB ≥ PT level but
≤ 30 above line
Box A
Step down PT or stop PT.
Repeat SB in 6-12 hrs
Yes
No
Start Multiple PT
See Box A
Further Ix for NNJ
For Intensive PT or ET.
Further Ix for NNJ
SB < 20 below ET
or above ET
Yes
See Early NNJ Mx
Routine Care
SB > 30 above PT
& > 20 below ET
See gestation specific Rx threshold
SB < 50 below PT
Only 1 reading
Repeat SB
4-24 hours later
Box B
SB ≥ 50 below PT
A
No
Yes
Visible Jaundice or elevated TCB
Check SB level
(excluding early NNJ < 24 hrs)
Management of NNJ for
infants ≥ 35 wks
38
Monitor SB until > 24
hrs old. Routine Care
if Stable SB.
Yes
Repeat SB
12 hours later
SB below PT
A
(Infants ≥ 35 wks)
Suspected early Jaundice
only 1 SB available
Box A
Stop PT if SB ≥ 30 below
PT. Repeat SB in 6-12
hrs
Yes
SB > 30 above PT
& > 30 below ET
No
Box A
See Box A
Further Ix for NNJ
For Intensive PT or ET.
Further Ix for NNJ
SB <30 below ET
or above ET
Yes
Step down PT or stop PT.
Repeat SB in 4-8 hrs
Yes
Start Multiple PT
Repeat SB in 4-6hrs
SB Stable or falling?
Start Single PT
SB ≥ PT level but
≤ 30 above line
See gestation specific Rx threshold
No/
SB rising > 8.5 μmol/l/hr?
Check SB. Identify risk factors and treat accordingly.
Management of Early NNJ
Chapter 8 – Patent ductus arteriosus in preterm infant
MC Chan, E Chan, KL Kwok, YY Lam
Background:
Patent ductus arteriosus (PDA) occurring in about 1/3 infants <30 weeks’ gestation and up to
60% of infants <28 weeks
PDA closure can be delayed in preterm infants, and PDA may re-open following constriction
when compared with term infants.
Clinically significant PDA is associated with increased risk of pulmonary edema, pulmonary
haemorrhage, NEC, intraventricular haemorrage, heart failure and BPD.
Clinically significant PDA usually develops during first 2 to 3 days after birth.
Physical examination in clinically significant PDA: tachycardia, tachypnea, hyperactive
precordium, bounding pulse, widened pulse pressure (>25mmHg), systolic murmur,
hepatomegaly. Severe PDA: signs of congestive heart failure or decreased cardiac output i.e.
shock
In premature neonates, clinical symptoms can mimic other diseases e.g. sepsis, RDS;
Suspicion of significant PDA should be raised if increased oxygen requirement or failure to
decrease ventilator settings.
Investigation findings in significant PDA:
ECG: LVH +/- LAE
CXR: cardiomegaly and pulmonary plethora
Echo evidence of haemodynamically significant PDA (≥ 2 features from 1 to 3 or presence of
4)
1. size of PDA (≥ 2mm)
2. LA/Ao ratio (>1.5)
3. PDA shunt flow pattern (growing pattern/ pulsatile pattern)*
4. Absence of antegrade or presence of retrograde flow in diastolic flow in the post-ductal
descending aorta (absolute indication)
Watch out for evidence of ductal dependent circulation e.g. coarctation of aorta as this
may not be evident when a large PDA is present.
Consult cardiologist when there is clinical suspicion of aortic lesions
* Refer to Arch Dis Child and Fetal Neonatal Edition 1997:77;F36-40
Indication for treatment:
1. For asymptomatic premature newborn < 29 weeks (up to 28 weeks 6 days), early Echo within
first 48 hours of life, serial daily monitoring help to check the haemodynamic change associated
with PDA and delineate natural course of PDA. Treatment is indicated if with echo evidence of
haemodynamically significant PDA.
2. Premature babies with symptoms suspected of significant PDA
Fluid management:
- Fluid restriction: subtract 30-50ml/kg/day from baseline (minimum fluid usually not less than
60ml/kg/day). Serial clinical and biochemical assessment of hydration status should be done to
achieve optimal hydration. Lasix may promote ductal patency by its effects on renal
prostaglandin synthesis and should be avoided.
- Correction of anemia with blood transfusion, preferably without Lasix
- Transfusion of packed cell preferably ≤10ml/kg over at least 4 hours, if repeat transfusion is
needed, preferably 24-48 hours apart.
39
Indication for pharmacological treatment:
Treatment indicated in haemodynamically significant PDA, evidenced by clinical or
Echo findings. Drug used: Ibuprofen
Treatment with Ibuprofen:
Consider NPO and start TPN during Ibuprofen
Use of sucralfate in case of upper GI bleeding
Contraindications:
*Impaired renal function (Urea> 14mmol/L, Cr> 140umol/L)
Active bleeding (e.g. recent grade III/ IV IVH)
Platelet count <60,000/mm3, Coagulation defects
Suspected NEC
Severe hyperbilirubinaemia (>ET level)
Caution with concurrent administration of aminoglycosides (gentamicin): it may result in
unexpected elevation of gentamicin level; may consider switching to another group of antibiotics
(e.g. cephalosporin or augmentin) if necessary.
* in babies with high risk of renal impairment, a lower threshold (Cr >100) may be considered as
contraindication.
Investigations before start of Ibuprofen:
CBP with differential count +/- PT/ APTT
RFT, electrolytes, SB
USG brain to document any severe IVH
Monitoring during Ibuprofen:
Urine output (keep > 1ml/kg/hr); if oliguria, consider to withhold and resume when urine
output improves and no other contraindications
RFT and electrolytes (twice a day)
CBP (once daily)
Observe for bleeding tendency (i.e. GI bleeding, IVH)
BP, pulse pressure, PDA murmur for success or failure of therapy
Daily bilateral femoral pulses and upper/ lower BP during PDA treatment
Successful closure of PDA with Ibuprofen is about 60-80% (c.f. spontaneous closure rate ~ 30%)
Treatment with Ibuprofen (IV or enteral)
IV infusion over at least 15 min every 24 hours, preferably undiluted; can add normal saline or D5
to make up the desired volume of infusion. The 2nd course of Ibuprofen can be considered 24 hours
to 48 hours after last dose of the 1st course, if PDA remains haemodynamically significant and no
contraindications.
Oral Ibuprofen (100mg/5ml):
Enteral form is preferred, the safety profile is comparable with the conventional IV form; the
efficacy of enteral route is comparable with or superior to IV form (70-80% vs 60-70%).
Osmolarity of Ibuprofen is ~3900mOsm/kg (KWH preparation Nurofen), dilution with water to 5
times is preferable in order to have reasonable osmolarity and volume.
40
Dosage: mg/kg/dose
mg/kg/dose (24 hours apart)
1st course
2nd course
Infusion time
1st
10
10
30min
2nd
5
5
15min
3rd
5
5
15min
Use IVI Ibuprofen if:
Contraindicated for enteral feeding, e.g. surgical abdomen
Patients with high risk of NEC/ gut perforation i.e. severe IUGR, absent end-diastolic flow in
AN USG
Decision of attending team physician in-charge
Side effects:
Thrombocytopenia, neutropenia, increased creatinine, hyponatreamia
Less common: oliguria, fluid retention, haematuria, intestinal perforation, NEC, IVH, PVL,
pulmonary haemorrhage
Surgical ligation
Surgical ligation if drug closure failed or contraindicated and PDA haemodynamically significant.
Other alternative: Paracetamol IV/ PO (after discussion with attending team physician in-charge
or on call senior)
15mg/kg/dose Q6H for 3 days (1st course) + 3 days (2nd course) if presence of persistent
haemodynamically significant PDA after the 1st course
Monitor LFT daily.
KWH Oral preparation: Endopain (125mg/5ml); Osmolarity: ~3900mOsm/kg. Dilution with
water to 5 times is preferable in order to have reasonable osmolarity and volume.
41
Chapter 9 - Persistent pulmonary hypertension of neonate (PPHN)
M C Chan, E Chan, YY Lam
Definition:
- Disruption in the normal perinatal foetal-neonatal circulatory transition
- Characterized by sustained elevation in pulmonary vascular resistance (PVR) at birth
- Leading to R to L shunt via PDA or PFO and decrease pulmonary blood flow
Clinical features:
- PaO2 < 5-6 kPa in 100% oxygen
- Differential cyanosis with more than 10% pre/post-ductal difference in oxygen saturation in the
absence of cyanotic heart disease (note: the difference may be less than 10% if shunting occurs
mainly in the foramen ovale)
Aetiology of PPHN:
- Idiopathic (20%), MAS (50%), pneumonia/sepsis (20%), RDS (5%), asphyxia, maternal diabetes,
polycythaemia, congenital diaphragmatic hernia
- DDx: cyanotic heart disease, severe pulmonary parenchymal disease
Investigations:
- Blood x glucose, Hct, Ca, Mg, blood gas
- Sepsis work-up if indicated
- Measurement of pre/post-ductal SaO2
- Echo: to exclude cyanotic heart disease, and to document R to L shunt; estimate pulmonary
systolic pressure by measuring TI pressure gradient; assess ventricular function
Treatment:
1) Supportive
- Correct acidosis, hypoglycaemia, hypothermia, polycythaemia, hypocalcaemia,
hypomagnesaemia
2) Ventilation
- Consider connecting to ventilator which is compatible with iNO in case iNO is needed
- Aim for normocapnia and normal SpO2
- HFOV is beneficial for heterogenous lung disease and in most cases of lung condition leading
to PPHN
- Sedative +/- paralytic agents may be needed, but use with caution for hypoperfusion (* assess
the haemodynamics before use)
3) Haemodynamic support
- Initial treatment goals: MBP 50-60 mmHg, systolic BP 60-80 mmHg, subsequent goal adjusted
with echo findings and clinical response
- Volume support with NS or packed RBC for infants with volume depletion (e.g. haemorrhage)
- Adrenaline (inotrope of choice in PPHN) – low dose with β effects i.e. increase cardiac output
and HR: 0.05-0.1mcg/kg/min, dose >0.1mcg/kg/min will have additionalα1 effect which
leads to increase in BP and peripheral resistance; usual ref range up to 0.2 mcg/kg/min
- Dopamine – It can be an alternative to adrenaline or added with adrenaline.
Start with 5-10mcg/kg/min to stimulate β receptors to increase myocardial contraction and
increase cardiac output. Step up if needed to maximum 20mcg/kg/min. It stimulates α1
receptors which increase arteriolar and venous constriction and increases afterload .
42
-
Hydrocortisone – induces expression of down regulated cardiovascular adrenergic receptors;
start together with adrenaline or dopamine at dosage 1mg/kg Q8H
Dobutamine – if echo shows poor myocardial contractility
Mirilone – use with caution (risk of profound hypotension). Consider in case of poor
contractility and high afterload
4) Nitric oxide treatment (iNO)
Indication
OI > 25 (consider iNO when OI is 15-25, especially in infants who are rapidly deteriorating)
in infants ≥35 weeks’ gestational age at birth
*The use of iNO in very sick premature infants <35 weeks’ gestational age with PPHN is not
well proven to be effective
Calculation of OI:
MAP (cmH2O) x FiO2%/ PaO2 (mmHg)
Example: 20 x 100 / 40 = 50
Conversion of kPa to mmHg = kPa x 7.5
Regime of nitric oxide treatment
- Start with 20ppm
- The expected response is rapid, occurring in less than 30 min with a PaO2 increase
≥20mmHg.(2.7kPa)
- If there is no response, consult senior if higher dose will be considered or nitric oxide is
ineffective to be taken off.
- Monitor met Hb daily, keep <2.5%
- With improvement in oxygenation and after 4-6hours period of stability, start weaning
Weaning process:
- After oxygenation improves ( ↑PaO2 ≥20mmHg (2.7kPa) and FiO2 can be reduced to 0.6,
decrease of OI to ≤ 10), iNO can be reduced to 50% over 4-6hrs as long as OI remains at
≤10
- Repeat the process as above till iNO is reduced to 5ppm
- Wean from 5ppm to 1ppm by 1ppm every 2-4 hours
- Off iNO from 1ppm with if infant remains well oxygenated in FiO2 <0.6 with PaO2
consistently >50mmHg (6.7kPa)
- If deterioration occurs during weaning or after treatment has been discontinued, the dose
of iNO should be increased to the previous level or restarted. Once the infant has improved,
weaning should be taking place over 24-48hr period
- Sildenafil may be added at dose of 0.25-0.5mg/kg PO q 4-8 hours during weaning,
especially in cases with iNO dependence
43
Reference: Inhaled nitric oxide use in newborns; Canadian Paediatric Society; Paediatr Child Health 2012;
17(2):95-7
Algorithm for iNO treatment:
Indication: OI >25 AND ≥35wk
Consider if OI 15-25
Yes
Start iNO = 20ppm for 30min
Positive Response
- ↑PaO2 ≥2.6kPa
Yes
No
Keep iNO 20ppm for 4-6hr,
start to wean FiO2 if well
Consult senior to
increase or stop
Weaning iNO criteria:
-OI≤10
OR
- ↑PaO2 ≥2.6kPa AND FiO2<0.6
Yes
No
Keep same dose and back to
weaning criteria 24-48hr later
↓iNO 50% over 4-6hr till 5ppm if OI≤10
Yes
↓ 5ppm to 1ppm by 1ppm Q2-4H
Fail at any step of weaning
Stable
Yes
FiO2<0.6 AND PaO2>6.7kPa
Yes
Yes
Off iNO
Back to previous iNO level or
restart iNO
44
Chapter 10 - Management of neonates with risk factors of
early onset neonatal infection
MT Soo
Early onset neonatal sepsis:
- Definition: perinatally acquired bacterial infections in the first 3 days of life
- Incidence: ~1-5 per 1,000 live births (i.e. 0.1-0.5%), mortality: ~5-15%
Incidence
Histologic
chorioamnionitis
Clinical
chorioamnionitis
22 weeks
23 weeks
24 weeks
25 weeks
26 weeks
27 weeks
28 weeks
70%
61%
59%
51%
48%
41%
34%
28%
26%
20%
19%
19%
15%
14%
Stoll et al (2010) Pediatrics 126: 443-456
Clinical features:
Often non-specific at onset like vomiting, poor feeding, ‘not looking well’etc.
Over 90% present with symptoms in the first 24 hours of life, and the rest mostly present
before 48 hours
Risk factors for neonatal sepsis:
1. Prolonged rupture of membrane (> 18 hours): increases risk 10 fold to 1%
Prolonged rupture of membrane (PROM) + prematurity: increases risk to 4-6%
PROM + low Apgar score: increases risk to 3-4%
2. Maternal fever or clinical chorioamnionitis*: increases risk to 3-20%
(*maternal fever > 38°C with ≥ 2 out of 4: fetal tachycardia, uterine tenderness, foul smelling
vaginal discharge, maternal leukocytosis)
3. Maternal GBS carrier
+ no antibiotic prophylaxis: risk 0.5-1% (vs antibiotic prophylaxis: 0.1-0.2%)
+ PROM, maternal fever, or prematurity: increases risk to 4-7%
+ chorioamnionitis: increases risk to 6-20%
4. Prematurity (gestation < 37 weeks): odds ratio for early-onset GBS sepsis 4.8-26.7
5. Maternal UTI
6. Other risk factors: perinatal asphyxia not explained by obstetric cause
Online calculator of probability of neonatal early-onset sepsis:
http://www.dor.kaiser.org/external/DORExternal/research/InfectionProbabilityCalculator.aspx
Investigations and management:
Trace Placenta histology for evidence of Chorioamnionitis
Asymptomatic infants at risk: CBP D/C, CRP, ± blood culture (especially if preterm labour
< 35 weeks); repeat CRP at 12-24 hours
Symptomatic infants: CBP D/C, CRP, blood culture and CXR; lumbar puncture if indicated;
start antibiotics (see footnote(a) of algorithm below)
45
Indications for antibiotic treatment:
1. All symptomatic infants
2. Asymptomatic infants at high risk (individual assessment required)
Examples of high-risk factors:
suspected/confirmed chorioamnionitis
maternal high fever ≥ 39oC
evidence of bacterial infection in mother e.g. bacteraemia
multiple risk factors
preterm labour < 35 weeks
3. Patients with abnormal laboratory results:
White cell count (term, at birth) < 5 x 109/L or > 30 x 109/L (normal range for
white cell count is broad and may not be very useful, unless it is low)
Neutropenia: absolute neutrophil count (ANC), at 6-12 hours < 8 x 109/L in
term infants or < 2.2 x 109/L in preterm infants
Left shift, toxic granulation, I/T (immature/total WBC) ratio > 0.2, or band
cells > 2 x 109/L
CRP > 10 mg/L
Predictive values of adjunctive laboratory tests
Sensitivity
Specificity
Positive predictive value
Negative predictive value
ANC < 1.75 x 109/L
38-96%
61-92%
20-77%
96-99%
I/T ≥ 0.2
90-100%
30-78%
11-51%
99-100%
I/T ≥ 0.25
45%
84%
6%
98%
I/T ≥ 0.3
35%
89%
7%
98%
CRP ≥ 10 mg/L
70-93%
78-94%
7-43%
97-99.5%
(Ref:Gerdes JS. Diagnosis and management of bacterial infections in the neonate. Pediatr Clin N Am
2004;51:939-959)
Lower limits for absolute neutrophil counts at 6-12 hours
>36 weeks
28-36 weeks
< 28 weeks
9
Manroe
7.8 x 10 /L
Mouzinho
2.2 x 109/L
2.2 x 109/L
Schelonka (term)
9.5 x 109/L
Schmutz
7.5 x 109/L
3.5 x 109/L
1.5 x 109/L
(Ref: Polin RA and the Committee on Fetus and Newborn. Management of neonates with suspected or proven
early-onset bacterial sepsis. Pediatrics 2012;129:1006-1015)
Practical considerations for antibiotic treatment:
1. Duration:
Antibiotics should be considered to be stopped, usually after 48-72hours, if:
- blood investigations (preferably serial CRPs, at least 12 hours apart were normal),
- blood cultures, with at least 48 hours incubation, were negative, and
- the neonate remains asymptomatic.
If sepsis is established, antibiotics can be given for a course, at a minimum period of 5 days;
the duration depends on the diagnosis and progress. Caution notes: prolonged initial empirical
antibiotic therapy (≥ 5 days) especially in premature infants is associated with increased risk
of necrotizing enterocolitis and mortality.
(Cotten et al. Pediatrics 2009; 123(1): 58-66, Kuppala et al. J Pediatrics 2011; 159(5): 720-5)
2.
Choice of antibiotics:
- 1st line: penicillin (preferred in our department) /ampicillin + gentamicin
- 2nd line: Augmentin (amoxicillin + clavulanic acid),
or Tazocin (tazobactam + piperacillin) to cover pseudomonas
or 3rd generation cephalosporin (Claforan), to cover meningitis
- 3rd line if indicated: Meropenem (if septic),
or vancomycin (for MRSA/MRCONS)
46
KWH Algorithm for prevention of early onset GBS disease among newborns
Yes
Admit to neonatal ward
Signs of neonatal sepsis?
Full diagnostic evaluation
Antibiotic therapy
No
Maternal chorioamnionitis?
a
b
Yes
Admit to neonatal ward
Limited evaluation
No
GBS prophylaxis indicated for mother?
ce
+/- Antibiotic therapy
de
No
f
Routine clinical care
g
Yes
Observation in postnatal ward
Yes
Mother received intravenous penicillin,
(routine care) for ≥ 48 hours
ampicillin, or cefazolin for ≥4 hours before
gh
delivery?
No
≥ 37 weeks and duration of
membrane rupture < 18 hours?
Yes
Observation in postnatal ward
gh
(RR/Temp Q8H) for ≥ 48 hours
Examination by paediatrician daily during
newborn screening exam for 2 days
No
Admit to neonatal ward,
Either < 37 weeks or duration of
membrane rupture ≥ 18 hours?
Yes
CBC, CRP (at birth and at 12-24 hours)
+/- blood culture
Observation for ≥ 48 hours
a
Full diagnostic evaluation includes a blood culture, a complete blood count (CBC) including white blood cell
differential and platelet counts, CRP, chest radiograph +/- lumbar puncture (only when patient is stable enough to
tolerate procedure)
b
Consultation with obstetric providers is important to determine the level of clinical suspicion for chorioamnionitis.
Chorioamnionitis is diagnosed clinically and some of the signs are nonspecific.
c
Limited evaluation includes CBC with differential and platelets , CRP (at birth and 12-24 hours of life) and blood
culture.
d
Antibiotic therapy should be directed toward the most common causes of neonatal sepsis, including intravenous
ampicillin / penicillin for GBS and coverage for other organisms (including Escherichia coli and other gram-negative
pathogens) and should take into account local antibiotic resistance patterns.
e
CBC D/C, CRP at birth and 12-24 hours and observation ≥ 48 hours can be an alternative if the level of clinical
suspicion for chorioamnionitis is low e.g. isolated feature of intrapartum fever of mother, fetal tachycardia and baby
well after birth.
f
GBS prophylaxis is indicated if 1 or more of the following is true: (1) mother is GBS-positive within the preceding 5
weeks; (2) GBS status is unknown and there are 1 or more intrapartum risk factors, including <37 weeks’ gestation,
rupture of membranes for >18 hours, or temperature of >100.4°F (38.0°C); (3) GBS bacteriuria during current
pregnancy; or (4) history of a previous infant with GBS disease.
g
If signs of sepsis develop, a full diagnostic evaluation should be conducted and antibiotic therapy initiated.
h
Mother with GBS +ve would be alerted about signs and symptoms of early and later neonatal GBS sepsis and given
education pamphlets on discharge.
47
Chapter 11 – Necrotizing enterocolitis (NEC)
MT Soo, YY Lam, E Chan
Necrotizing enterocolitis is a disease of multifactorial aetiology leading to inflammation and
necrosis of the neonatal intestines, especially in the preterm very-low-birth-weight infants. It may
occur singly or in clusters, and the incidence varies among different centers, estimated to be 0.3-2.4
cases in every 1,000 live births, or 2-5% of all NICU admissions, or 5-10% of all VLBW infants.
The overall mortality is about 9-28%, but can be up to 45% in VLBW infants.
Risk factors:
1. Prematurity (most important: 90% of NEC patients are preterm)
2. Gut ischaemia (likely final common pathway)
Conditions that lead to shunting of oxygenated blood from intestine, e.g. maternal use of
cocaine, maternal preeclampsia, perinatal asphyxia, polycythaemia, patent ductus
arteriosus, cyanotic congenital heart disease, reversed diastolic flow in abdominal aorta,
umbilical artery catheter insertion
3. Enteral feeding
>90% of patients diagnosed to have NEC have been fed before its onset
Decreased risk in those with breast milk feeding
Increased risk if feeding increment > 35ml/kg/day and high osmolality of feed (human
milk is about 300 mOsm/L; preterm formula, including fortified EBM, should not be
more than 400 mOsm/L)
4. Infection
Temporal and geographic clustering of outbreak
No single infectious agent consistently identified, but increased risk in those with altered
gut flora and colonization by potential pathogens
Infectious agents include clostridium, gram negative and anaerobic bacteria
Clinical features: (Table 1)
Management:
1. Prevention
Stringent hand hygiene and infection control
Early recognition and treatment of correctable factors such as hypoxia, hypothermia,
acidosis and hypotension
Encourage human milk feeding, and follow standardized feeding regime guideline;
caution in feeding of neonates with PDA
Probiotics (such as Lactobacillus and Bifidobactirium species) are found to be effective
in preventing NEC in premature babies (Cochrane Review 2014). NNT is 29 for babies
<1.5kg, but the optimal regimen and duration is not known
(In our department, for premature babies < 33 week gestation and > 1 kg, we have
experience in using Lactobacillus GG 6 × 109 CFU with milk once daily, from day 4 of
life until 36 weeks post-conceptional age, or until discharge, whichever is shorter, for the
prophylaxis of NEC. Discuss with the neonatologist in charge when considering
probiotics.)
48
2.
Treatment: (see table below)
If there is discordance between clinical and radiological staging, the management should
be based on the more advanced one
Consult paediatric surgeon for NEC stage IIA or above
Suggested empirical antibiotic combination:
- ampicillin + gentamicin (or cefotaxime) for both gram +ve and -ve organism
coverage
- ± metronidazole (for anaerobes)
- meropenem (if critically ill, to cover both aerobes and anaerobes)
Consider early elective intubation
Serial monitoring of infective markers, blood indices and AXR for progress
Table 1 : Modified Bell’s Staging Criteria for NEC
Stage
IA –
Suspected NEC
Systemic signs
Temperature
instability, apnoea,
bradycardia,
lethargy
IB –
Suspected NEC
IIA –
Definite NEC
Mildly ill
Same as above
IIB –
Definite NEC
Moderately ill
Same as above, plus
mild metabolic
acidosis, mild
thrombocytopenia
IIIA –
Advanced NEC
Severely ill,
Intact bowel
Same as IIB, plus
hypotension, severe
apnoea, combined
respiratory and
metabolic acidosis,
disseminated
intravascular
coagulation,
neutropenia
Same as IIIA
IIIB –
Advanced NEC
Severely ill,
Perforated
Bowel
Same as above
Intestinal signs
Elevated pre-gavage
residuals, mild
abdominal distension,
vomiting, occult
blood positive stool
Blood from rectum
Same as above, plus
absent bowel sounds,
+/- abdominal
tenderness
Same as above, plus
absent bowel sounds,
definite abdominal
tenderness, +/abdominal cellulitis or
right lower quadrant
mass
Same as above, plus
signs of generalized
peritonitis, marked
abdominal tenderness
and distension
Same as IIIA
Radiological signs
Normal or intestinal
dilation. Mild ileus.
Treatment
NPO for 2-3 days, stop
antibiotics after 3-5 days if
culture negative
Same as above
Same as above
Intestinal dilation,
ileus, pneumatosis
intestinalis
NPO, antibiotics x 7-10 days,
if exam is normal in 24-48
hours. Consult paediatric
surgeon.
NPO, antibiotics x 14 days,
supportive treatment e.g. fluid
resuscitation, NaHCO3 for
acidosis
Consult paediatric surgeon.
Same as IIA, plus
portal gas, +/- ascites
Same as IIB, plus
definite ascites
Same as above, inotropic
agents, ventilation therapy,
paracentesis
Same as IIB, plus
pneumoperitoneum
Same as above, plus surgical
intervention
(Ref : Modified from Kliegman RM, Walsh MC. Neonatal necrotizing enterocolitis: pathogenesis, classification, and
spectrum of disease. Curr Probl Pediatr 1987;17(4):243-288)
3.
Post-NEC management
- Resume small amount of feeding and step up cautiously (around 10-20ml/kg/day)
- Continue parenteral nutrition till full feeding established
- Watch out for complications:
(a) GI: stricture (25-35%), enteric fistulae, short bowel syndrome after surgery
(10-20%), malabsorption syndrome, chronic diarrhea,
dumping syndrome, fluid and electrolyte loss, hepatitis, cholestasis
(b) Metabolic: failure to thrive, metabolic bone disease, increased risk of
impaired neurodevelopmental outcome
49
Chapter 12 - Neonatal parenteral nutrition
YY Lam, F Poon
Total parenteral nutrition
Indications:
Unlikely to establish enteral feeding in 1 week (V Yu)
Enteral feeding is contraindicated or delivers less than 75% of total protein and energy
requirement (Avery)
Contraindications:
Fulminant sepsis prior to adequate clinical control with antibiotics
Uncontrolled acidosis
Severe circulatory instability or acute renal failure
Intravenous access:
Limit dextrose < 12.5% in peripheral vein (V Yu)
The solutions to be infused for peripheral parenteral nutrition must have an osmolarity
< 900mOsm/L within a pH range of 7.2-7.4 (Culebras) (AAP recommendation)
Central line must be used if dextrose > 12.5% is used, amino acid concentration >3.5%,
osmolality > 900mOsm/L
20% fat emulsion is isotonic and can be given peripherally
Energy:
Goal for energy intake in preterm baby is 120 Kcal/kg/day
In long-term ventilated infants with CLD, requirement increases by 25-30% (Cairns) (V Yu)
BMR of preterm baby is 40 Kcal/kg/day. If an infant is nursed in a thermoneutral environment,
an input of 50 Kcal/kg/day is sufficient to match ongoing expenditure but it does not meet
additional requirements of growth (Cairns) (V Yu)
Resting energy expenditure is 65 Kcal/kg/day
The energy cost of gaining 1 gram of new tissue is 5 Kcal. To achieve the equivalent of third
trimester intrauterine weight gain of 14-15 gram/kg/day, an additional 70 Kcal/kg/day is
required (Cairns) (V Yu)
Total fat calories should be 30-40% and < 60% of the diet (Avery)
Fluid:
Fluid may be adjusted according to serum sodium level in the first week of life.
When less than 100ml/kg/day is prescribed, the input of nutrients is reduced proportionally (V
Yu). A restrictive early fluid approach significantly reduced the risks of PDA, NEC and death
(Cochrane)
Glucose:
GIR should be started at 4 to 6 mg/kg/min. The glucose infusion may be increased gradually
by 1-2 mg/kg/min per day to maximum 14 mg/kg/min if there is no significant
hyperglycaemia (serum glucose level > 10 or glycosuria). If still significant hyperglycaemia
on TPN with GIR 6 mg/kg/min, may start insulin infusion from 0.01 to 0.1 U/kg/hr and adjust
accordingly.
50
Lipid:
Start as soon as possible within first 24-48 hours. Use 20% emulsion in preterm infants as
lower plasma triglyceride, cholesterol and phospholipid concentrations than those on 10% (V
Yu) (Shulman) (Haumont 1989)
-
Intravenous lipid must be > 0.5-1 gram/kg/day to prevent essential fatty acid deficiency. If
septic or serum bilirubin approaching exchange transfusion level, limit lipid to 2 gram/kg/day.
Check triglyceride level after increase in lipid emulsions and after full TPN established
increase of lipid emulsion. If triglyceride > 1.7 mmol/L, withhold fat for 1 day and start at a
lower dose. When baby is on phototherapy, ensure lipid emulsion is shielded.
Suggested regimen of lipid:
Start at 0.5-1 gram/kg/day; advance at around 1 gram/kg/day to the maximum of 3 gram/kg/day
Amino acids:
Start as soon as possible after RCT in sick and premature infants showed that an intake of
birth, especially important for 1.5gram/kg/day amino acid from the day of birth in sick,
those < 1,250g.
premature infants resulted in nitrogen retention and improved
protein synthesis (Cairns) (V Yu). Day 1 amino acid also decreased
“starvation response” of hyperglycaemia and hyperkalaemia
(Adamkin). There are no adverse effects from prompt initiation of
PN. It should therefore be started within a few hours of birth.
(Ziegler)
May use lower dosage in septic or less stable infants.
Suggested regimen of amino acids:
Start at 1.5-2 gram/kg/day; advance at 0.5-1 gram/kg/day, maximum 3.5 gram/kg/day for term and
4 gram/kg/day for preterm.
Electrolytes:
Withhold or minimum sodium and potassium in first 1-2 days of life. The dosages are not rigid
but depend on the condition and electrolyte balance of the infant. Suggest regimen:
i.
Sodium: 2-5 mmol/kg/day
ii.
Potassium: 1-4 mmol/kg/day
(Extremely preterm babies have risk of non-oliguric hyperkalaemia from immature
distal tubular function)
iii.
Acetate:
Acetate may be given to adjust baby’s acid-base status. Anion in excess of specified
Cl can be supplied as acetate. Acetate may be maximized for acidosis or minimized
for alkalosis. Be aware that minimizing or maximizing acetate can lead to wide
swings in acid-base status.
51
Calcium and Phosphate:
Infant are prone to hypocalcaemia in the first 72 hours due to transient hypoparathyroidism
and to hypophosphataemia. Both calcium and phosphate should be added early during TPN
therapy.
Calcium around 1 mmol/kg/day from birth in preterm babies ≤ 32 weeks to prevent neonatal
hypocalcaemia. Adjust clinicaly, preterm around 1-2 mmol/kg/day and term 0.5-1.5
mmol/kg/day
The molar ratio of calcium and phosphate should preferably be 1:1 although it can be up to
1.3:1. The exact ratio is governed by the occurrence of precipitation if inorganic phosphate is
used.
Heparin:
0.5-1 unit/ml must be added to the infusate to reduce the incidence of phlebitis and thrombosis
of both peripheral and central venous catheter
Useful Reference (from Department web: Prescription Section)
Kwong Wah Hospital Neonatal TPN order form
Starter TPN order form (Starter TPN can be considered if Pharmacy TPN service is not available)
52
Chapter 13 - Transpyloric tube feeding in neonate
E Chan, YY Lam
Indication:
Severe gastroesophageal reflux that cannot be adequately managed by other treatments.
Complications:
Dumping, diarrhea, ischaemic enteritis, duodenal perforation
Caution:
- Discuss with seniors and preferably in ground round before use.
- Not preferred to use in premature babies if <=34wks or <1.8kg
- When used in premature babies, you need to execute extreme caution.
- Use non-weighted polyurethane enteral feeding tube (Vygon) with appropriate size
(<=F8)
Estimation of Length of insertion:
- 1st mark (distance from mouth or nose to the gastro-oesophageal junction):
Identify the lower oesophageal sphincter (LES) based on standard measurement techniques,
or use the Strobel formula
From nares: (5 + 0.252 x height) cm
From incisor: (6.7 + 0.266 x height) cm
- 2nd mark (distance from gastro-oesophageal junction to antrum):
Distance from the xiphoid process to the right lateral costal margin
- 3rd mark (distance from antrum to duodenum):
For term baby and infant, further advance the tube for about 5cm
Insertion
Insert the tube through either nostril or mouth beyond 1st mark
Confirm gastric placement by aspiration of acid gastric juice and testing with pH test strip
(pH ≤ 5.5)
Place patient in a right lateral oblique position with the head of bed elevated 15-30°
Advance the tube until resistance is felt at the 2nd mark (at the antrum)
For neonate, further advance the tube for about 5cm at 1-2cm every 15 minutes until it
reaches the target marking
Instill 5-10ml of air until air entry is heard over the RUQ. When the tip is placed in the
duodenum, the sounds will be changed from low-pitched gurgles to high-pitched crackles
near the right upper quadrant and it will be unable to withdraw air from the tube
If the tube is in the duodenum, bile or alkaline fluid may be aspirated
Take AXR for confirmation of the position of the tube
The ideal position for the tip of the tube is in 3rd or 4th part of the duodenum
Feeding regime: slow infusion of milk to decrease dumping, consider monitor BSL initially
53
Chapter 14 - Surfactant therapy
B Pau, YY Lam
The primary cause of RDS is inadequate pulmonary surfactant. The structurally immature and
surfactant-deficient lung has decreased compliance and a tendency to atelectasis leading to V/Q
mismatch, alveolar hypoventilation with resultant hypoxemia and hypercarbia. The use of
exogenous surfactant in preterm infants improves oxygenation, decreases air-leak, reduces
mortality due to RDS, and decreases overall mortality. Evidence has shown that, in the era of
antenatal steroid use and early CPAP, prophylactic surfactant at birth is not superior to early rescue
therapy (i.e < 2 hrs after birth).
Approach and Surfactant use in infants with suspected RDS:
- Early nCPAP at the delivery room should be given to all preterm infants (≤1.5 kg or <32
weeks).
- Surfactant therapy should be considered in conjunction with early CPAP if RDS is suspected.
- Surfactant is given ASAP (within 2 hrs) for all preterm infants born < 28 weeks or < 1000
grams (if uncertain gestation)
- Premature infants <32 week or </=1.5 kg, after initial stabilization at the delivery suite, who
requires mechanical ventilation for RDS should receive surfactant.
- Early selective use of surfactant in other preterm infants ( ≥28 wks) with RDS who failed
nCPAP, defined by at least one of the follows:
Failure to maintain SaO2 ≥ 88% despite FIO2 > 0.40 or CPAP > 7 cm H2O
Respiratory acidosis (PaCO2 ≥ 60 mm Hg (8 kPa) and pH ≤ 7.2) documented by
capillary or arterial blood gases
Apnea defined as > 4 episodes of apnea/hr or > 2 episodes of apnea/ hr requiring bag and
mask ventilation.
Early signs of significant respiratory distress (e.g tachypnea, insucking, grunting)
- Discussion with senior if indications besides the above mentioned groups
- Consider possible complications (e.g. PPHN, pneumothorax, atelectasis etc) that other
management strategies may be needed
Surfactant use other than RDS:
- Meconium aspiration syndrome requiring mechanical ventilation
- Acute RDS secondary to pneumonia which required mechanical ventilation
Surfactant Dosage and preparations:
-
-
-
Curosurf
2 preparations: 1.5ml vial (120mg phospholipid), 3ml vial (240mg
phospholipid) i.e.80mg phospholipid/ml. First dose recommended 200mg/Kg (2.5mls/Kg), dose
between 100 to 200 mg/kg has been used especially in milder case or in MIST. It can be
considered in prophylactic cases, confirm with senior if with doubt. Subsequent dose 100mg/Kg
(1.25ml/kg). Repeat dose (if indicated) 12 hrs later.
Survanta
2 Preparations: 4ml vial (100mg phospholipid) / 8ml vial (total 200mg
phospholipid i.e. 25mg phospholipid /ml. Dosage 100 mg/Kg (4mls/kg), repeat dose same (if
indicated) 12 hrs later
MIST (Minimally Invasive Surfactant Treatment) is currently under further investigation and
studies, it is only practiced in selected cases with approval or under supervision by neonatal
team doctors and should follow pre-defined instructions. Only Curosurf is used when MIST is
practiced.
54
Surfactant Administration
- Ensure proper placement and patency of the ETT by auscultation and chest rise ± end tidal
CO2.
- Hold surfactant in hands a few mins to warm the preparation before use and do not shake. Do
not place under radiant heater
- Continuous monitoring of vital signs and clinical condition during administration.
- Curosurf: Can instil as one aliquot with baby supine and head in neutral position. Ensure that
the NG tube used to administer Curosurf is not extending any further beyond the tip of ETT
- Survanta: Instil via a closed circuit system using ’trach care’ in-line catheter with minimal
disruption to ventilation. Tip of catheter should protrude just beyond the tip of ETT above
infant’s carina. Give 4 aliquots as bolus with baby supine and head in neutral position Allow
ventilation for 30 seconds in between bolus to allow for stabilization. Slow or stop Survanta
administration if deterioration in vital signs or if there is back flow of Survanta up the ETT.
- Avoid excessive IPPV in between instillations as inadvertent over-inflation may occur, causing
barotrauma.
- Consider INSURE approach with surfactant administration (Intubate-SURfactact-Extubate)
After surfactant
- Stay with the infant after administration as surfactant causes rapid changes in lung mechanics.
- Avoid suctioning for at least 1 hour after dosing unless signs of significant airway obstruction
occur.
- Advanced ventilator settings such as Volume Guarantee modes should be considered in VLBW
<1.5Kg.
- Pay attention to changes in SpO2 (first to improve), Tidal volume, PV loops, Dynamic
compliance (Cdyn usually 0.3-0.5mls/cmH20/Kg in RDS infants, studies suggest good success
rate in extubation when Cdyn > 1)
- Titrate down FiO2 and ventilation pressures as condition improves.
- Early blood gas after surfactant (30 mins)
- Target for pCO2 of 45-55mmHg (6 – 7.3 kPa) for babies on mechanical ventilation, provided
that the pH is > 7.25 and that significant respiratory distress or recurrent apnoeas are absent.
- If the pCO2 is < 40mmHg or > 60mmHg, the baby should be promptly assessed and
appropriate action taken.
- Consider ‘INSURE’ (INtubate – SURfactant –Extubate to CPAP) technique in preterm babies
with mild RDS. Extubate after surfactant to nCPAP or NIV when ventilator requirement is
appropriate for extubation and respiratory effort is satisfactory ( FiO2 < 0.3 and MAP < 8 cm
H2O)
- Consider 2nd dose (12 hours after 1st dose) if baby is still ventilated and requires either: FiO2
>0.3, MAP≥ 8cm H2O or Cdyn < 0.5mls/cmH20/Kg. Discuss with senior if in doubt.
55
Chapter 15 – Hypoxic-ischaemic encephalopathy
B Pau, S Cherk
Definition:
A hypoxic-ischaemic insult occurring around the time of birth resulting in an encephalopathic state
characterized by the need for resuscitation at birth, neurological depression, seizures and
electroencephalographic abnormalities.
Background:
Moderate to severe cases occurs in approximately 2/1000 births. The risk of death or severe
handicap in survivors of moderate and severe HIE is approximately 25 and 75% respectively, and
children without motor impairments have lower cognitive scores on long term follow‐up.
Management strategies include maintaining physiological parameters within the normal range,
treating seizures with anticonvulsants and hypothermia therapy. Hypothermia refers to cooling to a
core temperature of 33‐34C which is started within six hours of birth and continued for 72 hours.
This reduces death and disability at 18 months of age and improves a range of neurodevelopmental
outcomes in survivors
History and Examination, communication:
Document clearly antenatal events, delivery and resuscitation details. Obtain maternal history
including significant events during pregnancy. Document discussion with parents in the medical
records.
Hypothermia therapy
Initiate cooling therapy within 6 hours of birth (preferably sooner) for moderate to severe HIE
infants ( ≥ 36 completed weeks of gestation) as defined by perinatal AND neurological abnormality
criteria (see below). Alert NICU for early preparation if case is identified. Studies have shown that
the earlier the cooling is commenced the better the outcome. So far, there is a lack of data to
support the use of cooling for neuroprotection in infants of lower gestational age or for other
conditions such as sudden postnatal collapse. Babies that fulfilled the perinatal criteria (A) but not
the neurological abnormality criteria (B) may also be considered for hypothermia if aEEG is
moderately or severely abnormal. The use of hypothermia for all borderline cases should be
discussed with senior.
Entry Criteria
A) Perinatal Criteria (at least one of the following):
• Apgar score of ≤ 5 at 10 minutes after birth
• Continued need for resuscitation, including endotracheal or mask ventilation, at 10
minutes after birth
• Acidosis within 60 minutes of birth (defined as any occurrence of umbilical cord, arterial
or capillary blood pH <7.00)
• Base Deficit ≥ 16 mmol/L in umbilical cord or any blood sample (arterial, venous or
capillary) within 60 minutes of birth
AND
56
B) Ongoing Neurological Abnormality entry criteria:
Altered state of consciousness (lethargy, stupor or coma) AND at least one of the following:
• Hypotonia
• abnormal reflexes including oculomotor or pupillary abnormalities
• absent or weak suck
• clinical seizures
Hypothermia procedure:
Avoid hyperthermia for HIE babies. Passive cooling can be started, after the initial resuscitation, in
cases suspected to have HIE by switching off the radiant warmer. Monitor the temperature closely.
Active hypothermia by servo-controlled cooling blanket targeted at 33.5oC rectal temp should be
started once criteria A and B as stated above are fulfilled. (All external heat sources must be
switched off). At the completion of 72 hours, rewarming gradually by 0.5oC per hour until the
rectal temperature is at 36.5oC for one hour. (Refer to Department Guideline “Hypothermia
Therapy in Neonate” for the procedure)
Discontinue hypothermia if occurrence of serious adverse event requiring therapy: cardiac
arrhythmia, persistent acidosis, major thrombosis or bleeding, skin breakdown.
Monitoring during Hypothermia:
Continuous Core/skin temp, delta Temp, SpO2, AR/RR, ECG and aEEG. Meticulous skin care.
Continuous arterial BP monitoring if require ventilatory support or haemodynamically unstable.
Monitor urine output (consider indwelling urine catheter), Glasgow Coma Scale
Investigations:
Baseline CBP/clotting/RFT/LFT/glucose/blood gas/troponin
Q6h to Q12 H blood gas/K/glucose
Q12 H to daily CBP and clotting, L/RFT
Maintaining physiological Parameters
Cardio-Respiratory
•
•
•
•
•
•
•
Avoid hypocapnia (pCO2 <5 kPa) or hypercapnia ( pCO2 >7 ) if ventilated
Correct underlying cause for persistent severe metabolic acidosis
Maintain SaO2 ≥ 92% to avoid pulmonary hypertension in a term baby
Ventilate if incipient respiratory failure with rising FiO2 and pCO2 and pH < 7.25.
Obtain arterial access to monitor BP if mechanical ventilation required
Aim for the mean BP to be ≥40mmHg in a term baby.
Echo, cardiac enzymes, troponin I and ECG (ST elevation) if hypotensive. Consider fluid bolus
if hypovolaemia and inotropes if poor contractility.
• Bradycardia down to 80-100 common during hypothermia therapy. Perform 12 lead ECG if
HR <80.
• Consider CVP monitoring via UVC with regular echo assessment of cardiac contractility and
stroke volume to guide fluid/inotrope administration
• May require hydrocortisone if intractable hypotension, after discussion with senior.
57
Fluid Balance/Metabolic Management
• Fluid restricted to 60 ml/kg/24 hours D10 in first 24 hours.
• Aim for neutral fluid balance (Output=Urine output + IWL).
• Monitor urinary output closely and maintain ≥1ml/kg/hr. Observe for bladder retention. Insert
urinary catheter to monitor urine output if needed.
• Ensure adequate intravascular volume before attributing oliguria to SIADH or renal failure.
• Consider adding electrolyte supplements or start TPN after 24-48 hours when electrolytes/
renal function stable
• Withhold potassium supplementation until urine output is good.
• Monitor plasma glucose closely and increases GIR if control suboptimal.
• Monitor calcium levels.
CNS
• Continuous aEEG monitoring until 24hrs after rewarming.
• Regular assessment of neurological condition, primitive reflex, pupil size (see HIE staging
table).
HIE staging (Sarnat and Sarnat, modified by Levene et al)
I
Clinical
Grade
Mild
II
Moderate
III
Severe
Staging
Symptoms
Hyper-alert, irritable, very reactive to stimulation
May be tachycardia, have dilated pupils and jittery
Normal EEG, no seizures.
Last 3-4 days
Lethargic, hypotonic, proximal and central weakness
Weak/ absent sucking
Low heart rate, small pupils, secretions++
Occasional Apnoea
Seizures and abnormal EEG common
Last 2-14 days
Unresponsive, flaccid
Absent reflexes/ absent sucking
Seizures common, may be prolonged
Abnormal EEG with suppressed background activity
Last up to weeks.
Outcome
Usually normal, may
have minor disability
37-54% Death or
major disability #
70-86% Death or
major disability #
# Ref:
Cochrane Neonatal Group. Cooling for newborns with hypoxic ischaemic encephalopathy. CochraneDatabase of
SystematicReviews 2013, Issue 1.Art.No.:CD003311.DOI: 10.1002/14651858.CD003311.pub3.
• The prognosis from the grading schemes should be taken from the maximal worse grade and
cannot be used for this purpose before day 3 if the grade is <3.
• Watch for the presence of seizures – clinical or on aEEG
• Seizures will be missed in heavily sedated and paralysed children and continuous aEEG
monitoring is needed
• Treat seizures, exclude metabolic derangements.
• Refer to chapter on Neonatal seizure on management of seizure.
• Anticonvulsants can be discontinued once seizure control has been attained and the infant is
neurologically normal (e.g Day 14)
58
Monitoring for multi-organ failure
In addition to Resp/ CVS/ CNS systems:
• Haematological: Clotting problem/DIC/thrombosis/ thrombocytopenia
• Renal failure: Serial RFTs
• Liver failure: LFT +/- ammonia
• GI complications: Necrotising enterocolitis. Keep NPO until after rewarmed and not on
inotropes. Risk of aspiration if pharyngeal incoordination is present.
• Sepsis: empirical antibiotics after sepsis work-up.
Classifications of 5 example traces by using the EEG pattern recognition method (right) and
voltage method (left) to assess the aEEG background.
From
Thoresen M, et al. Effect of hypothermia on amplitude-integrated electroencephalogram in infants with
asphyxia. Pediatrics. 2010 Jul;126(1):e131-9
Cranial US scan
US brain is helpful in monitoring the progress on admission, 7 and 14 days (preferably by a
neonatologist/radiologist with experience in neonatal US brain)
Pay attention to:
• Normal/abnormal anatomical development
• Abnormal echogencity/ calcification from the parenchyma (insult predating labour)
• Haemorrhage
• Swelling, loss of normal tissue differentiation often seen in the first few days.
• Increasing white matter echogenicity over time
o focal suggesting infarction (stroke) or haemorrhage
o more generalised and bilateral suggesting a more global insult
• Increasing echogenicity in the basal ganglia and thalami usually bilateral and typical of an
acute hypoxic-ischaemic insult. Such changes can be subtle and not be seen before day 7
59
•
•
Anterior cerebral or middle cerebral artery doppler. Abnormal if Resistant index < 0.55 on
2-3 occasions within 24- 72 hours from birth (in the absence of large PDA)
Typically the RI is normal on day after intrapartum asphyxia and then becomes abnormal on
days 2 and 3 before normalising again
RI= (peak systolic velocity – end diastolic velocity)
peak systolic velocity
Follow-up investigations
1. Serial US brain
2. EEG at 24-48 hrs (for all cases):
Result of 1st EEG:
N/near N
Intermediate Abn
Severely Abn
Second EEG
No need
48-72 hr after first EEG
24 hr after stopping
hypothermia (to rule out
hypothermia effect)
3rd EEG
+/- if second EEG
before D4
3. MRI brain to be performed between 5 – 14 days post injury
• MRI Sequences acquired include T1, T2, diffusion weight imaging (DWI) +/- T2* (for
haemosiderin)
• DWI performed on Day 5-7 is useful for delineating white matter ischaemia but may
underestimate basal ganglia and thalamic injury.
• Conventional sequences (T1/T2) performed early may underestimate extent of
injury. When performed after 7 days it is helpful for ascertaining the maximum extent of
lesions.
4. SSEP at end of first week depending on availability, if not before discharge
5. BAER
6. VEP
Prognosis
When the results of the follow-up investigations are available (esp MRI and SSEP), arrange joint
counselling with O&G, neurologist, +/- MSW/CP.
Document full neurological examination before discharge
Abnormal aEEG pattern persisting >48 hrs predicts severe disability or death in term asphyxiated
infants treated with hypothermia, PPV 80%. All infants who developed sleep wake cycling had a
favorable outcome.
60
EEG
Normal EEG good prediction of outcome if done >/=24 hr ( before 1 week)
As all EEG improves with time, not reliable if 1st EEG done >1 wk
Serial EEG improves prognostic value :
-A severely abnormal EEG in first 2 days, if much improvement within 1 week, suggestive of
outcome better
A study of 23 severe HIE term infants showed inactive EEG pattern in 1st 48 hr life associated with high risk of death.
At 1 week, presence of low voltage continuous pattern associated with unfavourable outcome at age 1yr. Persistent
abnormalities associated with neurological sequelae (sensitivity 86%, specificity 75%, PPV 67%, NPV 90%)
(Ref: E Mariani , Ped Neurolo 2008; 39:317-324)
MRI:
A study in UK based on a cohort of 175 infants has shown that the pattern of ischaemia on early
MRI was a good predictor of outcome at 2 years in different developmental domains.
(Ref: M Martinez-Biarge et al. Outcomes after central grey matter injury in term perinatal hypoxic-ischaemic encephalopathy. Early Human
Development 86(2010) 675-682.)
61
Chapter 16 - Brain death in the neonate
S Cherk
Current knowledge is inadequate to diagnose brain death in neonate less than 7 days old or born
prematurely. One or both paediatrcians who will certify brain death should have the skill and
knowledge in the diagnosis of brain death.
Brain death clinical assessment methods for neonates > 7days:
1) Pre-requisites to be met:
- No hypothermia (Core/rectal temp ≥ 35 °C)
- No hypotension
- No profound abnormality of serum electrolytes, acid base balance or blood glucose
- Remediable and reversible condition excluded
- No paralytic agent / profound CNS depressant
2) Assessment criteria:
1)
document coma
2)
document apnoea
3)
absence of brain-stem reflexes
Examination should remain consistent for brain death throughout the pre-determined period of
observation
3) Assessment methods:
1) Coma
flaccid tone and absence of spontaneous or induced movements, excluding activity
mediated at spinal cord level #
lack of response to pain, light or auditory stimuli
no eye opening towards painful stimulus to supra-orbital area or nail bed
2) Absence of brain stem function (careful and repeated examinations are necessary)
midposition or fully dilated pupil with absent light reflex
absent corneal reflex (beware of corneal damage due to other causes e.g. corneal
irritation, and eye drops)
absent spontaneous oculocephalic (doll’s eye) reflex
absent oculo-vestibular response (may be difficult due to small neonatal external ear
canals)
absent movement of bulbar musculature:
●
gag reflex: tracheal stimulation by movement of ETT (repeat several times with
observation periods of 10-15 seconds)
●
cough, sucking and rooting reflex
3) Absence of respiratory effort with standardized apnoea test
pre-oxygenate with 100 % O2 while patient is normally ventilated for 10 minutes
disconnect ventilator; 100 % O2 via cannula into endotracheal tube
monitor ABG: +ve test if total apnoea when PaCO2 raises to ≥ 60 mmHg
4) EEG
electrocerebral silence in the absence of serum phenobarbital level > 25
microgram/ml
performed under American EEG Society guideline
62
4) Observation period:
Two full examinations and EEGs performed 48 hours apart
# examples of movement mediated at spinal cord level:
- withdrawal
- decerebrate posture
- complex leg activity
63
Chapter 17 - Neonatal hypocalcaemia
MC Chan, L Leung
Definition:
Term infant: total serum Ca (tCa) < 2 mmol/L (Avery 2005), ionized Ca (iCa) < 1 mmol/L
Preterm infant: total serum Ca < 1.75 mmol/L (taking into account low albumin, acidosis frequently
found in these infants), ionized Ca < 1 mmol/L
Early onset: typically first few days after birth, lowest at 24-48 hours of age
Late onset: end of first week (≥ D7)
Symptoms varied and subtle especially in premature infants: irritability, jitteriness, lethargy, poor
feeding +/- feeding intolerance, abdominal distension, apnea, cyanosis, seizures.
In newborn, Trousseau sign, Chvostek sign and laryngospasm are uncommon.
For sick newborns with cardiovascular compromise or organ insufficiency (e.g. BW < 1kg, severe
RDS, asphyxia, septic shock, PPHN) requiring BP support, it may be desirable to prevent
hypocalcaemia by continuous Ca infusion (4 ml/kg/day), preferably by central catheter to maintain
total Ca > 1.75 mmol/L or ionized Ca > 1.0 mmol/L (Manual of Neonatal Care 5th Ed 2004.)
Management of early-onset hypocalcaemia in preterms
- Severely symptomatic (e.g. seizures): IV 1-2 ml/kg 10% Ca gluconate over 5-10 minutes under
ECG monitor in ICU setting. Maintenance IV infusion with 10% Ca gluconate at 4 ml/kg/day.
- Asymptomatic well preterms: observe, avoid peripheral Ca infusion, may give oral Ca
supplement (usually resolves spontaneously by D3)
- If Ca decreases to 1.65 mmol/L: begin continuous Ca infusion: 4-6 ml/kg/day of 10% Ca
gluconate (1 mmol/kg/day)
IV Ca supplement: treatment risks
- Peripheral extravasation → inflammation and subcutaneous necrosis
- Rapid Ca infusion can cause sudden elevation of Ca, bradycardia or other dysrhythmias, thus
IV Ca should only be “pushed” for hypocalcaemic crisis (e.g. seizures)
- If Ca infused through UVC lodged in portal vein, it may cause hepatic necrosis
10% Ca gluconate
- 0.22 mmol or 9 mg Ca per ml
- pH: 6-8.2; Osmolarity: 700 mOsm/L
- Maximum administration rate: 0.045 mmol/kg/hour (or in neonates max. 0.02 mmol/min). May
be given more concentrated via a central venous line. Undiluted calcium gluconate can be given
in emergency.
64
Early Neonatal Hypocalcaemia in premature infant
tCa < 1.75 mmol/L or iCa < 1.0 mmol/L
Severely Symptomatic
Asymptomatic
IV bolus 10% Ca gluconate
(1-2 ml/kg over 5-10 minutes) then
IV maintenance (4 ml/kg/day)
tCa <or = 1.65 mmol/L
To observe +/- oral
Ca supplement (1 mmol/kg/day
dilute 1:1 with water)
continuous Ca infusion
(10% Ca gluconate 4-6 ml/kg/day)
65
Chapter 18 – Neonatal bacterial meningitis
MT Soo, C Tse, YY Lam, F Poon
Meningitis is present in 10-25% of bacteraemic or fungaemic infants. Up to one third of infants
with meningitis have negative blood cultures. The 2010 CDC-GBS guidelines recommend a lumbar
puncture in every symptomatic infant with suspected sepsis. In our practice, lumbar puncture is
indicated in infants with symptoms / signs suggestive of meningitis, with a positive blood culture,
or a high probability of bacterial or fungal sepsis, or who do not respond to conventional antibiotic
therapy. In late onset sepsis without a definite focus, LP is indicated.
Common causative organisms:
- Early onset: Group B Streptococcus (GBS), Escherichia coli, Listeria monocytogenes, herpes
simplex virus
- Late onset (nosocomial or community acquired): gram negative bacteria
Lumbar puncture - contraindications or precautions:
- Haemodynamic instability, platelet count < 50 x 109/L, raised intracranial pressure
Normal CSF values:
No CSF white cell count rules out bacterial meningitis. LP is completely normal in 2-3% of culture
proven meningitis. A wide range of normal CSF values is quoted by different sources. > 20 white
blood cells/mm3 and/or > 5 polymorphs in a neonatal CSF sample is considered abnormal. Normal
CSF should contain predominantly mononuclear cells, if any. Using the ratio of red cell count to
white cell count in the peripheral blood to adjust the CSF white cell count in a traumatic tap is
controversial.
Treatment:
1) Suggested empirical therapy for bacterial meningitis: ampicillin + cefotaxime or high dose
penicillin/ampicillin + aminoglycoside or cefotaxime + aminoglycoside, or meropenem ±
vancomycin (if resistant gram negative bacteria and MRSA are strongly suspected)
Dosages (from Neofax, version Q2-2014):
Please refer to updated reference in Neofax regularly.
Ampicillin
7 days and younger: 200-300 mg/kg/day IV divided Q8H,
8 days and older: 300 mg/kg/day IV divided Q6H
Cefotaxime
50mg/kg/dose (see dosing interval chart 1)
Penicillin
7 days and younger: 250,000- 450,000 units/kg/day IV divided
Q8H, 8 days and older: 450,000-500,000 units/kg/day IV divided
Q6H
Gentamicin
(see dosing interval chart 2)
Meropenem
40mg/kg/dose; less than 32 weeks GA and less than 14 days
PNA: Q12H; less than 32 weeks GA and 14 days PNA and
older: Q8H; 32 weeks GA and older: Q8H
Vancomycin
15mg/kg/dose (see dosing interval 3)
66
PMA (weeks)
≤ 29
30-36
37-44
≥ 45
PMA (weeks)
≤ 29
or significant asphyxia, PDA,
or treatment with indomethacin
30-34
≥ 35
PMA (weeks)
≤ 29
30-36
37-44
≥ 45
Dosing interval chart (1) - Cefotaxime
PNA = Postnatal (days)
0-28
> 28
0-14
> 14
0-7
>7
All
Dosing interval chart (2) - Gentamicin
Postnatal (days)
Dose (mg/kg)
0-7
5
8-28
4
≥ 29
4
0-7
4.5
≥8
4
All
4
Dosing interval chart (3) - Vancomycin
Postnatal (days)
0-14
> 14
0-14
> 14
0-7
>7
All
Interval (hours)
12
8
12
8
12
8
6
Interval (hours)
48
36
24
36
24
24
Interval (hours)
18
12
12
8
12
8
6
(Ref : Neofax (electronic resource) accessed via eKG on 18 Jun 2014)
2) Consider to repeat lumbar puncture at 48 hours after initiation of effective treatment,
(controversial, not universally practised). Persistence of positive CSF culture may indicate
complications e.g. obstructive ventriculitis, subdural empyema, or multiple small vessel
thrombi.
3) Indications to repeat lumbar puncture in neonates with
- persistent or re-emergent fever
- deterioration in clinical condition
- new clinical findings (especially neurological findings)
- persistently abnormal inflammatory markers
4) In case of persistently positive CSF cultures, or clinical suspicion of neurological complications,
perform cranial ultrasound and/or CT brain with contrast. The choice and dosage of antibiotics
should be reviewed, and rarely intraventricular administration of antibiotic may be considered.
5) Duration of antibiotic for specific organisms
- GBS and Listeria: continue antibiotics for at least 2 weeks;
- GBS: high dose penicillin; if on aminoglycoside, discontinue when clinically stable and
CSF sterilized
- Gram negative bacteria: cefotaxime + aminoglycoside; discontinue aminoglycoside after 2
weeks of CSF sterilization; total duration : at least 3 weeks after CSF sterilization
6) Consider longer duration of therapy under these situations (complicated meningitis): focal
neurological signs at 2 weeks, time to CSF sterilization > 72 hours, obstructive ventriculitis,
infarct, encephalomalacia, brain abscesses etc.
67
7) Watch out for complications
- Early complications: seizure, shock, SIADH with electrolyte disturbance, focal
neurological signs, hydrocephalus, subdural effusion, ventriculitis, abscess, haemorrhage
etc
- Late complications: hearing impairment, cortical blindness, persistent hydrocephalus,
developmental delay, cerebral palsy, epilepsy etc
68
Chapter 19 - Paramortem studies for suspected inborn error of metabolism
MT Soo, L Leung, Phyllis Leung, KP Chan
Specimens should be taken as far as possible within office hours; after-hour lab service regarding
muscle biopsy processing may not be guaranteed. Please liaise with lab beforehand.
Other useful contact: Chem Lab. Reception Desk, PWH: 26322331 (office hours only)
Specimen
1.
Clinician’s action and information
Transport
Test to be done
Test done in
precautions
Blood
a. Exactly 1 ml lactate and
blood in a
pyruvate
trichloroacetic
acid (TCA)
bottle
(available in
ward); using a
pipette for
measurement
is preferred
b.
1 ml blood in ammonia
paediatric
lithium
heparinised
bottle
c.
3 ml EDTA
blood
Chemical
Pathology
Special Lab
(6/F,
YCKMMC,
KWH)
Chemical
Pathology Lab
(5/F,
YCKMMC,
KWH)
send sample to
lab in ice
send sample to
lab in ice
carnitine gene PWH Chemical
DNA studies or Pathology lab
other DNA
studies as
indicated by
other metabolic
results
Contact
KWH Lab action
Clinicians should
contact Chemical
Pathology Lab, KWH
If specimen is received
outside office hours,
centrifuge and separate
supernatant, store
Office hours (Monday supernatant at -20°C and
to Friday: 9 am to 5 pm; send to Chem Lab on the
Saturday: 9 am to 1
next working day.
pm): 35175140 or
35172447
Outside office hours:
35172464 or 35172489
Clinicians should
contact Chemical
Pathology Lab, KWH:
35172464 or 35172489
outside office hours,
centrifuge and separate
plasma, store plasma at
-20°C and send to Chem Lab
on the next working day.
Clinicians will contact Store whole blood at 4°C.
on-call biochemist
Lab will send to PWH
through PWH 26322211 (through G/F Office) on next
working day
69
Specimen
Transport
Test to be done
Test done in
precautions
amino-acids and PWH Chemical
carnitine
Pathology lab
d.
2 x 3 ml
lithium
heparinised
blood
e.
3 ml EDTA
blood
mitochondrial Cheung Sha
DNA analysis - Wan (CSW)
a few common Genetics
point mutations
f.
3-5 ml
heparinised
blood
Chromosomes Cheung Sha
study if suspect Wan Genetics
dysmorphic
syndrome
g.
Dried blood
spot test
Broad spectrum
screening for
metabolic
diseases, in
particular,
aminoaciduria,
urea cycle
defect, organic
acidemia and
fatty acid
oxidation defect
HA hospital
pathology
laboratories,
sent by KWH
Chem Path Lab
70
Contact
KWH Lab action
Clinicians will contact Centrifuge & separate
on-call biochemist
plasma. Store plasma at
through PWH 26322211 -20°C. Lab will send to
PWH (through G/F Office)
in ice box on next working
day.
Store any left over plasma
at -20°°C in the lab in case
more tests are needed for
future studies.
Clinicians will contact Return specimen to ward if
on-call geneticist at
received in lab
97261332. Clinicians
store blood at 4°C in
ward, and send to CSW
on next working day
through Central Porter
Service (clinicians’ clerk
will call them to get
specimen)
Clinicians will contact Return specimen to ward if
on-call geneticist at
received in lab
97261332. Send
immediately through
Central Porter Service.
If not, clinicians will
store blood at 4°C in
ward, and send to CSW
on next working day
through Central Porter
Service (clinicians’ clerk
will call them to get
specimen)
Obtain Whatman filter
paper from KWH Chem
Path Lab (5/F,
YCKMMC, KWH):
35172464 or 35172489
Allow spots to dry for at
least 3 hours. Deliver to
the lab within the same
day. If not achievable,
keep in room temp,
away from sunlight /
moisture, and deliver to
lab within 3 days.
2.
Transport
Specimen
Test to be done
Test done in
precautions
Urine:
organic acids
PWH Chemical
Collect as much as and amino acids Pathology lab
possible in plain
bottle
3.
CSF:
lactate
Collect 300 ul in
sterile plain bottle
(5 drops),
4.
Skin biopsy:
Ensure sterile
technique, full
thickness, put in
sterile bottle filled
with normal saline
skin fibroblast
culture for
future enzyme
essays
Chemical
Pathology
Special Lab
(6/F,
YCKMMC,
KWH)
send sample to
lab in ice
PWH Chemical Transport at
Pathology lab
room temp
Do not freeze
5.
Muscle or liver
for enzyme
Anatomical
biopsy or other
assays as needed Pathology Lab.
tissues requested
KWH
for freezing
procedure (frozen
section service is
NOT available after
office hours)
6.
Postmortem
specimens:
If inadequate blood
taken for DNA
extraction, blood
and spleen tissue
can be taken during
postmortem.
Spleen tissue put in
sterile bottle. No
need to add normal
saline.
Anatomical
Pathology Lab.
KWH
Contact
Clinicians will contact
Dr Nelson Tang at
26322320 or page
on-call biochemist
through PWH 26322211
Clinicians should
contact Chemical
Pathology Lab, KWH
Office hours (Monday
to Friday: 9 am to 5 pm;
Saturday: 9 am to 1
pm): 35175140 or
35172447
35172464 or 35172489
Clinicians should
contact Anatomical
Pathology Lab.
(35175141) during
office hours
35172464 or 35172489
Clinicians will contact
Dr Nelson Tang at
26322320 or page
on-call biochemist
through PWH 26322211
Clinicians should
contact Anatomical
Pathology Lab.
(35175141) during
office hours
35172464 or 35172489
Staff on duty in Stat
Lab. shall put the
specimens and request
form (wrapped in plastic
bags) into -70 °C deep
freezer in 5/F upon
receipt
KWH Lab action
Store at -20°C. Lab will
send to PWH (through G/F
Office) in ice box on next
working day.
outside office hours, store
specimen at -20°C and send
to Chem Lab on the next
working day.
Store any remaining CSF in
Chem Lab at -20°C.
Lab will store at 4°C.
Lab will send to PWH
(through G/F Office) on
next working day.
Staff on duty in Stat Lab.
shall notify AP Lab staff to
collect back the specimen
for examination on the next
working day
(To be performed by
pathologists)
71
Chapter 20 – Bronchopulmonary dysplasia (BPD)
MT Soo, YY Lam
Classification of severity of bronchopulmonary dysplasia:
Grade 1
Supplemental oxygen for ≥ 28 days AND
Mild
- On room air at 36 weeks post-menstrual age (PCA) or at discharge (infants < 32 weeks’ gestation)
- On room air at 56 days or at discharge (infants ≥ 32 weeks’ gestation)
Whichever comes first
Grade 2
Supplemental oxygen for ≥ 28 days AND receiving supplemental effective oxygen < 30% at 36 weeks PMA /
Moderate
discharge (< 32 weeks) or at 56 days / discharge (≥ 32 weeks)
Grade 3
Supplemental oxygen for ≥ 28 days AND receiving supplemental effective oxygen ≥ 30%, or on CPAP, or
Severe
mechanical ventilation at 36 weeks PMA / discharge (< 32 weeks) or at 56 days / discharge (≥ 32 weeks)
Modified from Jobe and Bancalari, Am J Respir Crit Care Med 2001;163:1723-1729.
Radiographic changes are often present but not required in the definition of BPD. Infants treated
with oxygen > 21% and/or positive pressure for non-respiratory disease (e.g. central apnoea or
diaphragmatic paralysis) do not have BPD unless they also develop parenchymal lung disorder and
exhibit clinical features of respiratory distress.
Neurodevelopmental and growth outcomes at 18 to 22 months’ corrected age:
BPD
Mild
Moderate
Severe
Wt <10th%
49.8%
55.2%
62.6%
Growth
Ht <10th%
28.9%
37.9%
46.2%
HC <10th%
21.7%
27.3%
39.4%
% MDI < 70
(mental development index)
25.6%
35.1%
49.8%
Rehospitalization for
pulmonary causes (OR)
1.16
1.61
2.08
Extracted from Ehrenkranz et al, Pediatrics 2005;116;1353-1360
Prevention of BPD
- Avoid intubation, minimize ventilator duration
- Careful ventilation strategy, avoid barotrauma and volutrauma; optimal tidal volume 4-6ml/kg;
accept pCO2 up to 60 mmHg (8 kPa) with pH >7.2 and SaO2 88-95% for < 34 weeks corrected
gestation age
- Vitamin A: ELBW (< 1kg), administered at least 3 times per week at 5,000 units IMI for 4 weeks,
can decrease the incidence of BPD by 7% (NNT 14)
- Caffeine citrate (20 mg/kg loading and 5 mg/kg/day maintenance) started during first 10 days in
infants with birth weight 500-1,250g reduced incidence of BPD from 47% to 36% (CAP trial,
NNT 9). Improved neurodevelopment outcome at 18-21 months in caffeine group as compared to
controlled group is no longer statistically significant at 5 years of age. Caffeine citrate should be
considered for those born before 32 weeks’ gestation, on triggered mode ventilation, or with any
apnoea. It should be given until at least 1 week after last apnoea, or > 34 weeks corrected
gestational age.
- Careful fluid, avoid over-hydration
72
- Systemic steroid reduced the incidence of BPD (caution with associated complications and
increased risk of intestinal perforation especially when combined with NSAIDs); long term
neurodevelopmental effect e.g. cerebral palsy and decreased head growth, needs to be considered;
avoid early use (first 1-2 weeks, especially in the first 96 hours). It may be beneficial in selective
groups with a short course and a minimal dose; needs to be balanced with risk and benefit, and
thoroughly discussed beforehand.
Management of BPD:
General:
- Optimize growth: may require higher caloric content as much as 125% of standard infant caloric
input
- Fluid restriction
- Attention to oxygenation target and CO2 target
Specific:
Prevention of hypoxia:
- Stringent management of oxygenation with a targeted saturation level i.e. > 90% (in > 34 weeks
corrected gestational age) with minimal oxygen support
- Higher PaCO2 is generally acceptable (up to 60 mmHg)
- Consider oxygen reduction test at 36 weeks corrected gestational age if <30% O2 is used.
Oxygen Reduction Test
This test may be considered before O2 is taken off for preterm at gestational age of 36 week (36
+/-1 week) who is currently receiving < 30% O2 supplement with SpO2 > 90% and not noted to
have desaturation during sleep or feeding by nurses.
Part 1: Baseline
Duration: 15 minutes
30 minutes after a feeding
Monitor HR, RR, SpO2, apnoea, bradycardia (< 80 bpm for > 10 seconds)
Record every 60 seconds
Part 2: Reduction phase
Reduce oxygen by 2% every 5 minutes to room air as tolerated
For babies on nasal cannula and O2, reduce flow at rate of 0.5 L/min till flow is 1 L/min and
then decrease with rate of 0.1 L/min till flow is 0.1 L/min. O2 concentration is then reduced
by 20% every 5 minutes, till in room air and the cannula is off
Aim to keep SpO2 90%
Monitor the infant every 60 seconds
Resume baseline oxygen if apnoea (> 20 seconds), bradycardia (HR < 80 bpm for > 10
seconds) or SpO2 between 80-89% for 5 consecutive minutes or SpO2 < 80% for 15 seconds
73
Part 3: Room air observation
Observe the infants for 30 minutes for adverse outcomes (as stated above)
Part 4: Possible outcome
Pass: pass all 3 parts, try off-O2 and observe any problems for next 2-3 days, especially
during feeding or sleeping
Fail: fail either part 2 or part 3 put back on O2
(Extracted and modified from Journal of Perinatology 2003; 23:451-456 and Pediatrics 2004;
114: 1305-1311)
Corticosteroids:
- Systemic steroid regime (use in those who are ventilator dependent > 2 weeks)
(a) “Minidex” regime
Dexamethasone iv 0.05mg/kg daily for 10 days then alternate day for
6 days (Yates and Newell, Arch Dis Child Fetal Neonatal Ed 2011;
96(3): F190-4) – total dose 0.65mg/kg
Consult the attending neonatologist if considering its use
Aim to try extubation after 3 days of steroid; consider to stop steroid
after 3 days if failed
Give topical/nebulized adrenaline if vocal cord oedema present
(b) DART protocol
Dexamethasone iv 0.15mg/kg/day for 3 days, 0.1mg/kg/day for 3
days, 0.05mg/kg/day for 2 days, and 0.02mg/kg/day for 2 days – total
dose 0.89mg/kg
- Ventilated infants receiving inhaled steroids over a prolonged period of time (1-4 weeks) have
been shown to be successfully extubated
Diuretic:
- Evidence does not support the routine use of diuretics, but in some cases these may be indicated
and therapeutic goals may be defined e.g. frusemide may improve lung compliance. However,
chronic use of diuretics may lead to osteopenia and nephrocalcinosis. These drugs should be
taken off if therapeutic goals are not reached.
- Rapid-acting diuretics were shown to decrease the invasive ventilator days and oxygen
requirement in some studies
- Short course diuretic: IV frusemide 0.5-1 mg/kg/day for 3-7 days
- Oral diuretics: hydrochlorothiazide 1-2 mg/kg BD + spironolactone 1-3 mg/kg daily
Bronchodilator:
- May decrease airway resistance
- e.g. salbutamol 2 puffs inhaled QID: therapeutic response in the presence of wheeze or increased
airway resistance
74
Investigational treatment and second line medications for refractory cases: (discuss with attending
neonatologist first)
- Nebulized pentoxifylline for 10 days (days 1-3: 0.25 mg/kg BD; days 4-6: 0.2 mg/kg BD; days
7-8: 0.1 mg/kg BD; days 9-10: 0.1 mg/kg BD; repeat course five days later if needed, until off
ventilator and oxygen independent)
- Intratracheal budesonide 0.25mg/kg in beractant (Survanta) 4ml/kg (repeat doses every 8 hours
until extubation or FiO2 < 0.4)
- Inhaled nitric oxide or oral sildenafil if pulmonary hypertension present
Immunisation etc:
- RSV passive immunization (Palivizumab): 15 mg/kg/dose monthly for 2-5 months (Refer to
Indications for HA funding in Chronic Lung Disease; can prescribe as self-financed item if
indications not met)
- Educate parents on infection control, flu vaccination, hand washing and avoidance of smoking
75
Chapter 21 - High frequency oscillation
DK Ng
Indication:
Failed conventional ventilation, or routine use for RDS requiring surfactant
Frequency:
10-15 Hz
Amplitude:
Large enough to see vibration of the chest wall
Continuous distending pressure:
Oscillate the neonate at optimal continuous distending pressure CDP OPT as listed below.
1. Start the CDP same as the mean airway pressure during conventional ventilation and whatever
FiO2 to keep SpO2 between 86-92%
2. Determine the opening pressure CDPo by increasing CDP 1-2 cm water every 2-3 minutes.
Simultaneously, step down oxygen by 5% as SpO2 goes above 92%. CDPo is achieved when
oxygenation no longer improve and / or FiO2 ≤ 25% (mean 20 +/- 4.3 cm water for RDS) or
significant haemodynamic compromise occurs
3. Decrease the CDP 1-2 cm water every 2-3 minutes until SpO2 drops below 86% or CDP = 6 cm
water. This is the closing pressure CDPc (mean 12 +/- 4.0 cm water for RDS)
4. Recruit the collapsed alveoli again as shown by restoration of SpO2 by stepping up of CDP to
CDPo for 2-3 minutes
5. Set down the CDP at CDP OPT = CDPc + 2 cm water (minimum 6 cm water)
6. Mean CDPOPT is 14 +/- 4.0 cm water for RDS
7. 5-10 minutes after surfactant, repeat steps 3 to 5
76
Chapter 22 – Neonatal narcotic withdrawal
YY Lam
Drug abuse identified antenatally:
Document the substance exposed, dose, last dose
Suspicious case: SGA, IUGR, small head, irritability, jitteriness, convulsion
Differential diagnoses: hypoglycaemia, hypocalcemia, hypomagnesaemia, sepsis, hyperthyroidism,
intracranial bleeding
Preliminary investigations: infection screen, RFT, Ca, Mg, urine for toxicology screen (to QEH),
+/- TFT, cranial USG
Also check maternal HIV, HBV, VDRL +/- HCV status and STD screening
Others: Refer MSW +/- CCDS (Comprehensive Child Development Service)
Treatment:
Supportive
Swaddling, holding, reduce light exposure, minimize excessive noise, avoid unnecessary
handling
Pacifier, frequent diaper changes
Hypercaloric formula, small frequent feeds if poor milk tolerance or weight gain
If no signs of drug withdrawal, Finnegan score < 8 for 2 to 5 days, can discharge home and FU
outpatient for growth, development and social aspects
Drug treatment
Morphine: use in heroin / methadone abusing mother
Preparation: 0.4 mg/mL solution
Indications: seizures, poor feeding, diarrhoea and vomiting resulting in excessive weight loss and
dehydration, inability to sleep, fever unrelated to infection, or Finnegan neonatal abstinence score
≥ 8 for 3 successive scores
Finnegan score
Morphine solution (0.4mg/mL)
8-10
0.32 mg/kg/day divided Q4H (i.e. 0.05 mg/kg/dose or 0.13 ml/kg/dose)
11-13
14-16
17 or greater
0.8 mg/kg/day divided Q4H, (i.e. 0.13 mg/kg/dose or 0.33 ml/kg/dose);
↑0.16 mg/kg/day increment until controlled
Add phenobarbitone to control irritability if morphine solution > 0.8 mg/kg/day
Once an adequate dose is found, and Finnegan score is < 8 for 72 hours, wean by 10% of total dose
every 2-3 days
If weaning results in score ≥ 8, restart the last effective dose
Discontinue morphine when daily dose < 0.12 mg/kg/day (0.02 mg/kg/dose)
Discharge when withdrawal score < 8 for 72 hours
77
Phenobarbitone (Luminal)
Loading 10 mg/kg
May reload 10 mg/kg Q8-12H (until maximum 40 mg/kg) if 3 consecutive scores ≥ 8 or 2
consecutive scores ≥ 12
Cumulative sum of loading doses
Maintenance phenobarbitone (daily dose)
20 mg/kg
5 mg/kg/day
30 mg/kg
6.5 mg/kg/day
40 mg/kg
8 mg/kg/day
Check serum phenobarbitone level:
Before any additional loading dose beyond 30 mg/kg
Before first maintenance dose
If symptom score persistently > 8, or < 4 but overly sedated
Taper by 10% every days after improvement of symptoms and with mean score <8 for 72 hours on
a maintenance dose
If use morphine and phenobarbitone together, morphine should be withdrawn first and the infant
observed for 2 to 3 days
Appendix 1: Neonatal narcotic withdrawal score chart
Appendix 2: Flowchart of management of Narcotic Withdrawal Syndrome
78
Appendix 1: Neonatal Narcotic Withdrawal Score Chart
Paediatric Dept, KWH
Chart at 2 hours after birth, then Q4H at NICU or Q8H at SCBU if total score ≤ 7, preferably 30
minutes to 1 hour after a feed. If total score ≥ 8, inform doctor. If symptoms severe, consider
increase to Q2H in NICU and Q4H in SCBU (step down if stable after 24 hours)
Systems
Signs and Symptoms
CNS
High pitched cry
Continuous high pitched cry
Sleeps<1hr after feeding
Sleeps<2 hr after feeding
Hyperactive Moro reflex
Markedly hyperactive Moro reflex
Mild tremors disturbed
Moderate/severe tremors disturbed
Mild tremors undisturbed
Moderate/severe tremors undisturbed
Date/
Time
Score
2
3
3
2
2
3
1
2
3
4
Increased muscle tone
2
1
3
5
1
1
2
1
1
1
1
2
1
2
1
2
2
3
2
3
Excoriation (specify area:_______)
Myoclonic jerks
Generalized convulsions
Metabolic
Vasomotor
Respiratory
Sweating
Fever <39.3oC
Fever >39.3oC
Frequent yawning (> 3-4 times/interval)
Mottling
Nasal stuffiness
Sneezing (> 3-4 times/interval)
Nasal flaring
GI
RR > 60/min
RR > 60/min with insucking
Excessive sucking
Poor feeding
Summary
Regurgitation
Projectile vomiting
Loose stools
Watery stool
Total score
Scorer’s initial
Status of therapy
(drug / dosage)
Guide to assessment and scoring can be found in department web
(Ref : Modified from Finnegan Neonatal Drug Withdrawal Scoring System)
79
Appendix 2 Neonatal Narcotic Withdrawal Score Chart
80
Chapter 23 – Normal Range of Neonatal Haematological Values
MT Soo
A. Reference ranges of common coagulation tests
Gestational age
<28 weeks
28-34 weeks 30-36 weeks Term infants
Reference range – PT(s)
> 21
> 21
> 16
> 16
95th centile
Reference range – aPTT(s)
> 64
> 57
> 55
> 55
95th centile
Fibrinogen level
0.71-5.35
0.87-4.70
2.25-3.41
1.50-3.73
(5th-95th centile, g/dL)
Reference ranges are taken from the Christensen et al paper for neonates <34 weeks gestation
and from the Andrew et al paper for those 30-36 weeks’ gestation and term infants.
(Ref : Arch Dis Child Fetal Neonatal Ed 2015;100:F270-F274)
B. Neutrophil count
Normal values (5th centile to 95th centile), from Schmutz (2008)
Neutrophil
count (x109/l)
>36 weeks
28-36 weeks
<28 weeks
At delivery
3.5-18.0
1.0-10.5
0.5-8.0
Time of peak
(hours after birth)
8 hours
6 hours
24 hours
At peak
7.5-28.5
3.5-25.0
1.5-41.0
At 72-240 hours
(3-10 days)
2.7-13.0
0.8-12.5
1.3-15.3
Neutrophil count during first 72 hours of life of term and near-term (>36 weeks gestation)
neonates
81
Neutrophil count during first 72 hours of life of 28- to 36-week gestation preterm neonates
Neutrophil count during first 72 hours of life of <28-week gestation preterm neonates
(Ref : Schmutz N et al. Expected ranges for blood neutrophil concentrations of neonates: the Manroe and
Mouzinho charts revisited. Journal of Perinatology 2008; 28, 275–281)
82
Section 2: Respiratory System
83
Chapter 24 - Allergic rhinitis
DK Ng
Definition: recurrent nasal symptoms of sneezing, discharge, itch and blockage in an atopic
child, i.e. concomitant asthma +/- eczema +/- urticaria +/- allergic conjunctivitis with either
elevated IgE or positive skin prick test
Severity (graded by ARIA guideline)
Intermittent
< 4 days/week
Persistent
≥ 4 days/week
or
< 4 consecutive weeks
and
≥ 4 consecutive weeks
Mild: none of the following items are present:
Sleep disturbance, Impairment of daily activities, leisure and/or sport, Impairment of school or
work, Symptoms present but not troublesome
Moderate/severe: one or more of the following items are present:
Sleep disturbance, Impairment of daily activities, leisure and/or sport, Impairment of school or
work, Troublesome symptoms
Differential diagnosis:
Subacute rhinosinusitis (headache, decreased smell or taste, halitosis)
Foreign body (unilateral)
Investigations:
-Nasal smear for eosinophil (abnormal if > 4%), +ve skin prick test,↑IgE, Normal sinus X-ray
Treatment: - Allergen, irritant avoidance 1.5% NaCl nasal lavage
- 2nd generation antihistamine: Cetirizine or loratadine
- Intranasal steroids, i.e., for >=2yrs old: fluticasone furoate (Avamys),
mometasone (Nasonex); for >=6yrs old: budesonide (Rhinocort aqua) or
beclomethasone (Beconase aqua) or ciclesonide (Omnaris)
Mild intermittent
2nd generation oral
antihistamine PRN
(1st 2 rows are the usual preferred treatment)
Moderate to severe
Moderate to severe
Mild persistent
intermittent
persistent
Intranasal corticosteroid +
PRN short course
Intranasal corticosteroid
2nd generation oral
(2-4wks) intranasal or regular 2nd generation
antihistamine or
corticosteroid
H1 blocker
montelukast
1st generation oral
antihistamine PRN
(before sleep)
Oral antihistamine
PRN
Oral antihistamine PRN
If poor control, consider
sublingual immunotherapy
for those sensitive to
aeroallergens – contact
Respiratory team
Please chart allergic rhinitis diary to monitor progress
84
Chapter 25 - Bacterial tonsillitis
E Chan
Symptoms:
High fever, sore throat, pain on swallowing.
Signs:
Tonsils – inflammed with exudate
Solitary cervical lymph node with tenderness
Hoarseness
If there is respiratory distress, consider other diagnoses
Test:
Throat swab for culture, rapid test if available, other test - Blood for ASOT
Treatment:
Antipyretics + hydration
Penicillin V 30 mg/kg/dose PO BD, max 1 gram BD for 10 days if suspected / confirmed
bacterial (GAS) tonsillitis
Complications:
Rheumatic fever, post streptococcal glomerulonephritis, quinsy, retropharyngeal abscess
Retropharyngeal abscess
Symptoms: very poor feeding, toxic, stridor, marked neck swelling, pharyngeal swelling,
torticollis
Organisms: Streptococcus pyogenes, Staphylococcus aureus, Haemophilus influenzae,
Bacteroides, Peptostreptococcus, Fusobacterium, Streptococcus milleri
Investigations: Pre-vertebral soft tissue shadow by lateral neck Xray: > 7 mm at C2 or > 14 mm
at C6 for children, > 22 mm at C6 for adult suggestive of retropharyngeal
abscess.
CT neck with contrast is done for confirmation, although differentiation between
retropharyngeal abscess and retropharyngeal cellulitis can be difficult at times.
Need to seek surgical opinion.
Antibiotic:
Clindamycin (broader coverage for anaerobe), and
Amoxycillin / clavulanate (better gram negative coverage)
85
Chapter 26 - Common cold (URI)
E Chan, DK Ng
Common cold – a short, usually mild illness in which upper respiratory and nasal symptoms,
such as runny nose, are the most frequent (the so-called Kleenex sign).
Diagnosis:
If there is respiratory distress, this is not common cold.
For patients with a relative long history of cough and runny nose, consider other causes like
allergic rhinitis, subacute rhinosinusitis.
Investigations:
Consider CBC and CXR if other differential diagnosis strongly suspected
Causes:
Rhinoviruses & RSV account for the majority of common colds
Others – influenza A, B; adenovirus; parainfluenza; RSV; enterovirus; coronavirus; C.
pneumoniae; M. pneumoniae; pneumococcus; H. influenzae; M. catarrhalis
Treatment:
1. Antipyretics – paracetamol 10-15 mg/kg/dose Q4H PRN if temp ≥ 38.5°C and no more
than 60 mg/kg/day
2. Adequate hydration
3. Nasal drops – infants and young children: 0.9% NaCl nasal drops for nasal blockage
4. Nasal decongestant – i.e. 0.5% Ephedrine nasal drops, not recommended for use in young
children with the common cold. It is moderately effective for the short term relief in adults,
while there is no evidence available to show benefit after repeated use over several days.
5. Antihistamine – chlorpheniramine – caution in < 2 years old, 2-5 years old 1 mg tds, 6-11
years old 2 mg tds (not > 12 mg/day). Beware of CNS depression and thickening of
bronchial secretion.
6. Cough suppressant – not recommended
86
Chapter 27 - Childhood pneumonia
E Chan
Definition:
Infection of the lung parenchyma
Diagnosis:
Clinical presentation: fever, tachypnoea, respiratory distress, ↓ chest expansion, percussion
dullness, bronchial breath sound, crackles, ↑ vocal resonance
CXR: Air space consolidation: homogeneous opacities of lung parenchyma; or interstitial
infiltrate or both.
Severity (for 28d – 59m old)
Very severe: not able to drink, central cyanosis (consult PICU)
Severe: lower chest in-drawing
Moderate severe: >50 breaths/min (age 2-11m), >40 breaths /min (age 12-59m)
Diagnostic specimens:
Sputum culture (induced or otherwise) – specimen not appropriate for culture if WBC<10 per
low power field and squamous epithelial CELL >25 per low power field
Induced sputum (by nebulized normal saline or hypertonic saline as required)
NPA for viral immunofluorescence/PCR
Blood culture (positive yield < 2.7%), indicated in cases that require IVI antibiotic
CBP/DC and CRP
BAL if not responsive to treatment, recurrent pneumonia, suspected unusual organisms,
suspected aspiration
Common causative agents and initial treatment:
Birth to D20:
GBS, gram negative enteric bacteria, Listeria monocytogenes, TORCH
(usually part of systemic infection)
Treatment:
i.v. penicillin and gentamicin or augmentin and gentamicin
3 weeks to 3 months:
RSV, parainfluenza, Chlamydia trachomatis, pneumococcus,
Staphylococcus aureus, Bordetella pertussis
Treatment: If afebrile, oral azithromycin 10mg/kg daily for 5 days (cover for pertussis)
If febrile or in distress, add i.v. augmentin (5:1) 30 mg /kg q12 h, i.e. amoxicillin 25mg/kg/dose,
or cefotaxime
4 months to 4 years:
Usually viral (RSV, influenza, parainfluenza, adenovirus, rhinovirus),
Treatment:
Likely viral cause: supportive treatment
Likely bacterial (most likely pneumococcus, non-typable H influenza, M.Catarrhalis ). If not ill,
oral augmentin (Table 1). If ill, i.v. augmentin (5:1) at 90 mg/kg/day, i.e. amoxicillin
75mg/kg/day+clavulante 15mg/kg/day
87
Table 1: Oral augmentin regime for pneumonia in children >=3 months
`Pathogens
Empirical
Strep. pneumoniae
Haemophilus
infuenzae
Moraxella
Catarrhalis
Augmentin preparation
475mg/5ml(7:1)
Amoxicillin
(Max.1,750mg)
90mg/kg/day
(TDS)
Amoxil alone at
90mg/kg/day
TDS
40mg/kg/day
BD
40mg/kg/day
BD
Clavulanate(max. 250mg)
12.9mg/kg/day
6.4mg/kg/day
6.4mg/kg/day
Use of mega-dose penicillin in pneumococcal pneumoniae
The MIC for resistant pneumoccus (non-meningitis) is different between PO (<2) and IV
(<8) penicillin meaning high dose IV penicillin can be prescribed to overcome PO amoxil
treatment failure. [high dose IVI penicillin 300,000unit/kg/day (divided into 4-6doses;
adult: 3 million units Q4H) or IVI ampicillin 300mg/kg/day (divided into 4-6doses)]
5 to 15 years:
Walking pneumonia-most likely Mycoplasma pneumonia, Chlamydia
pneumoniae
Pneumonia with systemic inflammatory response syndromeStreptococcus pneumoniae, H. influenza, M. catarrhalis
Treatment for walking pneumoniae : oral Azithromycin 10mg/kg/day for 3 days (max: 500mg
per dose) Note: watch out for co-morbid bacterial infection and/or macrolide resistant
moderate/severe mycoplasma; observe clinical response accordingly, if required, get relevant
sample for culture, mycoplasma PCR study for resistant strain (need special arrangement with
microbiologist/DH); Treatment for pneumonia with SIRS: add i.v. augmentin for ill patients.
For macrolide resistant moderate/severe mycoplasma pneumonia, quinolone or doxycycline
(for>8 years old, 2.2mg/kg/dose BD, up to 100mg BD)
Duration of treatment = usually 10 days in uncomplicated cases
FU for clinical resolution +/- CXR resolution
Recurrent pneumonia:
> 2 episodes of pneumonia in 1 year or > 2 in any time frame
Refer to respiratory team for further investigations
88
Chapter 28 - Chronic cough
E Chan, DK Ng
Definition: cough lasting for > 3 weeks.
Causes: active or passive smoking, asthma, gastroesophageal reflux, post nasal drip, habit
cough, foreign body aspiration, congenital lung anomalies, tic
Infancy
Early childhood
Post viral
GERD
Asthma
Infection
Persistent bacterial bronchitis
Congenital malformation
GERD
Congenital heart disease
Passive smoking
Passive smoking
UACS(PND)
Environmental pollution
Foreign body
Asthma
Bronchiectasis
Chronic cough can be due to multiple causes
Late childhood
Asthma
UACS(PND)
Smoking
TB
Bronchiectasis
GERD
Habit cough
Tic
History
Look for characteristics of cough, environmental factors, other associated symptoms, family
history, and history of exposure to infectious disease, drug history
1. Nocturnal cough, precipitated by cold air, exercise, aerosols – asthma 56% positive
predictive value (ppv)
2. Throat clearing, nasal discharge, previous sinusitis – post nasal drip or upper airway
cough syndrome 52% ppv
3. Dyspepsia, cough worse after meals – GERD 40% ppv
Most important environmental factors – smoking or passive smoking
History of wheeze, family history or personal history of atopy – likely asthma
Mostly wet cough: think of Persistent bacterial bronchitis (PBB: +ve sputum culture and normal
CXR), bronchiectasis
Any history of TB / sick contact
Upper airway cough syndrome(UACS): Cough due to upper airway irritation by post nasal drip
(PND)
GERD
Investigations**
Drug – any ACEI
Depend on history and physical exam
May need multiple / sequential investigations to find causes of cough
Treatment
Treat accordingly
If cough not resolved, check compliance to medication, review diagnosis from time to time.
Beware of multiple causes of cough that mandate simultaneous treatment
** refer to flow chart
89
Chronic cough, avoid passive smoking
History, physical exam, spirometry, CXR
with BD challenge
Suspected underlying airway/ear pathology
Observe x
total cough
duration of
10 weeks
No
Cough >
10 weeks
or severe
cough
Yes
Investigate and
treat accordingly
No
Yes
Recent viral illness
Resolve
No
Yes
Resolve
No
No
Yes
Manage accordingly
Nasal smear x eosinophils
CBP D/C, IgE, skin test, FeNO
Airway resistance (IOS)
Spirometry with challenge (exercise
if history of exercise intolerance/
otherwise methacholine or
mannitol); bronchodilator response
PFR/FEV1 diurnal variability
Induced sputum x eosinophil,
neutrophil, C/ST
Empirical Rx
Resolve
Abnormal
tests
Treat
accordingly
No
Likely asthma /
allergic rhinitis/
PBB / Habit cough
Yes
Yes
Resp clinic
Investigations
(individualized
clinically)
Investigation for atopy /
infection
24 hour pH study / OGD
impedance / CT
paranasal sinuses
Bronchoscopy / VFSS
Repeat CXR / HRCT
thorax
Mantoux test
If abnormal
Treat
accordingly
No
Co-morbid psychosocial conditions
Yes
Tests normal
No suspicious organic causes
No
Yes
Refer CP or MSW
For case
conference
No
Resolve
Yes
Cure
90
Chapter 29 - Acute asthma
E Chan, DK Ng
Initial assessment of severity
Speech
Alertness
Accessory muscles
and suprasternal
retractions
SpO2%
(in room air)
Mild
Moderate
Severe
Sentences
May be agitated
Phrases only
Usually agitated
Words only
Usually agitated
Usually not
Usually
Usually
> 95%
91-95%
< 90%
Respiratory arrest
imminent
Drowsy or confused
Paradoxical chest wall
movement
Continuous
bronchodilator
Contact senior/PICU immediately
treatment and
Management
Continuous neb
steroids
Give steroids
Consider PICU
admission
Hypercapnia (hypoventilation) develops more readily in young children than in adults and
adolescents.
Inhaled
bronchodilator x 3,
Consider systemic
steroids for those
on ICS
For tracking of progress of asthma
Clinical Asthma Score (Ref : Van Der Windt DA,
Nagelkerke AF, Bouter LM, et al. Clinical scores for acute asthma in pre-school children: a
review of the literature. J Clin Epidemiol 1994;47:635-646)
Score= 0
Score= 1
Score= 2
Absent or Mild
Moderate
Severe
Respiratory Rate
24 to 36 months
<35
35-55
>55
3 to 6 years
<30
30-50
>50
> 6 years
<20
20-40
>40
O2 Requirement to keep sat ≥ 93%
FiO2
0.21
0.22-0.35
>0.35
18 to 35 months
LPM- N/C
0
>2
≤2
FiO2
0.21
0.22-0.35
>0.35
3 to 6 years
LPM- N/C
0
>3
≤3
FiO2
0.21
0.22-0.35
>0.35
> 6 years
LPM- N/C
0
>4
≤4
Mild
Moderate
Severe
Dyspnoea
Mild
Moderate
Severe
WOB
Mild
Moderate
Severe
Wheezing
Mild
Moderate
Severe
Cough
Total (out of 12)
91
Dyspnea
Mild (Score =0)
Toddler normal speech
Child speaks in complete sentences
Wheezing
Mild (Score =0)
Breath sounds clear or coarse with good air
entry
Moderate (Score =1)
Toddler crying
Child speaks in phrases or partial sentences
Moderate (Score =1)
Inspiratory and/or expiratory wheeze
Absent wheeze but moderate dyspnea and/or
work of breathing
Mildly decreased air entry
Severe (Score =2)
Toddler no cyring
Child speaks in single words or short phrases
Severe (Score =2)
Breath sounds nearly inaudible
Air entry markedly decreased
Absent wheeze but severe dyspnea and/or
work of breathing
Work of Breathing
Mild (Score =0)
No retractions or mild intercostal retractions
Cough
Mild (Score =0)
No or mild cough.
Moderate (Score =1)
Moderate intercostal retractions
Moderate accessory muscle use
± Nasal flaring
Moderate (Score =1)
Frequent dry, tight, or hacky cough without
loss of breath
Severe (Score =2)
Severe intercostal retractions
Severe accessory muscle use
Nasal flaring
Severe (Score =2)
Frequent dry, tight, or hacky cough with loss
of breath
CAS Initial Treatment Guide
>8=
Contact senior/PICU immediately
Continuous neb
Give steroids
6-8 =
Continuous bronchodilator treatment and steroids
Consider PICU admission
4-5 =
Inhaled bronchodilator q 20 min x 3,
Give steroids
2-3 =
Inhaled bronchodilator q 30 min x 2,
Consider steroids
0-1 =
Inhaled bronchodilator
x1
92
MDI
Salbutamol
– Using pMDI + spacer provides equivalent bronchodilatation with a more rapid
onset and fewer side effects compared to nebulizedβ2-agonists
Dosage: 8 puffs (up to 12 puffs can be given) Q15min to Q4H depending on severity
Ipratropium bromide
– Use with B2 agonist
– Dosage: 4 puffs Q6H
Corticosteroids
– Should be given in moderate to severe cases
– Prednisolone 1-2 mg/kg/day in single or 2 divided doses for 3-5 days (50 mg
/day max)
– iv methylprednisolone 1 mg/kg Q6H (max 40mg/day) for 2 days followed by
prednisolone for 3 days
– Oral preparation is as effective as parenteral route
– Early concomitant use of inhaled corticosteroid provide an earlier steroid effect
Leukotriene Modifiers
In severe attack, continuous nebulized salbutamol
• Dosage: 0.5 mg/kg/hour (up to ~10mg over 1 hr)
• 0.1% nebulized salbutamol solution = 1 mg/ml
• Option 1. Consider put on CPAP/NIV if not intubated, give the neb via the in-limb of
ventilator circuit; ultrasonic nebulizing device via in-limb of ventilator circuit; output:
12ml/hr, ie, for a 30kg child, 10mg salbutamol (10ml) + 2ml normal saline (instill 3ml
into the device and infuse med at 12ml/hour into the device by syringe pump)
• Option 2. Continuous Neb via Vent-stream nebulizer (7-8 L/m), output: 20ml/hr, ie, for
a 10kg child, 5mg salbutamol (5ml) + 15ml normal saline (instill 5ml into vent stream
device and infuse med at 20ml/hr into the device by syringe pump)
IVI Magnesium sulphate
– Potent bronchodilator acting on the bronchial smooth muscle
– Used in severe cases and in PICU
– Dosage: (50) mg/kg (max 2 gram) infusion over 20 mins followed by 30mg/kg
/hour to keep serum Mg level 1.5-2.5 mmol/L.
93
– Under PICU monitoring
• 49.3% MgSO4 = 2,470 mg / 5 ml vial
• diluted with D5 or H2O 60mg/ml (max conc. 200 mg/ml) infused over
20 minutes, max 125 mg/kg/hour
e.g. 15kg pt: prescribe 600mg MgSO4 IVI over 20 mins
(dilution: 49.3% MgSO4 4ml + 29ml D5 = 59.9mg/ml) infuse 10ml
over 20 min
Avoid anti-histamines
Mucolytic drugs have no established role
Chest physiotherapy has no proven value
Antibiotic only if there is strong evidence to suggest bacterial infection
Use of CPAP & Non-invasive ventilation
Start with CPAP of 5 cmH2O, clinically check for expiratory breath sound and wheeze;
gradually titrate up CPAP to attain good expiratory breath sound and decrease loud wheeze
(from experience, up to 7-10cmH2O for kids, 10-12cmH2O for teenagers)
If poor response intubate electively by flexible bronchoscope with Ketamine sedation. If
bronchoscopy is not available, intubate with Ketamine/Suxamethonium +/- Atropine &
micro-cuff ET tube. If plastic bronchilitis is seen, remove with 0.9% NaCl / 8.4% NaHCO3
(ratio 4:1). Chest compression is often necessary to remove air trapping after intubation.
To reduce air trapping, pre-oxygenate, disconnet from ventilator circuit for 30-60 seconds
hourly with firm chest compression.
Pre-discharge planning:
Acute asthma pre-discharge planning
1.
2.
3.
4.
5.
6.
7.
8.
Grading of severity of asthma by clinical features and spirometry and start preventive
medications as per current protocol
Perform SPT if not done before to confirm atopy
Look for other concomitant atopic diseases and treat accordingly
Started inhaled corticosteroid if patient requires systemic corticosteroid during admission
unless parental objection
See Asthma Nurse for education
Asthma diary and action plan
Refer to general paediatric clinic or respiratory clinic for follow-up as appropriate
Book relevant lung function tests
94
Chapter 30 – Ambulatory care of asthma
E Chan, DK Ng
Children with asthma usually presented with recurrent cough, wheezing, chest tightness or
shortness of breath. Asthma is a chronic airway inflammation and the airway is
hyper-responsive, causing reversible airway obstruction when airway is exposed to various risk
factors. The patient is usually atopic with other co-morbid allergic diseases, positive skin prick
test to aeroallergen and/or elevated IgE.
Local prevalence: 13-14 years old: 10.2% in 2002
Initial assessment: classify severity of asthma
Table 1. Severity of Asthma (to be filled in during the first visit) – start prophylaxis if ≥ step 2
Severity of Asthma
Daytime Symptoms** - Wheeze,
Nighttime
Lung Function
coughing bout, SOB
Symptoms
STEP 5
Continual symptoms
Frequent
FEV1 or PEF ≤ 60%
Severe
Limited physical activity
predicted
Frequent exacerbations
Persistent
PEF variability >
30%
> 1 time a week FEV1or PEF > 60%
STEP 4
Daily symptoms
Moderate
Daily use of inhaled short-acting
to < 80% predicted
β2-agonist
PEF variability >
Persistent
Exacerbations affect activity
30%
Exacerbations ≥ 2 times a week;
may last days
STEP 3
Symptoms > 2 times a week but > 2 times a month FEV1or PEF ≥ 80%
Mild Persistent
< 1 time a day
predicted
Exacerbations may affect activity
PEF variability
20-30%
STEP 2
Symptoms ≥ 1 time a month but ≥ 1 time a month FEV1or PEF ≥ 80%
Frequent
predicted
≤ 2 times a week
Episode
PEF variability <
Asymptomatic and normal PEF
20%
between exacerbations
Exacerbations brief (from a few
hours to a few days); intensity
may vary
STEP 1
Symptoms < 1 time a month
< 1 time a month FEV1 or PEF ≥ 80%
Infrequent
Asymptomatic and normal PEF
predicted
Episode
between exacerbations
PEF variability <
Exacerbations brief (from a few
20%
hours to a few days); intensity
may vary
Asymptomatic No troubling cough
No sleep
Ditto
No SOB
disturbance
No wheeze
Normal exercise tolerance
95
Assess level of control during follow-up (Table 2)
Check patient’s medications and compliance
Review exposure to risk factor. ie, passive smoking, smoking, house dust mites: any
regular cleaning of beddings with water > 55°C, any curtain, carpet, incense burning
Look for any co-existing allergic conditions like allergic rhinitis or infections like sinusitis.
For any exacerbation, take note of duration and amount of bronchodilator used
For those with isolated genuine exercise induced asthma, start prophylaxis if EIA symptom
>=1 per week
Table 2. Level of control
Characteristic
Daytime
symptoms
Nocturnal
symptoms/
awakening
Need for
reliever/ rescue
medication
Limitations of
activities
Lung function
(PEF or FEV1)
Controlled
(all of the following)
Partly Controlled
(any measure present in
any week)
None (≤ 2/week)
> 2/week
None
Any
> 3 features of
partly controlled
asthma present in
any week
None (≤ 2/week)
> 2/week
None
Any
Normal
< 80% predicted or
personal best (if known)
None
One or more / year
One in any week
Consider step down
after 3-6 months
Consider step up after
3-6 months
Step up
Exacerbations
Rx direction
Uncontrolled
Table 3. Treatment Steps
Start with ICS or LTA
uncontrolled
ICS + LABA
or
ICS + LTA
uncontrolled
↑ICS + LTA + LABA
controlled
Grand Round
96
Severe asthma for patients >= 6-year (for resp grand round)
Definition
“Asthma” requiring treatment according GINA steps 4-5 for previous year, i.e. high dose
inhaled steroids + LABA +/- LTRA/theophylline OR.
“Asthma” requiring oral steroids for >50% of previous year.
Above medications needed to maintain control or uncontrolled asthma despite all of the
above.
May consider trial of systemic steroid for a period to demonstrate the bronchoconstriction
is revesible as below
Systemic steroid trial:
Prednisolone, 0.5-2 mg /kg /day (40mg max) for 2 weeks
If FEV-1 not increase by 15%, double for 2 more weeks (80 mg max)
If effective, taper to the minimum level of systemic steroid required
Triamcinolone 20-60 mg imi every 4 weeks at gluteal region
Step up if partially controlled or uncontrolled despite good compliance and technique with
medications and environmental control. (Beware of contribution from co-morbid conditions
like allergic rhinitis, rhinosinusitis and alternative diagnoses, like foreign body, bronchiectasis).
Step down if controlled > 3-6 months (may take into account of other factors)
You may consider various lung function tests, i.e. spiromety / airway resistance studies with /
without challenge / bronchodilator and FeNO assessment to give an objective assessment of the
degree of control in lung function and airway inflammation.
Difficult-to-treat asthma: ~5% of asthma cases
Definition: symptoms interfering with daily living despite long-term treatment with inhaled
corticosteroids in high doses
Causes of difficult-to-treat asthma:
Common: Adherence issues, Psychosocial issue, Environment (indoor and outdoor allergens
and irritants, eg, tobacco smoke, NO2), cultural practices
Wrong Dx of asthma, DDx: Hyperventilation, Vocal cord dysfunction,
Gastroesophageal/supraesophageal reflux disease, Restrictive lung disease, Sleep apnea,
Bronchiectasis, Endobronchial lesions, PCD, congestive heart failure
Co-morbid condition that worsen asthma: Gastroesophageal/supraesophageal reflux disease,
Allergic rhinitis, Chronic rhinosinusitis, Hyperventilation, Endocrinopathies (eg,
hyperthyroidism, carcinoid syndrome), Allergic bronchopulmonary aspergillosis,
Aspirin-exacerbated respiratory disease, Churg-Strauss syndrome/other vasculitis
Genuine impaired effect of medication (rare)
Beta 2 agonist: genetic polymorphism that results in homozygosity for arginine (Arg/Arg),
rather than glycine (Gly/Gly), at amino acid residue 16 of the β2-adrenergic receptor
97
Inhaled corticosteroid: smoking and/or passive smoking may impair the effect of inhaled
corticosteroid; Glucocorticoid receptor anomalies: (1) genetically determined CS insensitivity
through mutations in the glucocorticoid receptor (GCR) gene, (2) altered expression of GCR
splice forms associated with CS insensitivity, (3) post-translational modifications of the GCR (4)
conditions with decreased GCR binding affinity, (5) changes in regulation of CS-responsive
genes, (6) altered CS metabolism
LTRA: Lima and co-workers showed that a series of DNA sequence variants in the promoter
regions of the arachidonate 5-lipoxygenase (ALOX5) gene were associated with a decreased
response to montelukast and an increased risk of exacerbations
Low, medium and high daily doses of inhaled corticosteroids (mcg)
(GINA, April 2005)
Adults and adolescents
Inhaled corticosteroid
Low
Medium
High
Beclometasone dipropionate (CFC)
Beclometasone dipropionate (HFA)
Budesonide (DPI)
Budesonide (nebules)
Ciclesonide (HFA)
Fluticasone propionate (DPI)
Fluticasone propionate (HFA)
Mometasone furoate
200-500
100-200
200-400
>500-1000
>200-400
>400-800
>1000
>400
>800
80-160
100-250
100-250
110-220
>160-320
>250-500
>250-500
>220-440
Triamcinolone acetonide
400-1000
>1000-2000
98
Children 6-11 years
Low
Medium
High
>320
>500
>500
>440
100-200
50-100
100-200
250-500
80
100-200
100-200
110
>200-400
>100-200
>200-400
>500-1000
>80-160
>200-400
>200-500
≥220-<400
>400
>200
>400
>1000
>160
>400
>500
≥440
>2000
400-800
>800-1200
>1200
Chapter 31 - Acute bronchiolitis
E Chan, D Ng
Bronchiolitis: usually in children <3yrs old, caused by diffuse airway obstruction in the small
bronchi and bronchioles
Aetiology:
RSV, Parainfluenza, influenza, adenovirus, rhinovirus
Co-infection: Chlamydia trachomatis or Mycoplasma pneumoniae
History:
Cough, difficult breathing
Feeding: Poor feeding, choking or vomiting
Sleeping: irritability / unable to sleep through the night
Cyanosis in young infant
Examination:
Hydration status, Respiratory rate, Signs for respiratory distress (insucking / use of
accessory muscles), bilateral expiratory wheeze +/- creps, Modified CAS score, SaO2;
Apnoea in young infant (consult PICU)
Modified CAS Score:
Score points
SpO2
Wheezing
Accessory
Muscle Use
Inspiratory
BS’s
CNS
0
95+ in RA
None/end
expiratory
None
Normal
Normal
1
<95 in RA
Entire
expiratory
phase
Unequal
Altered
mental
status/
agitated
2
<95 with
FiO2 30%
Expiration &
inspiration
Decreased
Depresse
Substernal,
subcostal,
intercostal,
nasal flaring
Supraclavicular,
paradoxical
respiration
1-2: Mild, 3-5: Moderate, >5: Severe
Risk Factors:
Boys, Low birth weight, Low socio-economic class, Crowded living condition, Parental
smoking, Absence of breast-feeding (IgA in colostrum is protective)
Investigation:
CXR – hyperinflation (CXR not routinely indicated in afebrile child)
NPA for viral IF
Watch out for SIADH
99
Asthma Predictive Index (for children < 3 years old)
Major criteria
Minor criteria
Parental history of MD diagnosed asthma Allergic rhinitis
Wheezing without infections
Eosinophilia ≥ 4%
Loose criteria:
any wheeze in first 3years of life + one major or 2 minor criteria
Stringent criteria: ≥ 3 wheezes in first 3 years of life + one major or 2 minor criteria
Prediction of asthma at 6-13 years old:
Loose
–
sensitivity 42%, specificity 84%, PPV 59%, NPV 73%
Stringent
–
sensitivity 15.7%, specificity 97%, PPV 76%, NPV 68%
Other predicting factors: allergy to house dust mite: OR = 3.23
documented airway hyper-responsiveness: OR = 4.94
Management:
Treatment of acute attack
Oxygen supplement up to FiO2 40% to maintain awake SpO2≥95%
Consider high flow humidified nasal cannula oxygen started at max 8 L/min with FiO2 max
40% in moderate cases and take capillary gases (if >=normocapnea, consult PICU), Tube
feeding or IV fluid if poor feeding affects hydration
Bronchodilators (experience based, need to check individual response) – see Flow Chart
Consider systemic steroid or high dose inhaled corticosteroids (e.g. fluticasone propionate
1,000 mcg/day) in those with severe attack
Treatment
If wheeze present
↓
Trial of ipratropium bromide (atrovent) 4 puffs through aerochamber
↓
Reassess 1/2 hour later
↙
↘
Not useful
Useful,
Then Q6H prn + check wheeze Q6H
Trial of salbutamol (ventolin) 4 puffs through aerochamber
↓
Reassess 20mins later
↙
↘
Not useful
Useful, then Q4H prn + check wheeze Q4H
↓
↗
Trial of 3% hypertonic saline Neb 4ml (consider to use with bronchodilator)*
↓
Trial of 1 : 1,000
Adrenaline (nebulized)*
(0.5 ml/kg, max 3 ml) – mixed up to total 4ml with NS
↓
If not useful,
↘
useful, Q4H prn for wheeze
Significant respiratory distress (e.g. score >5) or requiring frequent inhaled medication (ie, Q1H)
↓
To PICU for NIV
100
*If pt has partial response to 3% saline & adrenaline, consider 1.5mg 1:1000 adrenaline + 2.5ml
3% saline Neb
Management options in recurrent cases, i.e., PRN 1-2wks montelukast; ICS (fluticasone
100mcg BD or equivalent)
Preventions of RSV infection: Consider Palivizumab in infant with other risk factors
(prematurity, chronic lung diseases, heart diseases)(consult resp team)
101
Chapter 32 – Sleep-disordered breathing (SDB)
DK Ng, E Chan
Definitions:
1) Primary snoring
- Snoring without any abnormalities, i.e. apnoea, hypoventilation, hypoxaemia,
hypercarbia, sleep disturbance and daytime symptoms
2) UARS
- AHI < 1 with daytime symptoms and paradoxical breathing
3) OSAS
- AHI > ULN
4) Obstructive hypoventilation
- PaCO2 > 50 mmHg > 25% of TST
Normal Values
Parameters
Reference values
Comment
≦1
AASM
≦0.4
Traeger N, only study using
AASM criteria
Time with SpO2 <90% (%TST)
0
Montgomery
Desaturation (>4%) index (N/h)
<1.6
Montgomery, Marcus
SpO2 nadir (%)
≧92
Marcus, Uliel
Periodic limb movement index (N/h)
≦4.3
Traeger, Montgomery
Modified ESS (<12-year-old)
Normal <=8
Marcus, Chan
PDSS (>=12-year-old)
Normal <=17
Yang CM
WASO
Refer to overleaf chart
Maurice M. Ohayon,
Mary Carskadon,
Christian Guilleminault,
Michael V. Vitiello
PaCO2
>50mmHg <25%
of TST
AASM
Apnea-hypopnea index (N/h)
Central apnea index (N/h)
102
Wake After Sleep Onset
(Ref : Maurice M et al, Sleep 2004;27(7):1255-73)
Investigations:
- All children should be screened for habitual snoring
- Polysomnography (PSG) should be performed if the attending clinician has a high
suspicion of SDB
- Give Melatonin 0.25-0.5 mg per kg (to be rounded up to whole number, max 3 mg)
a) for all Down syndrome patients
b) for patients who have difficulty in falling asleep
Sleep endoscopy should be used to identify the main site(s) of obstruction. The most
likely sites would be tonsils and/or adenoids.
Multiple sleep latency test (MSLT) is helpful in children with suspected UARS
Treatment:
- Avoid sleep deprivation and medications with sedating effect
- Surgery: e.g. tonsillectomy and adenoidectomy, uvulopalatopharyngoplasty (UPPPP),
laser or radio-frequency ablation of redundant tissue, maxillo-mandibular advancement
and tracheostomy
- Continuous positive airway pressure (CPAP)
- Weight reduction
- Orthrodostic devices like rapid maxillary expansion, mandibular advancement device.
- Myofunctional treatment maybe helpful
103
Medical Rx of childhood OSA
Goldbart AD et al. Pediatrics 2012;130:e575; Goldbart AD et al. Am J Respir Crit Care Med. 2005;172:364–370;
Kheirandish-Gozal L et al. Pediatrics. 2008;122; Alexopoulos EI et al. Pediatr Pulmonol. 2004;38:161–167;
Brouillette RT et al. J Pediatr. 2001;138:838–844; Kheirandish-Gozal L et al, Chest. 2014 Feb 6. ;
Kheirandish L et al. Pediatrics. 2006;117:e61-e66
Follow-up:
- Male gender and T&A undertaken before the age of 5 years have been found to be risk
factors for OSAS recurrence after T&A.
- Regular follow-up is important for children and adolescents with SDB. Post-operative
PSG should be arranged, 3-6months, after surgery
104
Table I.
Approach to habitual snoring
Habitual snoring (>3 nights / week)
assess severity clinically (in resp clinic
or sleep clinic) very severe
No
Hospital admission
For overnight oximetry
Yes
Normal
refer to have overnight PSG
AHI > 1
No
ABNORMAL
Yes
Primary snorer or UARS
sleep endoscopy
Daytime symptoms/ Abnormal ABP readings
ADHD sypmptoms
Yes
No
UARS
Treat obesity, allergic rhinitis
refer for myofunctional therapy
Normal
MSLT
Repeat PSG 1 year later
with MSLT the next day
105
ABNORMAL
Chapter 33 - Parapneumonic effusion and empyema
E Chan, DK Ng
Grading
U/S grading
1. Anechoic
2. Ecogenic
3. septa
4. homogeneous echogenic
106
Light’s classification and treatment scheme for parapneumonic effusions and empyema
*Intrapleural fibrinolytic (Urokinase)
Dose: 56,000units per m2 BSA (round up to nearest 1,000units, maximum 100,000units), dwell
time 4hrs, Q12H, for 3 days (concentration 10,000units in 10ml NS); individualized extended
use (up to 6 days) may be considered for cases with persistent drainage.
Failure: limited drainage but persistent pleural effusion, persistent fever and respiratory
symptoms after 3days of intrapleural urokinase.
**watch out for high output within a short period of time, clamp drain if output >10-15ml/kg
within 4 hrs to avoid pulmonary re-expansion edema and hypovolemic shock.
107
Blood tests + CXR
Start antibiotics + Chest Sonography
Pleural effusion > 1cm
No
Yes
Chest drain** +
Pleural fluid x pH, WBC, Gram stain, C/ST, LDH, protein,
glucose (AFB Smear, C/ST, TB PCR, ADA as indicated)
(cytology, pleural Bx as indicated (serosanguinous fluid))
Cont. Antibiotic + monitoring
Remember to get urgent pH with capillary tube for
analysis by blood gases machine, WBC, Gram stain
Gram stain +ve or
pH < 7.2 or glucose < 2.2
or LDH >1000 µ/L, or
WBC >10,000/mm3 or
protein > 5gram/dL or
USG showed fibrin/septa
+ ve
Intrapleural Fibrinolytic*
- ve
Cont. Antibiotic
+ Chest drain
Pleural effusion<1cm +
drain output <20ml/day
consider early referral if
frank pus/poor response
Success
Failed
No
VATS
Yes
Clamp drain; off drain if no re-accumulation
Follow by 1-4 wks PO antibiotic guided by CRP, fever,
O2 dependency
108
Chapter 34 - Pulmonary function tests in children
E Chan, J Wong, DK Ng
Test
You are looking for
Spirometry
Spirometry with bronchodilator
(include FeNO)
Exhaled NO
Basic parameters: Flow volume loop, FEV1, FVC, FE50
Asthma, may need repeated testing to demonstrate
bronchodilator response
Eosinophilic airway disease
IOS with bronchodilator
Bronchodilator response, can be performed by ≥ 3yrs old
Exercise challenge test
MIP/MEP
Exercise induced bronchoconstriction
Airway hyper-responsiveness
Assess severity of asthma
Respiratory muscle weakness
Erect and spine VC
Total lung volume
TLC, lung volume
DLCO
Diffusing capacity, TLC, FRC
VO2 Max
The fitness of child, the limiting factor of exercise
A test for fitness in patients with chronic
cardio-respiratory disease
Methacholine/mannitol challenge test
6 minutes walk
In general, a cooperative child (usually ≥ 6 yrs old) with coordinated expiratory and inspiratory
effort is required to perform spirometry. Spirometry can be booked in those < 6 years after
special consideration. Otherwise, IOS is an alternative. Children who can perform spirometry
and run on a treadmill can perform VO2 max (~ at least 6 years old). Measuring DLCO and lung
volume required patience and good breath holding technique, i.e. at least 9-year-old)
Relative contraindications for spirometry: active respiratory infections, low FEV1 (see low
FEV1 protocol), history of recurrent pneumothorax, aortic aneurysm, any unstable respiratory
or cardiac conditions, such as uncontrolled hypertension, heart attack or stroke in recent 3
months. Please obtain written consent for the test.
1.
Basic lung function
Baseline spirometry (FEV1, FVC, flow volume loop), refer chart for lower limit of normal
Obstructive
Restrictive
FEV1
↓↓
→
FVC
↓ or →
↓↓
FEV1/FVC
↓
↑
FRC
↑
↓
RV
↑
↓
TLC
↑ or →
↓
RV/TLC
↑
→ or ↓
109
Spirogram from Merck
Manual
A. Normal
B. Obstructive
C. Restrictive
D. Fixed upper airway
obstruction
E. Variable
extrathoracic
obstruction
F. Variable
intrathoracic
obstruction
2.
Airway bronchodilator response and response to challenge, usually used to investigate
asthma, chronic cough and chronic lung diseases
Bronchodilator test (spirometry with pre and post bronchodilator) + FeNO
It is a simple test. It is good for monitoring and use as an initial screening test. However, we
may need to repeat the tests over a period of time to document a positive bronchodilator
response in asthma.
Positive test: FEV1 increase ≥ 12%
110
Impulse Oscillometry System (IOS)
-A tidal breathing test
-It is a measure of airway resistance by oscillation technique and it is a reasonable alternative in
young children. A single measurement is of limited value. It is used to look for bronchodilator
response. R(5) decreases by >=29% is defined as significant bronchodilator response.
-Test quality is influenced by pt’s breathing pattern. Apart from visual confirmation by Tech.
Coherence of R(5) and R(20) should be >=0.7 and >=0.9 respectively.
-R(5)= Central + Peripheral Resistance
-R(20)= Central Resistance
R(5) – R(20) = peripheral Resistance
IOS Curve pattern
1) Normal Lung Function
4) Extra Thoracic Airway Obstruction
Resistance
R
R5, R20 normal
R
R(f) no frequency
dependence
R5
R20
Normal reference
5
20
5
HZ
2) Peripheral obstruction
R5, Increased, > ULN
R
R20 is normal
R(f) frequency
Dependence present
Normal
5
20
HZ
3) Central obstruction
R
R
R5, Increased, >ULN
R20 increased, >ULN
R(f) no frequency dependence
Normal
5
20
HZ
111
Normal
f [Hz]
20
HZ
Challenge test (Methacholine, mannitol and exercise)
Exercise test is important to assess exercise induced bronchospasm
To rule out asthma, use methacholine challenge test.
To rule in asthma, use mannitol challenge test
Medication challenge test has a better negative predictive value, may help assess the risk of
developing asthma, assess severity of asthma & assess response to treatment. In general,
mannitol test has a better J-index (i.e. sensitively + specificity) than methacholine challenge test
(Patient need to inhaled dry powder for mannitol test, ie, >60L/min inspiratory flow required)
For patient who cannot tolerate a large drop in FEV1, step wise tests (medication challenge) is
more suitable. If the patient cannot tolerate any drop in FEV1, challenge test should not be
booked.
1) Exercise test: EIB: mild, moderate, or severe if the percent fall in FEV1 from the
pre-exercise level is >10%-25%, >25%-50%, and >50%, respectively
2) Methacholline challenge
PC20 = provocative concentration causing a 20% decrease in FEV1
PC20 (mg/ml)
Interpretation
> 16
Normal bronchial responsiveness
4.0-16
Borderline BHR
1.0-4.0
Mild BHR (positive test)
< 1.0
Moderate to severe BHR
Extrathoracic airway hyper-responsiveness (EAHR) with methacholine challenge: PD25FIF50;
cutoff concentration <8mg/ml = +ve, EAHR is found in those with upper airway cough
syndrome usually due to allergic rhinitis.
3) Mannitol Challenge test: PD15= provocative dose causing a 15% drop in FEV1
FeNO = exhaled nitric oxide
A non-invasive measure of airway inflammation
ATS: <25ppb(<20ppb in children) indicate non-eosinophilicor no airway inflammation; high
FeNO >50ppb(>35ppb in children) or rising FeNO (>40% change from previous stable levels)
implies uncontrolled or deteriorating eosinophilic airway inflammation.
112
Lung volume: Book DLCO and TGV(Pleth) +/- nitrogen washout
DLCO (Hb corrected) normal values: less than the lower limit of normal (LLN) but greater than
60% of predicted is mild, between 40 and 60% of predicted is moderate, and less than 40% is
severe.
Low DLCO: restrictive lung disease, isolated low DLCO with normal lung volume: anaemia,
pulmonary vascular disease
High DLCO: in pulmonary haemorrhage, polycythaemia, increase pulmonary blood flow, such
as asthma, pregnancy and obesity
RV/TLC normal: <0.35
Exercise tolerance/cardiopulmonary fitness
1) 6 minutes walk: refer to chart for normal values
VO2 Max/Peak (a cardiopulmonary challenge test)
2) CPET (cardiopulmonary exercise test)
113
Peak VO2
Normal
Anxiety
Obesity
Low <80%
Mild disease
Anaerobic threshold
Abnormal
(AT <0.4 of predicted VO2 max)
Normal
Breathing
reserve
Breathing
reserve
Low <0.2
Normal
Poor
effort
Deconditioning
Ventilatory
impairment
Coronary
disease
Normal
Low <0.2
Cardiac
impairment
O2 pulse
Cardiopulmonary
lesion
↓
Exercise induced arterial hypoxemia may occur in trained athletes: mild(93-95% SaO2)
moderate(88-93% SaO2), severe (<88% SaO2)
Book spirometry, DLCO, MIP, MEP, erect and supine VC
Normal values:
MIP [boys: (2.58 + age x 0.39) x 10 cmH2O; girls: (2.43 + age x 0.28) x 10 cmH2O]
MEP [boys: (35 + 5.5 x age) cmH2O; girls: (24 + 4.8 x age) cmH2O]
MIP helps to differentiate whether restrictive lung disease is due to respiratory muscle
weakness or chest wall limitation
MEP is usually > MIP, if MEP is < MIP, there may be a prevailing expiratory muscle weakness,
i.e. SMA
MEP > 45 cmH2O is necessary for effective cough. Checking peak cough flow is an alternative
to monitor a patient’s coughing ability.
Fall in VC when the patient changes from seated to supine position
< 10% : normal,
10-20% : suspicious of diaphragmatic paralysis
> 20% : significant diaphragmatic paralysis
Infant Lung function test
Restrictive if FVC less than LLN
Obstructive if MEF 75/25 and / or FEV 0.5 or Rrs <LLN
114
Chapter 35 - Bronchoscopy
E Chan, D Ng
Indications:
Stridor / noisy breathing
Persistent / recurrent wheezing
Recurrent / persistent consolidations
Atypical and unknown infiltrates
Localized hyperinflation
Chronic cough
Suspected foreign body aspiration
Haemoptysis
Evaluation of the artificial airway
Look for the underlying causes in CPAP/oxygen dependency in neonates
Pre-bronchoscopy preparation
For children with history of asthma or wheeze, please give bronchodilator, e.g. salbutamol 8
puffs through aerochamber, on call to endoscopy suite.
Therapeutic bronchoscopy:
Restoration of airway patency
Mucus plugs or blood clots
Alveolar filling disorders (alveolar proteinosis, lipid pneumonia)
Special procedures:
Bronchoalveolar lavage
Brushing or biopsy of bronchial mucosa
Biopsy of endobronchial lesions
Administration of drugs like DNAase
Endoscopic intubation
Contraindications:
Absolute
Procedure will not yield any further useful clinical information
Diagnosis of acute epiglottitis
Relative
Pulmonary hypertension
Baseline hypoxia
Uncorrected bleeding diathesis
Duties of bronchoscopist :
Fill in time out form
Perform procedure with clear objective in mind
Start the procedure upon clear signal from the sedation medical staff after checking the
sedation staff has been appropriately trained.
Maintain clear communication with sedation staff and endoscopy nurse.
115
Chapter 36 - Preparation for endoscopy
E Chan, DK Ng
1.
On admission for endoscopy, please check the endoscopy list to confirm booking. If not,
send another booking form.
2. Check for signed consent form.
3. Clear fluid (GES / water / fruit juice without pulp) allowed for up to 2 hours before
endoscopy.
4. Breast milk can be taken 4 hours prior to endoscopy
5. No solid food (including milk / jelly) for 6 hours prior to endoscopy
6. Inform the parents to deprive sleep by 3 hours the night before the procedure
7. For sleep endoscopy, give Melatonin 0.25-0.5 mg per kg (to be rounded up to whole
number place, max 3 mg) 45 minutes before the scheduled procedure
8. Keep the child on the stretcher in a quiet and darkened room to facilitate sleep and be
accompanied by parents
9. Heparin block with short extension set before endoscopy (size of at least gauge 22 if
patients > 6 years old and >=20G for patient >10yrs old)
10. Case doctor completed the sedation form before endoscopy, prescribe prophylactic
antibiotic as per protocol.
11. M.O. assigned for sedation complete the time in form and he/she is responsible for
administering sedatives, maintain ventilation (ie, may need CPAP, BiPAP or
nasopharyngeal airway and T-piece resuscitator) and resuscitation during and after the
procedure
12. Please discuss with endoscopist about desired level of sedation and potential complications
of the case
116
Chapter 37 - Positive Mantoux test
E Chan, DK Ng
1.
Risk of TB among Primary Schoolchildren with MT2 ≥ 20mm in 5-year FU
- 1% of primary school children had this reaction
- Relative risk of PTB
Male
:
49
Female :
33
2. Relationship of size of MT2 and development of PTB in 5-year FU
Size of MT2 (mm)
% of development of PTB
0-4
2
5-9
2
10-14
3
15-19
15
≥ 20
34
3. Risk of TB with different MT2 responses in 4-year FU
Size of MT2 (mm)
odds ratio
10
4
20
16
4. Risk of TB among young household contacts in 6-year FU
Out of 50 patients with MT2 ≥ 10mm, 4 (8%) developed PTB in 5-year FU
Flow chart for positive Mantoux test (consult resp team)
+MT2 (≥ 10mm induration)
Refer resp team
Pul. TB
NPA after cough / EMGL x AFB smear, C/ST x (3) PCR x (1)
CXR + ESR
+ve
-ve
Symptoms, clinical risk (ie, close TB contact)
-ve
+ve
Contrast CT thorax (preferably with 320 CT
Interferon Gamma
scanner to decrease radiation by 50%)
+ve
-ve
+ve
Pul. TB
LIBI
-ve
Bronchoscopy + BAL
Normal
+ve
Pul. TB
-ve
LTBI
Latent TB infection (LTBI) : Isoniazid 10-15 mg/kg/day for 9 months would decrease the
chance (life time risk around 10% and higher in those < 3 years) of TB disease by up to 90% in
the absence of new contact with open PTB.
117
Chapter 38 - Pulmonary tuberculosis
DK Ng
Clinical features:
1) persistent cough for > 2 weeks
2) objective weight loss in the preceding 3 months
3) fatigue
Presence of all 3 symptoms is suggestive of PTB (80% sensitivity, 90% specificity) in HIV -ve
children ≥ 3 years
Radiological imaging:
Hilar lymphadenopathy is the most common feature in CXR
Normal CXR in 20% of PTB
CXR may be repeated after one month of treatment and at the end (60% have persistent albeit
improved CXR).
Contrast CT scan of thorax is very sensitive but not routine
Bacteriology:
Sputum: 3 specimens (one early morning)
Early morning gastric lavage (EMGL): 3 specimens for TB culture or Xpert test
Nasopharyngeal aspirate after cough: any time of the day for TB culture or Xpert test
AFB smear positive only in 10-15%
Culture positive in < 40%
Treatment:
Isoniazid 10-15 mg/kg/day (max 300 mg) for 6 months
Rifampicin 10-20 mg/kg/day (max 600 mg) for 6 months
Pyrazinamide 20-40 mg/kg/day (max 2-3 gram) for 2 months
Ethambutol 15-25 mg/kg/day (max 2-5 gram) for 2 months
Referral to DH Chest clinic may be made for DOTS
All cases should be referred to respiratory clinic for follow-up
Pyridoxine supplement to avoid peripheral neuropathy of isoniazid is indicated for HIV positive
children, malnourished, breastfed or premature infants
Corticosteroids (prednisolone 2 mg/kg for 4-6 weeks then taper off in 2-4 weeks) is indicated
for endobronchial TB or profuse pleural effusion or TB meningitis
Isolation policy:
Children with suspected or confirmed TB should be isolated if
• presence of cough
• cavitation on CXR
• sputum or EMGL is AFB smear positive
• respiratory tract disease with involvement of the lung / airways, including larynx
• extensive pulmonary infection
• suspected congenital TB
Children with little cough and negative sputum / EMGL x AFB can be hospitalised in an open
ward.
118
Chapter 39 - Primary spontaneous pneumothorax in adolescents
KL Kwok, DK Ng
Definition of large pneumothorax (Any one)
●
≥ 3cm apex to cupola (ACCP)
●
≥ 2cm between lung margin and chest wall (BTS)
●
Complete dehiscence of the lung from the chest wall (Belgian)
●
% of pneumothorax = (DH3- DL3)/DH3 ≥ 50% (Light Index) – see appendix
Management
●
Any symptomatic (SOB or significant chest pain) pneumothorax regardless of size or
large pneumothorax warrants treatment
●
Persistent (> 4-7 days): surgical intervention
●
Small: treat with HHHF of FiO2 just enough to keep SpO2 = 100%
●
CXR 2 weeks after discharge,
●
no air travel for 6 weeks, check FiO2.
Simple aspiration
●
Exclusion criterion: tension pneumothorax
●
16G catheter (ID of 1.7 mm that allows guidewire of 0.87 mm to pass through: see
picture) and 50 cc syringe and three-way tap and underwater exit tube, aspirate air up to
4 L or resistance
●
CXR immediately after procedure to confirm success and 4 hours later to look for
reaccumulation
●
Failure i.e. still have free drainage after 4L has been aspirated should lead to in-dwelling
catheter insertion
●
Success rate: 50-72%
●
Recurrence at 1 year: 20%
●
Mean time of recurrence: 3 months
●
Advantage: less painful, cheaper, shorter hospital stay
●
Problem: frequent kink, time consuming, difficult to keep sealed catheter in place for
chest X-ray
Small bore in-dwelling catheter + Heimlich valve +/- suction
●
8F to 14F
●
Success rate with Heimlich valve: 66% at 48 hours
●
Success rate for the group that required follow-on -10 to -20 cm water: 71%
●
Recurrence rate: 24%
●
Mean time of recurrence: 3 months
●
No diving after pneumothorax unless bilateral surgical pleurectomy done
Surgical intervention
●
Indications: second ipsilateral, first contralateral, first bilateral, persistent, spontaneous
haemothorax, high risk occupations e.g. pilots
●
VATS
●
Bleb removal
●
Talc or minocycline pleurodesis
119
Summary of success rates for management strategies
for primary spontaneous pneumothorax
Strategy
Conservative
Aspiration
ICC
Small bore / pigtail catheter
Success Rate (%)
79-90
50-83
66-97
74-100
Curr Opin Pulm Med 2009;15:376-379
Appendix: Formula for Calculating Pneumothorax
Light Index (The only formula used in our unit)
DH3 - DL3
DH3
At hilar level
Picture:
120
= % of pneumothrax
Primary Spontaneous Pneumothorax
Symptomatic (regardless of size)
or
Large pneumothorax
Small pneumothorax
Conservative
management with high
flow heated humdified
oxygen nasal cannula
(FiO2 ~ 40%)
Try simple aspiration in first attempt
Aspiration > 4L
Insert guidewire
through the angiocath
+ with help of dilator,
insert chest tube
(pigtail) *see picture
Aspiration till resistance
CXR to confirm
lung expansion
Symptomatic or
large pneumothroax
Connect to Heimlich valve
or underwater seal
Small pneumothorax
Insert chest tube (pigtail preferable)
CXR to confirm position of chest tube
CXR 24 hours after insertion
(see next page)
Next page
121
CXR 24 hrs after insertion
Failure
Suction (-20 cmH2O)
and watch out for S/S
of pulmonary edema
Daily CXR
Persistent airleak > 4 days
Lung Expanded
For VATS or chemical
pleurodesis
off suction for 1 day
clamp drain
*monitor closely for
reaccumulation of
pneumothorax
S/S of pneumothorax
Immediate CXR
CXR 24 hours later
Persistent airleak
Unclamp chest drain
Lung expanded
Remove chest tube
122
Chapter 40 – Modified bronchoalveolar lavage
E Chan, DK Ng
1. Prepare appropriate size suction catheter, equipments and body temperature normal saline:
Each aliquot: 1 ml/kg for < 5kg, 10 ml for 5-40 kg, 20ml for > 40kg
2. Gently advance the end-hole catheter till resistance. Attach the syringe with warm saline to
catheter. Inject saline into the catheter whilst occluding the side opening of ET Tube adaptor.
Allow a few breaths. Aspirate BAL by syringe.
3. Repeat step 2 for another aliquot (aliquot and volume required depends on tests ordered)
20ml Syringe
Suction catheter
Connect to
T-piece or
Ventilator or
Neo puff
To Suction
Disinfected
L – Shape adaptor
Mucus Extractor
Advanced down the airway
until resistance
Quantitation of Lipid-Laden Alveolar Macrophages (Pediatr Pulmonol 1999;28:83-88)
900 alveolar macrophages were evaluated microscopically for lipid phagocytosis (level of
magnification: 40 x 10). Each macrophage was graded according to the amount of lipid in the
cytoplasm, with a score of 0-4 (0, 1, 2, 3, 4 = 0, 1/4, 1/2, 3/4, totally filled respectively). The
total score (0-3600) was determined by taking the summed total grades of 900 cells.
LLAM score > 200 is highly suggestive of aspiration pneumonia
If total number of macrophage counted is less than 900 and the total score of the counted
macrophage criteria is less than 200, check the number of macrophage counted. If less than
500, use Furiza criteria by pro rata division to 100. (Furuya et al 2007: LLMI >165, sen
98.6% spec 78% for patients with aspiration.) If more than 500, use Colombo by pro rata
multiplication to 900.
123
Chapter 41 - Skin Prick Test
E Chan, A Yip
Indications:
- Confirm sensitivity (relevance of such sensitivity to allergens should be carefully interpreted in
the light of clinical suspicion)
- To confirm atopy
- To confirm food allergy (type I allergy)
- To predict outcome of open food challenge
Results in KWH:
Top 5 allergens = House dust mite*, dog, cat, cockroach and grass pollen
Chance of major systemic reaction: 0.033% in literature and “NIL” in KWH case series (n= 1,365)
Procedure:
1. Explain the procedure to parents and child and child must be physically well
2. Ensure anti-histamines, cough medications or TCM has not been taken for at least 1 week
3. Ensure topical steroid has not been applied to the tested area for at least 1 week
4. Sit the child comfortably; request nursing staff’s assistance if envisaging child will be
struggling
5. The volar surface of the forearm is usually chosen but ensure that there is no active eczema.
The back is an alternative site.
6. Ensure that the skin is clean, and if in doubt wash the site
7. Use a marking pen to divide the skin into areas
8. Place positive & negative control onto skin. Specific food allergen should be tested for food
allergy. Whole panel of aeroallegen should be tested for asthma/ atopy/ recurrent bronchiolitis/
pre-school wheeze
9. A small drop of allergen solution is placed on the skin with at least 2-3 cm apart
10. Avoid placing allergen solution in areas 5 cm from the wrist and 3 cm from the antecubital
fossa if possible (this may be difficult in infant)
11. A sterile lancet is passed through the solution at 45° to 60° angle to the skin with the bevel
facing up, the skin is then gently lifted, creating a small break in the epidermis through which
the suspected allergen solution penetrates without drawing blood, or Stallerpoint inserted at
90°
12. This step is then repeated for each allergen
13. The excess solution is removed with cotton wool making sure that there is no cross
contamination
14. Wait for 15 minutes then examine for wheal (not erythema)
15. Cover the reaction site with a cellulose tape & outline the wheal with a marking pen
16. Transfer the cellulose tape to a piece of paper. Obtain wheal mean diameter (WMD), which is
the average of the largest wheal diameter & length perpendicular to it
17. The child is observed for another 15-20 minutes & can be discharged
Definition of positive SPT:
- WMD Reported = WMD Allergen – WMD Negative Control
- Positive if WMD Reported ≥ 3mm
*House Dust Mite
- B tropicalis is the most common & most important mite species in tropical countries & Hong
Kong.
- B tropicalis 5 is the major allergen with 92% of allergic patients sensitized to it.
124
Chapter 42 - Primary ciliary dyskinesia and non-CF bronchiectasis
E Chan, A Yip, DK Ng
Features of PCD: Chronic oto-rhino-sinopulmonary (ear, nose, sinus and lung) disease +/situs inversus/heterotaxy
Signs & symptoms: persistent rhinorrhea (76% PCD), serious otitis media (very common in
young children), acute otitis media (common >50% in <5yrs old, uncommon afterwards),
sinusitis, chronic wet cough (persistent bacterial bronchitis, bronchiectasis affecting >50% PCD
children & 100% PCD adult, middle & lower lobe affect more), clubbing (increase with age,
>80% in adult PCD), infertility (~50% in male, variable in female), ectopic pregnancy (female),
hydrocephalus (rare), situs inversus (40-50% PCD), situs heterotaxy (6% PCD) , unexplained
oxygen dependency in neonate (>75% PCD)
Dx investigations:
• Saccharin test (out of favor because of inaccuracy especially those <6yo)
• Nasal FeNO: screening test (very low in PCD, may be normal in some cases)
• Ciliary beat pattern & frequency study (depends on availability)
• Electronic microscopy exam of nasal/bronchial cilia ultrastructure (current method of
choice but false +ve happens with intercurrent infection)
• Cell culture (eliminate environmental influence, free from secondary changes; depends
on availability)
• Genetic testing: Test may be considered for DNAI1 and DNAH5 (outer dynein arm
proteins defects which account for <40% of PCD mutations)
• Semen study in adult men
Follow up investigation:
• Sinopulmonary symptoms & exacerbation diary +/- peak flow/FEV1 diary
• Pneumatic otoscopy / tympanogram at least 6 monthly, in cases with chronic SOM, use
of ear drops (antibiotic + hydrocortisone) & hearing aid are preferable to grommet
insertion (which may lead to unresolved ear discharge)
• Sputum/induced sputum C/ST every 3-6 months
• Lung function test with bronchodilator every 3-6 months
• HRCT (to detect bronchiectasis, balance risk with radiation)
• Psychosocial assessment as needed
Early diagnosis & implementation of multi-disciplinary approach in an experienced center is
associated with better outcome
Nasal management: baseline: daily hypertonic saline nasal irrigation, BD-TDS nasal irrigation
+/- antibiotics with increased symptoms, consider nasal corticosteroid in selected cases
Ambulatory pulmonary management, watch out for aggravating/co-morbid factors
Steps of management go up and down according to worsening or improving level of symptoms
respectively.
125
Severity classification
Symptoms in the
Controlled
previous 4 weeks
Partly controlled
Cough
Mild/baseline
Significant Increased
Sputum volume
and color
Limitation of
physical activities
Affect social
life/daily activities
Lung function
(FVC or FEV1)
Emergency
admission
Baseline volume/
Whitish sputum
Signiciant Increased volume
or Yellowish/greenish color
None
Any
None
Any
Normal
< 80% predicted or personal
best
None
One or two / year
Uncontrolled
> 3 features
Three or more /
year
Management
Aims: to maintain lung function, decrease exacerbation & emergency admission, allow
normal daily life
Methods:
Education about PCD, avoid pollutants exposure
Aerobic exercise 45 minutes/day
Flu immunization
Adequate nutrition (caloric requirement 110-120% of RDA in symptomatic PCD)
Acute pulmonary exacerbation management
Patient with underlying lung disease may deteriorate quickly.
Close monitoring, prompt and appropriate antibiotics, adequate respiratory support (ie, NIV)
are usually required.
Choice of antibiotic is usually based on latest sputum result.
126
Steps in managing PCD, step up if not controlled despite good adherence with current step
Step 1
Daily 5.85%
hypertonic
saline Neb
Step 2
BD 5.85%
hypertonic
saline Neb
Daily chest PT
BD chest
PT
Daily Breathing exercise
with resistor (Acapella)
BD Breathing exercise
with
resistor
(Acapella)
*Bronchodilator prn
*Bronchodilator
prn
#Antibiotic
(2 weeks course)
Step 3
TDS 5.85%
hypertonic
saline Neb
TDS chest
PT
TDS Breathing
exercise with
resistor
(Acapella)
*LABA + ICS
#”Eradication and/or ^long
term cycled therapy with
Neb and/or systemic
antibiotic
Consider other measures to
help airway clearance (ie,
CPAP, cough assist)
*Only in those with documented airway bronchodilator responsiveness
#Sputum/induced sputum should be performed at least every 3 months, prescribe antibiotic
according to latest sensitivity result; start with amoxil if sputum showed commensals only/
amoxil + clavulanic acid if the patient is at risk of aspiration. Dosage according to BNF for
severe infection
#Most commonly encountered organisms: Haemophilus influenza, Staphylococcus aureus,
Streptococcus pneumonia. Atypical Mycobacterium & Pseduomonas species tend to affect
children of older age
“Eradication therapy for pseudomonas: IV anti-pseudomonal antibiotics for 2 weeks +/Colistin neb 75-150mg (1-2 million units) BD for 2wks-3 months
^long term cycled therapy, usually start with 2-4wks of PO and/or Neb antibiotic, to be given
every 3 months. Nebulized therapy: Gentamicin 80mg BD or colistin 1-2MU BD (depends on
bacterial culture sensitivity)
^Three times per week azithromycin (10mg/kg/dose) or once a week of 30mg/kg/week may
help to reduce exacerbation and cough
127
Chapter 43 - Nasal lavage
A Yip, DK Ng
Indication: Rhinosinusitis, allergic rhinitis, rhinitis & common cold
Action:
- Flushes dirt, airborn allergens (dust, pollen etc), pollutants & bacterial-filled mucus
- Remove thickened mucus, decrease inflammation, improve mucociliary clearance
- Also loosen & thin the mucus, easier to expel
Prescription:
- 1.5% NaCl 5-10ml to each nostril LA daily to TDS (allergic rhinitis, sinusitis)
- 1.5% NaCl 60ml to each nostril LA daily to TDS (PCD, step up treatment for allergic
rhinitis & sinusitis), using a commercial squeeze bottle (below)
- Commercial preparation Different content in different sachets preparation; as per
instruction
Ingredients in Commerically Available Sachet*:
o NaCl + Baking Soda (NaHCO3): Sometimes used, buffering agent, alkaline pH
7.6 is better for ciliary function, higher mucus fluidity
o Sodium Citrate/ Citric Acid: Optional, balance pH, improve sense of smell
o Aloe Extract: Optional, prevent nasal dryness
Nasal Devices*:
- Syringe: Head tilt; cheap, repeated small volume lavage
- Neti Pot: Head tilt; rely on gravity; repeated practice
- Squeeze Bottle (different brands): Head upright; positive pressure to drive water into
sinuses & nasal cavities for more complete rinsing; avoid high pressure that force fluid into
middle ear, causing infection & earache; anti-backwash valve preferred
- Electric Irrigator: Head upright; expensive; convenient; pulsatile water pumping action at a
predetermined fixed pulse cyclic rate, claimed to simulate nasal cilia hairs, promote better
sinus health & reduce severity of allergic reaction
Methods:
Method 1 (Head-tilt)
1. Tilt head to one side or lie on bed on the side
2. Breath through the mouth. Avoid nasal breathing,
talking or swallowing for the risk of aspiration
3. Push in irrigation fluid via one nostril (via nostril on
upper side) and the fluidwill exit from the other
nostril or through the mouth.
4. Repeat Step 3 with head tilted to the other side
128
Method 2 (Upright)
1. Sit down with head up.
2. Hold the breathe.
3. Push in irrigation fluid via one nostril
4. Lean forward with head down and
allow irrigation fluid to drip out from
nostrils or split out from throat.
*Choices Available for Nasal Lavage/ Irrigation/ Douche
129
Chapter 44 – Reflux Laryngitis
E Chan
Laryngopharyngeal reflux (LPR) is the retrograde movement of gastric contents into the larynx,
pharynx, and upper aerodigestive tract
Symptoms
Dysphonia, globus sensation, cough, subglottic stenosis, muscle tension dysphonia,
laryngospasm, vocal process granuloma, apnoea, asthma/wheeze, and possibly chronic
sinusitis
Reflux finding score (RFS): 8-item clinical severity scale; 0 (no abnormal findings) to a
maximum of 26 (worst score possible)
One adult study showed RFS greater than 7 as suggestive of LPR.
•
•
•
•
•
•
•
•
Pseudosulcus (infraglottic edema)
Ventricular obliteration
Erythema/hyperemia
Vocal cord edema
Diffuse laryngeal edema
Posterior commissure hypertrophy
Granuloma/granulation
Thick endolaryngeal mucus
0 absent, 2 present
0 absent, 2 partial, 4 complete
0 absent, 2 arytenoids only, 4 diffuse
0 absent, 1 mild, 2 moderate, 3 severe, 4 polypoid
0 absent, 1 mild, 2 moderate, 3 severe, 4 obstructing
0 absent, 1 mild, 2 moderate, 3 severe, 4 obstructing
0 absent, 2 present
0 absent, 2 present
130
Chapter 45 - Useful value
E Chan, DK Ng
Ventilation
Normal dead space in adult = 150 ml
Minute ventilation - dead space ventilation = alveolar ventilation = 5-6 L/min (adult)
Pleural pressure
Normal value from -3 to -5cm water
Keep suction pressure no more negative than -20 cmH2O during aspiration of pleural
effusion to avoid trauma to the lung
Pleural effusion:
Posterior costophrenic angle obscured in lateral CXR = 50 ml
Costophrenic angle obscured in PA CXR = 200ml
Diaphragm contour obscured = 500ml
Chylothorax:
> 1.1 mmol/L triglyceride (with oral intake) and a total cell count > 1,000 cells/µL with a
lymphocyte fraction > 80%
Respiratory Indices Calculation
PaO2/ FiO2 ratio:
Remarks
e.g. PaO2 = 8kPa, Fio2 = 60%
＜300 = mild ARDS
＜200 = moderate ARDS
＜100 = severe ARDS
=
2 8 × 7.5
=
= 100
2
0.6
i.e. severe ARDS
Oxygen Index (OI):
=
＞8.1 = ARDS
＞15－25 consider iNO in case of PPHN
＞40 ＝ ECMO
MAP × FiO2 × 100
PaO2 × 7.5
Alveolar- arterial O2 Gradient:
= 2(. − −
= 716 × 2 −
2
− 2
0.8
＜10 mmHg (normal)
2 × 7.5
− 2 × 7.5
0.8
(Hong Kong is at sea level)
Ventilation Index (VI):
See trend for↓or↑ventilation
PaCO2(mmHg) × PIP × RR
=
1,000
Compliance / kg:
=
Newborn 2－2.5ml/cmH2O/ Kg
＜0.6ml / cmH2O/ Kg → RDS
＜1ml/ cmH2O/ Kg → BPD
Cdynamic
BW
131
Section 3: Cardiovascular system
132
Chapter 46 - Ambulatory management of hypertension
L Leung
1.
Definition of hypertension
Hypertension = BP ≥ 95th percentile on at least three separate occasions. Each occasion: at
least 2, preferably 3 measurements taken at least 2 min apart, the average compared with
age, gender and height (4th report mercury sphyg norms or 2008 HK oscillometric norms).
4th report recommends that oscillometric readings ≥ 90th percentile repeated by
auscultation.
Standards for systolic and diastolic BP for infants < 1 year old are according to the 2nd
Task Force.
1.1
Stage 1 and 2 Hypertension
“Stage 1” hypertension: recheck in 1-2 weeks; if persistently elevated on 2 more
occasions, evaluate within a month or sooner if symptomatic.
“Stage 2”: evaluate within 1 week, or immediately if patient is symptomatic.
1.2 Those with high casual BP should have 24hr ABP done to exclude WCH, elucidate BP
pattern. (HK 2014 ABP norms)
2.
Commonest causes of secondary hypertension (HT) in children
2.1
Causes of HT classified according to age (in decreasing order of frequency): Table 1
The younger the age, the higher the BP, the greater the chance of a secondary cause.
Table 1 Commonest causes of secondary hypertension in children
Newborn
First year
1-6 years
6-12 years
Renal vascular
♦ Renal artery
thrombosis or stenosis
♦ Renal vein
thrombosis
Renal impairment
Congenital renal
abnormalities
Coarctation of aorta
Others: Drugs, BPD
Coarctation of
aorta
Renal vascular
disease
Renal
parenchymal
disease*
Iatrogenic
Tumours
Renal parenchymal
disease*
Renal vascular
disease
Rarely:
Endocrine diseases
Essential HT
133
Obesity
OSA
Renal parenchymal
disease*
Renovascular
disease
Essential HT
Rarely:
Endocrine diseases
Iatrogenic
12-18 years
Obesity
OSA
Essential HT
Iatrogenic
Renal parenchymal
disease*
Renovascular disease
Rarely:
Monogenic HT
Endocrine diseases
3.
Diagnostic Approach to child with persistent hypertension See Fig 1 Evaluation
Algorithm
3.1
History
Symptoms suggestive of secondary HT: eg. Urinary symptoms, joint pain, abdominal pain,
oedema, muscle weakness or cramps, weight loss, palpitations, sweating, fevers, flushing
attacks
Symptoms suggestive of TOD: headache, epistaxis, vertigo, impaired vision, chest pain,
dyspnoea
Sleep history: habitual snoring, observed apnea, daytime somnolence or hyperactivity
Antenatal/neonatal history: LBW, oligohydramnios, anoxia (ATN or renal vein thrombosis),
umbilical artery catheterization, bronchopulmonary dysplasia.
Past history: recurrent UTI, renal, cardiac, thyroid disorders
Family history: hypertension, diabetes, dyslipidemia, obesity, premature cardiovascular or
cerebro-vascular disease, hereditary renal or endocrine disease, neurofibromatosis, sleep
apnoea.
Risk factors: physical inactivity, dietary habits, smoking, alcohol, caffeine
Drugs: eg. oral contraceptives, cyclosporin, steroids, tricyclic antidepressants,
decongestants, excessive licorice, Ritalin, over-the-counter drugs or Chinese herbs, illicit
drugs (cocaine, amphetamines), athletic performance-enhancing drugs including
erythropoietin
3.2 Physical Examination
General/Skin
Height, weight, BMI: poor growth or obesity
Pallor, facial or peripheral oedema
Signs of neurofibromatosis, Turner, Williams, Tuberous sclerosis, Marfan’s, Cushing’s
synd.
Haemangioma in von Hippel-Lindau disease, Klippel-Trenaunay-Weber
Signs of hyperthyroidism, SLE
CVS
BP measured both arms and a leg. If leg BP is lower than arm BP, suspect coarctation.
Pulses of all extremities
Bruits over large vessels in cranium (infants), neck, flank, abdomen
Tachycardia, LV impulse, heart failure
Eyes
Retinal changes of hypertension, retinal vascular hamartoma (von-Hippel-Lindau
disease)
Hyperthyroid eye signs, EOM palsy
Face / neck
VII palsy, goitre
ENT
tonsillar hypertrophy, allergic rhinitis
Abdomen
Mass (Wilms tumour, neuroblastoma, phaeochromocytoma, polycystic kidneys,
obstruction)
Renal bruit
Hepatosplenomegaly (infantile polycystic disease)
Ambiguous genitalia / virilization
134
4.
Investigations
4.1 Basic diagnostic tests for all
a. Evaluation for cause
Urea, creatinine, electrolytes
Complete blood picture
Urinalysis, urine culture, freshly voided centrifuged specimen x casts etc
Renal ultrasound
CXR, ECG
b. Evaluation for comorbidity
Uric acid, fasting lipids and glucose, including lipid fractions, fasting insulin in obese
hypertensives to look for metabolic syndrome*
HbA1c or glucose tolerance test in those with strong family history of Type 2 diabetes
Drug screen if suspicious history
Polysomnography if history of habitual snoring
*National Cholesterol Education Program Definition for adults: 3/5 risk factors: Abdominal obesity (waist
circumference ≥ 90cm for men, ≥ 80cm for women); hypertriglyceridemia > 1.69mmol/L; low HDL < 1.04
mmol/L in men, < 1.30 mmol/L in women; high BP ≥ 130/85 mmHg; high fasting glucose ≥ 6.1 mmol/L
c.
Evaluation for TOD
Urine microalbumin (normal =2-30mg/mmol urinary Cr)
Echocardiogram
4.2 Additional diagnostic tests as necessary
Renin profiling (supine: overnight or supine for at least 30 minutes. Erect: ambulant >
60 minutes): low in mineralocorticoid diseases, monogenic HT, corticosteroid excess;
high in 70-80% of RAS.
Aldosterone
- high in 85% patients with renal artery stenosis, in primary hyperaldosteronism
- low in monogenic HT
Plasma cortisol and urine steroid metabolites
Plasma and urine VMA, HVA and catecholamines
DMSA for scarring
Renal vascular imaging:
- Doppler flow studies of renal hilum
- MAG3 or DMSA before and after ACE inhibitor
- MRA or 3-dimensional or spiral CT angiography
- Digital subtraction angiography (the gold standard)
Others: renal vein renin sampling for RAS; caval sampling for catecholamines; MIBG
or Indium-octreotide scan for phaechromocytoma; CT or MRI for adrenal and other
tumours; genetic studies for monogenic hypertension
135
Fig 1. Evaluation Algorithm for child with elevated BP (modified from 4th Report)
Child with BP
─
─
Prehypertensive
Stage 2 HT
Stage 1 HT
BP ≥ (99% +5mmHg)
BP 95% to < (99% +5mmHg)
immediate referral to center with
expertise in paediatric HT within
1 week or
admission if patient symptomatic
BP 90%to < 95% or
≥120/80mmHg even if < 90%
90 to95%
Repeat BP
over 3 visits
Lifestyle changes
≥95%
Repeat BP in 6 months
Diagnostic tests (basic± additional)
± emergency treatment
ABPM
Consider basic
diagnostic tests
including evaluation for
TOD*
Sustained
HT
Whitecoat
HT
BP ≥ 95% or TOD
Basic diagnostic tests including
evaluation for TOD
* if overweight, comorbid conditions,
especially if younger, very high BP
or no family history HT.
Additional diagnostic tests if
young child or evaluation
suggestive of secondary causes
Treat
specific
cause
Secondary
HT
Primary
HT
Abbreviations: HT =hypertension, TOD=target organ damage
136
Lifestyle
± drug
treatment
5.
Non pharmacologic Treatment of Hypertension
For patients with borderline HT: a 6-month trial of salt and caloric restriction and a
regular exercise program.
5.1 Salt restriction, weight loss and other dietary modifications
Current recommendation of salt is < 1.5 g (~1/4 teaspoon) per day (2/3 already in the
food itself).
DASH diet emphasizes intake of fruits, vegetables, low-fat dairy, whole grains; and
reduced intake of saturated fat and refined sugar.
5.2
Increase exercise and reduce sedentary behavioural patterns
30-60 minutes per day of continuous or accumulated aerobic physical activity (such as
stationary bicycle or brisk walking) where they “work up a sweat” on most days.
Sedentary activities (such as TV, computers, video games etc) to be limited to < 2
hours/ day.
5.3 Hypertension and sports participation (Table 2)
Table 2 Recommendations for participation in competitive sportsa for the Pediatric
Hypertensive patient
1.
Children with significant hypertension (95th - 98th percentile) and no evidence of target
organ involvementb can participate in all competitive sports. BP should be remeasured at least
every 2 months to monitor the impact of competition.
2.
Children with severe hypertension (≥ 99th percentile) who do not have target organ
involvement should be restricted from competitive sports, particularly from high static sportsc,
until their high blood pressure is controlled.
3.
The eligibility for participation in competitive athletics for children with hypertension and
target-organ damage or other cardiovascular diseases should be determined on an individual
basis based on severity of both their hypertension and associated conditions.
a.
b.
c.
A competitive athlete is one who participates in sport that requires competition against others as a central
component and requires vigorous training in a systematic fashion.
TOD: 1) cardiac TOD = clinical, ECG or radiologic evidence of coronary artery disease; LVH by ECG or
echo; left ventricular dysfunction or cardiac failure. 2) Renal TOD = pathologic proteinuria or subnormal
GFR. 3) Eye = retinal hemorrhages or exudates. 4) cerebrovascular = history of TIA or stroke. 5) peripheral
vascular = absence of one or more major pulses in extremities with or without claudication or an aneurysm.
High static sports include field events (throwing), gymnastics, karate / judo, water skiing, weight lifting, body
building, downhill skiing, wrestling, boxing, cycling, decathlon, rowing and speed skating.
5.4 Obstructive Sleep Apnea
nasal steroids, montelukast, weight loss, T&A, orthodontic procedures or nasal CPAP
5.5 Other lifestyle modification: caffeine, cigarettes, alcohol, oral contraceptives
Limit caffeine & caffeinated soft drinks.
To cease / not start smoking and stimulant drugs, avoid drinking too much alcohol.
Best to avoid oral contraceptives in adolescent girls.
137
6.
Pharmacological treatment of hypertension
6.1 In children, there is scant evidence of long term benefits of lowering BP. Thus the decision
to begin pharmacologic treatment in children is not taken easily.
6.2
6.3
Indications for drug therapy
1. symptomatic HT
2. secondary HT
3. hypertensive TOD
4. other conditions e.g. DM type 1 or 2, chronic or proteinuric kidney disease
5. consider in multiple cardiovascular risk factors (dyslipidemia, smoking, severe
obesity)
General principles of treatment
6.4
Aim lower BP to < 95th percentile. With co-morbidities such as diabetes or if TOD
present, lower to <90th. With non-proteinuric CKD, to <75th. With proteinuric CKD:
to <50th.
Aim: fewest medications at the lowest daily dosage and frequency
Start single drug at the lowest recommended dose; adjust up if target not reached in
4-8 weeks. Exception = hypertension is severe and symptomatic when IV therapy is
indicated.
Once highest recommended dose reached or side effects +, a second from a different
class should be added, one with complementary mechanisms of action, such as ACEI
+ diuretic, vasodilator + diuretic or β-blocker.
For essential hypertension in children generally, no specific class of drug is preferred.
Diuretics and β-blockers have a long history of safety and efficacy. Newer classes
including ACEI, CCB and ARB also effective and safe in children.
Long-term treatment in children and adolescents: ABCD
The British Hypertension Society launched ABCD algorithm for adults, the principles
also apply to children.
ACEI and ARB
Beta-blocker
Calcium Channel Blocker
Diuretic
Children generally respond better to drugs that block the renin system (A and B drugs)
If combination treatment is needed, it is recommended to combine (A or B) with (C or D)
The third step would involve triple therapy with either A+C+D or B+C+D.
6.5
Specific recommendations in choice of class of drug
ACEI or ARB preferred in children with diabetes and microalbuminuria or
proteinuric renal diseases. Combination of ACEI and ARB may have synergistic
effects.
ACEI and ARB may be the drugs of choice for patients with end-organ damage such
as cardiac hypertrophy.
β-blockers or CCB in hypertensive children with migraines.
β-blockers for hypertension that persists after coarctation of aorta.
Phaechromocytoma: cocaine or methamphetamine overdose need both alpha and
beta blockade (phenoxybenzamine and propranolol). Inadequately blocked
α-adrenergic activity can increase BP if β blocker is not complete.
For athletic adolescents, avoid diuretics; β-blockers may also affect exercise
138
6.6
performance. CCB and ACEI or ARB are drugs of choice for athletes as they lower
peripheral vascular resistance without affecting exercise capacity.
In the treatment of Metabolic Syndrome (obesity, insulin resistance, hyperlipidemia
and hypertension), where there is sympathetic over-stimulation, peripherally acting
α1-adrenergic receptor antagonists like prazosin may be first choice.
For infants, use shorter-acting agents for flexibility of dosage – propranolol instead of
atenolol, captopril instead of enalapril. Once stable, the patient may be changed to the
longer-acting antihypertensives.
Additional notes on drug treatment
Diuretics: High salt intake will negate the antihypertensive effect of thiazides.
Loop diuretics generally less effective in BP control in patients with normal kidney function.
Potassium-sparing diuretics reserved for patients with mineralocorticoid excess or to treat
thiazide-induced hypokalaemia.
ACEI and ARBs are both teratogenic. Adolescent girls should be counselled about birth control.
Infants and young children are more sensitive to their antihypertensive effect and side effects
including acute renal failure.
Centrally acting α agonist clonidine may be useful in hypertensive urgencies or weaning off from
IV drugs in hypertensive emergencies. It must be tapered slowly best over 6-10days, as rebound
hypertension may occur.
Staging of ABP levels in Children (AHA Scientific Statement 2014)
Office BP*
Mean Ambulatory
SBP or DBP
SBP or DBP Load, %§
Normal BP
<90th %tile
<95th %tile
<25
White coat hypertension
≥95th %tile
<95th %tile
<25
≥90th %tile or >120/80 mm Hg
<95th %tile
≥25
<95th %tile
>95th %tile
≥25
>95th %tile
>95th %tile
Classification
Prehypertension
Masked hypertension
Ambulatory hypertension
‖
25
–50
Severe ambulatory hypertension
>95th %tile
>95th %tile
>50
(at risk for end-organ damage)
%tile indicates percentile; BP, blood pressure; DBP, diastolic blood pressure; and SBP, systolic blood pressure.
*Based on National High Blood Pressure Education Program Task Force normative data.101a
Based on normative pediatric ABPM values in Appendix Tables A1 through A4.
For either the wake or sleep period of the study, or both.
For patients with elevated load but normal mean ambulatory BP and office BP that is either normal (<90th percentile) or
hypertensive (≥95th percentile), no specific ambulatory BP classification can be assigned based on current evidence and
expert consensus. These unclassified
patients should be evaluated on a case-by-case basis, taking into account the
presence of secondary hypertensiona or multiple cardiovascular risk factors.
Some clinicians may prefer the term sustained hypertension rather than ambulatory hypertension.
§
‖
”
139
Chapter 47 - Management of severe hypertension
L Leung
Definition
Stage 2 hypertension (HT) = SBP or DBP > 99th percentile + 5 mmHg for sex, height
percentile for age. Severe HT is not rigorously defined in children (adult is often taken as
≥180/110) but often taken as Stage 2 HT with severe symptoms. This is a level at which a
patient, at presentation or in very near future, will likely manifest serious clinical signs,
symptoms and target organ damage. It depends on the rate of BP rise and duration as much as
the actual BP level.
Hypertensive emergency is severe hypertension with life threatening symptoms +/- acute
target organ damage, e.g. encephalopathy and seizures.
Hypertensive urgency:
Severe hypertension without target-organ damage or major symptoms, but may still have
symptoms that are less significant like headache, nausea or vomiting.
Symptoms and signs of hypertensive emergency:
severe hypertension with retinopathy 27% (haemorrhage, papilloedema, anterior ischaemic
optic neuropathy → may infarct optic nerve from ciliary arterial hypertensive damage,
especially when BP is reduced too quickly)
CNS: encephalopathy 25%, convulsions 25%, hemiplegia 8%, facial palsy 12%
heart failure 13%, aortic dissection.
renal failure
GI haemorrhage
microangiopathic haemolytic anaemia
Symptoms and signs of hypertension in neonates:
may be none
tachypnoea, cardiomegaly, congestive heart failure
seizures
retinopathy
lethargy, failure to thrive
Conditions that may mimic hypertensive emergency/ where rapid BP reduction might be
harmful (eg intracranial mass or injury/ NAI, coarctation of aorta) must be excluded. Also
exclude causes where BP reduction should be achieved by other means (eg benzodiazepine and
phentolamine for cocaine OD or analgesia for severe pain).
Treatment of Hypertensive Emergencies and Urgencies
Important to determine if HT is acute or chronic. If this history not available, lower BP slowly.
General measures
Assess ABC: avoid drugs like ketamine for rapid sequence intubation.
Best obtain intra-arterial line for BP measurement, but do not delay treatment for this. If
not available: auto-cycling oscillometric BP every 1-2 min.
Seizures treated with anticonvulsants like lorazepam until seizures stop.
140
Hypertensive emergency
Requires urgent treatment to reduce within minutes to hours to avoid life-threatening
complications.
Goal = prevent HT-related damage by slow, controlled reduction of BP, minimize
complications of over-rapid BP reduction due to HT induced abnormalities in
autoregulation (cerebral ischaemia, ischaemic neuropathy of optic nerve, transverse
ischaemic myelopathy, renal impairment).
Best is to use IV antihypertensive medication given by continuous infusion in an
intensive care setting. e.g. labetalol, sodium nitroprusside and nicardipine
Two IV lines, one reserved for saline or plasma infusion to increase BP by volume
expansion if sudden hypotension.
Strategy is to decrease systolic pressure by ≤ 25% of original value over the first 6-8
hours after presentation, then gradually normalizing BP over the next 24-48 hours.
Another well-tried strategy used by GOS is to reduce BP by one-third of the amount to be
reduced in the first 12 hours, a further third over next 12 hours and to the proposed
maintenance level over another 24 hours.
Monitor carefully pupillary reactions, vision, consciousness and neurological findings. In
ischaemic neuropathy of optic nerve, there will be loss of pupillary reflex,
accommodation preserved, then saline should be given to rapidly increase BP.
See Table 1 for antihypertensive drugs in children. Preferred drug for hypertensive
encephalopathy is labetalol infusion. If contraindications (eg. Asthma, heart failure), IV
nicardipine can be used, including in patients with hepatic and renal failure. Sodium
nitroprusside is less used due to cyanide toxicity.
Chronic oral anti-HT should be introduced in a conscious child after BP reasonable
controlled within 24-48 hrs of starting infusions of anti-HT. Oral counterparts of IV drugs
used are a good choice (e.g. oral labetalol, titrate every 6-12 hrs.), and rate of IV infusion
can be slowly decreased. Prolonged use of IV anti-HT may result in Na and water
retention and tachyphylaxis.
Some patients, esp. those with normal kidney function, may have some volume depletion
from pressure natriuresis due to very high BPs. In absence of signs of volume overload,
some volume expansion with IV saline solution will help to suppress renin secretion and
prevent significant hypotension once the vasodilating medications begin to act.
Special situations in Hypertensive emergency
Phaechromocytoma/ catecholamine-induced HT: α-blockers: phenoxybenzamine,
phentolamine, prazosin. Pre-op management should include Na and vol repletion to
prevent hypotension. Once α-blockade achieved, β- blockers may be used. CCB also
useful.
Renin-dependent hypertension (renovascular, renal parenchymal disease): ACEI except
if main renal artery stenosis is suspected.
Diuretics can be effective in severe HT caused by actue GN. Renal impairment with salt
and water retention: UF, dialysis or high dose diruetics in those with residual urine
output.
Low renin hypertension (Apparent Mineralocorticoid Excess or Liddle) can present with
life-threatening hypertension that only responds to specific agents that act on collecting
tubules like triamterene or amiloride.
Those with cerebral vascular disease or ↑ICP may need higher BP to maintain cerebral
perfusion – not same approach. If need to use, labetalol is safer.
141
Neonates and infants: little data. Need very careful and slow lowering. Nicardipine and
nitroprusside has been used.
Hypertensive urgency
Important to assess whether elevated BP is acute or chronic event. If from acute process
(eg PSGN): intervene within hours and IV treatment (eg. labetalol or hydralazine) is
appropriate.
If it is a chronic process, BP can be gradually reduced within a few days, using oral
medications like clonidine (not for those with encephalopathy as it is centrally acting) or
isradipine. It is preferred to use short-acting oral drugs initially so that any sudden drop
in BP can be reversed more readily. Conversion to once daily agents can be made
subsequently.
The Fourth Report does not recommend the use of short-acting nifedipine for HT
emergencies due to the unpredictable degree of BP reduction. In HT urgency, if IV
access cannot be obtained quickly, it has been used judiciously with the lowest effective
dose.
TABLE 1. Antihypertensive Drugs for Management of Severe Hypertension in Children 1-17 Years Old
Drug
Class
Dose*
Route
Onset
Duration
Comments
Contraindicatied in 2nd or 3rd
degree heart block, low
cardiac output. Asthma and
overt heart failure are relative
contraindications.
Side effect: nasal congestion,
rash, pruritus, nausea,
vomiting. Severe
hepatocellular damage has
been reported. May mask
symptoms of hypoglycemia.
May cause reflex tachycardia,
phlebitis.
Intravenous drugs for HT emergencies and urgencies in children
Labetalol
α-1 and
- Blocker
β
Infusion:start
0.25-0.5 mg/kg/hr,
to maximum 3.0
mg/kg per hr
IV bolus
or
infusion
5-10 min
Peak 5-15
min
2-6 hrs
T½ 3-5h
Nicardipine
(time of
writing: N/A
in HK)
Calcium
channel
Blocker
(dihydropy
ridine)
Bolus 30mcg.kg up
to 2mg/dose
Infusion:
0.5-4mcg/kg per
min
IV bolus
or
infusion
5-10 min
100-500mcg/kg per
min
IV
infusion
Within
secs
30min-4
hrs
(↑with
time of
infusion)
T½ 1015min
10-20
min
T½
10min
0.5 -10mcg/kg per
min. Increase
slowly (risk of
tachycardia) and
discontineu over
15-30 min to
prevent rebound
effect.
IV
infusion
1-2 min
Esmolol
Sodium
nitroprusside
β- Blocker
Direct
Vasodilator
(arterioles
& venules)
↓TPR &
venous
return
(afterload
& preload).
Used in
Protect from light.
142
< 10 min
Needs constant infusion. May
cause profound bradycardia.
Avoid if history of asthma and
in acute decompensated heart
failure. Metabolism
independant of kidney and
liver.
Monitor cyanide levels with
prolonged use (>48 hours) or
in renal/hepatic insufficiency;
or coadminister with sodium
thiosulfate. Cyanide iinhibits
cellular oxidative metabolism.
Excessive concentrations can
cause tachycardia, sweating,
hyperventilation, caridaic
arrhythmias and metabolic
acidosis. Tachyphylaxis with
acute
pulmonary
edema.
Hydralazine
Direct
Vasodilator
(arterial)
0.2-0.6 mg/kg per
dose, max single
dose 20mg.
IV, IM
10-30 min
Peak
10-80 min
after IV
2-6 hrs,
up to
12hrs –
unpredic
table.
Enalaprilat
ACE
inhibitor
5-10 mcg/kg/dose
up to 1.25 mg/dose
IV bolus
15 min
4-6 hrs
prolonged use.
Do not use in patients with
vitamin B12 deficiency,
impaired liver function,
Leber’s optic atrophy. Caution
in hypothyroid pts.
Should be given every 4 hours
when given IV bolus.
Recommended dose is lower
than FDA label. Must have 2
large bore IV cannulae: NS
can be given if BP reduced
too quickly. Causes reflex
tachycardia, headaches,
flushing and fluid retention.
Effect less predictable, more
difficult to titrate. Can be
given IM: useful when
immediate need to lower BP
but no IV access.
May cause prolonged
hypotension and acute renal
failure in neonates and
hypovolemic patients. Avoid
if severe renal artery stenosis
suspected, especially if
bilateral.
Oral drugs for treatment of hypertensive urgencies in children
Drug
Class
Dose*
Route
Onset
Duration
Comments
Clonidine
Central
α2-agonist
po
15-30 min
6-10 hrs
Side effects include dry mouth
and sedation. Avoid in
encephology. Can be used in
renal failure (no need dose
adjustment), esp in older
children and adolescents.
Narrow safety profile in
young children.
Isradipine
Calcium
channel
blocker
po
1 hour
Peak
2-3hrs
12 hrs
Stable suspension can be
compounded and used in
infants. Rapid metabolism in
children, usu need 3-4x daily.
Hydralazine
Direct
vasodilator
(arterial)
Direct
Vasodilator
(arterial)
Limited info. In
adults, initial dose
100-200 mcg
followed by
repeated hourly
doses of 50-100
mcg until BP goal
reached (max
800mcg total dose).
In child, initial 1-2
mcg/kg /dose titrate
hourly to BP goal
(max 800mcg total
dose or 25mcg
/kg/day in divided
doses)
0.05-0.1 mg/kg per
dose, up to
5mg/dose. Lower
doses in <2yr olds.
(0.03-0.05mg/kg)
0.25 mg/kg per dose
up to 25 mg max
single dose
0.1-0.2 mg/kg per
dose
up to 10mg/dose
po
30min
2-8 hrs
Variable response
po
30 mins
2-5 days
Most potent oral vasodilator,
long-acting.
Minoxidil
Ref. Chandar 2012, Flynn 2009, Patel 2005
143
Chapter 48 - Management of Kawasaki disease
(I)
Classical diagnostic criteria:
1. Fever of at least 5 days duration
2. Presence of 4 of the following 5 principal clinical features
Bilateral conjunctival injection
Oral changes including red and/or fissured lips, strawberry tongue, injected oral
mucosa and pharynx
Extremity changes including edema and/or erythema of hands and/or feet in the acute
phase, periungual desquamation in the convalescent phase
Polymorphic rash
Cervical lymphadenopathy, at least 1.5 cm diameter
3. Illness not explained by other known disease process.
Incomplete Kawasaki Disease# (see diagram)
Fever ≥ 5 days with < 4 principal clinical features
Echocardiographic or angiographic abnormalities such as
Coronary arteries: perivascular brightness, lack of tapering, ectasia or aneurysm
Decreased LV function, mitral regurgitation, pericardial effusion
1. Diagnosis can be flexibly made on D4 (for earlier treatment) in the presence of ≥ 4 principal
clinical features
2. Consider Kawasaki disease as differential diagnosis in young children with unexplained
fever ≥ 5 days with any principal clinical features. Consult cardiologist / Kawasaki disease
specialist at low threshold.
3. Commencement of treatment may have to be considered on an individual basis for cases
with insufficient diagnostic criteria.
# The term “Atypical Kawasaki Disease” is reserved for those with features that not usually
present in KD such as renal impairment.
(II)
The following may help in diagnosing Incomplete Kawasaki Disease:
A. Supplemental Laboratory criteria (if >= 3 criteria, can treat before echo)
Albumin <=30g/L
Anemia for age
ALT elevation
Platelet after D7 >= 450
WCC >= 15
Urine >= 10 WCC/HPF
144
B. Positive Echo* (any one of THREE)
1. Z score of LAD or RCA >= 2.5
2. Coronary arteries meet Japanese Ministry of Health criteria (>3mm in <5yo or >4mm in
≥5yo; diameter of a segment = 1.5 x adjacent segment)
3. >= 3 other features:
Perivascular brightness
Lack of tapering
Decreased LV function
Mitral regurgitation
Pericardial effusion
> Z score of LAD or RCA > 2 but <2.5
*internal diameter: inner edge to inner edge
Diagnostic Pathway of KD
Fever ≥ 5 days and 2 or 3 clinical criteria
Assess Patient Characteristics
Consistent
with KD
Persistent
Fever
Inconsistent
with KD
Assess Laboratory Tests
KD Unlikely
CRP ≥3.0 mg/DL and/or
ESR ≥ 40 mm/hr
CRP <3.0 mg/DL and ESR
<40 mm/hr
Follow Daily
Fever continues
for 2 days
Fever resolves
No
Peeling
No f/u
≥3 Supplemental
Laboratory Criteria
<3 Supplemental
Laboratory Criteria
Echo
Typical
Peeling
Echo
Treat and
Echo
Echo +
Echo Fever
Persists
Fever
Abates
Newburger JW et al, Pediatrics 2004
Dec;114(6):1708-33
Repeat Echo Consult
KD Expert
145
KD Unlikely
Treat
Initial investigations:
1. CBP, ESR, blood culture, LRFT, lipid, viral titre
(leukocytosis with neutrophilia and immature forms; raised ESR; raised CRP; anaemia;
abnormal plasma lipids; hypoalbuminaemia; hyponatremia; thrombocytosis after week 1 or
thrombocytopenia/DIC; sterile pyuria; raised serum transaminases; raised serum GGT;
pleocytosis of CSF; leukocytosis in synovial fluid)
2. ECG: arrhythmia, prolonged PR interval or non-specific ST and T wave changes
3. Echocardiogram in the acute phase
Treatment in the acute phase when fever is still present (within 10 days ** of illness):
1. IVIG 2g/kg infused over 12 hours with blood pressure and pulse rate measured hourly and
preferably cardiorespiratory monitoring. Infusion rate can be slowed down (> 24 hours)
when occurrence of allergic reaction (e.g. chills and rigors or hypotension) or presence of
cardiac and renal insufficiency.
Additional doses of IVIG may be given if fever does not subside promptly after the initial
dose or recurs afterwards.
**If possible, treatment to be given within 7 days of illness. For incomplete Kawasaki,
IVIG can be given before D5, but it may be associated with an increased need for IVIG
retreatment. IVIG should be given even after the 10th day of illness (missed earlier) if they
have either persistent fever without other explanation or aneurysms and ongoing systemic
inflammation, as manifested by elevated ESR or CRP.
2. Aspirin 30-50 mg/kg oral in 3-4 divided doses with food. Routine prescription of antacid is
not required. Aspirin can be changed to low dose (Aspirin 3-5 mg/kg/day for 8 weeks) when
fever has subsided for 48 hours.
Avoid Ibuprofen as it will decrease anti-platelet function of aspirin.
Antacids may decrease efficacy of aspirin.
Aspirin can be omitted in the acute phase if there are contraindications such as G6PD
deficiency, bleeding tendency or aspirin-induced asthma. Mild to moderate elevation of
transaminases commonly found in Kawasaki disease is not a contraindication to use of
aspirin.
3. Steroids may be considered for cases with persistent/ recurrent fever after receiving ≥ 4
g/kg of IVIG. The most commonly used regimen is IV pulse methylprednisolone 30 mg/kg
over 2-3 hours, once daily for 1-3 days, followed by prednisolone 2mg/kg/day po until D7
Or until CRP normalizes; then wean over in next 2-3 weeks.
Echo performed at
1. Diagnosis
2. 2 weeks
3. 6-8 weeks
a. Saccular if axial and lateral diameters
are nearly equal
b. Fusiform if symmetrical dilatation
with gradual proximal or distal
tapering
c. Ectasia = dilatation
146
Definition of coronary artery abnormalities:
Either
Japanese Ministry of Health Criteria1. 3mm in < 5 years;
2. 4mm in > 5 years;
3. diameter of a segment = 1.5 x adjacent segment
OR
Z score > 2
Long term management is according to the following protocol depending on the coronary
artery involvement:
1. No CAA or only transient dilatation
Aspirin 3-5 mg/kg/day for 8 weeks
No restriction of physical activity beyond 8 weeks
FU and Echo at 2 weeks; 2, 6 and 12 months
Then yearly FU without Echo
2. CAA at acute stage but resolved
Aspirin 3-5 mg/kg/day for 8 weeks
No restriction of physical activity beyond 8 weeks
FU and Echo at 2 weeks, 4 weeks; 2, 6, 12 months
Then yearly FU without Echo
3. CAA < 8mm
Aspirin until CAA resolved
Recommendation on physical activity guided by stress test / myocardial perfusion scan
Competitive sport discouraged
FU and Echo at 2 weeks, 4 weeks; 2, 6, and 12 months, and then yearly
Myocardial perfusion scan every 2 years
Angiogram at 12 months if CAA persists or if Echo shows stenosis or if perfusion scan
abnormal
4. Giant CAA ≥ 8mm
Long term aspirin +/- warfarin
Only recreational sport allowed, level to be guided by perfusion scan / stress test
Myocardial perfusion scan yearly
Angiogram at 12 months or if symptoms or results of other tests suggest coronary
artery stenosis
5. CAA + obstruction
Long term aspirin +/- warfarin
Only recreational sport allowed, level to be guided by perfusion scan / stress test
Myocardial perfusion scan yearly
Angiogram for evaluation of symptoms or previous intervention
Patients with contraindications to aspirin can be given dipyridamole (persantin) instead at a
dosage of 5 mg/kg/day in 2-3 divided doses in multiple of the 25mg tablet.
147
Patient counselling:
1. General heart health: diet, weight control, blood pressure
2. Exercise recommendation (certifying letter)
3. Yearly influenza vaccination for children on long term aspirin and > 6 months of age
4. Measles and varicella vaccine should be delayed until 11 months after the infusion of IVIG.
Or MMR can be given at 6 months and then another dose 11 months from receiving IVIG to
have better protection to the child from measles in the interim period.
Aspirin should be avoided for 6 weeks after administration of varicella vaccine and aspirin to
be replaced by dipyridamole.
148
Risk Level
I
II
III
IV
V
Coronary
No abn at
any stage
Transient
ectasia /
dilatation
>3mm- <6mm or
z-score = 3-7 in ≥1
coronary artery
≥6mm, including giant aneurysm, multiple
(segmental) or complex aneurysm Without
obstruction
Coronary artery
Obstruction
Anti-platelet therapy
beyond 6-8 weeks
×
Aspirin + clopidogrel for multiple and
complex aneurysm
×
Aspirin
Aspirin +/- warfarin
Aspirin + warfarin for giant aneurysm
(INR = 2-2.5)
Avoid contact / high impact sports because of bleeding risk while on aspirin
Physical activity
Counselling, ECG, Echo
No restriction beyond 6-8
weeks
Every 5
years
No restriction 0-10 years
old, then myocardial
perfusion test to guide
recommendation
Every 3-5 yrs
Myocardial Perfusion
Test
×
Coronary angiography
Not recommended
- Annual stress test, myocardial perfusion test
to guide recommendations.
- Recreational non-contact sports encouraged if
no evidence of stress-induced myocardial
ischemia
Beta-blocker to
reduce myocardial
oxygen consumption
Annual
6 monthly
Every 2 years in patients
>10 yrs
Only if myocardial
ischemia demonstrated by
stress test
Annual myocardial perfusion test + screening for risk factors for
atherosclerosis
Done 6-12 months after recovery to address therapeutic options of
bypass grafting or catheter intervention and identify extent of collateral
perfusion (sooner if clinically indicated)
Contact sports include rugby, karate, hockey and wrestling
High impact sports include netball, step aerobics, basketball, football, boxercise, squash and tennis.
References:
Newburger JW et al. Circulation 2004
Eleftheriou D et al. Arch Dis Child 2014
149
Chapter 49 - Treadmill (Exercise stress test)
YM Fu, KL Kwok
Indications:
1. Exertional chest pain
2. Arrhythmia
a) Ventricular arrhythmias increasing in frequency with exercise may require therapy. If
the arrhythmias can be abolished by exercise and are not associated with organic
cardiac disorders, they are generally benign.
b) AV block: if it worsens with exercise, it may require therapy.
3. Aortic valve disease :
a) Aortic stenosis: ischaemic changes on ECG during exercise may be an indication for
surgery
b) Aortic regurgitation: ST changes or failure to raise HR with exercise may indicate LV
dysfunction and may need valve replacement
4. Post-operative evaluation:
a) Cyanotic congenital heart diseases: those which develop multiform PVC or VT may
lead to sudden death and require therapy (either antiarrhythmic therapy or surgery).
b) Post-coarctectomy patients who develop an excessive increase in BP with exercise
may need antihypertensive treatment.
5. Exercise prescription for participation in vocational, recreational, and competitive
activities.
Absolute Contraindications
Recent significant change in the resting ECG suggesting infarction or other acute cardiac
1
event
2
Recent complicated myocardial infarction
3
Unstable angina
4
Uncontrolled ventricular arrhythmia
5
Uncontrolled atrial arrhythmia that compromises cardiac function
6
Third degree AV block without pacemaker
7
Acute congestive heart failure
8
Severe aortic stenosis
9
Suspected or known dissecting aneurysm
10 Thrombophlebitis or intracardiac thrombi
11 Active or suspected myocarditis or pericarditis
12 Recent systemic or pulmonary embolus
13 Acute infections
14 Significant emotional distress (psychosis)
150
Relative Contraindications
1
Resting diastolic blood pressure > 115 mmHg or resting systolic blood pressure > 200 mmHg
2
Moderate valvular heart disease
3
Known electrolyte abnormalities (hypokalaemia, hypomagnesaemia)
4
Fixed-rate pacemaker (rarely used)
5
Frequent or complex ventricular ectopy
6
Ventricular aneurysm
7
Uncontrolled metabolic disease (e.g. diabetes, thyrotoxicosis or myxoedema)
8
Chronic infectious disease (e.g. mononucleosis, hepatitis, AIDS)
9
Neuromuscular, musculoskeletal, or rheumatoid disorders that are exacerbated by exercise
10 Advanced or complicated pregnancy
Source: From ACSM Guidelines for Exercise Testing and Prescription ed 5, Williams &
Wilkins, Baltimore, 1995, p.42, with permission.
Interpretations:
Symptoms: Anginal chest pain, fatigue, dizziness, shortness of breath
Blood pressure: normal response is elevated systolic BP and little change on diastolic BP;
failure to increase systolic BP or falls by ≥ 10mmHg indicates LV dysfunction.
Heart rate (HR): rises with exercise intensity; maximal HR = 220 - age; arbitrary target is a rise
of > 85% maximal HR.
Exercise tolerance
Ventricular arrhythmia during exercise or the recovery phase
ST changes: the most common manifestation is ST segment depression (≥ 1 mm horizontal or
downsloping); ST segment elevation (uncommon in the absence of prior infarction, but implies
severe transmural ischaemia, can locate the site of involvement)
Not useful in
1. Chest pain not likely cardiac origin
2. Screening for healthy children before athletic participation
3. Premature atrial contraction (PAC) or premature ventricular contraction (PVC) in
otherwise health children
Booking Preparation:
Consent: inform the risk of arrhythmia or myocardial infarction, may need resuscitation
Booking form (exercise challenge)
Baseline ECG, together with the consent and booking form to N8 ward clerk (Mr Wong)
May need Echo before treadmill in case to rule out LVOT obstruction
Ask patient to wear sports shoes and avoid heavy meal before treadmill
151
Chapter 50 – Treatment regime for patients with heart diseases that mandate
prophylactic antibiotics
According to Infective Endocarditis (IE) Prophylaxis Guideline 2010:
Cardiac Condition Associated With the Highest Risk of Adverse Outcome From
Endocarditis for Which Prophylaxis With Dental Procedures is recommended.
1. Prosthetic cardiac valve or prosthetic material used for cardiac valve repair
2. Previous Infective Endocarditis
3. Congenital Heart Disease (CHD) *
Unrepaired cyanotic CHD, including palliative Shunts and conduits
Completely repaired congenital heart defect with prosthetic material or device,
whether placed by surgery or by catheter intervention, during the first 6 months after the
procedure #
Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic
patch or prosthetic device (which inhibit endothelialization)
4. Cardiac Transplantation recipients who develop cardiac valvulopathy.
* Except for the conditions listed above, antibiotic prophylaxis is no longer recommended for
any other form of CHD.
#
Prophylaxis is recommended because endothelialization of prosthetic material occurs within 6
months after the procedure.
Regimes for Dental Procedures
Dental Procedures for Which Endocarditis Prophylaxis is recommended
All dental procedures that involve manipulation of gingival tissue or the periapical
region of teeth or perforation of the oral mucosa*
• The following procedures and events do not need prophylaxis: routine anesthetic injections
through noninfected tissue, taking dental radiographs, placement of removable
prosthodontic or orthodontic appliances, adjustment of orthodontic appliances, placement
or orthodontic brackets, shedding of deciduous teeth, and bleeding from trauma to the lips
or oral mucosa.
152
Regime: Single Dose 30-60 min Before Procedure
Situation
Agent
Adults
Children
Oral
Amoxicillin
2 grams
50 mg/kg
Ampicillin
or
Ceftriaxone*
Cephalexin*
or
Clindamycin
or
Axithromycin/
Charithromycin
2 grams IM or IV
50 mg/kg IM or IV
1 grams IM or IV
2 grams
50 mg/kg IM or IV
50 mg/kg
600 mg
20 mg/kg
500 mg
15 mg/kg
1 grams IM or IV
50 mg/kg IM or IV
60 mg IM or IV
50 mg/kg IM or IV
Unable to take oral
medications
Allergic to
Penicillins or
Amoxicillin - oral
Allergic to
Penicillins or
Ceftriaxone*
Ampicillin and
or
unable to take oral
Clindamycin
medication
IM indicates intramuscular, IV intravenous
*Cephalosporins should not be used in an individual with a history of anaphylaxis, angioedema
or urticaria with penicillins or ampicillin.
Antibiotic prophylaxis is recommended for procedures on respiratory or infected skin, skin
structures or musculoskeletal tissue only for patients with underlying cardiac conditions
mentioned above.
Antibiotic prophylaxis soley to prevent infective endocarditis is NOT recommended for
gastrointestinal (GI) or genitourinary (GU) tract.
An antibiotic for prophylaxis should be administered in a single dose before the procedure.
If the dosage of antibiotic is inadvertently not administered before the procedure, the dosage
may be administered up to 2 hours after the procedure. However, administration of the dosage
after the procedure should be considered only when the patient did not receive the
pre-procedure dose.
153
Chapter 51 – ECG criteria for LVH & RVH & prolonged QT interval
KL Kwok
Criteria for LVH:
1. Left axis deviation for patient’s age
2. a. R in I, II, III, aVL, aVF, V5 or V6 greater than the upper limits of normal for age
b. S in V1 or V2 greater than the upper limits of normal for age
3. R/S ratio in V1 and V2 less than the lower limits of normal for the patient’s age
4. Q in V5 and V6, 5mm or more, coupled with tall symmetric T waves in the same leads
(volume overload)
5. Wide QRS-T angle with T axis outside the normal range indicates a strain pattern. This is
manifested by inverted T waves in lead I or aVF.
Simplified version of ECG definition for LVH:
R/S (V1)
R (V6) mm
S (V1) mm
0-7 days
< 0.1
> 10
>20
7-30 days
<1
> 15
> 10
1-3 months
< 0.3
> 20
> 15
3-12 months
< 0.1
> 20
> 15
1-3 years
< 0.1
> 20
> 25
3-16 years
< 0.02
> 25
> 25
Criteria for RVH:
1. Right axis deviation for patient’s age
2. a. R in V1, V2, or aVR greater than the upper limits of normal for patient’s age
b. S in I and V6 greater than the upper limits of normal for the patient’s age
3. Abnormal R/S ratio in favour of the RV in the absence of BBB
a. R/S ratio in V1 and V2 greater than the upper limits of normal for age.
b. R/S ratio in V6 less than 1 after 1 month of age
4. Upright T in V1 in patients more than 3 days of age, provided that T is upright in the LPLs
(V5, V6). Upright T in V1 is not abnormal in patients 6 years or older.
5. A q wave in V1 (qR or qRs pattern) suggests RVH.
6. Wide QRS-T angle with T axis outside the normal range indicates a strain pattern.
Simplified version of ECG definition for RVH:
R/S (V1)
R (V1) mm
S (V6) mm
0-7 days
> 10
> 25
> 10
7-30 days
> 10
> 25
> 10
1-3 months
>6
> 20
> 10
3-12 months
>4
> 20
> 10
1-3 years
>4
> 20
>5
3-16 years
>2
> 10
>5
Criteria for RVH in Newborn:
S waves in lead I ≥ 12 mm
R waves in aVR ≥ 8 mm
Abnormalities in V1:
1. Pure R wave (no S wave) in V1 greater than 10mm
2. R in V1 ≥ 25 mm
3. qR pattern in V1 (also in 10% of healthy newborn)
4. Upright T waves in V1 in newborns more than 3 days of age with upright T in V6
RAD greater than +180º
154
Criteria for bi-ventricular hypertrophy:
1. Positive voltage criteria for RVH and LVH in the absence of BBB or WPW syndrome
2. Positive voltage criteria for RVH or LVH and relatively large voltages for the other
ventricle
3. Large equiphasic QRS complexes in two or more of the limb leads and in the
mid-precordial leads (V2 through V5), called Katz-Wachtel phenomenon
Prolonged QT interval:
Corrected QT interval > 0.44 sec
Higher risk for fatal arrhythmia if QTc > 0.53 sec
Diagnostic criteria LQTS—1993 Schwartz
ECG findingsa
(A) QTcb
≥480 ms
460–479 ms
450–459 ms (in males)
3 points
2 points
1 point
(B) Torsade de pointesc
2 points
(C) T wave alternans
(D) Notched T wave in three leads
1 point
1 point
(E) Low heart rate for aged
0.5 point
Clinical history
(A) Syncopec
With stress
Without stress
(B) Congenital deafness
2 points
1 point
0.5 point
Family historye
(A) Family members with definite LQTSf
1 point
(B) Unexplained sudden cardiac death below age 30 among
immediate family members
a
0.5 point
In the absence of medications or disorders known to affect these ECG features.
Calculated by Bazett's formula, where QTc = QT/√ RR.
c
Mutually exclusive.
d
Resting heart rate below the second percentile for age.
e
The same family member cannot be counted in A and B.
f
Definite LQTS is defined by an LQTS score ≥4. Scoring: ≤1 point, low probability of LQTS;
2–3 points, intermediate probability of LQTS; ≥4 points, high probability of LQTS.
b
155
Drugs affecting QT interval (List of drugs is not exhaustive)
Common Drugs used in children that prolong QT interval and/or induce Torsade De
Pointes
1. Anti-arrhythmics—
e.g. Amiodarone, Flecainide , Procainamide, Quinidine, Sotalol
2. Antibiotics—
e.g. Clarithromycin, Erythromycin, Levofloxacin, Azithromycin
3. Others:
e.g. Octreotide, Salmeterol
Drugs to be avoided in patient with Long QT interval:
1. Bronchodilator—
e.g. Albuterol, Salmeterol, Terbutaline
2. Antiviral—
e.g. Amantadine
3. Catecholamine—
e.g. Dobutamine, Adrenaline, Nor-adrenaline
4. Decongestant—
e.g. Ephedrine, Phenylephrine, Phenylpropanolamine, Pseudoephedrine
5. Antibiotics—
e.g. Azithromycin
156
Section 4: Central nervous system
157
Chapter 52 - Acute management of post-neonatal convulsion
S Cherk
1. Monitor vital signs
2. Maintain airway, protect from injury and place the child in semi prone position. Apply suction
for nasal or oral secretion if any
3. Give oxygen supplement during seizure until full post-ictal recovery of conscious state
4. If convulsion lasts for more than 5 minutes:
a) If IV access present or attained readily
IV Lorazepam 0.1 mg/kg/dose (maximum 4 mg/dose),
may repeat dose 10 min later, max total dose 8 mg in adolescent
b) If no IV access
give rectal diazepam 0.5 mg/kg/dose
or consider
buccal midazolam 0.4-0.5 mg/kg/dose (method #) (Panayiotopoulos 2007)
Refer to protocol of management of generalized convulsive status epilepticus if prolonged
convulsion.
5. Detailed history and examination to look for underlying cause of convulsion.
# Method
- child lie on side in coma position
- open lips, trickle midazolam from syringe into inside of cheek (dependent side) between the
cheek and lower gum.
- no need to open jaw
158
Chapter 53 - Generalized convulsive status epilepticus
(Excluding neonates)
S Cherk
Airway – Recovery position, suction (Yankauer sucker if food in mouth)
Breathing – SpO2 monitor, high flow O2 by mask
Circulation – AR/ BP/Capillary return
Immediate IV Access+ Blood taking (Glucostix, blood sugar, e, Ca, Mg (<1yr) , CBP, blood gas,
L/RFT, NH3 +/- blood culture, +/- toxicology/anticonvulsant level),save plasma 1-2 ml & urine 20
ml for later analysis
ANTICIPATION
aim to abort seizure as quickly as possible to prevent status epilepticus
SEIZURE duration ≥ 5 min (prolonged seizure/ impending status)
1. IV Lorazepam 0.1 mg/kg
Max 4mg/dose, over 60sec
Rpt dose at 5-10 min if still Sz
If no IV access
Diazepam PR 0.5mg/kg
or Buccal midazolam 0.4-0.5mg/kg
Rpt dose at 10 min if still Sz & no IV access
SEIZURE continues at 25 minutes (Impending status)
To PICU
No IV access
IV access +
2. * IV Phenytoin 20 mg/kg in NS over 20 min
or IV Phenobarbitone if already on Phenytoin,
20mg/kg over 15 min
Paraldehyde PR 0.4ml/kg
max 5ml if < 50kg
max 10ml if ≥ 50kg
AND PR paraldehyde if not already given 0.4ml/kg
(+ same volume Olive oil) glass syringe + feeding tube
SEIZURE CONTINUES AT 45 minutes (Established Status Epilepticus by 30 min)
Patient not on
maintenance
Benzodiazepine
Patient already on maintenance Benzodiazepine
• Thiopentone
– Loading IV 3-5 mg/kg bolus
– Then infusion 3-5 mg/kg/hr
– EEG iso-electric / burst suppression
– Intubate & ventilate before loading
IV Midazolam
Loading 0.1-0.5 mg/kg
Infusion 1 -2 mcg/kg/min, incr by
1-2mcg/kg/min every 5-10 min until
seizure stops
Usu dose range :1-30 mcg/kg/min
C
159
Other IV anticonvulsants to consider:
-IV Levetiracetam 20-60mg/kg @2-5 mg/kg/min
-IV Valproate 20-40mg/kg IV @1.5-3 mg/kg/min ( but hyperNH3, pancreatitis, hepatotoxicty, decr
Plt)
General precautions:
- close monitor cardio-respiratory function & blood gas/ electrolytes
- ensure large vein IV access
- be prepared for intubation & ventilation and hemodynamic support
Consider IV pyridoxine /enteral pyridoxal phosphate in children < 3yr with unknown aetiology:
- IV Pyridoxine 100 mg/dose + 2nd dose 100 mg within 30 minutes, can repeat up to total
500mg preferrably under EEG monitor (prepare for intubation /ventilatory support as risk of
apnea ) followed by enteral pyridoxine 5-15mg/kg/day q12h if response
- if no response, consider trial enteral Pyrioxal Phosphate(PLP) 30 mg/kg/d in 3 divided doses
- send specimens:
- blood pipeocolic acid
-Urine and plasma xαAASA( immediate freezing needed)
-Urine x vanilly-lactic acid
- when patient stable and no C/I for LP : send CSF-HVA,HIAA, AA’s ( threonine, glycine)
- continue Pyridoxal phosphate if seizure stopped after pyridoxine/PLP until Ix results incl
above Biochemistry Ix reviewed by and discussed with Neuro Team
*- watch hypotension /arrhythmia- slow down infusion rate if mild bradycardia
- C/I in second degree heart block / severe hypotension/ TCA anti-depressant toxicity
- caution use in Dravet Syndrome
160
Chapter 54 - Febrile convulsion
MS Choi, S Cherk
Background:
Febrile convulsion occurs in 2-5% of all children.
Risk of recurrent febrile seizure following a first febrile seizure is around 30%.
50-75% & 90% recurrence occurs within one year & two year of initial seizure respectively.
Definition:
Febrile convulsion is defined as convulsion occurring in a child, aged 6 months to 60 months,
associated with fever without evidence of intra-cranial infection or other causes and who is
otherwise neurologically normal.
Simple febrile convulsion:
It is defined as primary generalized convulsion lasting less than 15 minutes and not recurring
within 24 hours.
Complex febrile convulsion:
It is defined as focal or prolonged (>15 minutes), and/or more than one convulsion in 24 hours.
Investigation:
1. CBP, D/C, CRP
2. RFT / Calcium / Glucose / H’stix / Blood gas
3. ± Blood culture
4. ± Urine for R/M and culture
5. ± CXR
6. Lumbar puncture is indicated if suspected CNS infection
7. EEG is rarely indicated in the management of a simple febrile convulsion
8. CT brain is not necessary in most cases except for the following situation:
- Papilloedema
- Cranial nerve palsy
- Persistent focal neurological signs
- Marked depression in mental status or comatosed
Management of febrile convulsion:
1. Convulsion chart
2. Neuro-observation
3. Monitor vital signs
4. Maintain airway, protect from injury and place the child in semi prone position
5. Give oxygen supplement during seizure until full post-ictal recovery of conscious state
6. Apply suction for nasal or oral secretion if any
7. Treat fever by tepid sponging and syrup panadol 10-15 mg/kg/dose Q4H prn
8. Identify the focus of infection and treat accordingly
9. For acute treatment of convulsion, please refer to chapter 49
10. Refer to protocol of management of generalized convulsive status epilepticus (chapter 53) if
prolonged convulsion
161
Prophylaxis for recurrent febrile convulsion:
- Intermittent diazepam prophylaxis seems to be effective in reducing recurrence rate if
sufficient doses are given
- In selected cases, give oral Valium 1 mg/kg/day Q8H for consecutive 6 doses whenever the
rectal temperature is ≥ 38.5oC
- Side effects of diazepam include ataxia, lethargy and irritability. Alert parent to monitor the
child regularly in case the underlying infection may be masked due to lethargy from the
effect of diazepam.
Prognosis:
- Prognosis in terms of intellectual outcome is good
- Recurrence risk is 50% if febrile convulsion occurs in the first year of life
Prediction for seizure recurrence
Major :
Early age of first seizure (<18 mo)
Positive FH of febrile seizure (1st degree relative)
Others :
- Low degree of fever prior to initial seizure (<38˚C)
- Brief duration between fever onset and initial seizure (<12 hour)
Risk ≥70% vs ≤ 20% (all 4 risk factors above vs none)
- Abnormal neurologic background
- Positive F/H afebrile seizure (1st degree relative)
- Seizure recurrence within same febrile illness
Risk of later epilepsy:
- Risk following a simple febrile seizure:
- 1-2.4 % (vs 0.4% in general population)
- Risk of epilepsy following a complex febrile seizure depends on number of risk factors
present:
Risk factor for developing epilepsy:
- * Preexisting neurological abnormality
- * Family history of afebrile convulsion
- * Complex first febrile convulsion
When a single complex feature present: risk 6-8%
When all three complex features* present: 49%
Immunization:
No contraindication for the current standard vaccination
162
Chapter 55 - Approach to a child with decreased conscious level
S Cherk
Ensure child is maximally aroused from sleep when assessed.
-Excluded :
-children with known condition for episodes of reduced conscious level
( e.g. epilepsy, DM) where management plan available
-children whose baseline GCS is <15
GCS <15
Assess A,B,C ;
Give O2
Consider intubation if : airway obstruction/airway compromised;
RR inadequate for ventilation; SaO2 <92% despite high flow
O2/airway opening maneuvers; signs of shock despite 40 ml/kg
fluid; exhaustion; GCS≤8 or deteriorating; signs of ↑ICP
Assess for -↑ICP: (GCS, pupils, fundi, bradycardia, HT, irregular
breathing)
-ongoing seizure
Monitor vital signs
Monitor GCS
Consider ICU care if GCS≤10 /
deteriorating / fluctuating GCS /
suspected ↑ICP/ potential need resp
support
Core Ix:
Dextrostix
Blood x gases, gluc (even if D’stix N), U&E,
Ca, Mg
LFT,CBP
Blood culture, NH3,lactate
X5-6 ml ( to be kept in fridge)
X 3ml Lithium blood-sent in ice for
centrifuge for AA & carnitine
P/E, in particular
Urine x bedside multi-stix
Rash (purpuric, vesicular) ; odour
X RM, culture
Subtle motor seizure( mouth, digit, eyelid twitch)
x 20 ml for toxicology ( send out)
Involuntary movements/ abn posture
X 20 ml to be kept in fridge
Wounds/ bites/ injection sites
CT scan+/- contrast to look for intracranial
Signs of raised ICP
SOL/swelling/ brain shift if:
- condition stable and safe for transfer (need MO
escort with readiness for O2,airway support
and intubation)
Identify problems and manage accordingly ( these may
be aetiology
effects )
- consider
priororintubation
Hx, particular attention to includes:
Alternating periods of consciousness
PH similar episodes
Recent illness (rash- VZV, measles)
animal or insect bites
steroid intake/adrenal insufficiency
Any prev FHx infant deaths/ALTE /consanguinity
163
Problem list ( aetiology or complications)
shock
sepsis
trauma
CNS
infection
or
inflamm
ation
↑ICP
Prolonged
convulsion
Post
convul
-sion
(if
>1hr)
Meta-bolic
e.g.
e-disturba
nce
Hypogly
DKA
HyperNH3
HT
Others
Drugs
Unknown#
If CNS infection suspected
Ix:
LP if no contra-indication (*) and intracranial SOL/ swelling/ brain shift excluded by CT scan (**):
-opening pressure
-Gluc (paired with blood gluc)& protein
-G stain, RM (+/- AFB smear) ,culture (+/-TB )
-viral PCR( HSV, VZV,enterovirus, +/-TB) (beware of false –ve CSF HSV PCR within first 3D of illness)
-viral culture,bacterial culture, +/- TB culture
-IgM and IgG for virus , mycoplasma
-lactate
-+/- oligoclonal band (paired with serum if suspected non-infectious related encephalitis)
-spare specimens ( 3 bottles) to be kept in fridge
NPAx resp virus, mycoplasma PCR
Urine x pneumococcal Ag
throat and rectal swab x enterovirus
Blood x serology
Vesicular fluid swab x VZV,HSV
Empirical Tx ( Don’t delay if LP contra-indicated):
Consider
IV Cefotaxime + IV ampicillin (<3 mo), IV vancomycin (if suspect pneumococcus)
IV Azithromycin (caution high macrolide resistant mycoplasma common)
IV acyclovir : Neonate -3mo : 20mg/kg Q8h
3mo-12 yr :10-15 mg/kg Q8h
12-18 yr : 10 mg/kg Q8h
Adjust dose in renal impairment
Total 3 weeks (lower relapse rate if Tx high dose ≥30mg/kg/D and duration > 14D; otherwise
relapse rate up to 26%)
Consider oseltamivir
164
If no obvious cause after initial assessment and initial Ix ( Unknown #)
-CT scan
-LP if safe
-urine x toxicology screen
-urine OA, AA
-blood x AA, acylcarnitine
-ESR/ AI screen ; TFT/ thyroid auto-antibodies
-urgent EEG
-Empirical treatment for CNS infection
*Contra-indication for immediate LP :
Features suggestive of raised ICP:
-moderate to severe impaired conscious state (<13), or fall in GCS >2
-focal neurological signs (unequal/dilated or poorly responsive pupils)
-abn posture or posturing
-papilloedema
-bradycardia (HR<60/min)
-Hypertension ( BP>95% for age)
-abnormal doll’s eyes
-abn breathing pattern
-had seizure lasting >10 min and still has GCS ≤12
Systemic factors:
-shock
- Respiratory insufficiency
-coagulation abnormalities ( e.g. platelet <100 x109/L, abn clotting profile, if
on warfarin, need to change to heparin first)
-suspected meningococcal septicemia (extensive or spreading purpura)
Local factors:
-local infection at LP site
** A normal CT scan does not exclude acutely raised ICP
165
Chapter 56 - EEG
CS Ho
Purpose:
- Most commonly done for the diagnosis of seizure disorders
- Certain manifestations such as impaired learning, strange behaviour or drop attack may be due
to an underlying seizure disorder so EEG may sometimes be done
- Certain neurodegenerative disorders
- As an ancillary diagnosis of brain death
Sedation for EEG:
- Avoid using sedation as far as possible, refer to department sedation protocol
- Even in small children, a quiet, comfortable and child-friendly environment may allow the
child to go into natural sleep without using sedation
- Sleep deprivation the previous night is useful both as an activation procedure to increase yield
and to induce natural sleep during recording
- Preferable to have recording in all stages from awake, drowsy to light and deep sleep. This is
part of the reason why sedation is not preferred.
Diagnosis:
Significance
- The diagnostic hallmark for epileptic disorders, the paroxysmal discharges (spikes), may be
present in 3.5% of children with no clinical seizure manifestation. A small percentage (<10%)
of these may subsequently develop clinical seizure in later life.
- The EEG can be normal in half of the epileptic patients in the interictal stage.
Patterns in epileptic disorders
Interictal Findings
Persistent burst suppression in neonates
Hypsarrhythmia
Generalized “slow” spike-waves
Frequent / Continuous spike-waves during slow wave sleep
Generalized 3/second spike-waves
Epileptic Disorder
Ohtahara Syndrome
Infantile Spasm
Lennox-Gastaut
Landau-Kleffner
CSWS
Primary generalized epilepsy
(If ictal
absence epilepsy)
Focal / Partial epilepsy
Rolandic epilepsy
→
Focal spikes, sharp waves, spike-waves
Centro-temporal spikes (increase during sleep)
Other abnormalities:
- Focal slowing: postictal change; mass lesion
- Asymmetric background: congenital malformations; subdural effusion / haematoma;
postoperative changes
- Excessive generalized beta waves: drug effect; mental retardation
EEG in the newborn:
- Individual sharp waves difficult to interpret in newborns – may be normal in premature
neonates. Only significant if frequent and persistently localized.
- The background pattern is more important. Even in the quiet sleep stage the background should
be bilaterally synchronous after 40 weeks gestational age and continuous by 44 weeks
gestational age. A grossly suppressed background or a discontinuous background indicates
serious underlying illness and/or bad prognosis.
166
Chapter 57 - Sedation
DK Ng, CS Ho
Classification of physical status (American Society of Anesthesiologists)
1) A normal healthy patient
2) A patient with mild systemic disease (e.g. asthma with mild wheeze)
3) A patient with severe systemic disease (e.g. asthma with active wheeze)
4) A patient with severe systemic disease that is a constant threat to life (e.g. status asthmaticus)
5) A moribund patient who is not expected to survive without the operation (e.g. cardiomyopathy
awaiting heart transplant)
6) For organ donor
Four stages of Depth of Sedation:
1) Minimal Sedation / Analgesia (Anxiolysis)
A drug-induced state during which patients respond normally to verbal commands. Cognitive
function and cooperation may be impaired, ventilatory and cardiovascular functions are
unaffected.
2) Moderate Sedation / Analgesia (Conscious Sedation)
A drug-induced depression of consciousness during which patients respond purposefully to
verbal commands, either alone or accompanied by light tactile stimulation. Spontaenous
ventilation is adequate. Cardiovascular function is usually maintained.
3) Deep Sedation
A drug-induced depression of consciousness. Patients cannot be easily aroused but respond
purposefully following repeated or painful stimulation. Reflex withdrawal is not considered a
purposeful response. The ability to maintain ventilatory function may be impaired; may require
assistance in maintaining a patent airway; spontaneous ventilation may be inadequate.
Cardiovascular function is usually impaired.
4) Anaesthesia
A drug-induced loss of consciousness during which patients are not arousable, even by painful
stimulation. Ability to independently maintain ventilatory function is often impaired. Patients
often require assistance in maintaining a patent airway or drug-induced depression of
neuromuscular function. Cardiovascular function may be impaired.
Pre-sedation steps:
1. Monitoring of vital signs +/- SpO2 is essential during and after sedation
2. Appropriate sized mask and bag, oxygen and suction must be available at the bedside for
immediate use.
3. All patients who will be given sedatives (including syrup chloral hydrate) for elective
investigations / procedures should be put on NPO for at least 4 hours beforehand, to minimize the
risk of vomiting / aspiration.
167
Cautions:
1. Sedation must not be given to calm an irritable child when the underlying reasons, e.g.
hypoxaemia, hypercapnia, cerebral hypoperfusion, are not clear.
2. When sedation is given to a child with borderline organ perfusion, a large patent IV access must
be ensured beforehand and a bottle of normal saline must be immediately available.
Medications:
All intravenous sedatives must be titrated against the patient’s response. The initial calculated dose
should be given in a stepwise fashion instead of one go.
1) Give melatonin 0.25-0.5 mg per kg (to be rounded up to no decimal place, up to 3 mg max.) 45
minutes before scheduled procedure. Keep the child on the stretcher in a quiet and darkened
room to facilitate sleep and accompanied by parents
2) Chloral hydrate
(A) Usual paediatric patient
Initial dose: 50-75 mg/kg
2nd dose if first dose cannot adequately sedate patient in 30 minutes.: 25 mg/kg
Cumulative dose should not exceed 2 gram
(B) Reduce dosage
Neonates: 50 mg/kg
Patients with suspected ↑ intracranial pressure, respiratory depression, impaired liver / renal
function: 25-50 mg/kg
Give one dose only
N.B. (a) Chloral hydrate should not be given in patients with liver / renal failure or in patients with
gastritis
(b) Syrup chloral hydrate has to be diluted before administration
3) Dormicum up to 0.1 mg/kg ivi
4) Fentanyl 1-3 mcg/kg ivi
5) Ketamine 1 mg/kg ivi, or 2 mg/kg imi (give atropine 0.01 mg/kg, minimum 0.1 mg before
ketamine to decrease risk of laryngeal spasm)
6) Propofol 2.5-3.5 mg/kg (Caution : hypotension is common and is to be treated with iv fluid bolus +
iv ephedrine)
168
Chapter 58 - Normal neuro-developmental milestones
MS Choi
1. Gross motor:
1 month:
3 months:
4 months:
5 months:
6 months:
7 months:
11 months:
12 months:
15 months:
18 months:
2 years:
3 years:
4 years:
5 years:
2. Fine motor:
1 month:
3 months:
4 months:
5 months:
6 months:
9 months:
12-15 months:
15 months:
18 months:
2 years:
2.5 years:
3-4 years:
5 years:
Almost complete head lag when pulled to sit
Complete flexed on ventral suspension
Only moderate head lag when pulled to sit
Extend head above plane of body on ventral suspension
No head lag
Draw feet to mouth and play with feet
Roll over from prone to supine
Sit with hands forward for support
Bear weight when supported
Sit without support
Roll over from supine to prone
Pivoting
Walk while holding on furniture
Crawl like a bear
Stand up without help
Sit in a chair
Walk with mature gait
Climb up and down stairs two feet per step
Climb up stairs one foot per step
Stand on one leg
Hop on one foot
Climb down stairs one foot per step
Skip on both feet
Fisting of hands
Hands open
Outreaching
Hold on milk bottle
Transfer
Mouthing
Finger-thumb grasp
Throw objects
Feed self with spoon
Turn 2-3 pages of a book
Turn single page
Thread beads
Fasten buttons
Tie shoe lace
169
2.1. Drawings:
18 months:
2 years:
3 years:
4 years:
4.5 years:
5 years:
From 3 years:
Scribble
Imitate circular scribble
Copy a circle
Copy a cross
Copy a square
Copy a triangle
Draw a man (for every additional part of body, add 0.25 years)
2.2. Handedness:
1 year:
2-6 years:
Shift from side to side
Definite hand dominant
2.3. Cubes:
15 months:
18 months:
2 years:
2.5 years:
3 years:
4 years:
3. Speech:
3 months:
6 months:
8 months:
1 year:
15 months:
18 months:
2 years:
2.5 years:
3 years:
4 years:
Tower of 2
Tower of 3
Tower of 6
Imitate train
Tower of 8
Imitate train with chimney
Tower of 9
Imitate bridge of 3
Imitate gate of 5
Cooing
Babbling
Respond to his name
Respond to ‘NO’
Understand people’s name
Use 2-6 recognizable words
Use 6-20 words
Point to 3-4 body parts
Use 2-3 words simple sentence
Give first name
Give full name
Full sentence of 4-5 words
Give full name and sex
Count 1-10
Give full name, age, sex and address
Name primary colours
170
4. Hearing:
3 months:
6 months:
9 months:
5. Vision:
1 month:
3 months:
6-9 months:
6. Social:
1.5 months:
3 months:
6 months:
1 year:
2 years:
3 years:
4 years:
Turns head to the direction of nearby noise or meaningful sounds
Localize sounds at 18 inches on ear level
Localize sound at 3 feet above or below ear level
Follow objects to midline
Follow objects beyond midline
Fixate on hundreds and thousands at 12-15 inches
Fixate and follow small object at 3 meters distance
Graded ball vision tests usually applicable
Social smile
Interest in surroundings
Stranger anxiety
Kiss on request
Wave ‘bye-bye’
‘Parallel play’
Dry by day
Join and play with other children
Dry by night with occasional wet bed up to 4-5 years old
Go to toilet alone
171
Chapter 59 - Childhood epilepsy natural history (counselling)
KK Chan, S Cherk
Risk of seizure (Sz) recurrence:
- 2nd sz after first sz ~40% (Berg & Shinnar)
- 3rd sz after 2nd sz (less info) at least 80% (Camfield, Shinnar)
- Predictor for 2nd sz:
- remote symptomatic cause
- partial sz
- intellectual or mental handicap
- EEG spikes
- prior acute sz including febrile sz
- status epilepticus
- multiple sz at the index episode
- Todd’s paralysis
e.g. recurrence risk 20-30% in a normal child with GTC + normal intelligence and normal
EEG
vs
80-90% mental handicap + partial sz + spike discharge EEG
Starting medication
- no evidence prescription of medications alters long term prognosis of childhood epilepsy
(Camfield 1996)
- medications are anti-seizure rather than anti-epileptogenic (Kwan, Sander)
- main reason to treat with medications: avoidance of bodily harm from sz and improvement in
psychosocial function
- only 20% will have “smooth-sailing epilepsy”, i.e. sz free immediately + later able to wean off
AEDs without ever recurrence
- only 50% children continue to receive the same medication 1 year after starting medication
Long term remission
- for many children, sz is transient and seems to vanish as the child gets older
- at time of diagnosis: possible to predict at least 50% children will outgrow the disorder and be
able to discontinue AEDs
- the longer the follow-up period, the higher rate of remission
- good prognostic factors: normal intelligence, normal physical examination, relatively small
number of sz at diagnosis, age of onset younger than 12 years, absence of a remotely
symptomatic cause, generalized onset of sz
- good prognosis: 80% chance remission vs 40% in those with ≥ 1 adverse factor
172
Stopping medications
- ~70% children with epilepsy who have been sz free for 1-2 years can successfully stop AED
(rate of success is not greater if medication is continued for up to 5 years)
- Factors for successful discontinuation of AED:
- generalized sz
- age of onset < 10-12 years
- normal neurological findings
- resolution of interictal EEG spikes (some studies)
- Children who have no adverse factors may have 80-90% success rate
- Additive effect on adverse factors: those with all adverse factors have only 10-20% success rate
- If initial discontinuation trial unsuccessful: re-start anticonvulsant previously on
~ 50% will become sz free again for sufficient time to try discontinuation of medications for 2nd
time
- 70 % success rate
Ref: Swainman et al, Principle in Paed Neurol 2006
Kevin Farrell, E Wirrell. Definition & Prediction of Intractable Epilepsy in Children
173
Chapter 60 - Therapeutic hypothermia in paediatric patients
S Cherk
Indication:
Coma in patients who respond to resuscitation from cardiac arrest
Aim:
- Start cooling as soon as possible; can be started even up to 8 hours post arrest
- Aim at target core temperature 32-34°C (avoid over-cooling and excessive fluctuation)
- Cool to reach target as fast as possible e.g. 3-4 hours
- Hypothermic duration 12-24 hours
- Slow controlled re-warming at 0.25-0.5°C/hour to target 36°C
Patient Preparation:
- DO NOT actively re-warm patients who are spontaneously hypothermic
- Inspect whole body for potential pressure sores. Need meticulous skin care.
- Set arterial BP monitor (more difficult with subsequent vasoconstriction)
- Prevention and control of shivering important:
- Consider IV pethidine which increases threshold of shivering + prn neuromuscular blocker
Method:
- BLANKETEROLL II cooling blanket (adult / child / infant size +/- ice packs)
- Preferably patient is sandwiched between 2 blankets (if not, patient covered by 1 cooling
blanket)
- Bed sheet between patient and cooling blanket
- Meticulous nursing care (see Nurses’ protocol)
Monitor:
- Continuous core temperature monitor e.g. oesophageal temp
- Secondary temperature device (core temp probe preferred) e.g. rectal / (skin temp)
- Continuous BP monitor, maintain arterial BP
- Watch hypotension especially during induction (diuresis) and re-warming (vasodilatation)
- Continuous cardiac and SaO2 monitor
- Watch for arrhythmia
- Bradycardia often occurs: continue hypothermia if no haemodynamic problems
- If ICP monitor present, maintain cerebral perfusion pressure > 55 mmHg (mean arterial BP - ICP)
- blood tests
- At 0 hour: CBC / clotting / RFT / PO4 / glu / arterial blood gases / troponin
- Q6H: glu / K / ABG
Watch hypoK during hypothermia; treat when K<3.5
Watch hyperK during re-warming
Stop K administration once re-warming starts
Need tight control of blood glucose
(avoid hyperglycaemia – deleterious to injured brain)
-Q12H: clotting / CBP Q12H
(clotting may be falsely normal, as test is done at room temp)
-Skin care Q2-6H for thermal injury
-Watch for bleeding / abnormal clotting tendency
174
Adverse reactions to watch out for:
Arrhythmia
Hypotension
Initial decreased urine output
Shivering – increased acidosis,
decreased efficiency of hypothermia
Prolonged half-life of drugs
Electrolyte – K/PO4
Hyperglycaemia
Abnormal acid base
Decreased and impaired platelet count /
function; bleeding tendency
Increased risk of infection
Discontinue active cooling and start re-warming if:
- Life-threatening arrhythmia
- Haemodynamic instability
- Bleeding due to clotting dysfunction
Re-warmimg (most critical)
- Start 12-24 hours from initiation of hypothermia
- Watch BP closely – high risk of hypotension as vasculature dilates (may need IV bolus if BP
drops)
- Watch hyperK- stop K infusion if any
- Re-warm slowly at 0.25-0.5°C/hour to target 36°C (takes approximately 8 hours)
- Maintain paralytic agent and sedation until temp ≥ 35°C
- Check electrolytes (especially serum K) at start of re-warming and q4H until re-warming
complete
Others
- No nutrition during whole period of hypothermia and re-warming
- Don’t forget other neuro-protective measures
e.g. head central and up 30°
normocarbia
175
Chapter 61 - Tics and Tourette’s syndrome in childhood
TH Fung, S Cherk
Tics- sudden, stereotyped, coordinated and involuntary movements or sounds
Simple: single movement e.g. eye blinking
Motor
Complex: sequential pattern or coordinated actions
Tics
Vocal
Simple: inarticulate noises or sounds
Complex: partial words, words or phrases
Features: - premonitory urge or sensation that improves after performing the movement
- may be suppressible for a brief period of time
- can lead to pain, injury
- does not occur in sleep
- onset < 18 years of age
- not due to direct effects of drug / general medical condition
- occur many times a day nearly every day
Classification: DSM IV – TR:
Type
Transient tic disorder
Chronic motor or chronic vocal tic
disorder
Tourette’s syndrome / disorder (TS)
Features
- at least > 4 weeks but < 12 months
- either single or multiple motor and / or vocal tics
- at least 1 year duration with no tic free period of > 3
consecutive months
- single or multiple tics but confined to one class
(either motor or vocal)
- combination of motor and vocal tics
(not necessarily at the same time)
- at least 1 year duration with no tic free period > 4
consecutive months
Evaluation
- To distinguish from other type of involuntary movments: myoclonic jerks, stereotypies, dystonia
and compulsions
- Need to exclude: underlying organic cause e.g. CNS disorder, drug effect etc
- Thorough history and neurologic examination generally sufficient
- Imaging and EEG usually not needed
- Check for
- associated neuropsychiatric disorders like ADHD, OCD, mood disorders
- psychosocial stressors
- To determine which symptoms are disabling (target symptoms for treatment)
Epidemiology
- Chronic tic disorders: ~ 2-5% school-age children
- Transient tic disorders at least as common as chronic tics
- TS: ~10-30 cases per 10,000 children
- M : F = from 10 : 1 to 2 : 1
- Peaks between 7 and 15 years
- In TS, high co-morbidity rate of attention deficit hyperactivity disorder (ADHD) and obsessive
compulsive disorder (OCD)
176
Prognosis and treatment
- Natural history: symptoms wax and wane
- 1/3 complete remission in late adolescence or young adulthood
- Further 1/3 improves to mild severity
A) Most need parental education and reassurance only
B) Refer Clinical Pyschologist for behavioural therapy and look for co-morbid conditions
e.g. Habit Reversal Therapy: application competing response whenever the patient notices tic or
has urge to tic
C) Refer Child Psychiatrist if Tourette Syndrome
D) Treatment directed first at the most troublesome symptoms
E) Medications (last resort): suppresses tics; choice depends on presence of co-morbidity:
i) Clonidine:
- first line in mild to moderate tics: 0.05 mg bd, gradually↑to 0.1mg bd / qid
- if also ADHD: may be additive effect with Methylphenidate
ii) neuroleptics
a)
fluphenazine, haloperidol, pimozide: tics decrease by 50-80%, but extrapyramidal side
effects / tardive dyskinesia
b)
risperidone: fewer side effects
E) Treatment co-morbid conditions e.g. OCD and ADHD
177
Chapter 62 – Global developmental delay/ Intellectual Disability
(Mental retardation) – diagnostic approach
S Cherk
Definition:
Global developmental delay (GDD)
= significant delay in ≧ 2 domains in children < 5 years:
- GM + FM; Speech and language; Cognition; Personal and social; ADL
- Significant = performance ≧ 2 SD below mean
Intellectual Disability (ID)
= significant sub-average intellectual ability accompanied by significant limitation in adaptive
functioning
- GDD is not always predictive of ID (environmental factors), but many cases will
Classification of intellectual disability
DQ level
Mild intellectual disability
50-55 to approximately 70
Moderate intellectual disability
35-40 to 50-55
Severe intellectual disability
20-25 to 35-40
Profound intellectual disability
20-25
(Developmental Quotient (DQ): functional age/ chronological age )
Aetiology:
- Estimate of diagnostic yield of GDD 10-81% (yield higher if moderate/ severe ID)
- Commonest:
- Genetic
- Syndromal
- Structural brain abnormalities
- Genetic cause, test by
- G-banded karyotype -> 4% (mild-mod ID: 3.7-10%)
- FISH/ MPLA – 3.5%
- Microarray – 7.8%
- X-linked ID genes in male with appropriate F/H – up to 42%
- IEM only found in 1-5% cases
Diagnostic approach:
History
- Maternal history-e.g. recurrent spontaneous miscarriages suggests chromosomal
rearrangement/ unbalanced translocation;
- Previous stillbirths /neonatal deaths/ sudden infant death may underlie an IEM problem;
- Exposure to potential teratogens, for example anti-epileptics, antidepressants, warfarin,
alcohol (e.g. binge drinking in the first trimester), nicotine and illicit drugs;
- Early neonatal events: complications of delivery, hypotonia, hypoglycaemia/seizures;
- Family history - parental consanguinity (3 generation pedigree) (genetic syndrome ;
neurological disorders /learning/ developmental problems)
- Sleep disturbance / nocturnal snoring
- Diet and pica
- General medical history
- Delay static or progressive/regression
- Autistic features
- Seizures
178
-
Hearing/ visual problem/eyes (+/- ophthalmological referral)
Repetitive stereotypic hand movements (e.g. Rett, Happy puppet)
Clinical examination
- Growth parameters
- Neurocutaneous stigmata
- Dysmorphism, congenital abnormalities and reduced family resemblance
- Features of storage disorders, –e.g. hepatosplenomegaly, corneal clouding
- Cardiomyopathy –e.g. mitochondrial respiratory chain disorders
- Visual impairment –e.g. retinitis pigmentosa and ciliary disorder
- Neurological signs
- Vision and hearing
Diagnostic approach
- Features syndromic or non-syndromic ?
- refer for formal developmental assessment /Formal hearing assessment / formal vision
assessment
Need review regularly for regression or emergence of suggestive phenotype
179
Investigations
1.
2.
Thorough history and PE
If diagnosis not apparent consider following investigations:
First line investigations
Full blood count
Vitamin B12 /Ferritin
Urea and electrolytes ,CPK, Lead
Thyroid function tests (TT4/T3/TSH)
Urine metabolic screen (including amino acid, organic acid, sugar chromatography &
glycosaminoglycans (GAG) screen )
Refer Clinical Genetics (e.g. Molecular karyotype/ array CGH/XL DNA)
Second line
Consider discuss with or referral to neurologist or metabolic person or further discussion with
geneticist for further investigations which may include:
Metabolic
Family history, consanguinity
developmental regression, acute/
recurrent encephalopathy
Recurrent vomiting
Organomegaly, coarse features,
hypotonia, myopathy
Neuroimaging
Abnormal
head size
seizures, focal
neurological
sign
EEG
Speech regression
Seizures
neurodegenerative
disorder
Genetics
Dysmorphism
abnormal growth
sensory
impairment, odd
behavior, family
history
consanguinity
Consider 24-h EEG
MRI/ MRS
CT (bones, calcification)
Blood
NH3, uric acid
transferrin isoforms
VLCFA, homocysteine
paired blood and CSF
lactate, pyruvate, glucose
and amino acids
+/- CSF neurotransmitters
Urine
EMU uric acid/creatinine
Urine x homocysteine
Consider :
Urine & serum creatine and
guanidinoacetate
Priority in Ix: look for potentially treatable disorders
Further tailored investigation depends on associated findings
Repeated evaluation important as symptoms and signs may evolve
180
Consider skeletal
survey
Specialized
genetic diagnostic
testing
Table I History suggestive of IEM
Features sugg of IEM
Pregnancy
HELLP, AFLP
Family history
Consanguinity, unexplained
neonatal or infantile deaths
X-linked inheritance pattern :
Past medical history
Type of developmental delay
Other problems
Unexplained hypoglycaemia
Encephalopathy
Protein aversion
Self injurious behaviour
Psychotic symptoms
Regression/ progressive
developmental delay
Hypotonia
Sensorineural deafness
Seizures
- Severe sz + Neonatal onset
- Severe seizure infantile
onset
Seizures
+ extrapyramidal movement
+ hypotonia
Progressive Neurological
Symptoms
Examples of IEM
FAO
-Creatine transporter deficiency
-MCT8 mutations
-Occipital Horn syndrome
Urea cycle disorder
Lesch-Nyhan, hyper-ammonaemia,
purine/pyrimidine metabolism
Cobalamin disorder, LSD, Wilson’s
Strongly suggestive of IEM
(+ severe sz: LSD)
OA, FAO, urea cycle disorder
Mitochondrial disease
- NKH, perioxisomal disorders
- Sulphite/ molybdenum cofactor
deficiency
- Glut Transporter Deficiency
AA, CDG, Glycogen synthetase def,
LSD, Menkes’ Dis, Mitochondrial dis,
purine/ pyrimidine metabolism
Creatine deficiency
purine/ pyrimidine metabolism
Neurotransmitter disease
e.g. Biotinidose deficiency, purine/
pyrimidine metabolism, perioxisomal
dis, folic metabolism
HELLP – haemolysis elevated LFT & low platelet; AFLP – acute fatty liver pregnancy;
FAO – fatty acid oxidation; LSD – lysosomal storage dis; OA – organic aciduria;
AA – amino-acidopathy ; NKH – non-ketotic hyperglycinemia; CDG- congenital glycosylation defect
181
Table II Examples Physical Findings suggestive of IEM or other underlying causes
Feature
Examples of Disorders
Dysmorphism
Cytogentic disease; syndromal diagnosis; CDG
Hepato(spleno)megaly
LSD, GSD
Cardiomyopathy
LSD, FAO, mitochondrial disease
Smell
OA (sweet – maple syrup urine disease; sweaty feet – isovaleric
aciduria)
Neurological signs:
- dystonia
Mitochondrial disease, OA, Pterin defects
- macrocephaly
Canavan disease, L-2-hydroxyglutaric aciduria, Glutaric aciduria I
- microcephaly
Sulfite oxidase deficiency, previous metabolic encephalopathy e.g.
previous hyperammonemia/ hypoglycaemia, GLUT-1 deficiency,
neuronal ceroid lipofuscinosis
Growth
Many IEMs e.g. OA, AA, urea cycle disorder
(FIT, short stature)
Hair – coarse, “kinky”
Menkes disease, MPS, arginosuccinic aciduria
Coarse skin, hair or
Lad, Conradi-Hunermann
facial features
Ichthyosis
Sjogren-Larsson
Eczema
Biotinidase deficiency
Always consider possibility of a treatable disorder:
- ↑T3, low N /↓T4 , N TSH ( Thyroid hormone transporter gene MCT8 mutation)
- PKU (Pl AA)
- Homocystinuria (plasma AA,↑blood total homocysteine)
- Late-onset UCD (↑pl NH3, Pl AA)
- Occipital Horn Syndrome (↓se Cu & ceruloplasmin)
- Hartnup disease (neutral amino-aciduria)
- Cerebrotendinous xanthomatosis (fasting↑pl cholestanol , n/↑cholesterol)
Other second line investigations that may be considered:
- Glycosaminoglycans – coarse facial dysmorphism may be absent in MPS III
- VLCFA – progressive encephalopathy with mental deterioration
- Iso-form transferrin – CDG: suspect in all unexplained encephalopathy (+ abnormal fat
subcutaneous accumulation, cerebellar atrophy) or multi-organ disorders (heart, liver,
kidney, GI tract, skeletal, gonads, coagulation defects causing stroke-like episodes)
- Paired CSF / serum glycine – NKH (infantile onset severe seizures)
- Paired CSF / serum glucose – Glut Transporter deficiency (infantile onset severe seizures)
- Plasma homocysteine – Sulphur AA disorder (progressive dev delay)
- Fresh urine x sulfite – sulphite delay oxidase / molybdenum co-factor deficiency
(infantile encephalopathy, progressive dev delay, severe microcephaly, lens
dislocation)
Example of disorders according to investigations:
- Ca: Williams syndrome, Di-George Syndrome, pseudo-hypoparathyroidism
- Lactate: screening for gluconeogenesis, disorders of pyruvate metabolism; respiratory
chain mitochondrial disease
- NH3: urea cycle problem; AA
- Amino acid chromatography: AA
- Urine OA: OA and some FAO
- CK: FAO (non-specific), muscle disorders
- Urate: ↓ in purine metabolism; molybdenum cofactor deficiency; ↑ in Lesch-Nyhan,
glycogen storage disorders
182
Chapter 63 - Anti-convulsants use in children with epilepsy
Table 1. Choice of AED in different situation
Seizure (Sz)
1st line drugs
2nd line drugs
types
Focal seizure +/- ※Carbamazepine
※Oxycarbazepine
secondary
⊕Levetiracetam
GTCSs
Topiramate
※Lamotrigine
1’ GTCSs only
Myoclonic
seizure only
Absence seizure
only
Valproate
⊕Levetiracetam
Topiramate
※Lamotrigine
Valproate
§Clonazepam
⊕Levetiracetam
Valproate
(ethosuximide)
※Lamotrigine
§Clobazam
Valproate
Gabapentin
3rd line drugs
Phenobarbital
※Phenytoin
lacosamide
Vigabatrin
(zonisamide)
※Carbamazepine
※Oxycarbazepine
※Phenytoin
(ethosuximide)
Topiramate
Valproate
(ethosuximide)
※Lamotrigine
Tonic or atonic
seizures
Valproate
※Lamotrigine
Topiramate
§Clonazepam
§Clobazam
Photosensitive
or other reflex
seizures
Valproate
⊕Levetiracetam
§Clonazepam
§Clobazam
§Clonazepam
(zonisamide)
§Clonazepam
§Clobazam
⊕Levetiracetam
Topiramate
(zonisamide)
(Rufinamide)
※Lamotrigine
※Na channel blocker- CBZ,OXC,LGT,PHT
Multiple mechanisms, mainly or incl Na channel blocking- PB,VPA,TPM,Zonisamide
§ ↑GABA- benzodiazepines, VGB
Synaptic SV2A-LVTM
⊕
Try to choose a drug with a difference mechanism in combination therapy
183
Drugs to be
avoided
※Carbamazepine
※Oxycarbazepine
※Phenytoin
Vigabatrin
Gabapentin
If also absence /
myoclonic Sz
※Carbamazepine
※Oxycarbazepine
※Phenytoin
Vigabatrin
Gabapentin
※Carbamazepine
※Oxycarbazepine
※Phenytoin
Vigabatrin
Gabapentin
※Carbamazepine
※Oxycarbazepine
Vigabatrin
Gabapentin
Table 2 Drug options by epilepsy syndrome
Epilepsy syndrome
Childhood absence
epilepsy
Juvenile absence
epilepsy
Juvenile myoclonic
epilepsy
(ethosuximide)
Lamotrigine
Valproate
※
§Clobazam
§Clonazepam
⊕Levetiracetam
Topiramate
⊕Levetiracetam
Focal epilepsies:
cryptogenic,
symptomatic
※Carbamazepine
※Lamotrigine
※Oxcarbazepine
Benign epilepsy
with occipital
paroxysms
Severe myoclonic
epilepsy of infancy
Continuous spike
wave of slow sleep
Lennox-Gastaut
syndrome
Myotonic astatic
epilepsy
Topiramate
※Lamotrigine
Valproate
Topiramate
Valproate
Topiramate
Valproate
Topiramate
Steroids
Vigabatrin
※Carbamazepine
※Lamotrigine
※Oxcarbazepine
Valproate
※Carbamazepine
※Lamotrigine
※Oxcarbazepine
Sodium valproate
§Clobazam
§Clonazepam
Valproate
Topiramate
Clobazam
Clonazepam
(ethosuximide)
Lamotrigine
Valproate
Steroids
Lamotrigine
Valproate
Topiramate
§Clobazam
(Gabapentin)
⊕Levetiracetam
※Phenytoin
§Clobazam
§Clonazepam
Valproate
Topiramate
Levetiracetam
Topiramate
⊕
Acetazolamide
Clobazam
Clonazepam
Oxcarbazepinea
Phenobarbital
Phenytoin
(Primidone)
Acetazolamide
Clonazepam
Phenobarbital
(Primidone)
§
§
※
※
※Carbamazepine
※Oxcarbazepine
※Phenytoin
Vigabatrin
※Carbamazepine
※Oxcarbazepine
※Phenytoin
Vigabatrin
※Carbamazepine
※Oxcarbazepine
※Phenytoin
Vigabatrin
Vigabatrin
§
Nitrazepam
※Carbamazepine
※Oxcarbazepine
(Sulthiame)
Topiramate
⊕
Levetiracetam
(Stiripentol)
⊕Levetiracetam
※
§Clobazam
§Clonazepam
(ethosuximide)
⊕Levetiracetam
※Lamotrigine
⊕Levetiracetam
Valproate
Topiramate
Acetazolamide
Drugs to be avoided
⊕Levetiracetam
§
§
※
§Clobazam
§Clonazepam
3rd line drugs
⊕Levetiracetam
⊕Levetiracetam
Valproate
Generalised tonic–
clonic seizures only
Benign epilepsy
with centrotemporal
spikes
2nd line drugs
※Lamotrigine
※Carbamazepine
※Lamotrigine
Infantile spasms
(
1st line drugs
Phenobarbital
Topiramate
※Carbamazepine
※Lamotrigine
※Oxcarbazepine
Vigabatrin
※Carbamazepine
※Oxcarbazepine
Vigabatrin
) drugs not available in HK
184
(Sulthiame)
※Carbamazepine
※Oxcarbazepine
※Carbamazepine
※Oxcarbazepine
Table 3. Commonly used AED and major side effects
*Carbamazepine
Drowsiness, rash, Steven Johnson syndrome (SJS), anticonvulsant
hypersensitivity syndrome (AHS), hepatic failure, headache, hypoNa+, diplopia,
ataxia, nystagmus, arrhythmia, tremor, hematological
#Valproate
Nausea, vomiting, weight gain, tremor, hair loss, hepatic failure, pancreatic
failure, hormonal change in women
Phenobarbitone
Rash, SJS, severe drowsiness, impaired cognition and concentration, agitation
/hyperactivity , hepatic failure,AHS, hematological, shoulder hand syndrome
Phenytoin
Rash, SJS, drowsiness, ataxia, gum hypertrophy, hirsutism, AHS, hepatic failure,
hematological, encephalopathy, rickets,
oxycarbazepine
Rash, SJS, drowsiness, ataxia, diplopia, weakness, hematological
##Lamotrigine
Rash, SJS, tics, ataxia, asthenia, insomnia, diplopia, dizziness, headache, hepatic
failure, hematological, AHS
^Topiramate
Anorexia, weight loss, drowsiness, renal stone, metabolic acidosis, impaired
concentration/ memory, psychomotor slowing, nervousness, acute glaucoma,
hepatic failure, anhidrosis
Irritability, behavioral changes, asthenia, dizziness
♣Levetiracetam
- *Carbamazepine – check HLA B *1502 first
- #Use of VPA unsuitable in children who are at considerably risk of fatal hepatoxicity (e.g. young children
esp. <2yrs old, those with polypharmacy or with congenital metabolic disorders or organic brain disease)
Warning signs of hepatic failure: clinical and non-specific e.g. malaise, weakness, lethargy, facial edema,
anorexia, vomit and loss of seizure control.
Risk 1/600 in <3yr, 1/8000-1/10,000 in 3-20yr
- AHS – Anticonvulsant hypersensitivity syndrome: rash, fever, tender lymphadenopathy, hepatitis or
eosinophilia; potentially fatal; usually cross sensitivity between AEDs that can cause AHS
- #caution in female – VPA in pregnancies→1-2%with neural tube defects, 2-3x higher major congenital
anomalies, probably associated with poor cognitive outcome in offsprings
Switch valproate to other less teratogenic drugs in childbearing age female well before pregnancy
- ##lamotrigine – dose in combination with VPA needed to be halved
- ^topiramate – special precaution in those predisposed to acidosis (eg renal
disease, ketogenic diet) or renal stone formation ( family history, hypercalciuria);
Avoid therapy predispose to heat related disorders (other carbonic anhydrase
inhibitor, anticholinergic drugs)
- ♣levetiracetam – likely the AED most free from side effects
185
Chapter 64 - Migraine
CL Yuen, S Cherk
Migraine without aura (ICHD-II)
Diagnostic criteria
A At least five attacks fulfilling criteria B–D
B Headache attacks lasting 4–72 h (including the time when patients fall asleep till awakening)
C Headache has at least two of the following characteristics:
1 Unilateral location (commonly bilateral in young children)
2 Pulsating quality
3 Moderate or severe pain intensity
4 Aggravation by or causing avoidance of routine physical activity (e.g. walking or
climbing stairs)
D During headache at least one of the following:
1 Nausea and/or vomiting
2 Photophobia and phonophobia
E Not attributed to another disorder
Migraine with aura
Diagnostic criteria
A At least two attacks fulfilling criteria B–D
B Aura consisting of at least one of the following, but no motor weakness:
1 Fully reversible visual symptoms including positive features (e.g. flickering lights,
spots or lines) and/or negative features (i.e., loss of vision)
2 Fully reversible sensory symptoms including positive features (i.e. pins and needles)
and/or negative features (i.e., numbness)
3 Fully reversible dysphasic speech disturbance
C At least two of the following:
1 Homonymous visual symptoms and/or unilateral sensory symptoms
2 At least one aura symptom develops gradually over ≥5 min and/or different aura
symptoms occur in succession over ≥5 min
3 Each symptom lasts ≥5 min and ≤60 min
D Headache fulfilling criteria B–D for Migraine without aura begins during the aura or follows
within 60 min
E Not attributed to another disorder
Features of aura in migraine
Visual and/or sensory and/or speech symptoms. Gradual development, duration ≤1 h, a mix of
positive and negative features, and complete reversibility
Acute drug treatments - to be given at onset of attacks
Panadol 15mg/Kg/dose (max dose at 1000 mg) (repeat in 4 hours PRN, max 3 doses in 24 hours)
NSAID e.g. Ibuprofen 10mg/Kg/dose (repeat in 4 to 6 hours PRN, max 4 doses in 24 hours)
Zolmitriptan 2.5mg (repeat in 2 hours PRN; max 15mg in 24 hours)
186
Preventive drug treatments - no well established effective treatments in paediatrics
Flunarizine 5-10mg Daily
Cyproheptadine 0.1-0.2mg/Kg/dose BD dose (max daily dose: 0.5mg/Kg/day)
Propranolol 0.2-0.5mg/Kg/dose TDS dose (max dose 4mg/Kg/day)
Others: topiramate and valproate
Behavioural therapy
Life style and diet modification: balanced and healthy diet without skipping meals, adequate
hydration, avoid caffeine, regular exercise and sufficient sleep
Headache diary and headache education leaflet (available from Neurology Section of Department
web page)
187
188
Chapter 65 - Neonatal seizure
Acute Neonatal seizure management
Is it a seizure ?
Vs other movements: jitteriness, benign sleep
myoclonus, reflex behaviors etc
Yes seizure
characterize the seizure
ABC
Start oxygen if seizures are continuous
IV access
baseline investigations including CBP d/c, RLFT, glu, Ca2+, Mg+, Na+, K+ , blood gas,
infective screen, TFT, uric acid, ammonia, lactate, urine ketones
brain imaging – urgent CT brain
To NICU/ PICU
Follow this pathway if seizure ongoing > 3mins or seizure impairing vital functions
Phenobarbitone 20mg/kg iv loading over 20mins
If no response by 10mins
Further 10mg/kg iv x once or twice until seizure
cessation orl total 40mg/kg phenobarbitone given
Phenytoin 10mg -20mg/kg iv over 20mins
Phenytoin 10mg/kg iv further
( + PR paraldehyde 0.1ml per dose)
Lorazepam 0.05mg/kg iv q6-8hr
Or
midazolam 0.15 -0.5mg/kg/hr for full term
189
If still seizure
Pyridoxine 100mg iv stat (best under EEG;
cardiopulmonary monitor and resuscitation standby for
possible apnea or cardiorespiratory collapse)
If response
Pyridoxine
maintenance:
-5-15mg/kg/day po
in 2 divided doses
if no response
Other AED
-Iv Levetiracetam ( status: 20-30mg/kg iv loading over 15mins,
then 10m/kg/day ÷2, ↑by 10mg/kg/day over 3days to
30mg/kg/day-> may up to 45-50mg/kg/day)
-Iv lidocaine (2mg/kg iv over 10mins followed immediately
6mg/kg/hr x 6hrs-> 4mg/kg/hr x 12hrs->2mg/kg/hr x 12hrs)
-Iv valproate (status: 20-40mg/kg over 15mins then 5mg/kg/hr)
plus
-Pyridoxal-5-phosphate (PLP) po 30-50mg/kg/day in 3 divided
doses
-Folinic acid po 3-5mg/kg/day
-biotin po 5-20mg/day
For frequent but brief seizures shorter than 3mins each, anticonvulsant(AED) treatment is still
warranted for seizure attacks abortion. The sequence of medication choice generally follows the
above but the timing of escalation of AED treatment can be variable and individualized depending
on the underlying causes, seizure types, seizure frequencies, systemic stability and need to balance
with side effects of AED.
Neonatal seizure:
to differentiate from other paroxysmal movements that are not seizures :
Jitteriness – involuntary rhythmical rapid alternating contractions of agonist and antagonist
muscles, 4-5Hz, equal intensity; mainly limbs, can be asymmetrical
Benign sleep myoclonus – during NREM sleep, myoclonic movements in an otherwise normal
neonate, usu over distal parts of ULs but also LLs and axial muscles, can be violent, last usu for
10-20s but may up to 30mins in unusual cases
Other reflex behaviors – eg exaggerated startle
Generally seizures are not suppressible by passive restraints over the “ seizing” joints
190
Types and characteristics :
-Subtle seizures (50%) (imitate normal behavior; ocular, oral-buccal-lingual, progression
movement, complex purposeless movement)
-Tonic seizure (5%)
-Clonic seizure (25%)
-Myoclonic seizure (20%)
-1/4: have multiple Sz types
-Autonomic changes (HR, RR, BP, apnea (seldom alone), salivation, pupillary changes)
-Subclinical seizure common; only ~20% of neonatal seizure had definite clinical signs
-Clinical silent Sz are more common after initiation of AED - “ decoupling response”
Causes:
-Most are acute reactive Sz from acute encephalopathy:HIE ( most common cause,65%- 80%)
metabolic (electrolyte, glucose)
trauma/haemorrhage
Infection
drug (toxic/withdrawal)
-Neurometabolic (IEM)
-Cerebral malformation
-benign neonatal convulsions (familial, non familial)
Diagnoses:
History :
1) seizure hx: seizure type, day of onset
2) antenatal hx: maternal illness, AN infection, AN drug use, abnormal AN fetal movement
3) perinatal hx: birth hx, NRFS, need resuscitation, apgar score, cord blood pH
4) feeding hx: is seizure onset related to feeding
5) family hx
Baseline investigations:
CBP d/c, RLFT, glu, Ca2+, Mg+, Na+, K+ , blood gas, infective screen, TFT, uric acid, ammonia,
lactate, amino acid
urine ketones
Urine organic acid, metabolic screen
CSF infective screen
Neuroimaging:
Urgent CT brain
MRI brain in all cases
EEG
Urgent EEG
Consider aEEG monitoring
Further investigations if causes not elicited from above/ not typical for benign idiopathic neonatal
seizure ( familial/non familial) / if clinical encephalopathic/ relative difficult to treat seizures:
191
Blood – acylcarnitines, NH3, lactate, pyruvate, very long chain fatty acids, copper and
ceruloplasmin
Urine – organic acids, purines and pyrimidines + sulfites ( PMH urine metabolic screen), alpha
AASA + guanidoacetate + creatine (available in QMH)
CSF – glucose+ lactate + amino acids (these to be paired with serum sample); neurotransmitters +
pipecolic acid (available in QMH)
Consider Investigation for specific IEM if seizure resistant :
- pyridoxine dependent epilepsy
- pyridoxal-5-phosphate (PLP) dependent epilepsy
- biotin responsive -> biotinidase def or holocarboxylase synthetase deficiency
Duration of treatment:
-Depends on cause, severity, recovery, neurological outcome, EEG abnormality
-Current trend: to withdraw AED 2weeks after last Sz with normal EEG and good outcome
predictors (clinical impression of benign neonatal convulsions, neuroimaging and neurological
examinations normal)
-practically, often re –evaluation in 1-2mths after discharge to discontinue AED
Outcome:
-28% death, 72% survivor
-2yr follow up of 86% of survivors –
42% abnormal PE
55% MDI (mental developmental index) <80
50% PDI (physical developmental index) <80
26% epilepsy
192
Chapter 66 – Screening/quick reference
Cerebral Palsy
LY Wong, S Cherk
Definition:
Permanent disorder of the development of movement and posture, causing activity limitation, that
are attributed to non-progressive disturbances occurred in the developing fetal or infant brain. It is
often accompanied by disturbances of sensation, perception, cognition, communication,
behaviour, by epilepsy and by secondary musculoskeletal problems.
Although the manifestations may change over time, the causative lesion is static.
Overall prevalence remain unchanged at 2.11 per 1,000 live birth. Highest pooled prevalence in
children weighing 1000 to 1499g at birth. Overall point prevalence 1.3 per 1000 children in Hong
Kong.
Clinical approach to patient with “Cerebral palsy”
Family history
Birth and past medical history:
In general: preterm in symmetrical or asymmetrical spastic diplegia; full term in
hemiparesis. History of term asphyxia in dyskinetic CP.
Age of presentation
Any unusual presentations/ mimics of cerebral palsy
Hereditary spastic paraparesis- +ve Family history of “cerebral palsy”
Dopa responsive dystonia- might have diurnal variation of symptoms
Other inborn errors of metabolism-progressive signs and symptoms (regression), unusual
associated problems e.g. hypoglycemia, recurrent vomiting, multi-organ involvement or
progressive worsening seizures; FH of early death
Idiopathic toe walking- Normal deep tendon reflexes
Cerebral palsy “of unknown etiology”: be vigilant for the appearance of a late symptom that might
suggest a more specific diagnosis
International Classification of Function (ICF) Enablement framework in assessment and
management of children with cerebral palsy
Health Condition
Cerebral Palsy
Body Function and Structure
Tone, Strength,
Range Selectivity
Activity
GMFCS and
gait GMFM
Environmental Factor
Accessibility
Familial and
Emotional Support
Participation
Involvement in Home,
School and Community
Events, Social relationship
Personal Factor
Age, Cognitive
Function, Personality
193
Assessment: Body Function and Structure
• Tone: Measurement of Spasticity:
Modified Ashworth Scale (Bohannon)
0= No ↑ in muscle tone
1= Slight ↑ in tone with a ‘catch and release’, or minimal resistance at end of ROM.
1+= Slight ↑ in tone, catch followed by a minimal resistance through <1/2 remainder of ROM
2= More marked ↑ in tone through most of the ROM, but limb moves easily
3= Considerable ↑ in tone, passive movement difficult
4= Affected part is rigid in flexion or extension
Modified Tardieu Scale (Boyd 1998, 1999)
Measurement of R1 and R2 :
R2-R1 dynamic component
R2
static contracture
•
•
Assessment of Activity in Cerebral Palsy
Gross Motor Function Classification System (GMFCS)
Level 1
Walks without restrictions: limitations in more
advanced gross motor skills.
Level 2
Walks without assistive devices: limitations walking
outdoors and in the community.
Level 3
Walks with assistive mobility devices: l limitations
walking outdoors and in the community.
Level 4
Self mobility with limitations: children are
transported or use power mobility outdoors and in
the community.
Level 5
Self mobility is severely limited even with the use of
assistive technology.
•
•
•
Manual Ability Classification System(MACS) for upper limb
Communication Function Classification System (CFCS)
Gait analysis
194
• Hip surveillance: (Part of assessment of body structure)
Depends on GMFCS level
GMFCS Level 1: low risk of hip displacement
(Migration percentage >30% : Hip subluxation, >50% Hip dislocation)
Migration percentage (MP) = A÷B x100%
GMFCS
GMFCS Level 1
GMFCS Level 2
GMFCS Level 3
GMFCS Level 4
GMFCS Level 5
Start of screening: 12-24 months
Frequency thereafter
Review with P/E at 3 year
Every 12 mo till MP stable, then review
at 4-5 years
Every 12 mo if MP stable, 6 mo if MP
unstable
Same as level 3 but 6 monthly
surveillance if with scoliosis or pelvic
obliquity
6 monthly till 7 year
End of surveillance
Review with P/E at 5 year
8-10 year
Yearly till skeletal maturity
Interventions for children with cerebral palsy
Conventional therapy
Splinting, Casting
Orthoses, Seating modification
Stretching
Tone Management
Botulinum toxin type A
Localization method: Ultrasound guided preferred
Effect: Initial effect seen at 24-72 hrs
Maximal effect 2-4 weeks
Effect last for 4-6 months
Best combined with casting
Selective Dorsal Rhizotomy
Reduce lower limb spasticity by removal of the excitatory influences from the dorsal roots
Suitable candidates: Spastic, Straight, Strong, Smart, Slim, Support
Usual treatment timeline: Between 5-8 years of age
Intrathecal Baclofen
Not readily available in Hong Kong
Oral medications
Might consider in whole body involvement
Drugs: Diazepam, Baclofen, Dantrolene, Tizanidine
Orthopedic Surgery
Single Event Multi Level Surgery
195
FU issues in Cerebral palsy
1) Medical co-morbidities
-epilepsy, scoliosis, perineal care
2) visual/hearing impairment (VA; visual field defect in hemiplegic CP)
3) GIT- GERD, constipation (in low GMFCS level)
4) Swallowing problems, nutrition, dental care (especially in low GMFCS level)
5) bladder dysfunction (in spastic cerebral palsy)
6) Mobility and physical activity
7) Communication
8) Cognitive impairment/specific learning needsSelf Care
9) Self Direction (especially for those studying in mainstream school)
Frequency of impairment in CP
Impairment
Motor
Spasticity
Dyskinesias
Ataxia
Isolated hypotonia
GMFCS
I
II
III
IV
V
IQ <70
Ongoing epilepsy
Visual impairment
Blind
Hearing impairment
Deaf
% of ALL CP Affected
100
77-93
2-15
2-8
0.7-2.6
32-51
17-21
9-12
10-15
12-19
17-60
31-40
21-63
1-7
11-13
1.7-3
Prediction for ambulation
Ref : Developmental Medicine & Child
Neurology 2009;51:295-302
196
Chapter 67 – Screening/quick reference
Special note on management of various types of cerebral palsy
LY Wong, S Cherk
Goal setting:
short,
intermediate and
long term
Structural and
Activity
assessment
Treatment and
Medications
Orthosis
Watch out for
complications
Spastic Diplegia
Define functional
level (GMFCS)
Spastic Hemiparesis
Define Upper limb
functional level:
MACS
Spastic Quadriparesis
General Health, Body
structure nutrition and
feeding
Mobility and
prevention of
complications
UL: Early Tx of
spasticity
Seating, mobility and
communication needs
Assess UL tx outcome
by Goal Attainment
Scale (GAS)
Study gait + P/E
to decide
medical
treatment
Botox
Consider SDR
Orthorpaedic
interventions at
school age
Depends on gait
In general hinged
AFO NOT
recommended
Hip surveillance
based on
GMFCS
recommendation
Medical
complications
Schooling
Early consideration of
AAC and AT (Assisted
technology)
Watch out for visual
and hearing impairment
Watch out for hearing
loss if history of severe
NNJ
Botox
To increase UL use by
*CIMT or **BOT
Oral medications might
be tried
Oral medications might
be tried
Might consider ITB if
available
Might consider hinged
AFO
UL functional splint
To prevent
complications and to
aid training such as
standing exercise
Hip surveillance
Watch out for scoliosis
In general not
recommended
Look for sensory
impairment ; visual
field defect
Watch out for epilepsy
Watch out for
word learning
difficulties,
visual perceptual
problem and
attention deficit
especially those
in normal school
Education and
social support
Early plan for
transition
Vocational plan
Social
LL: Early treatment of
spasticity
Same as diplegia
Dyskinetic CP
Define functional level
Communication Function
Classification System
(CFCS)
Seating, mobility and
communication needs
Watch out for pain and
discomfort
Watch out for epilepsy
Screen for osteoporosis
/pathological fracture
Nutritional need
Maintain hydration and
nutrition
Family and social
support
+/-Home modification
Early plan for long term
care
Family and social support
Early plan for long term
care
Watch out for learning
needs (usually attend
normal school)
Early plan for transition
Vocational plan
CIMT (Constraint Induced Movement therapy)
** BOT – Botulinum toxin
*
197
Section 5. Gastroninterstional system
Section 5: Gastrointestinal system
198
Chapter 68 - Acute Gastroenteritis
PT Yu, L Leung, MC Chan
Definition and Diagnosis
-
Sudden change in stool consistency to loose or watery stools, and/or a sudden onset of
vomiting, +/ - fever.
Diarrhea usually lasts 5-7 days (<2 weeks), vomiting 1-2 days (in most stop by 3 days)
Possible indicators of diagnoses other than gastroenteritis:
- Fever: >38°C in children <3 mo; 39°C in children aged 3 >/=3 mo
- Shortness of breath or tachypnoea
Altered conscious state
Neck stiffness
Bulging fontanelle in infants
- Non-blanching rash
- Blood and/or mucus in stool
- Bilious (green) vomit
- Severe or localised abdominal pain
Abdominal distension or rebound tenderness.
-
-
Clinical Feature That suggests Bacterial versus Viral Etiology
High fever (>40°C), overt fecal blood, abdominal pain, CNS involvement
Vomiting and respiratory symptoms are associated with a viral etiology
-
Investigations
No routine blood test for children who are not septic, not dehydrated
Na, K, Ur, Cr , glucose , blood gas for those with dehydration/ need IVF
CBP with differential count, CRP only for suspected bacterial GE
Blood culture only when started antibiotics
Stool for culture should NOT be routinely performed
-
Indications for stool culture
-
Suspect septicaemia
Septic or toxic looking
Blood and/or mucus in stool
diarrhea not improved by day 7
uncertainty about the diagnosis of GE
-
Immunocompromised patient
recent travel history
infants <3 months old
specific pathogen community outbreak
Assessing dehydration / shock
The best measure is % body weight loss from recent (< 2 wks) weight. Clinical signs are
imprecise. The 3 best signs are: prolonged capillary refill, reduced skin turgor and
abnormal respiratory pattern.
199
Interpret symptoms and signs taking risk factors# for dehydration into account. Within the category of
‘clinical dehydration’ there is a spectrum of severity indicated by increasingly numerous and more
pronounced symptoms and signs. For clinical shock, one or more of the symptoms and/or signs listed
would be expected to be present. Dx of shock is based on clinician’s global assessment. Dashes (–)
indicate that these clinical features do not specifically indicate shock. Symptoms and signs with red flags
may help to identify children at increased risk of progression to shock. If in doubt, manage as if there
are symptoms and/or signs with red flags.
From NICE 2009
Clinical Dx dehydration shown to be imprecise. Presence
Suspect hypernatraemic dehydration if
of one or more symptoms or signs conventionally used in
- Jittery movements
assessment would suggest clinically significant
- Increased muscle tone
dehydration.
★
-
Hyperreflexia
Convulsions
Drowsiness or coma.
Risk Factors# for dehydration
•
•
•
•
•
•
★
★
Red flag sign = alert clinician to risk of progression to
shock
Dx of shock based on physician’s global assessment. If
unsure severe dehydration or early shock, treat as for
shock.
Infants, esp <6 months
Infants who were of low birth weight
Children who have passed ≥ 6 diarrhoeal stools or vomited ≥3x in last 24 hrs
Children who have not had/ not tolerated supplementary fluids
Infants who have stopped breastfeeding during the illness.
Infants with signs of malnutrition
200
Management
Oral rehydration therapy: (ORT first line always, unless indicated for IVF)
•
For clinical dehydration but no signs of shock: replace deficit 40-50ml/kg + maintenance
fluids as low osmolality ORS over 3-6 hours frequently (longer duration for older
children), in small amounts (eg by cup, syringe or teaspoons up to every 1-2 mins by
parent). (Cincinnati: minimal amount is 240ml over 4 hrs for <5 yr olds and 480 ml over 4
hrs for ≥5 yr olds)
•
Always try ORT first (including in hyperNa and severe dehydration unless indications for
IVF is seen), may set up IV access for patient admitted late in the evening in case of ORT
failure and need IVF
•
When oral rehydration not feasible, NG rehydration is preferred and should be proposed
before IV therapy.
•
Allow milk, breast milk and water during rehydration if they refuse ORS and have no red
flag signs (but avoid carbonated drink, juice).
•
For ongoing loss: add 5ml/kg per large watery diarrhea (NICE).
•
Reassess frequently patients with red flag signs for any need of escalation of management.
Write down alert criteria for nurses.
Intravenous Fluid Therapy (IVT) indication
-
Suspected/ confirmed shock
Dehydration with altered consciousness or severe acidosis.
Patient with red flag signs shows clinical evidence of deterioration/ lack improvement
despite ORT
Persistently vomit ORS solution given orally or via a nasogastric tube
Severe abdominal distension and ileus.
Switch to oral rehydration as soon as indications for IV rehydration no longer seen.
A. For Shock: arrange admission to PICU
- Rapid infusion of 20ml/kg NS or Ringer’s lactate (esp. in extremely severe cases of shock)
bolus, repeat 2nd bolus if BP has not improved, consider other causes of shock and PICU
admission if not satisfactory after 2nd bolus.
-
After signs of shock resolve, start rehydration with IVT (see below).
B. For cases with significant (moderate/ severe) dehydration without shock
- Can replace deficit 40-50ml/kg isotonic solution (NS or Ringer’s lactate) over 2-4 hrs
(NICE, ESPGHAN) on top of maintenance.
- Regular reassessment to see if this reverses signs of clinical dehydration and guide
ongoing fluid needs.
201
IV rehydration rate
IV Rehydration has been traditionally over 24 hours, but latest guidelines (NICE, ESPGHAN, WHO)
favour rapid replacement 20ml/kg/hr of NS for 2-4 hrs (in an otherwise well child with no
hypernatraemia **) as this improves gut and renal perfusion, faster recovery and LOS.
C. Subsequent fluid regime
- Rapid rehydration is followed by: oral rehydration or continuous IV infusion of dextrose
containing crystalloid solution once fluid volume is restored
-
For those who presented with shock: additional 100ml/kg for replacing deficit on top of
maintenance, using NS or NS 5%D for deficit replacement and maintenance (NICE). For
those without shock, as for B.
-
A solution containing not <0.45% saline is recommended during the first 24 hours of IV
rehydration therapy to prevent hyponatremia (ESPHGAN).
-
Early start of ORT after 1-2 hrs of IVT. If tolerated, stop IVT and complete rehydration
with ORT.
-
After child urinates or K+ come back low, may add KCl supplement 20mmol/L, or add oral
K supplements.
-
Remember to add maintenance and continuing losses into fluid calculation and to reassess
patient.
-
Restart ORS if dehydration recurs after rehydration.
-
Careful monitoring of electrolytes for those on IVT, alter fluid composition or rate of IVT
as needed.
**Hypernatremic dehydration (Na >145mmol/L)
Oral or NG rehydration with hypoosmolar ORS is effective and safer treatment of hypernatremic
dehydration than IV rehydration. If child needs IV rehydration:
1) use isotonic solution (N/S or N/S+5% D) for fluid deficit replacement and maintenance
2) replace deficit slowly (over 48 hours) esp in those with Na >160mmol/L
3) reduce Na level at a rate < 0.5 mmol/l per hour, slower if hypernatremia >5 days.
Others
Do not give antibiotics routinely. Give antibiotic treatment to children with:
-
Suspected septicaemia
Salmonella GE in those< 3 months, malnourished or immunocompromised.
Clostridium difficile (ie Pseudomembraneous enterocolitis), dysenteric shigellosis,
dysenteric amoebiasis, cholera or giardiasis
Antiemetics , anti-motility agents, prebiotics are not recommended.
Probiotics (eg: Lactobacillus GG ) are effective in reducing the duration of diarrhea ( can be considered
in cases with prolonged symptoms): dose of at least 10 billion CFU/day of LGG -for total 5 to 7 days
Major references: NICE 2009, ESPGHAN 2014 guidelines.
202
Chapter 69 - Gastro-oesophageal reflux
MC Chan
Gastro-oesophageal reflux (GOR): retrograde flow of gastric content into oesophagus
Gastro-oesophageal reflux disease (GORD): symptoms or complications of GOR
Population at high risk for GERD and its complications: neurological impairment, obese,
repaired esophageal atresia, hiatal hernia, achalasia, chronic respiratory disorders (e.g. BPD),
history of lung transplant, preterm infants
Evaluation:
History and physical examination:
- Identify pattern of vomiting, important to rule out bowel obstruction (bile stained vomitus,
forceful vomiting), infection, metabolic diseases, food allergy, and neurological diseases
- Pay attention to feeding volume and frequency, weight gain, irritability and unusual neck or
body posturing
- Typical presentation of uncomplicated GER: non-bilious effortless painless regurgitation
in an apparently healthy infant with normal growth and without irritability – ‘happy spitter’
- Esophageal manifestations: vomiting, abdominal or substernal / retrosternal pain, poor
weight gain, dysphagia
- Extra-esophageal manifestations: respiratory symptoms (cough, laryngitis, wheezes),
recurrent pneumonia, dental erosion, pharyngitis, sinusitis, recurrent otitis media
- Check the growth parameters, nutritional status; look for anaemia, abnormal respiratory /
abdominal signs
Warning signs indicate alternative diagnoses or complications:
choking, gagging, coughing with feeds or significant irritability, consistently forceful vomiting,
bilious vomiting, onset of vomiting after 6mo, diarrhea, constipation, fever, lethargy, bulging
fontanelle, hepatosplenomegaly, distended or tender abdomen, poor weight gain, anaemia
Investigation:
- Faecal occult blood
- Pyloric USG for possible pyloric stenosis in baby with persistent forceful vomiting in first
few months of age
- Upper GI series: useful for the detection of anatomic abnormalities e.g. pyloric stenosis,
malrotation, stricture, hiatal hernia.
-
pH-multichannel intraluminal impedance monitoring (pH-MII)
- To detect movement of both acidic and non-acidic fluid, solid, air in esophagus
- To detect temporal relationship between specific symptoms and reflux of both acidic
and non-acidic reflux
Abnormal study if reflux episode over 24hrs >100 in patients < 1 year, >70 in
patients ages ≥1 year.
-
24 hour oesophageal pH monitoring: measurement of acid reflux only
Normal reference
- Reflux index (percentage of total time that oesophageal pH < 4)
< 12% in infant
< 6% in age > 1 year
- Prolonged reflux (> 5 minutes)
< 10 episodes in infant
203
< 7 episodes in children
-
Endoscopy and biopsy: Indications:
- Failure to respond to pharmacologic therapy or as part of the initial management of
symptoms of poor weight gain, unexplained anaemia or faecal occult blood, recent
pneumonia or haematemesis
- To evaluate the presence and severity of injury from reflux of gastric contents to
esophagus (i.e. erosion, ulcer, stricture, esophagitis, Barrett esophagus,
adencocarcinoma) and exclude other disorders e.g. hiatal hernia, eosinophilic
oesophagitis, Crohn’s disease, infection
Management:
Reassurance and education for non-complicated reflux.
Lifestyle modification is first line treatment
Infants:
a. Positioning therapy
- For infants birth to 12 months old, risk of SIDS outweighs the potential benefit of
prone sleeping
- Left side positioning during sleep and elevation of head at end of the bed may help.
- Avoid semisupine positioning particularly in infant carrier or car seat after feeding
because it exacerbates GER
b. Small and frequent feed
c. Milk thickening agents/ anti-reflux formula decrease frequency of overt vomiting.
(but the reflux index is similar to control)
Children and adolescent:
a. Positioning therapy
- For older children, slumped or supine postures should be avoided particularly in
postprandial period.
- Left-side sleeping posture, or prone and/ or elevation of head of the bed
b. Avoid caffeine, spicy foods, large meal volume, late night eating and chocolate
c. Weight reduction, cessation of smoking, avoid alcohol
May consider trial of 2-4 week extensively hydrolysed or amino acid-based formulae in
formula-fed infants; maternal exclusion diet (restrict milk and egg) in exclusive breastfed
infants with GERD symptoms because cow’s milk protein allergy symptoms overlap with
GERD, both conditions may co-exit in 42-58% of infants)
Medications:
a. Acid suppressant therapy
- Proton pump inhibitors (PPIs) = mainstay of treatment.
Esomeprazole (Nexium), approved in US for short-term treatment of GERD with
erosive esophagitis aged from 1-12mo
Omeprazole, lansoprazole approved in North America for > 1 year old.
Pantoprazole approved for children > 5 years old.
- Histamine-2 receptor antagonists
Ranitidine
Famotidine
b. Prokinetic therapy (ESPGHAN practice guidelines conclude that there is insufficient
evidence to justify its routine use)
- A trial of domperidone (Motilium) <35kg 0.25mg/kg/dose tds; ≥35kg 10mg tds for 1
204
week, continue only when it is useful.
- Metoclopramide
- Erythromycin (Cochrane review concludes there is insufficient evidence to recommend its
use in low or high doses for preterm infants <32 weeks’ gestation with feeding
intolerance)
c. Other agents
- Surface protective agents: none is recommended for sole treatment for severe symptoms
or erosive esophagitis
- Antacids can be considered in mild infrequent symptomatic cases as on-demand basis,
not for chronic use because of risk of aluminum toxicity
Surgical therapy
- Consider when medical treatment fails and in highly selected cases (i.e. underlying
neurological impairment, chronic respiratory conditions or repaired esophageal atresia)
- Fundoplication
205
Recurrent vomiting and/or
regurgitation
Vomiting/regurgitation
and poor weight gain
History and physical exam
History and physical examination
Are there warning
signals ?
Yes
Evaluate further
Are there warning
signals ?
Yes
No
No
Further evaluation
Adequate caloric
intake?
No
Education
Close follow-up
Are there signs
of complicated
GER disease?
Yes
Yes
No
Workup for Failure to
Thrive
Consider: Upper GI series
Abnormal?
Uncomplicated infantile GER“Happy spitter”
Yes
Manage
accordingly
No
Dietary Management
Protein hydrolysate/amino acid formula
Thickened feedings
Increased caloric density
Improved?
Yes
No testing;
Education: Warning signals
Reassurance.
Consider: Thickened formula
Resolves
By 18 months of age
Education
Close follow-up
No
No
Consultation with Pediatric GI
Consider: OGD & biopsy
Consultation with Pediatric GI
Consider: acid-suppression therapy
Consider: Hospitalization : Observe parent/child
interaction
Consider: NG or NJ tube feedings
Fig 2
Fig 1
Approach to the infant with recurrent regurgitation and
weight loss
206
Approach to the infant with recurrent regurgitation and
vomiting
Chronic
Heartburn
History and physical examination
Education;
Life-style change;
PPI for 2-4 weeks
Yes
No
Improves
Continue PPI
For 8-12 weeks
Discontinue PPI
Yes
Consultation with
Pediatric GI
Relapse
No
Observation
Fig 3
Approach to the older child or adolescent with heartburn.
Ref : Journal of Ped Gastroenterology and Nutrition 2009;49:498-547
207
Chapter 70 - 24 hours oesophageal pH monitoring and pH-impedance
monitoring (MII-pH)
MC Chan
Aims of the study:
- To quantify reflux in patients with mainly extra-esophageal symptoms
- To measure GER in patients not responding to antireflux treatment
Indications:
- Unexplained apnoea spell
- Unexplained cough or choking
- Unexplained colicky crying
- Unexplained recurrent pulmonary infection or wheezing
- Unusual neck or body posture
- Prior to placement of feeding gastrostomy to determine the need for simultaneous anti-reflux
procedures
- Monitor response to treatment
Not indicated:
- Obvious GOR by history
- Patients who may remove or destroy probes
- Respiratory embarrassment from nasal probes
- Gastric achlorhydria
To eliminate the effect of drugs:
- Prokinetic agents should be stopped for at least 48 hours
- Antacids should be stopped for at least 24 hours
- H2 antagonist / proton pump inhibitors should be stopped for at least 3-4 days
Patient instruction before measurement:
- Document mealtimes (beginning and end), position (prone, supine), symptoms and relevant
events (e.g. correction catheter position, disconnection of skin electrode)
- Avoid “acid” foods and carbonated beverages (e.g. Coca-Cola)
- Avoid extremely hot or ice-cold drinks and food (as the reactivity of the pH electrodes is
influenced by temperature)
Potential complications:
- Technical failure (device, catheter)
- Probe misplacement (height, bronchus)
- Mucosal trauma (bleeding, laceration)
Catheter insertion and its correct position:
Both pH and MII-pH catheters are passed transnasally preferably without sedation, the use of
local anesthesia (e.g. intranasal anesthetic spray) may be beneficial in some children.
Gel is often used to ease the passage through the nostrils, the gel should not be placed directly
on the antimony electrodes because it may decrease its accuracy.
The pH electrode should be positioned 2 vertebrae above the diaphragm at the level of the
vertebral column.
208
Strobe formula (0.252 x body length [cm] + 5) to calculate the estimated appropriate probe
position
Confirm the position by X-ray before measurement.
Comparsion between pH monitoring and impedance
Parameter
Acid GER
Nonacid GER
Superimposed acid reflux
Gas reflux
Height of reflux
Chemical clearance
Bolus clearance
Postprandial GER
pH monitoring
Yes
Blind
Blind
Blind
1 or 2 levels
Yes
Blind
Blind
MII-pH
Yes
Yes
Yes
Yes
6 levels
Yes
Yes
Yes
Definitions of reflux parameters:
Liquid MII-reflux episode : decrease in impedance with ≥ 50% from baseline
Acid MII reflux : with a pH <4.0
Weakly acid reflux : with a pH ≥4.0 but <7.0
Weakly alkaline reflux : with a pH ≥ 7.0
Gas MII-reflux episode : sharp increase of impedance > 3000 Ohm
Mean bolus clearance time : time needed for a bolus to be cleared from the esophagus
Bolus exposure index : the percentage of time that a bolus is present in the esophagus
Mean acid clearance time : time needed for acid to be cleared from the esophagus (previously
better known as the reflux index)
209
Chapter 71 - Helicobacter pylori infection
MC Chan, WF Lau
Gram-negative, spiral shaped, flagellated, microaerophilic bacteria
Strongly associated with socioeconomic condition: > 80% in developing countries and 20-50%
in developed countries
Often acquired before 5 years of age; rate of infection 1% per year after 5 years old.
Diagnostic tests:
Invasive:
Endoscopic gastric biopies (antrum, corpus)
Rapid urease (CLO) test and histopathology +/- culture
Non-invasive:
Urea breath test
Stool antigen
For the diagnosis of H pylori infection is based on either a positive histopathology + positive
rapid urease test or a positive culture.
Associated disease:
Peptic ulcer
- present in 60% in adult with gastric ulcer
- 80% adults and 90% children with duodenal ulcer
Non-ulcer dyspepsia
- all with chronic gastritis but most are asymptomatic
Gastric cancer
- adenocarcinoma ~ 1% infected patients
- mucosa-associated lymphoid tissue (MALT) lymphoma
Atherosclerosis
Eradication rate ~ 92%
Clarithromycin resistant H pylori in HK is low (~10%)
1st line eradication regimen:
Amoxicillin
50 mg/kg/day up to 1g BD
Clarithromycin
20 mg/kg/day up to 500 mg BD
Esomeprazole
1 mg/kg/day up to 20 mg BD
For 1-2 weeks
2nd line eradication regimen:
PPI + levofloxacin + amoxyicillin BD for 14 days
Metronidazole 20mg/kg/day up to 500mg BD to replace amoxicillin if amoxicillin allergy
Reliable non-invasive test to confirm eradication should be performed at least 4-8 weeks
following completion of therapy.
210
Chapter 72 - Recurrent abdominal pain
WF Lau
Definition:
At least 3 attacks in at least 3 months
Severe enough to interfere with normal daily activities
10-15% children between 4 -16 years old has recurrent abdominal pain
Another 10-15% has chronic pain with normal activities
Rare before 5 years of age
Peak at 10-12 years of age
Before 9 years of age, boys and girls equally affected; boys to girls 1:1.5 afterward
5-10% with organic causes
Presentation:
Paroxysmal, variable in severity
50% last for < 1 hour, 90% < 3 hours
Periumbilical or mid epigastric region usually no radiation
Clustering of pain alternating with pain free periods of variable length
No temporal relation with meals, exercise, stress
At least 50% with associated symptoms (headache, pallor, dizziness, nausea, fatigability)
Differential diagnoses:
Functional
- Irritable bowel syndrome
- Functional abdominal pain
- Abdominal migraine
- Aerophagia
Infection
- GI: Giardia, TB, Yersinia, Campylobacter
- Urinary tract
Inflammation
- Inflammatory bowel disease
- Coeliac disease
- Eosinophilic gastroenteropathy
GI obstruction
- Malrotation, postsurgical adhesion, angioneurotic oedema, constipation
Gynaecological
- Dysmenorrhoea, endometriosis, pelvic inflammatory disease, ovarian cysts
Others
- Pancreatitis, hepatitis
- PUJ obstruction,
- Acute intermittent porphyria
- Physical / sexual abuse
- School phobia, conversion reaction, somatization disorder
211
Alarm signals on history
- Localization of pain away from midline
- Pain awakening patient from sleep
- Pain radiated to other area
- Repeated vomiting or altered bowel pattern like profuse diarrhoea
- GI bleeding
- Constitutional symptoms (fever, rash, arthralgia)
- Consistent sleepiness after pain attack
- Loss of appetite
- Positive family history of IBD, peptic ulcer
- Children under 5 years old
Alarm signals on physical exam
- Growth disturbance
- Localized tenderness
- Organomegaly
- Joint inflammation
- Perirectal disease (ulcer, fistula, skin tags)
Alarm signals on investigation
- Elevated inflammatory markers
- Anaemia
- Hypoalbuminaemia
- Positive stool occult blood
Management
- Refer to GI clinic
212
Chapter 73 – Cow’s milk protein allergy
DK Ng
Introduction:
Commonly presents in neonatal and infancy period
50-80% of cases presents with gastrointestinal symptoms
20-40% cutaneous symptoms
4-25% respiratory symptoms
Symptoms and signs:
Gastrointestinal: vomiting, diarrhoea, abdominal colic and bloating, constipation and in severe
cases, haematemesis and bleeding per rectum (enterocolitis syndrome)
Refusal to feed
Dehydration
Failure to thrive
Urticaria, atopic eczema, angioedema
Rhinitis, asthma
Anaphylactic shock
Diagnosis:
Peripheral eosinophilia is uncommon
RAST test and skin prick test
Frequently negative in neonates and infants
A positive skin prick test may not necessarily mean clinical problem but a negative skin
test result has a high predictive accuracy (estimated to be > 95%) in older children
Stool for eosinophils
Stool for occult blood
OGD / colonoscopy with biopsy
Infiltration of the mucosa and submucosa with eosinophils (> 5-20 per high power field)
Management:
Resuscitate if necessary
Advise breastfeeding mother to avoid dairy products
Avoidance of cow’s milk products for 1-2 years.
Over 50% of children with cow’s milk protein allergy may also be allergic to soy protein.
5% may be allergic to semi-elemental milk like Pepti-Junior, and elemental diet like
Neocate may be necessary in such cases. A period of total or partial parenteral feeding
may be necessary.
Open challenge with Cow’s milk should be offered at 2-year-old to confirm remission.
213
Chapter 74 - Management of Idiopathic constipation in children
MC Chan, L Leung
Definition of constipation: delay or difficulty in defecation present for 2 or more weeks (Ref:
NICE guideline May 2010, NASPGHN guideline 2006)
Features suggesting constipation: (table 1)
Child <1yr
Child >1yr
<3 complete stools per week (type 3/4) # <3 complete stools per week (type 3/4)#
Hard stool
Overflow soiling, commonly very loose
and smelly
Rabbit droppings (type1)#
Rabbit droppings (type1)#
Large, infrequent stools that can block
toilet
Distress on stooling
Poor appetite that improves with passage
of large stool
Bleeding asso with hard stool
Intermittent abd pain with passage of
stool
Straining
Retentive posturing: typical straight
legged, tiptoed, back arching
Straining
Anal pain
Painful bowel movements and bleeding
aso with hard stools
Previous episode of constipation
Previous or current anal fissure
#
Bristol Stool Form Scale
(adapted from Lewis SJ, Heaton KW (1997) stool form scale as a useful fuide to intestinal
transit time)
Type 1
Type 2
Type 3
Type 4
Type 5
Type 6
Type 7
Separate hard lumps, like nuts (hard to pass)
Sausage-shaped but lumpy
Like a sausage but with cracks on its surface
Like a susage or snake, smooth and soft
Soft blobs with clear-cut edges (passed easily)
Fluffy pieces with ragged edges, a mushy stool
Watery, no solid pieces; entirely liquid
Table 1. Normal frequency of bowel movements:
Age
0-3 months
- breast-fed
- formula fed
6-12 months
1-3 years
>3 years
Bowel movements per week
Mean bowel movements per day
5-40
5-28
5-28
4-21
3-14
2.9
2.0
1.8
1.4
1.0
(Adapted from Fontana M. Bianch C, Cataldo F, et al. Bowel frequency in healthy children. Acta Paediatr Scand
1987;78:682-4.)
214
Physical exam:
Growth, Abdomen, anal inspection, spine, neurological exam.
At least one PR is recommended: assesses perianal sensation, anal tone, the size of the rectum,
and the presence of an anal wink, the amount and consistency of stool and its location within
the rectum.
Investigations:
AXR – not indicated to establish the presence of fecal impaction if PR reveals large amounts of
stool
– Helpful in obese/ refuses PR or good history of constipation but no large amounts of
stool on PR
Barium enema
– Usually unnecessary beyond infancy
– May be indistinguishable from cases of functional constipation with ultra-short-segment
Hirschsprung; may fail to show transition zone in cases of total colonic Hirschsprung disease
Management algorithm:
Establish the diagnosis of constipation (2 or more symptoms from table 1)
Any RED FLAG symptoms or signs?
History
Signs
From birth or first few weeks of life
Abnormal appearance/ position/ patency
of anus: fistulae, bruising, multiple
fissures, tight or patulous anus,
anteriorly placed anus, absent anal wink
Failure to pass meconium/ delay >48hrs Gross abdominal distension
after birth in term baby
“Ribbon stools”
Asymmetry or flattening of the gluteal
muscles, evidence of sacral agenesis,
discoloured skin, naevi or sinus, hairy
patch, lipoma, sacral dimple, scoliosis
Faltering growth
Lower limb deformity e.g. talipes
Abnormal neuromuscular signs
unexplained by any existing condition
e.g. CP
Previously unknown or undiagnosed
Abnormal reflexes
lower limb weakness, locomotor delay
Abdominal distension with vomiting
No
Yes
Idiopathic constipation
Reassure parents of suitable treatment but may
take several months for symptom resolution.
Assess for faecal impaction (overflow soiling +/faecal mass palpable abdominally and/ or rectally)
215
Test for hypothyroidism, Coeliac
disease, hypercalcaemia, lead toxicity,
cow milk protein allergy (trial of milk
free diet), spinal abnormalities,
Hirschsprung’s disease
Management : **
1. Faecal disimpaction if there is faecal impaction (PEG or lactulose/ stimulant
laxative)
2. Maintenance (PEG or lactulose +/- stimulant laxative)
3. Education, Diet & lifestyle modification, bowel training, diary
1.
FAECAL DISIMPACTION
i. PEG (i.e. Klean Prep) + lactulose
ii. Add a stimulant laxative (e.g. Senna) with or without lactulose for short periods
if Klean Prep is not tolerated or fail to disimpact.
iii. Use glycerin suppository in infants; suppository or fleet enema in children ≥ 2
yrs as last resort only after discussion with parents.
Problems with phosphate enemas: mechanical trauma to rectal wall, severe
hyperphosphatemia and hypocalcemia which may be lethal.
iv. Inform families that disimpaction treatment can initially increase symptoms of
soiling and abdominal pain
v. DO NOT perform manual evacuation of the bowel under anaesthesia unless all
oral and rectal medications have failed
vi. Review all children undergoing disimpaction within 1-2 weeks
2.
MAINTENANCE THERAPY
i. Start maintenance therapy as soon as the patient’s bowel is disimpacted
ii. Reassess the patient frequently to ensure they do not reimpact and assess
issues in maintaining treatment e.g. taking medicine and toileting
iii. PEG (i.e. Klean Prep) + lactulose as the first-line treatment
iv. Adjust the dose of PEG according to symptoms and response. As a guide for
patient who have had disimpaction the starting maintenance dose might be half
the disimpaction dose (table 2)
v. Add a stimulant laxative (e.g. Senna) intermittently, for short periods if PEG does
not work, or not tolerated
vi. Continue medication at maintenance dose for several weeks after regular bowel
habit is established. Children who are toilet training should remain on laxatives
until toilet training is well established.
vii. Do not stop medication abruptly: gradually reduce the dose over a period of
months in response to stool consistency and frequency.
3. EDUCATION, DIET & LIFESTYLE (DO NOT use dietary interventions alone as first-line
treatment)
i. Explain pathogenesis of constipation, remove blame if soiling, needs months of
treatment. Negotiated and non-punitive behavioural interventions. Consistent,
positive and supportive attitude of family.
ii. Scheduled unhurried time on toilet after meals (30min after meal for 10-15min).
216
iii.
iv.
v.
vi.
Use of encouragement, star chart and positive reinforcement.
Posture in defecation: hips abducted and flexed with feet support
Balanced diet should include adequate fibre (whole grain, fruit and vegetable)
and fluid intake. Sorbitol in prune, pear and apple juices can soften stool.
For 1-8yo: 4-5 glasses of water per day (complimentary water)
For 9-18yo: 7-10 glasses of water per day (complimentary water)
Advise daily physical activity
Table 2: laxative recommended dose
A. Stimulant laxatives
Bisacodyl (Dulcolax) (NICE recommended
doses)
PO 4-18yo: 5-20mg once daily
PR (suppository) 2-18yo: 5-10mg once daily
Senna (1 tab = 7.5mg)
2-4yo: 1/2 – 2 tab once daily
4-6yo: 1/2 – 4 tab once daily
6-18yo: 1-4 tab once daily
C. Osmotic laxatives
Lactulose
1 month to 1 year: 2.5ml BD, adjust
according to response
1-5 years: 2.5-10ml BD, adjusted
5-18 years: 5-20ml BD, adjusted
B. Polyethylene glycol (PEG) 3350 + electrolytes
(i.e. Klean Prep 68.6g/pack)
- Dilute 1 sachet of Klean Prep to 1000ml
- Advise to take Klean Prep in the early
evening, as bowel movement starts 1-2 hours
after Klean Prep.
Disimpaction:
<1yr
55-110ml daily (3.8g – 7.5g)
1-5yrs220ml (15g for 1st day) increase to
440ml (30g) daily for 2 days, and up to
660ml (45g) daily
5-12yrs 440ml (30g) (1st day) increase in
steps of 220ml daily to max of 1000ml
(68.6g) daily
Maintenance:
<1yr
55-110ml daily (3.8-7.5g)
1-5yrs
110ml (7.5g) daily; adjust dose to
produce regular soft stools (max 330ml
(22.5g) daily)
5-12yrs 220ml (15g) daily; adjust dose to
produce regular soft stools (max 440ml
(30g) daily)
217
Section 6: Renal system
218
Chapter 75 – Urinary Tract Infection in children 2-24 months
L Leung
Definitions:
Acute pyelonephritis/ upper urinary tract infection: defined as bacteriuria
with i) fever ≥38C or ii) loin pain/tenderness (NICE).
Cystitis/ lower urinary tract infection (bladder inflammation): dysuria,
frequency, suprapubic pain, girls >2yrs.
Asymptomatic bacteriuria: bacteriuria without symptoms.
Diagnosis
History:
Look for risk factors for underlying pathology
- bowel and bladder habits (look for soiling, constipation and voiding dysfunction like
frequency, urgency, squatting or other holding manoeuvres, day-wetting, poor or interrupted
stream, straining during voiding, prolonged voiding)
- past history of similar attacks or unexplained febrile episodes
- AN diagnosis of renal abnormality
- family history of VUR or renal disease
Physical examination:
- BW, Ht, BP
- abdomen (kidney, bladder)
- genitalia including phimosis
- spine, LL reflex
Investigations:
- blood culture if clinically indicated
- RFT
- CRP and ESR (for acute pyelonephritis)
- (G6PD status if not known)
219
Figure 1
Strategy to diagnose febrile UTI
Fever with no obvious focus of infection
Suspected UTI and ill
Suspected UTI and not ill
SPT or catheter urine
for urinalysis and
culture (+ other sepsis
workup), followed by
antibiotics
Option 1: SPT or catheter urine
for urinalysis and culture; or
Option 2: Bag/midstream urine
for urinalysis, if positive, proceed
to SPT or catheter or midstream
urine for urinalysis and culture
Start antibiotics if SPT/catheter/MSU
urine sample shows positive urinalysis
Likelihood Ratios of different enhanced urinalysis tests
Pooled +ve
Tests
Likelihood R (CI)
Pooled –ve
LE +ve
5.5 (4.1-7.3)
0.26 (0.18-0.36)
Nitrite +ve
15.9 (10.7-23.7)
0.51 (0.43-0.60)
Nitrite or LE +ve
6.1 (4.3-8.6)
0.20 (0.16-0.26)
Nitrite and LE +ve
28.2 (17.3-46.0)
Pyuria:
5.9 (4.1-8.5)
> 5/hpf (centrif)
3
> 10/mm (uncentrif)
Bacteriuria
2.5-3.9
7.7
likelihood R (CI)
0.37 (0.26-0.52)
0.27 (0.20-0.37)
#
7#
14.7 (8.6-24.9)
Gram stain (centrif)
18.6
Bacteria seen
4.8#
0.19 (0.14-0.24)
#
Pyuria or bacteriuria
4.2 (2.3-7.6)
0.11 (0.05-0.23)
Pyuria and bacteriuria
37.0 (11.0-126)
0.21 (0.13-0.36)
Any +ve test
(0.8-35.9)
(0.01-5.38)
From : Whiting P. 2005
Stratified by <2 yrs (less reliable)
# Moyer 2000
220
0.32
Diagnostic criteria for Positive Growth for UTI
Confirmed
UTI
Scenario : fever +/- urinary symptoms + pyuria (by dipstix or microscopy)
Any +ve growth of
SPT urine
Yes
uropathogens
>10^4, single growth
Yes
Catheter urine
10^3-10^4, or ≥2 uropathogens
No
<10^3
No
>10^5, single growth
Yes
Clean catch urine
10^4-10^5, or ≥2 uropathogens
No
<10^4
No
Scenario : asymptomatic + negative urinalysis
Colony-forming units on culture
SPT/catheter/
Clean catch urine
Suspected
UTI
Yes
No
Yes
No
Contaminant or
asymptomatic
bacteriuria
Any growth
* Urine should be plated immediately or sent on ice within 4 hours. Overnight samples should
be in boric acid bottles (follow recommended volume).
**All tests have False –ve results. Clinicians should use clinical criteria for their
decisions when urine testing does not support the findings
Treatment
Antibiotic Treatment: Pyelonephritis
If patient is toxic, vomiting or dehydrated (or <2 months), admit to hospital for IV
Antibiotics and fluid therapy. For ≥2 months, Switch to oral AB once fever subsided
provided compliance ensured.
For stable, non-toxic patients ≥2 months who can tolerate and likely compliant with oral
AB, oral antibiotics can be given.
Treatment should last for 7-14 days. (usually 10 days)
Empirical antibiotics depend on local susceptibilities. Usual choices for oral treatment
include cefuroxime, amoxicillin/clavulanic acid (Table 1) or co-trimoxazole (not for <3
mths). Usual choices for parenteral therapy: amoxicillin/clavulanic acid, 2nd or 3rd
generation cephalosporin or aminoglycoside +/- ampicillin (to cover enterococci). For
ESBL organisms: oral Augmentin; if sick: IV meropenam
if blood culture +ve, give iv antibiotics for 10-14 days
Antibiotic Treatment: Cystitis/lower UTI: oral antibiotics for 3-5 days.
Asymptomatic bacteriuria should not be treated.
Patients with UTI who do not show expected clinical response to AB should have urine
re-cultured, co-existence of septicaemia and meningitis should be considered, and US
kidneys performed urgently for abscess/ obstructive HN or complicated malformations.
221
Table 1
Urinary tract infection
Age
<3 months
>=3 months to
children <40kg
Augmentin preparation
156mg/5ml(4:1)
Amoxicillin
30 mg amoxicillin/kg/day
BD
475mg/5ml(7:1)
Amoxicillin
40mg/kg/day
BD (Max. daily dose 875mg)
Clavulanate
7.5mg/ kg /day
Clavulanate
6.4mg/kg/day
Follow up
Imaging
See Fig 2a, 2b
DMSA scan (at 6 mths after UTI) is recommended when:
1) ≥ Grade III VUR is detected on VCUG
2) patient has recurrent febrile UTI.
Antibiotic prophylaxis
Antibiotic prophylaxis should not be routinely prescribed to young children after first time
UTI. No need prophylaxis (whilst waiting for US) unless decided to do VCUG
When VCUG is performed for risk factor criteria and ≥Grade 3 VUR is diagnosed,
antibiotic prophylaxis can be considered, taking into account parental preference.
If UTI recurs, and VCUG reveals ≥Grade III VUR, antibiotic prophylaxis is
recommended.
Surgical referral
• If UTI recurs (2nd UTI), those with ≥Grade III VUR, and significant scarring on DMSA
may be offered a surgical referral to discuss the option of surgical intervention as an
alternative to AB prophylaxis.
• If UTI recurs again (3rd UTI) despite AB prophylaxis, those with ≥Grade III VUR (with or
without scarring) should be offered a surgical referral.
Others
• It is important that the family be educated to recognize the symptoms and signs of recurrent
UTI. Early recognition and treatment of acute pyelonephritis will limit renal damage.
• Dysfunctional elimination syndromes and constipation should be addressed.
• Drink adequate amounts of water
• Perineal hygiene, Urination should not be delayed.
Figures useful in counseling parents
From local cohort of 820 children <24 months old seen in HA hospitals in 2005-6 with full set
of imaging done, VUR found in 24%, of which Gd III 6%; Gd IV 3.9%; Gd V 0.6%.
Using Risk factors + USG criteria + FU as criteria for MCUG and DMSA chance of missing
abnormalities that potentially benefit from early detection (high grade reflux or significant renal
scars) is 0.8%.
222
*
* Risk factors
- Severe sepsis or
septicaemia
- Palpable abdominal mass.
- Impairment of baseline
renal function
- Hx abnormal urine stream
- UTI due to non-E coli
organisms
- No clinical response to
appropriate antibiotics
within 72 hrs
- VUR first degree relative
Major references:
HK- HA Paed COC QA subcommittee Clinical Guideline on The Diagnosis and Initial Management
of Urinary Tract Infections in Infants and Children aged 2 to 24 months (2013)
UK - NICE Guidelines 2007
USA - AAP. Pediatrics 2011; 128:595-610.
Italy - Ammenti et al. Acta Paediatr 2012; 101(5):451-457
Australia - Williams et al. J Paediatr Child Health 2012; 48(4):296-301
223
Chapter 76 – Monosymptomatic Nocturnal Enuresis
PH Chan, L Leung
Terminology
Enuresis – wetting during sleep in a child ≥ 5 years of age
Monosymptomatic enuresis (MNE) – Enuresis without any lower urinary tract symptoms.
Non-monosymptomatic enuresis (NMNE) – Enuresis with other lower tract symptoms
Primary enuresis – Enuresis in a child who has previously been dry for <6 months
Secondary enuresis – Enuresis in a child who has previously been dry for at least 6 months
Evaluation: Aim to identify
1. Organic diseases (neurogenic bladder, UTI, polyuric state like DM, DI, hypokalemia)
2. Voiding dysfunction/ lower urinary tract symptoms
3. Psychiatric comorbidities (e.g. ADHD)
4. Constipation
History
General - Health and development. Weight loss? Excessive thirst? UTIs?
Timeframe - Primary/secondary enuresis? Frequent/sporadic accidents?
Bladder – Voiding dysfunction e.g. frequency, urgency, dysuria, straining, weak or intermittent
stream
Bowel - Constipation symptoms, fecal incontinence?
Behaviour - Problems at home or at school? Distressed by enuresis?
Previous treatment strategies - Which strategies have been used? Have they been used
correctly?
Others - Enuresis in the family? Difficult to arouse from sleep? Sleeping arrangements.
- Habitual snoring, observed obstructive apnea
Physical Examination
General – Well-being, growth, BP
Back – Skin stigmata for spinal dysraphism, spinal deformity
Lower limbs – Neurology
External genitalia – Malformation, phimosis
Constipation – Abdominal (fecal) mass, soiling on underpants, +/- PR
48-hour frequency-volume chart (available on Department Web)
Daily fluid intake and urine output – Identifies those with polydipsia/ polyuria
Voiding frequency/ urgency – Identifies those with urinary frequency (>7x/day)/ urgency
Maximum voided volume – when compared to expected bladder capacity (30 x age +30 mL,
max 390mL), identifies those with bladder pathology (detrusor instability or underactivity)
Nocturnal urine volume – (diaper weighing) When compared to expected bladder capacity,
help to plan treatment
Investigations
Monosymptomatic enureisis: MSU x R/M, culture, protein, glucose, EMU x osmolality (>700
mOsmol/L rule out concentration defect
Secondary nocturnal enuresis or diurnal urinary incontinence: Plus RFT, Ca, Urine Ca/Cr
Initial evaluation suggestive of NMNE: Refer renal clinic, may need urodynamic study.
If suspect neurogenic bladder or posterior urethral valve: may need US with post void residue,
or MCU.
224
Treatment
General advice – for all
1. Treat constipation (Regular visit to toilet every night after dinner, foot support, stool
softener etc.)
2. Liberal fluid and solute during the day and limit fluid and solute during evening (practically
– avoid large dinner and food after dinner, except fruit)
3. Empty bladder before retiring
4. Easy access to bathroom (may need night light)
5. No lifting/ diaper/ training pants; protect bed (e.g. with plastic sheeting)
6. Routine awaking is unnecessary.
7. Child should bear age-appropriate responsibilities after wetting (e.g. soak or wash
underpants)
8. Star chart – charted by child under supervision. Lots of praise for dry night
Specific treatment – for those >= 6 years of age
The Enuresis Alarm
•
Good for motivated child and family
•
Early initial follow-up (2-3 weeks) is essential
•
The parent may help child wake up for initial 1-2 weeks, (but not do everything for him.)
•
Fill in ”Enuresis alarm recording sheet” (on Dept. web)
•
Praise Smaller wet patch.
•
Use consistently every night without interruptions, until 14 consecutive dry nights or 4
months without effect. If response, can try load with increased fluids before bed to
enhance response.
Explain anticipated response: gradual smaller wet patch; usually by 3-4 weeks: 3-4 dry nights/
week.
Success rate: 65-100% (85%) after 4-6 months, enhanced by support from parents and therapist
Relapse rate: 9-23% (23%), most respond quickly to another course of alarm treatment
If fail: Praise them for effort; say bladder not ready yet and try again later and advise follow-up
Desmopressin
Increase antidiuretic activity of DDAVP
Most efficient in children with nocturnal polyuria (document with frequency-volume chart)
Choose between daily medication or administration before important night e.g. camping
•
Desmopression 200–400µg PO taken at least 1 hour before sleep
•
Desmomelt 120-240µg PO taken 30-60 mins before sleep
Restrict fluids after dinner to <200mL till awakening next morning
Water intoxication and seizures reported
Headache, abdominal pain, nausea
Cure rate 25%
Response rate (half wet nights) 70%
Most relapsed after off drugs (5.7% still dry)
Priority of treatment
General advise PLUS Treat constipation Treat daytime bladder symptoms Treat enuresis
Referral to Renal Clinic
1. Non-monosymptomatic enuresis
2. Those who required specific treatment
225
Chapter 77 - Nephrotic syndrome
L Leung
Definition :
Nephrotic syndrome (NS) = heavy proteinuria severe enough to cause hypoalbuminaemia, and
usually hypercholesterolaemia and oedema.
Nephrotic range proteinuria is defined as spot protein / creatinine ≥ 200 mg/mmol or proteinuria
≥ 40 mg/m2/hour or ≥ 1,000 mg/m2 per day.
Pre-steroid renal biopsy should be considered in those whose features make minimal change NS
less likely:
- Age <1 year or >12 years
- Macroscopic haematuria
- Persistent hypertension
- Low C3, Hep B or C positive
- Impaired renal function
Post steroid-treatment: renal biopsy if steroid resistance or in steroid dependency before use of
cyclophosphamide (optional) or cyclosporin A
Table 1. Definition of terms used in children with NS
Remission
Dipstick negative or trace proteinuria for 3 days or urinary protein excretion < 4 mg/m2/hour
Relapse
Dipstick >= 2+ proteinuria for 3 consecutive days; or patient found to have 3-4+ proteinuria
plus edema
Frequent relapses (FR)
2 or more relapses within first 6 months after initial response, or
4 or more relapses within any 12 months period
Steroid dependency (SD)
2 consecutive relapses during tapering of glucocorticoid, or within 14 days of cessation
Steroid resistance (SR)
Persistent proteinuria despite full-dose prednisolone for 4 weeks, followed by 3 x 1g / 1.73 m2
IVI pulses of methylprednisolone. (Niaudet)
Steroid-responsive in 90% children. 70% will have relapses, ~50% FR or SDNS.
80% NS due to Minimal Change, GN.
Secondary causes of NS
• Infection: HepB, HepC, Syphilis,TB, Mycoplasma, HIV, congenital CMV/ toxo/ rubella
• Systemic diseases: HSP, SLE, vasculitis
• Structural glomerular changes (eg. Alport)
• Malignancy: lymphomas, leukaemias, solid tumours like nephroblastoma
• Drugs: NSAID, Antimicrobials (ampicillin, rifampicin, cephalosporins), Lithium,
D-penicillamine, bisphosphates, Sulfasalazines.
Investigations
CBP, RFT, LFT, cholesterol and triglycerides, ANF, anti-dsDNA, C3C4, Ig pattern, HBsAg,
HBeAg, Hep C, antibodies to measles and varicella, EBV, CMV.
Urinalysis: RBC, casts; 24-hour urine x protein and creatinine clearance
226
Mantoux test: if positive, exclude TB before treatment
Acute complications of NS
Hypovolaemia, hypervolaemia
Infections: peritonitis (Strep. pneumoniae, E. coli), cellulitis
Venous, and rarely, arterial thrombosis, rare in Chinese children
Anasarca leading to respiratory distress, skin breakdown and cellulitis
General aspects of management of children with NS
Assess fluid status
Hypovolaemic children may appear tired, have decreased urine output, abdominal pain,
prolonged cap refill, tachycardia, postural hypotension (but may be hypertensive from
vasoconstriction).
Lab tests may show raised Hct, urine Na < 10 mmol/l or urinary FENa of < 1%, Urine K+ / Urine
K+ + Urine Na+ > 60% (indicating aldosterone activation). However, urine Na may also be
low in hypervolaemic NS from primary Na retention.
Those with hypovolaemia may be promptly treated with 10-20ml/kg 4.5% albumin.
Diet: salt restriction to 2-3 mEqNa/kg/day, max 2g/day, but generally not need fluid restriction;
adequate in protein. When on steroids, recommend a nutritious, relatively low-fat diet.
Oedema: If severe symptomatic oedema with normal intravascular status: frusemide +/spironolactone. Caution: as may precipitate shock in a volume depleted child. In oedematous
children with marked hypoalbuminemia, may give daily or bd salt-poor albumin 1 g/kg over 4
hours with IV frusemide 1-2mg/kg. Caution: may precipitate pulmonary oedema in
hypervolaemic patients.
Hypertension: may be due to hypervolaemia or excessive vasoconstrictive response to
hypovolaemia. Latter: urine Na low. Former: raised venous pressure, cardiomegaly. Treat with
atenolol 0.5-1 mg/kg or nifedipine 0.25-2 mg/kg.
Others: Encourage mobilization. Prophylactic antibiotics not recommended, but infections to
be promptly treated. Education of parent and child about NS, side effects of treatment and
regular urine dipstick monitoring at home to identify early relapse.
Specific therapy for Nephrotic Syndrome
Initiating and maintenance of steroids (HKPNS)
Prednisolone 60 mg/m2 (max 60 mg) x 4weeks; as single daily morning dose.
40 mg/m2 alternate day for 4 weeks, then 30mg/m2 alternate day for 4 weeks, 20mg/m2
alternate day for 4 weeks, 10mg/m2 alternate day for 4 weeks, 5mg/m2 alternate day for 4
weeks, then off (Total treatment duration of 6 months).
For late responder (those could not achieve remission in first 2 weeks, ~ 20% responders)
Prednisolone 60mg/m2/day (maximum 60mg/day) for 6 weeks, followed by 40mg/m2 on
alternate day (maximum 60mg alternate day) for 6 weeks, then similar tapering doses for 4
weeks each time.
(Total treatment duration of 7 months)
Monitor for steroid side effects: Cushingoid features, weight gain, gastric irritation, ulcers,
pancreatitis, hypertension, fluid retention, bone demineralization and avascular necrosis,
decreased immunity, posterior subcapsular cataract, diabetes, pseudotumour cerebri, proximal
myopathy, growth retardation, psychological changes (depression, psychosis, mood lability).
227
Treatment of relapses
60 mg/m2 till protein free 3 days consecutively, then 40 mg/m2 alternate day therapy for 4
weeks, then taper.
Other issues related to steroid therapy
Hypothalamic-Pituitary-Adrenal axis suppression occurs when steroid treatment lasts > 2 weeks.
Needs 2-3x physiological dose during surgery, trauma, infection. Children already on larger
than physiologic doses of steroid do not need additional coverage. Give coverage for 1 year
post-steroid weaning: hydrocortisone 1-2 mg/kg Q6H x 24-48 hours post-op.
Osteoporosis: those on more than 5 mg daily or > 15 mg alternate day for at least 3 months are
at risk of osteoporosis. Measures to decrease risk:
Children: elemental calcium (diet or supplement) 800 mg/day for 1-5 yr olds, 1,200
mg/day 6-10 yr olds, and 1,500 mg/day for 11-24 yr olds + supplemental Vit D 400 IU/day
increase physical activity (especially weight bearing activities such as walking).
avoid heavy lifting, high-impact aerobics and contact sports.
Infections and immunizations
a.
Vaccines should be given ideally when patient is in remission. Killed vaccines can be
given any time. Avoid live vaccine when on high dose steroids or other
immunosuppressives. Live vaccines preferably given when child has been off steroids for
6 weeks (best 3 months after stop steroids or cyclosporine, or 6 months after stop
cyclophosphamide) or at least, on low-dose (< 0.5 mg/kg) alternate day steroid.
b.
Children not previously immunized against measles should receive immunoglobulin when
exposed.
Check chickenpox / measles antibody status. Varicella vaccine, 2 doses 4 weeks apart,
should be given to all non-immune nephrotic patients on immunosuppressives, ideally
when child in remission & on low alternate day steroids or off steroids. If a susceptible
child on steroids is exposed to chickenpox, varicella-zoster immunoglobulin VariZIG
should be given within 96 hours of exposure. Steroid should be tapered to ≤ 1 mg/kg/day
until incubation period has passed. Acyclovir should be given if varicella does develop.
Varicella vaccine should be given 5 months after VariZIG.
c.
d.
Pneumococcal vaccine is recommended for all nephrotic children (Table 2) ideally when
child in remission & off daily steroid, though high antibody levels still found when given
whilst child on daily high dose steroid.
e.
Give annual Influenza vaccine.
f.
Household contacts of children on high dose prednisolone should be given inactivated
polio rather than live oral polio.
g.
Nephrotic children with positive tuberculin reaction and no active TB should receive
Isoniazid prophylaxis for 6 months if interferon-gamma is +ve.
228
Table 2. Suggested pneumoccocal vaccine schedule for nephrotic children (AAP 2010)
Recommendations
Age
Previous Doses
none
PCV13
as
normal
schedule
≤ 23 months
24-59 months 4 doses PCV13 1 dose 23PS at 24 months, at least 6-8 weeks after last PCV7
2nd dose 23PS, 5 years after 1st dose 23PS
1-3 doses PCV3 1 dose PCV13
1 dose 23PS, 6-8 weeks after last PCV13
24-59 months none
2 doses PCV13 6-8 weeks apart
1 dose 23PS, 6-8 weeks after last PCV13
1 dose 23PS
2 doses PCV13 6-8 weeks apart, at least 6-8 weeks after last 23PS
1 dose 23PS, 3-5 years after 1st dose 23PS
6-18 years
none
1 dose PCV13
1 dose 23 PS 6-8 weeks after last PCV13. 2nd dose 23PS 5 yrs after
1st dose 23 PS
PCV13= pneumococcal conjugate vaccine 23PS= 23-valent pneumococcal polysaccharide
vaccine.
Children with frequently relapsing (FRNS) or steroid dependent (SDNS) nephrotic
syndrome
Renal biopsy should be considered. Consult Renal team.
May be maintained on Prednisolone 0.1-0.5 mg/kg/alt day for 3-6 months then reduce.
If child relapses on > 0.5 mg/kg/alt day or is steroid-toxic: may require alternative drugs to
control the disease and decrease steroid side effects.
Levamisole:
effective for milder disease; 2.5 mg/kg/alt day, usually for 2-3 yrs if remission maintained.
Cyclophosphamide:
more effective for FRNS, can keep 70% SDNS in remission
some evidence 12-week course of cyclophosphamide 2 mg/kg/day is superior to 8-week
course 3 mg/kg/day. Total cumulative dose should be less than 170 mg/kg to minimize
long-term risks of azoospermia and ovarian fibrosis.
Other side effects: bone marrow suppression, hair loss, haemorrhagic cystitis, long term
increased risk of malignancy
Cyclosporin A:
indicated where relapses occur after cyclophosphamide. However, children may become
cyclosporin A dependent.
Side-effects include hypertension, nephrotoxicity, increased K+, decreased Mg2+,
hypertrichosis and gingival hyperplasia.
Mycophenolate mofetil:
Useful, especially in children who are at risk of nephrotoxicity after on prolonged course of
Cyclosporin A.
Steroid sensitive NS generally has a good prognosis and likely to improve with time. When
potentially toxic drugs are used; one has to balance the benefit against the potential side effects
of the drugs.
Steroid resistant NS
Renal biopsy. Consult Renal team.
229
Chapter 78 - Fluid and electrolytes therapy
B Pau, L Leung, DK Ng
Principle: Maintain fluid homeostasis.
– Replacement of deficit
– Maintenance therapy
– Replacement of ongoing loss: excessive urine loss , GI loss. Skin (infective/ immune/
burns). 3rd space loss. Hyperventilation/ fever.
Daily requirement of fluid can be estimated from body weight:
First 10Kg
100mls/kg
Subsequent 10Kg
50mls/kg
Remaining Body Wt over 20Kg
20mls/kg
For example: A 25Kg child would require:
10 x 100mls + 10 x 50mls + 5 x 20mls
for a total 1600mls/day
Clinical assessment of fluid deficit: (1% deficit = 10mls/Kg)
- Mild dehydration (Deficit: infant 5%, children 3%). History of vomiting/ diarrhea,
decreased intake, decreased urine output, thirst. P/E usually unremarkable.
- Moderate dehydration (Deficit: infant 10%, children 6%). History of fluid loss. P/E:
decreased skin turgor, weight loss, sunken eyes +/- fontanel, slight lethargy, and dry mucous
membranes.
- Severe dehydration (Deficit: infant 15%, children 9%). Cardiovascular instability (e.g.
prolonged CRT, skin mottling, tachycardia, hypotension) and neurologic involvement (e.g.
irritability, coma).
Principles of Fluid therapy
- Use oral hydration first (including in hyperNa and severe dehydration) unless oral intake
not tolerated/ contraindicated
- In GE cases, oral rehydration with Oral Rehydration Solution (ORS) 40-50mls/Kg for initial
deficit over 3-6 hrs (longer duration for older children), frequently in small amounts
(minimal 240ml for <5 yrs and 480 ml for ≥5 yrs). Replace on-going loss: 5mls/Kg per
large watery diarrhoea and 2mls/kg per vomit. (Please refer to KWH GE guidelines for
details)
- Traditionally dehydration is replaced over 24 hrs (unless hypertonic dehydration) in
addition to daily maintenance fluids. Recent literature are advocating faster rehydration in
the absence of hypernatraemia. (Replace deficit in moderate / severe dehydration with
40-50ml/kg isotonic solution (NS or Ringer’s lactate) over 2-4 hrs)
- Frequent reassessment and adjust accordingly, esp when there is significant ongoing loss
- If evidence of shock, give rapid infusion (over 30-60min) of 20ml/kg NS bolus, repeat if
needed. In severe cases of shock, use Ringer’s Lactate solution.
- Consider other causes of shock.
- Admit ICU if fluid resistant shock (Not responsive after 2 NS bolus)
- K+ is not routinely prescribed in IVF in the general ward. Consider oral potassium
supplement in mild hypokalaemia. Significant / symptomatic hypokalaemia warrants ICU
admission.
230
Monitoring fluid status:
- Clinical examination: Secretions (tears, saliva), mucosal surfaces, skin turgor, perfusion and
haemodynamic status, conscious level.
- Urine output , In/ out fluid balance
- GI loss (vomitus/ gastric aspirates, Stool)
- Body weight
- Renal function (serum sodium level, urea), Base excess.
- Echocardiogram for circulatory volume (LA size, IVC, Flow time constant)
Some clinical scenarios may require increased or decreased fluids.
In critical cases daily fluid requirement can be estimated by: Urine output (in past 24 hrs) + any
fluid deficit+ On-going loss + Insensible loss (40-50mls per 100kcal expended)
Increased maintenance fluid requirement:
- Fever (additional 10-20%)
- On-going loss (diarrhoea and/ or vomiting)
- Burns, Skin infection/ inflammation (streptococcal scaled skin syndrome, Steven
Johnson syndrome/ TEN)
- Neonates (daily IV fluid requirements up to 150mls/Kg/day)
Decreased maintenance fluid requirement:
- Brain-injury/cerebral oedema (60-80% restriction)
- SIADH (~ 60% restriction or guided by urine output and Na level)
- Renal failure (Insensible water loss + urine output)
- Heart failure (50-80% restriction)
- Inactive/ bed bound (75% restriction)
- Mechanical ventilated with humidified gas (75% restriction)
Choice of IV fluids:
Neonates: 10% dextrose + electrolyte supplements as indicated.
Paediatric cases:
D5 ½ NS solution: - Most cases
D5 NS solution: - Hypernatraemia, Hyponatraemia/ risk of hyponatraemia
Normal Saline bolus for shock
Ringer’s Lactate solution in severe shock.
Clinical risk of Hyponatraemia:
- GE (see GE protocol)
- Chronic lung disease/ bronchiolitis
- Post op
- CNS pathologies e.g infection, Head injury, tumour
Daily Electrolyte requirements:
Sodium: 2-4 mmol/Kg/day
Potassium: 1-2 mmol/Kg/day (if indicated)
Calcium: 0.5-1 mmol/Kg/day (if indicated)
Usual preparations, to be added to IV fluids as indicated:
5.85% NaCl
1mmol Na/ml
14.9% KCl
2mmol K/ml
10% Ca Gluconate
0.22mmol Ca2+/ml
231
Special Considerations:
Hypertonic dehydration (Na >150mmol/L)
- Occurs when water loss from ECF is greater than solute loss.
- Common causes include: Diabetic Ketoacidosis and Diabetes Insipidus, hyperventilation,
pure water loss with high fevers, and osmotic diarrhea.
- Iatrogenic Causes (prolonged NPO, excessive hypertonic fluids, sodium bicarbonate, or
tube feedings with inadequate water)
- Aim to lower Na levels to normal (<150mmol/L) by 10 mmol/L/24h.
- Rapid correction of hypernatremic dehydration can have disastrous neurological
consequences, including cerebral edema and death.
- Slow correction of the fluid deficit over 48 hours. Rehydration with D5/NS.
- Frequent monitoring of Na levels
Hyponatraemia (Na < 130mmol/L)
-
-
-
-
-
Consider: The patient’s fluid status (normo/hyper/ hypovolaemia).
Duration and magnitude of the hyponatremia.
Degree and severity of clinical symptoms
Free water restriction is generally the treatment of choice for normovolemic asymptomatic
hyponatremic patients.
In asymptomatic hypovolemic hyponatremia, replace the fluid as well as the sodium deficit.
Sodium deficit = (sodium desired - sodium actual) X volume of
distribution (i.e. 0.6)
X
Body Weight (kg)
Hypervolemic hyponatremia: Treat patients who are hypervolemic with salt and fluid
restriction, plus loop diuretics, and correction of the underlying condition.
In chronic, severe hyponatremia (i.e. >48hrs) sodium correction should not exceed 8mmol/L
per day.
In severe symptomatic hyponatremia (eg, seizures, overt neurological deficits) give
hypertonic (3%) saline in 4ml/Kg bolus, preferably via central line over 15-30 mins, and
recheck Na level afterwards. Repeat hypertonic saline bolus if there are persistent severe
CNS symptoms attributable to hyponatraemia or until serum sodium level is above
120mmol/L.
Once the CNS symptoms have abated, the sodium correction should be adjusted so that the
total daily sodium correction (including the hypertonic saline) is no more that 8mmol/L in
24 hours.
Monitor Na levels closely.
232
Chapter 79 – Systemic lupus erythematosus
L Leung, A Yuen
Introduction:
Systemic lupus erythematosus (SLE) is a chronic multisystemic inflammatory disorder of
unknown etiology. The clinical manifestation is variable involving different end organs.
Male to female ratio = 1 : 9
Common age of onset: 15-45 years old
Prevalence: 15-52 per 100,000 in Western world
Diagnosis:
According to the ACR criteria: when a patient fulfills 4 or more of the 11 criteria serially or
simultaneously, the diagnosis of SLE can be made with a specificity of around 95% and a
sensitivity of 85%
1997 updated Criteria for Classification of Systemic Lupus Erythematosus (ACR)
Criterion
Definition
1. Malar rash
Spare nasolabial folds
2. Discoid rash
3. Photosensitivity
4. Oral ulcers
Erythematous rasied patches, keratotic scaling, follicular plugging
5. Arthritis
Non-erosive arthritis involving 2 or more joints
6. Serositis
7. Renal disorder
Pleuritis or pericarditis
Persistent proteinuria>0.5g/day or >+++ or Cellular casts
8. Neurologic disorder
Seizures or psychosis
9. Haematologic disorder
Haemolytic anemia, leukopenia, lymphopenia or thrombocytopenia
Oral of naspharyngeal, usually painless
10. Immunologic disorder Anti-DNA, Anti-Smith, Anti-phospholipid antibodies
11. Anti-nuclear antibody
Found in more than 98% of patients with SLE, usu ≥1:640
Other criteria = SLICC 4/17 criteria
Investigations:
Blood: CBC, D/C, L/RFT, CaPO4, Glucose, ESR, ANA, anti-dsDNA, C3, C4
+/- CK; LDH if muscle pain, +/- troponin if chest pain
To allow better assessment of risks for complications: antibodies against extractable nuclear
antigens - ENA (e.g. Ro, La, Sm, nRNP), the phospholipids (e.g. anti-cardiolipin, lupus
anticoagulant and anti-beta2-glycoprotein)
Urine: protein, microscopy, cast
CXR +/- ultrasonography to look for pericardial / pleural effusion
ECG
233
Monitoring:
New symptoms (e.g. weight loss, arthritis), new skin rashes
Blood pressure monitoring
Fluid input / output charting and daily body weight for those with renal impairment
Urinalysis with urine sediment, multistix for RBC, protein
Regular monitoring of disease activity: CBC, D/C, ESR, C3, C4, CH50, anti-dsDNA, CRP (in
infection, also SLE eye, pulmonary, GI, neurological activity), RLFT
Treatment
General: Sun-protection by physical barrier or sunscreens of SPF ≥55 blocking both UVA & B.
Adequate sleep and exercise
Minimise cardiovascular risk factors (blood lipids, BMI, smoking cessation, BP)
Immunisations: Flu A and pneumococcal, quadrivalent HPV when stable.
Vit D if on steroids.
Avoiding sulphonamide-containing antibiotics and minocycline
Consider contraception
Non-organ threatening:
Simple analgesics e.g. paracetamol and NSAID (Avoid ibuprofen due to the association of
aseptic meningitis), physiotherapy for musculoskeletal complaints.
Topical steroid in cutaneous lupus
Antimalarials e.g. hydroxychloroquine good for musculoskeletal and skin; beneficial effect
on disease activity and survival.
Low dose systemic steroid (<0.35mg/kg/day)
Disease modifying agents e.g. methotrexate, azathioprine if needs maintained on
significant steroid dose (>0.2mg/kg/day)
Serositis:
A) Pleuritis OR Pericarditis
Treatment:
NSAID especially indomethacin
Anti-malarial
Low dose steroid
Immunosuppressant
Surgical drainage
Renal disorder:
Treatment: depends on WHO classification and activity / chronicity indices
Steroid is first line treatment
Antimalarials
For Class III or IV: high dose prednisolone or IV methylprednisolone +
cyclophosphamide or MMF for induction, azathioprine or MMF for maintenance.
For Class V: may not respond to steroid, Cyclosporin A, MMF may be useful
Other drugs for severe refractory nephritis: Tacrolimus, Rituximab
234
Chapter 80 – Postnatal management of antenatally diagnosed
hydronephrosis
PH Chan, L Leung
Working definition of antenatally diagnosed hydronephrosis (ANH)
All neonates whose antenatal ultrasound scans show:
- Anterior-posterior diameter (APD) of renal pelvis ≥ 4mm at 2nd trimester and/or ≥7mm at
3rd trimester.
AN USG findings, in conjunction with ANH that point to significant urinary tract
obstruction (please refer to Fig. 2)
- Oligohydramnios
- Abnormal bladder (thickened wall, ureterocele)
- Bilateral renal tract dilatation with APD >15mm
- Solitary kidney with APD >15mm
Tips on initial management
- Routine urinalysis or urine culture is NOT needed for all neonates with ANH.
- Observation in SCBU (urine output, blood pressure and RFT at 48 hours) is recommended
only for neonates who have AN USG findings that indicate significant urinary tract
obstruction (see above and Figure 2). Renal team should be notified in such situations.
- For those who do not require admission, investigation and follow-up can be arranged in
postnatal (PN) ward (Figure 1), trimethoprim (TMP) prophylaxis can be started on
discharge from PN ward.
- Dose of trimethoprim: 1-2mg/kg PO nocte
- Parents should be warned of symptoms of UTI and instructed to seek early medical
attention.
Timing of and preparing request for investigations
- PN USG should be done >72hrs of age in well-hydrated baby.
- Liaise with radiologist for arrangement of investigations that need to be done within 1
month
- Specify clearly in request form AN USG finding and time frame of investigation
- MAG3 should preferably be done after 6 weeks to allow for renal maturation
Role of MCUG in evaluation of ANH is controversial
- Neither the grade of dilatation nor gender is a predictive factor for VUR in ANH.
- The clinical relevance/ benefit of identifying VUR (especially of low grade) in infants who
have not had any UTI is unknown.
- Indications are controversial. It is advised when USG identifies ureteric dilatation, as per
algorithm in Figures 1 and 2, and whenever there is UTI associated with HN.
Consult renal team at any stage in the presence of
Any complications (like UTI, gross haematuria, voiding abnormalities)
Any unusual radiographic features (like thickened bladder)
Any queries
235
Figure 1. Algorithm of management of unilateral ANH with no feature of significant
obstruction
Antenatal ultrasound finding
APD <10mm
APD 10-15mm
APD >15mm
Book early renal USG
(within 4-8weeks)
Start trimethoprim
(within 3 months)
Admit SCBU
(within 2-4 weeks)
Start trimethoprim
Postnatal ultrasound finding
Ureteric dilatation
With any degree of HN
Start TMP if not yet done
Book MCUG and MAG3 scan
Refer renal clinic
Yes
No
Bilateral HN with
APD ≥ 10mm bilaterally
Start TMP if not yet done
Book MCUG within a week
Follow Fig. 2 from broken line-bordered box
Yes
No
APD >15mm or
Calyceal dilatation
with any degree of HN
No
No
Yes
Start TMP
No
APD < 6mm
APD 6-9.9mm
APD 10-15mm
If USG done
beyond 1m:
Off TMP &
Close case
If USG done
beyond 1m:
Off TMP
Close case
after 1yr if no
complications
like UTI
Repeat renal
USG 3 and
6-9m
after 1st USG
If USG done
within 1m:
Off TMP
Repeat USG
3-6m later
Repeated USG
(if needed)
HN static or
improved
If USG done
within 1m:
Off TMP
Repeat USG
3-6m later
MAG3 scan
No obstruction
AND
relative renal
function >40%
for both kidneys
Obstruction or
a kidney with
relative renal
function ≤40%
MCUG
APD >10mm
persists beyond
1 year
VUR grade
III or above
Book MAG3
Book
DMSA
Refer renal clinic
Close
case
236
VUR grade
II or below
Figure 2. Algorithm of management of bilateral ANH/ ANH in solitary kidney/ ANH with
features of significant obstruction
Antenatal ultrasound finding
HN with ureteric dilatation or
HN with oligohydramnios or
HN in solitary kidney APD ≥10mm or
HN with APD ≥10mm bilaterally or
HN with abnormal bladder
No
Yes
Maximal APD 6 to 15mm
Ix and Mx according
to unilateral ANH
Follow Fig. 1 from
the start according to
maximal APD
Maximal APD >15mm
Admit SCBU for monitoring
Book renal USG and MCUG
>72hrs to within 1 week
Start trimethoprim
Admit SCBU for monitoring
Book renal USG and MCUG
within 3 days
Start trimethoprim
Postnatal Ix result
Suggestive of PUV, PUJO, VUJO,
duplex kidneys, ureterocele or other
structural anomalies
Yes
Liaise with renal team &
refer to urology
No
USG normal or APD <10mm
with no calyceal/ ureteric dilatation
Yes
MCUG result
No
USG APD ≥10mm or
calyceal/ ureteric dilatation
MCUG result
VUR Grade
III or above
VUR Grade
II or below
Book MAG3
& DMSA
Book MAG3
scan
VUR Grade II
or below
VUR Grade III
or above
Repeat USG at 3 months and follow
Fig. 1 starting from double-bordered
box using maximal APD as a guide
No need to repeat MCUG
Book DMSA
scan
Refer renal clinic
237
Chapter 81 – Systemic corticosteroids therapy
E Ho, YY Lam, L Leung
Relative potencies and equivalent doses of corticosteroid:
Dosage of corticosteroids varies widely depending on the disease states, and their relative
glucocorticoid and mineralocorticoid activity should be considered when deciding the
appropriate treatment. The comparison table below summarises the relative potencies and
administration precautions:
Equivalent Glucocorticoid Mineralocorticoid
dose
potency
potency
Betamethasone
(inj disod
phosphate)
Dexamethasone
(inj Na phosphate)
0.15 mg
0.15 mg
No significant
Fludrocortisone tab anti-inflamma
tory effect
Hydrocortisone
(inj succinate)
Methylprednisolone
(inj succinate)*
Prednisolone tab
Administration
Half-life
(hours)
0
Inj (suspension):
not for IV
36-54
25 – 30
0
PO: with food
Inj: IV push if < 10
mg; high dose should
be given as infusion
over 15-30 minutes
36-54
10
125
PO: with food
No inj available
18-36
25
4 mg
1
2
0.8 mg
5
0
1 mg
4
1
238
PO: with food
Inj: bolus – dilute to
50 mg/ml and give
over 3-5 minutes
Infusion – dilute to 1
mg/ml and give over
20-30 minutes
Inj: ≤ 1.8 mg/kg or ≤
125 mg/dose, IV push
over 3-15 minutes
≥ 2 mg/kg or 250
mg/dose, IV push over
15-30 minutes
> 15 mg/kg or ≥ 1
g/dose, infuse over 1
hour*
PO: with food
8-12
18-36
18-36
Special aspects in corticosteroid administration:
* Association of high dose IV methylprednisolone and cardiac toxicities have been reported :
1. Hypotension, bradycardia and asystole after high-dose IV methylprednisolone
2. Recurrent cardiocirculatory arrest after kidney transplantation
3. Avoid long line administration of IV methylpredisolone.
Although the exact mechanism is not known, rapid infusion and underlying cardiac conditions
were considered important factors.
Ca and Vit D supplement
Many guidelines in adults suggest adding Ca and vitamin D if > 3 months steroids and ≥ 5 mg
prednisolone a day, though negative bone effects have been found even at 2.5 mg daily.
Adults: Calcium 1500 mg/day (diet + supplement) or 1000 mg/day supplement
Vit D: 400-500 IU/day in < 65 years, 800-1000 IU/day in older
Activated vit D (calcitriol or alfacalcidol) more effective than vit D but need greater
monitoring for hypercalciuria or hypercalcemia
Some suggest if > 3 months: add biphosphonate, but avoid in those who wish to
conceive
Children: no specific recommendations beyond 1996 American College of Rheumatology
guideline.
consistently ingest, through either diet or supplements, the following daily calcium
intake: 800 mg/day at ages 1-5 years, 1,200 mg/day at ages 6-10 years, and 1,500
mg/day at ages 11-24 years.
at least 400 IU/day of vitamin D
may use activated vitamin D such as calcitriol 0.25 mcg daily but need to monitor for
hypercalciuria and hypercalcaemia
KWH Ca preparation
CaCO3 1 g tab
Calcium lactate 300 mg tab
CaCl2 10% inj
Calcium gluconate 10% inj
“Calperos D3” tab
Elemental Ca2+ content
10 mmol or 400 mg
1 mmol or 39 mg
0.68 mmol or 27.3 mg Ca2+ ml
0.22 mmol or 9 mg Ca2+ / ml
Ca 500 mg + Vit D 400 IU
Corticosteroid treatment and weaning:
Physiological replacement dose:
- hydrocortisone: 6-8 mg/m2/day q6h IVI/IMI
- methylprednisolone 2 mg/m2/day q6-8h IVI
- hydrocortisone 8-12 mg/m2/day PO tds
- predisolone 2-3 mg/m2/day PO bid
- dexamethasone 0.2-0.3 mg/m2/day PO QD
239
Stress Dose Replacement:
- IM/IV if vomiting or diarrhoea
- Minor stress (fever, minor infection)
Double to triple i.e. 2-3x physiological replacement dose
- Major stress (surgery, major infection, trauma)
Load with 50mg/m2 IV/IM Hydrocortisone, followed by 5-6x replacement dose at
around 100 mg/m2/day Q6H
Mineralocorticoid dose:
Fludrocortisone: 0.1-0.2 mg/m2/day daily to BD dose
Infants with mineralocorticoid deficiency may also need salt supplement, usual dose around
NaCl 1 gram/day
Children on stress dose of hydrocortisone also have mineralocorticoid activity (40 mg
hydrocortisone equivalent to 0.1 mg fludrocortisone)
Empirical method for weaning high dose steroid:
1. High dose steroid for 1-4 weeks, cut by 25% every 4 to 7 days
2. High dose steroid for > 1 month, wean first stepwise to stress dose, then cut by 10-25%
every 1 to 2 weeks
3. With long weaning schedule, can give all dose once in the morning or alternate day to allow
HPA axis to activate and minimise growth retarding effect
Test for suppression:
1. Morning cortisol 24 hours after last dose of corticosteroid can be used as a screening test for
basal secretion (not stress response), level usually ≥ 200 nmol/L
2. Low dose synacthen test: test whether adrenal can respond to stress signal of pituitary.
Pituitary-adrenal axis is the last to recover; if this test is passed, the axis is not suppressed.
Dose of synacthen used is 1 mcg/m2 IVI. Cortisol level at baseline, 20 minutes, 30 minutes
and 60 minutes. Peak level should be > 500 nmol/L.
240
Chapter 82 - Intravenous cyclophosphamide
L Leung
Protective isolation (Place patient in a single room is preferable)
DAT
Renal chart
ARRR Q4H
Strict Chart I/O
Urine Q8H for SG, ketone (aim: keep SG < 1.010), RBC, start 1 hour after IV fluid infusion
Save urine for inspection.
Inform if gross haematuria, urine SG > 1.020, ketone ++
Blood for CBP D/C, ESR, L/RFT, CaPO4, glucose, C3, ANA, Anti-ds DNA
1.
2.
3.
4.
IV fluid start infusion 1 hour before CYP: 1/2 saline + 5% dextrose _________ ml/hour (~ 2
L/m2/day) *
IV Cyclophosphamide ___________ mg in 150 ml NS over 1 hour **
IV Mesna _________ mg in 50 ml Normal Saline (20% of total CYP dose) for 4 doses at 0,
3, 6, 9 hours of CYP infusion
IV Ondansetron 0.15 mg/kg (adults 4-8 mg) in 50 ml Normal Saline for 4 doses at 0, 4, 8, 12
hours of CYP infusion.
Encourage fluid intake and frequent bladder emptying.
FU ________ in 2/52 and check CBP D/C
*Fluid: adult 125 ml/hour for a total of 3 L; Our patient – iv fluid at 125 ml/hr for > 8 hours,
follow with comparable rates of oral fluid for 24 hours. If greater than 0.5 litre positive balance,
diuretics is indicated. For those who have oliguria or difficulty voiding, may insert 3-way Foley
catheter (minimum size Fr14) with continuous bladder flushing with standard irrigating solution
for 24 hours (adult 3L)
**Cyclophosphamide:
If CrCl < 40 ml/min, initial dose at 0.5 g/m2
If CrCl > 40 ml/min, initial dose at 0.75 g/m2
Follow up doses determined by WBC nadir (10-14 days) of previous dose:
< 1500/mm3, reduce dose by 0.25 g/m2
Repeat dose monthly for 6 months induction therapy
Maintenance therapy may be considered, q 3 months for 2 years
Contraindications:
Pregnancy (screen with urine pregnancy test before each dose if indicated)
Breast feeding, active or chronic infection, history of malignancy
241
Chapter 83 - Formulae related to Nephrology
L Leung
Total body water = 80% body weight (Preterm)
70% (term)
65% (toddler / children)
60% post-pubertal male
50% post-pubertal female
TBW deficit = 0.6 × premorbid weight (kg) × (1 - 140/Se Na+mmol/L)
Free water deficit = TBW × (Na+/140 – 1) for hypernatremia
Na deficit = TBW × (Desired [Na] - Plasma [Na])
where TBW (Total Body Water) in adults = 0.6 (men) or 0.5 (women) × Body weight (kg)
0.8 in premature infants, 0.7-0.75 in term infants, 0.65-0.7 in toddler, 0.6 after puberty.
Since fat has much lower water cantaint than muscle, TBW as %BW is lower with
increasing obesity.
Prerenal FENa
Neo<2%
Child ≤ 1%
Adult <1%
Prerenal Ur Na
Neo <10mmol/l
Child <10
Adult <20
Renal FENa
Neo >2%
Child >3%
Adult >3%
Renal Ur Na
Neo >40mmol/l
Child
Adult >25
Calculating true Na in Pseudohyponatremia due to hyperglycaemia:
Expect a 1.4 mmol/L fall in Na for every 5.5mmol/L (100mg/dL) rise in BSL. Na falls 1mmol/dL
with a 4 mmol/L rise in BSL.
Serum osmolality formula (LeFever Kee)
2x serum Na + urea (mmol/l) + glucose (mmol/l) = Se Osmo (mOsm/kg), normal = 280-295
In DKA, effective Plasma osmolality = 2x serum Na + glucose (mmol/l) as urea freely diffusible
and not cause major intracellular volume changes.
Hypokalemia
24 hr urine K
Urine [K]*
Urine K/Cr mmol/mmol
Urine Na:K
K conserve
Adults <30mmol/day
<15mmol/l
<1.5
>1
Urine K loss
>30 mmol/day
>15mmol/l
>1.5
<1
Note: Random [K] measurements not accurate if urine sodium is < 30 meq/L and/or urine
osmolality is lower than the plasma osmolality since urine [K] is determined by both the amount
of potassium in urine and urine volume.
Acidosis lead to hyperK from redistribution: decrease pH 0.1 will increase K by 0.7meq/L.
Phosphate handling
% tubular reabsorption of phosphate (TRP)
Tubular Reabsorption of PO4 is 80-90% (Feld: 80- 97%) in normal circumstances in >6 mths old.
TRPi (%) = ( 1- FEPi) = 1 – Upi x PCr x 100
UCr x P pi
NB. Blood PO4 should be taken at time of urine collection.
Hyperphosphatemia: expect TRP <70% (increased PO4 excretion)
Hypophosphatemia: expect TRP >95% (some say >80%) (decreased PO4 excretion)
242
Maximum tubular reabsorption of PO4 per unit volume of GFR (TmPi/GFR)
TRPi is markedly influenced by changes in GFR as well as dietary PO4 intake. More reliable
measure of overall tubular reabsorptive capacity = TmPi/GFR. This is because in severe
hypophosphatemia or decreased GFR, filtered load may be so low that TRP is within normal range.
This is derived either by Walton-Bijvoet nomogram or by Brodehl formula (found to be
satisfactory in spot specimens, no need fasting)
TmPi/ GFR = Ppi - Upi x PCr
UCr
In Hypophosphatemic patient,
High TmPi indicates an appropriate renal response to hypophosphatemia which is usually
due to gastrointestinal loss or intracellular shift.
Low TmPi indicates increased renal excretion secondary to primary or secondary
hyperPTH, Fanconi syndrome, X LH, autosomal dominant hypophosphatemic rickets or
oncogenic osteomalacia.
TMPi/GFR
<3 months: 1.02-2mmol/L
3-12months: 1.13-1.88mmol/L
1-15yrs: 0.9-1.7mmol/L
mmol/L
mg/100ml
mmol/L
243
mg/100ml
Renal threshold phosphate concentration (TmPO4/GFR), serum phosphate, and other indices of
renal handling of phosphate at different ages (K Kruse et al, 1982).
Index
TmPO4/GFR
(mg/100 ml GF)
TRP
(%)
Age
(years)
6-6.9
7-7.9
8-8.9
9-9.9
10-10.9
11-11.9
12-12.9
13-13.9
14-14.9
15-15.9
16-16.9
17-17.9
20-40
6-6.9
7-7.9
8-8.9
9-9.9
10-10.9
11-11.9
12-12.9
13-13.9
14-14.9
15-15.9
16-16.9
17-17.9
20-40
Girls
n
9
27
29
29
19
27
28
31
26
22
33
11
12
9
27
29
29
19
27
28
31
26
22
33
11
12
Median
6.00
6.50
6.00
6.10
5.70
5.70
5.67
5.58
4.60
4.45
3.45
4.17
3.87
92.4
95.5
93.4
94.2
94.7
92.9
93.7
94.6
92.9
93.2
91.0
90.5
89.5
Mean
5.71
6.40
6.02
6.07
5.84
5.71
5.50
5.50
4.61
4.59
4.07
3.99
3.55
91.2
94.7
93.5
93.6
93.4
92.8
93.2
93.1
93.0
92.1
89.8
89.9
89.9
Boys
SD
0.85
0.83
0.81
0.83
0.94
1.08
0.88
0.88
0.69
0.83
0.66
0.51
0.66
3.86
2.68
2.26
2.69
2.66
4.46
4.67
4.46
3.01
3.17
3.60
3.50
4.30
Range
4.50-6.90
4.70-8.00
4.30-7.70
4.70-7.40
4.40-7.70
3.94-8.20
3.42-7.30
3.30-7.25
3.41-6.25
3.25-6.41
2.48-5.10
3.18-4.57
2.58-4.85
83.9-95.8
89.0-98.1
85.7-97.5
83.5-97.2
88.7-97.9
79.9-97.9
76.2-97.7
81.1-98.5
86.8-98.3
85.7-97.5
82.3-95.8
82.7-95.3
80.7-96.1
n
15
33
25
20
27
31
36
29
19
10
15
13
12
15
33
25
20
27
31
36
29
19
10
15
13
12
Median
6.40
5.80
5.80
6.15
6.10
5.25
5.51
5.85
5.40
4.70
4.23
4.13
3.54
94.5
93.8
93.6
94.0
94.4
93.4
94.9
95.4
94.0
90.6
90.5
89.3
89.3
Mean
6.25
5.85
5.97
5.96
5.89
5.21
5.47
5.89
5.39
4.69
4.37
4.27
3.21
94.1
93.4
93.8
94.1
93.4
92.4
93.1
94.7
92.6
91.4
90.0
90.5
87.8
SD
0.89
0.74
0.66
0.94
0.96
0.72
0.80
0.78
0.94
0.72
0.66
0.66
0.78
2.68
1.86
2.01
2.64
3.78
2.96
4.89
2.41
4.29
2.94
3.75
3.10
5.00
Range
4.80-8.00
4.50-7.00
4.90-7.10
4.20-7.80
4.07-7.50
3.88-6.60
3.70-6.92
4.27-7.47
2.58-7.05
3.60-5.90
3.47-5.88
3.33-5.90
2.05-4.28
86.8-98.1
88.3-98.1
90.7-98.4
88.5-98.1
82.1-99.3
85.9-96.7
79.6-98.6
88.1-98.7
80.2-98.4
88.2-95.7
83.8-96.4
85.8-94.8
81.3-95.5
Increased FE Mg
(urine Mg x Se Cr / Se Mg x Ur Cr normal range from Conti 2009 is 0.5-4%)
Aminoaciduria
% tubular reabsorption (Taa) = 1- [ Uaa / Paa] x 100%
Ucr / Pcr
Taa for most amino acid is >98%, except for glycine (95%) and histidine (92%)
Serum anion gap = Na − (Cl + HCO3). Normal 12-14mEq/L
Urine anion gap = Na + K - Cl, negative in normal during acidosis, 0 or positive in RTA
does not correlate will with urinary NH4+excretion in neonates or infants in first few weeks
of life.
Bladder size: < 2 yrs: (2x age +2) oz
> 2 yrs: (age/2 +6) oz
244
Chapter 84- Normal Urine Values
L Leung
< 4mg/kg/24hrs or 0.10 mmol/kg/24hrs
24 hr calcium*
#
nd
Ca/Cr in 2 void urine(Laufer 1989 in Paed
r/v 2001 RTA article by J Chan) adults < 0.21 mg/mg
or 0.7 mmol/mmol
………………………………19mth to 6 yr < 0.41 mg/mg
(not as accurate as 24 hr Ca)
7-18 mth
< 0.60 mg/mg
< 7 mth <0.86 mg/mg
In hypocalcemia, a urine Ca/Cr of > 0.3 mmol/mmol on spot samples suggests inappropriate
excretion (Yamamoto 2000)
Ca/Cr <0.2 mmol/mmol (some quote <0.1
Hypocalciuria
mmol/mmol) or <0.5mg/day
Creatinine# (indicator for adequate urine
collection)
newborns
8-10mg/kg/24 hr
10-12mg/kg/24
hr
children
Adult females 12-15mg/kg/24 hr
15-20mg/kg/24 hr
Adult males
<50mg/1.73m2/24hr (or<2mg/kg/24hr)
Oxalate#
0.46mmol/1.73m2/24hr
1-5yrs: <0.12mmol/mmol(0.08mg/mg)
Oxalate/Cr
Graph ^
<815mg/1.73m2/24hr (35mg/kg/24hr)
Uric acid#
<75mg/g Cr
Cystine#
>180mg/g Cr
Citrate#
Male: >1.9mmol(365mg)/1.73m2
Female: >1.6mmol(310mg)/1.73m2
Manna: hypocitraturia=
girls <300mg citrate/g Cr
Boys<125
urine uric acid(mg/dL) x plasma Cr (mg/dL):urine Cr
Hyperuricosuria
(mg/dL) > 0.53mg/dL of GFR(La Manna 2001@)
FE potassium
14.5 ±8.9%
<5%
FEmagnesium
TMP/GFR Threshold for maximum PO4
reabsorption:PlPO4 – [(UrPO4/UrCr) x Pl Cr]
<3 months: 1.02-2mmol/L
3-12months: 1.13-1.88mmol/L
1-15yrs: 0.9-1.7mmol/L
*Noncalculous symptomatic Idiopathic Hypercalciuria reported in association with micro and gross
haematuria, recurrent abdo pain or flank pain, urine incontinence, dysuria, urgency-frequency syndrome,
mild proteinuria, recurrent UTI, in addition to renal stones (Vachvanichsanong Scand J U”rol Nephrol
2000)
# from Laufer J. Urolithiasis in children: current medical management. Pediatr Nephrol 1989;3:317-331;
Sargent JD. Normal values for random urinary calcium to creatinine ratios in infancy. J Pediatr
1993;123:393-397; and Manz F. Urinary calcium excretion in healthy children and adolescents. Pediatr
Nephrol 1999;13: 894-899; Pediatr Nephrol 2010;25:403-413
@
Stapleton FB, A screening test for hyperuricosuria. J Pedatr 1983;102:88-90
245
^ Urine Oxalate/ Cr ratio
Normal values for spot urine samples: creatinine ratios (solute/creatinine). Ratios are more prone to error
than are timed samples. Interpret with respect to daytime, relation to meals, diet, medication, age and
regional differences [5, 6, 36–41] (Ca calcium, RTA renal tubular acidosis)
Bernd Hoppe et al, Pediatr Nephrol (2010) 25:403–413
Parameter age
Calcium
<12 months
1–3 years
1–5 years
5–7 years
>7 years
Oxalate
0–6 months
7–24 months
2−5 years
5−14 years
>16 years
Citrate
0–5 years
>5 years
Magnesium
Uric acid
>2 years
Ratio of solute to creatinine
mol/mol
mg/mg
<2
0.81
<1.5
0.53
<1.1
0.39
<0.8
0.28
<0.6
0.21
mmol/mol
mg/g
<325–360
288–260
<132−174
110−139
<98−101
80
<70−82
60−65
<40
32
mol/mol
g/g
>0.25
0.42
>0.15
0.25
mol/mol
g/g
>0.63
> 0.13
<0.56 mg/dl (33 µmol/l) per GFR
(ratio × plasma creatinine)
Remarks
Highest Ca excretion with breast milk feeding, ratio increasing
after meals (up to 40%), by loop diuretics, immobilization and
steroids
Primary hyperoxaluria types I/II for constant excessive elevation,
check also urinary glycolate, L-glycerate and plasma oxalate.
Secondary hyperoxaluria: determine intestinal oxalate absorption
and stool Oxalobacter formigenes colonization
Low with tubular dysfunction: RTA, prematurity, hypokalemia,
renal transplantation
For <2 years, no reliable data
Higher than in adults throughout childhood; no reliable data for
age <2 years
246
Section 7: Endocrinology, Growth &
Nutrition
247
Chapter 85 - Nutritional assessment in children
YY Lam
Purpose of nutritional assessment:
To define state of nutritional well being by assessing the body composition and size of
metabolic active mass
Methods of Nutritional Assessment:
Anthropometry
Calorimetry and prediction formula
Biochemistry
Anthropometry Measures:
- *Weight
- *Height: Stadiometer
Head position: Frankfurt plane – defined by a line joining the superior border of
tragus to the most inferior point of infra-orbital rim
Pressure on mastoid process
- Arm span
- *Weight for height (> 120% = overweight, < 80% = wasting)
- *BMI (> 90% = overweight, > 97% = obesity)
- *Skinfold thickness (optimal > 10% and < 90%) of triceps and subscapular skinfold
- *Bioimpedance
Assess body composition by the measurement of resistance and reactance when a weak
electric current is passed through the body
- Mid-arm circumference (MAC)
index of muscle mass
midpoint of upper arm (non-dominant arm)
Mid arm muscle circumference (MAMC)
MAMC = MAC in cm–(3.14 x Triceps skinfold in cm)
- Waist circumference
measured midway between lower rib margin and iliac crest laterally
- Hip circumference
measured horizontally over the trochanter region
*Standard charts available
Indirect Calorimetry:
- measurement of the heat of metabolism (energy output) via oxygen consumption (VO2) and
carbon dioxide production (VCO2)
- BMR (basal metabolic rate)
- minimum energy to sustain the organism; carried out in early morning within 30 minutes
upon wakening, 12 to 18 hours after ingestion of food, in complete muscular rest and a
comfortable environment
- REE (resting energy expenditure)
- around 10% > BMR, taken anytime of the day, at least 2 hours after meal, in a resting
state for at least 30 minutes and have no skeletal movement during the rest
- TEE (total energy expenditure)
- the sum of energy expenditure during sleep, rest, thermogenesis and physical activity
248
Measurement of Energy Expenditure (EE) by IC
WEIR’s equation: EE = [3.941 (VO2) + 1.106 (VCO2)] 1.44 – (2.17 UN) or
WEIR’s abbreviated equation: EE = [3.9 (VO2) + 1.1 (VCO2)] 1.44
EE: energy expenditure (kcal/day)
VO2: oxygen uptake in ml/min
VCO2: carbon dioxide produced in ml/min
UN: total urea nitrogen (N) in gram/day
Utilization of REE for Nutritional goal (Repletion, Depletion or Maintenance)
110% REE for weight reduction, 130% REE for maintenance and 150% for weight gain
Biochemical and immune markers for nutritional assessment (indicators for protein
status)
1) Albumin
T1/2: 18-20 days, but significant drop can occur in < 7 days in patients under stress with
catabolic state
21-27 g/L = Moderate malnutrition
<21 g/L = Severe malnutrition
2) Total iron binding capacity (TIBC)
TIBC < 200 mcg/dL (x 0.179 µmol/L) indicative of malnutrition
3) Transferrin
T1/2: 8-10 days, serum transferrin (mg/dL) = (0.68 x TIBC) + 21
100-150 mg/dL = Moderate malnutrition
< 100 mg/dL = Severe malnutrition
4) Prealbumin (T1/2: 2-3 days), Retinol-binding protein (T1/2: 12 hours) and IGF-1 (T1/2: 2-6
hours) may reflect acute decrease better
5) Nitrogen (N) balance
- Around zero in healthy adults, N output estimated from 24-hour total urine nitrogen
- Urinary [N] output in grams = (urea in mmol / 24hours) / 1,000 × 28
- Total daily [N] output = Urinary [N] output + 2g (estimated loss from stool + skin)
- Nitrogen intake: dietary intake of protein, 1 gram protein = 0.168 g Nitrogen
- Nitrogen balance = [N] intake – [N] output
- A positive 3 to 5 grams per day nitrogen balance is desired to promote anabolism and
wound healing
249
Chapter 86 - Management of obesity
YY Lam
Definition of obesity:
- Obesity: excessive accumulation of fat in adipose tissue to the extent that health may be
impaired (WHO 2000)
- Hong Kong data: BMI > 90% = overweight; BMI > 97% = obesity
Parameters measured to reflect degree of obesity:
- Wt, Ht, BMI, % of Wt for Ht, waist and hip circumference, Fat % (BIA)
Investigations required for obesity:
- Rule out underlying pathology if pathological obesity suspected (hypothyroidism, Cushing
syn, dysmorphic syndromes etc)
- Look for obesity related complication (hyperlipidaemia, DM, OSAS, HT etc)
BP, TSH, FBS, fasting cholesterol (LDL-C, HDL-C), fasting triglyceride
Abnormal glucose/strong family history of DM
Suspected DM: OGTT, Hb Alc
Check for habitual snoring, enlarged tonsils: PSG
Orthopaedic complication
Hirsutism, abnormal menstruation (PCOS)
Abnormal LFT, abdominal pain: USG to rule out steatohepatitis and gallstone
Management of Obesity (multidisciplinary):
- < 7 years, weight maintenance as a goal unless with complication
- ≥ 7 years, weight reduction diet usually 1,000-1,500 kcal/day (< 1,000 kcal not advisable)
- Weight loss of 0.5-1 kg/month is well tolerated
- Indirect calorimetry may help to establish energy requirement, ≤ 110% REE for weight
reduction
- Set a practical and achievable goal; seek support from family
- Empathetic and supportive to patients
- Regular weighing to keep track of weight changes
- Identify unhealthy habits and modify behaviour e.g. reduction of TV watching / computer
playing time to < 2 hours/day
- Diet advice: food diary for self monitoring, education on food labeling and caloric content
of food (a can of soft drink/day = 1 lb of weight/month)
Exercise: increase activity, decrease sedentary habits, prescribe around 200-300 kcal
exercise/day
250
Chapter 87 - Diabetic ketoacidosis
YY Lam
Definition of DKA:
hyperglycaemia (> 11 mmol/L)
venous pH < 7.3 and/or bicarbonate < 15 mmol/L
mild
pH < 7.3; HCO3 < 15 mmol/L
moderate
pH < 7.2; HCO3 < 10 mmol/L
severe
pH < 7.1; HCO3 < 5 mmol/L
associated with glycosuria, ketonuria and ketonaemia
Causes of DKA:
- undiagnosed type 1 DM (TIDM)
- insulin omission or manipulation, insulin pump failure
- inadequate insulin during periods that increase needs (illness, infection, stress, puberty,
pregnancy)
Signs and symptoms of DKA:
Polyuria, polydipsia, dehydration, weight loss, lethargy, nausea, vomiting, abdominal pain,
fruity smelling breath, flushed face, confusion, hyperventilation and Kussmaul breathing
Morbidity and mortality of DKA:
- mortality from 0.15% to 0.31%, cerebral oedema accounts for 57-87% of all DKA deaths
- incidence of cerebral oedema from 0.46% to 0.87%
- reported mortality rates from cerebral oedema from 21% to 24%
- significant morbidity evident in 10-26% of survivors after DKA and cerebral oedema
Presentation of cerebral oedema:
It typically occurs 4 to 12 hours after treatment. Symptoms and signs are variable and include
headache, gradual deterioration in level of consciousness, inappropriate slowing of the pulse
rate, and increase in BP
Management of DKA:
- Mild DKA without vomiting and dehydration may be managed at home in established DM
with well trained parents, close monitoring of glucose level and frequent evaluation are
needed
- For severe DKA, need admission and close monitoring
Management after hospital admission:
- Use admission BW for calculation in fluid management (for severe obesity, fluid calculation
may need to be adjusted to avoid overhydration)
- Hourly HR, RR, BP
- Strict I/O
- Airway management, catheterize bladder, NG tube if impaired consciousness
- Good venous access (can serve as blood taking access)
- ECG monitor for hyper or hypo K
- D’stix hourly, monitor urine sugar and ketone
- Electrolytes, urea, Hct, blood sugar level (BSL), blood gas 2 to 4 hourly
- Close neuro-observation (hourly or more frequent)
- Principles of fluid and electrolyte management:
251
-
-
-
Restore circulating volume
Correct electrolyte, fluid deficit
Restore GFR for glucose and ketones clearance
Avoid large fluid boluses and rapid infusion
N.S bolus only if in shock, 10-20 ml/kg over 1-2 hours
NaHCO3 not recommended
Deficit replaced slowly over at least 48 hours (fluid regime as per British Columbia
Children’s Hospital protocol)
Corrected Na level by adding 0.3 mmol/L Na for every 1 mmol/L glucose above 5 mmol/L
[True Na = measured Na + 0.3 x (BSL – 5)]
NS as initial fluid for 4 to 6 hours, subsequent fluid tonicity ≥ 0.45 NS (consider 0.45%
NaCl if serum Na ≤ 145 mmol/L)
Add K 40 mmol/L fluid if +ve urine output
Start insulin infusion 0.05-0.1 unit/kg/hour (included in total fluid calculation)
Follow instruction of preparing solution A, B, C (see table and diagram)
Start IV glucose when BSL ≤ 17mmol/L or glucose drop > 5 mmol/L/hour, adjust rate of
solution A and B to give fluid with NS or 1/2 NS with various glucose concentration (see
table and diagram)
Keep BSL > 15 in first 24 hours, avoid rapid drop, aim < 5 mmol/L/hour
Na usually rises with fall of glucose, unexpected drop of Na may be sign of overhydration
and potential cerebral edema, keep highish effective osmolality [2 x (Na + K) + plasma
glucose] and avoid rapid drop
Total fluid per day seldom exceeds 1.5-2x normal daily maintainence
Consider PO4 supplement for deficiency or to avoid hyperchloridaemia; closely monitor
Ca2+ level if PO4 given
Management of cerebral oedema:
Keep head elevated
Rate of fluid administration reduced by around one third
IV mannitol (0.25–1.0 g/kg over 20 minutes) in patients with signs of cerebral oedema before
impending respiratory failure; repeat in 2 hours if no initial response
Hypertonic saline (3%) 5-10 mL/kg over 30 minutes may be an alternative to mannitol
Intubation and ventilation if necessary. Brain imaging only when patient is stable.
Introduction of oral feeding and change to subcutaneous insulin:
- oral fluid introduced with clinical improvement and DKA corrected
- reduce IVF if oral intake tolerated
- discuss with endocrinologist for dose and regime of subcutaneous insulin; first dose usually
starts before a meal
- allow 1 hour after short acting insulin before stopping IV insulin infusion.
Reference: http://endodiab.bcchildrens.ca/pdf/dkaprt.htm
252
Solution A and solution B preparation
1) For NaCl 0.45% / Dextrose solution with K 40mmol/L (when blood glucose ≤ 17 mmol/L or
glucose drop > 5 mmol/L/hour)
Solution A (per 1,000ml) – NaCl 0.45% + 40 mmol KCl
Solution B (per 1,000ml) – NaCl 0.44% / Dext 12.46% + 39.2 mmol KCl
To prepare the above solutions using the IV fluids and electrolytes available in KWH:
Ingredients
Solution A
Solution B
NaCl 0.9%
250 ml
----NaCl 23.4%
----9.6 ml
KCl 14.9% (2 mmol K+/ml)
10 ml
10 ml
Water for Injection
240 ml
Dextrose 5%
----230 ml
Dextrose 20%
----260 ml
Final volume
500 ml
509.6 ml
Final osmolarity
234 mOsm/L
920 mOsm/L
2) For NaCl 0.9% / Dextrose solution with K 40 mmol/L (when blood glucose ≤ 17 mmol/L or
glucose drop > 5 mmol/L/hour)
Solution A (per 1,000 ml) – NaCl 0.88% + 40 mmol KCl
Solution B (per 1,000 ml) - NS / Dextrose 12.5% + 40 mmol KCl
To prepare the above solutions using the IV fluids and electrolytes available in KWH:
Ingredients
Solution A
Solution B
NaCl 0.9%
490 ml
----NaCl 23.4%
----19.2 ml
+
KCl 14.9% (2 mmol K /ml)
10 ml
10 ml
Dextrose 10%
----432 ml
Dextrose 50%
----39 ml
Final volume
500 ml
500.2 ml
Final osmolarity
381.6 mOsm/L
1081.3 mOsm/L
Solution A: NS or 1/2 NS solution with K
Solution B: NS/D12.5 or 1/2 NS/D12.5 with K
Solution C: Insulin Infusion
253
Chapter 88 – Normal values
YY Lam
Bone age interpretation (Ref : Radiographic Atlas of Skeletal Development of the Hand and
Wrist by Greulich WW and Pyle S1):
Normal bone age should fall within the range defined by the chronological age +/- 2 SD
The variability of skeletal age of girls in the Brush Foundation study
Skeletal Age (in months)
Chronological Age
Standard Deviation
3 months
6 months
9 months
12 months
18 months
0.72
1.16
1.36
1.77
3.49
2 years
2 1/2 years
3 years
3 1/2 years
4 years
4.64
5.37
5.97
7.48
8.98
4 1/2 years
5 years
6 years
7 years
8 years
10.73
11.65
10.23
9.64
10.23
9 years
10 years
11 years
12 years
13 years
10.74
11.73
11.94
10.24
10.67
14 years
15 years
16 years
11.30
9.23
7.31
254
The variability of skeletal age of boys in the Brush Foundation study
Skeletal Age (in months)
Chronological Age
Standard Deviation
3 months
6 months
9 months
12 months
18 months
0.69
1.13
1.43
1.97
3.52
2 years
2 1/2 years
3 years
3 1/2 years
4 years
3.92
4.52
5.08
5.40
6.66
4 1/2 years
5 years
6 years
7 years
8 years
8.36
8.79
9.17
8.91
9.10
9 years
10 years
11 years
12 years
13 years
9.00
9.79
10.09
10.38
10.44
14 years
15 years
16 years
17 years
10.72
11.32
12.86
13.05
Fasting blood glucose and OGTT interpretation:
Fasting blood glucose: < 6 mmol/L
= normal
6.1 to 7 mmol/L= impaired fasting glucose
≥ 7 mmol/L
= suspicious of diabetes mellitus
OGTT Test: glucose load = 1.75 gram/kg (maximun 75 grams),
Unrestricted diet, fast overnight, check glucose at baseline and 2 hours after
glucose loading
2-hour blood glucose: ≥ 11.1 mmol/L
= diabetes mellitus
7.8 to < 11.1 mmol/L = impaired glucose tolerance
255
Section 8: Miscellaneous
256
Chapter 89 – Management of eczema
DK Ng
-
Avoid soaps, detergents, chemicals and abrasive clothing like woollen jumpers
Aqueous cream or soft paraffin or emulsifying ointment as barrier cream to prevent loss
of moisture, the main pathology of eczema skin. They can also be used as cleanser.
Topical corticosteroid forms the main stay of treatment, cream for weepy lesion and
ointment of dry lesions. For the face, only apply 1% hydrocortisone cream
For the same concentration of medication, ointment is more potent than cream
For weepy lesion, 1% acetic acid helps to dry up the skin
For recalcitrant lesions, wet wrap with elomet cream diluted 10 times with aqueous
cream may be applied at night with one layer of moist gauze overlaid with second layer
of dry gauze to be washed off the next morning followed by emollient for a week.
Potency of topical corticosteroid
Preparation
Potency
1% hydrocortisone acetate
Mild
Clobetasol butyrate (Eumovate)
Moderate
Fluocinolone acetonide (Synalar)
0.005% cream
Moderate
0.0125% cream
Moderate
0.025% cream
Potent
Mometasone furoate (Elomet)
Potent
Betamethasone valerate
(Betnovate)
Potent
Clobetasol propionate (Dermovate)
Very potent
Topical immunosuppressant agents
Tacrolimus (0.1%, 0.03% ointment) and pimecrolimus (1% cream) mainly for eyelids and
periorbital skin.
The FDA has recently issued a warning about these 2 drugs because of possible link of cancer
with their use.
Antibiotics
Systemic antibiotics (flucloxacillin, or erythromycin in penicillin allergy) may be required in
short courses during acute exacerbation
If recurrent Staph aureus infection occurs, nasal and perineal swabs should be obtained from the
patient and parents / carers. Carriers should be treated with topical mupirocin for about 10 days.
Anti-histamines
First generation of anti-histamines, e.g. piriton, atarax, are used for their sedative effect before
bedtime
257
Chapter 90 – Infantile scabies
KT Chan, F Poon,DK Ng
Organism:
Mite Sarcoptes scabiei var hominis – an obligate human parasite
Presentation:
- Generalized itch worse at night, especially over wrists, nipples, axilla folds and scrotum.
- Pathognomonic burrows are rarely seen in infantile scabies
- Nodules may be seen over scrotum
- Erythematous papules, vesicles, pustules, bullae, and crusts can be present in all body areas
including face
Diagnosis:
- Skin scrapings from the end of the burrow for microscopy to demonstrate mites, eggs or
mite faeces (scybala)
Management:
Prophylactic treatment of all household contacts at the same time to prevent reinfection by
those incuabing scabies (incubation period up to 2 months)
Bed linen and clothings in skin contact during the 3 days before treatment must be washed with
hot water and dried using a hot cycle (mite dies within 3 days without skin contact)
Patient’s clothing, bed linen, pillow case should be washed separately from those of their family
members in hot water (60oC or above) for not less than 10 minutes to kill the mites and their
eggs.
Place all non-washable personal items such as shoes, mattress in a plastic bag and seal them up
for at least 14 days before they can be used as usual.
Medications – must apply over the whole body, including head and face in infants and young
children. For older children without face involvement, apply to whole body below the neck.
Preferred treatment: 5% Permethrin cream for those older than 2 months: leave for 8-12 hours.
Repeat application 1 week later
0.5% Malathion: leave for 24 hours. Repeat application 1 week later. However, neurotoxicity is
a concern and it is not recommended in infants below 6 months of age
12.5% Benzyl benzoate: 3 applications in a 24-hour period. Apply the emulsion on the evening
of Day 1. Allow to dry then apply a 2nd coat. Apply a 3rd coat on the following morning. Wash
off on the evening of Day 2. However, it could lead to skin irritation. Dilution can reduce
irritant effect but also reduce its efficacy. It is not recommended for infant or children
Post-scabies treatment itchiness is very common and treated with antihistamines and/or topical
corticosteroids, 10% Crotamiton cream
258
Chapter 91 - Fever of unknown origin
DK Ng, C Tse
Definition:
1) Documented fever for more than 7 days AND
2) Admitted for more than three days and assessed by second-round staff for at least 3 days
AND
3) Absence of diagnostic features (clinical or otherwise)
Causes:
More than 95% of these cases in our experience were related to infection
A few cases were related to autoimmune diseases
1 to 2 cases were related to drugs, hypothalamus control, haemophagocytosis, malignancy
Review of symptoms and signs (from head to toes, from skin to viscera to sinuses) is VERY
IMPORTANT as symptoms and signs are often present in retrospect. It is important to get the
relevant signs and symptoms not in retrospect.
Investigations:
Infection: Viruses: Monospot, viral titres, dengue titre, NPA for respiratory viruses, HIV
Small bacteria: cold agglutinin, mycoplasma titre, Weil-Felix, rickettsia Ab, B.
burgdorferi Ab
Bacteria: Mantoux test, Widal test, blood / stool / urine cultures, CXR
Protozoa: fresh stool for amoeba, ultrasound of liver
Parasites: blood smear for malaria, CPK, Brucella titre
Fungi: blood culture
Autoimmune: ANF, ANCA
Malignancy: blood smear, urine for RBC, ultrasound of adrenal glands and kidneys
Haemophagocytosis: bone marrow examination
259
Chapter 92 – Medical management of phimosis using topical corticosteroids
MT Soo, DK Ng
Phimosis is traditionally treated surgically but medical management may be offered if deemed
appropriate by the attending clinician.
Kikiros’ grading of phimosis (Kikiros, 1993):
Retractability of foreskin:
0 – full retraction
1 – full retraction of foreskin and tight ring behind the glans
2 – partial exposure of glans
3 – partial retraction, meatus just visible
4 – slight retraction but distance between tip and glans (neither meatus nor
glans could be exposed)
5 – absolutely no retraction
(Indications for treatment: grade 3 to 5)
Regime of topical corticosteroids (usually for Kikiros’ grade 5 phimosis):
Betamethasone dipropionate: 0.05% cream BD for 1 month (Monsour, 1999) BD for 1-2
months (Wright, 1994)]
Clobetasol propionate 0.05% (Dermovate) ointment daily for 1-2 months (Lindhagen,
1996)
Betamethasone valerate 0.06% cream [BD for 2 weeks (Chu, 1999); BD for 4-8 weeks
(Yang, 2005)], 0.05% ointment [BD to QID for 2-12 weeks (Kikiros, 1993)], 0.1%
ointment [BD for 6 weeks (Ashfield, 2003)]
Clobetasol butyrate 0.05% BD for 4-8 weeks (Yang, 2005)
Triamcinolone: 0.02% [BD for 4-6 weeks (Ng, 2001)]
Hydrocortisone: 1% and 2% [BD to QID for 2-12 weeks (Kikiros, 1993)]
Treatment regime (Ku, 2007):
Apply corticosteroid to the foreskin twice daily, after washing or bathing, for 4 weeks.
After the foreskin becomes retractable, retract the foreskin gently without causing any pain,
and wash the prepuce daily during bathing. Most papers advise to retract the foreskin as
much as possible without causing pain or discomfort, and then apply a thin layer on the
tightest part of the prepuce.
Follow-up at 4 weeks: if phimosis does not resolve, give another 4-week course
Maximum consecutive treatment period is limited to 8 weeks. Further treatment courses
may be given if phimosis recurs.
Topical steroid treatment should be combined with good hygiene practice of the foreskin
with daily cleansing and retraction.
It is worth noting that co-existing balanitis, history of urinary tract infection [Ashfield,
2003], age below 3 year [Elmore, 2002; Yang, 2005] are not contraindications for topical
steroid treatment
Contraindications:
Buried penis (Chu, 1999) – poor response to treatment
Balanitis xerotica obliterans (Monsour, 1999) – indication for circumcision
260
Mechanism:
Make foreskin thinner, improve its elasticity and reduce any inflammatory component
Allow the foreskin to be retracted and daily hygiene to be performed
Cessation of steroid may lead to restitution of dermis and epidermis, known as rebound
phenomenon
Outcomes:
Reported success rate: 67-100%
Relapse rate: from 10-15% (Monsour, 1999) to 26.1% (Ku, 2007)
Treatment with 0.05% betamethasone ointment for 4 weeks results in a success rate of
81.5% (defined as Kikiros’ grade 0 to 2). During follow-up, 60.2% of boys remained free
from phimosis upon latest assessment. (Ku, 2007)
14.6% of the boys underwent circumcision because of failed treatment or recurrent
phimosis. (Ku, 2007)
No local or systemic side effects reported (except for a case of gynaecomastia after
treatment with topical conjugated equine estrogen) (Yanagisawa, 2000)
No significant change in early morning blood spot cortisol levels (Golubovic, 1996)
Benefits:
Avoid unnecessary circumcision and the risks of surgery and general anaesthesia
Treatment cost: about 25% of circumcision (Van Howe, 1998)
Allow urine surveillance in boys with history of urinary tract infection as proper exposure
of meatus allows less contamination of urine with skin flora during voiding
261
Chapter 93 - Dental service for children
S Cherk
Dental service for children
Normal Children
Children with special needs
School dental
care service
Designated
dentists
NGO
dental clinic
- primary
school children
- children on
CSSA
e.g. Yang Memorial
Methodist Social
Service
- need
subscription
$20/year
- list of dentists
available from
field unit of
SWD
學童牙科保健
*
**
* Government
dental clinic
循道衛理
楊震社會服務處
** HA dental clinics
with provision for
children with special
needs
- QEH
- CMC
- UCH
- PMH
Prince Philip Dental
Hospital
Government free extraction session for public: for pain relief and extraction only
Need medical referral letter
262
Chapter 94 – Antibiogram
C Tse
Resistance of Common Bacterial Isolates in Paediatrics Department in Kwong Wah Hospital (2013)
PICU
NICU
SCBU
38
0
0
0
0
10*
20
10
0
0
0
0
0
60
0
0
20
0
0
0
0
83
0
0
50
0
0
0
50
0
0
0
Nitrofurantoin 3
Meropenem
0
0
23
0
13
0
67
0
0
0
0
0
0
0
0
0
0
0
0
0
0
75
14
0
0
0
0
13
0
0
0
0
0
0
100
63
63
0
0
13
25
0
57
50
Cotrimoxazole
Levofloxacin
20
0
0
100
Vancomycin
Fusidic Acid
Erythromycin
33
0
Cloxacillin 2
33
0
Amikacin
0
0
Gentamicin
1
0
Ceftazidime
Cefotaxime
0
Cefuroxime
(parenteral)
38
Sulperazon
4
0
Tazocin
83
100
Penicillin
(parenteral)
Escherichia coli (84)4
Klebsiella species (17)4
Staphylococcus aureus (10)
Haemophilus influenzae (8)
Pseudomonas aeruginosa (8)
Enterococcus species (7)
Streptococcus pneumoniae (7)5
Citrobacter species (5)
Streptococcus agalactiae (group B) (4)
Moraxella species (3)
Burkholderia cepacia (8)
Staphylococcus, coagulase negative (8)
Penicillin
PAD
(exclude
PICU,
NICU,
SCBU)
Augmentin
Organism (no. of isolates)1
Amoxycillin
Unit
Ampicillin
% Resistance
0
0
0
0
14
30
29
30
* 1 strain from blood is borderline resistant to cloxacillin.
1 Organisms isolates from blood, urine and respiratory specimens. Interpreted according to CLSI.
2 Cloxacillin used to detect methicillin-resistant Staphylococci.
3 Urine isolates only.
4 Overall prevalence of extended-spectrum _-lactamases (ESBL) were 33% for E.coli, and 0% for Klebsiella species in PAD.
ESBL-producing strains should be interpreted as resistant to all penicillins, cephalosporins and aztreonam.
5 In Streptococcus pneumoniae, resistance to azrithromycin & clarithromycin can be predicted by testing erythromycin (CLSI M100-S21).
6 Overall prevalence of extended-spectrum _-lactamases (ESBL) were 0% for E.coli in PICU, 14% for E.coli in NICU and 30% for E.coli in SCBU.
ESBL-producing strains should be interpreted as resistant to all penicillins, cephalosporins and aztreonam.
30
30
14
30
0
80
50
20
0
0
0
0
22
ANTIBIOGRAM
Prepared by Infection Control Team, Kwong Wah Hospital
263
0
0
0
0
Resistance of Common Bacterial Isolates in BLOOD in Paediatrics Department in KWH (2013)
Cefotaxime
Gentamicin
Amikacin
Cloxacillin 2
Erythromycin
Fusidic Acid
Vancomycin
0
0
17
33
83
0
67
0
0
0
33*
100
0
67
0
67
0
0
Meropenem
Cefuroxime
(parenteral)
17
Cotrimoxazole
Sulperazon
100
Levofloxacin
Tazocin
Augmentin
Organism (no. of isolates)1
Ampicillin
% Resistance
50
0
0
0
* 1 strain is borderline resistant to cloxacillin.
Top 3 Isolates from Paediatrics Department in KWH (2013)
Unit
PAD
and
PICU
SCBU
and
NICU
Organism
Blood (n = 12)
Staphylococcus aureus
Salmonella species
Staphylococcus, coagulase
negative8
Blood (n = 17)
negative8
Escherichia coli
No. of
isolates
% of
Total
3
2
25%
17%
2
17%
10
59%
6
35%
1
6%
Bacillus species9
Organism
Respiratory (n = 47)
Staphylococcus aureus
Haemophilus influenzae
Pseudomonas aeruginosa (7) /
Streptococcus pneumonia (7)
Respiratory (n = 19)
Burkholderia cepacia
negative
Acinetobacter species (2) /
Escherichia coli (2) /
7 Overall
No. of
isolates
% of
Total
9
8
19%
17%
14
30%
No. of
isolates
% of
Total
Urine (n = 124)
Escherichia coli
Klebsiella species
87
13
70%
10%
Enterococcus species
7
6%
9
36%
5
20%
9
36%
Organism
Urine (n = 25)
5
26%
3
16%
6
33%
Escherichia coli
negative
Burkholderia cepacia (3) /
Candida albicans (3) /
Enterococcus species (3)
prevalence of extended-spectrum _-lactamases (ESBL) were 17% for E.coli. ESBL-producing strains should be interpreted as resistant to all penicillins, cephalosporins and aztreonam.
were skin contaminant in PAD + PICU and 70% were skin contaminant in SCBU + NICU from blood.
9 Common skin contaminant from blood.
8 100%
264
Chapter 95 - Megavitamin Cocktail Regimen
Freddie Poon
Megavitamin Cocktail Regimen
Daily dose
Route
Availability
Examples of related conditions
Thiamine
50mg
IV/PO
Formulary drug
mitochondrial disorders, MSUD, PDH deficiency, complex I deficiency
Riboflavin
100mg - 300mg
PO
Formulary drug
glutaric aciduria type I/II, mild variants of ETF, ETF-DH, complex I deficiency
(congenital lactic acidosis)
Biotin
10mg
PO
Non-formulary drug
Pyridoxine
100mg
IV
Formulary drug
pyridoxine dependency with seizures, homocystinuria, primary hyperoxaluria type I
Vitamin B12
1mg
IM/SC/PO
Formulary drug
methylmalonic academia, homocystinuria
Ascorbic acid
100mg/kg
PO
Formulary drug
tyrosinaemia III, transient tyrosinaemia of the newborn, glutathione synthase
deficiency, abetalipoproteinaemia
Carnitine
25mg/kg Q6H
PO
Formulary drug
organic acidaemia, carnitine deficiency
Co-enzyme Q10
5mg/kg
PO
Formulary drug
respiratory chain defects
Pyridoxal phosphate
20mg/kg
PO
Non-formulary drug
PNPO deficiency: pyridoxal phosphate responsive seizures
Folinic acid
20mg
PO
Non-formulary drug
hereditary orotic aciduria, methionine synthase deficiency, cerebral folate transporter
deficiency, hereditary folate malabsorption, Kearns-Sayre syndrome
multiple carboxylase deficiency (biotinidase, holocarboxylase synthetase)
updated on Oct 2013
Indication:Megavitamin cocktail therapy should be considered in those patients who present with an acute severe illness of unknown aetiology in which inborn error
of metabolism is highly suspected. This may be in the form of emergencies such as encephalopathy, seizures, liver failure, metabolic acidosis, shock or others.
Therapy should commence as soon as possible, and should be directed to reduce the formation or enhance the secretion of toxic metabolites, provide adequate calories
and prevent catabolism, and to provide co-factors empirically if a specific diagnosis is not established. Appropriate immediate treatment not only improves survival
but also reduces the chances of neurodevelopmental sequelae.
265
Chapter 96 - Immune Thrombocytopenia (ITP)
KL Kwok, TH Fung, MT Soo, E Chan
Definition and Terms (ASH 2011):
Primary ITP as a platelet count < 100 x 10^9/L in the absence of other causes or disorders.
- Newly diagnosed (diagnosis to 3 months)
- Persistent (3 to 12 months from diagnosis)
- Chronic (lasting for more than 12 months)
Secondary causes of immune thrombocytopenia:
- Anti-phospholipid syndrome
- Autoimmune thrombocytopenia (e.g. Evans syndrome)
- Common variable immune deficiency
- Drug administration side effect
- Infections: CMV, Helicobacter pylori, hepatitis C, HIV, varicella zoster
- Lymphoproliferative disorders
- Bone marrow transplantation side effect
- Vaccination side effect
- Systemic lupus erythematosus
Diagnosis of primary ITP:
Careful history-taking + physical exam + review of CBP and peripheral blood smear
History:
Isolated bleeding without constitutional symptoms
P/E:
No hepatosplenomegaly, lymphadenopathy or skeletal abnormalities
CBP:
Isolated low platelet < 100 × 10^9/L; anaemia only if due to significant bleeding,
otherwise normal red cell indices, white cell count and differentials
Peripheral blood smear: normal or large platelets; normal red cell and white cell morphology
Any atypical features should prompt more investigations accordingly.
Bone marrow examination in children and adolescents with typical features of ITP is unnecessary; it
is also unnecessary for those who fail IVIG therapy. Some suggested it is also unnecessary before
initiation of steroid and before splenectomy.
Management:
- No intramuscular injection, arterial puncture or deep vein puncture
- Avoid contact sports
- Avoid drugs that increase bleeding: e.g. NSAIDs and aspirin
266
Drug treatment:
- Aim for haemostasis, not “normal” platelet count
Children with typical features of ITP
No bleeding, or only mild
bruising / petechiae on skin
No mucosal bleeding
Mucosal bleeding or significant bleeding
Conservative management
regardless of platelet count*
(need discussion with family)
# i) IVIG (faster rise in platelet)
ii) or short course of steroid
iii) or anti-D (less effective)
*For practical purposes, consider treatment if (i) platelet count < 10 x 10^9/L, or (ii) platelet count
10-30 x 10^9/L and clinical bleeding including mucosal bleeding.
Platelet count of >30 x 10^9/L is considered safe, but aim for >= 50 x 10^9/L for minor procedures.
Consider lower threshold for treatment if there is a higher risk of bleeding due to patient’s activity
level, or if follow-up cannot be ascertained.
# i) IVIG (preferred): 0.8-1 gram/kg over 4 hours (slower initial infusion)
- initial response 1-3 days, peak 2-7 days
ii) Steroid: no evidence to support any one dose or dosing regimen over others
- Oral prednisolone 2 mg/kg/d for 2 weeks then taper over 1 week (preferred)
- Oral prednisolone 4 mg/kg/d for 7 days then taper
iii) anti-D: 50-75µg/kg IV over 10 min for Rh-positive, non-splenectomized children
- not for those with decreased Hb or evidence of autoimmune hemolysis
2nd line treatment (rarely needed):
- high dose steroid, rituximab, azathioprine, cyclosporin, MMF, other immunosuppressants;
splenectomy
Splenectomy:
- Chronic symptomatic thrombocytopenia lasting for > 12 months (> 12-24 months in the British
guideline) and a platelet count < 10 x 10^9/L being unresponsive to standard treatment and
presenting with no surgical contraindications
- Rarely recommended in paediatric ITP cases
Monitoring:
- Check platelet count initially 1-2x/week and post drug treatment; when a trend is observed,
gradually space out till platelet count normal for few months
- Recurrence of acute ITP is rare
267
Prognosis:
- 75-80% should be expected to go into remission by 6 months
- Chronic disease (platelet < 150 × 10^9/L in study by Kuhne) is more common in older children.
> 3 months to < 12 months: 23.1%
> 12 months to < 10 years: 28.1%
> 10 years: 47.3%
Persistent / chronic ITP:
- Recommend re-evaluation if no improvement after 3-6 months: bone marrow (if ITP persists or no
prior response to treatment)
- Evaluate for infection (HIV/HCV/H pylori) if clinical suspicion or high local incidence
- ANA, anti-phospholipid Ab; immunoglobulins
- Review medications
- Periodically reconsider (every 6-12 months) other diagnoses
Management of persistent / chronic ITP:
- Drug treatment does not alter the chance of recovery
- Management of children with persistent/chronic ITP is essentially the same as those with newly
diagnosed ITP i.e. to maintain a haemostatic platelet count with first-line therapies (e.g. IVIG,
anti-D, short course of steroid) and to minimize the use of prolonged steroid therapy
- Many children stabilize with an adequate platelet count (> 20-30 x 10^9/L) and are asymptomatic
- Majority of chronic ITP children do not require treatment
- Some children with ITP and platelet counts of 10-30 x 10^9/L may be troubled by purpura
although no significant bleeding; treatment may be beneficial in these cases
Prognosis of chronic ITP:
- ~66% spontaneous remission within 5 years; 10-15% of patients per year achieve normalization of
platelet count during this time period
ITP and emergency treatment:
- Severe or life threatening bleeding
- IVIG + high dose steroid (e.g. 30 mg/kg methylprednisolone daily for 3 days, ASH guideline 1996)
- Platelet transfusion (larger-than-usual dose, 2- to 3-fold usual dose)
ITP and surgery:
- A platelet count of > 50 x 10^9/L is considered sufficient in chronic ITP for a normal surgical
intervention, with the exception of neurosurgery and high-risk surgery (AIEOP Consensus
Guidelines 2010)
268
Chapter 97 - Haemophilia
TH Fung, MT Soo, E Chan
I.
Introduction
- Haemophilia A (85% of cases ) and B (15% )
- X-linked recessive, rarely affect female (extreme lyonization)
- Incidence - haemophilia A: 1 in 5,000-10,000; haemophilia B: 1 in 30,000-50,000
II.
Diagnosis
- Family history: affected male; up to ~1/3 de novo mutation
- Prolonged APTT in moderate to severe cases (may be normal in mild cases)
- Factor assay < 40%
Clinical classification of patients with either haemophilia A or haemophilia B
Severe haemophilia
Moderate haemophilia
Mild haemophilia
Factor level < 1%
Factor level 1-5%
Factor level 6-40%
Spontaneous bleeding
Characteristic
Can bleed with slight injury
May bleed 1-2 times per week
May bleed once per month
Bleeding typically only with
severe injury, surgery, invasive
procedures
May never have a bleeding
problem
Characterized by joint
May have joint bleeding
Rarely has joint bleeding
bleeding (haemarthrosis)
- severe haemophilia account for 70% of cases
- refer patient’s immediate female relatives to check for factor level (carriers may have abnormal
factor level and caution needed before surgery)
III.
Incidence of different sites of bleeding
- Haemarthrosis: 70-80%, muscle/soft tissue: 10-20%, central nervous system (CNS) bleeding <5%,
other major bleeds: 5-10%
Incidence of bleeding into different joints
- Knee: 45%; elbow: 30%; ankle: 15%; shoulder: 3%; wrist: 3%; hip: 2%; others: 2%
IV.
Principles of management
- goal -prevention of bleeding
- Treat bleeding early: < 2 hours of onset of symptoms
- During bleeding: R (rest) I (ice) C (compression) E (elevation)
- Treat veins with care
- Avoid drugs that cause platelet dysfunction e.g. NSAIDs, aspirin
- Clotting factor concentrate replacement or DDAVP prior to invasive procedures
- Multidisciplinary approach
Alert card/letter to patients (available in department web)
269
V.
Management of bleeding episodes
i) Haemophilia A:
Factor VIII concentrate (FVIII)
- Each FVIII unit/kg raises plasma FVIII level by 2%
- Dose (unit) = BW (kg) x desired % level rise x 0.5
- 1/2 life = 8-12 hours, with individual patient response
- slow iv; not > 100 units/min in children (not > 3 ml/min in adults)
- Give the entire vial of FVIII even it exceeds the calculated dosage (in moderate and severe
haemophilia)
- Continuous infusion by experienced haematologist: 50 U/kg bolus followed by 4-5 U/kg/hr
provides ~100% FVIII level in severe haemophilia
- Monitor factor level daily
DDAVP
- In mild haemophilia (or moderate), can raise level to 2-8x baseline
- Need pre-testing of response (Challenge test: 0.3 mcg/kg in 30-50 ml NS over 15-30
minutes. Check factor level at 1 hour: +ve response = FVIII ≥2x baseline and >30%)
- Given as daily dose
- Tachyphylaxis: decreased response after 1-2 days
- Avoid using in children < 2 years old
- Fluid restriction to 3/4 of maintenance
Anti-fibrinolytic agents
- As treatment for minor mucosal bleeding or as adjuncts in more severe mucosal bleeding,
e.g. Tranexamic acid (25 mg/kg po or 10-15 mg/kg iv q8h for 5-10 days)
- should not be given concurrently (wait for 4-6hrs) with non-activated or activated
prothrombin complex concentrate (PCC) as potential thrombotic complications
- Not to be used in urinary tract bleeding or thoracic surgery
Recombinant activated factor VIIa (Novoseven):
- Used in those with inhibitors; dosage: 90 mcg/kg q2-3h until haemostasis (adjust to nearest
vial, dosage from 35mcg to 120mcg/kg has been used with success); for severe bleed that
requires longer duration of treatment to maintain post haemostatic plug, dosage adjusted to
q3-6h in the post haemostatic stage
270
ii) Haemophilia B:
Factor IX concentrate (FIX) (currently pure factor IX)
- Each FIX unit/kg raises the plasma FIX level by 1%
- Dose (unit) = BW (kg) x desired % level rise (lower bioavailability for recombinant FIX :
thus a multiplication factor of 1.2 for adult, 1.5 for children)
- Half-life = 18-24 hours, subject to individual patient response
- Slow iv, no more than 100 unit/min in children or 3 ml/min in adults
- Continuous infusion by experienced haematologist
- monitor level
Anti-fibrinolytic agents or Recombinant activated factor VIIa-as in haemophilia A
- (Note: Cryoprecipitate does not contain FIX; FFP is also not recommended; DDAVP has no
value in haemophilia B)
Desired plasma factor level and dosage for bolus infusions
Type of
haemorrhage
Joint (children)
- initial (1st dose; if
target joint- first day)
- subsequent
CNS/head*
- initial ( 1st dose)
- maintenance
(long term
prophylaxis)
Throat and neck*
- initial (1st dose)
- maintenance
GI
- initial ( 1st dose)
- maintenance
Ophthalmic
- maintenance
Surgery
- maintenance
Iliopsoas muscle
- maintenance
Muscle
(except iliopsoas)
Haemophilia A
dose (units/kg)
Haemophilia B
dose (units/kg)
X 1.5 times for
recombinant IX
80-100%
(subsequent
40-50%)
40-50
Then 20-25 (q12h)
80-100
Then 40-50 (q24h)
80-100%
>50%
40-50
25 (q12h)
80-100
50 (q24h)
At least 7-10 days; usually 2-3
weeks until haemorrhage
improved on imaging
80-100%
>50%
40-50
25 (q12h)
80-100
50 (q24h)
Until bleed resolves; at least 12weeks
80-100%
50%
40-50
25 (q12h)
80-100
50 (q24h)
7-14 days until origin of
bleeding identified and treated
80-100%
>50%
40-50
25 ( q12h)
80-100
50 ( q24h)
80-100%
50%
40-50
25 (q12h)
80-100
50 (q24h)
5-14 days, depending on type of
surgery
80-100%
>50%
40-50
25 (q12h)
80-100
50 (q24h)
2-4 days; may be longer as
dictated by symptoms
50%
25
50
50-100%
25-50
50-100
5-7 days
50%
25
50
3-5 days
Desired level
Duration
1-3 doses till pain largely
subsided; longer if response
inadequate
Until healing
2-3 days; longer if inadequate
response
Deep laceration
Renal
*medical emergency
271
Oral bleeding
- anti-fibrinolytic alone, or with factor (aim level 30-40%) if bleeding is prolonged, significant or
difficult to control
- Mouthwash with anti-fibrinolytic (eg tranexamic acid 250mg in 10-20ml water)
- Topical thrombin/fibrin glue, ice popsicle/custom-fit mouth piece; soft cold diet
Epistaxis
- Factor is usually not needed
- Head forward, firm pressure to the fleshy part of the nose for at least 10-20 min
- Anti-fibrinolytic, intranasal NaCl gel and nose clips
- ENT consultation if significant/ difficult control of bleeding
VI.
Prophylaxis
- Primary prophylaxis (the ideal treatment): start at < 2 years old, before or after the first
haemarthrosis
- Secondary prophylaxis: after the second episode of haemarthrosis
- Primary/secondary prophylaxis should be offered to all severe haemophilia patients
- Regimen:
- High dose: 25-40 units/kg 3x/week for haemophilia A; 30-50 units/kg
2x/week for haemophilia B; aim trough > 1%
- In some, low dose: 20 units/kg 1-2x/week for haemophilia A; 30-40 units/kg
1-2x/week for haemophilia B; titrate clinically
- Dose escalation protocol:
1st step : 50 units/kg once/ week
-> 2nd step: 30 units/kg 2 times/week
-> 3rd step: 25 units/kg QOD (3 times/week)
Step up when 3+ bleeds into any one joint over 3 months OR 4+ bleeds into any soft
tissue/ joint over 3 months OR 5+ bleeds into one joint
- WHO and WHF recommend indefinite primary prophylaxis but many discontinue as adults
- patient with target joints but refuse long term prophylaxis, short-term secondary prophylaxis
for 4-8 weeks (+ physiotherapy or synoviorthesis)
VII.
Surgery
- Best in Haematology centre
- Document individual response to replacement therapy prior to surgery; ensure adequate factor
concentrates availability
- Immediately prior to surgery: aim level 80-100%, then maintain at least 50%
- Monitor factor levels serially during surgery and then at least daily
- Continuous infusion may be preferable if data of stability for continuous infusion of factor
concentrates available
- Maintenance: 5-7 days for minor surgery; 10-14 days for major surgery
- Prophylaxis 3-4x/week for 6 weeks for orthopaedic procedures during rehabilitation
272
VIII.
Special procedures
- Factor coverage for LP, ABG, bronchoscopy, liver bx, endoscopy with brushings/bx
IX.
Dental care
- Ensure good dental and oral hygiene
- Oral infections should be treated with antibiotics before any dental procedures
- No factor concentrates needed for routine dental examination and cleaning
- Factor concentrates (and anti-fibrinolytics or DDAVP for mild haemophilia) for deep cleaning,
scaling, or removal of heavy plaque or calculus
- Always factor concentrates if needs local anaesthesia block, aim level > 50%
- Raise level to 50-100% if dental extraction, by factor concentrates and anti-fibrinolytics
(anti-fibrinolytic x 10 days until sutures removed and wound healed)
- Bleeding associated with 1’ teeth exfoliation managed as in oral bleeding;
those with hx of prolonged bleeding on tooth exfoliation, consider tooth extraction under
factor concentrate cover
- Hospitalize for extensive procedures
- In teenage patients, evaluate for wisdom teeth and consider early extraction
X.
Other precautions
- Sports: i)Encourage low impact activities to strengthen muscle e.g. swimming, golf
ii)Use protective gears iii) High impact sports not advisable e.g. football
- Immunizations: - Follow the routine vaccination schedule but no imi; administer
subcutaneously instead and apply pressure at injection site for 5 minutes
XI.
Complications
Factor inhibitor formation:
- Suspect when no response to usual dose of factor concentrates
- screen for inhibitors Q 3-12 months or Q10-20 exposure days (whichever occurs first); for
adults, screen as clinically indicated
- screen for inhibitors if patients switch to a new factor concentrate
- Low-responding inhibitor - specific factor replacement at a much higher dose (2-3x); patients
with hx of high responding inhibitor but with low titres may be treated similarly in an
emergency, until an anamnestic response occurs, usually in 3-5 days
- At a high inhibitor titre (≥ 5 BU), specific factor replacement unlikely effective without high
dose continuous infusion therapy; use bypassing agents in such cases e.g. recombinant factor
VIIa and PCC, including the activated ones such as FEIBA® /Autoplex®
Other complications:
- Chronic synovitis, chronic haemophilic arthropathy, fracture, infection, pseudotumour,
allergic reaction
273
Chapter 98 - Management of Haemangioma with Propranolol
KT Chan, Dr L Leung
Course of infantile haemangioma (IH)
- Most start proliferating noticeably between 2-4 weeks of age.
- Most rapid proliferation phase – first 6-8 weeks of age; 80% of maximum size reached by 3
months; 80% have completed growth by 5 months. Max size 9-12 months for almost all.
- Segmental & deep IH may longer growth phase.
- Regression – 50% max involution by 5 years, 70% by 7 years, 90% by 9 years.
- Up to 70% leave residua in studies (telangiectasia, fibrofatty plaques, atrophic scar, loose skin)
NB. associated complications of haemangiomas:
- Lumbosacral: high resolution US spine in ≤ 3 months; MRI in ≥ 6 months
- LUMBAR association, segmental genital and lower extremity haemangioma: US abdomen,
pelvis for genitourinary and anorectal anomalies,
- Segmental facial haemangiomas: MRI & MRA for head and neck, echocardiogram for brain/
vascular anomalies/ coarctation & eye consultation for PHACES.
- Multifocal (≥5 skin lesions: may visceral involvement like liver/ GI involvement)
Possible mechanisms of action of propranolol
- Vasoconstriction, inhibition of angiogenesis, and induction of apoptosis
Consult skin clinic doctor for cases considering treatment (at 1-2 mths old). Treat BEFORE or
EARLY in rapid growth phase.
Decision to treat: based on IH location, size, slope, depth, age of patient, extent of growth and
likelihood of future growth, presence and risk of complications. Discuss with parent. Examples are:
-
-
Lesions that are likely to involve airway (mandibular, “beard distribution” including parotid or
neck area) or obscure vision (peri-orbital area) or cause obstruction/ necrosis (nasal, ear or
pinna)
Lesions that are at high risk of ulceration/ bleeding (perioral location, perineal area, buttock,
axilla, sites which are likely to rub against clothes).
Central facial lesions that may cause more residue and potential disfigurement
Segmental lesions (occupy subunit of a body part- 11x risk of complications)
Lesions that are likely to grow longer and leave residua (deep haemangiomas, nasal tip, lip,
parotid, head & neck)
Multifocal/ diffuse hepatic haemangiomas: cardiac overload, consumptive hypothyroidism.
IMPORTANT: For lesions likely fall into above categories: follow-up every 2-4 weeks in first 2-5
months of life: Aim to treat BEFORE active proliferative phase, but may still be useful in children
up to 15 months old.
Small superficial haemangiomas: topical timolol 0.5% (eyedrop formulation) 3-4x per day for 4-6
weeks may be effective if given early. Follow closely, consider systemic β-blocker if not responding.
Contraindications to propranolol
- Sinus bradycardia, hypotension, greater than first-degree heart block, heart failure, asthma,
hypersensitivity to propranolol, cardiogenic shock
- Special precaution – PHACE syndrome (Discuss with senior if facial haemangioma > 5cm)
274
Baseline investigations
- CBC, RFT, LFT, Glucose (preferably before feed), TFT
- ECG (advised when the HR is below normal, arrhythmia detected on cardiac exam, or there is a
family history of arrhythmias or maternal history of connective tissue disease)
Propranolol regimen (inpatient)
- First day – 1mg/kg/day po ÷ BD or TID
- Second and subsequent days – 2 mg/kg/day po ÷ BD or TID
- Feeding should be given shortly after propranolol
(For high risk patients: ≤1 month old, premature or hx of hypoglycemia: First day - start
0.5mg/kg/day po ÷TID, subsequent increase as above)
Sites that are less responsive (e.g. parotid area) may need doses up to 3mg/kg/day
Monitoring
- Baseline and Hourly AR / BP at first 2 hours after each dose of propranolol (peak effect on HR
and BP is 1 to 3 hours, especially after first dose and significant dose increase of >0.5mg/kg/day)
- Inform if AR / BP less than age-specific range.
- Dextrostix before feed
- Inform if sweating, jitteriness, irritable, lethargy, poor feeding – may be subtle symptoms of
hypoglycaemia
- Discharge D3 if tolerated.
Side effects
- More common: changes in sleep (fatigue, insomnia, nightmares, night restlessness, sleep
disturbance) and acrocyanosis
- Less common but serious: Hypotension, hypoglycaemia, bradycardia
- Others: respiratory symptoms (infections, wheeze), GI symptoms (GOR, diarrhoea), irritability
or agitation, profuse sweating, rash and temporary hypotonia, hyperkalaemia
Advice to parents
- Propranolol should be withheld during intercurrent illness (risk of hypoglycaemia)
- Child who need to fast during procedures / investigations should have glucose-containing fluids
(as ORS or IV fluid)
Duration of treatment
- Minimum for 11 months; usually keep till 15 to 18 months (rebound is more frequently seen if
propranolol is stopped before 1 year old)
- Nodular haemangioma on sites that involute slowly may need treatment for 2-3 years
Tapering of treatment
- Propranolol should be tapered over 1-3 months to avoid rebound tachycardia, stepwise by
0.5mg/kg/day.
Other treatment options for systemic β-blockers: nadolol or atenolol.
275

Basic Paediatric Management

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