SIRS, Sepsis, and MODS Claudio Martin, MSc, MD Programme in Critical Care

SIRS, Sepsis, and MODS
Claudio Martin, MSc, MD
Programme in Critical Care
University of Western Ontario
London, Ontario, Canada
Objectives
• To know definitions of SIRS, sepsis, septic shock,
MODS
• To become familiar with the epidemiology of sepsis
• To learn basic pathophysiology (inflammation,
cardiovascular physiology) of SIRS and sepsis
But first, a real case:
Case presentation
• 43-year-old male
• Flu-like symptoms for 1 day
• In ER
– Temp 39.5
– Pulse 130
– Blood pressure 70/30
– Respirations 32
– Petechial rash
– Chest, CV, Abdominal
exam normal
Case presentation - 2
• Laboratory
– pH 7.29, PaO2 82,
PaCO2 29
• Investigations pending
– Blood, urine cultures
• Orally intubated and placed
on mechanical ventilation
• Central venous catheter
inserted
– Cefotaxime 2 g iv
– Normal saline 2 litres
initially, repeated
• Admitted to ICU
Case presentation - 3
• In ICU:
– Noradrenaline started to
support blood pressure
– Additional fluid (saline and
pentastarch) given based
on low CVP
– Pulmonary artery catheter
inserted to aid further
hemodynamic
management
• Despite therapy patient
remained anuric
– Continuous venovenous
hemofiltration initiated
Case presentation - 4
• Early gram stain on blood revealed gram negative
rods
• Patient started on:
– Hydrocortisone 100 mg iv q8h
– Recombinant activated protein C 24g/kg/hour for
96 hours
– Enrolled in RCT (double-blind) of vasopressin vs
norepinephrine for BP support
– Enteral nutrition via nasojejunal feeding tube
– Prophylaxis for stress ulcers, deep venous
thromboses
Case Presentation - Resolution
• Patient gradually stabilized and improved with
complete resolution of organ dysfunction over 5 days
• Final cultures confirmed diagnosis as
meningococcemia
Infection: Part of a bigger picture
•
Infection:
–
Presence of organisms in a
closed space or location
where not normally found
Infection
Adapted from: Bone RC et al. Chest. 1992;101:1644-55.
Opal SM et al. Crit Care Med. 2000;28:S81-2.
SIRS: Systemic Inflammatory
Response Syndrome
• SIRS: A clinical response
arising from a nonspecific
insult manifested by
2 of the following:
– Temperature
38°C or 36°C
– HR 90 beats/min
– Respirations 20/min
– WBC count 12,000/mL or
4,000/mL or >10%
immature neutrophils
Adapted from: Bone RC et al. Chest. 1992;101:1644-55.
Opal SM et al. Crit Care Med. 2000;28:S81-2.
Sepsis: More Than Just Inflammation
• Sepsis:
– Known or suspected
infection
– SIRS criteria
Adapted from: Bone RC et al. Chest. 1992;101:1644-55.
Severe Sepsis: Acute Organ
Dysfunction
• Severe Sepsis =
Sepsis with signs of acute
organ dysfunction in any of
the following systems:
– Cardiovascular (septic
shock)
– Renal
– Respiratory
– Hepatic
– Hemostasis
– CNS
– Unexplained metabolic
acidosis
Adapted from: Bone RC et al. Chest. 1992;101:1644-55.
Sepsis: A Complex Disease
Adapted from: Bone RC et al. Chest. 1992;101:1644-55.
Opal SM et al. Crit Care Med. 2000;28:S81-2.
Jargon 2002: PIRO
Infection
Inflammation
Physiologic
Biochemical
Severe
Sepsis
Specific Organ
Severity
Predisposition
• Pre-existing disease
– Cardiac, Pulmonary, Renal
– HIV
• Age (extremes of age)
• Gender (males)
• Genetics
– TNF polymorphisms (TNF promoter high secretor
genotype)
Response
• Physiology
– Heart rate
– Respiration
– Fever
– Blood pressure
– Cardiac output
– WBC
– Hyperglycemia
• Markers of Inflammation
– TNF
– IL-1
– IL-6
– Procalcitonin
– PAF
Organ Dysfunction
•
•
•
•
•
•
•
•
•
•
Lungs
Kidneys
CVS
CNS
PNS
Coagulation
GI
Liver
Endocrine
Skeletal Muscle
 Adult Respiratory Distress Syndrome
 Acute Tubular Necrosis
 Shock
 Metabolic encephalopathy
 Critical Illness Polyneuropathy
 Disseminated Intravascular Coagulopathy
 Gastroparesis and ileus
 Cholestasis
 Adrenal insufficiency
 Rhabdomyolysis
Specific therapy exists
Magnitude of the Problem
• Estimated 215,000 deaths from US 1995 data
• High cost for management (ICU care, diagnostic
testing, drugs)
– Estimated 20 day LOS; $22,000 cost
• Represents 9.3% of all deaths
• Equals deaths after acute myocardial infarction
Sepsis: Defining a Disease Continuum
Infection/
Trauma
SIRS
A clinical response arising
from a nonspecific insult,
including 2 of the
following:
– Temperature ≥38oC or
≤36oC
– HR ≥90 beats/min
– Respirations ≥20/min
– WBC count ≥12,000/mm3
or
≤4,000/mm3 or >10%
immature neutrophils
Sepsis Severe Sepsis
SIRS with a presumed or
confirmed infectious
process
SIRS = systemic inflammatory response
syndrome.
Bone et al. Chest. 1992;101:1644.
Sepsis: Defining a Disease Continuum
Infection/
Trauma
SIRS
Sepsis Severe Sepsis
Shock
• Sepsis with ≥1 sign of organ
failure
– Cardiovascular (refractory
hypotension)
– Renal
– Respiratory
– Hepatic
– Hematologic
– CNS
– Unexplained metabolic
acidosis
Bone et al. Chest. 1992;101:1644; Wheeler and Bernard. N Engl J Med. 1999;340:207.
Epidemiology of Sepsis
The International Cohort Study
Infection
Sepsis
Severe
Sepsis
Septic
Shock
Percent of cases within each category
18
28
24
30
35% mortality
8353 patients with LOS > 24h
4277 infections (2696 on admission)
Alberti, Int Care Med 2002
Sources of Sepsis
The International Cohort Study
Severe
Sepsis
Septic
Shock
Respiratory
66
53
Abdomen
9
20
Bacteremia
14
16
Urinary
11
11
Multiple
-
-
Microbiology of Sepsis
The International Cohort Study
Severe
Sepsis
Septic
Shock
Gram-positive
44
40
Gram-negative
47
47
Fungal
9
13
Polymicrobial
-
-
Pathogenesis of SIRS/MODS
Preoperative Illness
Trauma or
Operation
Tissue Injury
optimal oxygen
delivery and
support
Recovery
Excessive
Inflammatory
Response
Inadequate
Resuscitation
SIRS/MODS
Initiation of Inflammatory Response
From Wheeler & Bernard, NEJM 1999
Homeostasis Is Unbalanced in
Severe Sepsis
Carvalho AC, Freeman NJ. J Crit Illness. 1994;9:51-75; Kidokoro A et al. Shock.
1996;5:223-8; Vervloet MG et al. Semin Thromb Hemost. 1998;24:33-44.
Coagulation and Fibrinolysis
Bernard, GR. NEJM 2001;344;10:699-709
Pathogenesis of SIRS/MODS
Preoperative Illness
Trauma or
Operation
Tissue Injury
optimal oxygen
delivery and
support
Recovery
Excessive
Inflammatory
Response
Inadequate
Resuscitation
SIRS/MODS
Regulation of oxygen delivery
Normal
Abnormal
Cardiac
output
BP=CO * SVR
Cardiac
Output
regional distribution
regional distribution
Intra Organ Distribution
Intra Organ Distribution
Microcirculation
Microcirculation
QO2 = Flow * O2 content
Oxygen Delivery
• Delivery:Demand mismatch
• Diffusion limitation (edema)
Oxygen Consumption
H+
H+
I
Q
NADH + H+
H+
Cytc
III
H+
H+
IV
1/2 O2 + H+ H2O
NAD+
ADP + Pi
•Pyruvate Dehydrogenase (PDH) activity decreased
•Decreased delivery of Acetyl CoA to TCA cycle
•Mitochondrial dysfunction
ATP
Severe Sepsis:
The Final Common Pathway
Endothelial Dysfunction and
Microvascular Thrombosis
Hypoperfusion/Ischemia
Acute Organ Dysfunction
(Severe Sepsis)
Death
Severe Sepsis:
Management of Our Case
Endothelial Dysfunction and
Microvascular Thrombosis
rhAPC
Corticosteroids
Hypoperfusion/Ischemia
Fluids
Vasopressors
Acute Organ Dysfunction
(Severe Sepsis)
CVVHF
Enteral nutrition
Death
Survival