2015 Dr. Stanley F. Malamed

Transcription

2015 Dr. Stanley F. Malamed - Fourth District Dental Society

LOCAL ANESTHETICS:
Dentistry’s Most
Important Drugs
Stanley F. Malamed, DDS
Dentist Anesthesiologist
Emeritus Professor of Dentistry
Ostrow School of Dentistry of USC
Los Angeles, California, USA
Saratoga Dental Congress
4th District Dental Society
1
© 2015 Dr. Stanley F. Malamed
All Rights Reserved
Stanley F. MALAMED, DDS
Ostrow School of Dentistry of U.S.C.
Los Angeles, CA, USA
I have a relationship with the following companies that may
be relevant to this presentation.
I am a paid consultant to:
Septodont, Inc
OnPharma
St. Renatus
3M ESPE
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21 May 2015
PM session
1. Current Local Anesthetic
Formulations
2. What’s New?
a. Articaine
b. LA ‘OFF’ Switch
c. LA ‘ON’ Switch
3. Maxillary Anesthesia
Without Injection
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Local Anesthetic Use in Dentistry
LOCAL ANESTHETICS are the
SAFEST and MOST EFFECTIVE
drugs in medicine for the
PREVENTION & MANAGEMENT of pain
Annual LA usage (approximate)
300 x 106 USA (300,000,000)
80 x 106 Germany
40 x 106 U.K.
Amides have been available since 1948
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AMIDES
ESTERS
Esters
Cocaine
Procaine
Tetracaine
Articaine
1948
Lidocaine
Benzocaine
Mepivacaine
Chloroprocaine
Amides
Prilocaine
Propoxycaine
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Bupivacaine
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Local anesthetics (worldwide)
Articaine
Bupivacaine
Lidocaine
Mepivacaine
Prilocaine
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Local Anesthetics by
EXPECTED duration of PULPAL anesthesia
•
Normal
Distribution
Curve
BellShaped
Curve
Short-duration (~30 minutes)
•
•
Intermediate-duration (~60 minutes)
•
•
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Lidocaine 2%, Mepivacaine 3%, Prilocaine 4%
Articaine 4%, Lidocaine 2%, Mepivacaine 2%,
Prilocaine 3% or 4% (all with vasoconstrictor)
Long-duration (>90 minutes)
•
Bupivacaine 0.5% (with vasoconstrictor)
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All injectable local anesthetics are VASODILATORS
Blood flow through area is INCREASED
Short - Duration LAs
Cocaine
~ 30 minutes
Mepivacaine
3%
No vasoconstrictor
Prilocaine
4%
No vasoconstrictor
LA diffuses OUT of AREA more rapidly
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Short - duration LAs - USA
PLAIN LAs
provide a
SHORT-DURATION
of
NOT AS PROFOUND
anesthesia
Drug
Onset (textbook)
Mepivacaine
3 - 5 min
3%
Prilocaine
4%
3 - 5 min
Pulpal
20 - 40 min
infiltration - nerve
block
10 - 60 min
infiltration - nerve
block
© 2015
2014 Dr. Stanley F. Malamed
©All
2013
Rights
Dr. Stanley
Reserved
F. Malamed
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Soft Tissue
2 - 3 hours
2 - 4 hours
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Intermediate - Duration LAs
To increase DURATION, and
to increase DEPTH, of anesthesia,
~ 60 minutes
a VASOCONSTRICTOR is added to the LA solution
USA
Worldwide
Epinephrine
Levonordefrin
Epinephrine
Norepinephrine
Felypressin
Articaine
4% + vasoconstrictor
Lidocaine
Mepivacaine
Prilocaine
© 2015
©All
2013
Rights
Dr. Stanley
Reserved
F. Malamed
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Intermediate - duration LAs - USA
Through addition of a vasoconstrictor, the
ensuing BLOOD LEVEL of the local
anesthetic is significantly decreased,
making the LA drug SAFER by minimizing
risk of overdose (toxic reaction)
Drug
Onset (textbook)
Pulpal
Soft Tissue
Articaine 4%
Epi
1:100k
1:200k
2 - 3 min
60 min
3 - 5 hours
Lidocaine
2%
Epi
1:50k, 1:100k
3 - 5 min
60 min
3 - 5 hours
Mepivacaine Levonordefrin
1:20k
2%
3 - 5 min
60 min
3 - 5 hours
3 - 5 min
60 min
3 - 8 hours
Prilocaine
4%
Epi
1:200k
Epinephrine
Epi = Epinephrine (Adrenalin)
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Levonordefrin
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Local Anesthetic Blood Levels
•
•
Long - Duration LAs
MEPIVACAINE
> 90 minutes
•
5 mg/kg - NO epinephrine - PEAK LEVEL 1.2 ug/mL
•
5 mg/kg - Epi 1:200,000 - PEAK LEVEL 0.7 ug/mL
Bupivacaine
LIDOCAINE
•
400 mg - NO epinephrine - PEAK LEVEL 2.0 ug/mL
•
400 mg - Epi 1:200,000 - PEAK LEVEL 1.0 ug/mL
0.5% + vasoconstrictor
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Long - duration LAs - USA
Bupivacaine 0.5% with vasoconstrictor
Drug
Bupivacaine
0.5%
Epi
1:200k
Onset (textbook)
Pulpal
6 -10 min
90 - 180
min
(up to 7 hours)
Soft Tissue
up to 12
hours
•
Indicated for:
•
Dental therapy of > 2 hour duration
•
Post-surgical pain control
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Bupivacaine 0.5% with vasoconstrictor
Post-surgical pain control
Pre-surgical NSAID po 1 hr. prior to appointment
Ibuprofen 600 mg QID PO
•
LA of choice for surgery
Articaine, Lidocaine, Mepivacaine
Not indicated for:
•
Long-acting LA at end of surgery just prior to discharge of patient
Rarely indicated for administration to children (long
duration soft tissue anesthesia = increased risk of self-inflicted
soft tissue injury)
Bupivacaine
NSAID on timed basis (q4,6,8h) for xx days
Ibuprofen 600 mg QID PO
Post-surgical telephone call early evening
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Maximum recommended
therapeutic dosages
•
Drug
Mg/kg
Absolute maximum
Articaine HCl
7
n/a
Bupivacaine HCl
***
90
Short-duration (~30 minutes)
•
•
Intermediate-duration (~60 minutes)
•
Lidocaine HCl
7
500
Mepivacaine HCl
6.6
400
Prilocaine HCl
8
600
•
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Mepivacaine 3%, Prilocaine 4%
Articaine 4%, Lidocaine 2%, Mepivacaine 2%,
Prilocaine 3% or 4% (all with vasoconstrictor)
Long-duration (>90 minutes)
•
Bupivacaine 0.5% (with vasoconstrictor)
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USA
What’s NEW in Local Anesthesia
Jan-Dec2014
Lidocaine
49.35%
Articaine
34.86%
Mepivacaine
9.82%
Bupivacaine
3.3%
Prilocaine
2.7%
84.21%
By MARKET SHARE
Articaine - Mandibular Infiltration
The LA ‘OFF’ Switch
The LA ‘ON’ Switch
Maxillary Anesthesia without Injection
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Buccal infiltration ARTICAINE
Articaine HCl
by Mandibular Infiltration
in Adults
Mandibular infiltration
John Meechan (UK)
Al Reader (USA)
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2014 Dr.Reserved
Stanley F. Malamed
All
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Articaine infiltration
as a sole injection
for mandibular anesthesia
Robertson D, Nusstein J, Reader A, Beck M, McCartney M.
The anesthetic efficacy of articaine in buccal infiltration
of mandibular posterior teeth.
J Am Dent Assoc 138:1104-1112, 2007
2007
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Design:
N = 60
Infiltration mandibular buccal fold by #30
• Lidocaine 2% + epi 1:100K
• Articaine 4% + epi 1:100K
Randomized
• At least 7 days apart
• 60 on right side
• 60 on left side
1.8 mL in 60 seconds
2007
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EPT
Teeth tested: 1st and 2nd molar, 1st and 2nd premolar
• Baseline
• EPT @ 1 min = molars
• EPT @ 2 min = premolars
• EPT @ 3 min = Control (contralateral canine)
• Repeated cycle every 3 minutes for 60 minutes
Criteria for success:
• No response to 2 or more consecutive 80uA tests
•
2007
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Results -2:
JADA 138(8):1104-1112, 2007
Pulp test every
3 min
SUCCESS =
80/80 on 2
consecutive
tests
2007
Mandibular
2nd Molar
Mandibular
1st Molar
Mandibular
2nd Premolar
Mandibular
1st Premolar
Articaine
Lidocaine
75%
87%
92%
86%
45%
57%
The onset of successful anesthesia was significantly faster
for articaine than lidocaine for all 4 teeth tested
p value for all:
>.0001
67%
61%
2007
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Thiophene ring:
> lipid solubility
Lidocaine
Meechan JG, Ledvinka JI.
Pulpal anaesthesia for mandibular central incisor teeth: a
comparison of infiltration and intraligamentary injections.
Int Endod J 35:629-634, 2002
Benzene ring
Articaine
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2002
Mandibular Incisors
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Pulpal anaesthesia for mandibular central incisor teeth: a comparison of
infiltration and intraligamentary injections.
Int Endod J 35:629-634, 2002
Int Endod J 35:629-634, 2002
Design:
Articaine 4% + epi 1:100K
Lidocaine 2% + epi 1:80K
Infiltration buccal fold by lateral incisor
• 0.5 mL
Infiltration buccal & lingual by lateral incisor
• 0.5 mL per site
EPT q 3 min for 45 minutes
2002
Results-1:
Infiltration buccal fold by lateral incisor
• 94% articaine; 70% lidocaine
• Infiltration buccal & lingual by lateral incisor
• 97% articaine; 88% lidocaine
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Int Endod J 35:629-634, 2002
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2002
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Mandibular Incisors
Buccal
Buccal infiltration
infiltration -ARTICAINE
ARTICAINE
Articaine B&L
Advantages
Articaine B
1. Profound pulpal anesthesia
2. 30 to 40 minute duration of pulpal anesthesia
3. Minimal accessory soft tissue anesthesia
• Tongue
Lidocaine B&L
Lidocaine B
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Rights
© 2015 Dr. Stanley
Malamed
©F.
2013
Dr.Reserved
Stanley F. Malamed
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Comment
Disadvantage
1. The research required articaine infiltration
by tooth #30
2. In clinical situations you would logically
infiltrate the articaine in the buccal fold
adjacent to the tooth to be treated.
I can’t think of any,
unless it doesn’t work!
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Kanaa JM, Whitworth JM, Corbett IP, Meechan JG
Articaine buccal infiltration enhances the effectiveness of lidocaine inferior alveolar nerve block.
Int Endodont J 42:238-246, 2009
as a supplement
to IANB
IANB’s at each of 2 visits = 2% lidocaine + epi 1:80K
One visit = 4% articaine + epi 1:100K infiltration buccal fold 1st
molar (2.0 mL)
One visit = ‘dummy injection’ buccal fold 1st molar
Pulp test for 45 minutes
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as a supplement to IANB
as a supplement to IANB
1st Molar
1st Premolar
88.9%
91.7%
66.7%
55.6%
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Anesthesia
success
>2 consecutive
80/80 readings
50
IA + a-caine
infiltration
IA + a-caine
infiltration
IA + dummy
infiltration
IA + dummy
infiltration
Failure
n (%)
Success
n (%)
Failure
n (%)
Success
n (%)
1st molar
3 (8.3)
Premolars
4 (11.1)
33
(91.7)
16 (44.4)
32
(88.9)
12 (33.3)
The local anesthetic
“OFF SWITCH”
McNemar Test
P-value
20
(55.6)
<0.001
24
(66.7)
0.021
Phentolamine Mesylate
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To increase DURATION, and to increase
DEPTH, of anesthesia, a
VASOCONSTRICTOR is added to the LA
solution
PLAIN LAs
provide a
SHORT-DURATION
of
NOT VERY PROFOUND
anesthesia
Epinephrine
Felypressin
Levonordefrin
Norepinephrine
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Drug
Onset (textbook)
Pulpal
Soft Tissue
Articaine 4%
Epi
1:100k
1:200k
2 - 3 min
60 min
3 - 5 hours
The PROBLEM,
Lidocaine
2%
Epi
1:50k, 1:100k
3 - 5 min
60 min
3 - 5 hours
on occasion,
1:20k
2%
3 - 5 min
60 min
3 - 5 hours
3 - 5 min
60 min
3 - 8 hours
Prilocaine
4%
Epi
1:200k
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is RESIDUAL
SOFT TISSUE ANESTHESIA
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13% of pediatric patients receiving IANB suffer post-treatment traumatic injury to soft tissues.
Age
< 4 years
4-7
years
8 - 11
16%
“OFF SWITCH”
13%
%
with soft tissue
trauma
18%
years
12+
7%
College C, Feigal R, Wandera A, Strange M. Bilateral versus
unilateral mandibular block anesthesia in a pediatric population.
Pediatr Dent. 22(6):453-457, 2000.
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Phentolamine mesylate is a vasodilator (an alpha adrenergic
antagonist) that increases vascular perfusion in the area of injection.
Local Anesthesia Reversal
Phentolamine dilates
blood vessel
Epinephrine
constricts blood vessel
This increased perfusion leads to an increased rate of the LA
diffusing out of the nerve into the cardiovascular system, thereby
decreasing the duration of residual soft tissue anesthesia.
Does it work?
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UPPER&LIP
Percep&on)of)normal)
appearance)and)func&on
)
Control
133&minutes
PM
50&minutes
Accelerated&by:
83&minutes
Accelerated&by&60&min.
YES!
YES!
)
Restora&on)of)normal)
sensa&on)of)tongue
1
3
4
1
)
Restora&on)of)normal)
func&on
&&LOWER&LIP
Control
PM
Accelerated&by:
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155&minutes
70&minutes
85&minutes
Thanks to:
Suzete Brasil, Erica Dicterow, Fariba Neumann & Joan Ong
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OraVerse
“ON SWITCH”
Conservative dental treatment
Non-surgical periodontics (SRP)
Pediatric dentistry
Medically compromised patients:
e.g.: Diabetics
Buffered Local Anesthetics
Alkalinized Local Anesthetics
Geriatric patients
Special needs patients
Post-mandibular implants
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Drug
How long does it take for pulpal
anesthesia to develop?
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Lidocaine
2%
Onset (textbook)
Pulpal
Epi
1:50k, 1:100k
3 - 5 min
60 min
3 - 5 hours
1:20k
2%
3 - 5 min
60 min
3 - 5 hours
Prilocaine
4%
Epi
1:200k
3 - 5 min
60 min
3 - 8 hours
Articaine 4%
Epi
1:100k
1:200k
2 - 3 min
60 min
3 - 5 hours
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Six-Hour Time Course for Pulpal Analgesia (EPT)
IANB Second Premolar
So the question is:
The other 5% are anatomical misses
95% of
patients will
(eventually) get
numb
if given a
45-minute
waiting period
Why?does it REALLY take for
How long
pulpal anesthesia to develop?
45 minutes
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Soft Tissue
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30-Minute Time Course for Pulpal Analgesia - Lidocaine IANBs
Data from 28 PRP Studies - 1078 Subjects (1991 - 2008)
IANB - Lido
28 peerreviewed
trials
100%#
#Kanaa#(2006)(m)(L)#
#Nist#(1992)(m)(L)#
90%#
#Chaney#(1991)(m)(L)#
#Hinckley#(1991)(m)(L)#
#McLean#(1993)(m)(L)#
80%#
N = 1078
#Childers#(1996)(m)(L)#
#Dagher#(1997)(m)(L)#
#Goldberg#(2008)(m)(L)#
70%#
#Goodman#(2006)(m)(L)#
Infiltration - Lido
#Hannan#(1999)(1m)(L)#
60%#
8 peer-reviewed
trials
#Hannan#(1999)(2m)(L)#
#Steinkruger#(2006)(m)(L)#
#Willet#(2008)(m)(L)#
50%#
#Vreeland#(1989)(m)(L)#
N = 416
The
SPAGHETTI
graph
40%#
IANB - Articaine
5 peer-reviewed
trials
30%#
20%#
N = 222
10%#
#Kanaa#(2006)(p)(L)#
#Chaney#(1991)(p)(L)#
#McLean#(1993)(p)(L)#
#Dagher#(1997)(p)(L)#
#Goldberg#(2008)(p)(L)#
#Goodman#(2006)(p)(L)#
#Hannan#(1999)(p)(L)#
#Willet#(2008)(p)(L)#
#Mikesell#(2005)(m)(L)#
#Mikesell#(2005)(1p)(L)#
0%#
0#
2#
4#
6#
8#
10#
12#
14#
16#
18#
20#
22#
24#
26#
28#
30#
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30 Minute Time Course for IANB Soft Tissue Analgesia (sharp dental explorer)
Data from 28 PRP Studies - 1078 Subjects (1991 - 2008)
100%#
Lai, et al, OOOOE, Vol 102, No 4, P 462-68 (2006)
100%#
#Kanaa#(2006)(m)(L)#
#Nist#(1992)(m)(L)#
#Chaney#(1991)(m)(L)#
90%#
90%#
#McLean#(1993)(m)(L)#
80%#
80%#
#Dagher#(1997)(m)(L)#
70%#
70%#
Lidocaine#IANB#Mean#
70%
#Hannan#(1999)(1m)(L)#
#Hannan#(1999)(2m)(L)#
60%#
60%#
#Willet#(2008)(m)(L)#
50%#
50%#
‘MEAN’
40%#
30%#
50% above
50% below
20%#
10%#
#Kanaa#(2006)(p)(L)#
#Chaney#(1991)(p)(L)#
At 4 minutes:
70% soft tissue numb
25% pulpal anesthesia
40%#
#McLean#(1993)(p)(L)#
#Dagher#(1997)(p)(L)#
30%#
25%
20%#
#Hannan#(1999)(p)(L)#
#Willet#(2008)(p)(L)#
#Mikesell#(2005)(m)(L)#
10%#
Lai,#et#al,#so>#?ssue#v.#EPT#
0%#
0#
2#
4#
6#
8#
10#
12#
14#
16#
18#
20#
22#
24#
26#
28#
0%#
30#
0#
2#
4#
6#
8#
10#
12#
14#
16#
18#
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20#
22#
24#
26#
28#
30#
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100%#
90%#
Soft tissue anesthesia
is NEVER
a guaranteed sign of
pulpal anesthesia
85%
80%#
70%#
60%#
50%#
40%#
At 6 minutes:
85% soft tissue numb
40%
30%#
20%#
10%#
0%#
0#
2#
4#
6#
8#
10#
12#
14#
16#
18#
20#
22#
24#
26#
28#
30#
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100%#
90%#
Soft tissue anesthesia
is NEVER
a guaranteed sign of
pulpal anesthesia
85%
80%#
OW!
70%
70%#
60%#
50%#
40%
40%#
30%#
25%
20%#
10%#
0%#
0#
2#
4#
6#
8#
10#
12#
14#
16#
18#
20#
22#
24#
26#
28#
30#
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Average for 28 PRP Studies - 1078 Subjects (1991 - 2008) with Lidocaine IANB Mean
100%#
Is there a guarantee?
Most doctors
wait ~10 minutes
90%#
80%#
70%#
N = 1078
The best* we have is using an
electric pulp tester
or
Freezing spray (e.g. Endo-Ice)
60%#
50%#
40%#
At 10 minutes:
30%#
20%#
10%#
0%#
*Assumes no pulpal involvement
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0#
2#
4#
6#
77
8#
10#
12#
14#
16#
18#
20#
22#
24#
26#
28#
30#
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Average for 28 PRP Studies - 1078 Subjects (1991 - 2008) with Lidocaine IANB Mean
IANB: Lidocaine + epinephrine
100%#
Some
doctors
Many
practitioners
wait
15
minutes
(67%)
wait ~15 minutes
90%#
80%#
70%#
N = 1078
% clinically effective pulpal anesthesia
60%#
50%#
•
25% at 4 minutes
•
40% at 6 minutes
•
60% at 10 minutes
•
67% at 15 minutes
•
95% at 45 minutes
40%#
At 15 minutes:
30%#
20%#
10%#
0%#
0#
2#
4#
6#
8#
10#
12#
14#
16#
18#
20#
22#
24#
26#
28#
30#
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80
100%#
Why do doctors LIKE articaine?
#Kanaa#(2006)(m)(L)#
#Nist#(1992)(m)(L)#
90%#
#Chaney#(1991)(m)(L)#
80%#
#McLean#(1993)(m)(L)#
#Dagher#(1997)(m)(L)#
70%#
60%#
#Hannan#(1999)(1m)(L)#
#Hannan#(1999)(2m)(L)#
50%#
#Willet#(2008)(m)(L)#
40%#
#Kanaa#(2006)(p)(L)#
#Chaney#(1991)(p)(L)#
30%#
#McLean#(1993)(p)(L)#
20%#
#Dagher#(1997)(p)(L)#
Anecdotal comments from dentists:
10%#
#Hannan#(1999)(p)(L)#
#Willet#(2008)(p)(L)#
0%#
0#
2#
4#
6#
8#
10#
12#
14#
16#
18#
20#
22#
24#
26#
28#
30#
“It works better”
Can we speed the onset of
anesthesia . . .
“I don’t miss as often”
“Hard to get ‘numb’ patients are
easier to numb with articaine”
with Articaine?
“It works faster”
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30-Minute Time Course, Pulpal Analgesia, IANB,
Lidocaine,
Articaine
100%#
90%#
80%#
Can we speed the onset
of anesthesia
Ar/caine#IANB#Mean#
with Articaine?
70%#
N = 222
Articaine
Lidocaine
N = 1078
60%#
50%#
40%#
ARTICAINE
+ epinephrine
30%#
20%#
10%#
0%#
0#
2#
4#
6#
8#
10#
12#
14#
16#
18#
20#
22#
24#
26#
28#
30#
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NO
84
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100%#
100%#
#Kanaa#(2006)(m)(L)#
#Kanaa#(2006)(m)(L)#
#Nist#(1992)(m)(L)#
90%#
#Nist#(1992)(m)(L)#
90%#
#Chaney#(1991)(m)(L)#
#Chaney#(1991)(m)(L)#
80%#
80%#
#McLean#(1993)(m)(L)#
#McLean#(1993)(m)(L)#
#Dagher#(1997)(m)(L)#
70%#
#Dagher#(1997)(m)(L)#
70%#
60%#
60%#
#Hannan#(1999)(1m)(L)#
#Hannan#(1999)(1m)(L)#
#Hannan#(1999)(2m)(L)#
50%#
#Hannan#(1999)(2m)(L)#
50%#
#Willet#(2008)(m)(L)#
#Willet#(2008)(m)(L)#
40%#
40%#
#Kanaa#(2006)(p)(L)#
#Kanaa#(2006)(p)(L)#
#Chaney#(1991)(p)(L)#
30%#
#Chaney#(1991)(p)(L)#
30%#
#McLean#(1993)(p)(L)#
20%#
#McLean#(1993)(p)(L)#
20%#
#Dagher#(1997)(p)(L)#
#Dagher#(1997)(p)(L)#
10%#
10%#
#Hannan#(1999)(p)(L)#
#Hannan#(1999)(p)(L)#
#Willet#(2008)(p)(L)#
0%#
0#
2#
4#
6#
8#
10#
12#
14#
16#
18#
20#
22#
24#
26#
28#
#Willet#(2008)(p)(L)#
0%#
30#
0#
2#
4#
6#
8#
10#
12#
14#
16#
18#
20#
22#
24#
26#
28#
30#
anesthesia . . .
anesthesia . . .
by buffering the LA solution?
by changing the pH of
the LA solution?
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30-Minute Time Course, Pulpal Analgesia, IANB,
Buffered Lidocaine
Lidocaine,
Articaine
Can we speed the onset
of anesthesia
100%#
90%#
Ar/caine#IANB#Mean#
80%#
67%
N = 18
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70%#
by buffering the solution?
60%#
50%#
40%#
30%#
BUFFERED
lidocaine + epinephrine
20%#
10%#
#Buffered#Lido#IANB#
0%#
0#
2#
4#
6#
8#
10#
12#
14#
16#
18#
20#
22#
24#
26#
28#
30#
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YES
88
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Lidocaine
Local
anesthetics
are
INSOLUBLE
in water.
“ON SWITCH”
Mepivacaine
Articaine
Prilocaine
Bupivacaine
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90
Mepivacaine HCl
Lidocaine HCl
We inject the
acid-salt of the
local anesthetic
Hydrochloric acid
is added
to make the
drug water-soluble
Bupivacaine HCl
Articaine HCl
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Prilocaine HCl
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Let’s look at the anesthetic cartridge
pH
Lidocaine = RN
+
Hydrochloric acid = H
‘Plain’ LA solution (mepivacaine 3%) = ~6.5
Vasoconstrictor LA solution = ~3.5
Lemon juice = 3.3
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94
the greater the number of H
H+
RN
The more acidic the solution
+
+
Some H attach to RN forming RNH
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+
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The LA must diffuse through the nerve
membrane to block Na+ channels
So . . . inside the LA cartridge we have
+
three things: RN
H and RNH
+
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98
RN is LIPID SOLUBLE and CAN cross the lipid-rich nerve membrane
% Un-ionized (RN) LA
pH
Lidocaine
Articaine Mepivacaine Bupivacaine
pKa 7.9
pKa 7.8
pKa 7.6
pKa 8.1
0.004
0.005
0.008
0.003
RN
RN
3.5
(with epi)
RN
RNH+ CANNOT cross the nerve membrane
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pH 3.5
The body will
SLOWLY
buffer the
anesthetic
solution to a
pH of 7.4
pH
Lidocaine
7.4
24.03%
75.97%
0.004%
99.996%
45 minutes ?
pKa 7.9
(body pH)
3.5
(with epi)
45 minutes ?
3.4
3.6
3.8
4
4.2
4.4
4.6
4.8
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6000x increase
in RN
5.8
5.9
6
6.2
6.4
6.6
6.8
7
7.2
7.4
7.6
7.8
8
8.2
8.4
8.6
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Articaine Mepivacaine Bupivacaine
pKa 7.9
pKa 7.8
pKa 7.6
pKa 8.1
24.03
28.47
38.69
16.63
3.83
4.77
7.36
2.45
0.004
0.005
0.008
0.003
BUFFERING
with
Sodium Bicarbonate
(plain)
3.5
5.6
pH = 7.35
(body pH)
6.5
5.4
102
% Un-ionized (RN) LA
7.4
5.2
The human body is a magnificent buffering machine
101
Lidocaine
5
pH
RNH+
RN
pH
pH 7.4
45 minutes ?
pH = 7.35
(with epi)
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Malamed SF, Hersh E, Poorsattar S, Falkel M. Faster onset and more comfortable injection with
alkalinized 2% lidocaine with epinephrine 1:100,000. Compendium 34:(spec issue #1):1-11, 2013
•
•
Summary
•
•
Clinical Trial Data
•
•
•
•
Patients were appointed twice.
Received IANB each time
• At least 1 week between appointments
Pulp tested mandibular premolar prior to start
IANB administered
• Traditional lidocaine + epi 1:100k (pH ~3.5)
• Buffered lidocaine + epi 1:100k (pH 7.35)
Timer started
Endo-ice applied to premolar q20sec until no response
Confirmed with EPT
Onset of anesthesia when BOTH tests negative
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Clinical Data – Pain Free Injections
50%
44%
38%
44% of buffered anesthetic patients
experienced zero injection pain
6:37
25%
6% of traditional anesthetic patients
13%
experienced zero injection pain
1:51
6%
0%
Control
Buffered
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Clinical Data – Onset less than 2 minutes
Clinical Data – Patient Preference
80%$
71%$
70%$
80%
72%
72 % of patients
rated buffered
anesthetic as the
more
comfortable
injection
60%$
50%$
60%
40%$
40%
30%$
20%
17%
20%$
11%
0%
No)Difference
Control
0%$
Buffered
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Lidocaine$w/$Epi$
Buffered$Lidocaine$w/$Epi$
alkalinized 2% lidocaineWhat%Percentage%of%Par.cipants%Achived%Pulpal%
with epinephrine 1:100,000. Compendium 34:(spec issue #1):1-11, 2013
Anesthesia%in%Under%2%Minutes?%
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Buffering Lidocaine HCl
When buffering is done properly the following advantages
can be expected from the increase in pH:
Lidocaine 2% + epinephrine 1:100,000 = pH 3.5
BUFFERED
Lidocaine 1.75% + epi 1:125,000 + CO2 + NaHCO3 = pH 7.4
More dilute
6,000x more active ions to enter nerve
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12%$
10%$
(1) More comfortable injection for patient
pH of anesthetic 7.35 to 7.5
(2) More rapid onset on pulpal anesthesia
(3) More profound anesthesia
(4) Less post-injection soreness
(5) No effect on duration of action
(6) No increase in LA blood level (safety)
112
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The
Onset® approach
The
Onset® approach
Maxillary anesthesia
1.
2.
3.
4.
Administer buffered lidocaine IANB
DO NOT LEAVE PATIENT !!!
You will know if your block is successful in 2 minutes
Check for pulpal anesthesia:
• EPT or Endo-Ice
5. In 2 minutes following
IANB begin tooth preparation
Follow same procedure for maxillary teeth.
Onset time is at least as rapid
- if not faster following infiltration
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ADA Center for Evidence Based Dentistry
Increasing the pH of
lidocaine with sodium
bicarbonate
decreased pain on
injection and
augmented patient
comfort and
satisfaction.
“ON SWITCH”
ADA Evidence
Quality Rating =
Good
Alkalinized Local Anesthetics
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Intranasal Drug Administration
Intranasal Local Anesthesia
in the Maxilla
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118
Emergency medicine
Pediatric grand mal status . . . Midazolam
Pediatric sedation (dentistry) . . . Midazolam
Illicit drugs:
Cocaine
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Intranasal Local Anesthetic Mist
Intranasal Local Anesthetic
• NDA (New Drug Application) filing anticipated second quarter 2015;
anticipated FDA approval in early 2016 for USA
• The goal is to administer a local anesthetic to provide pulpal
anesthesia on teeth numbers 4 through 13 (#1.1 to 1.5 and 2.1 to 2.5)
• All planned FDA Phase 1, 2 & 3 Clinical Trials Completed in Fall 2013
Intranasal Local Anesthetic Mist
2015 DR. STANLEY F. MALAMED | ALL RIGHTS RESERVED |
KOVANAZE™ INVESTIGATIVE NEW DRUG
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122
KOVANAZE™
KOVANAZE™
3% Tetracaine
•Ester-type local anesthetic
•Commonly used by ENT surgeons
•Has ‘track record’ as safe & effective IN
Oxymetazoline
•Vasoconstrictor
•Active ingredient in ‘Afrin’ & other
nasal decongestants
CH3
H
N
HCl
N
H3C
H3C
CH3
CH3
OH
123
124
Maxillary anesthesia without injection
•Phase 2 Clinical Trial: 2009
•Dr. Sebastian Ciancio, SUNY Buffalo
•Nasal spray of local anesthetic
provides pulpal anesthesia to
maxillary anterior teeth
125
126
Injectable (lidocaine + epi)
PHASE 2 CLINICAL TRIAL
94% success
st
1 molar to 1 molar
st
3 % Tetracaine
Oxymetazoline
(active ingredient in Afrin nasal spray)
Sprayed into R & L nares
N=48
CH3
H
N
HCl
N
H3C
H3C
CH3
CH3
OH
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128
Kovanaze™ st
Whats’s New
in
Local Anesthesia
st
84% success - 1 molar to 1 molar
100% success - premolar to premolar
In the more distant future
Palate
16% failure on 1st molar
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130
Optical control of painsensing neurons. QAQ
selectively enters pain
sensing neurons and
silences their activity (top,
green light). Illumination
with violet light (bottom)
quickly restores signal
conduction
Light-activated / Light-inactivated
Local Anesthetic
© 2015© 2014
Dr. Dr.
Stanley
F. Malamed
Stanley F. Malamed
All Rights Reserved
© 2015 Dr.Reserved
Stanley F. Malamed
All Rights
© 2015© 2014
Dr. Dr.
Stanley
F. Malamed
Stanley F. Malamed
All Rights Reserved
© 2015 Dr.Reserved
Stanley F. Malamed
All Rights
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131
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132
A basic truism regarding ANATOMY:
Now for a
change of subject
Everybody is different
We teach ‘normal’ anatomy:
Insert the needle here
Advance 25 mms
Aspirate
Deposit the drug
We HOPE the nerve is in the area
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134
A basic truism regarding INJECTIONS:
Once a needle penetrates the
skin or mucous membrane,
every injection is
BLIND
A basic truism regarding LOCAL ANESTHETICS:
LAs are chemicals that interrupt
nerve conduction
(producing anesthesia)
transiently
(hopefully)
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136
Another truism regarding LOCAL ANESTHETICS
ALL LAs are neurotoxic
(they can damage nerves)
If all LAs were equally neurotoxic
the % of cases of paresthesia would be
equal to the drugs % market share
50% of market share = 50% of cases of paresthesia
25% of market share = 25% of cases of paresthesia
Ratio should be 1.0
% Cases of paresthesia
% Market share
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138
A basic truism regarding PARESTHESIA:
Just the Facts
Paresthesia has existed
ever since injections
were first administered
Articaine
and
Paresthesia
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140
Haas, D A. Lennon, D.
A 21 year retrospective study of reports of paresthesia
following local anesthetic administration.
J. Canadian Dental Association). 61(4):319-20, 323-6, 329-30, 1995
Overall incidence of paresthesia (all LAs) = 1:785,000
2% and 3% LAs = 1:1,250,000
4% prilocaine = 1:588,235
4% articaine = 1:440,529
Ontario, Canada
(0.000000227%) (2.2699e-06)
Mepivacaine
1:623,112,900
Lidocaine
1:181,076,673
Bupivacaine
1:124,286,050
OVERALL
1:13,800,970
Articaine
1:4,159,848
Prilocaine
1:2,070,678
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USA
(0.000000024%)
(2.403934e-07)
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142
% Cases of paresthesia
1.0
is
expected
% Market share
Pogrel MA
J. Calif Dent Assoc 40:795-797, 2012 (October)
2012
2007
2012
Lidocaine
0.64
0.5
Articaine
1.19
0.97
Mepivacaine
Prilocaine
2.2
4.96
3.25
M. Anthony Pogrel, DDS, MD
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144
Author
Country
Year
%
Lingual
Haas,
Lennon
Canada
1995
70.6
Hillerup
Denmark 2006
77
Kingon,
Australia 2011
Sambrook
80
Garristo,
Haas
USA
2010
So, why is it that the lingual nerve
is primarily involved in cases of
paresthesia?
92.7
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146
Professor Dr. Stanley F. Malamed
IMO . . . IF it’s the distribution of the lingual
nerve (loss of taste, paresthesia) . . .
“The Lingual Nerve
is In the Way”
It’s MECHANICAL
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147
Not chemical
148
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Paresthesia in dentistry
> 95% of reported cases occur in the MANDIBLE
Is rarely observed in the maxilla
< 5%
Of these the overwhelming percentage
involve only the lingual nerve
Yet 1/2 of all dental care is in the upper arch
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150
Paresthesia and 4% Anesthetics
Articaine is used in medicine:
Is rarely (no reported cases) observed following:
Gow-Gates mandibular nerve block
Ophthalmology
Vazirani-Akinosi mandibular nerve block
Orthopedic surgery
No lingual nerve in area
Arthroscopic, hand, foot
Only occasionally following mental/incisive nerve block
Plastic and reconstructive surgery
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152
Articaine in Mediocine
Local and Regional Anesthesia 2012:5 23–33
Articaine is used in medicine:
NO reports of paresthesia from
articaine following use in medicine
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154
Question:
Question:
Is it possible that articaine is so
specifically neurotoxic that it only
affects nerves within the mouth and
more specifically the lingual nerve?
Is it possible that articaine is so specifically
neurotoxic that it only affects nerves within the
mouth and more specifically the lingual nerve?
Answer:
NO !
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Benefit v. Risk
The doctor MUST always consider the BENEFIT to
be gained from use of a procedure or drug versus
the RISK involved in the procedure or drug.
So, what should YOU do?
ONLY when the benefit to be gained CLEARLY
OUTWEIGHS the risk should the procedure be
done or the drug administered
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158
ALL reports claiming an increased risk
of paresthesia with articaine are
ANECDOTAL
So, what should YOU do?
There is absolutely NO scientific
evidence articaine has a greater risk
of paresthesia than other LAs
Continue to use Articaine
by IANB block
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160
IF you are unconvinced:
Use Lidocaine or Mepivacaine for IANB
NOT Prilocaine
Follow Lidocaine IANB with Articaine buccal
infiltration
At apex of tooth being treated
½ cartridge
LOCAL ANESTHETICS:
Dentistry’s Most
Important Drugs
Los Angeles, California, USA
Saratoga Dental Congress
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162
malamed@usc.edu
Thank you for
listening . . .
All Rights Reserved
163
4th District Dental Society
All Rights Reserved

2015 Dr. Stanley F. Malamed - Fourth District Dental Society

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