Transcript Local and Nitrous Review

LOCAL ANESTHESIA
Ester Local Anesthetics
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Cocaine
Benzocaine
Procaine
Tetracaine
Chloroprocaine
Amide Local Anesthetics
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Lidocaine
Mepivacaine
Prilocaine
Bupivacaine
Etidocaine
Articaine
Metabolism of Amide
Local Anesthetics
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Biotransformation by hepatic microsomal
enzyme system
Drugs may increase metabolism via
enzyme induction
Liver disease may decrease metabolism
via decreased functional tissue
Decreased metabolism secondary to
decreased hepatic blood flow
Metabolism of Ester Local
Anesthetics
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Hydrolyzed by plasma cholinesterase
Factors which may lead to
decreased plasma esterase activity
– Liver dz—decreased protein synthesis
– Pregnancy—decreased
pseudocholinesterase activity
– Atypical pseudocholinesterase
Excretion of Local
Anesthetics
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Active metabolites excreted by
kidney
Severe renal disease may result in
accumulation of active metabolites
and produce toxicity
Local Anesthetics: pKa vs.
Onset of Action
AGENT
Mepivacaine
Lidocaine
Articaine
Etidocaine
Prilocaine
Bupivacaine
Procaine
pKa
7.7
7.8
7.8
7.9
7.9
8.1
9.1
ONSET (MIN)
2-4 min
2-4 min
2-4 min
2-4 min
2-4 min
5-8 min
14-18 min
Local Anesthetics: Protein
Binding vs. Duration
Bupivacaine
RELATIVE
PROTEIN
BINDING
95
Etidocaine
94
LONG
Mepivacaine
75
MODERATE
Lidocaine
65
MODERATE
Prilocaine
55
MODERATE
Procaine
5
SHORT
AGENT
DURATION
LONG
Manufacturers’
Recommended Dose
AGENT
Lidocaine
+Epinephrine
Mepivacaine+/- Vaso
Prilocaine +/- Epi
Articaine + Epi
Bupivacaine + Epi
ADULT ABSOLUTE
DOSE MAXIMUM
(mg/lb)
(mg)
2
300
3
500
3
400
3.6
400
3.2
500
0.6
90
Local Anesthetics:
Adverse Effects
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Central Nervous System
Cardiovascular System
Respiratory System
Local Toxicity (skeletal muscle)
Local Anesthetics:
CNS Effects
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Anticonvulsant Properties
– Procaine, lidocaine, mepivacaine
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Low dose; 1-4.5 ug/ml
CNS depression; preconvulsant
– 4.5-7 ug/ml
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CNS depression; tonic-clonic seizures
– 7.5-10 ug/ml
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Generalized CNS depression
– >10 ug/ml
Preconvulsant: Signs and
Symptoms (4.5-7 ug/ml)
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SIGNS
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Slurred speech
Shivering
Muscular twitching
Tremor in muscles of
face and distal
extremities
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SYMPTOMS
– Numbness of tongue
and circumoral region
– Warm, flushed feeling
of skin
– Pleasant dream-like
state
– Generalized lightheadedness
– Dizziness
– Visual and auditory
disturbances
– Disorientation
Local Anesthetics: PaCO2 vs.
Convulsant Threshold
(Cats)
AGENT
Procaine
PaCO2
(25-40 torr)
35
PaCO2
(68-81 torr)
17
Prilocaine
22
12
Mepivacaine
18
10
Lidocaine
15
7
Bupivacaine
5
2.5
Local Anesthetics:
CV Effects
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Decreased electrical excitability,
conduction rate and force of myocardial
contraction (1.8-5 ug/ml)
– .5-2 ug/ml—normal blood level following
intraoral injection (no CV effects)
– 5-10 ug/ml—myocardial depression and
peripheral vasodilation
– >10 ug/ml—massive peripheral vasodilation,
intensive myocardial depression, arrest
Local Anesthetics:
Drug Interactions
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Tricyclic antidepressants
Cocaine
Beta-adrenergic blocking agents
Phenothiazines
– alpha blocking effect
Local Anesthetic Toxicity: Interaction w/
Opioids
4
Opio id Dose (Multip le sofMRD)
3
Re c o v e ry
Bra in Da m
age/
De a th
2
1
Redrawn from Moore & Goodson,
Anesth Prog 32:129 (1985)
0
0
1
2
3
L o c a lAn e s
th e tic Do s
e (Mu ltip le s
o fMRD)
4
Reversal of soft-tissue local anesthesia
with phentolamine mesylate in adolescents
and adults.Hersh E,et al. JADA; 139 August 2008; 1080-1093
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Objective
– To determine the efficacy of soft tissue
reversal
– Phentolamine mesylate
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Non-selective alpha-adrenergic blocking agent used
for the treatment of HTN associated with pheo.
– 1.7 ml carpule with 0.4 mg phentolamine mesylate
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Methods
– Four different locals with epi utilized
– All injections resulted in soft tissue
anesthesia to the lower/upper lip
– 244 subjects
Reversal of soft-tissue local anesthesia
with phentolamine mesylate in adolescents
and adults.Hersh E,et al. JADA; 139 August 2008; 1080-1093
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Methods
– Randomized to phentolamine or sham
injection
– Subjective analysis of numbness q 5
min and function testing (speech,
drooling, etc)
Reversal of soft-tissue local anesthesia
with phentolamine mesylate in adolescents
and adults.Hersh E,et al. JADA; 139 August 2008; 1080-1093
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Results
– Tongue function
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Phentolamine group; 60 min
Sham group; 125 minutes
– Lower lip
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Phentolamine group; 70 min
Sham group; 155 min
– Upper lip
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Phentolamine group; 50 min
Sham group; 133 min
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Not significant between the two groups
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– Vital sign changes and adverse events
Reversal of soft-tissue local anesthesia
with phentolamine mesylate in adolescents
and adults.Hersh E,et al. JADA; 139 August 2008; 1080-1093
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Conclusions
– “...safe and efficacious in reducing the
duration of soft tissue anesthesia and
function”
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Studies have also found the drug to be
safe and efficacious in children 6-12
– Children 4-6 were not included secondary to
poor historians in determining level of soft
tissue anesthesia, but the drug was found to be
safe with no adverse events
ANALYSIS
OF
N2O/O2 SEDATION
N2O/O2 ADVANTAGES…
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Analgesia: variable
– 20% = 15mg morphine
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Sedation
– Calm, relaxed, and tolerant
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Amnestic
– Passage of time becomes unclear
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Rapid Onset
– Clinical effects < 30 seconds, peak effects < 5
minutes
N2O/O2 ADVANTAGES…
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Titration
– Sedation depth is easily controlled
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Recovery
– Complete recovery in < 3-5 minutes
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In combination
– Sophrology, distraction techniques,
premedication, local anesthesia
DISADVANTAGES
N2O/O2…
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Weak anesthetic
– MAC 104-105%
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Air space expansion
– N2O is 35 times as soluble as N2
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Diffusion hypoxia
– HA, N/V, and lethargy
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Need for cooperative patient
Contraindications to
N2O/O2 sedation…
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Absolute
– Respiratory tract infection
– Craniofacial deformity
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Relative
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Severe emotional and behavior problems
Clinically significant COPD
Pregnancy
Drugs: potentiating effects of N2O/O2
Properties of N2O…
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Manufacturing
– NH4NO3  N2O + 2H2O
99.5-99.9% pure
– Major contaminant is nitrogen
– Sweet smelling and nonflammable
– Will support combustion in the proper
concentration
Properties of N2O…
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Stored as a liquefied compressed
gas
– Full cylinder = 95% liquid, 5% vapor
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35 times more soluble than N2
Stable, does not react with soda
lime, anesthetic drugs, or metal
anesthesia equipment
PHARMACOLOGY
OF
NITROUS OXIDE
Pharmacokinetics N2O…
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Relatively insoluble in blood
– Quick onset
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N2O replaces N2
– 35 times more soluble than N2
– Rigid body spaces—increase pressure
– Non-rigid spaces—increase volume
Pharmacokinetics N2O…
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Tissue concentrations
– Gas solubility
– Blood flow to tissue
– Conc. of gas in arterial blood
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Factors for elimination of N2O
– Same as uptake factors
– Diffusion hypoxia
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Metabolism
– N2O not metabolized
– 99% eliminated through lungs
Central Nervous System…
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Mechanism of action: unknown
Cerebral cortex: depression of all
forms of sensation. Memory and
concentration minimally affected
Cerebellar functions: ataxia and
uncoordinated movements, nystagmus
Chronic exposure
Pneumocephalus
Hematopoietic System…
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Megaloblastic bone marrow changes:
primarily seen with abuse cases
Drug
Reactions/Interactions
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No reported allergies to N2O in 150
years of use
Drug interaction: no direct
interactions reported, but may
enhance other CNS depressants
OCCUPATIONAL
EXPOSURE
History of Controversial
Literature…
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Vaisman 1967
Cohen et al 1970
Bruce, Bach, and Arbit 1970
– OSHA standards
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Clark 1995
Specific Biologic Issues and
Health Concerns
Biochemical and Metabolic
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Inactivation of Vit. B12
– Enzyme Systems Blocked
Methionine synthase
 Methylmalonyl-CoA mutase
 Leucine 2,3-aminomutase
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– Studies and clinical significance
Health Concerns…
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Nunn et al
– Deoxyuridine Supression Test—detects
early signs of inactivation of the
enzyme methionine synthase
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No alteration if this enzyme occurred in
anesthetists exposed to between 150-400
ppm
Health Concerns…
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Because of the demands for folic
acid during organogenesis (first
trimester) postponement of N2O
sedation is recommended.
Pregnant females employed in a
setting using N2O– important to
know the exposure levels of N2O
– Safe use of scavenging systems.
Health Concerns…
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Abuse: chronic—MS like symptoms and
myloneuropathies
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Paresthesia of extremities
Loss of dexterity
Loss of balance
Muscle weakness in legs
Gait ataxia
Impotence
Avoidance of Nitrous Oxide for Patients
Undergoing Major Surgery.
A Randomized Controlled Trial
Myles P, Leslie K et al Anesth. 2007; 107:221-31
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3,187 patients scheduled for GA for
abdominal procedure
– One group received 70% nitrous and
30% oxygen with anesthetic
– One group received 80% oxygen and
20% nitrogen with anesthetic
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End-points included: N/V,
complications, arousal, quality of
recovery, etc
Avoidance of Nitrous Oxide for Patients
Undergoing Major Surgery.
A Randomized Controlled Trial
Myles P, Leslie K et al Anesth. 2007; 107:221-31
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Results
– Nitrous group had a lower incidence of major
complications and N/V
– No difference in length of hospital stay
– Shorter time spent in ICU
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Conclusions
– Avoidance of nitrous oxide and concomitant
increase in oxygen decreased the incidence of
complications after major surgery
CONTROL OF
OCCUPATIONAL
EXPOSURE
Detection and Monitoring
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Establish base-line and monitor
exposure
Limit legal liability
Techniques of monitoring
– Infrared spectrophotometry
– Time-weighted average dosimetry
Dosimetry Devices
ADA Recommendations…
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Monitor office with N2O analyzer
Use scavenging mask
Vent gases outside of building
Minimize patient conversation
Test equipment for leaks monthly
Employ air sweep ventilation
Achieve levels of < 50ppm
Sexual Phenomena with
N2O…
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Euphoric effects associated with N2O:
hallucinations, visualizations, auditory
illusions, and sexual stimulation
Legal and personal consequences
Common sense approach to N2O
administration
– Concentration < 50%,
– 3rd person,
– No suggestive language