1. LOCAL ANESTHESIA

3. Ester Local Anesthetics
Cocaine
Benzocaine
Procaine
Tetracaine
Chloroprocaine

4. Amide Local Anesthetics
Lidocaine
Mepivacaine
Prilocaine
Bupivacaine
Etidocaine
Articaine

6. Metabolism of Amide Local Anesthetics
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

7. Metabolism of Ester Local Anesthetics
Hydrolyzed by plasma cholinesterase
Factors which may lead to decreased plasma esterase activity
Liver dz—decreased protein synthesis
Pregnancy—decreased pseudocholinesterase activity
Atypical pseudocholinesterase

8. Excretion of Local Anesthetics
Active metabolites excreted by kidney
Severe renal disease may result in accumulation of active metabolites and produce toxicity

12. Local Anesthetics: pKa vs. Onset of Action
AGENT
pKa
ONSET (MIN)
Mepivacaine
7.7
2-4 min
Lidocaine
7.8
Articaine
Etidocaine
7.9
Prilocaine
Bupivacaine
8.1
5-8 min
Procaine
9.1
14-18 min

13. Local Anesthetics: Protein Binding vs. Duration
AGENT
RELATIVE PROTEIN BINDING
DURATION
Bupivacaine 95
LONG
Etidocaine 94
Mepivacaine 75
MODERATE
Lidocaine 65
Prilocaine 55
Procaine 5
SHORT

14. Manufacturers’ Recommended Dose
AGENT
ADULT DOSE
(mg/lb)
ABSOLUTE MAXIMUM
(mg)
Lidocaine
+Epinephrine 2 3
300
500
Mepivacaine+/- Vaso
400
Prilocaine +/- Epi
3.6
Articaine + Epi
3.2
Bupivacaine + Epi
0.6 90

15. Local Anesthetics: Adverse Effects
Central Nervous System
Cardiovascular System
Respiratory System
Local Toxicity (skeletal muscle)

16. Local Anesthetics: CNS Effects
Anticonvulsant Properties
Procaine, lidocaine, mepivacaine
Low dose; ug/ml
CNS depression; preconvulsant
4.5-7 ug/ml
CNS depression; tonic-clonic seizures
ug/ml
Generalized CNS depression
>10 ug/ml

17. Preconvulsant: Signs and Symptoms (4.5-7 ug/ml)
Slurred speech
Shivering
Muscular twitching
Tremor in muscles of face and distal extremities
SYMPTOMS
Numbness of tongue and circumoral region
Warm, flushed feeling of skin
Pleasant dream-like state
Generalized light-headedness
Dizziness
Visual and auditory disturbances
Disorientation

18. Local Anesthetics: PaCO2 vs. Convulsant Threshold (Cats)
AGENT
PaCO2
(25-40 torr)
(68-81 torr)
Procaine 35 17
Prilocaine 22 12
Mepivacaine 18 10
Lidocaine 15 7
Bupivacaine 5
2.5

19. Local Anesthetics: CV Effects
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

20. Local Anesthetics: Drug Interactions
Tricyclic antidepressants
Cocaine
Beta-adrenergic blocking agents
Phenothiazines
alpha blocking effect

21. Local Anesthetic Toxicity: Interaction w/ Opioids
Redrawn from Moore & Goodson, Anesth Prog 32:129 (1985)

22. Reversal of soft-tissue local anesthesia with phentolamine mesylate in adolescents and adults.Hersh E,et al. JADA; 139 August 2008;
Objective
To determine the efficacy of soft tissue reversal
Phentolamine mesylate
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
Methods
Four different locals with epi utilized
All injections resulted in soft tissue anesthesia to the lower/upper lip
244 subjects

23. Reversal of soft-tissue local anesthesia with phentolamine mesylate in adolescents and adults.Hersh E,et al. JADA; 139 August 2008;
Methods
Randomized to phentolamine or sham injection
Subjective analysis of numbness q 5 min and function testing (speech, drooling, etc)

24. Reversal of soft-tissue local anesthesia with phentolamine mesylate in adolescents and adults.Hersh E,et al. JADA; 139 August 2008;
Results
Tongue function
Phentolamine group; 60 min
Sham group; 125 minutes
Lower lip
Phentolamine group; 70 min
Sham group; 155 min
Upper lip
Phentolamine group; 50 min
Sham group; 133 min
Vital sign changes and adverse events
Not significant between the two groups

25. Reversal of soft-tissue local anesthesia with phentolamine mesylate in adolescents and adults.Hersh E,et al. JADA; 139 August 2008;
Conclusions
“...safe and efficacious in reducing the duration of soft tissue anesthesia and function”
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

26. ANALYSIS OF N2O/O2 SEDATION

27. N2O/O2 ADVANTAGES… Analgesia: variable Sedation Amnestic Rapid Onset
20% = 15mg morphine
Sedation
Calm, relaxed, and tolerant
Amnestic
Passage of time becomes unclear
Rapid Onset
Clinical effects < 30 seconds, peak effects < 5 minutes

28. N2O/O2 ADVANTAGES… Titration Recovery In combination
Sedation depth is easily controlled
Recovery
Complete recovery in < 3-5 minutes
In combination
Sophrology, distraction techniques, premedication, local anesthesia

29. DISADVANTAGES N2O/O2… Weak anesthetic Air space expansion
MAC %
Air space expansion
N2O is 35 times as soluble as N2
Diffusion hypoxia
HA, N/V, and lethargy
Need for cooperative patient

30. Contraindications to N2O/O2 sedation…
Absolute
Respiratory tract infection
Craniofacial deformity
Relative
Severe emotional and behavior problems
Clinically significant COPD
Pregnancy
Drugs: potentiating effects of N2O/O2

31. Properties of N2O… Manufacturing NH4NO3  N2O + 2H2O 99.5-99.9% pure
Major contaminant is nitrogen
Sweet smelling and nonflammable
Will support combustion in the proper concentration

32. Properties of N2O… Stored as a liquefied compressed gas
Full cylinder = 95% liquid, 5% vapor
35 times more soluble than N2
Stable, does not react with soda lime, anesthetic drugs, or metal anesthesia equipment

33. PHARMACOLOGY OF NITROUS OXIDE

34. Pharmacokinetics N2O… Relatively insoluble in blood N2O replaces N2
Quick onset
N2O replaces N2
35 times more soluble than N2
Rigid body spaces—increase pressure
Non-rigid spaces—increase volume

35. Pharmacokinetics N2O… Tissue concentrations
Gas solubility
Blood flow to tissue
Conc. of gas in arterial blood
Factors for elimination of N2O
Same as uptake factors
Diffusion hypoxia
Metabolism
N2O not metabolized
99% eliminated through lungs

36. Central Nervous System…
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

37. Hematopoietic System…
Megaloblastic bone marrow changes: primarily seen with abuse cases

38. Drug Reactions/Interactions
No reported allergies to N2O in 150 years of use
Drug interaction: no direct interactions reported, but may enhance other CNS depressants

39. OCCUPATIONAL EXPOSURE

40. History of Controversial Literature…
Vaisman 1967
Cohen et al 1970
Bruce, Bach, and Arbit 1970
OSHA standards
Clark 1995

41. Specific Biologic Issues and Health Concerns

42. Biochemical and Metabolic …
Inactivation of Vit. B12
Enzyme Systems Blocked
Methionine synthase
Methylmalonyl-CoA mutase
Leucine 2,3-aminomutase
Studies and clinical significance

43. Health Concerns… Nunn et al
Deoxyuridine Supression Test—detects early signs of inactivation of the enzyme methionine synthase
No alteration if this enzyme occurred in anesthetists exposed to between ppm

44. Health Concerns…
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.

45. Health Concerns… Abuse: chronic—MS like symptoms and myloneuropathies
Paresthesia of extremities
Loss of dexterity
Loss of balance
Muscle weakness in legs
Gait ataxia
Impotence

46. 3,187 patients scheduled for GA for abdominal procedure
Avoidance of Nitrous Oxide for Patients Undergoing Major Surgery. A Randomized Controlled Trial Myles P, Leslie K et al Anesth. 2007; 107:221-31
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
End-points included: N/V, complications, arousal, quality of recovery, etc

47. Avoidance of Nitrous Oxide for Patients Undergoing Major Surgery
Avoidance of Nitrous Oxide for Patients Undergoing Major Surgery. A Randomized Controlled Trial Myles P, Leslie K et al Anesth. 2007; 107:221-31
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
Conclusions
Avoidance of nitrous oxide and concomitant increase in oxygen decreased the incidence of complications after major surgery

48. CONTROL OF OCCUPATIONAL EXPOSURE

49. Detection and Monitoring
Establish base-line and monitor exposure
Limit legal liability
Techniques of monitoring
Infrared spectrophotometry
Time-weighted average dosimetry

50. Dosimetry Devices

51. ADA Recommendations… 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

52. Sexual Phenomena with N2O…
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