1. Principles of Anesthetics
Bucky Boaz, ARNP-C

2. Background Carl Koller 1884 Freud colleague Eye surgery
Carl Koller first introduced Cocaine as an anesthetic into clinical practice in 1884
He practiced medicine during the late 1800s and was a colleague of Sigmond Freud
He was an opthomologist and used cocaine for topical anesthesia in the eye

3. Background William Halsted 1885 Local injection of cocaine for surgery
Nerve block
In 1885 William Halstead demonstrated that cocaine could be used to block nerve transmission and laid the foundation for nerve block anesthesia

4. Background 1905 1884 Einhorn and Braun – Procaine Hall – Dentistry
1930
Chlorprocaine
1941
Nils Lofgren
Synthesized Xylocaine
Changed to lidocaine
1884
Hall – Dentistry
Zenfel – Ear
1890
Ritsert – Benzocaine
In 1884, Hall introduced cocaine into dentistry
Zenfel introduced a topical solution of alcohol and cocaine to anesthetize the ear drum.
In 1890, Ritsert introduced Benzocaine
In 1905, Einhorn and Braun introduced Procaine
In 1930, Chlorprocaine was introduced
In 1941, Nils Lofgren synthesized Xylocaine which was later changed into lidocaine

5. Physiochemical Properties
Aromatic
Segment
Hydrophilic
Segment
Intermediate
Chain
Amino-ester
Amino-amine
The linkage between the Aromatic and Hydrophilic segments is either an Amino-ester or an Amino-amine
These two chemical structures form the basis for the two main classifications of local anesthetics: Esters and Amines
The main difference between esters and amines is their metabolic pathways.
Esters are hydrolyzed by plasma pseudocholinsterase, whereas amides are metabolized by the liver through enzymatic degredation
Within the ester or amide groups, alterations in chemical structure to either the aromatic or the hydrophilic portion may affect the rate of metabolism and create a different activity profile for each agent within a given group
“Esters”
“Amines”

6. Physiochemical Properties
Amino-esters (“Esters”)
Older class of drugs
Derivatives of PABA (p-aminobenzoic acid)
Hydrolyzed by serum cholinesterase
Examples
Procaine (Novocaine)
Cocaine
Tetracaine
Benzocaine

7. Physiochemical Properties
Amino-amines (“Amines”)
Newer class of drugs
Derivatives of aniline
Hepatic degradation
Examples
Lidocaine
Bupivocaine (Marcaine, Sensoricaine, Polocaine)
Mepivocaine (Carbocaine)
Etidocaine
Prilocaine

8. Physiologic Basis
Prevention of sodium influx across the nerve membrane
Sufficient anesthetic present prevents firing threshold from being obtained
Prevents action potential from forming
No action potential, no impulse, therefore conduction blockade
End result is local anesthesia

9. Mode of administration Presence of vasoconstrictor
Mechanism of Action
Protein binding
Vasodilatation
Mode of administration
Presence of vasoconstrictor
Lipid solubility
Vasodilatation
Tissue pH
Concentration of drug
Duration
Potency
Onset
Inherent pKa
Myelination
Interspersed tissue
Dosage of drug

10. Ideal Anesthetic Immediate onset Reversible Appropriate duration
No permanent damage
No tissue irritation / pain
Wide therapeutic range
Effective regardless of application

11. Topical Anesthesia

12. Intact Skin Epidermis Dermis Avascular layer measuring 0.12 to 0.7 mm
Barrier to diffusion of topicals
Dermis
Support structure
Contains blood vessels and nerve endings
Anesthetic’s targeted site of action

13. Agents
Lidocaine Cream
EMLA
Ethyl Chloride

14. Uses Intact skin procedures Venopuncture Punch biopsies
Lumbar puncture

15. Lidocaine Cream 30% lidocaine cream
Saturated on gauze pad adherent to an elastic patch
45 minutes minimum application time
½ hour anesthetic duration = 2 hour application
Effective and safe, but not practical

16. EMLA (Eutectic Mixture of Local Anesthetics)
2.5% lidocaine and 2.5% prilocaine
1-hour application time
Maximum dose at 2-3 hours
Depth of anesthesia correlated to duration of application
Duration of 1-2 hours after removal
Hypersensitivity and systemic toxicity rare

17. Ethyl Chloride (C2H5CL) Not an anesthetic, but a vapocoolant
Immediate anesthesia, but limited duration
Spray for 3 to 7 seconds
Used for injections and lancing small abscesses or boils
Not used for punch biopsies

18. Mucous Membranes
Nose, mouth, throat, tracheobronchial tree, esophagus, and genitourinary tract

19. Agents
Tetracaine
Lidocaine
Cocaine
Benzocaine

20. Tetracaine Effective and potent agent Long duration of action
Downside = high toxicity
Maximum adult dose of 50mg

21. Lidocaine 2% solution 5% liquid 5% ointment
Swished inside the mouth then expectorated
5% liquid
Applied with a swab
5% ointment
Applied with a sterile gauze pad

22. Lidocaine
Indicated for painful, irritated, or inflamed mucous membranes of the mouth
2% good for aph-thous stomatitis and as adjunct before infraoral nerve block
5% ointment good for reducing pain during oral injection

23. Lidocaine Precautions Impaired swallowing Numbness of the tongue
Expectorate excess to avoid toxicity

24. Cocaine
Topical preparations available in 4% and 10% solutions and viscous formulations
Safe dose of 200mg (2 to 3 mg/kg)
Apply for 5-6 minutes
Works by vasoconstriction
Coronary vasoconstriction with 2mg/kg applied to the nasal mucosa

25. Benzocaine Available in 14% to 20% liquid, gel, or spray
Used to relieve pain in canker sores, cold sores, other minor inflammation
Very short duration and more allergenic
Can be used prior to infraoral nerve block

26. Ophthalmic Anesthetics

27. Agents
Proparacaine
Tetracaine

28. Proparacaine 0.5% solution
Indicated for removal of superficial foreign body
1 to 2 drops before procedure
Onset within 30 seconds
Duration 15 minutes
Have patient avoid touching eye

29. Tetracaine
0.5% solution
Onset, duration, and potency similar to proparacaine
Burning sensation worse and longer

30. Lacerations

31. TAC TAC (tetracaine-adrenalin-cocaine)
Used to anesthetize lacerations in children
Wounds < 5cm
Vasoconstrictor
More effective on face and scalp

32. TAC Advantages Disadvantages Painless No Distortion Hemostasis
Acceptance
Minimum of minute onset
Cost
Federal regulations

33. Agents and Effectiveness
0.5% tetracaine, 1:2000 epinephrine (adrenalin), and 11.8% cocaine
Epinephrine 1:2000, cocaine 11.8%
Tetracaine 0.25%, epi 1:4000, cocaine 5.9%
Tetracaine 1.0%, epi 1:4000, cocaine 4%
Lidocaine 4.0%, epi 1:1000, tetracaine 0.5%
Gel by adding 0.15g methylcellulose to 1.5ml of epi and cocaine solution

34. Application Fill wound with TAC solution
After 3 minutes, instill saturated gauze or cotton into wound
Leave in place minutes
SAFE dose maximum
Full strength TAC 0.09 ml/kg
Tetracaine 50mg, cocaine mg

35. Adverse Reactions
Can lead to systemic toxicity from mucosal application
Gel form reduces runoff
Ischemic complications

36. Precautions Avoid in: CAD Uncontrolled HTN Seizures PVD
Risk of Toxicity

37. Infiltration Anesthesia
Injection of anesthetic agent directly into tissue

38. Indications Excision of skin lesions Incision of abscess
Suturing of wounds

39. Advantages & Disadvantages
Quick and safe
Provides hemostasis
Disadvantages
Large dose for small area
Distorts wounds

40. Choice of Agent Lidocaine 0.5 to 1.0% Procaine 0.5% to 1.0%
Bupivacaine 0.25%

41. Choice of Agent Agent Maximum Dose Onset (min) Duration Adult (mg)
Concentration (%)
Maximum Dose
Onset (min)
Duration
Adult (mg)
Pediatric (mg/kg)
Procaine
500 (600)
7.0 (9)
2-5
15-45 min
Lidocaine
300 (500)
4.5 (7)
1-2 hr
Bupivacaine
0.25
175 (225)
2.0 (3)
4-8 hr

42. Choice of Agent Prolong duration by adding: Epinephrine
Sodium bicarbonate
Both
Use bupivicaine

43. Epinephrine Use Advantages Disadvantages 1. Prolongs duration
1. Impairs host defenses--increases infection *
2. Provides hemostasis
2. Delays wound healing *
3. Slows absorption:   Decreases agent toxicity potential   Allows increased dose
3. Do not use for:   Areas supplied by end arteries   Patients"sensitive" to catecholamines
4. Increases level of blockade
4. Toxicity--catecholamine reaction     
* Based on laboratory studies.    For example, in patients taking MAO inhibitors.

44. Injection Technique Bicarbonate Reduces pain of injection
Mechanism unclear
1 cc 8.4 % bicarb : 9 cc lidocaine
“Neut” 4.2 % bicarb (1cc:4cc)
Precipitates in bupivicaine
Shelf life : 1 wk (unref), 2 wks (refr)
Bartfield JM, et al: Buffered lidocaine as a local anesthetic: An investigation of shelf life. Ann Emerg Med 21:24, 1992.

45. Less cardiotoxic; equal CNS More cardiotoxic; equal CNS
Comparison of 1% Lidocaine (L) and 0.25% Bupivacaine (B)--Infiltration Anesthesia
Lidocaine
Bupivacaine
Advantage
Onset
2-5 min
Equal
Effectiveness (equianesthetic dose)
Excellent
Duration
1-2 hr
4-6 hr B
Infection potential No
Administration pain
Less
More L
Maximum volume --plain lidocaine
Maximum volume--epinephrine
Toxic potential
Less cardiotoxic; equal CNS
More cardiotoxic; equal CNS

46. Injection Technique Lowest concentration effective
Prep wound first if possible
Smallest needle available (27g)
Use wound margin
Subdermal injection
Insert, then inject

47. Injection Injection should be subdermal
Bury the hub and inject as you withdraw
Through wound edge

48. Injection Technique Warming No change in efficacy
Less pain of injection
Probably synergistic with buffering
Brogan GX, et al: Comparison of plain, warmed and buffered lidocaine in wound repair. Ann Emerg Med; Aug

49. Complications Effects on wounds Systemic toxic reactions
Catecholamine reaction
Allergic reactions

50. Effect on Wounds Wound healing Wound infection Local injuries
Wound strength
Avoid in poor healing wounds
Help prevent keloids
Wound infection
Local injuries

51. Systemic Toxic Reaction
High Blood Levels
Site and mode of administration
Rate
Dose of Concentration
Addition of epinephrine
Specific drug
Clearance
Maximum safe dose
Inadvertent intravascular injection

52. Maximum Dosage - Lido Without epi With epi 4.5 mg/kg 7 mg/kg
30 cc (1 ½ bottles) of 1 %
15 cc (3/4 bottle) of 2 %
With epi
7 mg/kg
70 kg = 500 mg
50 cc (2 ½ bottles) of 1%
25 cc (1 ¼ bottles) of 2%

53. Lidocaine Dosage administered Packaging (% = g / dl) 1 % 20 cc 2 %
4 %
20 cc
1 g/dl = 1000mg/100cc = 10 mg/cc
200 mg/bottle
2 g/dl = 2000mg/100cc = 20 mg/cc
400 mg/bottle
4 g/dl = 4000mg/100cc = 40 mg/cc
800 mg/bottle

54. Systemic Toxic Reaction
Host Factors
Hypoxia
Acid-base status
Protein binding
Concomitant drugs

55. Catecholamine Reaction
Excess levels produce:
Tachycardia
Palpitations
Hypertension
Apprehension
Tremulousness
Diaphoresis
Tachypnea
Pallor
Anginal chest pain

56. Adverse Effects - Systemic
“But I’m allergic to the numbing medicine”
Great, now what?

57. Adverse Effects - Systemic
Allergic reactions
1 – 2 % of total adverse reactions
Esters
Large majority
PABA
Amides
Rare
methlyparaben

58. Allergic Reactions Fisher,et al Anesthetic allergy clinic
208 patients with “allergy” to local anesthetic over 20 year period
Intradermal testing
4 immed, 4 delayed
39 to “additives”
Fisher MM, Bowie CJ Alleged Allergy to Local Anesthetics Anaesth Intensive care 1997 Dec;25(6):611-4

59. Allergic Reactions Recommendations 1. Define allergy vs. adverse rxn
2. Alternate class of anesthetics
3. Cardiac lidocaine
4. Test dose (0.1 cc SQ)
5. Diphenhydramine

60. Allergic Reactions Diphenhydramine Supplied as 5% solution (50 mg/cc)
Tissue necrosis
Must be diluted in NS
1 cc / 4 cc NS = 50 mg / 5 cc = 1 %
1 cc / 9 cc NS = 50 mg / 10 cc = 0.5%

61. Allergic Reactions Diphenhydramine 24 volunteers
DPH 1% as effective as Lido 1%
Injection more painful
Safety profile not well established
Green SM, Rothrock SG, et al: Validation of diphenhydramine as a local anesthetic. Ann Emerg Med; June, 1994.

62. Allergic Reactions Diphenhydramine 98 patients
DPH 0.5 % vs. lidocaine 1 %
No difference in pain of injection or efficacy, except face
Ernest AA, et al. Lidocaine vs. diphenhydramine for laceration repair . Ann Emerg Med; Jun, 1994.

63. Allergic Reactions Diphenhydramine Conclusions Dbl blinded
2 cc of Lido 1 % vs. DPH 1 %
10 adult volunteers - pinprick
Conclusions
No differences to 30 minutes, Lido better after 30 min
Duration Lido (81 min) vs. DPH (42 min)
1/10 developed skin necrosis
Dire DJ. Double blinded comparison of lidocaine vs. diphenhydramine as a local anesthetic. Ann Emerg Med ;22(9):

64. Allergic Reactions Recommendations 6. Normal saline 7. No anesthesia
8. Parenteral agents
9. General anesthesia
10. Nitrous oxide
11. Benzyl alcohol

65. Points to Remember Esters and Amines Factors affecting MOA
Types of anesthetics
How applied
Risks and Benefits
Contraindications
Adverse reactions

66. Questions?