Principles of Anesthetics Bucky Boaz, ARNP-C

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

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

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

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”

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

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

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

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

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

Topical Anesthesia

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

Agents Lidocaine Cream EMLA Ethyl Chloride

Uses Intact skin procedures Venopuncture Punch biopsies Lumbar puncture

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

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

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

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

Agents Tetracaine Lidocaine Cocaine Benzocaine

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

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

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

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

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

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

Ophthalmic Anesthetics

Agents Proparacaine Tetracaine

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

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

Lacerations

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

TAC Advantages Disadvantages Painless No Distortion Hemostasis Acceptance Minimum of 10-20 minute onset Cost Federal regulations

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

Application Fill wound with TAC solution After 3 minutes, instill saturated gauze or cotton into wound Leave in place 15-20 minutes SAFE dose maximum Full strength TAC 0.09 ml/kg Tetracaine 50mg, cocaine 150-300mg

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

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

Infiltration Anesthesia Injection of anesthetic agent directly into tissue

Indications Excision of skin lesions Incision of abscess Suturing of wounds

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

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

Choice of Agent Agent Maximum Dose Onset (min) Duration Adult (mg) Concentration (%) Maximum Dose Onset (min) Duration Adult (mg) Pediatric (mg/kg) Procaine 0.5-1.0 500 (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

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

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.

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.

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

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

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

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. 1995.

Complications Effects on wounds Systemic toxic reactions Catecholamine reaction Allergic reactions

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

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

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%

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

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

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

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

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

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

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

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%

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.

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.

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. 1993 ;22(9): 1419-1423.

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

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

Questions?