Test Review: Anesthesia

1. Test Review: Anesthesia Jenifer Sweet, B.A., S.R.S., L.A.T. MPI Research in coordination with The Academy of Surgical Research Testing Committee

2. Overview • General Anesthesia • Definition • Stages of Anesthesia • Considerations • Pharmacokinetics • Method of action • Modifying factors • Types of Anesthesia • Pre-anesthetic Agents and Adjuncts • Injectable Anesthetic Agents and Adjuncts • Inhalation Anesthesia • Local and Regional Anesthesia • Physical Methods of Anesthesia • Equipment • Review

3. General Anesthesia • What is general anesthesia? • Doses based on “average” animal • Biological variations • Metabolic rate • % fat • General health • Sex • Genetics • Time of day • Species • Individualized sensitivity • The perfect anesthetic agent does not exist

4. Stages of Anesthesia 4 Stages of Anesthesia • Stage I: “The stage of voluntary movement” • Initial administration of anesthetic to the loss of consciousness • Tachycardia and hypertension • Irregular / increased respiration • Breath holding • Pupils dilate • Struggling as animal becomes ataxic • Some analgesic effects • Stage II: “The stage of delirium or involuntary movement” • CNS depression • Loss of voluntary control • Exaggerated reflexes • Struggling, breath holding, tachypnea, hyperventilation • Cardiac arrhythmias may occur • Eyelash and palpebral reflexes present • Vocalization • Salivation • Laryngeal spasm

5. Stages of Anesthesia • Stage III: “Stage of Surgical Anesthesia” • Pulse rate returns to normal • Muscles relax • Swallowing and vomiting reflexes lost • 3-4 planes • Plane I: • Eyeball movement ceases • Normal BP with strong pulse • Decrease of respiratory rate and depth • Pupils less dilated • Eyeball may rotate • Palpebral reflex present • Slight reaction to surgical manipulation • Loses jaw tone • Plane II: • Surgical Anesthesia • Bradycardia • Hypotension • Capillary refill slows • Palpebral reflex diminishes and disappears • Eyeball rotates ventrally • Abdominal muscle tone lost • Minimal jaw tone • Pedal reflex absent • Dysrhythmia possibility low

6. Stages of Anesthesia • Stage III (cont): “Stage of Surgical Anesthesia” • Plane III: • Deep surgical anesthesia • Intercostal and abdominal muscle tone minimum • Weak corneal reflexes • Diaphragmatic breathing • Profound muscle relaxation • Centered and dilated pupils • Bradycardia intensifies • Hypotension increases • Respiratory rate and depth decrease • Plane IV: • Deep/ Overdose • Dysrhythmia probability • Respirations slow and irregular • Lowered HR • Cyanosis • Widely dilated pupil and unresponsive to light • Flaccid muscle tone • Jaw tone lost • Sphincter control lost

7. Pharmacokinetics • Action of anesthetic on CNS • Partial pressure gradients • Inhalants vs. Injectables • Distribution and clearance • Modifying factors • Concentration • Plasma pH • Protein binding • Hydration • Multiple drugs present

8. Effects of Disease • Cardiovascular dysfunction • Most anesthetics cause CV depression • Animals prone to fluid overload & arrhythmias • Pulmonary dysfunction • Most anesthetics cause pulmonary depression • Balancing between lowering doses and preventing anxiety • Intubation and ventilation are key • Nitrous oxide contraindicated • Neurologic disease • Loss of ICF and CBF regulation • Watch for respiratory depression • Nitrous oxide contraindicated • Renal disease • Stress and anesthetic agents decrease rate of filtration • Reduction in elimination = increase in acidity and plasma concentrations • Lingering effects • K+ increases in serum

9. Effects of Disease • Hepatic disease • Acepromazine, thiobarbiturates and α-2-adrenergic agents contraindicated • Propofol, ketamine and inhalation the safest • Lowered elimination rate and coagulation • Gastrointestinal disease • Damaged GI can release toxins • Decrease in cardiac function and ventilation • Endocrine disorders • Select anesthesia for easiest reversibility

10. Pre-anesthetic Agents and Adjuncts • Anticholinergics • Tranquilizers • Opioids • Alpha2adrenergic agonists • Alpha2adrenergic antagonists • Tranquilizer-opioid combinations • Paralytic agents

11. Anticholinergics • Block acetylcholine receptors • Reduce secretions • Prevent vagal inhibition and GI stimulation • Reduce vagus nerve response (vomiting and laryngospasm) • Promote bronchodilation • Dilate the pupil • Treatment of choice for opioid, xylazine and vagal reflex activity induced bradycardia

12. Anticholinergics • Atropine Sulfate • Contraindicated with tachycardia, constipation and obstruction • May cause thick mucus secretions in cats • Atropine esterase occurs in cats, rats, and rabbits • Minimally effective in sheep and goats • Increased incidence of bloat • Prolongs thiopental anesthesia • Overdose: dry mucous membranes, thirst, dilated pupils and tachycardia (dogs most susceptible) • Can be treated with physostigmine IV over several minutes • Glycopyrrolate • Reduces diffusion over blood brain or placental membranes • Lasts longer than atropine • Prevents ketamine/xylazine associated bradycardia in rabbits • Longer onset of action in ruminants

13. Tranquilizers • NO ANALGESIC EFFECTS • Relieve anxiety • Decrease anesthetic dosages • Reduce histamine release and vomiting • Make anesthetic recovery smoother • Promote skeletal muscle relaxation and vasodilatation • May lead to hypotension and excessive heat loss • May raise seizure thresholds/ act as anticonvulsants

14. Tranquilizers Acepromazine Maleate Phenothiazine May reduce or prevent malignant hypothermia in swine Droperidol Butyrophenone Alpha-adrenergic antagonist May prevent epinephrine induced dysrhythmias Decreases barbiturate doses Primarily used as a component of InnovarVt in a mixture with fentanyl Diazepam Benzodiazepine Prevents seizures Rapidly passes blood-brain and placental barriers Should be injected slowly to prevent venous thrombosis and should not be injected IA IM injection not recommended- painful

15. Tranquilizers Midazolam Benzodiazepine Shorter duration of action and clearance than diazepam May cause behavioral changes in dogs and cats Suitable for IM injection Can be mixed with other preanesthetic agents Flumazenil Reverses CNS action of benzodiazepine without anxiety, tachycardia, or hypertension Rapid action (24 minutes) Replaced aminophylline and physostigmine

16. Opioids Depress CNS Lower the amount of anesthetic agents needed Do not cause unconsciousness at therapeutic levels Addictive Most are controlled substances Best for continuous dull pain

17. Opioids Methadone hydrochloride (Methadone, Dolophine) Synthetic opioid unrelated to morphine 2-6 hours of analgesia Decreases barbiturate dose by 50% Oxymorphone hydrochloride (Numorphan) Semi synthetic 10 times more potent than morphine Provided effective epidural analgesia Morphine sulfate Stimulates vomiting Decreases BMR and body temp Variable effects Poor effects on neuropathic pain Meperidine hydrochloride (Demerol, Pethidine) Analgesic effect 1/10 of morphine Rapidly excreted Does not cause vomiting Slow administration recommended

18. Opioids Fentanyl citrate 250 times more potent than morphine Rapid onset of action Short duration; peak at 30 minutes Depressed respiration Exaggerated response to loud noise Little cardiac output or BP effects Carfentanil citrate 10,000 times more potent than morphine Used primarily for capture of wild animals Sufentanil 5 to 10 times as potent as fentanyl Provided unpredictable anesthesia in dogs Provides neuroleptanalgesia when combined with tranquilizers and glycopyrrolate Alfentanil 1/5th to 1/10th as potent as fentanyl 80-1000 times more potent than morphine SC More rapid onset than fentanyl or sufentanyl Used primarily for the capture of wild animals

19. Opioids Pentazocine lactate (Talwin) 1/3rd as effective as morphine Minimal CV effects • Buprenorphine (Buprenex) • 25 to 30 times as potent as morphine • Max analgesic effect less than morphine • Slow onset of action (20-30 minutes) • Excreted in feces

20. Alpha 2 Adrenergic Agonists Produce sedation, muscle relaxation and analgesia Not potent respiratory depressant Non-addictive Anticonvulsants Wide range of drug interactions Barbiturate, inhalant and dissociative anesthetic doses should be lowered used in combination with alpha 2 adrenergic agonists

21. Alpha 2 Adrenergic Agonists Xylazine hydrochloride (Rompun) Most common sedative/analgesic in horses and cattle Short term surgical anesthetic when combined with ketamine Effects within 10-15 minutes IM or 3-5 minutes IV IV bolus causes bradycardia, hypotension followed by decreased CO and BP Poor efficacy in swine Wide margin of safety May cause emesis in cats and dogs Reduces insulin secretion, effecting blood glucose levels Medetomidine More potent than xylazine BP and RR decreases dose dependent Detomidine Sedative with analgesic properties Cardiac, respiratory and antidiuretic effects Primarily used in horses Dexmedetomidine (Precedex) More potent than medetomidine Sedative, analgesic, sympatholytic and anxiolytic effects Sedation without respiratory depression Shortens time to extubation Reduces anesthetic dosages Clonidine Alpha-methyldopa

22. Alpha 2 Adrenergic Antagonists Used as reversal agents for injectable anesthetics Yohimbine Reverses xylazine Also reverses ketamine and pentobarbital combinations when combined with 4-aminopyridine. Tolazoline Reverses xylazine and some anesthetic drug combinations with xylazine Atipamezole Selectivity ration 200 to 300 times higher than yohimbine Rapid IV doses may cause death or severe hypotension and tachycardia

23. Tranquilizer-Opioid Combinations Provide neuroleptanalgesia Intense analgesic action with short duration Fentanyl citrate Droperidol (Innovarvet) Wide margin of safety with easy recovery Partially reversed with opioid antagonists

24. Paralytics Provide superior muscle relaxation as an adjunct to general anesthesia DO NOT PROVIDE ANALGESIA OR UNCONSCIOUSNESS Prohibited as a sole anesthetic by the Guide Mechanical ventilation required More difficult anesthesia management

25. Paralytics Succinylcholine Depolarizing neuromuscular paralytic Marked twitching for 30 minutes before muscle relaxation Muscle pain and stiffness associated Rise in intraocular pressure Cats, swine and ponies resistant May not be reversible Pancuronium Lasts 20 to 30 minutes Causes increased HR Metabolized in liver, excreted via kidneys Vecuronium More potent and shorter acting than pancuronium rapid recovery no effect on HR Widely used do not use with renal or hepatic failure Pipecuronium Long acting- twice duration of pancuronium 2 to 4 times as potent as pancuronium Rapid onset Retained in kidneys for days no effect on HR

26. Paralytics (continued) • Rocuronium • 20% as potent as vecuronium • Rapid recovery • Curare (dTubocurarine) • Long acting • Increases HR • Metocurine • Safer than curare • Gallamine • Long acting • Produces tachycardia • The only non-depolarizing agent to cross the placenta • Atracurium • Unstable- refrigerate • Intermediate muscle relaxant • Widely used • Doxacurium • Long acting • No autonomic side effects • Mivacurium • Lasts slightly longer than succinylcholine and ½ the duration of vecuronium • No autonomic side effects

27. Paralytic Reversal Agents • Anticholinerases • Bradycardia, arrhythmias, secretions • CNS stimulation • Edrophonium, neostigmine, pyridostigmine • 4 Aminopyridine and Guanidine • Calcium • Only partially effective

28. Injectable Anesthetic Agents and Adjuncts Enter blood stream for transport to target tissues Require redistribution Generally detoxified in liver and excreted via kidneys Metabolism based on first order kinetics Constant fraction metabolized in a given period Less control of elimination process Barbiturates

29. Barbiturates Divided into Ultra short, Short, Intermediate and Long acting Depress CNS neurons May lead to respiratory depression, central and peripheral CV depression, decreased BP and BMR, reduced stroke volume and increased HR Hypnotic sedatives Cross cell walls and placental membrane Glucose effect in some animals Should not be administered to animals less than 3 months old IV administration preferred Barbiturate slough may occur Oxybarbiturates Thiobarbiturates

30. Oxybarbiturates Phenobarbital Sodium Long acting Effective anticonvulsant Excreted slowly and cumulative Pentobarbital Sodium Short acting Initial spike in HR followed by a decrease in HR and BP Prolonged use leads to decreased systolic BP, stroke volume, pulse pressure, CO, pH, and BT (shock-like) Crosses placenta Tranquilizers advised for smooth recovery Methohexital Sodium (Brevital) Ultra short acting (redistribution) Respiratory failure with overdose Good for induction

31. Thiobarbiturates Thiopental sodium Ultra short acting Most secreted in urine within 4 days Initial respiratory depression Increase in HR, BP and vascular resistance Thiamylal sodium Ultra short acting IV bolus lasts approx. 15 minutes Less cumulative than thiopental Less CV effects than thiopental

32. Non-Barbiturate Anesthetics Chloralose Minimal CV depression Less depression of neuronal function Long duration, acute procedures Urethane, N.F. Carcinogenic Magnesium sulfate Globally depresses CNS Means of euthanasia after unconsciousness Althesin Don’t use with barbiturates Good muscle relaxation May cause allergic reaction Chloral Hydrate, U.S.P. Oral admin may cause vomiting Depresses cerebrum Good hypnotic/poor anesthetic Amount needed for anesthesia close to lethal dose

33. Propofol Supports microbial growth Rapid uptake into CNS Quick and smooth recovery Minimal analgesic effects Propanidid Extremely short duration of action Difficult to administer fast enough Severe respiratory depression and hypotension in dogs Tricaine Methanesulfonate (MS222) Anesthesia of fish and amphibians Metomidate (Hypnodil) Hypnotic w/ relaxant properties Sleep without anesthesia Etomidate No depression of CV or respiratory centers Does not trigger MH in swine Anticonvulsant properties Venous pain during injection Non-Barbiturate Anesthetics

34. Dissociative Anesthetics Interrupts transmission from the unconscious to the conscious brain Characterized by a cataleptic state in which eyes remain open and nystagmus present • Ketamine • Least potent • Rapid onset of action • Rapid redistribution • Tissue irritation due to low pH (3.5) • Analgesic effects greater for somatic pain than visceral pain • Transient decrease in respiratory rate • Hallucinatory behavior • Telazol • Tiletamine hydrochloride and Zolazepam • Wide safety margin • Rapid and smooth induction/recovery • Good muscle relaxant • Lingering analgesic effects • May cause increased HR and respirations • Decrease in MAP

35. Inhalation Anesthesia Administration and elimination through lungs Dependent upon: Vapor pressure Boyle’s law Dalton’s law Temperature Charles’ law Solubility Partition coefficients Pharmacokinetics Biotransformation MAC Much more control

36. Inhalation Anesthetics • Historical Inhalant Agents • Chloroform • Cyclopropane • Diethyl ether • Fluroxene • Trichlorethylene

37. Inhalation Anesthetics Nitrous oxide Rapid onset Minimal cardiovascular, liver and kidney effects May cause pneumothorax, blood embolus, increase in middle ear pressure Must be combined with another agent Beware of diffusion hypoxia Halothane Potent and rapid onset High volatility Respiratory depression Mixed with thymol for stability Ether Explosive Highly irritating Methoxyflurane Low volatility High solubility Extensively metabolized Respiratory depressant Isoflurane Potent and low solubility Rapid induction and recovery “Safer” than halothane Coronary vasodilator

38. Inhalation Anesthetics Desflurane Very rapid induction and recovery Lower solubility than isoflurane Respiratory irritant Requires heated vaporizer Sevoflurane Very rapid induction and recovery Lower solubility than isoflurane, halothane or methoxyflurane

39. Local and Regional Anesthesia Administration Topical Solution in gel or aerosol Injectable local Ring block Brachial plexus block Epidural IV regional block Intercostal nerve blocks Affects 2 adjacent intercostal spaces Muscle nerve blocks For extensive surgical manipulation Interpleural admin Examples Lidocaine Proparacaine Benzocaine Tetracaine Butacaine

40. Physical Methods of Anesthesia Hypothermia Some vital organs can survive for longer periods at low temps with reduced blood supply Risks profound CNS and vital organ depression <28°C may cause VF Prolonged clotting time 3 methods of hypothermia Surface Body cavity extracorporeal Electronarcosis Delivered via electrodes applied to head Convulsions during induction Difficult to monitor and questionably humane Acupuncture Useful for chronic pain

41. Equipment Anesthesia machine Components Vaporizer in circuit or out of circuit? Rebreathing, non-rebreathing, semi-closed circuits CO2 absorber/ Scavenging Medical gas cylinders Color codes Airway maintenance Endotracheal tubes Laryngoscope blades

42. Review: What do you need to know? Know your drugs- what group they belong to and what they do Know the stages of anesthesia Have a basic understanding of the pharmacokinetics behind anesthesia Know your patient and how biological variations can effect anesthesia Be familiar with anesthetic equipment Areas not covered in depth: fasting, thermoregulation, fluids and acid/base balance

43. Good Luck!