Test Review Anesthesia Jenifer Sweet B A S

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

Overview ØGeneral Anesthesia Ø Definition Ø Stages of Anesthesia Ø Considerations ØPharmacokinetics Ø Method of action Ø Modifying factors ØTypes of Anesthesia Ø Pre-anesthetic Agents and Adjuncts Ø Injectable Anesthetic Agents and Adjuncts Ø Inhalation Anesthesia Ø Local and Regional Anesthesia Ø Physical Methods of Anesthesia ØEquipment ØReview

General Anesthesia ØWhat is general anesthesia? ØDoses based on “average” animal ØBiological variations ØMetabolic rate Ø% fat ØGeneral health ØSex ØGenetics ØTime of day ØSpecies ØIndividualized sensitivity ØThe perfect anesthetic agent does not exist

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

Stages of Anesthesia ØStage III: “Stage of Surgical Anesthesia” ØPulse rate returns to normal ØMuscles relax ØSwallowing and vomiting reflexes lost Ø 3 -4 planes Ø Plane I: ØEyeball movement ceases ØPlane II: ØSurgical Anesthesia ØBradycardia ØHypotension ØCapillary refill slows ØNormal BP with strong pulse ØPalpebral reflex diminishes and disappears ØDecrease of respiratory rate and depth ØEyeball rotates ventrally ØPupils less dilated ØAbdominal muscle tone lost ØEyeball may rotate ØMinimal jaw tone ØPalpebral reflex present ØPedal reflex absent ØSlight reaction to surgical manipulation ØDysrhythmia possibility low ØLoses jaw tone

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

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

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

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

Pre-anesthetic Agents and Adjuncts Ø Ø Ø Ø Anticholinergics Tranquilizers Opioids Alpha 2 adrenergic agonists Alpha 2 adrenergic antagonists Tranquilizer-opioid combinations Paralytic agents

Anticholinergics ØBlock acetylcholine receptors ØReduce secretions ØPrevent vagal inhibition and GI stimulation ØReduce vagus nerve response (vomiting and laryngospasm) ØPromote bronchodilation ØDilate the pupil ØTreatment of choice for opioid, xylazine and vagal reflex activity induced bradycardia

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

Tranquilizers ØNO ANALGESIC EFFECTS ØRelieve anxiety ØDecrease anesthetic dosages ØReduce histamine release and vomiting ØMake anesthetic recovery smoother ØPromote skeletal muscle relaxation and vasodilatation ØMay lead to hypotension and excessive heat loss ØMay raise seizure thresholds/ act as anticonvulsants

Tranquilizers ØAcepromazine Maleate ØDiazepam Ø Phenothiazine Ø Benzodiazepine Ø May reduce or prevent malignant hypothermia in swine Ø Prevents seizures ØDroperidol Ø Butyrophenone Ø Alpha-adrenergic antagonist Ø May prevent epinephrine induced dysrhythmias Ø Decreases barbiturate doses Ø Primarily used as a component of Innovar. Vt in a mixture with fentanyl Ø Rapidly passes blood-brain and placental barriers Ø Should be injected slowly to prevent venous thrombosis and should not be injected IA Ø IM injection not recommendedpainful

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

Opioids ØDepress CNS ØLower the amount of anesthetic agents needed ØDo not cause unconsciousness at therapeutic levels ØAddictive ØMost are controlled substances ØBest for continuous dull pain

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

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

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

Alpha 2 Adrenergic Agonists ØProduce sedation, muscle relaxation and analgesia ØNot potent respiratory depressant ØNon-addictive ØAnticonvulsants ØWide range of drug interactions ØBarbiturate, inhalant and dissociative anesthetic doses should be lowered used in combination with alpha 2 adrenergic agonists

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

Alpha 2 Adrenergic Antagonists Ø Used as reversal agents for injectable anesthetics ØYohimbine ØReverses xylazine ØAlso reverses ketamine and pentobarbital combinations when combined with 4 -aminopyridine. ØTolazoline ØReverses xylazine and some anesthetic drug combinations with xylazine ØAtipamezole ØSelectivity ration 200 to 300 times higher than yohimbine ØRapid IV doses may cause death or severe hypotension and tachycardia

Tranquilizer-Opioid Combinations Ø Provide neuroleptanalgesia Ø Intense analgesic action with short duration ØFentanyl citrate Droperidol (Innovarvet) ØWide margin of safety with easy recovery ØPartially reversed with opioid antagonists

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

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

Paralytics (continued) ØRocuronium Ø 20% as potent as vecuronium Ø Rapid recovery ØCurare (d. Tubocurarine) Ø Long acting Ø Increases HR ØMetocurine Ø Safer than curare ØGallamine Ø Long acting Ø Produces tachycardia Ø The only non-depolarizing agent to cross the placenta ØAtracurium Ø Unstable- refrigerate Ø Intermediate muscle relaxant Ø Widely used ØDoxacurium Ø Long acting Ø No autonomic side effects ØMivacurium Ø Lasts slightly longer than succinylcholine and ½ the duration of vecuronium Ø No autonomic side effects

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

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

Barbiturates ØDivided into Ultra short, Short, Intermediate and Long acting ØDepress CNS neurons ØMay lead to respiratory depression, central and peripheral CV depression, decreased BP and BMR, reduced stroke volume and increased HR ØHypnotic sedatives ØCross cell walls and placental membrane ØGlucose effect in some animals ØShould not be administered to animals less than 3 months old ØIV administration preferred ØBarbiturate slough may occur ØOxybarbiturates ØThiobarbiturates

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

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

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

Non-Barbiturate Anesthetics ØMetomidate (Hypnodil) ØPropofol Ø Hypnotic w/ relaxant properties Ø Supports microbial growth Ø Sleep without anesthesia Ø Rapid uptake into CNS ØEtomidate Ø No depression of CV or respiratory centers Ø Quick and smooth recovery Ø Minimal analgesic effects ØPropanidid Ø Does not trigger MH in swine Ø Extremely short duration of action Ø Anticonvulsant properties Ø Difficult to administer fast enough Ø Venous pain during injection Ø Severe respiratory depression and hypotension in dogs ØTricaine Methanesulfonate (MS 222) Ø Anesthesia of fish and amphibians

Dissociative Anesthetics Ø Interrupts transmission from the unconscious to the conscious brain Ø Characterized by a cataleptic state in which eyes remain open and nystagmus present ØKetamine Ø Least potent ØTelazol Ø Rapid onset of action Ø Tiletamine hydrochloride and Zolazepam Ø Rapid redistribution Ø Wide safety margin Ø Tissue irritation due to low p. H (3. 5) Ø Rapid and smooth induction/recovery Ø Analgesic effects greater for somatic pain than visceral pain Ø Transient decrease in respiratory rate Ø Hallucinatory behavior Ø Good muscle relaxant Ø Lingering analgesic effects Ø May cause increased HR and respirations Ø Decrease in MAP

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

Inhalation Anesthetics ØHistorical Inhalant Agents ØChloroform ØCyclopropane ØDiethyl ether ØFluroxene ØTrichlorethylene

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

Inhalation Anesthetics ØDesflurane Ø Very rapid induction and recovery Ø Lower solubility than isoflurane Ø Respiratory irritant Ø Requires heated vaporizer ØSevoflurane Ø Very rapid induction and recovery Ø Lower solubility than isoflurane, halothane or methoxyflurane

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

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

Equipment Ø Anesthesia machine Ø Components Ø Vaporizer in circuit or out of circuit? Ø Rebreathing, non-rebreathing, semi-closed circuits Ø CO 2 absorber/ Scavenging Ø Medical gas cylinders Ø Ø Color codes Airway maintenance Ø Endotracheal tubes Ø Laryngoscope blades

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

Good Luck!