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 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 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 Stages of Anesthesia 4 Stages of Anesthesia Stage I: “The stage of voluntary movement” Stage II: “The stage of delirium or involuntary movement” Initial administration of anesthetic to the loss of consciousness CNS depression Tachycardia and hypertension Exaggerated reflexes Irregular / increased respiration Struggling, breath holding, tachypnea, hyperventilation Breath holding Pupils dilate Struggling as animal becomes ataxic Some analgesic effects Loss of voluntary control Cardiac arrhythmias may occur Eyelash and palpebral reflexes present Vocalization Salivation Laryngeal spasm 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 Plane II: Surgical Anesthesia Bradycardia Hypotension Capillary refill slows Normal BP with strong pulse Palpebral reflex diminishes and disappears Decrease of respiratory rate and depth Eyeball rotates ventrally Pupils less dilated Abdominal muscle tone lost Eyeball may rotate Minimal jaw tone Palpebral reflex present Pedal reflex absent Slight reaction to surgical manipulation Dysrhythmia possibility low Loses jaw tone Stages of Anesthesia Stage III (cont): “Stage of Surgical Anesthesia” Plane III: Plane IV: Deep surgical anesthesia Deep/ Overdose Intercostal and abdominal muscle tone minimum Dysrhythmia probability Weak corneal reflexes Respirations slow and irregular Diaphragmatic breathing Lowered HR Profound muscle relaxation Cyanosis Centered and dilated pupils Widely dilated pupil and unresponsive to light Bradycardia intensifies Flaccid muscle tone Hypotension increases Jaw tone lost Respiratory rate and depth decrease Sphincter control lost 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 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 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 Pre-anesthetic Agents and Adjuncts Anticholinergics Tranquilizers Opioids Alpha2adrenergic agonists Alpha2adrenergic antagonists Tranquilizer-opioid combinations Paralytic agents 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 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 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 Tranquilizers Acepromazine Maleate Diazepam Phenothiazine Benzodiazepine May reduce or prevent malignant hypothermia in swine Prevents seizures 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 Rapidly passes blood-brain and placental barriers Should be injected slowly to prevent venous thrombosis and should not be injected IA IM injection not recommendedpainful 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 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 Opioids 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 Methadone hydrochloride (Methadone, Dolophine) Synthetic opioid unrelated to morphine 2-6 hours of analgesia Decreases barbiturate dose by 50% Oxymorphone hydrochloride (Numorphan) Rapidly excreted Semi synthetic Does not cause vomiting 10 times more potent than morphine Slow administration recommended Provided effective epidural analgesia 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 Opioids 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 Pentazocine lactate (Talwin) 1/3rd as effective as morphine Minimal CV effects 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 Alpha 2 Adrenergic Agonists Xylazine hydrochloride (Rompun) Detomidine Most common sedative/analgesic in horses and cattle Sedative with analgesic properties Short term surgical anesthetic when combined with ketamine Primarily used in horses 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 Cardiac, respiratory and antidiuretic effects 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 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 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 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 Paralytics Succinylcholine Depolarizing neuromuscular paralytic Marked twitching for 30 minutes before muscle relaxation Vecuronium More potent and shorter acting than pancuronium rapid recovery Muscle pain and stiffness associated no effect on HR Rise in intraocular pressure Widely used Cats, swine and ponies resistant do not use with renal or hepatic failure May not be reversible Pancuronium Lasts 20 to 30 minutes Causes increased HR Metabolized in liver, excreted via kidneys 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 Paralytics (continued) Rocuronium Atracurium 20% as potent as vecuronium Unstable- refrigerate Rapid recovery Intermediate muscle relaxant Curare (dTubocurarine) Long acting Increases HR Metocurine Safer than curare Gallamine Widely used Doxacurium Long acting No autonomic side effects Mivacurium Long acting Lasts slightly longer than succinylcholine and ½ the duration of vecuronium Produces tachycardia No autonomic side effects The only non-depolarizing agent to cross the placenta Paralytic Reversal Agents Anticholinerases Bradycardia, arrhythmias, secretions CNS stimulation Edrophonium, neostigmine, pyridostigmine 4 Aminopyridine and Guanidine Calcium Only partially effective 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 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 Oxybarbiturates Phenobarbital Sodium Methohexital Sodium (Brevital) Long acting Ultra short acting (redistribution) Effective anticonvulsant Respiratory failure with overdose Excreted slowly and cumulative Good for induction 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 Thiobarbiturates Thiopental sodium Thiamylal sodium Ultra short acting Ultra short acting Most secreted in urine within 4 days IV bolus lasts approx. 15 minutes Initial respiratory depression Less CV effects than thiopental Increase in HR, BP and vascular resistance Less cumulative than thiopental Non-Barbiturate Anesthetics Althesin Chloralose Don’t use with barbiturates Minimal CV depression Good muscle relaxation Less depression of neuronal function 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 Long duration, acute procedures Urethane, N.F. Carcinogenic Magnesium sulfate Globally depresses CNS Means of euthanasia after unconsciousness Non-Barbiturate Anesthetics Metomidate (Hypnodil) Propofol Hypnotic w/ relaxant properties Supports microbial growth Sleep without anesthesia Rapid uptake into CNS Etomidate No depression of CV or respiratory centers Does not trigger MH in swine Anticonvulsant properties Venous pain during injection 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 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 Inhalation Anesthesia Administration and elimination through lungs Dependent upon: Vapor pressure Temperature Charles’ law Solubility Partition coefficients Pharmacokinetics Biotransformation Boyle’s law Dalton’s law MAC Much more control Inhalation Anesthetics Historical Inhalant Agents Chloroform Cyclopropane Diethyl ether Fluroxene Trichlorethylene Inhalation Anesthetics Nitrous oxide Ether Rapid onset Explosive Minimal cardiovascular, liver and kidney effects Highly irritating 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 Methoxyflurane Low volatility High solubility Extensively metabolized Respiratory depressant Isoflurane Potent and low solubility Rapid induction and recovery “Safer” than halothane Coronary vasodilator 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 Local and Regional Anesthesia Administration Lidocaine Topical Solution in gel or aerosol Injectable local Ring block Brachial plexus block Epidural IV regional block Intercostal nerve blocks • Examples Affects 2 adjacent intercostal spaces Muscle nerve blocks • For extensive surgical manipulation • Interpleural admin Proparacaine Benzocaine Tetracaine Butacaine 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 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 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 Good Luck!