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Anesthesia Considerations in Rodent Biomedical Research Updated 5-16

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Anesthesia Considerations in Rodent Biomedical Research Updated 5-16 5/16/18 Anesthesia Types in Rodents • Injectable (e.g. ketamine cocktails) • Volatile gas (e.g. isoflurane, sevoflurane) • Physical (e.g. hypothermia) Marcel Perret-Gentil, DVM, MS University Veterinarian & Director Laboratory Animal Resources Center The University of Texas at San Antonio [email protected] 2 Injectable or Inhalation Why Anesthetize an Animal Anesthesia? 1 or more reasons: • Avoid pain (loss of sensation) • Immobilize (muscle relaxation) • Avoid distress (loss of consciousness) 3 4 Injectable Anesthetics - Injectable Anesthetics - Advantages Disadvantages • Simple • Higher morbidity & mortality when compared to inhalants • Cheap • Easier to overdose • Minimal equipment • Slow and variable absorption • Longer recovery times • Variable effects from a single dose • Strain and gender differences 5 6 1 5/16/18 Inhalant Anesthetics - Advantages Pentobarbital 60 mg/kg Usually suitable as sole agents to reach ‘balanced’ anesthesia • Loss of sensation • Loss of consciousness • Muscle relaxation 7 9 Lovell, 1986b Inhalant Anesthetics - Inhalant Anesthetics - Advantages Disadvantages " Precise control over anesthetic depth " Anesthetic " Rapid recovery delivery system - $??? " Requires a " Delivery of agents usually involves oxygen scavenging system " Greater consistency between strains and " Requires yearly genders = experimental consistency calibration (unless otherwise specified by manufacturer) 10 11 Volatile Anesthetics Ether Halothane Methoxyflurane Enflurane Isoflurane Desflurane Sevoflurane 13 2 5/16/18 Isoflurane - Advantages Isoflurane - Disadvantages % Rapid induction & recovery % Can manipulate depth of anesthesia Some respiratory depression easily & rapidly Pungent odor may lead to breath holding % Non-irritant, non-explosive & non- in rabbits, but does not appear to be a flammable problem in other spp % Nearly 100% eliminated in exhaled air… minimal interference in drug metabolism % Minimal cardiovascular depression % Inexpensive… eventually!!! 15 16 Sevoflurane - Advantages Sevoflurane - Disadvantages " Faster induction & recovery than isoflurane Undergoes slightly greater hepatic metabolism than isoflurane " Nonirritating to airways and well accepted, lending itself to mask or chamber inductions " Becoming increasingly more popular in rodents 17 18 Anesthetic Gas Recovery as Metabolite1 ( Methoxyflurane: 50% Desflurane ( Halothane: 20-25% Sevoflurane ( Sevoflurane: 2-5% ( Enflurane: 2.4% Isoflurane ( Isoflurane: 0.17% Halothane ( Desflurane: 0.02-0.2% 1Humans 19 20 3 5/16/18 Somnosuite (Kent Scientific) • Integrated digital vaporizer • Pre-warmed isoflurane gas • Tissue oxygen-hemoglobin concentration (SpO2) • Temperature control • Heart rate • Respiration rate • Ventilator 22 The Savings Somnosuite Traditional Isoflurane Isoflurane 1:38 1 38 Waste Gas Canister Waste Gas Canister Somnosuite Typical Anesthesia System ~6 lbs 30+ lbs 1:36 Warm gas Cold gas 9 325 Physiosuite (Kent Scientific) • Temperature control: Homeothermic (warms rodent at exact temp by far infrared warming that goes beyond cutaneous warming by heating deep into rodent’s body with temp feedback) • Pulse oximeter and heart rate • Automatic ventilator (ventilate animals as small as 3g – simple enter weight and press run) • End tidal CO2 monitor 26 4 5/16/18 Open Drop Pathology cassette with Centrifuge tube isoflurane or Depth of anesthesia sevoflurane can be controlled by soaked material moving the nose cone closer or farther away from the nostrils Wire or plastic grate Absorbent material soaked with 28 anesthetic Open Drop Quite useful & easy to apply, but… Prolonged use = deaths Used for short term anesthesia (minutes) 29 Pentobarbital - Advantages Pentobarbital - Disadvantages # Placental transfer of barbiturates • Pharmaceutical grade very pricey occurs rapidly. However, when used • High cost renders it “unavailable in pharm in proper induction doses, excessive grade” *** depression of the fetus does not • Chemical grade use must be addressed & occur justified # Administered IV or IP *** NIH statement 2013 # Neither hepato- or nephrotoxic 32 33 5 5/16/18 Ketamine Pentobarbital - Disadvantages ) Thought to be a specific antagonist of N-methyl- D-aspartate glutamate receptors (NMDA) Prolonged recovery esp. if additional doses administered ) "Cocaine-like" effect in that it inhibits uptake of catecholamines into postganglionic sympathetic Severe cardiovascular & respiratory nerves depression ) Cleared by hepatic metabolism – Anesthetic & lethal doses close to each ) Alone it is a poor anesthetic and analgesic in other… high mortality possible rodents (when used alone)… must be used with other tranquilizars &/or sedatives (‘cocktail’) 34 35 Ketamine Ketamine - Advantages - CV effects resemble sympathetic " In hypovolemic patients, arterial BP is nervous stimulation - i.e. increased maintained with ketamine because of arterial BP, HR, CO, cardiac workload peripheral vasoconstriction & myocardial oxygen consumption " No significant effect on hepatic or renal - Such effects obtunded by prior or co- function administration of tranquilizers or sedatives (‘cocktail’) " Increases myocardial contractility - Transient increase of norepinephrine & epinephrine in plasma 36 37 Ketamine ‘Cocktails’ Ketamine - Disadvantages Safer, more ‘balanced’ anesthesia than $ Increased airway & salivary secretions in pentobarbital or ketamine alone some species (mild in mice & rats) – Ketamine/xylazine $ Induces epileptiform bursts in thalamus & – Ketamine/dexmedetomidine limbic system, but w/o spread to cortical – Ketamine/xylazine/acepromazine areas – may increase seizure threshold in rats & mice – Other combinations $ Some respiratory depression following anesthetic doses in rodents 38 39 6 5/16/18 Ketamine ‘Cocktail’ Reversal Ketamine/Medetomidine Reversal with Atipamezole 0 Antagonist atipamezole shortens recovery of ketamine/xylazine & ketamine/dexmedetomidine 0 Atipamezole (0.5-1 mg/kg SC, IP, IM, IV) partially reverses xylazine & dexmedetomidine (not ketamine) 0 Early reversal (10–20 minutes after induction) associated with undesirable behavioral disturbances due to effects of ketamine Courtesy of Dr. Paul Flecknell 40 41 Video Mouse - Anesthetic recovery w Atimepazole reversal Ketamine ‘Cocktails’ # Use of yohimbine for reversal of ketamine/xylazine no longer recommended due to yohimbine’s reported side effects # For cocktail doses refer to http://research.utsa.edu/research- funding/laboratory-animal-resources- center/training/ 42 43 Tribromoethanol (Avertin) $ Adequate anesthesia up to 30 min $ Repeat doses not recommended due to Urethane abdominal irritation & peritonitis reports $ Degrades in presence of heat or light – refrigerate, wrap in foil $ Non-pharmaceutical grade compound 44 45 7 5/16/18 Urethane - Disadvantages Urethane - Advantages $ Peritoneal effusion & hemolysis " IP Administration results in long-lasting $ Mutagen/carcinogen unconsciousness of 6-10 hr $ Readily absorbed through skin " Cardiopulmonary functions minimally – pre-neoplastic changes in skin affected, including blood pressure due to effects on catecholamine release – targets multiple organs " Good analgesia for surgery in rodents – suppresses bone marrow – readily crosses the placenta 46 – fetal tumor formation (in utero) 47 Urethane Resources Strict guidelines (gloves, mask, prepare in fume hood) Presentations, References & Useful Notes Non-pharmaceutical grade compound http://research.utsa.edu/research- funding/laboratory-animal-resources- Not used for survival surgeries center/training/ 48 49 Marcel Perret-Gentil, DVM, MS University Veterinarian & Director Laboratory Animal Resources Center (LARC) The University of Texas at San Antonio San Antonio, Texas [email protected] vpr.utsa.edu/larc 50 8.
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