Iowa State University Institutional Animal Care and Use Committee. Institutional Animal Care and Use Committee (IACUC) Standard Operating Procedure

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Effective Date: 4-9-2014 Approved Date: 4-9-2014 Revised Date: 5-2-2018 Last Reviewed: 5-2-2018 Institutional Animal Care and Use Committee SOP ID Number: 211.04 SOP Title: Drug Formulary Institutional Animal Care and Use Committee (IACUC) Standard Operating Procedure DRUG FORMULARY 1. Purpose This procedure describes the recommended use of analgesics, anesthetics, sedatives and associated drugs such as anticholinergics and reversal agents in animals used for research and teaching on approved Institutional Animal Care and Use Committee (IACUC) protocols. Federal regulations mandate that animals undergoing potentially painful procedures be given anesthesia and/or analgesia to minimize their pain and distress. Exceptions to this are only permitted when scientific justification is included in the IACUC protocol and is approved by the ISU IACUC. 2. Scope This SOP is applicable to all ISU staff, research investigators, and technicians who provide care and/or use animals that will receive any analgesics, anesthetics, or sedatives. ISU staff, research investigators, and technicians are expected to understand the content of SOPs related to their work responsibilities. This policy is applicable to individuals from all colleges performing research-related procedures on animals. Veterinary medical and animal care procedures are outside the scope of this policy when they are unrelated to the research project and when they are performed to improve animal health or well-being or to treat an illness or injury under the direction of the Attending Veterinarian or designee. 3. General Requirements The Attending Veterinarian (AV) has the authority to ensure the provision of adequate sedation, analgesia, or anesthesia as mandated by the Animal Welfare Act and related animal care regulations. The AV or designee should therefore be directly involved in the selection of appropriate agents during protocol development. The procedures within this SOP for using analgesics, anesthetics, and sedatives are intended to assist investigators in their use of animals for research or teaching. Experimental design or special circumstances may dictate modification of dose levels or agents/methods Office for Responsible Research Page 1 of 29

outlined herein. We strongly encourage the use of pre-operative, intra-operative, and postoperative analgesics in ALL recovery surgical procedures. The ISU Institutional Animal Care and Use Committee will rely on the procedures outlined in this SOP when reviewing animal protocols and may request explanations or justifications for substantial deviations. Intravenous barbiturates (i.e., thiopental, pentobarbital) for use as an anesthetic should be administered by giving 1/3 1/2 of the total calculated dose as a bolus, followed by titration of the remaining volume to effect, if needed. Special considerations apply to late term fetal and neonatal altricial rodents (e.g., rats and mice between E15 and P7). Dosage intervals listed on tables are single doses unless otherwise noted. A veterinarian should be consulted to assist in determining the frequency and amount of drug needed for repeated dosing. Investigators who use controlled anesthetic or analgesic agents must comply with the special storage and record keeping requirements. When issued a controlled substance as defined by the U.S. Department of Justice Drug Enforcement Administration, the PI responsibilities are to keep the substance in a secure, locked location when not in use; record usage of the substance; maintain the record of usage for 3 years from the date that a substance is completely used; The ISU IACUC has a controlled substance record template available here. Environmental Health and Safety is available for consultation about safety of the agent prior to use. Investigators who use anesthetic gases must follow the IACUC SOP Anesthetic Gas Usage Safety Precaution. 4. Procedure A. See Appendix 1: Drug Formulary for drugs used in common research species used at. B. For species or agents not listed please contact LAR at larmedical@iastate.edu for a consultation to identify the appropriate analgesics and anesthetics or the Attending Veterinarian at msauer@iastate.edu. 5. Roles and Responsibilities ISU Attending Veterinarian or Designee Be involved in the selection of appropriate agents during protocol development. Investigators If the anesthetic or analgesic used is a controlled substance, follow the required special procedures for storage and record keeping see the IACUC Controlled Substance Record Template for details. Office for Responsible Research Page 2 of 29

Review proper handling procedures with Environmental Health and Safety prior to the use of specific agents. Responsible for following the procedures described in this guide and the final approved IACUC protocol. 6. Definitions A. Analgesia: loss of sensitivity to painful stimulation without loss of consciousness. B. Anesthesia: loss of feeling or sensation, which is often accompanied by loss of consciousness. C. Local anesthesia: the loss of sensation to a section of the body. D. Anti-cholinergics: A drug that inhibits acetylcholine as a neurotransmitter, decreases salivation, defecation, urination, and tear production associated with surgery. E. General Anesthesia: unconsciousness with adequate analgesia and muscle relaxation to allow for surgery. F. Sedation: a mild degree of central depression in a conscious but calm animal also referred to as tranquilization. G. Common Abbreviations 1. IM: intramuscular 2. IP: intraperitoneal 3. IV: intravenous 4. SQ or SC: subcutaneous 5. PO: per os means to be given by mouth or orally 6. q: every 7. bid: give medication twice a day 8. sid: give medication once a day 9. qxh or qxd: once every x hours or once every x days 7. Health and Safety Information Follow Safety Data Sheets (SDS) for specific drugs for hazard control, PPE, and waste disposal. 8. Appendices Appendix 1 Drug Formulary Office for Responsible Research Page 3 of 29

9. Forms and Templates N/A 10. References Fish R.E., Brown M.J., Danneman P.J., Karas A.Z., editors. Anesthesia and Analgesia in Laboratory Animals. 2nd Ed. New York: Academic Press; 2008. Plumb D.C. Veterinary Drug Handbook: Pocket Edition. 9th Ed. Ames: Iowa State Press.; 2018. University of British Columbia IACUC. Local Analgesia/Anesthesia for Rodents: Lidocaine/Bupivacaine/Ropivacaine. [PDF] Last Updated: 2014, Downloaded: 10-13-17; Available from: https://animalcare.ubc.ca/sites/default/files/documents/tech%2016%20- %20Local%20Anesthetic%20SOP%20%282014%29.pdf Carpenter J.W., editor. Exotic Animal Formulary. 3rd Ed. St. Louis: Elsevier Saunders; 2013. Boston University IACUC. Anesthesia of the Neonatal Mice and Rats. [Web Page] LastUpdated: 1 7 2012, Downloaded: 1 11 2012; Available from: http://www.bu.edu/orccommittees/iacuc/policies and guidelines/anesthesia oftheneonatalmice and rats/ Swindle M.M. Swine in the Laboratory. 2nd Ed. Boca Raton: CRC Press; 2007. Colditz I., Dart C. The Sheep. ANZCCART Fact Sheet [PDF] Last Updated: 2009, Downloaded: 412 2012; Available from: http://www.adelaide.edu.au/anzccart/publications/a9_sheepfactsheet.pdf Flecknell PA. Laboratory Animal Anesthesia, 3 rd Ed. London: Academic Press; 2009. Carbone ET, Lindstrom KE, Diep S, Carbone L. 2012. Duration of action of sustainedrelease buprenorphine in 2 strains of mice. J Am Assoc Lab Anim Sci 51:815 819. Clark TS, Clark DD, Hoyt RF, 2014. Pharmacokinetic comparison of sustained-release and standard buprenorphine in mice. J Am Assoc Lab Anim Sci 53:387-391. Chum HH, Jampachairsri K, McKeon GP, Yeomans DC, Pascharinsak C, Felt SA. 2014 Antinociceptive effects of sustained-release buprenorphine in a model of incisional pain in rats (Rattus norvegicus). J Am Assoc Lab Anim Sci 53:193-197. Foely OL, Liang H, Crichlow AR. 2011. Evaluation of a sustained-released and standard buprenorphine for analgesia in rats. J Am Assoc Lab Anim Sci 50:198-204. Wren, Geri. January 2008. Options in pain management. Bovine Veterinarian Downloaded 2-23-17; Available from: https://ahdc.vet.cornell.edu/programs/nyschap/docs/bovinevetpain01-08.pdf Danneman, P.J., & Mandrell, T. D. (1997). Evaluation of five agents/methods for anesthesia of neonatal rats. Lab Anim. Sci. 47(4):286 395. Office for Responsible Research Page 4 of 29

Flecknell, P.A. (2009). Laboratory animal anesthesia, 3rd Edition. Academic Press, London. Suckow, M.A., Stevens, K. A., and Wilson, R.P. (2012) The Laboratory Rabbit, Guinea Pig, Hamster and Other Rodents. ACLAM, Academic Press, Elsevier. 11. Contact Information Direct questions about this document to: Institutional Animal Care and Use Committee,, 515-294-1516, iacuc@iastate.edu Direct questions to the Attending Veterinarian, Dr. Mary Sauer, VMD, 515-294-0266. msauer@iastate.edu Office for Responsible Research Page 5 of 29

Appendix 1 Drug Formulary Amphibians Amphibians - Anesthesia MS-222 (Tricaine Methanesulfonate) Immersion in MS- 222 at.1.5% Induction 5 min. Recovery 15 30 min. Office for Responsible Research Page 6 of 29

Cattle Cattle - Injectable Anesthesia Agent Dose (mg/kg) Comments/Reference(s) Butorphanol Butorphanol 0.1-0.3 mg/kg IM 0.05-0.15mg/kg IV 0.3-0.5 IV or 0.1 IM or SQ 0.05-0.1 IV or 0.025 IM or SQ 0.025-0.05 IV or 0.05 IM or SQ 0.05-0.1 IV or 0.04 IM or SQ 0.02-0.05 IV or 0.01 IM or SQ 0.02-0.0275 IV or 0.02 IM or SQ Unpredictable in cattle, may have short duration of analgesia (30 minutes) (2) For recumbent procedures; IM dosages will give longer, less intense sedation (2) For standing procedures Give first to sedate (2) Cattle - Analgesia Acetylsalicylic Acid 100mg/kg PO q12hr (aspirin) Flunixin 1.1-2.2mg/kg IV q24hr Slow (2) Lidocaine 1-5 ml as caudal epidural Dose based on size Phenylbutazone 5mg/kg PO q24-48hr (2) Office for Responsible Research Page 7 of 29

Dog Dog - Anticholinergics Atropine 0.02-0.04mg/kg IM,SC,IV Reduces bradycardia and hypersalivation (2) Glycopyrrolate 0.01-0.02mg/kg SC,IM Reduces bradycardia and hypersalivation (2) Dog - Inhalant Anesthesia Isoflurane 1-3% maintenance Administer with a precision vaporizer and compressed oxygen Dog - Injectable Anesthesia Acempromazine 0.01-0.2mg/kg IM,SC,IV Sedative, not surgical anesthetic. (2) Midazolam 0.1-0.3mg/kg SC,IM,IV Combine with other premeds (2) Diazepam 0.5-1mg/kg IV bolus (2) Dexmedetomidine 375mcg/m2 body surface area IV or 500mcg/m2 IM 1.1-2.2mg/kg IM,IV (2) Propofol Tiletamine/zolazepam Acepromazine 5-6mg/kg IV induction 0.1mg/kg/min maintenance of sedation 6.6-9.9mg/kg IM (diagnostics) 9.9-13.2mg/kg IM (minor procedures) 0.02-0.05mg/kg IM (1) See dosing table in drug package. Mcg/kg decreases as BW increases (2) Give to effect, slowly (2) Similar to ketamine/valium Use with atropine 0.04mg/kg to control hypersalivation.(2) Office for Responsible Research Page 8 of 29

Butorphanol Butorphanol Dexmedetomidine 0.2mg/kg IM 0.2mg/kg IM 5-7.5ug/kg IM (1) Dog - Analgesia OPIOID Buprenorphine 0.005-0.03mg/kg IM,IV,SC q 6-12 hr Butorphanol 0.1-0.5mg/kg IM,IV,SC q 2-4 hr Tramadol (synthetic opiatelike drug) NSAID Carprofen (2) (2) 4-10 mg/kg PO q 8-24 (2) 2.2 (q12hr)-4.4 (q24hr)mg/kg PO Deracoxib 1-4 mg/kg PO q24hr 3-4 mg/kg should not be used for more than 7 days (2) Robenacoxib 1-2mg/kg PO or SC q24 hr At 2 mg/kg for a maximum of 3 days (2) Meloxicam 0.2mg/kg PO,SC q24hr, subsequent dosing at 0.1mg/kg PO,SC (2) (2) Dog Drug Antagonists Atipamezole Use same volume as alpha 2 agonist given Reverses alpha 2 agonists like xylazine Flumazenil 0.08-0.2 mg/kg IV Reverses benzodiazepines Tolazoline 4 mg/kg slowly IV Reverses alpha 2 agonists like xylazine Yohimbine 11 mg/kg IV Reverses alpha 2 agonists like xylazine Office for Responsible Research Page 9 of 29

Ferret Ferret - Anticholinergics Agents Dose Comments/Reference(s) Atropine 0.04mg/kg IM (1) Glycopyrrolate 0.01mg/kg IM (1) Ferret - Inhalant Anesthesia Isoflurane 1-3% maintenance Administer with a precision vaporizer and compressed oxygen Ferret - Injectable Anesthesia Acepromazine 0.1-0.3mg/kg IM Sedative, not surgical anesthetic. (1) 2mg/kg IM, SC (1) Butorphanol Tiletamine/zolazepam 30mg/kg IM 3mg/kg IM 35mg/kg IM 5mg/kg IM 1.0mg/kg IM 3mg/kg IM 3mg/kg IM (1) (1) (1) Office for Responsible Research Page 10 of 29

Ferret - Analgesia OPIOID Buprenorphine NSAID 0.1-0.02mg/kg SC, IV, IM q6-8hr Carprofen 1 mg/kg SC, PO q24 hr (1,4) Meloxicam 0.2mg/mg SC,PO,IM q24 hr (1,4) (1) Office for Responsible Research Page 11 of 29

Gerbil Gerbil - Inhalant Anesthesia Isoflurane 3-5% induction 1-3% maintenance Administer via precision vaporizer and compressed oxygen or drop method Gerbil - Injectable Anesthesia 5-10mg/kg SC,IM (4) Diazepam 3-5mg/kg SC,IM (4) Midazolam 1-2mg/kg SC,IM (4) Acepromazine 0.5-1.0mg/kg IM (4) Diazepam Tiletamine/Zolazepam (Telazol) 50-70mg/kg IP 2-3mg/kg IP 40-150mg/kg IP 3-5mg/kg IP (4) (4) 50-80mg/kg IP (4) Pentobarbitol 50-90mg/kg IP (4) Gerbil - Analgesia OPIOID Buprenorphine 0.1-0.2mg/kg SC q8 hr (4) NSAID Carprofen 5mg/kg SC q24 hr (4) Meloxicam 0.5/kg SC,PO q24 hr (8) Office for Responsible Research Page 12 of 29

Hamster Hamster - Inhalant Anesthesia Isoflurane 3-5% induction 1-3% maintenance Administer via precision vaporizer and compressed oxygen or drop method Hamster - Injectable Anesthesia Acepromazine 0.5-1.0mg/kg IM Sedative, not surgical anesthetic. (4) 20-40mg/kg IM 50-100 IP 1-5mg/kg IM, IP (8) Titelamine/Zolazepam (Telazol) 50-150/kg IP 10mg/kg IP Light/moderate sedation (4) Deep sedation (8) (,16) 50-80mg/kg IP (8) Hamster - Analgesia OPIOID Buprenorphine 0.01-0.5mg/kg SC q8-12 hr (4,8) NSAID Carprofen 5mg/kg SC (4) Meloxicam 1-2mg/kg SC,PO q24 hr (8) Office for Responsible Research Page 13 of 29

Horse Horse - Anticholinergic Agent Dose Comments Atropine 0.01-0.02mg/kg IV For treatment of bradyarrhythmias (2) Horse - Inhalant Anesthesia Isoflurane 3-5% Induction 1-3% Maintenance Administer via precision vaporizer and compressed oxygen. Horse - Injectable Anesthesia Guaifenesin (100mg (10mg) (0.5%) Guaifenesin 0.25-1.1mg/kg IV 2.2mg/kg IM 50mg/ml 1-2mg/ml 0.5mg/ml Standing sedation ~ 30 minutes (2) 1 liter guaifenesin + 1000mg ketamine + 500mg, maintenance is to effect. For terminal procedures only (2) CRI at 1.5-2.2 ml/kg/hr For IV anesthesia Detomidine (Dormosedan) 0.005-0.04 mg/kg IV or IM Sedation 90-120 minutes Horse - Analgesics Opioid Butorphanol 0.1mg/kg IV q3-4hrs (2) NSAIDs Office for Responsible Research Page 14 of 29

Flunixin 1.1mg/kg IV,IM,PO q24hr (2) Phenylbutazone 2.2-4.4mg/kg PO q12hr 2.2-4.4mg/kg IV q12hr Firocoxib 0.1 mg/kg PO q24hr (or 57 mg tablet) Tranquilizer 0.09 mg/kg IV q24 hr Reduce dose when possible to lowest effective dose (2) Label says oral up to 14 days; IV up to 5 days, followed by 9 days oral (2) Acepromazine 0.044-0.088mg/kg IM,IV Relaxation, not full sedation; caution with use in stallions (2) Acepromazine Romifidine 0.044-0.044 mg/kg IV 0.02-0.12 mg/kg IV (slowly) Caution with use of Acepromazine in stallions Sedation 45-60 minutes Horse Drug Antagonists Flumazenil (antagonist for benzodiazepems) Tolazoline (used to reverse alpha 2 agonists like xylazine) Yohimbine (to reverse xylazine like drugs) 0.01 mg/kg IV (2) 0.04 mg/kg slowly IV (2) 0.05-0.2 mg/kg IM or IV (2) Office for Responsible Research Page 15 of 29

Mouse Mouse - Inhalant Anesthesia Isoflurane 3-5% induction 1-3% maintenance Administer via precision vaporizer and compressed oxygen or drop method Mouse - Injectable Anesthesia 100 mg/kg IP Surgical anesthesia (8) 10 mg/kg IP 100mg/kg IP Immobilization/anesthesia (8) Acepromazine 5mg/kg IP 100mg/kg IP Immobilization/anesthesia (8) Midazolam 5mg/kg IP Acepromazine 80-100mg/kg IP 10-20mg/kg IP 2-3mg/kg IP Surgical anesthesia (8) Mouse - Analgesia OPIOID Buprenorphine 0.05-1.0mg/kg SC,IP q6-12 hr Preferred analgesic for rodents (1) Buprenorphine SR 1.0mg/kg SC q 48 hr Extended release buprenorphine (9,10) NSAID Office for Responsible Research Page 16 of 29

Carprofen 4-5mg/kg SC,IP q24 hr For optimal analgesia, give NSAID and buprenorphine Meloxicam 1-5mg/kg SC,PO q24 hr (4) Office for Responsible Research Page 17 of 29

Fetal and Neonatal Mouse (E15-P14) Fetal and Neonatal Mouse - Analgesia Buprenorphine 0.05-0.1mg/kg SC (14,15) Morphine 10mg/kg SC (14,15) Bupivicaine Local infiltration, max dose 2mg/kg 14,15 Fetal and Neonatal Mouse - Anesthesia Isoflurane Inhalant 5% Induction, 0.25 2.5% maintenance 0.25 2.5% maintenance Vaporizers should be calibrated yearly (14,15) Pentobarbital Max dose 30mg/kg IP Higher doses may result in significant mortality. Pentobarbital given to pregnant dams may anesthetize the fetuses. (14,15) Office for Responsible Research Page 18 of 29

Rabbit Rabbit - Pre-Medications Agent Dose Comments/References Acepromazine 0.5-1.0mg/kg IM Moderate sedation (1,8) Diazepam 0.5-2mg/kg IV Light to moderate sedation (8) Midazolam 0..5-2mg/kg IM, IV Light to moderate sedation (8) Rabbit - Inhalant Anesthesia Isoflurane 1-3% maintenance Administer with a precision vaporizer and compressed oxygen; not recommended for sole agent of induction due to potential for breath holding and distress (1) Rabbit - Injectable Anesthesia 50mg/kg IM Surgical Anesthesia (8) Acepromazine 1mg/kg IM 35mg/kg IM Surgical Anesthesia (8) 5mg/kg IM Acepromazine 35mg/kg IM 5mg/kg IM 1.0mg/kg IM Surgical Anesthesia (8) Office for Responsible Research Page 19 of 29

Dexmedetomidine 15mg/kg IM 0.12mg/kg IM Pentobarbitol 20-60mg/kg IV (1) Propofol 2-10mg/kg IV slowly over 60-90 seconds. Surgical Anesthesia (8) Induction/light anesthesia only. Less effective in rabbits, higher doses (15-20mg/kg) may result in respiratory arrest (8) Rabbit - Analgesia OPIOID Buprenorphine 0.1-0.05mg/kg SC, IV q8-12 hr Buprenorphine SR NSAID Carprofen Meloxicam Acepromazine Diazepam Midazolam 0.12mg/kg SC q72hr 1.5mg/kg PO q24 hr 2-4mg/kg SC q 24 hr 0.2-0.3mg/kg SC, PO q24 hr 0.6-1mg/kg SC, PO q24 hr 0.5-1.0 mg/kg SC, IM 0.5-2mg/kg IV 0.5-2mg/kg IM,IV (1,8) (8) (4) (8) Rabbit - Local Block Anesthesia Lidocaine (1-2%) 2-4mg/kg SC Onset 5-10 min, duration 0.5-1 hr (3) Bupivicaine (0.5%) 1-2mg/kg SC Onset 15-30 min, duration 4-8 hr (3) Office for Responsible Research Page 20 of 29

Rabbit - Anticholinergics Glycopyrrolate 0.01mg/kg IV 0.1mg/kg SC, IM Anticholinergic of choice to use as pre-anesthetic (4,8) Office for Responsible Research Page 21 of 29

Rat Rat - Inhalant Anesthesia Isoflurane 3-5% induction 1-3% maintenance Administer via precision vaporizer and compressed oxygen or drop method Rat - Injectable Anesthesia Acepromazine Midazolam Acepromazine 75-100mg/kg IP 5-10mg/kg IP 75mg/kg IP 1-2.5mg/kg IP 75-100mg/kg IP 4-5mg/kg IP 40mg/kg IP 5mg/kg IP 1mg/kg IP Propofol 10mg/kg IV (2) Provides a good surgical plane of anesthesia for most procedures.(5,8) Immobilization/anesthesia (8) Immobilization/anesthesia (8) Surgical anesthesia (8) Rat - Analgesia OPIOID Buprenorphine 0.01-0.05mg/kg SC,IP q6-12 hr Preferred analgesic for rodents (1,8) Buprenorphine SR 1.2mg/kg SC q 48 hr Extended release buprenorphine (11,12) NSAID Office for Responsible Research Page 22 of 29

Carprofen 5-10/kg SC,PO q24 hr For optimal analgesia, give NSAID and buprenorphine (1,4) Meloxicam 1-2mg/kg SC,PO q24 hr (4) Office for Responsible Research Page 23 of 29

Fetal and Neonatal Rat (E15-P14) Fetal and Neonatal Rat- Analgesia Buprenorphine 0.05-0.1mg/kg SC (14,15) Morphine 10mg/kg SC (14,15) Bupivicaine Local infiltration 14,15 Fetal and Neonatal Rat- Anesthesia Isoflurane Inhalant 5% Induction, 0.25 2.5% maintenance 0.25 2.5% maintenance Vaporizers should be calibrated yearly (14,15) Pentobarbitol 30mg/kg IP Higher doses may result in significant mortality. Pentobarbital given to pregnant dams may anesthetize the fetuses. (14,15) Office for Responsible Research Page 24 of 29

Reptile Reptile - Inhalant Anesthetic Isoflurane 4-5% induction 1-3% maintenance Standard agent for reptiles but may hold their breath and resist effects of exposure to high concentrations of agent. In anesthetic chamber +/- intubated after induction. Recover in room air (not pure O2) because reptiles are stimulated to breathe by decreasing O2 levels, not increasing CO2 levels Reptile - Injectable Anesthetic Diazepam 0.2-2mg/kg IM,IV Lizards and Snakes Medetomidine 5-30mg/kg IM (lizards) 10-60mg/kg IM (snakes) 0.05-0.1 mg/kg IM(lizard) 0.1-0.15 mg/kg IM,IV (snake) Sedation and anesthesia is species and dose dependent. May have prolonged recovery (1-4 days) Propofol 3-5mg/kg IV Lizards and Snakes Reptile - Analgesia Dose Agent Comments/Reference(s) Buprenorphine Carprofen 0.02 0.2 mg/kg SQ,IM q12-24hr 2-4mg/kg IM,IV,SQ,PO q24-72hr Lizards and snakes, for post-op analgesia Lizards and snakes Meloxicam 0.1-0.2mg/kg PO q24h Lizards and snakes Office for Responsible Research Page 25 of 29

Sheep and Goats Sheep & Goats - Inhalant Anesthesia Isoflurane 3-5% Induction 1-3% Maintenance Administer via precision vaporizer and compressed oxygen. Sheep & Goats - Injectable Anesthesia Diazepam Propofol 4-5mg/kg IV 0.4-0.5mg/kg IV 3-5mg/kg induction Induction, rapid onset, duration of effect 15 to 20 minutes allow intubation minimum regurgitation, little cardiopulmonary dysfunction (1,7) No analgesic effect (1,7,8) 0.4-0.5mg/kg/min CRI Sheep & Goats - Analgesia OPIOID Butorphanol 0.1-0.5mg/kg IM q2-4 hr (1) Buprenorphine NSAID 0.005-0.01mg/kg IV, IM, SC q4-6 hr Carprofen 2-4mg/kg SC q24 hr (1,2,7) Flunixin 1.1-2.2mg/kg IV, IM, q 8-24 hr Phenylbutazone 2-6mg/kg IV, PO q 24 hr (2) Meloxicam 0.5 mg/kg IV q 12 hrs (sheep) or q 8 hrs (goats); 2 mg/kg PO on day 1, 1 mg/kg PO on subsequent days (sheep); 0.5 mg/kg PO q24 hrs (goats) (1) (2) (2) Office for Responsible Research Page 26 of 29

Tranquilizers Acepromazine 0.02mg/kg IM Pre-anesthetic/sedative. Long duration of action. Will prolong anesthesia recovery. Not an analgesic. (1) Acepromazine Buprenorphine 0.05-0.1mg/kg IM 0.005-0.01mg/kg IM Pre-anesthetic/sedative (1,7) 0.05-0.2mg/kg IV,IM Pre-anesthetic/sedative (1,7) Office for Responsible Research Page 27 of 29

Swine Swine - Anticholinergics Atropine 0.02-0.05mg/kg SC,IM,IV Give 10-15 minutes prior to intubation. Reduces bradycardia and hypersalivation (4) Glycopyrrolate 0.005-0.01mg/kg SC,IM Reduces bradycardia and hypersalivation (4) Swine - Inhalant Anesthesia Isoflurane 1-3% maintenance Administer with a precision vaporizer and compressed oxygen Swine - Injectable Anesthesia Dexmedetomidine Tiletamine-Zolazepam Detomidine Butorphanol 10-20mg/kg IM,SC,IV 1-2.0mg/kg IM,SC,IV 10mg/kg IM,SC,IV 0.1mg/kg IM,SC,IV 4.4mg/kg IM,SC 2.2mg/kg IM, SC 2.2mg/kg IM,SC Mixture: 0.02-0.04 ml/kg 0.05-0.1 mg/kg IM 0.2 mg/kg IM (1,6) (1,6) Same as above, less volume to inject, useful in pigs >50kgs. (6) Mix by adding 2.5 ml and 2.5 ml 100 mg/ml xylaxine to Telazol powder Give detomidine and butorphanol; Give 5-10 minutes later; may reverse with 50 mg/kg atipamezole (6) Office for Responsible Research Page 28 of 29

3-5 mg/kg IM Propofol 2-6mg/kg IV (6) No analgesic effect Medetomidine, OR Dexmedetomidine 10 mg/kg 0.2mg/kg OR 0.1 mg/kg Reverse with atipamezole at 1 mg/kg Swine - Analgesia OPIOID Buprenorphine 0.01-0.05mg/kg IM, SC (6,8) Buprenorphine SR NSAID 0.18mg/kg SC q48-72 hr Meloxicam 0.1-0.3mg/kg SC, PO q24 hr (6) Flunixin 2.2 mg/kg IM (2) Tranquilizers Acepromazine 0.2-1.1mg/kg IM,IV,SC Sedation only (1) (variable results) Swine Drug Antagonists Tolazine 2-4 mg/kg slowly IV Reverses alpha 2 agonists like xylazine Yohimbine 0.1 mg/kg IM or IV Reverses xylazine like drugs Atipamezole 1 mg/kg Reverses alpha 2 agonists Office for Responsible Research Page 29 of 29