Procedure # IBT IACUC Approval: December 11, 2017

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1 IACUC Procedure: Anesthetics and Analgesics Procedure # IBT IACUC Approval: December 11, 2017 Purpose: The purpose is to define the anesthetics and analgesics that may be used in mice and rats. Scope: This procedure applies to all Animal Use Protocols (AUPs) subject to oversight by the Texas A&M University Houston/Kingsville Institutional Animal Care and Use Committee (IACUC). Responsibilities: Appropriately trained research staff are expected to monitor rodents in accordance with this procedure. Animal care staff will conduct routine health surveillance and any concerns will be reported to the veterinary staff. Definitions: Analgesic: Any member of the diverse group of drugs used to relieve pain (achieve analgesia). Analgesic drugs act in various ways on the peripheral and central nervous systems. They include acetaminophen, the non-steroidal antiinflammatory drugs (NSAIDs) such as the salicylates, narcotic drugs such as morphine, and synthetic drugs with narcotic properties. Pain control: Sedatives, analgesic agents, and general anesthetic agents must be utilized for the control of pain and distress unless their use is contrary to the achievement of the objectives of the study, in which case strong justification must be provided. Sedative: cause a state of calmness and a mild degree of CNS depression. They do not provide analgesic affects. This term is interchanged with tranquilizer. Tranquilizer: cause a state of calmness and a mild degree of CNS depression. They do not provide analgesic affects. This term is interchanged with sedative. Background: 1. The more common injectable anesthetic used is a ketamine/xylazine combination. The drugs can be mixed together and given as one injection. Though the drug combination can cause moderate respiratory depression and hypothermia, there is minimal mortality with its use. 2. The use of pentobarbital has historically been popular but provides poor analgesic properties and has a narrow margin of safety. Respiratory depression can be profound and circulatory depression moderate with the use of pentobarbital. 3. is the inhaled anesthetic of choice. Thermal support is critical to their recovery to prevent hypothermia. 4. Tribromethanol may not be used for survival surgery without scientific justification and IACUC approval. See following discussion: Tribromoethanol was first used in human clinical practice in the 1920 s at a time when other choices for general anesthesia were limited to diethyl ether and chloroform. As a pharmaceutical-grade anesthetic, tribromoethanol (TBE) was once marketed under several proprietary names including Avertin. However, commercial production of pharmaceutical-grade TBE was discontinued several years ago as better alternatives became widely available for both human and veterinary use. As an anesthetic, TBE is easy and inexpensive to make in the laboratory from readily available nonpharmaceutical-grade reagents, requires no special equipment for administration, and is not subject to Procedure #IBT Page 1 of 5

2 Guidelines: federal or state drug enforcement regulations. However, adverse reports about the efficacy and safety of TBE, combined with the availability of effective pharmaceutical-grade alternatives, have made the continued use of TBE for rodent anesthesia controversial. Many of the problems associated with TBE relate to improper storage and handling. This can lead to the formation of toxic degradation products which are potent gastrointestinal irritants. Adverse effects such as intestinal ileus, serositis and peritonitis have been widely reported as a leading cause of morbidity and mortality in rodents following intra-peritoneal administration of TBE. Even under ideal conditions, many have concluded that TBE should not be used in laboratory animals because it produces an anesthetic state which is often inconsistent and variable. Stock solution is light sensitive and evaporates rapidly. Do not leave the bottle open longer than is necessary. Label, date and refrigerate in tightly sealed, dark bottle. Yellowing of the solution indicates toxic degradation products and the stock must be replaced. Unused stock solution should be discarded after 6 months after opening. 1. Labeling If analgesics are removed from their original packaging, or mixed as a cocktail, the primary container must be appropriately labeled and stored. Details regarding labeling requirements for Controlled Substances are found in IACUC Procedure 215. In general, labels should include the following information: a. The name of the substance or mixture b. The date reconstituted (if the original was in powder form) or the date the substances were mixed c. The final concentration of the substance d. The date of expiration. Pharmaceutical mixtures (cocktails, e.g. ) should be prepared and used on acute basis only (1-7 days), and must be prepared and maintained under sterile conditions. 2. Anesthesia: Reflexes or response to surgical stimuli, body temperature, and the cardiopulmonary system should be thoroughly evaluated when monitoring an animal under anesthesia. Pedal withdrawal, or ocular reflexes can be used to assess anesthetic depth. ANESTHESIA FOR RATS Drug Dose Range Indications Duration (min) mg/kg Surgical anesthesia mg/kg IP Medetomidine / mg/kg mg/kg IP mg/kg +2-6 mg/kg +1-2 mg/kg IP Surgical anesthesia Surgical anesthesia Pentobarbital mg/kg IP Low margin of safety Recommend in non-survival surgery Procedure #IBT Page 2 of 5

3 3-4% for induction; followed by 1.5-3% for Maintenance dose depends on other drugs given and level of ANESTHESIA FOR MICE mg/kg Medetomidine +10 mg/kg IP / 50 mg/kg +5 mg/kg IP mg/kg mg/kg IP 100 mg/kg +2.5 mg/kg +2.5 mg/kg IP Major surgical Avertin mg/kg IP Major surgical Pentobarbital mg/kg IP Major surgical Procedures followed by 1.5-3% for Maintenance dose depends on other drugs given and level of ANESTHESIA FOR RABBITS 7.5 mg/kg mg/kg IM mg/kg: mg/kg IM min Light sedation to surgical anesthesia Ketamine: : 35:5:1 mg/kg IM, SC min Surgical anesthesia followed by 1-2% for Maintenance dose depends on other drugs given and level of ANESTHESIA FOR HAMSTERS Procedure #IBT Page 3 of 5

4 followed by 1-2% for 3. Analgesics: Analgesia and pain-relief protocols should be based upon the species, the procedure to be performed, the pharmacology and pharmokinetics of available agents, anesthetic-analgesic drug interactions, and adverse effect profiles of individual agents. The following table provides a quick reference for drugs, dosages and routes of administration for all drugs approved by the IACUC. Agent Mouse Rat Aspirin mg/kg PO BID mg/kg PO BID Buprenorphine mg/kg SC q 6-12 hr mg/kg SC q 6-12 hr 0.6 PO q 12 hr Butorphanol 1-5 SC mg/kg q 4-6 hr 2 mg/kg SC q 4-6 hr Carprofen 4 mg/kg PO q 24 hr (may be fatal) 5 mg/kg SC BID Flunixin Meglumine Ketoprofen 2 mg/kg PO SID Ketorolac mg/kg PO SID 3-5 mg/kg PO SID-BID; IM SID- BID Meloxicam 0.3 mg/kg IP, SC SID 1-2 mg/kg PO, IM, SC 20 mg/kg SC q 2-3 hr Meperidine 10 mg/kg SC q 2-3 hr Morphine Nalbuphine Oxymorphone Pentazocine 2-5 mg/kg SC q 2-4 hr 4-8 mg/kg SC, IM q 4-8 hr mg/kg SC, IV q 6-12 hr 10 mg/kg SC q 3-4 hr 2-5 mg/kg SC q 2-4 hr 1-2 mg/kg SC, IM q 4-8 hr 0.3 mg/kg SC q 4 hr 10 mg/kg SC q 3-4 hr 4. Neuromuscular blocking drugs (NMBD) Federal regulations and policies state that that may cause momentary or slight pain or distress to the animal will not include the use of paralytics without anesthesia. Procedures on animals that may cause more than momentary or slight pain or distress should be performed with appropriate sedation, analgesia, or anesthesia. Surgical or other painful must not be performed on unanesthetized animals paralyzed by chemical agents. Procedure #IBT Page 4 of 5

5 Where there are specific indications that NMBDs are scientifically justified, physiologic monitoring to determine appropriate anesthesia is necessary, and should include at minimum, adequate monitoring of the animal s pulse oximetry, blood pressure, or heart rate. Additional parameters that may be used for assessing depth of anesthesia and antinociception must be specified in the protocol. SPECIAL NOTE Several drugs listed are controlled drugs. Investigators are responsible for obtaining their own DEA registration. Please contact EHSD for controlled drug questions. References: 1. Fish, et al. Anesthesia and Analgesia in Laboratory Animals, 2 nd ed., Academic Press, Fox, et al. Laboratory Animal Medicine, 2 nd ed., Academic Press, Manning, et al. The Biology of the Laboratory Rabbit, 2 nd ed., Academic Press, Suckow, et al. The Laboratory Rabbit, Guinea Pig, Hamster and Other Rodents, 1 st ed., Academic Press, AALAS Learning Library, History: Version 00 Initial Approval: October 27, 2014 Version 01 Approval: August 24, 2015 Version 02 Approval: September 26, 2016 Version 03 Approval: October 23, 2017 Version 04 Approval: December 11, 2017 Procedure #IBT Page 5 of 5