Guidelines

Guidelines on Anesthesia and Analgesia in Rabbits

Unit for Laboratory Animal Medicine
Nov 1, 2018 12:00 am

This document has been designed by the ULAM veterinary staff as a guideline for sedation, anesthesia, and analgesia of laboratory rabbits. This is not intended to be an inclusive tutorial on all possible drug combinations that can be used in rabbits. The following guidelines are also general recommendations and consequently do not include reference to specific research associated concerns. 

All surgical procedures, anesthetics, analgesics, antibiotics or other medications used on animals must be approved by the IACUC, described in the animal use protocol, performed by personnel listed on the protocol, and appropriately trained for the surgical procedure. Any techniques or drug protocols deviating from this document must be justified and approved in the IACUC protocol prior to application.

  • Responsibility

    1. Principal Investigator: Responsible to ensure appropriate anesthesia and/or analgesia is provided for all rabbits undergoing potentially painful procedures, including survival surgery, unless otherwise indicated in the relevant approved protocol.
  • Glossary Definitions

    CRI

    Continuous rate of infusion.

    IM

    Intramuscular.

    IV

    Intravenous.

    SC

    Subcutaneous.

    Sedation

    Central depression causing stupor where the animal is unaware of its surroundings but still responsive to painful procedures.

  • Procedures

    1. Prior to Anesthetic/Analgesic/Sedative Event

    1. Special considerations when anesthetizing rabbits
      1. Acclimation: Animals should be acclimated to their environment for a minimum of 72 hours, habituated to handling, and evaluated for obvious clinical signs of disease prior to anesthesia. Non-SPF rabbits may be infected with Pasteurella multocida; underlying lung damage from this pathogen may lead to respiratory arrest under anesthesia.
      2. Handling and Restraint: Rabbits are easily stressed by handling and induction.
        1. To avoid excessive anxiety in the pre- and post- anesthetic periods, provide an environment devoid of extraneous noise, including loud talking.
        2. The amount of restraint and its duration should be kept to the minimum required to accomplish the necessary procedure.
        3. To reduce the time of restraint, equipment and reagents should be ready to use prior to handling the animal.
        4. Pre-anesthetic doses of sedative/tranquilizer agents are often used to facilitate immobilization and to reduce anxiety.
      3. Fasting: Rabbits cannot vomit, therefore fasting is not mandatory. They do tend to accumulate food and fluid within the oral cavity and oropharynx. For this reason, a pre-anesthetic fast of 1-4 hours is recommended. Fasting also reduces the overall volume of the gastrointestinal tract thus reducing pressure on the diaphragm while under anesthesia. Fasting for longer periods of time may predispose them to post-operative ileus and may decrease blood glucose levels. More information regarding fasting duration can be found in Guidelines on Experimental Food or Water Restriction or Manipulation in Laboratory Animals.
      4. Surgical Position: Tilting the surgical table so that the rabbit's head is slightly elevated will reduce pressure on the diaphragm. Anesthetizing a rabbit on a level surface is also acceptable, however, caution should be taken to avoid inadvertently elevating the rabbit's hindquarters.
      5. Ocular lubrication such as Paralube® must be used to prevent corneal drying during anesthesia or sedation.

    2. Routes of Administration

    1. More detailed information regarding injection techniques and maximum quantities safely administered to rabbits can be found in Guidelines on Administration of Substances to Laboratory Animals.

    3. Normal Monitoring Parameters

    1. More information on anesthetic/sedation monitoring requirements can found in Anesthesia and Sedation Monitoring Guidelines.
    2. The goal of monitoring should be to maintain normal cardiac function, respiratory function, and body temperature. Understanding the basic physiologic effects of the anesthetics used is paramount to correctly interpreting monitoring parameters. More information on anesthetic and sedative effects on physiologic parameters can be found in Anesthesia and Analgesia Drug Descriptions
    3. Table 1: Physiologic Data of Rabbits

         

         Temperature   

         Heart Rate
         Beats per minute   

         Respiratory Rate   
         Breaths per minute   

         Without Anesthesia   

         100.4 - 104 F (38.0 - 40 C)   

         130 - 325   

         30 - 60 in resting rabbit   

         With Anesthesia   

         T >98 F (>37 C)   

         

         20 - 30   

    4. Physiologic Support

    1. Hypothermia
      1. An external heat source should be provided during the entire anesthetic and recovery period. For examples of approved external heat supplementation products, please refer to Anesthesia and Sedation Monitoring Guidelines.
    2. Fluids
      1. Providing fluid support during anesthesia is important particularly if a procedure lasts one-half hour or more. More information on appropriate fluid rates can be found in Guidelines on the Performance of Surgery in Non-Rodent Mammals.
    3. Vascular Access
      1. The placement of indwelling catheters are advised. The lateral (marginal) ear veins are easily accessed and the preferred site. The application of lidocaine-prilocaine EMLA® cream to the ear 30 minutes before venipuncture has been recommended to reduce pain. A tranquilizer or sedative can also be given prior to catheter placement to help decrease the rabbit's stress level. The cephalic and recurrent tarsal veins can also be utilized.
    4. Endotracheal Intubation
      1. Several techniques have been devised to simplify the difficult task of endotracheal intubation. The narrow mouth diameter, large tongue, limited range of jaw opening, and prominent incisors make placement of an endotracheal tube challenging. Please contact the ULAM Training Core to set up a time to learn how to correctly and safely perform endotracheal intubation in the rabbit.
      2. V-Gel (supraglottic airway device) Intubation: This device allows easier airway access when compared to endotracheal tubes. However, the V-Gel does not protect the airway from aspiration as effectively as endotracheal intubation. Also, there is a risk of tongue cyanosis. Please contact the ULAM Training Core to set up a time to learn how to correctly and safely perform endotracheal intubation in the rabbit.

    5. Recovery

    1. More information on required monitoring parameters during post-operative recovery can be found in Guidelines on the Performance of Surgery in Non-Rodent Mammals and Anesthesia and Sedation Monitoring Guidelines.
    2. Recover animals in clean kennels or transport cages. Animals must be fully recovered prior to return to their home cage.
    3. If a large number of surgeries are being conducted at one time, post-surgical animals may be housed together following anesthesia and prior to full recovery if they are continually observed. This is to ensure that more alert animals do not injure non-responsive cage mates.
    4. Nutritional support should be withheld until the animal is fully recovered and ambulating normally.

    6. Sedation Protocols

    1. Detailed information on all approved anesthetics and sedatives can be found in Anesthesia and Analgesia Drug Descriptions.
    2. All premedicants and sedatives should be administered 15-20 minutes prior to restraint or induction. Duration of action for sedative-analgesic combinations for use in minor procedures is generally 15-60 minutes depending upon combination used.
    3. The following drug combinations are for use with minor procedures or as premedicants prior to anesthetic induction.
      1. For dose ranges listed as IV, IM, and SC, use lower end of the range for IV administration. All dosages given in mg/kg unless otherwise indicated.

           Drug or Combination   

           Dose (mg/kg)   

           Route   

           Comments   

           Acepromazine   
           0.25 - 1   
           SQ, IM, IV   
           Light to moderate sedation without analgesia.   
           Causes vasodilation even at low dosages.   
           Diazepam   
           0.5 - 3   
           IV, IM   
           Light to moderate sedation without analgesia.   
           Slow IV administration preferred as painful upon IM injection.   
           Sedation can be reversed with flumazenil (0.01 - 0.1 mg/kg IV)   
           Midazolam   
           0.25 - 2   
           SQ, IM, IV, IP   
           Light to moderate sedation without analgesia.   
           Sedation can be reversed with flumazenil (0.01 - 0.1 mg/kg IV)   
           Dexmedetomidine   
           0.05 - 0.25   
           SQ, IM   
           Light to deep sedation with mild to moderate analgesia.   
           Reverse with atipamezole at the same volume as   
           dexmedetomidine (SQ, IM, IV)
           Xylazine   
           1 - 5   
           SQ, IM   
           Light to moderate sedation with mild analgesia.   
           Reverse with yohimbine (0.2 - 1 mg/kg, IM or IV) or   
           atipamezole (1 mg/kg SQ, IM, IV)
           Buprenorphine   
           0.01 - 0.05   
           SQ, IM, IV   
           Mild sedation with analgesia.   
           Most effective when administered ~60 minutes prior to anesthesia.   
           May cause respiratory depression.   
           Butorphanol   
           0.1 - 0.8   
           SQ, IM, IV   
           Mild sedation with analgesia.   
           Alfaxalone   
           6   
           IM   
           Moderate sedation up to 40 minutes.   
           Midazolam +   
           Butorphanol   
           0.2 - 1 +   
           0.2 - 0.4   
           IM   
           Mild to moderate sedation with analgesia.   
           Acepromazine +   
           Butorphanol   
           0.2 - 1 +   
           0.1 - 0.8   
           SQ, IM   
           Moderate to deep sedation, moderate analgesia.   
           Ketamine +   
           Acepromazine   
           25 - 50 +   
           0.25 - 1   
           IM   
           Deep sedation, variable analgesia.   
           Alfaxalone +   
           Midazolam   
           6 +   
           1   
           IM   
           Moderate sedation up to 60 minutes.
           Alfaxalone +   
           Dexmedetomidine   
           6 +   
           0.2   
           IM   
           Deep sedation for up to 2 hrs.
           Alfaxalone +   
           Dexmedetomidine +   
           Butorphanol   
           6 +   
           0.2 +   
           0.3   
           IM   
           Deep sedation for up to 2 hrs, analgesia for 40 minutes.

    7. Anesthetic Protocols

    1. For dose ranges listed as IV, IM, and SC, use lower end of the range for IV administration.
    2. Anticholinergics: Approximately 1/3 of all domesticated rabbits have a naturally occurring enzyme in their blood (atropinesterase, AtrE), which causes them to metabolize atropine faster. Repeated dosing of atropine every 10-15 minutes may be required if the heart rate falls below 65 beats/minute. Alternatively, glycopyrrolate may be used. Glycopyrrolate has a slightly longer duration of action compared to atropine and is less affected by circulating serum atropinase.
      1. Atropine 0.1-1 mg/kg, SQ or IM.
      2. Glycopyrrolate 0.01-0.1 mg/kg, SQ, IM or IV.
    3. Injectable Anesthetic Induction Agents Used in Rabbits
      1. Supplemental oxygen should be provided for all injectable anesthetic protocols. These combinations may not provide a surgical plane of anesthesia and should be used in combination with isoflurane. If, for minor procedures, isoflurane is not utilized, in combinations involving ketamine, anesthesia can be prolonged by supplementing with 1/3 dose of ketamine only. All dosages given in mg/kg unless otherwise indicated.

           Drug or Combination   

           Dose (mg/kg)   

           Route   

           Notes   

           Ketamine   
           + Midazolam   
           10 - 25   
           + 0.2 - 3   
           IV, IM, SQ   

           

           Ketamine   
           + Diazepam   
           10 - 40   
           + 0.2 - 5   
           IV, IM   
        • Diazepam is not water soluble.   
        • Do not mix drugs in the same syringe.   
        • Provides approximately 20 - 30 minutes of anesthesia.   
           Ketamine   
           + Dexmedetomidine   
           15 - 35   
           + 0.125 - 0.25   
           IM, SQ   
        • Provides approximately 30 - 45 minutes of anesthesia.   
           Propofol   
           3 - 10   
           IV   
        • For anesthesia induction only. Utilize slow bolus dosing to effect.   
           Ketamine   
           +   Xylazine   
           10 - 50   
           3 - 5   
           IM   
        • Provides approximately 30 - 45 minutes of anesthesia.   
           Ketamine   
           + Xylazine   
           + Butorphanol   
           10 - 40   
           + 3 - 5   
           + 0.1   
           IM   
        • Prolongs duration of anesthesia to 50 - 70 minutes.   
           Sodium Pentobarbital   
           NOT RECOMMENDED   
           30 - 45   
           
           IP, IV   
        • Significant cardiovascular and respiratory depression.   
        • Wide variation in anesthetic response.   
        • No analgesic properties.   
        • Do not use in combination with buprenorphine.   
    4. Anesthetic Maintenance Protocols
      1. Inhalation Agents

           Drug   

           Dose (mg/kg)   

           Notes   

           Isoflurane (induction)   
           To effect.  Typically 3 - 5%   
        • Calibrated vaporizer and active scavenging use required.   
        • Sedation should be used in conjunction with mask or chamber induction to avoid injury and minimize breathholding.
           Isoflurane (maintenance)   
           RECOMMENDED   
           To effect.  Typically 1 - 3%   
        • Calibrated vaporizer and active scavenging use required.   

    8. Neuromuscular Blocking Agents (NMBA)

    1. Extreme care must be taken to ensure that a proper level of anesthesia and analgesia is achieved prior to administering a neuromuscular blocking agent.
    2. Neuromuscular blocking agents require special monitoring procedures which are detailed in Anesthesia and Sedation Monitoring Guidelines.
      1. Concurrent positive pressure ventilation is required. Reversal of NMBAs with neostigmine and glycopyrrolate is possible under specific conditions. Please consult the ULAM veterinarians for instructions on NMBA reversal.

           Drug   

           Dose (mg/kg)   

           Route   

           Duration of Effect   

           Notes   

           Cisatracurium   
           0.12   
           IV   
           34 - 46 (38 average) minutes   
        • Onset in 1.5 minutes.   
        • Less variability in response than pancuronium.   
           Pancuronium   
           0.1   
           IV   
           42 - 70 (55 average) minutes   
        • Onset in 1.5 minutes.   

    9. Local Anesthetics

    1. Appropriate for minimally invasive procedures such as skin biopsy, or as a supplement to sedation, anesthesia and analgesia.
      1. Local anesthetics are excellent analgesics for use in minor procedures or as "splash blocks" for post-operative incision pain.

           Drug   

           Dose (mg/kg)   

           Route   

           Duration of Effect   

           Notes   

           Lidocaine   

           <4 (<0.4 ml/kg of a 1% solution)   

           Infiltrate   

           <1 hour (quick onset)   

           May need to dilute to achieve   
           appropriate volume for infiltration.   

           Bupivacaine   

           <2 (<0.8 ml/kg of a 0.25% solution)   

           Infiltrate   

           4 - 8 hours (slow onset)   

           May need to dilute to achieve   
           appropriate volume for infiltration.   

    10. Analgesics

    1. Signs of pain in rabbits include but are not limited to the following:
      1. Anxiety
      2. Apprehension
      3. Restlessness
      4. Decreased appetite
      5. Dullness
      6. Elevated respiratory rate
      7. Inactivity
      8. Increased aggression
      9. Immobility
      10. Hunched posture
      11. Tooth grinding
      12. Salivation
      13. Scratch/lick painful area
      14. Social isolation
      15. Vocalization
    2. Preferred opioid analgesics are buprenorphine, hydromorphone, or morphine.
      1. Buprenorphine and other narcotic agonists can be completely reversed with naloxone.
    3. The preferred non-steroidal anti-inflammatory (NSAID) is carprofen because it is generally well tolerated by the gastrointestinal tract, has good duration of effect, and does not appear to adversely affect platelet function.
    4. Opioids and NSAIDs can be combined for their additive or synergistic analgesic effects.

         Drug   

         Dose (mg/kg)   

         Route   

         Duration of Effect   

         Notes   

         Buprenorphine   
         0.01 - 0.05   
         SQ, IM, IV   
         Q6 - 12 hours   
         
         Morphine   
         2 - 5   
         SQ, IM   
         Q2 - 4 hours   
         
         Hydromorphone   
         0.05 - 0.2   
         SQ, IM   
         Q6 - 8 hours   
         
         Butorphanol   
         0.4 - 2   
         SQ, IM   
         Q2 - 4 hours   
         
         Fentanyl   
         (transdermal patch)   
         25 mcg/hr   
         Transdermal   
         Q72 hours   
         (from time of placement)   
      • Hair should be clipped in the area of placement.
      • Do not shave or use depilatory cream as it changes the pharmacokinetics of the drug.
      • Analgesia onset is 12 hours. The patch should be placed 12 hours prior to the procedure or, if placed during the procedure, another opioid analgesic should be employed until efficacy.
         Oxymorphone   
         0.05 - 0.2   
         SQ, IM   
         Q6 - 8 hours   
         
         Carprofen   
         2 - 4   
         SQ, IM, PO   
         Q24 hours   
      • Use high end of dose range for PO administration.   
         Meloxicam   
         0.2 - 1   
         SQ, PO   
         Q24 hours   
      • Use high end of dose range for PO administration.   
         Ketoprofen   
         3   
         SQ, IM, PO   
         Q24 hours   
         
         Flunixin meglumine   
         0.3 - 2   
         SQ, IM, IV, PO   
         Q12 - 24 hours   
      • Do not use for more than 3 days.   
    5. Preemptive analgesia, particularly opiates like buprenorphine, can reduce the dose of anesthetics required for surgical anesthesia and increase the respiratory depression associated with anesthetics. When preemptive analgesia is used, consider reducing the dose of anesthetic (whether inhalant or injectable) to the low end of the recommended range. Anesthetic depth must be carefully monitored and drug doses may need to be titrated to maintain appropriate levels. With new projects, sexes, strains or anesthetic analgesic combinations, assess a subset of animals before expanding to use in a larger cohort.
  • References

    1. Carpenter JW. 2013. Exotic Animal Formulary, Fourth Edition. St Louis (MO):Elsevier-Saunders.
    2. Diaz LL, Zhang J, Heerdt PM. 2014. Comparative pharmacodynamics of pancuronium, cisatracurium, and CW002 in rabbits. JAALAS 53(3):283-9.
    3. Flecknell P. 2009. Laboratory Animal Anaesthesia, Third Edition. San Diego (CA):Elsevier-Academic Press.
    4. Foley PL, et al. 2001. Evaluation of fentanyl transdermal patches in rabbits: blood concentrations and physiologic response. Comp Med 51(3):239-44.
    5. Fredholm DV, Carpenter JW, KuKanich B, Kohles M. 2013. Pharmacokinetics of meloxicam in rabbits after oral administration of single and multiple doses. Am J Vet Res 74(4):636-41.
    6. Harkness JE, Turner PV, VandeWoude S, and Wheler CL. 2010. Harkness and Wagner's Biology and Medicine of Rabbits and Rodents, Fifth Edition. Ames(IA):Wiley-Blackwell.
    7. Lester PA, Moore RM, Shuster KA, and Myers DD. 2012. Anesthesia and analgesia, p33-56. In: Suckow MA, Stevens KA, Wilson RP, editors. The ## Laboratory Rabbit, Guinea Pig, Hamster, and Other Rodents. San Diego (CA):Elsevier-Academic Press.
    8. Lipman NS, Marini RP, Flecknell PA. 2008. Anesthesia and analgesia in rabbits, p299-333. In: Fish RE, Brown MJ, Danneman PJ, Karas AZ, editors. Anesthesia and Analgesia in Laboratory Animals. New York (NY):Academic Press.
    9. Maguire S and Hawk CT. 2012. Formulary, p1193-1229. In: Suckow MA, Stevens KA, Wilson RP, editors. The Laboratory Rabbit, Guinea Pig, Hamster, and Other Rodents. San Diego (CA):Elsevier-Academic Press.
    10. Muir WW, Hubbell JAE, Bednarski RM, and Lerche P. 2013. Handbook of Veterinary Anesthesia, Fifth Edition. St Louis(MO):Elsevier-Mosby.
    11. Murphy KL, Roughan JV, Baxter MG, Flecknell PA. Anaesthesia with a combination of ketamine and medetomidine in the rabbit: effect of premedication with buprenorphine. Vet Anaesth Analg 37(3):222-9.
    12. Plumb DC. 2015. Plumb's Veterinary Drug Handbook, Eighth Edition. Ames (IA):Wiley-Blackwell.
    13. Quesenberry KE and Carpenter JW. 2012. Ferretts, Rabbits, and Rodents Clinical Medicine and Surgery, Third Edition. St Louis (MO):Elsevier-Saunders.
    14. Schroeder CA and Smith LJ. 2011. Respiratory rates and arterial blood-gas tensions in healthy rabbits given buprenorphine, butorphanol, midazolam, or their combinations. JAALAS 50(2):205-11.
Species: Rabbits
Questions?

If you have questions or comments about this document, contact ULAM Veterinary Staff (ULAM-vets@umich.edu or 734-936-1696).

The ULAM Training Core (ULAM-trainingcore@umich.edu or 734-763-8039) can be contacted to provide training in techniques at no charge.

For any concerns regarding animal health after work hours or on holidays/weekends, contact DPS (3-1131) who will contact the on-call veterinarian.