Institutional Animal Care & Use Committee, Yale University

Yale University
Institutional Animal Care
& Use Committee
New Haven CT
USA 06510

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Policy for the Use of Avertin as an Anesthetic

Overview:

Tribromoethanol, also known as "Avertin" is a commonly used anesthetic for surgery. Literature shows that Tribromoethanol has toxic breakdown products that if not stored properly can kill mice. Even when stored properly (or freshly made) it has been reported to cause peritonitis in mice (Zeller 1998) and rats (Reid 1999). Although this peritonitis is only rarely associated with morbidity or mortality (Pappianou 1993), we have to presume that peritonitis is painful and should be avoided when possible. A prior report (Pappiannou 1993) found that avertin was "safe and effective", but the authors were primarily measuring clinical illness, not histological changes.

Regulatory Issues:

The drug Avertin was long ago discontinued as an anesthetic in the medical and veterinary fields and is no longer commercially available. When using "Avertin" what is actually used is a mixture of non-medical grade ingredients that duplicate Avertin.

USDA policy on Pharmaceutical-Grade Compounds in Research is as follows:

Investigators are expected to use pharmaceutical-grade medications whenever they are available, even in acute procedures. Non-pharmaceutical-grade chemical compounds should only be used in animals after specific review and approval by the IACUC for reasons such as scientific necessity or non-availability of an acceptable veterinary or human pharmaceutical-grade product. Cost savings alone are not an adequate justification for using non-pharmaceutical-grade compounds in regulated animals.

Policy:

Under normal circumstances, Avertin is not to be used for survival and/or non-survival surgery. If investigators have a need to use Avertin, written scientific justification must be provided for IACUC review and approval.

Guidelines:

100 mg/kg ketamine and 10 mg/kg xylazine IP or SQ is recommended as an alternative. This dose produces approximately 30 minutes of surgical anesthesia in mice; contact VCS for doses for other species, or for alternatives using inhalant or other anesthetics. {In direct comparisons of ketamine-xylazine versus tribromoethanol, ketamine-xylazine was reported to cause no peritonitis, and to result in a comparable success rate in embryo transfer. (Zeller 1998)}

References:

Papaioannou VE, Fox JG. Efficacy of tribromoethanol anesthesia in mice.Lab Anim Sci 1993 Apr;43(2):189-92

Reid WC, Carmichael KP, Srinivas S, Bryant JL. Pathologic changes associated with use of tribromoethanol (avertin) in the Sprague Dawley rat. Lab Anim Sci 1999 Dec;49(6):665-7

Zeller W, Meier G, Burki K, Panoussis B Adverse effects of tribromoethanol as used in the production of transgenic mice.Lab Anim 1998 Oct;32(4):407-13

REVIEWED AND APPROVED BY THE IACUC: JULY 19, 2000