Is it Time to Redefine “Major Operative Procedures?”

The Animal Welfare Act (AWA) regulations define a “major operative procedure” as “any surgical intervention that penetrates and exposes a body cavity or any procedure which produces permanent impairment of physical or physiological functions.” The differentiation of surgical procedures as major or minor impacts research because AWA regulations: 1) require that major operative procedures on nonrodent species be performed in dedicated surgical facilities, and 2) permit only a single major operative procedure to be conducted on an individual animal unless the multiple procedures are included within 1 study, are required for the veterinary care of the animal, or an exemption is granted by the USDA Deputy Administrator.

Although the definition of a major operative procedure may seem straightforward, IACUCs often grapple with its meaning,⁴ leading to diverse interpretations. For example, making a small opening through the cranial bone to inject a substance into the brain, or creating a small opening in the abdominal wall to obtain a biopsy could be interpreted by some as a minor procedure and by others as a major procedure. Laparoscopic procedures, natural orifice surgical procedures, and hybrid surgeries that combine both approaches may also fall into this gray zone.⁶

One reason for limiting the use of animals in major operative procedures is to prevent their exposure to repeated pain or distress simply as an economic contingency. Cost savings alone cannot provide a justification for using an animal in more than 1 study involving major surgery.³ However, an unintended side effect of this policy is that overly conservative classifications of procedures as major surgeries can require the use of greater numbers of animals for research. This occurs because an animal that has experienced 1 penetration of a body cavity (for example, a laparoscopic procedure) cannot be employed for another study involving such procedures. As a consequence, a second animal must be procured, requiring 2 animals where 1 would otherwise suffice.

Modern anesthetics, analgesics, and surgical methodologies can alleviate much, if not all, of the pain, distress, or impairment of physiological function that may arise after many operative procedures that penetrate and expose a body cavity.^1,2,5,6 In contrast, techniques involving manipulation of subcutaneous tissue can be very painful,⁵ although IACUCs could view them as minor procedures based on the AWA definition. Furthermore, the principles of Russell and Birch,⁷ which have been adopted by many regulatory and accrediting organizations, encourage an overall reduction in the number of animals used in research. Annual reports of animal usage posted on the United States Department of Agriculture (USDA) website indicate that a large fraction of AWA-regulated species are employed in “Category D” studies,⁸ many of which likely entail surgery. Finding a secondary use for animals that previously had surgery and therefore cannot be utilized for studies that require additional major surgery may be impossible, requiring euthanasia that serves no useful purpose with regard to advancing research goals or animal well being.

Minimizing and limiting animal pain and distress are clearly important goals, but should be pursued in balance with the complementary objective of limiting the number of animals used in experimentation. The considerations discussed here support reevaluation of the definition of a “major operative procedure.” An alternative approach is to classify surgical procedures as major or minor based on the expectation of significant postoperative pain, distress, or physiological impairment, rather than on whether a body cavity is penetrated. This approach could allow more animals to be used in multiple studies, thereby reducing the number of animals that are euthanized simply because they can no longer be used for research entailing surgery. A better option is to allow them to be used in a humane manner that contributes to the generation of knowledge, and, in concert, reduces the overall number of animals required for biomedical research.