Recovery, Post-Operative Care and Evaluations in Sheep for Neurological Models to Demonstrate Safety and Efficacy

Presenter: Jay Budrewicz, CBSET

Introduction: To have a neurological exclusion removed from a medical device, it must be evaluated in an appropriate animal model. There are appropriate preclinical ovine models for this type of study due their similarities in size and structure to the human neurological organs. Adverse local tissue effects and post operative bleeding following treatment with the test, control and sham treatment can cause complications that must be managed and documented. Methods will be described for ovine recovery post-operative care, neurological exams, physical therapy, and pain management during neurological exclusion studies.

Methods: Following surgery, animals are transferred to a sling and extubated. The sling is used to transport them safely back to their pen. Post procedural analgesics/medications consisted of routine treatment of buprenorphine, dexamethasone and methylprednisolone. Animal health was monitored, including clinical observations, neurological exams, body weights/condition, and clinical pathology, at pre-determined intervals. Neurological examinations were performed by a veterinarian to assess the acute and progressive deficits that may have been present in the central nervous system as well as the peripheral nervous system. Symptomatic physical therapy was offered daily for up to one-hour sessions per animal when necessary.

Results: Use of the sling for post-operative recovery protected the animals from injury during recovery and allowed the technicians to easily support the animal until it could stand on its own. Analgesics provided adequate pain relief while corticosteroids had a neuroprotective and anti-inflammatory effect on the animals. Corticosteroids appeared to be more effective in this model than NSAIDs with fewer side effects. During neurological exams, laminectomies had the greatest number of serious adverse examination findings (knuckling, ataxia, paresis), as compared to craniectomy animals. Findings were generally resolved after one week. Physical therapy was rarely necessary and typically consisted of massaging the animals’ hind limbs while standing.

Conclusion: Lack of scheduled and consistent post-operative and pain management strategies for previous neurological safety and efficacy studies, specifically ones involving laminectomy procedures, have often resulted in paralysis through loss of hind limb use. The inability to ambulate prevented the animals from easily accessing food and water. Playing catch up with post-operative neurological symptoms was not effective. This resulted in significant neurological exam findings, which challenges if the device was safe and if deficits are associated with the surgical model. When using the routine methods described, the incidence of these issues was significantly decreased, allowing animals to thrive during the post operative period.