Intraoperative Monitoring

Good surgical technique alone is not sufficient to ensure a successful outcome for complex procedures required for medical device implants. Intraoperative and postoperative monitoring of heart rate, electrocardiogram, blood pressure, and blood gases are essential contributors to a positive outcome.

Acute Studies

If the study is acute and the device-associated trends are expected to be transient during the period of acute observation and harvest, FDA recommends that you track and record vital signs such as cardiac rhythm, respiratory rate, pulse oximetery, and blood pressure on operative records. This information should be correlated with the timing of insertion, implantation, deployment, or use of the device, contrast agent, or other device-associated materials, and noted on the anesthetic and/or operative records.

Chronic Studies

Post Operative Period

FDA recommends that you follow the current standard of care for laboratory research animals by ensuring that investigators manage normal body temperature, minimize pain and infection, and provide adequate fluids and electrolytes. You should capture physiological information similar in quality to that obtained in human care and recovery areas. In addition, you should control stress variables by establishing a standard assessment paradigm for the monitoring of pain and body temperature, and directing the administration of additional warmth and pain killers based on interim outcomes.

Interim Period of Observation

During periods where animals have recovered from initial surgical procedures but are to be monitored for device-associated risks, FDA recommends that you monitor them at least twice daily at feeding times so that they may be observed when active. FDA also recommends that you consult your veterinarian and develop a weight monitoring plan. You should consider inclusion of body scoring as an adjunct to your periodic observations of the animal. If your study involves the collection of clinical chemistry data or more advanced diagnostics, it is recommended that you develop standard operating procedures that prescribe, when needed, a method of chemical restraint that does not interfere with the device. In our experience, some animals, such as dogs and sheep, may be conditioned to be compliant for these activities, while swine rarely are.

Terminal Study Period‍

FDA recommends that the study protocol include details of the terminal study and include all methodology for the examination, collection and processing of tissue. This section of the protocol should include the following information:

• methods for end-period examination;
• (if applicable) a statement that in-life radiographic analysis and/or imaging will be completed; and
• methods for establishing end weight and/or body score.

Necropsy and Post-Mortem Evaluation

Adverse events may present clinically or subclinically; therefore, FDA recommends that you include a comprehensive systematic necropsy in your study, including tissue collection and preservation for possible processing for histopathology examination as the resulting information can help FDA to determine whether observed adverse events are device-related. FDA generally recommends that you describe the rationale and process for how sectioning of organs is performed and the training and experience of the prosector in order to assure an objective process in the sampling of gross tissue for microscopic evaluation. You should support any statements regarding whether any adverse outcomes are device-related with appropriate evidence from the necropsy or histopathology report and from in-life observations. In the event of an unscheduled death, you should be able to provide evidence that supports your statement regarding cause of death.

‍