Given the number of opiates available and the different methods of administration available, choosing the best analgesic or premedication plan for patients can be overwhelming. As a result, it is easy to get used to using just one or a few protocols for each patient. At this week’s Fetch dvm360® virtual conference, Katrina Lafferty, RLAT, CVT, VTS (Anesthesia / Analgesia) discussed the many opioid options available and how protocols can best be tailored to meet individual patient needs.
Lafferty, a senior technician in the Department of Anesthesia and Surgery at the Wisconsin National Primate Center, first reminded the audience of the two main opiate receptors relevant in veterinary medicine: mu and kappa. Mu receptors, which are mainly located in the central nervous system and throughout the gastrointestinal system, have a stronger effect than kappa receptors and provide moderate to severe analgesia. The primary effects of mu-receptor stimulation are physical addiction, euphoria, analgesia, and respiratory depression. Sedation and constipation are also seen to a lesser extent.
Kappa receptors, which are also located in the central nervous system as well as in some peripheral sensory neurons, offer only mild to moderate analgesia. The primary effects of kappa receptor stimulation are sedation, analgesia, miosis (tiny pupils), and psychosomatic effects (e.g. anxiety, hallucinations, and nightmares). It is unclear how these psychosomatic effects affect veterinary patients.
The implications of agonists, antagonists, and mixed agonists / antagonists can extend beyond the immediate situation and decision. Pure agonists have a high binding affinity and lead to a highly potent response. Pure antagonists have a high binding affinity, but are not effective because they block the effects of other drugs on the receptor. Partial agonists can bind to the receptor, but in a way that confers less potency than pure agonists. Finally, mixed agonist-antagonists act as agonists on one receptor and as antagonists on another receptor.
In addition to these categorical characteristics, individual opioid drugs have specific side effects and areas of clinical effectiveness that need to be considered. Lafferty presented several cases to illustrate how the different characteristics and mechanisms of action of individual drugs affect clinical decision-making.
Case 1: Foreign body of the esophagus
Should morphine be used for premedication, sedation, or analgesia in a patient with a sharp foreign body in the esophagus? Given the high potential of morphine to cause vomiting, its use in such a case would be contraindicated due to the risk of perforation. However, morphine can be beneficial in a patient with a soft foreign body, allowing the object to be vomited, thereby avoiding the need for surgical or endoscopic removal in some cases.
Case 2: limb amputation
Is butorphanol a good option for analgesia in a dog presented for a foreleg amputation? Since butorphanol only has a mild to moderate analgesic effect and the duration of action is only about 1 hour, butorphanol does not fit this clinical situation well.
Case 3: mandibular fracture
Is buprenorphine a good pre-operative pain control option in a kitten with a mandibular fracture referred for emergency surgery? Although buprenorphine provides 6 to 12 hours of analgesia, it may not provide adequate analgesia for the level of pain that is experienced. If surgery is expected during this time, the weak antagonist effect may interfere with the anesthetic and analgesic protocol.
Route of administration
In addition to determining the most appropriate drug for a particular clinical situation and patient, the best route of administration must also be considered. Possible routes are constant rate infusions (CRI), epidural, localized blocks, transmucosal delivery, and transdermal delivery.
CRIs can circumvent the short half-life of some opiates and allow titration to a consistently effective dose, avoiding the peaks and valleys that lead to respiratory depression or breakthrough pain. Local blocks that combine opiates with lidocaine or bupivacaine can extend the duration of analgesia from the block and minimize systemic side effects of opiates. Furthermore, epidural or local blockages can reduce the concentration of inhalation anesthesia required for procedures. Transmucosal administration of buprenorphine is a useful option in cats, although it takes 60 to 90 minutes to take effect. In dogs, however, the dose requirements are much higher, making the transmucosal option impractical.
When administering naloxone, it should be noted that reversal agents reverse not only the adverse effects of opiates, but also their analgesic properties. Lafferty noted that there is no real “half dose” that uses naloxone. Regardless of the dose used, it should be assumed that the reversal will reverse all analgesia. It is also important to consider the duration of action of the opiates previously on board, as well as the reversal drugs administered. For example, the duration of naloxone is 30 to 60 minutes. So if the previously administered opiates have a longer duration of action, be prepared to re-dose the reversal drug if the signs relapse. Conversely, if additional analgesia is required after administration of naloxone, you should be aware that additional opiates can only be re-administered after the duration of action of naloxone has expired. Because of this limitation, in some cases where analgesia is still required but reversal may be beneficial, butorphanol may be a suitable option when partial reversal is sufficient.
Rebecca A Packer, DVM, MS, DACVIM (Neurology / Neurosurgery), is Associate Professor of Neurology / Neurosurgery at Colorado State University College of Veterinary Medicine and Biomedicine at Fort Collins. She is active in the clinical and educational training of veterinary students and local residents and has developed a comparative research program in neuro-oncology at Colorado State University.