With the number of opiates available and the various methods of delivery, choosing the best analgesia or premedication plan for patients can be overwhelming. As a result, it is easy to fall into the habit of using only 1 or a few protocols for every patient. At the Fetch dvm360® virtual conference this week, Katrina Lafferty, RLAT, CVT, VTS (Anesthesia/Analgesia), discussed the many opioid options available and how best to tailor protocols to individual patient needs.
Opiate receptors
Lafferty, a senior technician in the anesthesia and surgery department at the Wisconsin National Primate Center, started off by reminding the audience about the 2 main opiate receptors relevant in veterinary medicine: mu and kappa. Mu receptors, which are located primarily in the central nervous system and throughout the gastrointestinal system, have a stronger effect than kappa receptors, providing moderate to heavy analgesia. The primary effects of mu receptor stimulation are physical dependence, euphoria, analgesia, and respiratory depression. Sedation and constipation are also seen to a less significant degree.
Opioid terminology
Efficacy is the maximum response achievable from a drug under ideal circumstances. “This would be [the effectiveness of] a drug that is tested on a young, healthy animal in a perfect setting,” Lafferty said. “It is not a sick, compromised, extremely painful animal.” Efficacy is often confused with effectiveness, which is the level of clinically achieved analgesia.
Pure agonists have an affinity for binding to receptor sites and high efficacy. Pure antagonists also have a high affinity for binding but have no efficacy; rather they block the action of agonist drugs.
A mixed agonist-antagonist acts as an agonist at 1 site, exerting a full effect, and as an antagonist at another, blocking any kind of effect at that receptor site. Partial agonists typically have a strong affinity for binding to receptor sites but low efficacy. “This is one of those keys that doesn’t completely fit in a lock,” Lafferty said. “Partial agonists sit in the receptor but don’t fully activate it.”
Kappa receptors, also located within the central nervous system as well as in some peripheral sensory neurons, provide only mild to moderate analgesia. The primary effects of kappa receptor stimulation are sedation, analgesia, miosis (tiny pupils), and psychosomatic effects (eg, anxiety, hallucinations, and nightmares). It is unclear how these psychosomatic effects translate to veterinary patients.
The implications of agonists, antagonists, and mixed agonist/antagonists can extend farther than the immediate situation and decision at hand. Pure agonists have high binding affinity and result in a highly efficacious response. Pure antagonists have a high binding affinity but do not result in efficacy as they block actions of other drugs at the receptor. Partial agonists are able to bind to the receptor, but in a way that imparts lower efficacy than pure agonists. Finally, mixed agonist-antagonists act as an agonist at 1 receptor and as an antagonist at another receptor.
Individual opioids
Exploring beyond these categorical characteristics, individual opioid medications have specific adverse effects and ranges of clinical effectiveness to consider. Lafferty presented several cases to illustrate how the various characteristics and mechanisms of action of individual drugs affect clinical decision-making.
Case 1: Esophageal foreign body
Should morphine be used for premedication, sedation, or analgesia in a patient with a sharp esophageal foreign body? Given the high potential for morphine to cause vomiting, its use would be contraindicated in such a case due to the risk for perforation. However, morphine may be advantageous in a patient with a soft foreign body, such that the object may be vomited, 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 forelimb amputation? Given that butorphanol only has a mild to moderate analgesic effect, and the duration of action is only about 1 hour, butorphanol is not a good match for this clinical situation.
Case 3: Mandibular fracture
Is buprenorphine a good option for pain control prior to surgery in a kitten with a mandibular fracture that is being referred for emergency surgery? Although buprenorphine provides 6 to 12 hours of analgesia, it may not provide sufficient analgesia for the degree of pain involved in this case, and if surgery is anticipated during that time, the weak antagonist effect may interfere with the anesthetic and analgesic protocol.
Route of administration
In addition to determining the most appropriate medication for a particular clinical situation and patient, the best route of administration must also be considered. Potential routes include constant-rate infusions (CRI), epidurals, local 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 troughs that result in respiratory depression and breakthrough pain, respectively. 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. Further, epidurals or local blocks may reduce the concentration of inhalant anesthesia required for procedures. Transmucosal delivery of buprenorphine is a useful option in cats, although onset of action is 60 to 90 minutes. In dogs, however, the dose requirements are much higher, rendering the transmucosal option impractical.
When naloxone is administered, it is important to remember that reversal agents reverse not only the adverse effects of opiates but also their analgesic properties. Lafferty noted that there is no true “half-dose” where naloxone is used. No matter the dose used, the reversal should be presumed to reverse all analgesia. It is also important to consider the duration of action of the opiates previously on board, as well as the reversal agents being administered. For example, the duration of naloxone is 30 to 60 minutes, so if the opiates previously administered have a longer duration of action, be prepared to re-dose the reversal agent if a relapse of signs occurs. Conversely, should additional analgesia be needed after administering naloxone, realize that additional opiates cannot be readministered until the duration of action of naloxone has elapsed. Due to this limitation, in some cases where analgesia is still required but reversal may be beneficial, butorphanol may be an appropriate option where partial reversal is sufficient.
Rebecca A Packer, DVM, MS, DACVIM (Neurology/Neurosurgery), is an associate professor of neurology/neurosurgery at Colorado State University College of Veterinary Medicine and Biomedical Sciences in Fort Collins. She is active in clinical and didactic training of veterinary students and residents and has developed a comparative neuro-oncology research program at Colorado State University.
