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Opioids: Friend or Foe

Updated: May 19, 2022

This blog post was written by the fabulous Dr. Annatasha Bartel. She is a Board Certified Specialist in Veterinary Anesthesia and Analgesia. She currently lives, works, and creates in Toronto.

Veterinary medicine relies heavily on opioids both for sedation and analgesia. However, these drugs confer significant adverse effects and as such, need to be used judiciously and appropriately. Consideration should be given to opioid-sparing techniques, including locoregional anesthetic techniques, the use of alternative drug classes, and titrating opioid analgesics to effect.

Opioids are often described as analgesics, though they largely function as hypoalgesics, that is, they are potent at abating pain but cannot obliterate it. Local anesthetics, for example, are true analgesics as they stop both ascending and descending nerve impulses in the nociceptive pathways.

In addition to the desirable effects of modification of pain (or nociception in unconscious patients), sedative properties, and antitussive activity, opioids precipitate adverse physiological and even emotional consequences in every species studied. These include but are not limited to: bradycardia, hyperventilation or hypoventilation, bradypnea or tachypnea, hypothermia or hyperthermia, nausea, emesis, ileus, anorexia, urinary retention, euphoria or dysphoria, hyperexcitement, increased auditory sensitivity, pruritus, alopecia, and immunosuppression. Opioid tolerance has yet to be

recognized in veterinary medicine though opioid induced hyperalgesia has been.

The likelihood of inducing vomiting when administering an opioid is related to the type of opioid given, the dose, and the route of administration. The more hydrophilic the opioid, the more slowly it crosses the blood-brain barrier (BBB). This means that it has some time to activate the chemoreceptor trigger zone (CRTZ), which is outside the BBB. Binding at the CRTZ site will incite nausea and vomiting. Hydrophilic opioids include hydromorphone, oxymorphone, and morphine. Conversely, lipophilic opioids, such as fentanyl, methadone, & buprenorphine) rapidly traverse the BBB and interact with central mu opioid receptors that appear to mediate antiemesis, which is why less vomiting is observed with these drugs.

Often in anesthesia, we use opioids to reduce the amount of anesthetic inhalant needed to achieve an appropriate anesthetic plane, i.e. as MAC sparing agents. However, this phenomenon is drug, species, and dose dependent. In particular, opioids are only marginally MAC sparing in cats and horses.

Needless to say, it is important when making a clinical decision about the use of an opioid to weigh these factors against the patient’s analgesic requirements. If pain is present, what is the nature or type of pain and what is the grade of pain evident? Not all pain is equal in etiology and extent and therefore, there are often many instances where a full mu-agonist opioid is not an appropriate choice for the patient and other classes of drugs should be carefully considered, e.g. NSAIDs. If there is no clinical evidence of pain when examining the patient, then an opioid should not be administered presumptively, e.g non-obstructive gastric foreign body. Much like giving empirical antibiotics without any clinical indication of infection, dosing opioids in these cases will cause the patient more harm than good. To understand why this is the case, we must consider how the nociceptive/pain pathways work.

Transduction is the conversion of a noxious mechanical, thermal, or chemical signal into electrical activity in the periphery; transmission involves conduction along peripheral sensory nerves and relay of the information along the spinal cord; perception is conscious awareness occurring in higher brain centers; modulation occurs at all levels.

The pain pathways remain dormant until there is a thermal, mechanical, or chemical stimulus. Part of the activation of these pain pathways includes the expression of anti-nociceptive opioid receptors. There are, however, opioid receptors present and expressed continuously in other parts of the body such as the heart tissue, the gut, the vomiting center, etc.

What does this mean clinically? If you administer an opioid to a patient that is not painful, i.e. their pain pathways are inactive or dormant due to the absence of tissue injury, the opioid will bind to the receptors in other areas of the body outside the central nervous and precipitate the adverse effects discussed. Often you will notice these patients become nauseous and drool, they may vomit, they may pant, and will appear distressed from dysphoria. However, you do not usually observe these similar outcomes if you administer an opioid to a painful patient, e.g. fractured femur. That is because the opioids have bound to the receptors in the pain pathways that were activated at the initiation of bodily injury.

You can also observe a similar phenomenon related to the dose of opioid given. If you exceed the appropriate dose of opioid needed for a patient, you will saturate the anti-nociceptive opioid receptors and the remaining amount of opioid will then seek to bind elsewhere, the consequence being that you will likely see sedation, recumbency, urine retention, regurgitation, inappetence, dysphoria, etc. Remember: more opioid is not better for the patient, it is often simply just more. Each patient’s pain must be carefully evaluated and that patient dosed accordingly. It is better to give a lower dose of an opioid and administer additional analgesics as required than to overdose that patient and risk the less than desirable consequences.

In particular, opioid hyperalgesia needs to be taken into consideration. Opioid-induced hyperalgesia (OIH) is the paradoxical enhancement of nociceptive processing, e.g. opioid-induced neurotoxicity resulting in hyperexcitability and hyperalgesia. Patients who suffer from OIH will require higher doses of opioids at more frequent intervals for longer periods of time to mitigate their pain. Although somewhat controversial in the species of veterinary interest, this phenomenon has been detected in dogs who underwent repeated surgical decompression of the spinal cord and required ever increasing doses of fentanyl during subsequent surgeries and surgical recoveries. To put it simply, the overuse of opioids can precipitate a chronic state of hypersensitivity to painful states in our patients.

So what can we do clinically if we want to reduce the amount of opioid consumption in our patients? Ideally, we need to consider the different stages of patient management in regards to anesthesia and how this may affect our drug and handling choices. The three areas of consideration are: admission and handling, anesthesia, recovery and hospitalization.

· Admission + handling: consider pre-emptive anxiolytics, sedatives, and analgesics for your patient. For example, managing a very anxious patient with trazodone ahead of hospital admission may reduce the amount of sedation/pre-medication, maintenance, and recovery opioids needed.

· Anesthesia: use a multimodal approach to sedation and analgesia to target different analgesic pathways using combinations of non-opioid drugs such as alpha-2 agonists, local anesthetic infusions, regional anesthesia and analgesia, and NMDA-receptor antagonists. Try to titrate all drugs to best effect in each patient individually.

· Recovery and hospitalization: ensure patients are assessed routinely using a validated pain scoring system, titrate analgesics to effects, rely on secondary and tertiary analgesics such as gabapentin and NSAIDs to improve the patient’s comfort. Learn and the difference between pain, anxiety, dysphoria, and delirium and how each should be managed. A patient who is delirious at recovery from residual inhalant should not be treated with an opioid, for example.

Opioids are foundational for acute pain management but they are not without side effects. Your patients will benefit from a thoughtfully crafted, multimodal analgesic strategy - often including opioids - but balanced by other types of analgesics to keep them comfortable and pain-free.

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