Opioids

Opioids act centrally to limit the input of nociceptive information to the central nervous system (CNS), which will reduce central hypersensitivity.⁵ Receptors in the brain and dorsal horn of the spinal cord receive impulses from peripheral nerves, which are modulated before being transmitted to higher centers.⁶ Opioids commonly are used in critically ill patients because they have a rapid onset of action and are safe, reversible, and potent.⁷ As with all analgesic therapy in critically ill patients, opioids should be slowly titrated IV to effect, because drug pharmacokinetics may be altered.⁷ Opioid analgesics vary in effectiveness, depending on which receptor is stimulated and which class of opioid is being administered.

The four classes of opioids are pure agonists, partial agonists, agonist-antagonists, and antagonists. Pure receptor agonist stimulation results in a pronounced analgesic effect, and partial agonists bind at the same receptor but produce a less pronounced effect.⁶ Agonist-antagonists have mixed effects, with an agonist effect at one type of receptor and an antagonist effect at a different type of receptor. This results in an analgesic effect at one receptor and no effect (or a less pronounced effect) at the other receptor. Opioid antagonists (e.g., naloxone) bind to the same receptor as agonists but cause no effect, and can competitively displace the agonist from the receptor and therefore reverse the agonist effect.⁶ Partial agonists (e.g., buprenorphine 5 to 20 μg/kg IV, IM, or SC q6-8h) and mixed agonist-antagonists (e.g., butorphanol 0.1 to 0.4 mg/kg IV q1-4h) reach maximal effect at the upper end of the dosage range (see Table 164-1 for further information on appropriate dosing, routes of administration, and intervals).⁵ If the pain is severe or the analgesia is inadequate, additional doses of partial or mixed agonist-antagonists are unlikely to be effective.⁵ Using a pure μ-agonist (e.g., morphine, hydromorphone, fentanyl, oxymorphone) would be more effective, because there is no upper limit to the analgesia provided by these agents.⁵

Table 164-1 Analgesic Agents and Their Dosages

Potent side effects such as respiratory depression and bradycardia may be seen at the higher dosage range with a pure μ-agonist; therefore, the higher dosage range should be used cautiously in critically ill patients.^5,6 Additional side effects of μ-agonists (e.g., morphine and meperidine) include histamine release, particularly when given rapidly intravenously, which can lead to severe hypotension due to vasodilation.⁶ Opioids can create gastroparesis and ileus, which may result in vomition, regurgitation, and aspiration of gastrointestinal (GI) contents, particularly in depressed, sedated, weak, or critically ill patients.⁸ Gastric distention from opioids may also be a concern in patients with abdominal disease (e.g., pancreatitis), because stimulation of pancreatic secretions may occur.⁸ Patients at risk for pancreatitis or gastroparesis may require intermittent or constant gastric decompression (via nasogastric or gastrostomy tube) if they are treated with opioids for more than 12 to 24 hours, or they may require motility drug therapy (e.g., metoclopramide).⁸

In cats, opioids can be administered safely to provide analgesia.⁵ Morphine (0.05 to 0.5 mg/kg IM q3-6h) or oxymorphone (0.05 mg/kg IV titrated slowly) can be given for analgesia; however, side effects such as hyperexcitability or agitation may occur. It has been shown that the onset of mydriasis following administration of opioids correlates with adequate analgesia in cats; continued administration after achieving mydriasis may result in adverse side effects such as dysphoria and agitation.⁸ The mixed partial μ-agonist buprenorphine (10 to 20 μg/kg PO q6-8h) is an effective analgesic in cats and can also be used.⁶

One advantage of opioid administration in critically ill patients is that their effects can be reversed, if necessary, with a pure antagonist such as naloxone (0.002 to 0.1 mg/kg IV, IM, or SC). Naloxone can reverse CNS depression, respiratory depression, and bradycardia, but the reversal of sedation and analgesia can cause pain, excitement, emergence delirium, aggression, and hyperalgesia.⁹ Low-dose naloxone (0.004 mg/kg IV titrated slowly) has been recommended to reverse CNS depression without affecting analgesia.⁸ The duration of effect for naloxone is relatively short (20 to 30 minutes) because of its rapid metabolism in dogs and cats, which may predispose patients to renarcotization when the drug is used to reverse long-acting opioids.^9,10

Agonist-antagonists such as butorphanol (0.05 to 0.1 mg/kg IV) may also be used to reverse sedation and respiratory depression from μ-agonists.^8,9 The benefit of using butorphanol as a reversal agent is that complete reversal of analgesia does not occur because of its κ-agonist effects. Use of butorphanol as a reversal agent may produce additive analgesia with the μ-agonist.⁹ In contrast, buprenorphine is not as easily reversed as butorphanol, because it is difficult to displace from the receptor.⁶