Managing Opioid Overdose
48. W.C. accidentally received an excessive dose of methadone leading to a respiratory rate of 8 breaths/minute and excessive sedation. How should he be treated?
Methadone can accumulate when converting from short-acting opioids to this longer-acting opioid unless careful attention is paid to the differences in pharmacokinetic properties. Because methadone has a long half-life, steady-state plasma levels may not be achieved for5 to 10 days. In W.C., the challenge is to treat the respiratory depression induced by methadone without interfering with the desired analgesic effects and without precipitating narcotic withdrawal. Opioid toxicity is not life threatening if it is managed immediately. Naloxone reverses opioid-induced CNS sedation and respiratory depression after overdose of all opiates except buprenorphine. W.C. should be given naloxone 0.1 mg parenterally at 2- to 3-minute intervals until the desired effect (improved respiration rate and increased alertness) is achieved. Because methadone has a long half-life, the naloxone dose may need to be repeated every 15 to 20 minutes, sometimes for several hours, until the methadone toxicity dissipates. Overly aggressive dosing of naloxone can cause agitation and exaggerated responses to pain. The methadone dose will have to be adjusted accordingly if too much naloxone has been administered.
In the event of a massive overdose of opioid analgesics, naloxone can be given as a continuous infusion of 0.2 mg/hour to 0.4 mg/hour. In light of the low incidence of side effects from naloxone, it might be reasonable to start with a loading dose of 0.8 mg and a higher infusion dose such as 0.4 mg/hour, followed by subsequent dosage adjustments, depending on clinical response. The same approach may be utilized for the treatment of overdose with extended release formulations of opioids. As intermittent naloxone may reverse the immediate effect of opioids on receptors, extended release formulation would continue to deliver more drug and, therefore, further the effects of overdose. The required duration of naloxone infusion will vary, depending on the specific opioid and the amount involved.158,159
A longer-acting opiate antagonist, nalmefene (Revex), may provide an alternative to naloxone. Approved for the use of conscious sedation reversal and management of opioid overdose, nalmefene may be most beneficial in overdoses of methadone or propoxyphene where repeated administration of antagonists is necessary because of their long elimination half-lives.160 Nalmefene has a long half-life (8–11 hours) compared with naloxone (1–1.5 hours). Although fewer doses of nalmefene may be needed to reverse opioid intoxication, studies have not shown any difference in efficacy between nalmefene and naloxone.160,161
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