In this episode I’ll, discuss an article about using buprenorphine as an antidote in methadone overdose.
While naloxone is the standard treatment for opioid overdose, it does have two significant limitations when treating respiratory depression from methadone overdose. First, naloxone will precipitate opioid withdrawal in opioid-dependent patients and patients on methadone are highly likely to be opioid-dependent. Second, naloxone has a very short half-life when compared with methadone and therefore requires titration and continuous infusion in most methadone overdose cases. Buprenorphine has a much longer half-life than naloxone and being a partial opioid agonist is expected to cause less severe withdrawal.
Case reports suggest that buprenorphine will still reverse respiratory depression induced by full agonist opioids such as methadone. The authors of a study published February 2020 in the journal Critical Care sought to compare the efficacy and safety of buprenorphine and naloxone in reversing respiratory depression in methadone-poisoned opioid-dependent patients.
Patients with methadone-induced respiratory depression were randomized to receive naloxone in titrated doses, or one of two doses of buprenorphine (10 μg/kg or 15 μg/kg IV). The primary outcome was the immediate reversal of respiratory depression. The authors also examined rates of acute opioid withdrawal, need for intubation, recurrent apnea, repeated doses of opioid antagonists, length of hospital stay, and mortality.
There were 29 patients in the naloxone group and 28 patients in each buprenorphine group.
Naloxone worked in all but 1 patient however it caused withdrawal symptoms in 15 patients.
Buprenorphine worked in all but 1 patient and even though twice as many patients received buprenorphine compared to naloxone, only 7 buprenorphine patients experienced withdrawal.
This difference was significant, as was a reduced incidence of the need for intubation favoring the buprenorphine group at 28% vs 9%.
15% of the patients in the naloxone group developed ARDS, and there was 15% mortality compared to no cases of ARDS and no mortality in the buprenorphine group.
The authors concluded:
Buprenorphine appears to be a safe and effective substitute for naloxone in overdosed opioid-dependent patients. Further studies are warranted to explore the optimal dosing strategy for buprenorphine to consistently maintain reversal of respiratory depression but not precipitate withdrawal.
Back in episode 329, I discussed a single case report of buprenorphine’s successful use in a patient with methadone overdose. This randomized trial further delineates the role for buprenorphine in methadone overdose.
The 15-μg/kg buprenorphine dose provided a longer duration of action than 10-μg/kg, but the 15-μg/kg dose accounted for all of the cases of withdrawal in the buprenorphine group.
The near complete lack of need for repeat doses or continuous infusions in the buprenorphine group, and the lower rates of intubation, ARDS, and mortality present a compelling case for the use of IV buprenorphine being preferred in methadone overdose cases.
Outside of a controlled trial environment, making the switch to buprenorphine as an antidote for methadone would require significant effort on the part of hospital pharmacists. Automated dispensing cabinets in the emergency department would need to be pre-loaded with IV buprenorphine, and extensive education on the dose, administration and patient-centered benefits would need to be delivered to both nurses and physicians.
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