Naloxone reversal of buprenorphine-induced respiratory depression.
BACKGROUND
The objective of this investigation was to examine the ability of the opioid antagonist naloxone to reverse respiratory depression produced by the mu-opioid analgesic, buprenorphine, in healthy volunteers. The studies were designed in light of the claims that buprenorphine is relatively resistant to the effects of naloxone.


METHODS
In a first attempt, the effect of an intravenous bolus dose of 0.8 mg naloxone was assessed on 0.2 mg buprenorphine-induced respiratory depression. Next, the effect of increasing naloxone doses (0.5-7 mg, given over 30 min) on 0.2 mg buprenorphine-induced respiratory depression was tested. Subsequently, continuous naloxone infusions were applied to reverse respiratory depression from 0.2 and 0.4 mg buprenorphine. All doses are per 70 kg. Respiration was measured against a background of constant increased end-tidal carbon dioxide concentration.


RESULTS
An intravenous naloxone dose of 0.8 mg had no effect on respiratory depression from buprenorphine. Increasing doses of naloxone given over 30 min produced full reversal of buprenorphine effect in the dose range of 2-4 mg naloxone. Further increasing the naloxone dose (doses of 5 mg or greater) caused a decline in reversal activity. Naloxone bolus doses of 2-3 mg, followed by a continuous infusion of 4 mg/h, caused full reversal within 40-60 min of both 0.2 and 0.4 mg buprenorphine-induced respiratory depression.


CONCLUSIONS
Reversal of buprenorphine effect is possible but depends on the buprenorphine dose and the correct naloxone dose window. Because respiratory depression from buprenorphine may outlast the effects of naloxone boluses or short infusions, a continuous infusion of naloxone may be required to maintain reversal of respiratory depression.
van Dorp
Eveline
E
Department of Anesthesiology, Leiden University Medical Center, The Netherlands.
Yassen
Ashraf
A
Sarton
Elise
E
Romberg
Raymonda
R
Olofsen
Erik
E
Teppema
Luc
L
Danhof
Meindert
M
Dahan
Albert
A
D000328:Adult; D002047:Buprenorphine / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D009270:Naloxone / Q000627:therapeutic use*; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D012131:Respiratory Insufficiency / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology
D017450:Receptors, Opioid, mu; D009270:Naloxone; D002047:Buprenorphine