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Failure of Nalbuphine to Antagonize Morphine

A Double-blind Comparison with Naloxone

Received from the Department of Anesthesiology, University of Utah School of Medicine, Salt Lake City, Utah.

Abstract

The authors studied the respiratory and analgesic effects of nalbuphine (0.21 mg/kg, intravenous), naloxone (0.014 mg/kg, intravenous), and placebo (normal saline) when given after morphine (0.21 mg/kg, intravenous) in a double-blind, randomized fashion. Resting end-tidal CO₂ (PET_CO2), ven-tilatory and occlusion pressure responses to CO₂ rebreathing, and pain threshold were measured in 12 healthy adult volunteers before, 5 min, and 30 min after morphine. Nalbuphine, naloxone, or saline were administered 55 min after morphine, and the above measurements were repeated 5 min later (60 min after morphine) as well as 90, 120, 180, and 240 min after morphine. Whereas naloxone reversed respiratory depression as measured by all three respiratory parameters, nalbuphine either further depressed (resting ^PET_CO2) or did not affect (ventilatory and occlusion pressure responses to CO₂ rebreathing) respiratory drive. Morphine produced a significant elevation of the pain threshold. Significant decreases in the pain threshold were seen only after naloxone. Saline and nalbuphine did not significantly alter the pain threshold. The data indicate that nalbuphine may not reliably antagonize moderate doses of morphine.

Key Words: ANALGESICS—morphine • ANTAGONISTS, NARCOTIC-nalbuphine

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999