title: Opioid-induced respiratory effects: new data on buprenorphine.
abstract: When selecting the appropriate long-acting opioid to treat cancer pain, both analgesic efficacy and safety need consideration. Generally, opioids are well tolerated. However, of opioid-typical adverse events, respiratory depression is especially important because of the risk of a fatal outcome. Although all potent opioid analgesics act via the micro-opioid receptor system, they differ in how they affect respiratory control. Recently, the respiratory effects of fentanyl (1 7 microg/kg) and buprenorphine (0.7-9 microg g/kg) were compared in healthy opioid-naïve volunteers. Fentanyl produced dose-dependent depression of respiration with apnoea at doses > or = 3 microg/kg, while buprenorphine caused depression that levelled at approximately 50% of baseline with doses > or = 2 microg/kg. These findings indicate the occurrence of a ceiling in the respiratory depression induced by buprenorphine but not by fentanyl. Surprisingly few studies have addressed the clinically important ability to reverse the respiratory effects of opioids. A recent assessment of the naloxone dose required to reverse 0.2 mg intravenous buprenorphine-induced respiratory depression in healthy opioid-naïve volunteers, found that the accumulated naloxone dose causing 50% reversal of respiratory depression was 1.20 +/- 0.32 mg/70 kg (given in 30 min); 80% reversal was observed at 2.50 +/- 0.60 mg/70 kg (given in 30 min). At greater buprenorphine doses, full reversal is observed when the duration of naloxone infusion is increased. These findings indicate the need for a continuous rather than bolus administration of naloxone to reverse the respiratory effects of buprenorphine. In conclusion, buprenorphine is more favourable compared with fentanyl in respect to ventilatory control. Buprenorphine causes limited respiratory depression with a ceiling effect at higher doses, while fentanyl causes dose-dependent respiratory depression with apnoea at high dose levels. In the rare instance of respiratory depression, reversal is possible with a sufficient and continuous infusion of naloxone.
authors.affiliation: Department of Anesthesiology, Leiden University Medical Center P5-Q, P.O. Box 9600, 2300 RC Leiden, The Netherlands. a.dahan@lumc.nl
authors.forename: Albert
authors.initials: A
authors.lastname: Dahan
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects* / Q000627:therapeutic use; D001049:Apnea / Q000139:chemically induced; D002047:Buprenorphine / Q000009:adverse effects* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005283:Fentanyl / Q000009:adverse effects*; D006801:Humans; D009270:Naloxone / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000627:therapeutic use; D009369:Neoplasms / Q000150:complications*; D010146:Pain / Q000188:drug therapy*; D012131:Respiratory Insufficiency / Q000139:chemically induced* / Q000188:drug therapy
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009270:Naloxone; D002047:Buprenorphine; D005283:Fentanyl