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BJA Advance Access published online on March 17, 2006
British Journal of Anaesthesia, doi:10.1093/bja/ael051
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© The Board of Management and Trustees of the British Journal of Anaesthesia 2006. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
Accepted February 5, 2006

Clinical Investigation

Buprenorphine induces ceiling in respiratory depression but not in analgesia

A. Dahan 1 *, A. Yassen 2, R. Romberg 1, E. Sarton 1, L. Teppema 1, E. Olofsen 1, and M. Danhof 2

1 Department of Anesthesiology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands
2 Leiden/Amsterdam Center for Drug Research, Division of Pharmacology, Gorlaeus Laboratory, Leiden, The Netherlands

* To whom correspondence should be addressed.
A. Dahan, E-mail: a.dahan{at}lumc.nl


  Abstract

Background. We measured the effect of two weight adjusted i.v. doses (0.2 mg per 70 kg and 0.4 mg per 70 kg) of the potent opioid buprenorphine on analgesia and respiratory depression in healthy volunteers. The aim of the study was to compare buprenorphine's behaviour with respect to the occurrence of ceiling (or apparent maximum) in these typical µ-opioid protein-(MOP) receptor effects.

Methods. Ten subjects (5 males) received 0.2 mg per 70 kg, 10 others (5 males) 0.4 mg per 70 kg i.v. buprenorphine. Steady-state inspired minute ventilation at a fixed end-tidal PCO2 of 7 kPa was measured before drug infusion and at regular intervals after drug infusion. Experimental pain was induced using transcutaneous electrical stimulation and a gradually increasing current. Pain tolerance was measured at regular intervals before and after drug infusion. The studies lasted 8 h.

Results. After infusion of the drug ventilation showed a rapid decline and reached peak depression between 150 and 180 min after drug administration. This effect was dose-independent with respect to timing and magnitude. At peak respiratory depression minute ventilation was 13.1 (SD 1.8) litre min-1 in the 0.2 mg group vs 12.0 (SD 1.3) litre min-1 in the 0.4 mg group (n.s.). At buprenorphine 0.2 mg a small short-lived analgesic effect was observed with a maximum increase in pain tolerance current of 6.7 (SD 2.8) mA occurring at 75 min after drug administration. Peak analgesic effect was 29% above baseline current. In contrast, buprenorphine 0.4 mg caused a large and long-lived analgesic effect with a maximum increase in pain tolerance current of 23.8 (SD 7.4) mA occurring at 130 min after drug administration. Peak analgesic effect was 160% above baseline current (0.4 vs 0.2 mg, P<0.01).

Conclusions. While buprenorphine's analgesic effect increased significantly, respiratory depression was similar in magnitude and timing for the two doses tested. We conclude that over the dose range tested buprenorphine displays ceiling in respiratory effect but none in analgesic effect.

Keywords: analgesia, ceiling; analgesics opioid, buprenorphine; complications, respiratory depression; pain; respiratory depression; opioid-induced.
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