BJA Advance Access published online on June 25, 2004
British Journal of Anaesthesia, doi:10.1093/bja/aeh216
© 2004 by The Board of Management and Trustees of the British Journal of Anaesthesia
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1 Department of Anaesthesiology, Laboratory of Anaesthesia, University of Louvain, St Luc Hospital, av. Hippocrate 10-1821, 1200 Brussels, Belgium
* To whom correspondence should be addressed. E-mail: dekock{at}anes.ucl.ac.be.
Background. Opioid-induced hyperalgesia has been demonstrated in awake animals. We observed an increased haemodynamic reactivity in response to noxious stimuli in rats under sevoflurane anaesthesia treated with a very low dose of sufentanil. The aim of this investigation was to determine whether the two phenomena share a common origin: an opioid-induced excitatory reaction. To address this, we administered several drugs with proven efficacy in opioid hyperalgesia to rats presenting with haemodynamic hyper-reactivity. Methods. The MACbar of sevoflurane was measured in controls and in animals treated with sufentanil 0.005 µg kg-1 min-1 before and after administration of i.v. (0.25, 0.5 mg kg-1) and intrathecal (i.t.) (250 µg) ketamine, i.v. (0.5, 1 mg kg-1) and i.t. (30 µg) MK-801(NMDA antagonist), i.v. (0.1, 0.5 mg kg-1) naloxone, i.v. (10 mg kg-1) and i.t. (50, 100 µg) ketorolac or i.t. (100, 150 µg) meloxicam (COX-2 inhibitor). Results. Sufentanil 0.005 µg kg-1 min-1 significantly increased MACbar (3.2 (SD 0.3) versus 1.9 (0.3) vol%). With the exception of naloxone, all drugs displayed a significant MACbar-sparing effect (>50%) in controls. Naloxone completely prevented haemodynamic hyperactivity. Two patterns of reaction were recorded for the other drugs: either hyper-reactivity was suppressed and the MACbar-sparing effect was maintained (i.t. ketamine, i.t. MK-801, i.t. ketorolac [100 µg], i.t. meloxicam [150 µg]) or hyper-reactivity was blocked but MACbar-sparing effect was lost (i.v. ketamine [0.5 mg kg-1], i.v. MK-801 [0.5, 1 mg kg-1], i.v. ketorolac [10 µg kg-1], i.t. ketorolac [50 µg], i.t. meloxicam [100 µg]). Conclusions. We have demonstrated that low-dose sufentanil-induced haemodynamic hyperreactivity is an excitatory µ-opiate-related phenomenon. This effect is reversed by drugs effective in treating opiate-induced hyperalgesia.
Laboratory Investigation
Questioning the cardiocirculatory excitatory effects of opioids under volatile anaesthesia
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