BJA Advance Access originally published online on June 25, 2004
British Journal of Anaesthesia 2004 93(3):408-413; doi:10.1093/bja/aeh216
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© The Board of Management and Trustees of the British Journal of Anaesthesia 2004
Questioning the cardiocirculatory excitatory effects of opioids under volatile anaesthesia
Department of Anaesthesiology, Laboratory of Anaesthesia, University of Louvain, St Luc Hospital, av. Hippocrate 10–1821, 1200 Brussels, Belgium
* Corresponding author. 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 hyper-reactivity is an excitatory µ-opiate-related phenomenon. This effect is reversed by drugs effective in treating opiate-induced hyperalgesia.
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