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. 2004 Sep;93(3):408-13.
doi: 10.1093/bja/aeh216. Epub 2004 Jun 25.

Questioning the cardiocirculatory excitatory effects of opioids under volatile anaesthesia

M-A Docquier  1 , P Lavand'homme, V Boulanger, V Collet, M De Kock
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Free article

Questioning the cardiocirculatory excitatory effects of opioids under volatile anaesthesia

M-A Docquier et al. Br J Anaesth. 2004 Sep.
Free article

Abstract

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 micro g kg(-1) min(-1) before and after administration of i.v. (0.25, 0.5 mg kg(-1)) and intrathecal (i.t.) (250 micro g) ketamine, i.v. (0.5, 1 mg kg(-1)) and i.t. (30 micro g) 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 micro g) ketorolac or i.t. (100, 150 micro g) meloxicam (COX-2 inhibitor).

Results: Sufentanil 0.005 micro g 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 micro g], i.t. meloxicam [150 micro g]) 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 micro g kg(-1)], i.t. ketorolac [50 micro g], i.t. meloxicam [100 micro g]).

Conclusions: We have demonstrated that low-dose sufentanil-induced haemodynamic hyper-reactivity is an excitatory micro -opiate-related phenomenon. This effect is reversed by drugs effective in treating opiate-induced hyperalgesia.

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