Questioning the cardiocirculatory excitatory effects of opioids under volatile anaesthesia.
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.
Docquier
M-A
MA
Department of Anaesthesiology, Laboratory of Anaesthesia, University of Louvain, St Luc Hospital, av. Hippocrate 10-1821, 1200 Brussels, Belgium.
Lavand'homme
P
P
Boulanger
V
V
Collet
V
V
De Kock
M
M
D000701:Analgesics, Opioid / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects*; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D000077149:Sevoflurane; D017409:Sufentanil / Q000494:pharmacology
D000701:Analgesics, Opioid; D018685:Anesthetics, Inhalation; D018691:Excitatory Amino Acid Antagonists; D008738:Methyl Ethers; D009292:Narcotic Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D009270:Naloxone; D000077149:Sevoflurane; D007649:Ketamine; D017409:Sufentanil