Questioning the cardiocirculatory excitatory effects of opioids under volatile anaesthesia

Background. Opioid-induced hyperalgesia has been demonstratedin awake animals. We observed an increased haemodynamic reactivityin response to noxious stimuli in rats under sevoflurane anaesthesiatreated with a very low dose of sufentanil. The aim of thisinvestigation was to determine whether the two phenomena sharea common origin: an opioid-induced excitatory reaction. To addressthis, we administered several drugs with proven efficacy inopioid hyperalgesia to rats presenting with haemodynamic hyper-reactivity. Methods. The MACbar of sevoflurane was measured in controlsand in animals treated with sufentanil 0.005 µg kg^–1min^–1 before and after administration of i.v. (0.25, 0.5mg kg^–1) and intrathecal (i.t.) (250 µg) ketamine,i.v. (0.5, 1 mg kg^–1) and i.t. (30 µg) MK-801(NMDAantagonist), i.v. (0.1, 0.5 mg kg^–1) naloxone, i.v. (10mg 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 significantlyincreased MACbar (3.2 (SD 0.3) versus 1.9 (0.3) vol%). Withthe exception of naloxone, all drugs displayed a significantMACbar-sparing effect (>50%) in controls. Naloxone completelyprevented haemodynamic hyperactivity. Two patterns of reactionwere recorded for the other drugs: either hyper-reactivity wassuppressed 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-sparingeffect 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-inducedhaemodynamic hyper-reactivity is an excitatory µ-opiate-relatedphenomenon. This effect is reversed by drugs effective in treatingopiate-induced hyperalgesia.