The combined effects of sevoflurane and remifentanil on central respiratory activity and nociceptive cardiovascular responses in anesthetized rabbits

We studied the effects of sevoflurane and remifentanil, alone and in combin ation, on phrenic nerve activity (PNA), resting heart rate (HR), arterial p ressure (MAP), and changes in HR (Delta HR) and MAP (Delta MAP) evoked by e lectrical stimulation of tibial nerves in anesthetized rabbits. The 50% eff ective dose (95% confidence intervals) for the depressant effects of sevofl urane on Delta HR, Delta MAP, and PNA were 2.3 (1.8%-2.6%), 2.7 (2.3%-2.9%) , and 3.4 (3.1%-3.7%), respectively, and for remifentanil were 0.100 (0.050 -0.132), 0.850 (0.720-1.450), and 0.090 (0.080-0.145) mu g.kg(-1) min(-1), which were reduced to 0.046 (0.021-0.065), 0.110 (0.080-0.200), and 0.030 ( 0.020-0.040) mu g.kg(-1) min(-1), respectively, by 1% sevoflurane. Depressi on of evoked cardiovascular responses relative to PNA was greater for sevof lurane and less for remifentanil both alone and in combination with sevoflu rane. Sevoflurane acted synergistically with remifentanil on PNA and Delta MAP, but not Delta HR, for which their combined effect was additive. Coadmi nistration of 1% sevoflurane with the highest infusion rate of remifentanil (1.6 mu g.kg(-1) min) used during combined administration reduced resting HR and MAP by 25% (P < 0.05) and 41% (P < 0.05), respectively, which was gr eater than the predicted reductions of only 14% and 15% if their combined e ffects had been additive. We conclude that sevoflurane caused a relatively greater depression of nociceptive cardioaccelerator and presser responses c ompared with PNA and vice versa for remifentanil. When coadministered, thei r combined effects on PNA, resting HR, MAP, and Delta MAP were synergistic, whereas they were merely additive for Delta HR. Implications: Although sev oflurane caused relatively greater depression of nociceptive cardiovascular responses compared with phrenic nerve activity, remifentanil either alone or combined with sevoflurane caused a much greater depression of phrenic ne rve activity than cardioaccelerator and presser responses. This could imply that, during major surgery using anesthesia combining sevoflurane and remi fentanil, spontaneous ventilation is not acceptable, and depression of the resting circulation may be much greater than anticipated.