Nitrous oxide does not produce a clinically important sparing effect during closed-loop delivered propofol–remifentanil anaesthesia guided by the bispectral index: a randomized multicentre study†‡.

Background Nitrous oxide (N2O) offers both hypnotic and analgesic characteristics. We therefore tested the hypothesis that N2O administration decreases the amount of propofol and remifentanil given by a closed-loop automated controller to maintain a similar bispectral index (BIS). Methods In a randomized multicentre double-blind study, patients undergoing elective surgery were randomly assigned to breathe 60% inspired N2O (N2O group) or 40% oxygen (AIR group). Anaesthesia depth was evaluated by the proportion of time where BIS was within the range of 40–60 (BIS40–60). The primary outcomes were propofol and remifentanil consumption, with reductions of 20% in either being considered clinically important. Results A total of 302 patients were randomized to the N2O group and 299 to the AIR group. At similar BIS40–60 [79 (67–86)% vs 76 (65–85)%], N2O slightly decreased propofol consumption [4.5 (3.7–5.5) vs 4.8 (4.0–5.9) mg kg−1 h−1, P=0.032], but not remifentanil consumption [0.17 (0.12–0.23) vs 0.18 (0.14–0.24) µg kg−1 min−1]. For the subgroups of men, at similar BIS40–60 [80 (72–88)% vs 80 (70–87)%], propofol [4.2 (3.4–5.3) vs 4.4 (3.6–5.4) mg kg−1 h−1] and remifentanil [0.19 (0.13–0.25) vs 0.18 (0.15–0.23) µg kg−1 min−1] consumptions were similar in the N2O vs AIR group, respectively. For the subgroups of women, at similar BIS40–60 [76 (64–84)% vs 72 (62–82)%], propofol [4.7 (4.0–5.8) vs 5.3 (4.5–6.6) mg kg−1 h−1, P=0.004] and remifentanil [0.18 (0.13–0.25) vs 0.20 (0.15–0.27) µg kg−1 min−1, P=0.029] consumptions decreased with the co-administration of N2O. Conclusions With automated drug administration titrated to comparable BIS, N2O only slightly reduced propofol consumption and did not reduce remifentanil consumption. There was a minor gender dependence, but not by a clinically important amount. Clinical trial registration This study was registered at ClinicalTrials.gov, number NCT00547209. [ABSTRACT FROM PUBLISHER]