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 (N 2 O) offers both hypnotic and analgesic characteristics. We therefore tested the hypothesis that N 2 O 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 N 2 O (N 2 O group) or 40% oxygen (AIR group). Anaesthesia depth was evaluated by the proportion of time where BIS was within the range of 40–60 (BIS 40–60 ). 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 N 2 O group and 299 to the AIR group. At similar BIS 40–60 [79 (67–86)% vs 76 (65–85)%], N 2 O 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 BIS 40–60 [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 N 2 O vs AIR group, respectively. For the subgroups of women, at similar BIS 40–60 [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 N 2 O. Conclusions With automated drug administration titrated to comparable BIS, N 2 O 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.