Assessing the antinociceptive effect of nitrous oxide to tetanic stimulation in anaesthetised patients with new intra-operative nociception monitors: An observational study.

Background: Nitrous oxide (N2O) has been used since the 19th century for its analgesic, antinociceptive and anxiolytic effects during surgical procedures in awake and anaesthetised patients. However, quantification of noxious stimuli that occur under general anaesthesia is a constant challenge for anaesthesiologists, and recently two new indices have been developed to assess intra-operative nociception.

Objective: The aim of this study was to quantify with new indices as well as with more classical clinical parameters the antinociceptive effect of N2O during general anaesthesia.

Design: Prospective, open label, patient-blinded, observational and descriptive trial.

Setting: Single-centre academic hospital.

Participants: Forty American Society of Anesthesiologists' physical status 1 to 3 patients undergoing general anaesthesia for elective abdominal surgery via laparotomy were recruited.

Main Outcomes Measures: Intra-operative pain was assessed using a standardised electrical stimulation of the forearm (tetanic stimulation at 70 mA, 100 Hz for 30 s), at 0, 25 and 50% inhaled N2O/O2. Heart rate (HR), mean arterial blood pressure, bispectral index, the analgesia nociception index and the nociception level (NOL) index were used to evaluate intra-operative nociception before and after each standardised tetanic stimulation.

Results: There was a 16% reduction of the analgesia nociception index reaction, a 31% reduction of the NOL reaction and a 51% reduction of the HR reaction to a standardised electrical tetanic nociceptive stimulation during administration of 50% N2O. Administration of 50 or 25% inhaled N2O produced the same quality of antinociception based on HR and NOL index analyses. HR and the NOL index were the best parameters to identify the antinociceptive effect of intra-operatively administered N2O.

Conclusion: In anaesthetised patients, our study demonstrated clinically significant antinociceptive properties of N2O. Our results showed that low concentrations of N2O (25%) are as effective as higher concentrations (50%) to achieve a significant antinociceptive effect. These findings may help decrease negative effects of using higher concentrations of N2O, including its side effects and its environmental pollution.

Trial Registration: ClinicalTrials.gov registration identifier: NCT02701478.