A prospective randomized crossover study of the preemptive analgesic effect of nitrous oxide in oral surgery

Preliminary animal data has shown that nitrous oxide has a preemptive analgesic effect on postoperative pain. Whether a similar effect occurs in humans is not established. In this prospective randomized crossover study, we investigated the effect of preincisional versus postincisional nitrous oxide on postoperative oral surgical pain.Study design The trial was a crossover study where 36 patients had each of their symmetrical impacted mandibular third molars randomly scheduled for removal in 2 sessions. Each of the 36 patients acted as his or her own control; one side of the jaw was allocated randomly to receive nitrous oxide preoperatively (pretreated side) and the other side postoperatively (posttreated side). The pretreated side received 50% nitrous oxide preoperatively for 20 minutes and 100% oxygen postoperatively for 20 minutes as placebo. The posttreated side received 100% oxygen preoperatively for 20 minutes and 50% nitrous oxide postoperatively for 20 minutes. The difference in postoperative pain between the pretreated and posttreated sides was assessed by 4 primary end-points: pain intensity as measured by a 100-mm visual analog scale (VAS) hourly for 8 hours, time to first analgesic, total analgesic consumption during the first 48 hours, and a 5-point categorical patient global assessment scale (0=poor, 1=fair, 2=good, 3=very good, and 4=excellent).

The VAS scores did not differ between the 2 sides at any time (P=.50): neither did the time to first analgesic (P=.8), amount of total analgesic consumption (P=.77), and patient's global assessment differ (P=.63).

Our results do not support the preliminary animal data that nitrous oxide has a preemptive analgesic effect for postoperative pain. 50% nitrous oxide administered preoperatively for 20 minutes has no preemptive analgesic effect on postextraction pain.