Analgesia with nitrous oxide/oxygen and acetaminophen compared to morphine analgesia in patients with acute myocardial infarction: Results from the SCADOL II clinical trial.

Background The safety of morphine use has been questioned in the management of ST Elevation Myocardial Infarction (STEMI). Are there other analgesics that are at least as effective without adverse effects? Purpose Evaluate the non-inferiority of nitrous oxide/oxygen plus acetaminophen versus morphine in pre-hospital patients with STEMI. Method Multi-center, randomized, non-inferiority cluster study. Thirty-eight mobile intensive care unit centres were randomized. Inclusion criteria: patients with STEMI and pain intensity score ≥ 4 on the numerical rating scale (NRS). Outcome: proportion of patient with NRS ≤ 3, 30 minutes after starting analgesia without adding morphine in the nitrous oxide/oxygen group. Expected or unexpected events were measured at 30 minutes and 1 month. Estimated number of subjects: 684. Per protocol (PP) and intention to treat (ITT) statistical analyses were planned. A non-inferiority margin was specified as an absolute difference of − 10% in proportions. The cluster design of the trial was taken into account through generalised estimating equations. Results A total of 684 patients were included in ITT analysis and 644 in PP analysis. Pain relief was obtained in 73.6% patients in the morphine group versus 51.7% patients in the nitrous oxide/oxygen group in the PP analysis. The absolute risk difference was − 21.7% (95% CI − 29.6 to − 13.8) and was below the non-inferiority margin of − 10%. The incidence of expected and serious adverse events were 10.2% and 3.5% respectively in the morphine group versus 13.2% and 6.2% in the nitrous oxide/oxygen group. Conclusion Oxide/oxygen plus acetaminophen is inferior to morphine analgesia in patients with STEMI. Adverse effects were not different between the groups. [ABSTRACT FROM AUTHOR]