Nitrous oxide/oxygen plus acetaminophen versus morphine in ST elevation myocardial infarction: open-label, cluster-randomized, non-inferiority study

Sandrine Charpentier, Michel Galinski, Vincent Bounes, Agnès Ricard-Hibon, Carlos El-Khoury, Meyer Elbaz, François-Xavier Ageron, Stéphane Manzo-Silberman, Louis Soulat, Frédéric Lapostolle, Alexandre Gérard, Delphine Bregeaud, Vanina Bongard, Eric Bonnefoy-Cudraz, SCADOL II investigators, Vincent Bounes, Claire Vallenet, Elise Robeley, Frédéric Lapostolle, Catherine Pradeau, Patrice Serre, Carols El Khoury, Pascal Usseglio, Eric Revue, Christine Bregeaud, Christine Lespiaucq, Sonja Curac, Julie Jardon, Pierre Arnaud Fort, Armelle Severin, Guillaume Debaty, Anne-Sophie Lucas, Bahram Chaybany, Alexandre Gerard, Marc Fournier, Anais Bauer, Mustapha Sebbane, Tahar Chouihed, Camille Machet, Julie Labiau, Claire Broche, Céline Maisondieu, Matthieu Marchetti, Agnès Ricard-Hibon, François-Xavier Ageron, Nicolas Bohrer, Laurent Teillol, Muriel Vergne, Didier Dansou, Dominique Cailloce, David Sapir, Sandrine Charpentier, Michel Galinski, Vincent Bounes, Agnès Ricard-Hibon, Carlos El-Khoury, Meyer Elbaz, François-Xavier Ageron, Stéphane Manzo-Silberman, Louis Soulat, Frédéric Lapostolle, Alexandre Gérard, Delphine Bregeaud, Vanina Bongard, Eric Bonnefoy-Cudraz, SCADOL II investigators, Vincent Bounes, Claire Vallenet, Elise Robeley, Frédéric Lapostolle, Catherine Pradeau, Patrice Serre, Carols El Khoury, Pascal Usseglio, Eric Revue, Christine Bregeaud, Christine Lespiaucq, Sonja Curac, Julie Jardon, Pierre Arnaud Fort, Armelle Severin, Guillaume Debaty, Anne-Sophie Lucas, Bahram Chaybany, Alexandre Gerard, Marc Fournier, Anais Bauer, Mustapha Sebbane, Tahar Chouihed, Camille Machet, Julie Labiau, Claire Broche, Céline Maisondieu, Matthieu Marchetti, Agnès Ricard-Hibon, François-Xavier Ageron, Nicolas Bohrer, Laurent Teillol, Muriel Vergne, Didier Dansou, Dominique Cailloce, David Sapir

Abstract

Background: Studies have shown disparate results on the consequences of morphine use in ST-segment elevation myocardial infarction (STEMI). No study has evaluated alternative treatments that could be at least non-inferior to morphine without its potentially damaging consequences for myocardial function and platelet reactivity. The aim of this study was to evaluate whether nitrous oxide/oxygen plus intravenous acetaminophen (NOO-A) is non-inferior to morphine to control chest pain in STEMI patients.

Methods: This multicenter, open-label, cluster-randomized, controlled, non-inferiority study compared NOO-A with morphine in 684 prehospital patients with ongoing suspected STEMI of < 12 h duration and a pain rating score ≥ 4. The primary endpoint was the proportion of patients achieving pain relief (numeric rating score ≤ 3) after 30 min. Secondary safety endpoints included serious adverse events and death at 30 days.

Results: The median baseline pain score was 7.0 in both groups. The primary endpoint occurred in 51.7% of the NOO-A group and 73.6% of the morphine group (absolute risk difference - 21.7%; 95% confidence interval - 29.6 to - 13.8). At 30 days, the rate of serious adverse events was 16.0 and 18.8% in the NOO-A and morphine groups respectively (p = NS). The rate of death was 1.8% (NOO-A group) and 3.8% (morphine group) (p = NS).

Conclusion: Analgesia provided by NOO-A was inferior to morphine at 30 min in patients with acute STEMI in the prehospital setting. Rates of serious adverse events did not differ between groups.

Trial registration: ClinicalTrials.gov: NCT02198378.

Keywords: Analgesia, prehospital; ST-segment elevation myocardial infarction.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Patient flow chart. Centres 10 and 20 performed the study in the morphine arm and then in the oxide/oxygen plus acetaminophen arm
Fig. 2
Fig. 2
Percent of patients with pain score (numeric rating scale [NRS]) > 3. T, time in minutes
Fig. 3
Fig. 3
Primary endpoint. CI, confidence interval

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