Effect of Remifentanil vs Neuromuscular Blockers During Rapid Sequence Intubation on Successful Intubation Without Major Complications Among Patients at Risk of Aspiration: A Randomized Clinical Trial

Abstract

Importance: It is uncertain whether a rapid-onset opioid is noninferior to a rapid-onset neuromuscular blocker during rapid sequence intubation when used in conjunction with a hypnotic agent.

Objective: To determine whether remifentanil is noninferior to rapid-onset neuromuscular blockers for rapid sequence intubation.

Design, setting, and participants: Multicenter, randomized, open-label, noninferiority trial among 1150 adults at risk of aspiration (fasting for <6 hours, bowel occlusion, recent trauma, or severe gastroesophageal reflux) who underwent tracheal intubation in the operating room at 15 hospitals in France from October 2019 to April 2021. Follow-up was completed on May 15, 2021.

Interventions: Patients were randomized to receive neuromuscular blockers (1 mg/kg of succinylcholine or rocuronium; n = 575) or remifentanil (3 to 4 μg/kg; n = 575) immediately after injection of a hypnotic.

Main outcomes and measures: The primary outcome was assessed in all randomized patients (as-randomized population) and in all eligible patients who received assigned treatment (per-protocol population). The primary outcome was successful tracheal intubation on the first attempt without major complications, defined as lung aspiration of digestive content, oxygen desaturation, major hemodynamic instability, sustained arrhythmia, cardiac arrest, and severe anaphylactic reaction. The prespecified noninferiority margin was 7.0%.

Results: Among 1150 randomized patients (mean age, 50.7 [SD, 17.4] years; 573 [50%] women), 1130 (98.3%) completed the trial. In the as-randomized population, tracheal intubation on the first attempt without major complications occurred in 374 of 575 patients (66.1%) in the remifentanil group and 408 of 575 (71.6%) in the neuromuscular blocker group (between-group difference adjusted for randomization strata and center, -6.1%; 95% CI, -11.6% to -0.5%; P = .37 for noninferiority), demonstrating inferiority. In the per-protocol population, 374 of 565 patients (66.2%) in the remifentanil group and 403 of 565 (71.3%) in the neuromuscular blocker group had successful intubation without major complications (adjusted difference, -5.7%; 2-sided 95% CI, -11.3% to -0.1%; P = .32 for noninferiority). An adverse event of hemodynamic instability was recorded in 19 of 575 patients (3.3%) with remifentanil and 3 of 575 (0.5%) with neuromuscular blockers (adjusted difference, 2.8%; 95% CI, 1.2%-4.4%).

Conclusions and relevance: Among adults at risk of aspiration during rapid sequence intubation in the operating room, remifentanil, compared with neuromuscular blockers, did not meet the criterion for noninferiority with regard to successful intubation on first attempt without major complications. Although remifentanil was statistically inferior to neuromuscular blockers, the wide confidence interval around the effect estimate remains compatible with noninferiority and limits conclusions about the clinical relevance of the difference.

Trial registration: ClinicalTrials.gov Identifier: NCT03960801.

Figure 1.. Participant Flow

Data collection of the number of patients assessed for eligibility was not planned during the trial and these data are not available. ^aMultiple imputation model based on age, body mass index, medical history of ischemic cardiomyopathy, arterial hypertension, chronic pulmonary obstructive disease, asthma, or stroke, American Society of Anesthesiology Physical Status Classification System score, and urgent surgery (yes vs no). ^bDid not require general anesthesia (inclusion criterion) (n = 1), did not require orotracheal intubation (inclusion criterion) (n = 2), or did not undergo surgery (n = 2). ^cDid not require orotracheal intubation (inclusion criterion) (n = 1), preoperative hypoxemia (noninclusion criterion) (n = 1), or patient enrolled twice in the study (n = 2).

Figure 2.. Primary Outcome of Successful Intubation on the First Attempt Without Major Complications in the Randomized and Per-Protocol Populations, and Preplanned Subgroup Analyses in the Randomized Population

ASA indicates American Society of Anesthesiology. The vertical dashed line indicates the noninferiority margin of 7%. Body mass index is calculated as weight in kilograms divided by height in meters squared. ^aScore of I to II, major part of the uvula is visible; score of III to IV, the base of the uvula or less is visible. ^bScore of I to II, healthy or mild systemic disease without significant functional limitation; score of III to IV, significant functional limitation with potential constant threat to life. ^cOther hypnotics: thiopental or etomidate.