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
Grillot N, Lebuffe G, Huet O, et al. JAMA. 2023;329(1):28-38.
SUMMARY:
Rapid sequence intubation (RSI), the standard approach for ED intubations, combines preoxygenation with a sedative/hypnotic agent and usually a rapid-onset neuromuscular blocker, such as succinylcholine or rocuronium.
Providers may sometimes hesitate to use a neuromuscular blocker, eg, in neurological cases in which an ability to perform repeat examinations is critical.
Anecdotally, some reports and small studies have described used using remifentanil instead of a neuromuscular blocker during RSI and have shown satisfactory intubating conditions in 90 seconds. Remifentanil, a potent synthetic opioid with a rapid onset and short duration of action, is used primarily in the operating room for analgesia and for general anesthesia in combination with other medications.
This study was a multicenter, randomized, open-label, noninferiority trial in 1,150 adults at risk of aspiration (fasting for <6 hours, bowel occlusion, recent trauma, or severe gastroesophageal reflux) who underwent tracheal intubation in the operating rooms at 15 hospitals in France between October 2019 and April 2021.
Patients were randomized to receive a neuromuscular blocker (succinylcholine or rocuronium at 1 mg/kg; n = 575) or remifentanil (3-4 μg/kg; n = 575) immediately after a hypnotic agent. The primary outcome was first-attempt success without complications (eg, aspiration), and the noninferiority margin was set at 7%.
The groups were well matched at baseline. The average age was approximately 50 years, most patients were categorized into American Society of Anesthesiologists class I or II, and approximately 60% required urgent or emergent surgery rather than scheduled surgery.
Only 3 patients crossed over to the other arm, and only 7 were lost to follow-up.
The primary outcome of successful 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 patients (71.6%) in the neuromuscular-blocker group (adjusted between-group difference, –6.1%; 95% CI, –11.6% to –0.5%), thus demonstrating inferiority. The provided per-protocol results were comparable.
The rate of first-attempt success, not considering adverse events, was high in both groups (88.5% for remifentanil vs 93.5% for neuromuscular blockers), but the overall rates of severe adverse events were higher in the remifentanil group (2.1% vs 0.5%), as were the rates of hemodynamic instability (3.3% vs 0.5%).
This was a well-conducted trial with an excellent statistical plan including subgroup analyses, a regression model, and imputation for missing data; however, it was limited by its open-label design (which would be expected to bias the findings toward remifentanil) and its non-ED location.
EDITOR’S COMMENTARY: In this large and well-done randomized noninferiority trial from 15 operating rooms in France, remifentanil was found to be inferior to neuromuscular blockers during RSI. The authors suggest that the wide confidence interval leaves room for noninferiority, but no trends in any assessed outcomes favored remifentanil, and the nonblinded nature of the study should have biased the results toward a positive finding, making me less enthusiastic about use of remifentanil and future studies on the topic. In the era of short-acting neuromuscular blockers and reversal agents, I see the potential indications for remifentanil as an alternative to be pretty rare, so if you are going to add it to your toolbox, I would put it close to the bottom unless new data become available. One question not answered by this paper is whether remifentanil might be a valuable addition to a single agent, such as propofol, when you are not planning on using a neuromuscular blocker at all.
quick comment. i believe (pretty sure i'm correct) the order of pharmacologic manipulation is fentnayl -> carfentanil -> remifentanil (not fentanyl directly to remifentanil). they added a carboxyl group to the carfentanil so it is metabolized by non-specific tissues esterases found in many organs/tissues and thus not dependent on liver/renal metabolism. much akin to the same carboxyl addition to propranolol to create esmolol and to midazolam to create remimazolam.
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Sean R. - April 4, 2023 8:53 AM
quick comment. i believe (pretty sure i'm correct) the order of pharmacologic manipulation is fentnayl -> carfentanil -> remifentanil (not fentanyl directly to remifentanil). they added a carboxyl group to the carfentanil so it is metabolized by non-specific tissues esterases found in many organs/tissues and thus not dependent on liver/renal metabolism. much akin to the same carboxyl addition to propranolol to create esmolol and to midazolam to create remimazolam.