By Vibhu Sharma, MD, MS

Assistant Professor of Medicine, University of Colorado, Denver

Dr. Sharma reports no financial relationships relevant to this field of study.

SYNOPSIS: This randomized, single-blind, noninferiority trial compared rocuronium and succinylcholine for rapid sequence intubation. Rocuronium was noninferior to succinylcholine with respect to the primary endpoint of first-pass intubation success.

SOURCE: Guihard B, et al. Effect of rocuronium vs succinylcholine on endotracheal intubation success rate among patients undergoing out-of-hospital rapid sequence intubation: A randomized clinical trial. JAMA 2019;322:2303-2312.

In the Succinylcholine vs. Rocuronium for Out-of-Hospital Emergency Intubation (CURASMUR) trial, patients requiring intubation were randomized in single-blind fashion to succinylcholine or rocuronium. All patients were intubated outside the hospital by (emergency medicine or anesthesiology) physicians who are part of an advanced ambulance system in France. This system is dispatched to community calls of patients in-extremis, and decisions are made to intubate in the field. The trial enrolled 1,248 patients from January 2014 to August 2018. Consent was obtained either from a relative on site or mailed to the patient after discharge from the hospital or a relative after the patient’s death. Most patients were intubated due to coma related to neurologic disease (approximately 50% in each group). Coma due to self-poisoning, acute respiratory failure, trauma, shock, and “other” comprised the rest of the groups, in decreasing order of proportion. Exclusion criteria included known allergies to rocuronium or succinylcholine, known myasthenia gravis, muscular dystrophy, or absence of health insurance. Rocuronium was administered at a dose of 1.2 mg/kg and succinylcholine at 1.0 mg/kg, with patient weights “estimated,” although this was not defined. Hypnotics used were either etomidate 0.3 mg/kg or ketamine
2 mg/kg. One-quarter of the patients were intubated while they were on the ground in the field. Interestingly, none were obese, with a mean body mass index (BMI) of approximately 25 in each group. A Macintosh 3 or 4 curved blade was used as the first attempt instrument of choice, with a bougie or laryngeal mask airway (LMA) used for rescue. A video laryngoscope was not used, and reversal of paralysis with sugammadex was permitted, if necessary.

The primary endpoint was first-pass intubation success rate, with secondary pre-specified outcomes including Cormack-Lehane grade view of the cords, overall difficulty of intubation, percentage of patients intubated with an alternative technique, hypoxia, and intubation-related complications (cardiac arrest, arterial hypotension). The majority (98.6%) of the enrolled 1,248 patients completed the trial, and 98.2% completed a per-protocol analysis. The non-inferiority margin was set at 7%. The number of patients with first-pass success in the rocuronium group was 455/610 (74.6%) and in the succinylcholine group was 489/616 (79.4%), with a difference of -4.8% (one-sided 97.5% confidence interval [CI] -9 to ∞). No differences were noted in the overall intubation difficulty grade or the Cormack-Lehane grade view during direct laryngoscopy. With respect to secondary endpoints, intubation-related complications were more frequent in the succinylcholine group (23.2% vs. 18.2%; P = 0.04). Sugammadex had to be used to reverse rocuronium in only two of 610 patients.

COMMENTARY

This study concludes that rocuronium is noninferior to succinylcholine for intubation in the field and adds to the knowledge about the safety profile of rocuronium. Almost all patients enrolled were able to complete randomization and per-protocol analysis, a fairly remarkable achievement for a community-based trial of this kind. Although no major adverse effects were observed with the use of rocuronium, there were more intubation-related adverse effects (cardiac arrest and hypotension) with the use of succinylcholine. The authors urged caution in the interpretation of the higher rate of cardiac arrest and hypotension in the succinylcholine group; however, it remains true that succinylcholine is associated with numerous adverse effects, including severe hyperkalemia (which can occur within minutes of administration and result in cardiac arrest), while rocuronium is virtually free of adverse effects. The rates of death were equivalent. A higher proportion of patients receiving succinylcholine received post-intubation sedation with opiates and midazolam, presumably related to the shorter duration of action and perceived need for analgosedation in the succinylcholine group.

Some limitations deserve to be highlighted. First, none of the patients were obese; most had a normal BMI (mean ~ 25 in each group) and were intubated in the field. Second, most patients were intubated by experienced emergency medicine physicians and anesthesiologists. For these two reasons, the results of this study cannot be extrapolated to emergency department (ED) or intensive care unit (ICU) settings in the United States or other countries, where patients are intubated by a large variety of clinicians, and patient weights are more varied. Third, the first-pass success rate was lower than is expected in most ED settings1,2 and may be attributed to the fact that all patients were intubated in the field. Fourth, the noninferiority margin chosen at 7% was set arbitrarily and based on expert opinion. The authors acknowledged this, and cited the lack of randomized trial data as the reason for the arbitrary limit.

The most important conclusion for clinicians who intubate is that rocuronium is safe to use, and the need to reverse the effects should be rare. Intubating conditions and laryngoscopic grade of view are no different with rocuronium compared with succinylcholine in arguably difficult out-of-hospital settings, which should provide a measure of comfort to clinicians who prefer rocuronium in ED and ICU settings. Previous randomized trials3-5 and more recent large observational studies1 have demonstrated equivalent intubating conditions with rocuronium and succinylcholine, and this CURASMUR trial adds to the existing literature in this regard.

REFERENCES

  1. April MD, et al. Emergency department intubation success with succinylcholine versus rocuronium: A National Emergency Airway Registry Study. Ann Emerg Med 2018;72:645-653.
  2. Jung W, Kim J. Factors associated with first-pass success of emergency endotracheal intubation. Am J Emerg Med 2020;38:109-113.
  3. Magorian T, et al. Comparison of rocuronium, succinylcholine, and vecuronium for rapid-sequence induction of anesthesia in adult patients. Anesthesiology 1993;79:913-918.
  4. Marsch SC, et al. Succinylcholine versus rocuronium for rapid sequence intubation in intensive care: A prospective, randomized controlled trial. Crit Care 2011;15:R199.
  5. McCourt KC, et al. Comparison of rocuronium and suxamethonium for use during rapid sequence induction of anaesthesia. Anaesthesia 1998;53:867-871.