The ideal paralytic agent to use during rapid sequence intubation—rocuronium or succinylcholine—has been the subject of a longstanding debate in emergency medicine and critical care. This dispute has even given rise to slogans such as “roc rocks” and “sux sucks” as the sides attempt to proclaim their superiority through witty aspersions.
Fiercely-held opinions until now have been based mostly on theoretical advantages and surrogate endpoints suggesting the time to achieve optimal intubating conditions were superior in one or the other. Now we have the first randomized controlled trial examining rocuronium v. succinylcholine. Its results are far from conclusive, however, and I fear they will lead to each side becoming even further entrenched in their positions.
Guihard, et al., randomized patients in the prehospital setting requiring RSI to receive 1 mg/kg IV succinylcholine or 1.2 mg/kg IV rocuronium. (JAMA. 2019;322:2303; http://bit.ly/2TomIoP.) This single-blind, randomized, noninferiority clinical trial was conducted by 17 out-of-hospital emergency medical units throughout France. Patients were included in the trial if the prehospital physician determined that they needed emergent endotracheal intubation. Patients were excluded if they were in cardiac arrest, under 18, or pregnant.
A standardized intubation procedure was recommended, but the final choices of sedative agent and intubation technique were left to the treating clinician's judgment. The authors randomized 1248 patients from January 2014 to August 2016, and included 1226 in their final analysis.
A Disorienting Tilt
The authors determined their primary outcome to be the number of patients with successful first-attempt intubation—74.6 percent in the rocuronium group v. 79.4 percent in the succinylcholine group. The one-sided 97.5% CI (-9% to infinity) surrounding this 4.8 percent absolute difference crossed the authors' prespecified noninferiority margin of 7.0 percent, and the authors were not able to demonstrate rocuronium's noninferiority to succinylcholine.
The authors also reported a number of important secondary outcomes. Use of a supraglottic device was higher in the rocuronium group (1.6%) compared with the succinylcholine group (0.3%), as were the rates of patients requiring four or more attempts to secure a definitive airway (1.6% v. 0.5%). This was in contrast to the number of early intubation-related complications, which was higher in the succinylcholine group (23.3%) compared with the rocuronium group (18.2%). The increase in complications came in the form of higher rates of severe arrhythmia (4.2% v. 2.0%) and hypotension (10.1% v. 6.4%).
We are once again asked to decipher the disorienting tilt of noninferiority trials before applying the results to clinical practice. Perhaps sux does not really suck. Maybe roc does not rock. Noninferiority trials ask a very specific question in a very specific way. Ideally, they are performed when you have a standard therapy and an alternative treatment that offers some advantages that are not necessarily related to each therapy's efficacy. The novel treatment, for example, may be less expensive or logistically simpler to administer.
Specific to our discussion, rocuronium does not possess the long list of contraindications of succinylcholine, nor does it seem to cause the exceptionally rare malignant hyperthermia. There is concern that its slightly longer time to onset will be detrimental in a time-limited situation like RSI. A noninferiority study queries if the performance of the novel agent, in this case rocuronium, meets a certain comparative standard below which its logistic or financial advantages are not worth the loss of efficacy.
From the strictest frequentist perspective, this trial failed to meet the threshold to demonstrate noninferiority. But what if we permit our view to expand beyond the confines of a noninferiority trial design? The question we really want this trial to answer is whether one paralytic agent has an advantage over the other. What is the likelihood that the observed difference in first-pass success represents a true benefit associated with the use of succinylcholine?
An elegant Bayesian analysis that Fernando Zampieri, MD, PhD, performed suggests the likelihood that rocuronium is superior to succinylcholine is minimal. (Dec 17, 2019; http://bit.ly/2tihQHh.) Due to the limited prior data on the subject, however, a formal Bayesian analysis is unlikely to add much other than to remove the interpretative shackles imposed by a noninferiority trial design. This study suggests a small benefit in first-pass success with succinylcholine from a Bayesian or frequentist perspective, but we have seen many comparatively-sized studies reporting similar benefits later be disproven when larger, more robust studies are performed.
Even if this represents a true benefit, should small differences in first-pass success serve as the benchmark to determine the ideal paralytic in RSI? Does this represent enough of a clinical advantage to offset the increase in peri-intubation hemodynamic perturbations, not to mention the exceptionally rare but serious side effects associated with the use of succinylcholine (not evaluated in this study due to its small sample size)? Would these small benefits in first-pass success be eliminated by simply increasing the dose of rocuronium and waiting an additional 15 seconds until full paralysis is achieved?
This study is far from a definitive gauge of succinylcholine's superiority (or rocuronium's non-noninferiority). In fact, I am sure its results will only serve to embolden each side to rally around their previously held beliefs. I, for one, will be wearing a “Roc Rocks” shirt under my scrubs, but only because it is really, really comfortable.
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Dr. Spiegelis an assistant professor of emergency medicine and critical care at Washington Hospital Center in Washington, D.C. Visit his blog athttp://emnerd.com, follow him on Twitter @emnerd_, and read his past articles athttp://bit.ly/EMN-MythsinEM.