There has been a long-standing debate in the fields of emergency medicine and critical care regarding the ideal paralytic agent to use during RSI, rocuronium or succinylcholine. This dispute, has even developed slogans such as Roc Rocks, Sux Sucks as one side attempts to definitively proclaim its superiority through witty aspersions. But up until now fiercely held opinions have mostly been based on theoretical advantages and surrogate endpoints suggesting time to achieve optimal intubating conditions were superior in one or the other group. We now have the first RCT examining the use of rocuronium vs succinylcholine. But its results are far from conclusive, and I fear will lead to each side becoming even further entrenched in their long standing positions.
Published in JAMA, Guihard et al randomized patients in the prehospital setting requiring RSI to receive either 1 mg/kg of IV succinylcholine or 1.2 mg/kg of IV rocuronium (1). This single-blind, randomized, non-inferiority clinical trial was conducted at 17 out-of-hospital emergency medical units throughout France. Patients were included in the trial if they were determined to require emergent endotracheal intubation by the prehospital physician. Patients were excluded if they were in cardiac arrest, under 18 years of age, or pregnant.
A standardized intubation procedure was recommended, but the final choice of sedative agent, and intubation technique was left to the judgement of the treating clinician. From January 2014 and August 2016 the authors randomized 1248 patients, including 1226 in their final analysis. For their primary outcome, the authors determined the number of patients with successful first-attempt intubation was 74.6% in the rocuronium group vs 79.4% in the succinylcholine group. The 1-sided 97.5% CI (−9% to ∞) surrounding this 4.8% absolute difference crossed the authors prespecified non-inferiority margin of 7%. Thus, the authors were not able to demonstrate rocuronium’s non-inferiority 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 to the succinylcholine group (0.3%). As were the rates of patients requiring 4 or more attempts to secure a definitive airway (1.6% vs 0.5%). This was in contrast to the number of early intubation-related complications, which was higher in the succinylcholine group (23.3%), compared to the rocuronium group (18.2%). This increase in complications came in the form of higher rates of severe arrhythmia (4.2% vs 2.0%) and hypotension (10.1% vs 6.4%).
We are once again asked to decipher the disorienting tilt of non-inferiority trials before applying results to clinical practice. Perhaps sux does not really suck. And roc may not rock. Non-inferiority 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 respective therapy’s efficacy. For example, the novel treatment may be less expensive or logistically simpler to administer. Specific to our discussion, rocuronium does not possess the long list of contraindications enjoyed by succinylcholine. Nor does it seem to cause the exceptionally rare malignant hyperthermia. But there is concern that its slightly longer time to onset will be detrimental in a time limited situation like RSI. A non-inferiority 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 non-inferiority. But what if we permit our view to expand beyond the confines of a non-inferiority trial design? The question we really want this trial to answer is, whether there an advantage to using one paralytic agent over the other? What is the likelihood that the observed difference in first past success represents a true benefit associated with the use of succinylcholine?
An elegant Bayesian analysis performed here suggests the likelihood that rocuronium is superior to succinylcholine is minimal. Although, due to the limited prior data on the subject, a formal Bayesian analysis is unlikely to add much other than to remove the interpretative shackles imposed by a non-inferiority trial design. And while this study suggests a small benefit in FPS with the use of succinylcholine from either a Bayesian or frequentist perspective, 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? In the end 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 Roc Rocks shirt under my scrubs tonight on shift, but only because it is really, really comfortable…
- Guihard B, Chollet-Xémard C, Lakhnati P, 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(23):2303–2312.