CURASMUR

Effect of Rocuronium vs Succinylcholine on Endotracheal Intubation: Success Rate Among Patients Undergoing Out-of-Hospital Rapid Sequence Intubation

Bertrand Guihard et al. JAMA December 2019; 322(23):2303-2312. doi:10.1001/jama.2019.18254

Clinical Question

  • In patients requiring emergency out-of-hospital endotracheal intubation, is rocuronium non-inferior to suxamethonium in providing a successful first pass attempt?

Background

  • Suxamethonium and rocuronium are the two most commonly used paralytic agents when performing an emergency intubation
  • The side effect profile of suxamethonium (hyperkalaemia; malignant hyperthermia; muscle pain) is thought to be greater than that of rocuronium
  • A rocuronium dose of 1.2 mg/kg is thought to confer comparable intubating conditions to 1mg/kg of suxamethonium
  • A Cochrane review from 2015 combined the results of 50 trials and concluded that rocuronium was slightly less effective than suxamethonium for creating excellent and acceptable intubating conditions
  • There is little in the way of prospective data to determine whether these agents are equally effective in providing optimal intubating conditions in the emergency prehospital setting
  • This was the first randomised controlled trial to compare the performance of rocuronium and suxamethonium in prehospital emergency care

Design

  • A nationwide, single-blinded, randomised, non-inferiority study
  • Physicians non-blinded to study arm
  • Consecutive patients were randomised
  • Sample size calculated at 1204 based on a successful first-attempt intubation rate of 75% in the suxamethonium group, a non-inferiority margin of 7%, a type 1 error (alpha) of 5% and a type II error (1-beta) of 20%
    • This meant that if the lower margin of the 97.5% one-sided confidence interval crossed -7%, then the null hypothesis of rocuronium being inferior to suxamethonium would be accepted
    • 650 patients planned in each group to account for protocol violations
  • A per-protocol analysis was initially conducted, in line with the non-inferiority study design
  • Data was recorded by the intubating physician completing a paper case report form onsite. This was later verified by a clinical research associate at each centre
  • Patients were followed up until hospital admission
  • There were five secondary outcomes. These were: Cormack and Lehane intubation grade, difficulty of intubation (measured by the Intubation Difficulty Scale), intubation conditions (measured by the Copenhagen score), the percentage of patients intubated by alternative techniques and intubation-related complications in the first 15 minutes after intubation (cardiac arrest, hypotension, hypoxaemia, physician-reported aspiration, severe arrythmia or allergic reaction

Setting

  • Pre-hospital setting throughout France
  • 17 out-of-hospital emergency medical units
  • January 2014 – August 2016

Population

  • Inclusion: Patient in the pre-hospital setting requiring emergency intubation
  • Exclusion: Patients who had suffered a cardiac arrest
  • Patients younger than 18 years of age
  • Pregnant women
  • Contraindication to rocuronium or succinylcholine
  • 1326 patients assessed for eligibility; 78 patients excluded; 1248 patients randomised and enrolled in the study
  • Patients in the rocuronium arm had a greater incidence of chronic disease (hypertension, smoking, alcoholism, cancer, coronary heart disease and heart failure) than patients in the suxamethonium arm

Intervention

  • Rocuronium 1.2 mg/kg with dosage based on estimated patient weight

Control

  • Suxamethonium 1 mg/kg with dosage based on estimated patient weight

Management common to both groups

  • Recommended anaesthetic induction agents were etomidate (0.3mg/kg) or ketamine (2mg/kg)
  • Cricoid pressure was recommended but optional, according to the physician’s preference
  • It was recommended to perform intubation 60 seconds after administration of the paralytic agent
  • Single-use Macintosh blades (sizes 3 and 4) were used
  • When standard laryngoscopy-assisted intubation was not possible, an alternative procedure was recommended in accordance with the French Society of Anaesthesia and Resuscitation guidelines on difficult airway management, including gum elastic bougie, intubating laryngeal mask airway or cricothyroidotomy
  • Sugammadex could be used if required in the rocuronium group
  • No change from usual practice in management of deteriorating physiology during intubation e.g. hypotension managed with intravenous fluids and vasopressors

Outcome

  • Primary outcome: 455 of 610 (74.6%) patients in the rocuronium group had successful first-pass intubation, compared with 489 of 616 (79.4%) in the suxamethonium group
    • Absolute difference of -4.8% (1-sided CI -9% to infinity)
    • This was below the non-inferiority margin of 7%
  • Secondary outcomes: No difference in the following:
    • Cormack and Lehane airway grade between rocuronium and suxamethonium
    • Overall difficulty of the intubation process, measured by the Intubation Difficulty Scale score (range, 0 to infinite; score >5 indicates difficult intubation)
    • Intubation conditions, assessed by the Copenhagen score (poor, good, or excellent conditions)
    • % of patients intubated by alternative techniques (stylet, gum elastic bougie, ILMA [e.g. Fastrach], or cricothyrotomy)
    • Intubation-related complications in the first 15 minutes after intubation (cardiac arrest, arterial hypotension [systolic blood pressure <90 mm Hg], hypoxaemia [occurrence of new oxygen desaturation <90%], physician-reported aspiration, severe arrhythmia [ventricular tachycardia, ventricular fibrillation], or allergic reaction)
    • Significantly more intubation attempts were required in the rocuronium group than the suxamethonium group in the post-hoc exploratory outcomes analysis

Authors’ Conclusions

  • Among patients undergoing endotracheal intubation in a medical-based out-of-hospital emergency care system, rocuronium, compared with suxamethonium, failed to demonstrate non-inferiority with regard to first-attempt intubation success rate

Strengths

  • A pragmatic study enrolling a heterogenous group of patients
  • Attempting to answer a relevant clinical question that has been the source of much debate in recent years
  • Appropriate power calculation and non-inferiority study design
  • Minimal loss to follow-up of patients and only a small number of protocol violations

Weaknesses

  • Etomidate was the main sedative agent used in this study, but is seldom used in the emergency setting in the UK and Australia
  • First pass success and the documentation of complications was at the discretion of the intubating physician, who was unblinded to the study group
  • There was a difference in the prevalence of chronic disease between the suxamethonium and rocuronium arms
  • A first pass intubation success rate of 75-80% is lower than reported in other pre-hospital settings (87.5% in London HEMS) Harris EMJ 2011
  • The primary outcome of first pass intubation success is a surrogate outcome measure
  • No video laryngoscope, stylet or bougie was used as part of the intubation protocol
  • The major advantage of rocuronium (it’s lower side-effect profile) could not be demonstrated with this study design as these are rare, although still clinically relevant
  • There was no data provided on the seniority or experience of the physicians performing the intubation

The Bottom Line

  • I generally use rocuronium dosed at around 1.2 mg/kg for emergency intubations in the ED and ICU. I think that this is still a reasonable approach based on the data from this study
  • The difference in baseline characteristics between the groups and the study limitations mean that no firm conclusions can be drawn regarding the superiority of either agent
  • The question of whether potentially superior first pass intubating conditions outweighs a rare and potentially catastrophic adverse drug reaction remains a matter of debate

External Links

Metadata

Summary author: Fraser Magee
Summary date: 31st January 2020
Peer-review editor: Adrian Wong

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