Study design, setting, and participants

This study was a secondary analysis of the Japanese Emergency Airway Network (JEAN) Registry, a prospective observational multicenter data registry designed to characterize the current ED airway management in Japan. The study setting, methods of measurement, and measured variables were as previously described [6, 9–11]. Briefly, JEAN was initiated in April 2010 as consortium of 13 academic and community medical centers across Japan. All 13 EDs had emergency attending physicians, and 12 had affiliations with an emergency medicine residency program. The participating institutions were certified as Level I (n = 11) or Level II equivalent (n = 2) trauma centers and had a mean ED census of approximately 29,000 patient visits per year (range 10,000–67,000). In this multicenter observational study with an aim to describe the current airway management in Japanese EDs, we did not specify the drugs or dosages to be used. A prefixed or predetermined dose was not used across the sites. The Institutional Review Board of each participating hospital (Fukui University Hospital, Fukui Prefectural Hospital, Japanese Red Cross Medical Center of Wakayama, Kameda Medical Center, National Center for Global Health and Medicine, Nagoya Ekisaikai Hospital, Obama Municipal Hospital, Okinawa Chubu Prefectural Hospital, Osaka Saiseikai Senri Hospital, Shonan Kamakura General Hospital, Kurashiki Central Hospital, St. Marianna University School of Medicine Hospital and Niigata City General Hospital) approved the protocol with a waiver of informed consent obtained prior to data collection because it was not feasible to obtain consent from patients who require a life-saving emergency procedure-emergency airway management, and this observational study was considered a “minimal risk” study.

Data were gathered prospectively over a 29-month period (April 2010 to August 2012). Adult and pediatric patients who presented to one of these EDs and underwent emergency intubation were eligible for inclusion.

Outcome measures

The primary outcome measure was intubation success on first attempt. The secondary outcome measures were intubation success in ≤2 attempts and intubation-related adverse event rate. Intubation success was defined as proper placement of the endotracheal tube through the vocal cords with confirmation by quantitative or colorimetric end-tidal carbon dioxide monitoring [4, 6, 9, 10]. We defined the intubation-related adverse events as any adverse events that were potentially related to the procedure itself or occurred during the ED course after intubation. We did not define a specific time-period of intubation-related adverse events, as half-life of sedatives and neuromuscular blocking agents and the physiologic reserve of patients varied widely. Adverse event included esophageal intubation, main bronchial intubation, lip or dental trauma, vomiting, airway trauma, dysrhythmia, hypotension, hypoxemia and death [9]. Esophageal intubation was defined as misplacement of the tracheal tube in the upper esophagus or hypopharynx with a lapse of time and desaturation (pulse oximetry saturation <90%) before the removal of the misplaced tube. Vomiting was defined as gastric contents that required suction removal during laryngoscopy in a previously clear airway. A previous clear airway was defined as airway without visualized gastric contents during laryngoscopy. Hypoxemia was defined as pulse oximetry saturation <90% during an intubation attempt that was potentially-related to the intubation procedure, not secondary to esophageal intubation. Therefore, unchanged hypoxemia was not considered as an adverse event. Hypotension was defined as systolic blood pressure <90 mm Hg. Cardiac arrest included asystole or pulseless electric activity and cardiopulmonary resuscitation during or after intubation. By contrast, we excluded patients who already had cardiac arrest before the intubation procedures.

Data analysis

For the purpose of this analysis, we identified patients who underwent their first intubation attempt using NMB alone and those with RSI. We excluded patients involving cardiopulmonary arrest prior to emergency airway management, subsequent intubation with alternate methods when the first attempt failed. We also excluded intubation using non-direct-laryngoscopy (e.g. video laryngoscopy or fibroscopy) or the use of a gum-elastic-bougie because all cases which used these devices were intubated with only RSI.

We compared the outcomes between intubation attempts using NMB alone and RSI, by fitting two logistic regression models (unadjusted and adjusted for selected variables) using each of the three outcomes as dependent variables. A set of potential confounders was selected a priori based on biological plausibility and a priori knowledge. These included age, sex, body weight, primary indication for intubation (shock, altered mental status, or others) [2, 12, 13], and training level of intubator [4, 9, 10, 14, 15]. In the sensitivity analyses, we stratified the model by indication and intubator characteristics. All analyses were conducted with JMP statistical software version 9 (SAS Institute Inc., Cary, NC, USA).

Results in context

To our knowledge, the use of NMB-alone intubation in the ED has not been addressed in the literature, making our present findings difficult to compare. However, previous studies have reported that absence of concurrent sedation was common among patients receiving long-acting neuromuscular paralysis during transportation between hospitals and NMB-alone or inadequate sedation in non-comatose patients was an avoidable medical error [16–18]. One may argue that emergency airway management with NMB alone has advantages over that with RSI—e.g. a lower frequency of hypotension [3]. However, our data did not demonstrate superior effectiveness of intubation with NMB alone in either the adverse event rate or the success rate. This result persisted with several statistical assumptions. Additionally, paralysis without sedation causes pain and psychogenic trauma as well as sympathetic autonomic discharge leading to hypertension and tachycardia, which might worsen intracranial hemorrhage, vascular dissection, and other conditions [7, 8]. As the use of etomidate has been discouraged in Japan due to its spectrum of adverse effects, which have been addressed in previous studies, ketamine is a potential alternative to induce sedation in hemodynamically unstable patients [3, 19–22]. Collectively, our findings lend significant support to the concept that airway management with NMB alone should be avoided in the ED.

Variations in emergency airway management across EDs

We are struck by a high degree of variation in the use of NMB alone across the participating EDs. The reasons are likely multifocal. Potential explanations include differences in patient populations, physician preferences, procedural experience levels, training background, and institutional policies. In contrast, our previous study indicated a lack of robust evidence-based airway management education and a peer-review process for residency training programs in Japan [6]. Any or a combination of these factors might explain, at least in part, the wide inter-hospital variation in intubation practice observed in this study.

Limitations

Our study has several potential limitations. First, passive surveillance introduces the potential for self-reporting bias. Underestimation of adverse event rates is therefore possible. However, we used a standardized system with structured data forms, uniform definitions, and a high capture rate [4]. Additionally, assuming a similar underestimation rate of the outcome between groups, this non-differential misclassification would not have biased our inference. Second, our data predominantly consists of academic EDs in Japan. Our inferences might therefore not be generalizable to other clinical settings. Finally, our inferences might be confounded by unmeasured factors, such as levels of consciousness, pre-intubation blood pressure and the procedural experience of the operators. Granular data on the degree of altered mental status (e.g. Glasgow Coma Scale) would be informative. However, in the JEAN study, data on this medical condition were not collected. We adjusted for the primary indication and training level of the intubator. Although a randomized trial would help determine the efficacy of airway management with RSI compared to NMB alone, such a trial would be unethical. As an alternative, our prospective observational data reflect the effectiveness of airway management methods in the natural setting of a “real” population.