Endotracheal intubation during out‐of‐hospital cardiac arrest: New insights from recent clinical trials

Abstract Airway management is an important intervention during resuscitation of out‐of‐hospital cardiac arrest (OHCA). Endotracheal intubation is commonly used by emergency medical services paramedics in the advanced airway management of OHCA, but numerous studies question its safety and effectiveness. Furthermore, there is now increasing use of supraglottic airway devices. In this review, we provide an overview of 3 recent randomized clinical trials of advanced airway management (Pragmatic Airway Resuscitation Trial [PART], AIRWAYS‐2, and Cardiac Arrest Airway Management [CAAM]) and highlight new information that is available to guide OHCA airway management practices.


INTRODUCTION
Airway management is a core element of resuscitation from cardiopulmonary arrest. In the hospital setting, healthcare practitioners commonly perform the advanced technique of endotracheal intubation (ETI) during cardiac arrest resuscitation in the belief that it provides a direct conduit to the lungs, aids in controlling ventilation and oxygenation, and protects the airway from aspiration. Recognizing that cardiac arrest often occurs outside the hospital, clinical leaders have sought to improve cardiac arrest outcomes by training and equipping paramedics to perform ETI during out-of-hospital cardiac arrest (OHCA). [1][2][3][4][5] In countries with advanced emergency medical services (EMS) systems such as the United States and the United Kingdom, ETI has been the most common approach to advanced airway management in OHCA for over 40 years.
Numerous studies have questioned the role, safety, and effectiveness of ETI in out-of-hospital care. 1

PITFALLS AND CHALLENGES OF OUT-OF-HOSPITAL ENDOTRACHEAL INTUBATION
ETI is a complex procedure entailing over 100 separate manual or cognitive steps. 9 Studies of paramedic ETI in both OHCA and non-OHCA cohorts highlight the pitfalls of the intervention. Katz and Falk systematically examined 108 paramedic-placed endotracheal tubes in patients arriving at the emergency department (ED), finding 25% of the tubes misplaced; two-thirds were in the esophagus. 10

SUPRAGLOTTIC AIRWAYS AS AN ALTERNATIVE TO ENDOTRACHEAL INTUBATION
SGA devices include airway devices such as the esophageal-tracheal combitube (Combitube), laryngeal mask airway (LMA), laryngeal tube (LT), and i-gel, among others. 18 Historically, SGA devices were developed for use in the operating room. Prior to the availability of paramedic ETI, there was limited experience with paramedic use of the Combitube and other early SGA devices. 19,20 With the widespread practice of paramedic ETI, SGA devices were generally relegated to a rescue role after failed intubation efforts.
Pioneering work from Arizona demonstrating the benefit of continuous and minimally interrupted cardiopulmonary resuscitation (CPR) chest compressions resulted in a resurgence of interest in SGA devices. 21 Given the difficulty of ETI, many EMS agencies resorted to the simpler strategy of SGA insertion to avoid chest compression interruptions during OHCA. Some EMS agencies found that SGA techniques were sufficiently straightforward to allow basic life support rescuers to insert these devices, providing an alternative to bag valve mask (BVM) ventilation. 22,23 Compared with ETI, SGA devices have a simpler insertion technique and a lower training burden while facilitating ventilation characteristics similar to ETI. Given these factors, one would anticipate better OHCA outcomes with a SGA when compared to ETI insertion.
However, analyses of observational data have found better outcomes with ETI than SGA. In an analysis of 10 An important limitation of these observational studies is the influence of confounding-by-indication. Factors potentially influencing paramedic airway choice may have included the patient's condition, airway anatomy, perceived difficulty of airway management, or practitioner airway skill or comfort with specific airway techniques, among others. Even with the use of advanced analytic techniques such as multivariable adjustment and propensity score matching, it is difficult to fully account for the influence of confounding-by-indication, because many confounders may be unknown or unmeasurable. 27 Thus, randomization is the optimal approach for testing outcomes between different OHCA airway management techniques.

CLINICAL TRIALS OF ENDOTRACHEAL INTUBATION IN OUT-OF-HOSPITAL CARDIAC ARREST
Motivated by the prominence of airway management during OHCA, the uncertain safety of ETI, and the unclear effectiveness of SGA strategies, 3 recent multicenter clinical trials (the first ever of airway management techniques in adult OHCA) tested the effectiveness of ETI in the resuscitation of OHCA patients (Table 1).

The Pragmatic Airway Resuscitation Trial
The Pragmatic Airway Resuscitation Trial (PART) involved 27 US advanced life support EMS agencies from the Birmingham (Alabama), Dallas-Fort Worth, Milwaukee, Pittsburgh, and Portland (Oregon) sites of the ROC. 6 The trial included adult OHCA patients who required BVM ventilation or advanced airway insertion. The trial tested 2 airway strategies: (1) initial airway management with the LT, or (2)  There were several important secondary findings and limitations in PART. Elapsed time from EMS arrival to airway start was almost 3 minutes shorter with LT than ETI (median 9.8 versus 12.5 minutes), supporting the hypothesis that LT is more efficient than TI. The intubation success rate in the ETI arm was 51.6%, a figure below that reported by meta-analyses (91.2%). 28 However, the majority of these cases were successfully rescued by LT, resulting in an overall airway success rate of 91.5% in the ETI arm. Although the exact reasons for the lower ETI success rate were not clear, the observations were consistent with the common practice of limiting futile ETI efforts and favoring early rescue LT use. There were also imbalances in treatment allocation within select randomization clusters; post hoc multivariable adjustment to account for these imbalances attenuated some of observed associations between LT and OHCA outcomes.   Although CAAM's non-inferiority design led to an uninterpretable result, a repeat of the trial is unlikely given its important secondary findings.

UNANSWERED QUESTIONS
Despite the scale of the 3 trials, important scientific questions remain.
PART, AIRWAYS-2, and CAAM evaluated different airway devices; there has been only 1 direct randomized comparison between different SGA devices (eg, LT, i-gel, or LMA), and none between SGA and BVM in randomized clinical trials enrolling adult OHCA patients. 32 There is also limited information regarding the influence of airway management technique on chest compression continuity. AIRWAYS-2 and CAAM collected CPR process data on very few patients (n = 66 and 115, respectively), and PART lacked sufficient resources to support CPR process data collection and analysis.
Although widely used in clinical practice, there are relatively few large reports of adverse events associated with out-of-hospital SGA use. 33 In a porcine model of OHCA, Segal et al. showed that advanced airway devices-including ET tubes, LT, LMA, and Combitube-resulted in a reduction of carotid blood flow; these findings are potentially important but have yet to be confirmed in human cardiac arrests. 34 If SGA devices are broadly adopted into practice, continued surveillance for adverse events will be essential.
Although critics suspect the low ETI success rate of PART may have reduced survival in the ETI arm, this mediating relationship has yet to be verified. Portable video laryngoscopy (VL) is now broadly available in the out-of-hospital setting and could ease intubation efforts.
Widespread availability of VL could alter the perceived tradeoffs between ETI and SGA, but any impact on OHCA outcomes would merit formal evaluation. 32 The technique of passive ventilation (high flow oxygen by face-mask only, without BVM or advanced airway) was demonstrated in Arizona's implementation of minimally interrupted CPR; while potentially circumventing all issues with advanced airway management, this technique has yet to be tested in a randomized fashion. 21 Whereas PART, AIRWAYS-2, and CAAM focused on adult OHCA, other important patient groups include those with trauma (both traumatic brain injury and hemorrhagic shock) and medical non-arrest conditions such as acute pulmonary edema, seizures, and drug overdoses.