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Pediatric cardiac arrests occur rarely but carry a low likelihood of survival and functional outcome.1 Arrests are frequently precipitated by acute respiratory failure (accounting for 72% of hospital pediatric cardiac arrests and 42% of in-hospital pediatric cardiac arrests).2 Hence, considerable emphasis is placed on assisted ventilation as part of pediatric cardiopulmonary resuscitation (CPR), with rescuers often attempting endotracheal intubation early during CPR to “secure the airway” and ensure optimal ventilation and oxygenation.
Yet when pediatric cardiac arrest occurs outside the hospital, failed endotracheal intubation is common, especially when compared with adult arrests.3 Furthermore, even when intubation is successful in this setting, outcomes have not been shown to be superior to those with bag-valve-mask ventilation alone.4 One assumption is that the lack of benefit is because out-of-hospital practitioners encounter pediatric arrest too rarely to maintain adequate expertise, and thus current guidelines no longer emphasize intubation for out-of-hospital arrests. In contrast, in-hospital pediatric cardiac arrest is assumed to be managed by rescuers with greater experience, and intubation remains a mainstay in this setting, even though a small observational study failed to demonstrate benefit of intubation for in-hospital pediatric arrest.4,5
For the patient with cardiopulmonary arrest, intubation may eventually be required. Therefore, the issue is not just whether to intubate but when. Some reports suggest that early placement of advanced airways for adults with cardiac arrest facilitates high-quality CPR by allowing for the delivery of continuous chest compressions (and specifically improved no-flow ratios),6 as well as enabling measurement and targeting of end-tidal CO2 concentrations as a physiologic marker of the quality of chest compression. But to intubate the trachea typically requires a pause in chest compressions,7 which can compromise the effectiveness of CPR and potentially delay the delivery of other such interventions, such as epinephrine or defibrillation.8,9 Intubated children are also at risk of inadvertent hyperventilation,10 and the elevated intrathoracic pressure that results reduces venous return and the cardiac output achievable with chest compressions.11
In this issue of JAMA, Andersen and colleagues12 report findings from their analysis of in-hospital pediatric cardiac arrests recorded in the American Heart Association’s Get With The Guidelines–Resuscitation multicenter registry. The authors selected all pediatric (age <18 years) cardiopulmonary events occurring between 2000 and 2014 involving CPR durations of at least 1 minute. After excluding patients already receiving mechanical ventilation or those with invasive airways in place at the time of cardiac arrest, the investigators analyzed the associations between tracheal intubation and its timing during cardiac arrest and patient outcomes. Among the 2294 patients who met the inclusion criteria, 1555 were intubated during CPR, with a median time to intubation of 5 minutes (25th-75th percentiles, 2-11) from the time of onset of chest compressions.
Among patients who underwent tracheal intubation, the unadjusted risk ratios (RRs) suggested a lower likelihood of the primary outcome, survival to hospital discharge (RR, 0.64 [95% CI, 0.59-0.69]), as well as lower likelihoods of the secondary outcomes of return of circulation (RR, 0.84 [95% CI, 0.81-0.88]) and favorable neurologic outcome (RR, 0.55 [95% CI, 0.48-0.63]), based on a pediatric cerebral performance category score of 1 or 2 or no change from baseline.
In their primary analysis, designed to control for confounding by indication bias, the authors used a propensity score to match patients who were intubated or not based not just on demographic factors, underlying illness, presenting features, and location, but also on the timing (by minute) of the intubation. In this matched analysis, survival to hospital discharge remained lower in the intubated group (411/1135 [36%] vs 460/1135 [41%]; RR, 0.89 [95% CI, 0.81-0.99]; P = .03), with no significant differences in return of spontaneous circulation (770/1135 [68%] vs 771/1135 [68%]; RR, 1.00 [95% CI, 0.95-1.06]; P = .96) or favorable neurologic outcome (185/987 [19%] vs 211/983 [21%]; RR, 0.87 [95% CI, 0.75-1.02]; P = .08) between those who were intubated and not intubated. In addition, there was no significant interaction between the timing of intubation during CPR and any of the assessed outcomes.
Sensitivity analyses using multiple imputation to account for missing data and excluding patients who received cardiopulmonary bypass with extracorporeal membrane oxygenation also revealed reduced survival to hospital discharge and reduced favorable neurologic outcome among those patients intubated. In a subgroup analysis that included only patients who had received at least 2 minutes of CPR, intubation during CPR also was associated with a reduced survival to hospital discharge, although there was no association between intubation and return of circulation or favorable neurologic outcome. Thus, none of the analyses suggested any benefit associated with intubation during pediatric cardiac arrest.
The study by Andersen et al was observational, and patients were not randomized to be intubated or not. Thus, as with virtually all observational studies that evaluate health care interventions, the degree to which the validity of the findings is threatened by confounding by indication must be carefully considered. For example, sicker patients may have been more likely to be intubated but also would be more likely to have adverse outcomes. Thus, the authors have to attempt to control for the ways in which patients might be sicker when attempting to estimate the independent association of the decision to intubate with outcome. In this regard, the authors made several important efforts, particularly through their use of time-dependent propensity scores and extensive sensitivity analysis.
The use of the time of intubation in the propensity model allowed the authors to match patients intubated in each period with patients not intubated at that time who nonetheless appeared to be clinically similar. This approach is an advance over approaches that fail to consider that patients intubated at different points may differ in important ways. It also allows exploration of, for example, whether earlier intubation has effects different from those of later intubation. However, unmeasured confounders may have led to the decision to intubate or not at a specific point, and propensity scores can also only adjust for known risk factors. The propensity scores used only prearrest data, and there is no information on factors such as, for example, whether the decision to intubate was prompted by difficulty ensuring adequate noninvasive ventilation during the arrest. The analysis also relies on accurate coding of the time of intubation and compares intubation with no intubation in that particular minute, even though a patient selected as not intubated could then be intubated later. Although this technique statistically attempts to emulate a randomized trial by having patients with similar characteristics in each “treatment group,” the authors’ use of “replacements” allows for each matched (nonintubated) patient to be used more than once. This technique may help to avoid some types of bias, but it increases the possibility of other biases. Intubated patients were matched with children who were not intubated at that specific minute but who might have been intubated immediately after, raising the concern of questionable clinical relevance even if statistical significance was present. Likewise, because many of the patients selected as not intubated were intubated subsequently, the comparison blends the issue of intubation vs no intubation with a comparison of early vs late intubation.
The authors’ extensive sensitivity analyses yielded results that were broadly consistent with those of the primary analysis. Particularly, if there were an unmeasured confounder, the authors show it likely would have to be very common and exert a large effect, which clinicians may judge as implausible, given the richness of the data collected. Nonetheless, the sensitivity analyses largely provide reassurance regarding the reliability, rather than the validity, of the findings. In addition, almost 20% of the patients had missing data. The use of imputation techniques to handle missingness is a reasonable approach that helps to control for, but does not eliminate, the potential bias from nonrandom missing data.
Despite these caveats, the study by Andersen et al provides the best data to date about the association between intubation during cardiac arrest and outcomes among children. The results are highly provocative, but the study design precludes an ability to provide a definitive answer to the question of whether physicians and respiratory therapists should withhold intubation during resuscitation of children with in-hospital cardiac arrest.
Findings from studies of intubation among adults with cardiac arrest are also controversial but similarly suggest that intubation may not be required. The largest study on the association between airway interventions during adult out-of-hospital cardiac arrest and outcomes is based on the All-Japan Utstein Registry, involving 649 359 patients (57% received bag-valve-mask ventilation, 6% were intubated, and 37% had a supraglottic device placed during CPR).13 Better 30-day neurologic outcomes were observed for patients receiving bag-valve-mask ventilation than for those who had either endotracheal intubation or supraglottic device placement during CPR: compared with bag-valve-mask ventilation during cardiac arrest, the odds of neurologically favorable survival were lower for endotracheal intubation (adjusted odds ratio, 0.41 95% CI, 0.37-0.45]) and placement of supraglottic airways (adjusted odds ratio, 0.38 [95% CI, 0.36-0.40]). The findings were similar when a propensity score–matched cohort (357 228 patients) was examined.
However, extrapolation of conclusions from adult out-of-hospital cardiac arrest research to guide the management of pediatric in-hospital cardiac arrest should be done with caution. Moreover, even within the pediatric population, the characteristics and underlying etiologies of out-of-hospital cardiac arrest differ significantly from those of in-hospital cardiac arrest, emphasizing the importance of this study in its focus on pediatric in-hospital cardiac arrest in particular.
Prospective multicenter studies and the establishment of international cardiac arrest registries could generate better insights into the management of pediatric cardiac arrest, although overcoming issues of residual confounding will likely remain a difficult challenge. Although the question of whether or not to intubate the child during cardiac arrest could be answered through a randomized trial, it is unclear whether clinicians and ethics committees would see equipoise in randomizing patients to a “do-not-intubate” study group with neither a secure airway nor assured ventilation during CPR. The timing of intubation in relation to return of spontaneous circulation may also be important, necessitating careful stratification into subgroups so as to reduce the influence of confounding factors that exist due to the diverse etiologies of pediatric cardiac arrest. Thus, the report by Andersen et al offers important and provocative data to address the question of whether the current approach to managing the pediatric airway during CPR is correct, but further prospective studies are needed to provide more robust evidence for a more definitive answer to this critically important question.
Correction: This article was corrected online on October 13, 2016, for an incorrect value in the text.
Corresponding Author: Allan de Caen, MD, FRCP, Edmonton Clinic Health Academy, 11405 87 Ave, Room 4-522, Edmonton, AB T6G1C9, Canada (firstname.lastname@example.org).
Published Online: October 4, 2016. doi:10.1001/jama.2016.13905
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
deCaen AR, Garcia Guerra G, Maconochie I. Intubation During Pediatric CPREarly, Late, or Not at All?. JAMA. Published online October 04, 2016. doi:10.1001/jama.2016.13905