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When will we get there? The quandary of investigation in pediatric out-of-hospital cardiac arrest

Christopher M. Pruitt

 

Although out-of-hospital cardiac arrest (OHCA) is rare in children, it often results in death or considerable morbidity., ,  Intuitively, recent data suggest that adherence to established guidelines for pediatric OHCA in the pre-hospital setting is associated with improved survival.,  Less is known about factors associated with survival for children with OHCA who are admitted with return of spontaneous circulation (ROSC).

In this issue of the journal, Scholefield and colleagues present their data on children with OHCA collected through a prospective intensive care unit database (PICANet) in the United Kingdom and Republic of Ireland.Their primary aim was to establish the prevalence of these cases within their 33-center network. Secondarily, they sought to analyze the clinical factors linked with mortality in the pediatric intensive care unit (PICU).

The prevalence of PICU admissions with OHCA and ROSC was <1%, which translates to a population estimate of 1.3 children per 100,000 person-years in their setting. This number is lower than those published elsewhere,, ,  leading the authors to reasonably conclude that performing a prospective clinical trial for OHCA within their network is likely infeasible.

PICANet is a robust, prospectively-collected database for PICU patients in the United Kingdom. As the authors acknowledge, however, its design is not for resuscitation data, and many Utstein-type variables are missing for this cohort. Perhaps more problematically, a “probable cause for arrest” could not be attributed for nearly 50% of subjects. While other large studies have had even greater rates of unknown cause for arrest, only 12% of children in the recent study by Moler et al. had an unknown cause. To the authors’ credit, their attempted delineation of cause for arrest was more granular than that found in other studies. Moreover, being that data were extracted retrospectively, this considerable rate of unknown cause speaks to their caution against over-speculation.

The other limitation of the study that bears consideration is the authors’ selection of endpoint. When studying OHCA, much thought goes into the selection of clinically meaningful endpoints. Here, we are again limited by the database, as historical factors and interventions are analyzed in terms of survival to discharge from the PICU – not neurologic outcome, long-term survival, or even survival to hospital discharge. This renders the conclusions more narrowly applicable than similar studies.

The factors associated with survival to PICU discharge do, however, present some beneficial points of discussion. Echoing prior research, children less than 1 year of age were less likely to survive. Interestingly, children with chronic medical conditions, especially those of a respiratory or cardiac nature, were more likely to survive to PICU discharge. The data additionally demonstrate that those with a respiratory etiology, and possibly cardiac or submersion causes, of OHCA were more likely to survive, while those with traumatic brain injury or sudden infant death syndrome were more likely to die in the PICU.

Perhaps most intriguing is the positive association (in the multivariate model) between mortality and inter-hospital transfer to the PICU. These patients were more likely to expire in the PICU despite having overall lower pediatric index of mortality (PIM) scores. An over-representation of more critically ill children within this transfer group is unlikely, as all ventilated children with OHCA and ROSC within their region would, in theory, be transported to a participating center. One may speculate that there is clinical deterioration prior to definitive care during initial care and transport. Further, the PIM scores were calculated near the time of ICU arrival, possibly representing an under-estimation of initial clinical severity for these patients. It could be that this association more broadly reflects a need for early, specialized care for these critically ill children.

As with most observational research, the results from this study lead to more questions than immediate answers. Why were transferred patients less likely to survive to PICU discharge than those who initially arrived at the referral center? Is there something inherent in children with chronic medical conditions, especially those of a cardiac or respiratory nature, which makes them more likely to live? Does the increased survival of subjects with a respiratory etiology of arrest speak more to physiologic resilience of the patient, or skill of the medical care team?

Herein lies the difficulty with most studies on pediatric OHCA. Despite rigorous methodology and robust statistical analysis, the discovery of meaningful, prospective results remains elusive (though not impossible,). Consider the recent Therapeutic Hypothermia after Pediatric Cardiac Arrest (THAPCA) trial: even with years of meticulous forethought, with 38 centers over a more than 3-year period, the null hypothesis could not be rejected. Likewise, a recent study in this journal from the Resuscitation Outcomes Consortium failed to demonstrate an association between adherence to accepted cardiopulmonary resuscitation guidelines and ROSC during OHCA.

The uncertainties for research in this realm remain daunting. While the present manuscript provides novel information that will certainly shape future studies, the myriad questions bring us back to the primary conclusion of this paper – in spite of a well-organized, comprehensive network for data capture for their patient population, there simply are not enough subjects for practicable prospective research on OHCA. These findings, especially in light of those from other recent studies, beg for even more longitudinal collaboration as investigators seek further answers in the realm of pediatric OHCA.

Conflict of interest statement

Dr. Pruitt declares no financial conflicts of interest relevant to this publication.

References

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