In a study in this issue by Nasr et al.,1 the authors found a striking mortality rate in pediatric patients with pulmonary artery hypertension (PAH) from noncongenital cardiac disease who were treated with extracorporeal membrane oxygenation (ECMO) compared with a propensity-matched cohort of patients who were not treated with ECMO. This study, remarkable for its utilization of a large-scale database of administrative and hospital admission data collected from a broad variety of sizes and types of hospitals in a large cross-section of the United States, provides some insight into a relatively rare disease (1.4% of the database) and one of the most extreme methods available to clinicians to combat its effects, the use of which is also exceedingly rare (0.15%). From the outset, before propensity matching, we are introduced to a patient population that is younger (54% <12 months in age), less likely to be electively admitted (91%), admitted for longer periods of time, and who have a significantly higher likelihood for comorbidity (per Elixhauser scale) compared with those who do not require ECMO. This population profile discrepancy is reminiscent of the makeup of pediatric cardiac ECMO and ventricular assist device population versus those that do not require this support, or pediatric respiratory ECMO versus conventional therapy, which also tend to be younger, emergently admitted, and sicker as demonstrated through a variety of comorbidity scales.2,3 While the results of this study are somewhat disheartening from an outcomes standpoint (39% mortality vs. 8% mortality in matched cohorts), given that ECMO is generally utilized in the most extreme cases and as a last resort, it is hopefully apparent to the reader that clinicians in deciding to implement ECMO are faced with a significantly refractory patient population with few if any remaining options. In other words, despite the propensity matching, it is likely that there was a certain clinical “je ne sais quoi” certainly not captured by such an administrative database that required the utilization of ECMO. More bluntly, even if one picks the ripest apples from the bunch to compare with, they still are not oranges.
While ECMO is not a tool that is taken lightly by those who practice it, and is employed in the face of exhaustion of nearly all other medical therapies, there is significant debate in the clinical community over the timing and utilization of this therapy in a variety of disease states, with recognition that the earlier implementation of therapy, the fewer complications and the better the patient outcome.4,5 Some of the debate has been driven by the fact that the risks of complications from ECMO utilization have been dramatically reduced over the past decade thanks in large part to newer and better equipment: Polymethylpentene oxygenators that last for weeks, centrifugal pumps that cause little hemolysis, and a better understanding of pediatric anticoagulation and anticoagulation testing.6–10 However, the utilization of ECMO still is not without risks, and in this PAH population, Nasr et al.1 reported higher incidences of kidney failure, neurologic injury, thrombotic complications, and sepsis in their ECMO population compared with those who did not require ECMO with the same caveats as noted above.
A few key challenges are hopefully apparent when viewing this study in the larger context of outcomes, resource utilization, and healthcare costs. The first is that because this is a large retrospective dataset which primarily relied on administrative coding and inpatient reports, there is no chance to distinguish the events leading up to the utilization of ECMO. In fact, this study points to the need for a concerted effort to study the progression of apparently similar patients from the outset (i.e., prospective matching on age, elective admission, and the Elixhauser score) down two very different paths. One would expect that those that require ECMO might take a slow progressive march toward multiple organ failure as the strain on the right ventricle and limited oxygen supply leads to a chronic and progressive organ ischemia; or it might be a sudden onset of cardiac failure due to cardiac strain, or even adverse reactions to the medical therapy being received.11 For instance, how many of these patients saw the implementation of ECMO urgently, or even emergently following cardiac arrest? It is our hypothesis that these two scenarios represent a portion of the root cause for the increased kidney, neurologic, and septic injury that were found by Nasr et al.1 in the ECMO population of this study, and we would further hypothesize that these complications provided a significant contribution to the increased mortality of these patients as has been demonstrated in other studies,9,12–15 particularly with reference to neurologic14,16 and renal failure.17,18 Furthermore, viewed from the perspective of the non ECMO group, how many of these patients, if they had been placed on ECMO, might have survived? One might make the suggestion that fully 61% of these patients may have survived given the outcomes of the propensity-matched ECMO group.
Another question which must be asked is what were the circumstances that led to the termination of ECMO, and therefore death in these patients? In recent years, the decision to end ECMO in the face of futility has increasingly become controversial.19 We are experiencing longer, and more complication-free ECMO runs, and as a result may be finding that diseases which we thought were futile can be reversed with sufficient time and proper ECMO management. To wit, we have previously employed a pumpless lung technology in a pediatric patient with PAH following cardiac arrest onto ECMO. After 30 days on a central shunt and oxygenator with no pump and the initiation of pharmacologic therapy for pulmonary hypertension, the patient was weaned from the device and discharged to home.20 Similar results have also been published, both experimentally21 and clinically.22,23
In conclusion, we commend Nasr et al.1 for their study on the outcomes of ECMO utilization in PAH, and recognize the complexities and challenges of utilizing, and propensity matching, an unaudited, administrative database in a retrospective fashion. It is our hope that the questions raised by this article do not spur the “knee-jerk” reaction that ECMO is an inferior therapy in pulmonary arterial hypertension. Instead, we believe that thoughtful consideration will lead to the recognition of the need for further investigation into the underlying causes of this disparity in outcomes so that more targeted and effective therapies can be developed and utilized, perhaps even in conjunction with more timely implementation of ECMO, to effect a reduction in the mortality related to this disease.
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