Secondary Logo

Journal Logo

Invited Commentary

Adversity in Neonates and Children with Pulmonary Artery Hypertension: The Role of ECMO

Wearden, Peter D.*†; Maul, Timothy M.*‡

Author Information
doi: 10.1097/MAT.0000000000000459
  • Free

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.


1. Nasr VG, Faraoni D, DiNardo JA, Thiagarajan RRAdverse outcomes in neonates and children with pulmonary artery hypertension supported with ECMO.ASAIO J201662728731
2. Ibrahim AE, Duncan BW, Blume ED, Jonas RALong-term follow-up of pediatric cardiac patients requiring mechanical circulatory support.Ann Thorac Surg200069186192
3. Hervey-Jumper SL, Annich GM, Yancon AR, Garton HJ, Muraszko KM, Maher CONeurological complications of extracorporeal membrane oxygenation in children.J Neurosurg Pediatr20117338344
4. Chrysostomou C, Maul T, Callahan PM, et al.Neurodevelopmental outcomes after pediatric cardiac ECMO support.Front Pediatr2013147
5. Zabrocki LA, Brogan TV, Statler KD, Poss WB, Rollins MD, Bratton SLExtracorporeal membrane oxygenation for pediatric respiratory failure: Survival and predictors of mortality.Crit Care Med201139364370
6. Cornelius AM, Riley JB, Schears GJ, Burkhart HMPlasma-free hemoglobin levels in advanced vs. conventional infant and pediatric extracorporeal life support circuits.J Extra Corpor Technol2013452125
7. Northrop MS, Sidonio RF, Phillips SE, et al.The use of an extracorporeal membrane oxygenation anticoagulation laboratory protocol is associated with decreased blood product use, decreased hemorrhagic complications, and increased circuit life.Pediatr Crit Care Med2015166674
8. Kessel AD, Kline M, Zinger M, McLaughlin D, Silver P, Sweberg TMThe impact and statistical analysis of a multifaceted anticoagulation strategy in children supported on ECMO: Performance and pitfalls.J Intensive Care Med2015[Epub ahead of print]
9. Maul TM, Wolff EL, Kuch BA, Rosendorff A, Morell VO, Wearden PDActivated partial thromboplastin time is a better trending tool in pediatric extracorporeal membrane oxygenation.Pediatr Crit Care Med201213e363e371
10. Robak O, Lakatos PK, Bojic A, et al.Influence of different oxygenator types on changing frequency, infection incidence, and mortality in ARDS patients on veno-venous ECMO.Int J Artif Organs201437839846
11. O’Byrne ML, Glatz AC, Hanna BD, et al.Predictors of catastrophic adverse outcomes in children with pulmonary hypertension undergoing cardiac catheterization: A multi-institutional analysis from the pediatric health information systems database.J Am Coll Cardiol20156612611269
12. Maul TM, Kuch BA, Wearden PDDevelopment of risk indices for neonatal respiratory extracorporeal membrane oxygenation.ASAIO J201662584590
13. Ruth A, McCracken CE, Fortenberry JD, Hebbar KBExtracorporeal therapies in pediatric severe sepsis: Findings from the pediatric health-care information system.Crit Care201519397
14. Barrett CS, Bratton SL, Salvin JW, Laussen PC, Rycus PT, Thiagarajan RRNeurological injury after extracorporeal membrane oxygenation use to aid pediatric cardiopulmonary resuscitation.Pediatr Crit Care Med200910445451
15. Alsoufi B, Al-Radi OO, Gruenwald C, et al.Extra-corporeal life support following cardiac surgery in children: analysis of risk factors and survival in a single institution.Eur J Cardiothorac Surg200935100411; discussion 1011
16. Graziani LJ, Gringlas M, Baumgart SCerebrovascular complications and neurodevelopmental sequelae of neonatal ECMO.Clin Perinatol199724655675
17. Morris MC, Ittenbach RF, Godinez RI, et al.Risk factors for mortality in 137 pediatric cardiac intensive care unit patients managed with extracorporeal membrane oxygenation.Crit Care Med20043210611069
18. Rajagopal SK, Almond CS, Laussen PC, Rycus PT, Wypij D, Thiagarajan RRExtracorporeal membrane oxygenation for the support of infants, children, and young adults with acute myocarditis: A review of the Extracorporeal Life Support Organization registry.Crit Care Med201038382387
19. Gadepalli SK, Hirschl RBExtracorporeal life support: Updates and controversies.Semin Pediatr Surg201524811
20. Kuch BA, Maul TM, O’Malley E, et al.Novalung as a bridge to recovery in a six year old with undiagnosed pulmonary hypertension with right-heart failure requiring ECMO: A case reportin 27th Annual Children’s National Medical Center Symposium ECMO & Advanced Therapies for Respiratory Failure 2011Keystone, CO
21. El-Ferzli GT, Philips JB 3rd, Bulger A, Ambalavanan NEvaluation of a pumpless lung assist device in hypoxia-induced pulmonary hypertension in juvenile piglets.Pediatr Res200966677681
22. Mayes J, Niranjan G, Dark J, Clark SBridging to lung transplantation for severe pulmonary hypertension using dual central Novalung lung assist devices.Interact Cardiovasc Thorac Surg201622677678
23. Hoganson DM, Gazit AZ, Boston US, et al.Paracorporeal lung assist devices as a bridge to recovery or lung transplantation in neonates and young children.J Thorac Cardiovasc Surg2014147420426
Copyright © 2016 by the ASAIO