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The Evidence for ECMO Use in Severe Influenza

By Amesh A. Adalja, MD, June 11, 2010

When conventional mechanical ventilation of a patient suffering from respiratory failure cannot maintain adequate oxygenation, several advanced rescue measures can be employed, among them, extra-corporeal membrane oxygenation (ECMO). In the past year, use of venous-venous (VV) ECMO (ie, a heart lung machine) has been prominently featured in a journal article published in the Journal of the American Medical Association and proffered as a possible rescue therapy for those with severe lung injury from H1N1 influenza.1 A recent issue of Critical Care Medicine includes an article by researchers from the University of Pennsylvania, who conducted a systematic review of the effect of ECMO on the survival of adult patients with acute respiratory failure secondary to infection with H1N1 influenza virus.2

Clinical Evidence Scarce

The authors conducted an exhaustive, but futile, search for clinical practice guidelines or systematic reviews addressing ECMO use in acute respiratory failure secondary to infectious diseases. They did find 3 randomized controlled trials that included patients with infectious etiologies of Acute Respiratory Distress Syndrome (ARDS), 3 cohort studies, and the recently published case series of 2009 H1N1 patients—the only published study specific to influenza—which revealed a mortality rate of 23%.1

None of the randomized controlled clinical trials were specific to influenza or viral pneumonia, but they did include patients with bacterial pneumonia. A meta-analysis of these 3 trials, which had moderate heterogeneity, yielded a summary risk ratio of 0.93 (CI 0.71-1.22), translating to no mortality benefit. Of the 3, only the recently published CESAR trial, which studied the use of ECMO in cases of acute respiratory failure, yielded statistically significant 6-month decreases in mortality and disability (RR 0.69 attributable to ECMO).3

Insufficient Evidence to Recommend ECMO

Based on the dearth of clinical evidence supporting the use of ECMO in influenza patients, the authors do not endorse a general recommendation for ECMO use in these patients. However, they do suggest that ECMO may be indicated after all other rescue therapies have been exhausted. They also suggest that institutions without the ability to perform ECMO develop guidelines for triage of patients who might benefit from referral to an ECMO center.

Further Study Needed

As is clear from this systematic review, there is little evidence to support the use of ECMO in influenza patients; however, the potential benefits cannot be ignored. Once more data emerges from the experience with the 2009–10 H1N1 pandemic, it will be possible to weighs pros and cons of an ECMO-based approach as well as approaches based on other rescue techniques. While a general recommendation for ECMO use in influenza patients cannot be supported at this time, the development of clinical guidelines and policies and more research should be pursued to inform the clinical decisions of individual physicians and the economic decisions of institutions considering investment in EMCO machinery.


  1. The Australia and New Zealand Extracorporeal Membrane Oxygenation (ANZ ECMO) Influenza Investigators. Extracorporeal membrane oxygenation for 2009 influenza A(H1N1) acute respiratory distress syndrome. JAMA 2009;302(17):1888-1895.

  2. Mitchell MD, Mikkelsen ME, Umscheid CA, et al. A systematic review to inform institutional decisions about the use of extracorporeal membrane oxygenation during the H1N1 influenza pandemic. Crit Care Med 2010;38:1398-1404.

  3. Peek GJ, Mugford M, Tiruvoipati R, Wilson A, Allen E, Thalanany MM, Hibbert CL, Truesdale A, Clemens F, Cooper N, Firmin RK, Elbourne D. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet 2009;374:1351-1363.