ECMO as an emergency medical countermeasure
Authors: Subroto Paul, Bruce Campbell, Ellen C Meltzer, Art Sedrakyan
Journal: The Lancet Respiratory Medicine (2014)

The survival benefit for patients with acute respiratory distress syndrome (ARDS) due to extracorporeal membrane oxygenation (ECMO) treatment invites consideration of whether ECMO might provide an important medical countermeasure for ARDS resulting from natural hazards or acts of terrorism. Anthrax spores, bioengineered or native avian flu strains, or chemical agents (such as chlorine gas and its derivatives) can all lead to lung injury with resulting ARDS. A framework is needed for ECMO if it is to be incorporated into our comprehensive emergency preparedness programmes. ECMO provides continuous circulatory support or oxygenation to patients with cardiac failure and pulmonary failure. It is already established in the treatment of heart failure after cardiac surgery and has become increasingly accepted in the treatment of adults with lung injury who cannot be oxygenated by conventional means.1Peek GJ Mugford M Tiruvoipati R et al.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: 1351-1363Summary Full Text Full Text PDF PubMed Scopus (2647) Google Scholar Technological advances, facilitating the implementation of ECMO in critical care, have improved outcomes for patients with ARDS.1Peek GJ Mugford M Tiruvoipati R et al.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: 1351-1363Summary Full Text Full Text PDF PubMed Scopus (2647) Google Scholar Improved technology combined with an increasing confidence in the use of ECMO from shared experiences reported at international meetings and through registries such as the Extracorporeal Life Support Organization (ELSO), has led to a substantial increase in its use (figure). Our analysis of the US Nationwide Inpatient Sample (NIS) database shows that during the past decade, ECMO support after heart surgery (post-cardiotomy) and for respiratory failure has increased by more than six times.2HCUPOverview of the National (Nationwide) Inpatient Sample (NIS). Healthcare Cost and Utilization project.http://www.hcup-us.ahrq.gov/nisoverview.jspGoogle Scholar Severe acute respiratory syndrome (SARS) and H1N1 flu epidemics showed the need for lifesaving technologies and the ability of ECMO to potentially address this need in the treatment of ARDS;1Peek GJ Mugford M Tiruvoipati R et al.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: 1351-1363Summary Full Text Full Text PDF PubMed Scopus (2647) Google Scholar after its successful application in these outbreaks in 2007, rates of ECMO use for respiratory failure rapidly increased.3Brodie D Bacchetta M Extracorporeal membrane oxygenation for ARDS in adults.N Engl J Med. 2011; 365: 1905-1914Crossref PubMed Scopus (631) Google Scholar, 4Davies A Jones D Bailey M et al.Extracorporeal membrane oxygenation for 2009 influenza A (H1N1) acute respiratory distress syndrome.JAMA. 2009; 302: 1888-1895Crossref PubMed Scopus (1387) Google Scholar Portable ECMO devices are now available to allow ECMO initiation outside of a hospital setting. Some French, German, and Taiwanese centres have reported the feasibility of use of ECMO for cardiopulmonary arrest by trained interdisciplinary teams.5Chenaitia H Massa H Toesca R Michelet P Auffray JP Gariboldi V Mobile cardio-respiratory support in prehospital emergency medicine.Eur J Emerg Med. 2011; 18: 99-101Crossref PubMed Scopus (22) Google Scholar, 6Hilker H Philip A Arlt M et al.Pre-hospital cardiopulmonary resuscitation supported by ECMO—a case series of 6 patients.Thorac Cardiovasc Surg. 2013; 61: 45Crossref Google Scholar, 7Wang CH Chou NK Becker LB et al.Improved outcome of extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest—a comparison with that for extracorporeal rescue for in-hospital cardiac arrest.Resuscitation. 2014; (published online June 30.)https://doi.org/10.1016/j.resuscitation.2014.06.022Summary Full Text Full Text PDF Scopus (174) Google Scholar The French field ECMO programme was established to specifically deal with the anticipated need for mobile ECMO in an H1N1 epidemic.5Chenaitia H Massa H Toesca R Michelet P Auffray JP Gariboldi V Mobile cardio-respiratory support in prehospital emergency medicine.Eur J Emerg Med. 2011; 18: 99-101Crossref PubMed Scopus (22) Google Scholar This programme enhanced the possibility of incorporating ECMO into comprehensive emergency preparedness programmes as a medical countermeasure against epidemics or terrorist actions that could lead to ARDS. However, evidence on its use in this type of setting is limited. Although clinical information from case series, trials, and the ELSO registry provide some data, similar to other devices for disaster preparedness regimens, these devices cannot be fully tested until disaster situations arise. Bleeding, embolic, and infectious complications inherent in the use of ECMO might be increased when used in mass casualty settings in inexperienced hands. Indications for the use of ECMO could be inadvertently or erroneously expanded to include healthier patients in view of present enthusiasm for the technology because of its success in treating patients with H1N1 or SARS. Furthermore, ECMO might not be discontinued in futile cases whereby its further use leads to needless prolongation of patient discomfort and an inappropriate use of scare resources. All these factors make regulatory approval and consideration of ECMO as a medical countermeasure challenging; however, approval is needed to allow production and dissemination of sufficient devices for use in a public-health emergency. From a regulatory perspective, the development of ECMO as a medical countermeasure needs to follow a different pathway to the usual process. It invites an even more radical change than the innovation pathway used by the US Food and Drug Administration.8US FDAInnovation pathway. US Food and Drug Administration.http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDRH/CDRHInnovation/InnovationPathway/default.htmGoogle Scholar The type and number of patients affected by acts of bioterrorism or public-health emergencies that ECMO could treat is unknown; the device cannot be fully tested until those situations occur. For present approved devices, including ECMO, the approach to their use will be based on present clinical evidence, modelling, and expert opinion. For novel devices that are potential medical countermeasures, different types and thresholds of evidence are needed to accelerate approval. Appropriate systems of assessment need to be developed that can incorporate new concepts for using accumulated data as surrogate evidence of effectiveness (and safety) in medical countermeasure settings to allow ECMOs to be included into strategies of preparedness without delays. The amount and type of evidence will vary depending on whether the device used poses high clinical risks (eg, ECMO) or low clinical risks (eg, a novel type of wound dressing). An important consideration for regulatory bodies in approving devices for public-health emergencies is defining the indications for their use to prohibit inappropriate and futile care. An infrastructure is needed to develop decision support systems for the use of these devices by health-care professionals and to develop simulations of their use in public health emergencies. Regulatory bodies should formulate new policies to ensure effective medical care is provided and that ethical concerns of health-care professionals, patients, and families are addressed. Formal definitions of circumstances that these devices should be used in would reduce the burden on physicians in deciding when a device is appropriate or when its use is futile. Governmental and professional agencies worldwide should collaborate to build a framework for the most appropriate use of ECMO in public-health emergencies. Such a framework would need to include the evidence needed for regulatory approval and the various clinical, ethical, and financial aspects of ECMO availability and use. Combined global experiences from implementation of ECMO in influenza epidemics, as done already in many countries, could be the first phase of such a framework. In addition to this framework, the development of new systems for data collection and plans to incorporate new technologies, such as ECMO, is imperative. Guidance on the policy debate now could lead to a measured and thoughtful use of these technologies when a disaster occurs. This work was supported by the Medical Device Epidemiology Network's Science and Infrastructure Center. AS is the principal investigator or director and SP is a senior investigator within the centre. AS and SP report grants from the US Food and Drug Administration. BC and ECM declare no competing interests.