[dropcap]Over the last 5 years, the use of veno-venous ECMO for patients with severe respiratory failure has steadily increased (1). Part of this is of course the success of the CESAR trial performed at Glenfield Hospital in the UK where transfer to an ECMO capable centre for consideration of ECMO was explored (2). The CESAR study demonstrated a clear survival benefit for patients transferred to a specialist centre, even though only 80% received ECMO. Another key driver of the increasing use of VV ECMO was the Influenza A (H1N1) or “swine ‘flu” pandemic. From 2009-2011 VV ECMO use was associated with remarkably high survival for patients with severe respiratory failure, particularly in Australia and the UK (3). Both Australia and the UK have a centralised model of care with VV ECMO being delivered in specialist centres. This presents substantial organisational and logistical challenges that have had to be overcome, mainly through the provision of mobile ECMO to allow safer patient transfer. However it should be remembered that outcomes in other countries were not so encouraging, with survival of approximately 40% rather than the 80% observed in Australia and the UK (4). It is difficult to know what the reason for this striking difference in mortality is. It may be that specialist centres with a greater volume of cases have a mortality benefit, certainly this is in keeping with the wider ARDS literature. It may also be due to case selection or something intrinsic to the manner in which ECMO is applied. Regardless of the root cause of the differences, controversies remain as to the exact risk:benefit relationship of ECMO for the management of patients with severe respiratory failure and studies aimed at exploring this relationship are currently recruiting.[/dropcap]
Against this background, how should we choose whether or not patients receive ECMO? The commonest clinical trigger is hypoxaemia and/or hypercapnoea that is refractory to conventional ventilation. Some advocate the use of tools such as the Murray, or Lung Injury Score, which provides a composite of chest xray appearances, the level of positive end expiratory pressure, level of hypoxaemia and dynamic pulmonary compliance. The aim of such an approach is to attempt to delineate which patients are sick “enough” for the potential benefits ECMO to outweigh the possible risks. Aside from the use of the Murray Score in the CESAR trial, there is little evidence to support a role for its use in predicting patients who will benefit and it remains controversial.
One approach to trying to select patients who may benefit from ECMO is to look at the risk factors associated with mortality following the commencement of ECMO. Recent collaborative work performed using data provided by ELSO has done just that (5). The RESP score has been created from retrospective, observational data submitted to ELSO for patients who were commenced on ECMO. As such this assists in understanding the risks associated with increased mortality after commencing ECMO. Approximately half of the key risk factors relate to factors that are intrinsic to the patient, such as age, pre-ECMO immunosuppression and sequential organ failure assessment (SOFA) score. Interestingly profound hypoxaemia is not associated with outcome. This is likely to be because of selection bias, ie if clinicians are using a certain level of hypoxaemia as the selection criteria (for example PaO2:FiO2 ratio of less than 10kPa or 75mmHg), then hypoxaemia ceases to be discriminatory. The other half of the risk factors relate to the pre-ECMO management of patients and are potentially modifiable. These include factors such as inadequate levels of PEEP, use of high peak inspiratory pressures and a longer duration of mechanical ventilation prior to the commencement of ECMO. These risk factors are similar to the findings in other retrospective observational studies including PRESERVE. PRESERVE also highlighted the mortality excess associated with not trying prone positioning prior to ECMO. In both of these studies longer duration, less protective ventilation was associated with increased mortality and although studies of this type cannot tell us why these elements have such an association, it seems reasonable to assume that this is because of the secondary injury caused by ventilator induced lung injury which we know is also associated with higher pressure, longer duration ventilation.
Although these retrospective analyses only examine the risk factors associated with mortality after ECMO has commenced, they do present useful data, which can be used to assist in decision-making at the commencement of ECMO. The most useful and consistent message from this data is that it is important to ventilate patients in a protective manner prior to the onset of ECMO. Ventilate patients gently, limit peak pressures, consider prone positioning if it is safe to do so and make the decision for ECMO early in the patient stay. This is the key take home message – if we cannot achieve suitable levels of oxygen and carbon dioxide in a lung protective manner, this is when we should move towards ECMO and do so early in the admission, rather than waiting until the patient needs to be “rescued”.
Reference:
- Paden ML, Conrad SA, Rycus PT, Thiagarajan RR, (2013) Extracorporeal Life Support Organization Registry Report 2012. ASAIO J 59: 202-210
- Peek GJ, Mugford M, Tiruvoipati R, Wilson A, Allen E, Thalanany MM, Hibbert CL, Truesdale A, Clemens F, Cooper N, Firmin RK, Elbourne D, (2009) Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet 374: 1351-1363
- Noah MA, Peek GJ, Finney SJ, Griffiths MJ, Harrison DA, Grieve R, Sadique MZ, Sekhon JS, McAuley DF, Firmin RK, Harvey C, Cordingley JJ, Price S, Vuylsteke A, Jenkins DP, Noble DW, Bloomfield R, Walsh TS, Perkins GD, Menon D, Taylor BL, Rowan KM, (2011) Referral to an extracorporeal membrane oxygenation center and mortality among patients with severe 2009 influenza A(H1N1). JAMA 306: 1659-1668
- Takeda S, Kotani T, Nakagawa S, Ichiba S, Aokage T, Ochiai R, Taenaka N, Kawamae K, Nishimura M, Ujike Y, Tajimi K (2012) Extracorporeal membrane oxygenation for 2009 influenza A(H1N1) severe respiratory failure in Japan. J Anesth. 26(5):650-7
- Schmidt M, Bailey M, Sheldrake J, Hodgson C, Aubron C, Rycus PT, Scheinkestel C, Cooper DJ, Brodie D, Pellegrino V, Combes A, Pilcher D. (2014) Predicting survival after extracorporeal membrane oxygenation for severe acute respiratory failure. The Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) score. Am J Respir Crit Care Med. 189(11):1374-82.
- Schmidt M, Zogheib E, Roze´ H, Repesse X, Lebreton G, Luyt CE, Trouillet JL, Brechot N, Nieszkowska A, Dupont H, Ouattara A, Leprince P, Chastre J, Combes A (2013) The PRESERVE mortality risk score and analysis of long-term outcomes after extracorporeal membrane oxygenation for severe acute respiratory distress syndrome Intensive Care Med (2013) 39:1704–1713