Controversies in ECMO

Controversies in ECMO Parag Gharde, Sandeep Chauhan   Controversy is defined as â€Å"Public debate about a matter which arouses conflicting opinion.† (Oxford English Dictionary) ECMO or ECLS- To start with there is controversy regarding the name itself. There are two abbreviations that we commonly come across in literature ECMO- extracorporeal membrane oxygenation ECLS- extracorporeal life support This support system is used in different clinical settings where the reversible organ dysfunction has affected the lung, the heart or both. When lung rest is needed the veno-venous ECMO system is used and for providing cardiac rest veno-arterial system is used. The term extracorporeal membrane oxygenation (ECMO) came into being when Dr. J. Donald Hill first used it successfully in a road traffic accident victim who developed acute respiratory distress syndrome after multiple blood transfusions. Since lung rest and oxygenation was the main therapeutic requirement, the life support system was named ECMO. But since this support system is now often being used in patients requiring cardiac support where the native lung is functioning well, the term ECMO is not suitable and hence the term ECLS is now in common use in clinical practice. The ECMO society itself is named as â€Å"Extracorporeal Life Support Organization-ELSO†. Therefore the reader should not get confused when they come across the terms- ECMO and ECLS, both meaning the same but to the author the term ECLS appears to be more appropriate as it can be used interchangeably whether support is required for the lung, the heart or for both. The use of the term ECMO is justified only if it is being used to support pulmonary function with the aim of giving rest to the lung. Does ELSO work? After the first successful use of ECLS in an adult, which was reported by Hill etal in 1972 (NEJM 1972; 26: 629-34.), the National Institute of Health sponsored a multicenter randomized study by Zapol etal in 1974, which showed 90% mortality in both ECLS and conventional care group. The anticipated enrolment for the study was 300 patients but the study was stopped after just 92 patients, as the death rates were similar in both the groups. This prospective randomized trial deflated the initial euphoria that was generated by the report of Hill etal. Was this supposed to be a certain miscarriage of a support system devised to deal with patients who are non-responders to conventional medical practice, even before seeing the light of the day? This study was conducted in adults with hypoxic respiratory failure and published in 1979. (JAMA 1979; 242:2193-2196). This first prospective multicenter randomized clinical trial demands a close scrutiny. During the study period a nation wide epidem ic of influenza pneumonia broke out, which might have affected the results. Though the protocol included lung rest but the inflation pressures were high compared to the present recommendation, which may have caused lung injury. VA ECLS was used rather than VV ECLS, which may be responsible for high incidence of pulmonary micro-thrombosis due to decreased pulmonary blood flow. ECMO was instituted after a mean duration of 9 days of mechanical ventilation, which in the present era has been reduced to 7 days. Morrios etal (Am J Respir Crit Care Med-1994;149(3);88) randomized 40 patients with sever ARDS to either pressure controlled inverse ratio ventilation or extracorporeal carbon dioxide removal. Survival at 30 days was not significantly different (42% in mechanical ventilation group and 33% in ECLS group). After these two randomized trials, showing failure of ECLS in the adult setup had put ECLS into disrepute despite many anecdotal mini case series and isolated case reports showing the benefits were published. The much awaited CESAR trial (Efficacy and economic assessment of Conventional ventilator support versus Extracorporeal membrane oxygenation for Severe Adult Respiratory failure), a multicenter randomized controlled trial by Peek etal was published in Lancet 2009. (Lancet. 2009:374:1351-1363.) 180 patients were randomized and 90 patients were managed at the participating tertiary care centers while 90 were referred to Glenfield hospital. Five patients in the ECMO referral group died during transportation and thus the ECMO group consisted of 68 patients of which 43 survived to 6 months (63%). This study showed that survival apart from appropriate time of institution of ECLS also significantly depends on the expertise of the ECLS conducting center. There is no consensus on the optimal time for institution of ECLS. Waiting too long will result in danger of end organ dysfunction and poor outcome, while too early institution without optimizing medical therapy will expose the patient to the inherent risk of ECLS. The success in ECLS has been with neonatal acute hypoxemic respiratory failure with survival to discharge rates reaching 80%. The success story started with Bartlett etal reporting the first successful use of ECLS in a neonate in 1976. Extracorporeal carbon-dioxide removal (ECCO2R) A membrane lung is used to remove carbon dioxide in conditions of acute exacerbation of chronic obstructive pulmonary disease. A low flow is required and is perfused by femoral artery-venous shunt. Low blood flow is not adequate for performing oxygenation. Morris etal conducted a randomized control trial using this device to eliminate CO2. This trial showed no difference between ECCO2R and the conventional treatment and the study was stopped after enrolling 40 patients only. The ECCO2R arm used low flow in a group of patients with severe lung disease, which warranted higher ECMO flows. Before starting the trial, the trial team had limited experience on sheep and one patient.(Am J Respir Crit Care Med,1994:149; 295-305.) Effective CO2 clearance is achieved with blood flow as little as 10-15ml/kg/min, while oxygenation requires at least 50-60 ml/kg/min of blood flow. Nova lung (Germany) produces a membrane lung, which can be perfused using femoral arterio-venous shunt, enough blood flow for CO2 removal. ECLS Vs Ventricular assist device (VAD) Patients with failing heart and waiting for heart transplant need a bridge to transplant till the time a donor heart is available. If these patients develop acute exacerbation of cardiac dysfunction, which route should be chosen- ECLS or VAD? There are no guidelines regarding this situation. The main advantage ECLS holds over VAD is in patients with bi-ventricular dysfunction, which will require a bi-VAD. VA-ECLS on other hand can support both the ventricles along with respiratory failure and refractory pulmonary artery hypertension. The only limitation is the duration of support, which at most is 4-6 weeks. Cardiac ECLS The controversy is regarding patient selection. Though ECLS guideline clearly defines presence of a reversible condition before institution of ECLS, there are situation when it’s difficult to predict if the condition is reversible and most often the decision is surgeon dependent who may have a biased opinion regarding the true indication for instituting ECLS. This usually results in financial burden, resource and manpower wastage, bad outcome, lowers the moral of the team and loss of faith in the support system (ECLS). When is the ideal time to institute ECLS in cardiac surgical patient? Is it ideal to institute ECLS directly from CPB or to initiate it later in the intensive care unit after giving a trial? It has been shown that survival benefits were more in patients who went on ECLS directly from CPB thus avoiding the ill effects of prolonged low cardiac output state or subsequent to cardiopulmonary resuscitation (CPR) in the intensive care unit. Antegarde or retrograde ECLS Retrograde ECLS via femoral artery cannulation especially for cardiac support in a failing left ventricle is not a good option. The failing heart with this form of support has to compete with retrograde ECLS flow from the femoral artery cannula. This causes increase in LV wall stress and may even result in mitral regurgitation both of which increase left atrial (LA) pressure, thus affecting gas exchange due to pulmonary congestion. This may impair oxygenation and delivery of inadequately oxygenated blood to coronary and cerebral artery circulation will further worsen cardiac function and delay recovery. Therefore central ECLS with aortic cannulation has some advantage over peripheral ECLS, especially in case of cardiac support. But central ECLS takes time to initiate and is ideal in post cardiac surgery setup. In an emergency situation peripheral ECLS is easy to institute. Serial echocardiography needs to be done to rule out LA distention. If LA distention is present then placement o f an LA vent is necessary via percutaneous atrial septostomy. Some prefer retrograde ECLS because of the fact that 10-15% patients suffer from stroke when carotid artery was used for arterial cannulation in profound hypotension or arrest. Neck vessels are used in children up to 5-6 years and femoral access in older patients. Limb ischemia is common with femoral artery cannulation and may require additional distal limb perfusion. Is axillary artery cannulation a better option? This can provide sufficiently oxygenated blood to the upper body, which is lacking with retrograde flow. The issue of limb ischemia is also addressed. The decreased pulmonary blood flow in full support VA ECLS may increase the risk of thrombus formation, in the pulmonary circulation, because of lower levels of anticoagulation. Does the type of oxygenator influence outcome? In vitro studies reported problems with Biomedicus (Medtronic, USA) pump heads. Thiara etal demonstrated improved circuit durability and reduced hemolysis when changing from Biomedicus (Minimax oxygenator) circuit to a Rotaflow (Lilliput 2 oxygenator), but failed to demonstrate survival improvement. (Perfusion, 2007;22:323-26). The earlier oxygenators were spiral wound silicone membrane oxygenator (Affinity, Avecor Cardiovascular Inc, USA), and the recent multiple hollow fibers