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Chandni Ravi, MD, Department of Emergency Medicine, Rutgers New Jersey Medical School, Newark, NJ
Ilya Ostrovsky, MD, Assistant Professor, Department of Emergency Medicine, Ultrasound Director, Rutgers New Jersey Medical School, Newark, NJ
Kimberly Boswell, MD, Assistant Professor of Emergency Medicine, University of Maryland School of Medicine, Baltimore
Cardiopulmonary bypass in the emergency department (ED)? You must be crazy, or blindingly arrogant. Well, maybe. But to contemplate heroic measures in the ED requires a bit of arrogance. As described in this issue of Emergency Medicine Reports, extracorporeal membrane oxygenation (ECMO) can be lifesaving in selected patients, albeit with a high rate of complications and some long-term effects. Only a few emergency physicians in select hospitals in urban areas possibly will be able to implement ECMO in the ED. For the rest of us in community hospitals, awareness of this therapy and an understanding of potential candidates is the purpose of this article.
— Joseph Stephan Stapczynski, MD, Editor
Extracorporeal life support (ECLS) comprises several modalities for temporary mechanical cardiopulmonary support, including extracorporeal carbon dioxide removal (ECCO2R), cardiopulmonary bypass (CPB), and extracorporeal membrane oxygenation (ECMO). ECMO provides cardiac and respiratory support in patients who have potentially reversible causes of cardiac or respiratory failure. While CPB uses a heart-lung machine to completely bypass cardiopulmonary circulation, ECMO functions by augmenting oxygenation, ventilation, and cardiac output.1 Deoxygenated blood is drawn from venous circulation; pumped through an external membrane oxygenator, which eliminates carbon dioxide (CO2) and replenishes oxygen; and returned to venous or arterial circulation.
Because of the growth in ECMO research and training of intensivists, the use of ECMO in the United States increased 433% from 2006 to 2011.2 The number of U.S. hospitals offering ECMO has grown from 108 in 2008 to 264 today.3 About 14,000 adult patients received ECMO between 1990 and 2014, with a rate of survival to discharge of 57% for those in respiratory failure and 41% for those in cardiac failure.4
Initiation of ECMO by the emergency department (ED) is a relatively new development, but with significant potential for growth. This is particularly seen at centers already performing ECMO in the intensive care unit (ICU).5 Familiarity with the indications and mechanisms of ECMO is important for emergency providers on the frontlines of managing critically ill patients who require aggressive resuscitation.
The first successful use of extracorporeal circulation in humans with a heart-lung machine was by Gibbon in 1953 for the repair of an atrial septal defect.6 In 1971, ECMO was used successfully for 75 hours in a 24-year-old patient with respiratory failure in the setting of traumatic transection of the thoracic aorta, who eventually recovered.7 Robert Bartlett became known as the “Father of ECMO” for his successful use of ECMO in a neonatal patient with meconium aspiration in 1975.8 National registry data collected between 1980 and 1987 demonstrated a survival rate of 81% in newborn patients with severe respiratory failure supported by ECMO.9 This inspired a series of randomized, controlled trials that showed encouraging results of ECMO use in neonates.10-12
The use of ECMO in the adult population was met with mixed results. Initial reports were discouraging, with randomized, controlled trials failing to show any statistical difference in survival between the conventional intensive care and ECMO groups.13,14 The conventional ventilatory support vs. extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR) trial was the first study of ECMO in adult patients to demonstrate an increase in survival. Patients with acute respiratory distress syndrome (ARDS) did better when managed at an ECMO center (but not necessarily placed on ECMO) compared to conventional management.15 ECMO also was used widely to treat adult patients during the H1N1 influenza pandemic of 2009.16
The ECMO to rescue lung injury in severe ARDS (EOLIA) study was a large, multicenter, randomized, controlled trial which demonstrated that ECMO was safe and appropriate to use with no increased mortality compared to conventional therapy. Although EOLIA was meant to study the effects of early ECMO initiation, it was terminated because of a high crossover rate. However, it highlighted the role of ECMO as a rescue modality that may improve mortality in patients who fail conventional and other rescue therapies for ARDS.17
In ECMO, deoxygenated blood is drained from a vein, pumped through a membrane oxygenator that removes CO2 and replenishes oxygen, and then is reintroduced into the body via an artery or a vein.
The main purpose of ECMO is to facilitate successful gas exchange of both carbon dioxide and oxygen. The membrane oxygenator functions similar to the native lung in many ways — removing dissolved carbon dioxide from the blood and adding oxygen to the hemoglobin within red cells. The movement of these gases across the membrane is dependent on different factors. In general, CO2 removal is more efficient than oxygen addition, leading to a potential imbalance in gas exchange. Oxygen exchange across the membrane oxygenator is dependent on the thickness of the blood film, membrane material, fraction of inspired oxygen (FiO2), and hemoglobin concentration. Carbon dioxide exchange is determined by the total surface area, blood flow, and “sweep gas” flow rate. Occasionally, CO2 may need to be added to the sweep gas to prevent respiratory alkalosis due to the excessive removal of CO2.18
Unlike traditional CPB in which the heart is stopped, ECMO does not require total anticoagulation with heparin to prevent thrombus formation because of the higher blood flow rates (4 L/min vs. 2 L/min with CPB). An ECMO circuit also lasts for weeks compared to hours with CPB.19
Venovenous (VV) ECMO is used in cases of isolated respiratory failure with preserved cardiac function. It takes deoxygenated blood from the venous circulation and returns oxygenated blood to the veins. The ECMO circuit exists in series with the lungs.20
In contrast, venoarterial (VA) ECMO provides partial or complete respiratory and circulatory support. It takes deoxygenated blood from the venous system and returns oxygenated blood to the arterial system. The circuit functions in parallel to the native heart and lungs.20 A dialysis membrane may be added to either circuit to provide continuous renal replacement therapy.21,22
ECMO in the ED is used primarily either as a temporizing measure for refractory shock (ECLS) or in the setting of cardiac arrest (extracorporeal cardiopulmonary resuscitation or ECPR).4,23
The basic ECMO circuit is a closed system consisting of a venous drainage cannula, pump, membrane oxygenator, heat exchanger, blender, central console, in-line monitors, and return cannula.20,23 (See Figure 1.)
The pump is an essential component of the ECMO machine. It functions to circulate blood through the ECMO circuit as well as back to the patient while augmenting venous outflow. The pump must provide adequate flow to the patient within a safe range of pressures. Low output pressure can result in hemolysis, while a high output pressure can result in rupture of the circuit.24 Two types of pumps are used in ECMO devices: a roller pump and a centrifugal pump.
Roller pumps function by progressively compressing segments of circuit tubing and pushing blood through a curved raceway. This continuous peristalsis of the tubing system generates negative pressure that pulls venous blood from the patient, as well as positive pressure that pushes oxygenated blood back into the patient. The advantage of roller pumps is that they provide continuous flow in the circuit independent of preload. Their main disadvantage is that they cause hemolysis.18,20,24
Centrifugal pumps are smaller and consist of a pump head that contains a magnetically driven impeller spinning at a high rate. This generates a pressure differential that results in flow of blood across the pump. Centrifugal pumps are associated with a smaller degree of hemolysis.25 However, they also are associated with certain disadvantages, such as stagnation and heating in the pump head, thrombus formation in the outlet line at low flow rates, and inability to maintain a set flow rate.
Newer generations of centrifugal pumps have been designed to overcome most of these disadvantages and largely have replaced roller pumps. For instance, centrifugal pumps with magnetic levitations were found to be associated with improved outcomes.26 These modifications to centrifugal pumps have been key in making extended support via ECMO feasible.
The gas exchange membrane in an ECMO circuit performs the function of oxygen addition and CO2 removal. The efficiency or rated flow of an oxygenator is measured as the amount of desaturated blood that can be nearly fully saturated per minute. Membranes have been developed using various materials, including silicone rubber, polypropylene, polymethylpentene (PMP), polyvinyl chloride, polyurethane, and stainless steel.24
The two most commonly used membranes are the silicone membrane oxygenator and the hollow fiber oxygenator (HFO). The Kolobow silicone rubber membrane lung has been used in ECMO machines for decades. The silicone membrane was found to be very efficient at gas exchange; however, it had a few drawbacks. The size of the membrane requires adjustment based on the size of the patient. Therefore, hospitals needed to obtain different ECMO machines for the pediatric and adult populations. Resistance to flow was found to be high, which made the silicone rubber membrane less suitable for use with centrifugal pumps. Transportation also was challenging because of the bulky design and the longer duration required for priming.27
The newer class of hollow fiber PMP oxygenators have addressed most of these issues. These hollow fibers are capillary tubes that contain gas inside and blood on the surface. This allows gas exchange via a countercurrent mechanism. HFO membranes are more durable, extremely efficient at gas exchange, demonstrate minimal plasma leakage, and have a relatively low resistance to blood flow. Additionally, they have a lower incidence of thrombus formation, are easier to prime, are more compact, and are well suited for use with centrifugal blood pumps.28
Loss of heat occurs during ECMO because of the exposure of the patient’s blood to a large extracorporeal surface area, particularly in children. For this reason, all ECMO circuits require a heat exchanger to maintain temperatures between 37°C and 40°C. Heat exchangers typically use the flow of heated water countercurrent to blood flow. Excessive heat must be prevented because it will lead to hemolysis and bubble formation. Newer generation membrane oxygenators contain an integrated heat exchange device, which reduces the number of components and simplifies the ECMO circuit design.18
ECMO circuits contain in-line monitors that measure blood flow, chemistry, pressure, pH, oxyhemoglobin concentration, and partial pressure of CO2 (pCO2). These monitors are placed on both the venous and arterial ends of the circuit. They assist in the detection of problems, such as bubbles in the system, oxygenator failure, increased pressures, and disconnections. The oxyhemoglobin saturation on the venous access limb of the circuit in VA ECMO is especially useful in assessing the adequacy of oxygen delivery.24
Three options are available for VV ECMO cannula placement (see Figure 2):
Two basic options are available for VA ECMO cannula placement.
Femoral arterial cannulation is associated with many risks, such as lower limb ischemia, pulmonary edema, and watershed phenomenon (the mixing of de-oxygenated blood from the patient’s left ventricle with oxygenated blood from the ECMO unit) resulting in coronary and cerebral hypoxia. These risks are only partially present in subclavian arterial cannulation.32 Performing cannulation under resuscitation conditions may be challenging, and the use of transesophageal echocardiography (TEE) can be very useful in these cases.
Bleeding and thrombotic complications are the major complications seen with ECMO. According to the Extracorporeal Life Support Organization (ELSO) Registry Report, the rate of circuit replacement due to thrombotic complications is about 20%.33 As blood is exposed to large non-endothelial surfaces in the ECMO circuit, inflammatory and coagulation cascades are stimulated. The underlying disease process also can give rise to both a bleeding tendency and a hypercoagulable state, depending on its effect on the hemostatic system.
Therefore, patients placed on ECMO need to be anticoagulated. The most common anticoagulant used is unfractionated heparin, which is administered as a continuous infusion.34 In ECLS, heparin typically is administered as a 100 IU/kg bolus once vascular access has been established. The heparin infusion is titrated to maintain an activated clotting time of 160-220 or an activated partial thromboplastin time of 45-55 seconds.35 Low molecular weight heparin also can be given subcutaneously in adult patients during ECMO, but it is used less commonly. Direct thrombin inhibitors (e.g., bivalirudin) and factor Xa inhibitors (e.g., rivaroxaban, argatroban) have been described but with few large-scale studies.36 Anticoagulation is withheld in patients who are at risk of bleeding.
The advent of newer ECMO equipment and supportive evidence from prior studies has paved the way for its use as salvage therapy in the ED. Two terms associated with its use in the ED are ECLS and extracorporeal cardiopulmonary resuscitation (ECPR). ECLS is described as ECMO used to temporize a critically ill patient, while ECPR refers to the use of VA ECMO in cardiac arrest.
ECPR has been shown to play a role in ongoing refractory cardiac arrest,18 severe accidental hypothermia,37 near-drowning,38 pulmonary embolism,39 septic shock,40 and even severe electrolyte abnormalities.41 ECMO in the ED buys time for diagnostic workup or serves as a bridge to therapeutic interventions, such as percutaneous coronary intervention, rewarming, or damage control surgery in trauma.41
The decision to initiate ECMO in a patient in the ED is complex and varies based on institutional policies, patient factors, and the underlying disease process. In general, younger and healthier patients with an acute reversible insult leading to rapid cardiopulmonary collapse with a definitive management plan in place tend to have better outcomes. The following are some indications for ED ECMO:
VA ECMO for Cardiac Arrest (ECPR). For the emergency provider, application of VA ECMO in ECPR has been the most exciting development. ECPR may be useful in reducing the time from arrest to restoration of cerebral perfusion.1 Ultrasound-guided femoral arterial and venous catheters are inserted with ongoing cardiopulmonary resuscitation (CPR). Once connected to the extracorporeal circuit, complete cardiopulmonary bypass is confirmed, and CPR is discontinued.
Currently there is increasing evidence that patients in out-of-hospital cardiac arrest started on ECPR have better outcomes when compared to traditional CPR. Successful initiation of ECMO by ED physicians has been demonstrated with improved neurologically intact survival.42,43 Witnessed arrest or ED arrest, ventricular fibrillation or ventricular tachycardia as the initial rhythm, age range 18 to 70 years, presumed cardiac cause, and minimal interruption in chest compressions have been associated with positive outcomes and are instances in which ECPR should be considered. The outcomes of ECPR with in-hospital cardiac arrest have been relatively more promising, likely because of the shorter time to initiation of bypass.
The main limitation of studies on ECPR is that most of the data are retrospective and from single centers; therefore, they are prone to bias and confounders. Neurological outcomes following ECPR also may appear to be better in the ECMO group because these patients also were more likely to receive therapeutic hypothermia and percutaneous coronary intervention, both of which are interventions known to improve outcomes following cardiac arrest.
VA ECMO for Refractory Shock (ECLS). ECLS has shown promising results when used in septic shock or cardiogenic shock related to acute myocardial infarction, massive pulmonary embolism, or myocarditis.1 The inability to wean a patient from CPB following cardiac surgery and primary graft failure following cardiac transplantation are other common indications for ECMO.18 These are conditions with potential for recovery with time or definitive treatment (percutaneous coronary intervention, device implantation, or cardiac transplant). However, ECMO increases left ventricular afterload and oxygen demand due to retrograde aortic flow and potentially can worsen left heart failure. To combat this, a left ventricular drain often is added to the circuit.
VV ECMO for Severe Acute Respiratory Failure. Persistent hypoxemia despite maximum ventilator therapy in acute respiratory failure is an indication for VV ECMO. Since it allows the lungs to rest, VV ECMO prevents the deleterious effects of positive pressure injury, ventilator complications, and oxidative stress.44 Most commonly, it has been used in patients with ARDS or as a bridge in those awaiting lung transplantation. The EOLIA trial demonstrated that emergency ECMO improves outcomes by “buying time” in extremely hypoxemic patients.45 The CESAR trial found that patients who received ECMO in ARDS had a higher survival rate without severe disability at six months.15 Several scoring systems, such as the Murray score, age-adjusted oxygenation index score, and acute physiology of stroke score, have been used to determine appropriate candidacy. According to the ELSO Registry Report, ECLS should be considered when the risk of mortality is 50% or greater and is indicated when the risk of mortality is 80% or greater. Unfortunately, employing these scoring systems in the emergent setting might be challenging.
Conditions that are associated with a particularly poor outcome despite ECMO therapy typically are contraindications to its use. These include advanced age (> 65 years), chronic conditions such as end-stage heart failure or chronic obstructive pulmonary disease, irreversible multi-organ failure, untreatable malignancy, or conditions precluding the use of anticoagulation such as intracranial hemorrhage.
Patients with aortic dissections or aortic regurgitation are not ECMO candidates because there is a risk of propagating the dissection or over-distending the left ventricle leading to worsening congestive heart failure. For patients with ARDS, prolonged mechanical ventilation with high airway pressures is a relative contraindication.
Contraindications to ECPR include prolonged CPR without adequate tissue perfusion, unrecoverable heart disease, and non-transplant or left ventricular assist device candidates. Patients in these cases are relegated to a “bridge-to-nowhere” in that they cannot survive without ECMO and there is no hope for recovery.
Certain situations that previously were contraindications to ECMO are being reconsidered. Pregnancy and postpartum patients were considered high risk for bleeding and, therefore, not suitable candidates. There has been a change in this opinion recently because it has been demonstrated that they are at no increased risk for catastrophic bleeding when compared to non-
Traditionally, multi-trauma and severe traumatic brain injury were thought to be absolute contraindications. The advent of heparin-bonded circuits has obviated the need for systemic anticoagulation, therefore allowing ECMO use in select patients.47 Morbid obesity also once was considered a contraindication because of complex cannulation, but a lack of association between body weight and mortality has been demonstrated, likely because of the development of newer cannulas.48
The key to successful outcomes with the use of ECMO in the ED is the selection of patients who are appropriate candidates. The provider should consider the underlying diagnosis, patient-specific risk factors, anticipated duration of support, viable exit strategy, indications, and contraindications. While scores cannot substitute for clinical gestalt, and candidacy ultimately is determined by the provider, several scores have been described to provide objective assistance in this process. The use of scoring systems also is beneficial when developing a protocol at the departmental or hospital level.
The PRESERVE49 and RESP50 scores have been investigated for identifying suitable patients for use of
VV ECMO in ARDS in the ICU setting. Therefore, they may not be generalizable to the ED population, who predominantly require VA ECMO for ECPR. Furthermore, external validation of PRESERVE and RESP scores demonstrated poor performance in patients with severe ARDS receiving ECLS.
The Survival After Veno-arterial ECMO (SAVE) score is designed to assist with the prediction of survival for adult patients undergoing ECMO for refractory cardiogenic shock. Scoring parameters include diagnosis, age, weight, pre-ECMO diastolic blood pressure and pulse pressure, duration of intubation pre-ECMO, peak inspiratory pressures, and the presence of multi-system dysfunction.51 The modified SAVE score, which is equivalent to the combined lactate value and SAVE score, showed improved outcome predictions for patients who underwent urgent VA ECLS in the ED.52 The ENCOURAGE score may be useful in predicting mortality in patients with an acute myocardial infarction in cardiogenic shock on VA ECLS.53
Another scoring system that may be particularly useful in the ED setting is the pre-ECMO Simplified Acute Physiology Score (SAPS) II score. SAPS II has been studied in patients who require initiation of ECMO in the ED for acute circulatory and/or respiratory failure. Pre-ECMO SAPS II scores of ≤ 80 were associated with higher mortality at 28 and 60 days when compared to those with scores of > 80.54
Providers should bear in mind that while they are interesting and potentially useful in the future, many of these scores are not used in routine practice. The external validation that has taken place is based on studies with small numbers.
ECMO is associated with a high complication rate during both cannulation and ongoing management.55 (See Table 1.) At least one significant complication has been noted to occur in more than half of the patients on ECMO.56 Complications are commonly due to cannulation, bleeding, or infection.
Since ECMO patients need aggressive systemic anticoagulation because of the risk for arterial thrombosis, they are prone to hemorrhage at the cannulation site as well as other sites. Intracerebral hemorrhage (ICH) is the most devastating hemorrhagic complication seen in these patients and can lead to significant disability. Studies with higher rates of computerized tomography (CT) have described up to a 20% incidence of ICH. Because monitoring the patient’s neurological status accurately while the patient is sedated on ECMO is challenging, early head CT on admission has been proposed as a strategy for the timely detection of ICH.57 In patients who are at a higher risk for bleeding or who may have developed bleeding already, using heparin-bonded circuits without systemic anticoagulation or targeting lower levels of anticoagulation are recommended strategies.35
Complications related to cannulation include thrombus formation, limb ischemia, dissection or perforation of a vessel, cannula migration, pseudoaneurysm formation, and accidental decannulation leading to hemorrhage. Since ECMO requires a high rate of blood flow, large diameter cannulas are used. These can mechanically occlude flow to the distal artery. In a study of femoral arterial cannulation in
VA ECMO, peripheral vascular complications were reported in about 20% of patients, the majority (89%) of whom required surgery in the form of angioplasty, bypass, or amputation.58 The use of a distal perfusion catheter may help avoid ischemia. Risks of incorrect placement of cannulas is reduced with ultrasound-guided needle and guidewire insertion and TEE or fluoroscopy to confirm placement.
Infections are common in patients receiving ECMO. These may be catheter-related bloodstream infections, cannulation site infections, or worsening sepsis in patients with ARDS. Acute tubular necrosis leading to renal failure and the need for hemodialysis also is common and is reported in about 13% of patients on ECMO.4
For successful implementation of an ED ECMO program, a multi-disciplinary institutional commitment is necessary. Predetermined inclusion and exclusion criteria, as well as the threshold for discontinuing ECMO when a patient fails to improve, must be defined. Coordination is essential between emergency medical services (EMS), emergency medicine physicians, nursing staff, the blood bank, the cardiac catheterization lab, vascular surgeons, neurocritical care, and the intensive care unit. Prehospital EMS providers must be able to identify and transport potential ECMO candidates quickly. Emergency physicians must be competent in ECMO cannulation. Cardiology must be able and willing to provide definitive care for suitable patients in the form of left ventricular assist device or transplant. Capabilities for several days of bridging ECMO therapy and transplant must be available 24/7 from an infrastructural as well as nursing standpoint. Finally, a formal neuroprognostication scheme with continuous goals of care discussions by palliative care, case management, and social work is paramount.
In general, higher annual hospital ECMO volumes (> 30/year) are associated with improved mortality.59 Institutional capabilities in terms of the number of simultaneous ECMO patients also must be considered. Regional networks and communication with ECMO referral centers may be needed at many hospitals with resource limitations.
Institution-specific practices and guidelines likely exist, and abiding by those is crucial. Few emergency medicine physicians are able to cannulate for ECMO currently, and collaboration with surgical colleagues (cardiac, vascular, trauma, etc.) is necessary in most institutions to place a patient on ECMO.
Because of the increasing use of ECMO, novel ethical dilemmas have emerged. For instance, should discussions with patients regarding their desires for resuscitation in the event of cardiac or respiratory arrest include a discussion about ECMO? Who decides when to stop the circuit and under what circumstances?60 Other complexities include the pre-existing code status, degree of input from the surrogate decision maker, ethical obligation of the physician, costs involved, and finally long-term quality of life. Some studies report long-term neurocognitive abnormalities in more than 50% of ECMO survivors.1 These factors must be weighed carefully when considering the use of extracorporeal measures in a patient.
Financial Disclosure: To reveal any potential bias in this publication, and in accordance with Accreditation Council for Continuing Medical Education guidelines, we disclose that Dr. Farel (CME question reviewer), Dr. Schneider (editor), Dr. Stapczynski (editor), Ms. Light (nurse planner), Dr. Ravi (author), Dr. Ostrovsky (author), Dr. Boswell (peer reviewer), Ms. Mark (executive editor), Ms. Roberts (Associate Editor), and Ms. Coplin (editorial group manager) report no financial relationships with companies related to the field of study covered by this CME activity.