ECMO for Adult Respiratory Failure: Current Use and Evolving Applications : ASAIO Journal

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Review Article

ECMO for Adult Respiratory Failure

Current Use and Evolving Applications

Agerstrand, Cara L.*; Bacchetta, Matthew D.; Brodie, Daniel*

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ASAIO Journal 60(3):p 255-262, May/June 2014. | DOI: 10.1097/MAT.0000000000000062
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Extracorporeal membrane oxygenation (ECMO) is increasingly being used to support adults with severe forms of respiratory failure. Fueling the explosive growth is a combination of technological improvements and accumulating, although controversial, evidence. Current use of ECMO extends beyond its most familiar role in the support of patients with severe acute respiratory distress syndrome (ARDS) to treat patients with various forms of severe hypoxemic or hypercapnic respiratory failure, ranging from bridging patients to lung transplantation to managing pulmonary hypertensive crises.

The role of ECMO used primarily for extracorporeal carbon dioxide removal (ECCO2R) in the support of patients with hypercapnic respiratory failure and less severe forms of ARDS is also evolving. Select patients with respiratory failure may be liberated from invasive mechanical ventilation altogether and some may undergo extensive physical therapy while receiving extracorporeal support. Current research may yield a true artificial lung with the potential to change the paradigm of treatment for adults with chronic respiratory failure.

The use of extracorporeal membrane oxygenation (ECMO) for adult respiratory failure has markedly increased in recent years.1 Advances in device technology, increased use during the 2009 influenza A (H1N1) pandemic, and the results of a randomized controlled trial that suggested improved outcomes in the group considered for ECMO propelled the world into the modern era of extracorporeal support for adult respiratory failure.1–3 Despite limited high-quality evidence supporting its use, ECMO has expanded beyond its original application in the acute respiratory distress syndrome (ARDS) to include bridging patients to lung transplantation, managing pulmonary hypertensive crises, and treating patients with other forms of refractory hypoxemic or hypercarbic respiratory failure.4–6

Principles and Circuitry

Extracorporeal membrane oxygenation works by removing blood from a large central vein, typically from the femoral or internal jugular vein, and pumping it across a gas-exchange device known as an oxygenator (Figure 1). In venovenous ECMO, blood is returned to a central vein, whereas in venoarterial ECMO, blood is returned to an artery, most commonly the femoral artery. Therefore, venovenous ECMO provides respiratory support, whereas venoarterial ECMO provides both respiratory and hemodynamic support. Arteriovenous ECMO, comprised of a pumpless circuit driven by the patient’s femoral arterial pressure, generates low blood flow rates and is primarily used for carbon dioxide (CO2) removal.7

Figure 1:
Two-site approach to venovenous extracorporeal membrane oxygenation cannulation. The venous drainage cannula is typically placed in the femoral vein and extends to in the inferior vena cava; the venous return cannula is typically placed in the internal jugular vein and extends to the right atrium. Venous blood is drawn from the femoral vein into the pump and propelled into the oxygenator before being returned into the internal jugular vein. Reprinted with permission of

The oxygenator is divided into two chambers, separated by a semipermeable membrane, across which oxygen and CO2 are exchanged by diffusion. Modern oxygenators are comprised hollow fibers made of polymethylpentene which allow diffusion of gas, but not liquid. Driven by a centrifugal pump, blood flows along one side of the membrane while sweep gas flows along the other side. The composition of the sweep gas is oxygen and ambient air, in proportions controlled by a blender. Carbon dioxide is more soluble than oxygen and diffuses readily across the membrane, so CO2 clearance is primarily determined by the gradient across the oxygenator membrane. Sweep gas flow removes CO2 from the gas chamber, thereby maintaining the CO2 gradient and allowing for continued diffusion, so that higher sweep gas flow rates effectively provide more ventilation.8

Oxygenation is primarily determined by the blood flow rate across the oxygenator membrane.8 As the blood flow rate is largely limited by the size of the venous drainage and, to a lesser extent, the return cannulae, larger cannula sizes permit greater blood flow rates and allow for a greater percentage of a patient’s cardiac output to be oxygenated by the device. Arterial oxygen delivery varies according to changes in the cardiac output, which is a reflection of a patient’s physiologic demand. At a fixed device blood flow rate, the proportion of total oxygen delivered to the patient by ECMO will decrease as the patient’s cardiac output increases. In the normal patient with healthy lungs, this phenomenon is immaterial. However, this may be significant in a patient with pulmonary disease, as fixed oxygen delivery from the ECMO circuit with increased physiologic demand will be reflected as a decreased partial pressure of arterial oxygen (PaO2). In addition, recirculation, which occurs when reinfused, oxygenated circuit blood is drawn directly back into the venous drainage cannula and bypasses the patient’s native circulation, does not contribute to systemic oxygenation and will negatively impact systemic oxygen saturation.

Cannulation in venovenous ECMO can be two site or single site. In two-site cannulation, blood is typically removed from a femoral vein and returned to the internal jugular vein (Figure 1). In single-site cannulation, a dual-lumen cannula is positioned in the right or left internal jugular vein (or less commonly in the subclavian vein), with its distal end extending into the inferior vena cava (Figure 2). Venous blood is removed from two drainage ports positioned in the superior and inferior vena cavae, whereas oxygenated blood is returned through the other lumen of the same cannula with its outlet port positioned within the right atrium and the reinfusion jet directed toward the tricuspid valve. The advantages of a dual-lumen cannula are single-site cannulation, minimal recirculation, and improved patient mobility.9–12 Seldinger technique is used in both approaches; however placement of a dual-lumen cannula typically requires fluoroscopy, echocardiography, or both.13 Major risks of ECMO include hemorrhage, hemolysis, infection, and circuit- or cannula-related complications such as clotting, neurovascular damage, or limb ischemia.14 The rate of these and other complications is markedly lower in the modern era of ECMO.15

Figure 2:
Single-site approach to venovenous extracorporeal membrane oxygenation (ECMO) cannulation. A dual-lumen cannula is typically positioned in the internal jugular vein and terminates in the inferior vena cava. Venous blood from the drainage lumen is drawn into the ECMO circuit from ports positioned in the superior and inferior vena cavae. Blood oxygenated by the ECMO circuit is returned to the second lumen of the same cannula, through a port in the right atrium, with blood flow directed across the tricuspid valve. Reprinted with permission of


Severe ARDS is the most commonly accepted indication for ECMO in adult respiratory failure.1 Although ECMO was first successfully used in an adult with traumatic ARDS in 1971, its use during the ensuing decades was limited because of high mortality and complication rates.16–18 Two randomized controlled trials comparing ECMO with mechanical ventilation to mechanical ventilation alone, performed with what is now outdated technology, showed no survival benefit in the group receiving ECMO.17,18

However, with the advent of modern extracorporeal technology and critical care practices, a group of intensive care units in Australian and New Zealand reported a 73% survival rate in patients with severe ARDS treated with ECMO during the influenza A (H1N1) pandemic.19,20 Several European centers also reported high survival when using ECMO for H1N1-related ARDS.21,22 The efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR) trial published in 2009 randomized 180 adult patients with severe but potentially reversible respiratory failure to conventional management versus referral to an ECMO center for consideration of ECMO.23 The trial showed a 16% absolute reduction in the primary end-point of death or severe disability in the ECMO-referred group. Although impressive in design and execution, the lack of a standardized ventilator management protocol in the control group, among other criticisms, limits the strength of the authors’ conclusions.4

Because definitive evidence for its use in ARDS is lacking, ECMO is still considered to be a rescue therapy for this indication.24 An ongoing, international, randomized, controlled trial, ECMO to Rescue Lung Injury in Severe ARDS ( [NCT01470703]), seeks to address this by randomizing patients to standard-of-care mechanical ventilation or ECMO, thereby addressing some limitations of the CESAR trial.4

There are no universally agreed-upon criteria for when to initiate ECMO for severe ARDS, but reasonable indications include severe hypoxemia with PaO2 to a fraction of inspired oxygen ratio (FiO2) of less than 80 mm Hg, uncompensated respiratory acidosis with a pH less than 7.15, or potentially harmful end-inspiratory plateau airway pressures greater than 35 cm H2O despite optimized sedation and ventilator management.4 There are no absolute contraindications to ECMO, although consideration should be given to the patient’s likelihood of recovery with ECMO, especially in patients with advanced age, multiple organ failures, or severe comorbid disease.

Even high-volume centers may care for only a few patients annually with ARDS severe enough to be appropriate for ECMO, so many patients originate at other institutions. Ambulance and air transport of patients on ECMO have been shown to be both feasible and safe.25,26

The role of ECMO may be most apparent when ARDS is more severe that tissue hypoxia or life-threatening hypercapnia-mediated acidosis result. However, the benefit of ECMO may also lie in limiting the ventilator-associated lung injury resulting from the high-volume, high-pressure ventilation often necessary to maintain adequate gas exchange in the absence of ECMO.

Low-volume, low-pressure mechanical ventilation (ventilation at 6 ml/kg or less of predicted body weight [PBW] with an end-inspiratory plateau pressure of ≤30 cm H2O) reduces mortality compared with mechanical ventilation at higher pressures and volumes, even when associated with lower systemic oxygenation.27–29 The survival benefit of this strategy may extend for at least 2 years.30 Despite the benefit of lung-protective ventilation, its consistent use in ARDS may be limited by the poor lung compliance associated with severe lung injury and the unacceptable acidosis resulting from lowering tidal volumes sufficiently to achieve an acceptable end-inspiratory plateau pressure. In this circumstance, lung-protective ventilation is often forfeited to maintain pH.31,32 By correcting the acidosis while simultaneously oxygenating the blood, ECMO permits low tidal volume ventilation while maintaining an acceptable pH.

The benefit of ECMO may extend beyond facilitating low tidal volume ventilation. Enhanced lung-protective ventilation, sometimes referred to as “lung rest,” targets tidal volumes and end-inspiratory plateau pressures lower than the currently accepted standard of care (often <20–25 cm H2O) and may be beneficial. Similar to other applications of extracorporeal technology, this concept is not new and has undergone resurgence in the modern era of ECMO.33–36 Achieving such low end-inspiratory plateau pressures in the setting of poor pulmonary compliance may require tidal volumes of 1–3 ml/kg of PBW, relying on extracorporeal CO2 removal (ECCO2R) to correct the hypercapnia-mediated respiratory acidosis seen at lower minute ventilation. As opposed to the higher blood flow needed for oxygenation, enhanced lung-protective ventilation in patients who are not profoundly hypoxemic may be achieved with lower blood flow rates and smaller cannulae that target ECCO2R alone.37,38

Accumulating evidence suggests that the modern application of enhanced lung-protective ventilation strategies may attenuate lung injury and result in improved clinical outcomes.30,37–39 Lower tidal volume ventilation in ARDS has been prospectively associated with lower mortality, even at tidal volumes lower than 6 ml/kg of PBW.30 Retrospective analysis of the original ARDSnet low tidal volume data shows that lower day 1 plateau pressure is associated with lower mortality, even at an end-inspiratory plateau pressure less than 30 cm H2O.39 Reduction in plateau pressures in patients with ARDS from the currently accepted levels of 28–30 to 25–28 cm H2O with the use of ECCO2R to manage the ensuing hypercapnia-mediated acidosis decreased inflammatory cytokines known to be associated with ARDS.37 A recently published trial using ECCO2R with very low tidal volumes (3 ml/kg PBW) compared with low tidal volume ventilation (6 ml/kg IBW) showed a trend toward the primary outcome of ventilator-free days. Post hoc analysis demonstrated a significant difference in the group with more severe hypoxemia (PaO2/FIO2 <150 mm Hg).38 Additional trials are needed to further evaluate the benefit of very low tidal volume ventilation in patients with ARDS.

ECMO as a Bridge to Lung Transplantation

In patients with end-stage lung disease awaiting transplantation, invasive mechanical ventilation and ECMO have both been associated with high posttransplant mortality and have been considered relative contraindications to transplantation.40–42 For the thousands of patients who may wait 12–24 months or longer for a suitable organ, decompensation requiring either often represents a tipping point that significantly reduces their likelihood of long-term survival.43 Many of these patients experience complications of critical illness or mechanical ventilation that make them ineligible for transplantation.40,44

The use of ECMO to bridge patients to lung transplantation has become increasingly accepted as recent reports of experienced centers using ECMO in this population report improved outcomes.42,45–49 Notably, if extracorporeal support can provide adequate gas exchange, in select patients, ECMO can replace mechanical ventilation and eliminate the risk of ventilator-associated complications.47–51 Furthermore, patients receiving aggressive physical therapy while supported with ECMO may be able to increase their pretransplant conditioning, as ECMO may compensate for the exertional hypoxemia or hypercapnia that would typically limit physical activity.48–51 Small case series at high-volume centers suggest that this may translate into better outcomes compared with that of the general lung-transplant population.47–49,52,53

Pulmonary Hypertension

Patients with pulmonary arterial hypertension who experience an acute crisis or progressive right ventricular failure have high morbidity and mortality.54,55 In an acute crisis, this decompensation often occurs too rapidly for effective optimization of pulmonary vasodilator therapy and progressive cardiac dysfunction and multi-organ failure may ensue. In patients with refractory disease awaiting transplantation, mechanical offloading of the right ventricle may be the only remaining treatment modality. In these circumstances, venoarterial ECMO has been used successfully as either a bridge to lung transplantation or a bridge to recovery.45,56–59 By bypassing the failing right heart and delivering blood directly to the arterial circulation, venoarterial ECMO allows organ function to be preserved. Patients with acute decompensation can have pulmonary vasodilator medications optimized with ECMO as a bridge to recovery, whereas patients awaiting lung transplantation may have pulmonary vasodilators weaned to permit a greater proportion of the patient’s cardiac output to flow through the low-resistance ECMO circuit.59

Cannulation in venoarterial ECMO is traditionally performed via the femoral vein and artery, although this configuration has several notable limitations. In femoral venoarterial ECMO, oxygen delivery to the upper body is dependent on retrograde aortic blood flow and may be impeded by anterograde aortic blood flow from the native cardiac output. An alternative approach includes branching an internal jugular reinfusion cannula off the arterial cannula thereby splitting returned blood between the femoral artery and internal jugular vein and improving oxygen delivery to the upper body in a hybrid configuration known as venoarterial-venous ECMO. Because of the limited mobility and surgical and infectious risks incurred with multiple cannulation sites, this configuration is not ideal, particularly in patients awaiting lung transplantation.

Venoarterial ECMO provided through the upper body may address the limitations of femoral venoarterial cannulation. A novel configuration in which venous blood is removed from the internal jugular vein and returned to the right subclavian artery has been guarantees oxygen delivery to the upper body while optimizing mobility and minimizing infectious risk.56 To reduce the risk of limb ischemia, the arterial cannula may be inserted into a graft sewn in an end-to-side manner positioned in the distal end of the subclavian artery.60

Taking advantage of a patient’s anatomy, a dual-lumen cannula may be used to effectively provide venoarterial, upper-body support in patients with an atrial septal defect or patent foramen ovale.61,62 Positioning the cannula so that the reinfused blood is directed across the defect allows an oxygenated right-to-left shunt to be created, thereby delivering oxygenated blood to the systemic circulation while offloading the right ventricle via a single cannula.61,62 An atrial septostomy may provide the same opportunity in the absence of a preexisting intracardiac shunt.63,64

Chronic Obstructive Pulmonary Disease

The use of ECCO2R in acute exacerbations of chronic obstructive pulmonary disease (COPD) is an evolving and potential future application of extracorporeal technology.65–69 Patients requiring invasive mechanical ventilation for COPD exacerbations have an in-hospital mortality rate of up to 30% and survivors have high morbidity and healthcare costs.70,71 Although invasive mechanical ventilation can typically support the physiologic demands of a patient with COPD, it can lead to dynamic hyperinflation, high intrinsic positive end-expiratory pressure (PEEP), and ventilator-associated pneumonia, require higher levels of sedation, and result in deconditioning and long-term disability in an often older and sicker population.71–75

Extracorporeal CO2 removal has been used successfully as an adjunct to, or in lieu of, mechanical ventilation in patients with severe exacerbations of COPD and impending respiratory failure (Figure 3).65–69 The hypercapnic respiratory failure seen in acute exacerbations of COPD may be ameliorated with an ECCO2R device that functions at low blood flow rates via a smaller, potentially safer cannula and may obviate the need for invasive mechanical ventilation.65 As ECCO2R may compensate for the exertional dyspnea that would typically limit physical activity, physical rehabilitation can be enhanced relative to that possible with mechanical ventilation. When coupled with an upper-body, dual-lumen cannula, ECCO2R may allow for reliable and safe ambulation in this population.65 This strategy, which conceives the extracorporeal circuit as an artificial lung, has the potential to alter the paradigm for the treatment of patients with severe COPD exacerbations. Larger randomized, clinical trials are in the planning stages.

Figure 3:
A patient receiving venovenous extracorporeal carbon dioxide removal as part of a pilot study designed to facilitate early endotracheal extubation and ambulation in patients with severe exacerbations of chronic obstructive pulmonary disease.

Alternative Applications

Extracorporeal support has been used to treat patients with other underlying etiologies of acute respiratory failure, such as status asthmaticus.76–80 The acute hypercapnia-mediated respiratory acidosis in status asthmaticus is associated with dynamic hyperinflation and high levels of intrinsic PEEP which may result in pneumothorax, hemodynamic compromise, or death.81 The use of ECCO2R in this setting is similar to its use in acute exacerbations of COPD.

Venovenous ECMO has been used to manage patients with diffuse alveolar hemorrhage attributed to vasculitis, collagen vascular disease, and other causes.82–86 Bleeding, particularly alveolar hemorrhage, was typically considered a contraindication to ECMO with older technology because of the high levels of anticoagulation required to maintain the patency of the circuit, as well as the degree of hemolysis that necessitated frequent transfusions.87–90 However, newer, more biocompatible circuits have a reduced risk of hemorrhage and hemolysis, require only low-dose anticoagulation and, at times, may be run with no anticoagulation at all.4,91,92

Venoarterial ECMO may be used in patients with massive pulmonary embolism when thrombolysis is contraindicated or ineffective.93–95 It can be used to support these patients as a bridge to recovery—providing physiologic support while allowing time for systemic anticoagulation to take effect—or as a bridge to surgical embolectomy or possibly catheter-based therapies.94 Similar to patients with acute pulmonary embolism, venoarterial ECMO has been used to support women with amniotic fluid emboli after a Cesarean section.96,97

The Future

Despite a paucity of high-quality evidence, the use of ECMO for the management of adult respiratory failure is increasing throughout the world.1 More evidence is clearly needed to define the proper role of ECMO and ECCO2R in patients with severe respiratory failure. Studies are ongoing or in the planning stages for a wide variety of applications.

It is possible that the use of extracorporeal support may extend to those with milder forms of ARDS, using ECCO2R to facilitate enhanced lung-protective ventilation. Extracorporeal membrane oxygenation either as a bridge to recovery for acute forms of respiratory failure or as a bridge to transplantation for chronic, irreversible respiratory failure may permit more patients to be managed in an awake or extubated manner with reduced sedative use and increased physical therapy, which may have long-term physical, psychiatric, and neurocognitive benefits.98

A notable limitation of this technology, however, is that patients must be managed in an intensive care unit at a specialized center capable of performing ECMO. For patients with acute respiratory failure unable to be weaned from ECMO or for those with chronic respiratory failure ineligible for transplantation, no long-term or destination therapy exists. There is currently no pulmonary equivalent to a ventricular-assist device, no total artificial lung that meets a patient’s physiologic needs outside of the intensive care unit, or no lung-replacement center, akin to a dialysis center, where patients could receive intermittent, recurrent treatments. Efforts to decrease the size and improve the efficiency of existing extracorporeal technology, as well as create destination therapies, are underway, and in the future may be able to help those with acute and chronic respiratory failure on both a short- and long-term basis (Figure 4).

Figure 4:
Evolving approach to extracorporeal membrane oxygenation and extracorporeal carbon dioxide removal for adult respiratory failure. BTR, bridge to recovery; BTT, bridge to lung transplantation.

Extracorporeal membrane oxygenation and ECCO2R may demonstrate considerable, continued expansion in the coming years. The use of these devices as an artificial lung may liberate some patients from mechanical ventilation altogether, whereas the prospect of a pulmonary destination device holds the promise of transforming care for patients with chronic or irreversible respiratory failure.


1. Paden ML, Conrad SA, Rycus PT, Thiagarajan RRELSO Registry. . Extracorporeal Life Support Organization Registry Report 2012. ASAIO J. 2013;59:202–210
2. Pappalardo F, Pieri M, Greco T, et al.Italian ECMOnet. Predicting mortality risk in patients undergoing venovenous ECMO for ARDS due to influenza A (H1N1) pneumonia: The ECMOnet score. Intensive Care Med. 2013;39:275–281
3. Peek GJ, Mugford M, Tiruvoipati R, et al.CESAR Trial Collaboration. 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
4. Brodie D, Bacchetta M. Extracorporeal membrane oxygenation for ARDS in adults. N Engl J Med. 2011;365:1905–1914
5. Combes A, Bacchetta M, Brodie D, Müller T, Pellegrino V. Extracorporeal membrane oxygenation for respiratory failure in adults. Curr Opin Crit Care. 2012;18:99–104
6. Abrams D, Brodie D. Emerging indications for extracorporeal membrane oxygenation in adults with respiratory failure. Ann Am Thorac Soc. 2013;10:371–377
7. Zwischenberger JB, Conrad SA, Alpard SK, Grier LR, Bidani A. Percutaneous extracorporeal arteriovenous CO2 removal for severe respiratory failure. Ann Thorac Surg. 1999;68:181–187
8. Schmidt M, Tachon G, Devilliers C, et al. Blood oxygenation and decarboxylation determinants during venovenous ECMO for respiratory failure in adults. Intensive Care Med. 2013;39:838–846
9. Körver EP, Ganushchak YM, Simons AP, Donker DW, Maessen JG, Weerwind PW. Quantification of recirculation as an adjuvant to transthoracic echocardiography for optimization of dual-lumen extracorporeal life support. Intensive Care Med. 2012;38:906–909
10. Wang D, Zhou X, Liu X, Sidor B, Lynch J, Zwischenberger JB. Wang-Zwische double lumen cannula-toward a percutaneous and ambulatory paracorporeal artificial lung. ASAIO J. 2008;54:606–611
11. Bermudez CA, Rocha RV, Sappington PL, Toyoda Y, Murray HN, Boujoukos AJ. Initial experience with single cannulation for venovenous extracorporeal oxygenation in adults. Ann Thorac Surg. 2010;90:991–995
12. Javidfar J, Brodie D, Wang D, et al. Use of bicaval dual-lumen catheter for adult venovenous extracorporeal membrane oxygenation. Ann Thorac Surg. 2011;91:1763–1768
13. Javidfar J, Wang D, Zwischenberger JB, et al. Insertion of bicaval dual lumen extracorporeal membrane oxygenation catheter with image guidance. ASAIO J. 2011;57:203–205
14. Extracorporeal Life Support Organization. ECLS Registry Report, International Summary. 2013 Ann Arbor, MI Extracorporeal Life Support Organization
15. Extracorporeal Life Support Organization. ECLS Registry Report, United States Complications. 2014 Ann Arbor, MI Extracorporeal Life Support Organization
16. Hill JD, O’Brien TG, Murray JJ, et al. Prolonged extracorporeal oxygenation for acute post-traumatic respiratory failure (shock-lung syndrome). Use of the Bramson membrane lung. N Engl J Med. 1972;286:629–634
17. Zapol WM, Snider MT, Hill JD, et al. Extracorporeal membrane oxygenation in severe acute respiratory failure. A randomized prospective study. JAMA. 1979;242:2193–2196
18. Morris AH, Wallace CJ, Menlove RL, et al. Randomized clinical trial of pressure-controlled inverse ratio ventilation and extracorporeal CO2 removal for adult respiratory distress syndrome. Am J Respir Crit Care Med. 1994;149(2 Pt 1):295–305
19. Davies A, Jones D, Bailey M, et al. Extracorporeal membrane oxygenation for 2009 influenza A(H1N1) acute respiratory distress syndrome. JAMA. 2009;302:1888–1895
20. Davies A, Jones D, Gattas D. Extracorporeal membrane oxygenation for ARDS due to 2009 influenza A (H1N1)—Reply. JAMA. 2010;303:942
21. Noah MA, Peek GJ, Finney SJ, et al. Referral to an extracorporeal membrane oxygenation center and mortality among patients with severe 2009 influenza A(H1N1). JAMA. 2011;306:1659–1668
22. Patroniti N, Zangrillo A, Pappalardo F, et al. The Italian ECMO network experience during the 2009 influenza A(H1N1) pandemic: Preparation for severe respiratory emergency outbreaks. Intensive Care Med. 2011;37:1447–1457
23. Peek GJ, Mugford M, Tiruvoipati R, et al.CESAR Trial Collaboration. 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
24. Slutsky AS, Ranieri VM. Ventilator-induced lung injury. N Engl J Med. 2013;369:2126–2136
25. Javidfar J, Brodie D, Takayama H, et al. Safe transport of critically ill adult patients on extracorporeal membrane oxygenation support to a regional extracorporeal membrane oxygenation center. ASAIO J. 2011;57:421–425
26. Roch A, Hraiech S, Masson E, et al. Outcome of acute respiratory distress syndrome patients treated with extracorporeal membrane oxygenation and brought to a referral center. Intensive Care Med. 2014;40:74–83
27. Ranieri VM, Suter PM, Tortorella C, et al. Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: A randomized controlled trial. JAMA. 1999;282:54–61
28. Parsons PE, Eisner MD, Thompson BT, et al.NHLBI Acute Respiratory Distress Syndrome Clinical Trials Network. Lower tidal volume ventilation and plasma cytokine markers of inflammation in patients with acute lung injury. Crit Care Med. 2005;33:1–6; discussion 230
29. . Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med. 2000;342:1301–1308
30. Needham DM, Colantuoni E, Mendez-Tellez PA, et al. Lung protective mechanical ventilation and two year survival in patients with acute lung injury: Prospective cohort study. BMJ. 2012;344:e2124
31. Rubenfeld GD, Cooper C, Carter G, Thompson BT, Hudson LD. Barriers to providing lung-protective ventilation to patients with acute lung injury. Crit Care Med. 2004;32:1289–1293
32. Mikkelsen ME, Dedhiya PM, Kalhan R, Gallop RJ, Lanken PN, Fuchs BD. Potential reasons why physicians underuse lung-protective ventilation: A retrospective cohort study using physician documentation. Respir Care. 2008;53:455–461
33. Gattinoni L, Kolobow T, Agostoni A, et al. Clinical application of low frequency positive pressure ventilation with extracorporeal CO2 removal (LFPPV-ECCO2R) in treatment of adult respiratory distress syndrome (ARDS). Int J Artif Organs. 1979;2:282–283
34. Gattinoni L, Kolobow T, Damia G, Agostoni A, Pesenti A. Extracorporeal carbon dioxide removal (ECCO2R): A new form of respiratory assistance. Int J Artif Organs. 1979;2:183–185
35. Gattinoni L, Agostoni A, Pesenti A, et al. Treatment of acute respiratory failure with low-frequency positive-pressure ventilation and extracorporeal removal of CO2. Lancet. 1980;2:292–294
36. Gattinoni L, Pesenti A, Mascheroni D, et al. Low-frequency positive-pressure ventilation with extracorporeal CO2 removal in severe acute respiratory failure. JAMA. 1986;256:881–886
37. Terragni PP, Del Sorbo L, Mascia L, et al. Tidal volume lower than 6 ml/kg enhances lung protection: Role of extracorporeal carbon dioxide removal. Anesthesiology. 2009;111:826–835
38. Bein T, Weber-Carstens S, Goldmann A, et al. Lower tidal volume strategy (≈3 ml/kg) combined with extracorporeal CO2 removal versus ‘conventional’ protective ventilation (6 ml/kg) in severe ARDS: The prospective randomized Xtravent-study. Intensive Care Med. 2013;39:847–856
39. Hager DN, Krishnan JA, Hayden DL, Brower RGARDS Clinical Trials Network. . Tidal volume reduction in patients with acute lung injury when plateau pressures are not high. Am J Respir Crit Care Med. 2005;172:1241–1245
40. Mason DP, Thuita L, Nowicki ER, Murthy SC, Pettersson GB, Blackstone EH. Should lung transplantation be performed for patients on mechanical respiratory support? The US experience. J Thorac Cardiovasc Surg. 2010;139:765–773.e1
41. Orens JB, Estenne M, Arcasoy S, et al.Pulmonary Scientific Council of the International Society for Heart and Lung Transplantation. International guidelines for the selection of lung transplant candidates: 2006 update—A consensus report from the Pulmonary Scientific Council of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2006;25:745–755
42. George TJ, Beaty CA, Kilic A, Shah PD, Merlo CA, Shah AS. Outcomes and temporal trends among high-risk patients after lung transplantation in the United States. J Heart Lung Transplant. 2012;31:1182–1191
43. . Organ Procurement and Transplantation Network. Available at: Accessed December 30, 2013
44. O’Brien G, Criner GJ. Mechanical ventilation as a bridge to lung transplantation. J Heart Lung Transplant. 1999;18:255–265
45. de Perrot M, Granton JT, McRae K, et al. Impact of extracorporeal life support on outcome in patients with idiopathic pulmonary arterial hypertension awaiting lung transplantation. J Heart Lung Transplant. 2011;30:997–1002
46. Toyoda Y, Bhama JK, Shigemura N, et al. Efficacy of extracorporeal membrane oxygenation as a bridge to lung transplantation. J Thorac Cardiovasc Surg. 2013;145:1065–70; discussion 1070
47. Fuehner T, Kuehn C, Hadem J, et al. Extracorporeal membrane oxygenation in awake patients as bridge to lung transplantation. Am J Respir Crit Care Med. 2012;185:763–768
48. Javidfar J, Bacchetta M. Bridge to lung transplantation with extracorporeal membrane oxygenation support. Curr Opin Organ Transplant. 2012;17:496–502
49. Hoopes CW, Kukreja J, Golden J, Davenport DL, Diaz-Guzman E, Zwischenberger JB. Extracorporeal membrane oxygenation as a bridge to pulmonary transplantation. J Thorac Cardiovasc Surg. 2013;145:862–7; discussion 867
50. Mangi AA, Mason DP, Yun JJ, Murthy SC, Pettersson GB. Bridge to lung transplantation using short-term ambulatory extracorporeal membrane oxygenation. J Thorac Cardiovasc Surg. 2010;140:713–715
51. Garcia JP, Kon ZN, Evans C, et al. Ambulatory veno-venous extracorporeal membrane oxygenation: Innovation and pitfalls. J Thorac Cardiovasc Surg. 2011;142:755–761
52. Garcia JP, Iacono A, Kon ZN, Griffith BP. Ambulatory extracorporeal membrane oxygenation: A new approach for bridge-to-lung transplantation. J Thorac Cardiovasc Surg. 2010;139:e137–e139
53. Rehder KJ, Turner DA, Hartwig MG, et al. Active rehabilitation during extracorporeal membrane oxygenation as a bridge to lung transplantation. Respir Care. 2013;58:1291–1298
    54. Benza RL, Miller DP, Barst RJ, Badesch DB, Frost AE, McGoon MD. An evaluation of long-term survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL Registry. Chest. 2012;142:448–456
    55. Benza RL, Gomberg-Maitland M, Miller DP, et al. The REVEAL Registry risk score calculator in patients newly diagnosed with pulmonary arterial hypertension. Chest. 2012;141:354–362
    56. Abrams DC, Brodie D, Rosenzweig EB, Burkart KM, Agerstrand CL, Bacchetta MD. Upper-body extracorporeal membrane oxygenation as a strategy in decompensated pulmonary arterial hypertension. Pulm Circ. 2013;3:432–435
    57. Olsson KM, Simon A, Strueber M, et al. Extracorporeal membrane oxygenation in nonintubated patients as bridge to lung transplantation. Am J Transplant. 2010;10:2173–2178
    58. Lang G, Taghavi S, Aigner C, et al. Primary lung transplantation after bridge with extracorporeal membrane oxygenation: A plea for a shift in our paradigms for indications. Transplantation. 2012;93:729–736
    59. Rosenzweig EB, Brodie D, Abrams DC, Agerstrand CL, Bacchetta M. Extracorporeal membrane oxygenation as a novel bridging strategy for acute right heart failure in group 1 pulmonary arterial hypertension. ASAIO J. 2014;60:129–133
    60. Javidfar J, Brodie D, Costa J, et al. Subclavian artery cannulation for venoarterial extracorporeal membrane oxygenation. ASAIO J. 2012;58:494–498
    61. Javidfar J, Brodie D, Sonett J, Bacchetta M. Venovenous extracorporeal membrane oxygenation using a single cannula in patients with pulmonary hypertension and atrial septal defects. J Thorac Cardiovasc Surg. 2012;143:982–984
    62. Madershahian N, Salehi-Gilani S, Naraghi H, Stoeger E, Wahlers T. Biventricular decompression by trans-septal positioning of venous ECMO cannula through patent foramen ovale. J Cardiovasc Surg (Torino). 2011;52:900
    63. Hoopes CW, Gurley JC, Zwischenberger JB, Diaz-Guzman E. Mechanical support for pulmonary veno-occlusive disease: Combined atrial septostomy and venovenous extracorporeal membrane oxygenation. Semin Thorac Cardiovasc Surg. 2012;24:232–234
    64. Camboni D, Akay B, Sassalos P, et al. Use of venovenous extracorporeal membrane oxygenation and an atrial septostomy for pulmonary and right ventricular failure. Ann Thorac Surg. 2011;91:144–149
    65. Abrams DC, Brenner K, Burkart KM, et al. Pilot study of extracorporeal carbon dioxide removal to facilitate extubation and ambulation in exacerbations of chronic obstructive pulmonary disease. Ann Am Thorac Soc. 2013;10:307–314
    66. Burki NK, Mani RK, Herth FJ, et al. A novel extracorporeal CO2 removal system: Results of a pilot study of hypercapnic respiratory failure in patients with COPD. Chest. 2013;143:678–686
    67. Kluge S, Braune SA, Engel M, et al. Avoiding invasive mechanical ventilation by extracorporeal carbon dioxide removal in patients failing noninvasive ventilation. Intensive Care Med. 2012;38:1632–1639
    68. Brederlau J, Wurmb T, Wilczek S, et al. Extracorporeal lung assist might avoid invasive ventilation in exacerbation of COPD. Eur Respir J. 2012;40:783–785
    69. Cardenas VJ Jr, Lynch JE, Ates R, Miller L, Zwischenberger JB. Venovenous carbon dioxide removal in chronic obstructive pulmonary disease: Experience in one patient. ASAIO J. 2009;55:420–422
    70. Keenan SP, Sinuff T, Cook DJ, Hill NS. Which patients with acute exacerbation of chronic obstructive pulmonary disease benefit from noninvasive positive-pressure ventilation? A systematic review of the literature. Ann Intern Med. 2003;138:861–870
    71. Chandra D, Stamm JA, Taylor B, et al. Outcomes of noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease in the United States, 1998–2008. Am J Respir Crit Care Med. 2012;185:152–159
    72. Ward NS, Dushay KM. Clinical concise review: Mechanical ventilation of patients with chronic obstructive pulmonary disease. Crit Care Med. 2008;36:1614–1619
    73. Ai-Ping C, Lee KH, Lim TK. In-hospital and 5-year mortality of patients treated in the ICU for acute exacerbation of COPD: A retrospective study. Chest. 2005;128:518–524
    74. Spruit MA, Gosselink R, Troosters T, et al. Muscle force during an acute exacerbation in hospitalised patients with COPD and its relationship with CXCL8 and IGF-I. Thorax. 2003;58:752–756
    75. Rello J, Ollendorf DA, Oster G, et al.VAP Outcomes Scientific Advisory Group. Epidemiology and outcomes of ventilator-associated pneumonia in a large US database. Chest. 2002;122:2115–2121
    76. MacDonnell KF, Moon HS, Sekar TS, Ahluwalia MP. Extracorporeal membrane oxygenator support in a case of severe status asthmaticus. Ann Thorac Surg. 1981;31:171–175
    77. King D, Smales C, Arnold AG, Jones OG. Extracorporeal membrane oxygenation as emergency treatment for life-threatening acute severe asthma. Postgrad Med J. 1986;62:855–857
    78. Cooper DJ, Tuxen DV, Fisher MM. Extracorporeal life support for status asthmaticus. Chest. 1994;106:978–979
    79. Mikkelsen ME, Woo YJ, Sager JS, Fuchs BD, Christie JD. Outcomes using extracorporeal life support for adult respiratory failure due to status asthmaticus. ASAIO J. 2009;55:47–52
    80. Brenner K, Abrams DC, Agerstrand CL, Brodie D. Extracorporeal carbon dioxide removal for refractory status asthmaticus: Experience in distinct exacerbation phenotypes. Perfusion. 2014;29:26–28
    81. Afessa B, Morales I, Cury JD. Clinical course and outcome of patients admitted to an ICU for status asthmaticus. Chest. 2001;120:1616–1621
    82. Hartmann A, Nordal KP, Svennevig J, et al. Successful use of artificial lung (ECMO) and kidney in the treatment of a 20-year-old female with Wegener’s syndrome. Nephrol Dial Transplant. 1994;9:316–319
    83. Ahmed SH, Aziz T, Cochran J, Highland K. Use of extracorporeal membrane oxygenation in a patient with diffuse alveolar hemorrhage. Chest. 2004;126:305–309
    84. Mongero LB, Brodie D, Cunningham J, et al. Extracorporeal membrane oxygenation for diffuse alveolar hemorrhage and severe hypoxemic respiratory failure from silicone embolism. Perfusion. 2010;25:249–52; discussion 253
    85. Patel JJ, Lipchik RJ. Systemic lupus–induced diffuse alveolar hemorrhage treated with extracorporeal membrane oxygenation: A case report and review of the literature. J Intensive Care Med. 2012;0:1–6
    86. Barnes SL, Naughton M, Douglass J, Murphy D. Extracorporeal membrane oxygenation with plasma exchange in a patient with alveolar haemorrhage secondary to Wegener’s granulomatosis. Intern Med J. 2012;42:341–342
    87. Extracorporeal Life Support Organization. General Guidelines for All ECLS Cases. 2013 Ann Arbor, MI Extracorporeal Life Support Organization
    88. Butch SH, Knafl P, Oberman HA, Bartlett RH. Blood utilization in adult patients undergoing extracorporeal membrane oxygenated therapy. Transfusion. 1996;36:61–63
    89. Nehra D, Goldstein AM, Doody DP, Ryan DP, Chang Y, Masiakos PT. Extracorporeal membrane oxygenation for nonneonatal acute respiratory failure: The Massachusetts General Hospital experience from 1990 to 2008. Arch Surg. 2009;144:427–32; discussion 432
    90. Mols G, Loop T, Geiger K, Farthmann E, Benzing A. Extracorporeal membrane oxygenation: A ten-year experience. Am J Surg. 2000;180:144–154
    91. MacLaren G, Combes A, Bartlett RH. Contemporary extracorporeal membrane oxygenation for adult respiratory failure: Life support in the new era. Intensive Care Med. 2012;38:210–220
    92. Lappa A, Donfrancesco S, Contento C, et al. Weaning from venovenous extracorporeal membrane oxygenation without anticoagulation: Is it possible? Ann Thorac Surg. 2012;94:e1–e3
    93. Kawahito K, Murata S, Adachi H, Ino T, Fuse K. Resuscitation and circulatory support using extracorporeal membrane oxygenation for fulminant pulmonary embolism. Artif Organs. 2000;24:427–430
    94. Hsieh PC, Wang SS, Ko WJ, Han YY, Chu SH. Successful resuscitation of acute massive pulmonary embolism with extracorporeal membrane oxygenation and open embolectomy. Ann Thorac Surg. 2001;72:266–267
    95. Davies MJ, Arsiwala SS, Moore HM, Kerr S, Sosnowski AW, Firmin RK. Extracorporeal membrane oxygenation for the treatment of massive pulmonary embolism. Ann Thorac Surg. 1995;60:1801–1803
    96. Hsieh YY, Chang CC, Li PC, Tsai HD, Tsai CH. Successful application of extracorporeal membrane oxygenation and intra-aortic balloon counterpulsation as lifesaving therapy for a patient with amniotic fluid embolism. Am J Obstet Gynecol. 2000;183:496–497
    97. Ho CH, Chen KB, Liu SK, Liu YF, Cheng HC, Wu RS. Early application of extracorporeal membrane oxygenation in a patient with amniotic fluid embolism. Acta Anaesthesiol Taiwan. 2009;47:99–102
    98. Schweickert WD, Pohlman MC, Pohlman AS, et al. Early physical and occupational therapy in mechanically ventilated, critically ill patients: A randomised controlled trial. Lancet. 2009;373:1874–1882

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