ASAIO Journal 2014
Review Article
ECMO for Adult Respiratory Failure: Current Use and Evolving Applications Cara L. Agerstrand,* Matthew D. Bacchetta,† and Daniel Brodie*
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. ASAIO Journal 2014; 60:255–262.
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 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
Key Words: extracorporeal membrane oxygenation, acute respiratory distress syndrome, artificial lungs
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)
From the *Department of Medicine, Columbia University College of Physicians and Surgeons, New York-Presbyterian Hospital, New York, New York; and †Department of Surgery, Columbia University College of Physicians and Surgeons, New York-Presbyterian Hospital, New York, New York. Submitted for consideration January 24, 2014; accepted for publication in revised form February 7, 2014. Disclosures: The authors have no conflicts of interest to report. Reprint Requests: Cara L. Agerstrand, MD, Department of Medicine, Columbia University College of Physicians and Surgeons, New York-Presbyterian Hospital, 622 West 168th Street, PH 8–101, New York, NY 10032. Email: [email protected]. Copyright © 2014 by the American Society for Artificial Internal Organs DOI: 10.1097/MAT.0000000000000062
255
256 AGERSTRAND et al.
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 collectedmed.com.
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
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 collectedmed.com.
ECMO FOR ADULT RESPIRATORY FAILURE
port positioned within the right atrium and the reinfusion jet directed toward the tricuspid valve. The advantages of a duallumen 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 ECMO for ARDS 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 H 1N1-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 (www.clinicaltrials.gov [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 endinspiratory 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
257
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 endinspiratory 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
Review Article
ECMO for Adult Respiratory Failure: Current Use and Evolving Applications Cara L. Agerstrand,* Matthew D. Bacchetta,† and Daniel Brodie*
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. ASAIO Journal 2014; 60:255–262.
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 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
Key Words: extracorporeal membrane oxygenation, acute respiratory distress syndrome, artificial lungs
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)
From the *Department of Medicine, Columbia University College of Physicians and Surgeons, New York-Presbyterian Hospital, New York, New York; and †Department of Surgery, Columbia University College of Physicians and Surgeons, New York-Presbyterian Hospital, New York, New York. Submitted for consideration January 24, 2014; accepted for publication in revised form February 7, 2014. Disclosures: The authors have no conflicts of interest to report. Reprint Requests: Cara L. Agerstrand, MD, Department of Medicine, Columbia University College of Physicians and Surgeons, New York-Presbyterian Hospital, 622 West 168th Street, PH 8–101, New York, NY 10032. Email: [email protected]. Copyright © 2014 by the American Society for Artificial Internal Organs DOI: 10.1097/MAT.0000000000000062
255
256 AGERSTRAND et al.
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 collectedmed.com.
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
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 collectedmed.com.
ECMO FOR ADULT RESPIRATORY FAILURE
port positioned within the right atrium and the reinfusion jet directed toward the tricuspid valve. The advantages of a duallumen 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 ECMO for ARDS 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 H 1N1-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 (www.clinicaltrials.gov [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 endinspiratory 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
257
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 endinspiratory 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
