Extracorporeal membrane oxygenation: a literature review

Chaves, Renato Carneiro de Freitas; Rabello, Roberto; Timenetsky, Karina Tavares; Moreira, Fabio Tanzillo; Vilanova, Luiz Carlos da Silva; Bravim, Bruno de Arruda; Serpa, Ary; Corrêa, Thiago Domingos

doi:10.5935/0103-507X.20190063

Renato Carneiro de Freitas Chaves

Department of Intensive Care Medicine, Hospital Israelita Albert Einstein - São Paulo (SP), Brazil.

Department of Anesthesiology, Irmandade da Santa Casa de Misericórdia de Santos - Santos (SP), Brazil.

http://orcid.org/0000-0001-7324-272X

Roberto Rabello Filho

Department of Intensive Care Medicine, Hospital Israelita Albert Einstein - São Paulo (SP), Brazil.

Karina Tavares Timenetsky

Department of Intensive Care Medicine, Hospital Israelita Albert Einstein - São Paulo (SP), Brazil.

Fabio Tanzillo Moreira

Department of Intensive Care Medicine, Hospital Israelita Albert Einstein - São Paulo (SP), Brazil.

Department of Intensive Care Medicine, Hospital Municipal Dr. Moysés Deutsch - São Paulo (SP), Brazil.

Luiz Carlos da Silva Vilanova

Department of Intensive Care Medicine, Hospital Israelita Albert Einstein - São Paulo (SP), Brazil.

Bruno de Arruda Bravim

Department of Intensive Care Medicine, Hospital Israelita Albert Einstein - São Paulo (SP), Brazil.

Ary Serpa Neto

Department of Intensive Care Medicine, Hospital Israelita Albert Einstein - São Paulo (SP), Brazil.

Thiago Domingos Corrêa Corresponding author: Thiago Domingos Corrêa, Unidade de Terapia Intensiva Adulto, Hospital Israelita Albert Einstein, Avenida Albert Einstein, 627/701, 5º andar, Zip code: 05651-901 - São Paulo (SP), Brazil, E-mail: thiago.correa@einstein.br

Department of Intensive Care Medicine, Hospital Israelita Albert Einstein - São Paulo (SP), Brazil.

Department of Intensive Care Medicine, Hospital Municipal Dr. Moysés Deutsch - São Paulo (SP), Brazil.

Corresponding author: Thiago Domingos Corrêa, Unidade de Terapia Intensiva Adulto, Hospital Israelita Albert Einstein, Avenida Albert Einstein, 627/701, 5º andar, Zip code: 05651-901 - São Paulo (SP), Brazil, E-mail: thiago.correa@einstein.br

Conflicts of interest: None.

Responsible editor: Luciano César Pontes de Azevedo

Author	N	Design	Inclusion criteria	Exclusion criteria	Primary outcome	Main findings	Considerations
Combes et al.⁽¹1 Combes A, Hajage D, Capellier G, Demoule A, Lavoue´ S, Guervilly C, Da Silva D, Zafrani L, Tirot P, Veber B, Maury E, Levy B, Cohen Y, Richard C, Kalfon P, Bouadma L, Mehdaoui H, Beduneau G, Lebreton G, Brochard L, Ferguson ND, Fan E, Slutsky AS, Brodie D, Mercat A; EOLIA Trial Group, REVA, and ECMONet. Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome. N Engl J Med. 2018;378(21):1965-75.⁾	249	International multicenter, randomized, controlled clinical trial	1. Patient intubated on MV < 7 days 2. PaO₂/FiO₂ < 50mmHg for > 3 hours OR PaO₂/FiO₂ < 80mmHg for > 6 hours OR Arterial pH < 7.25 with PaCO₂ ≥ 60mmHg > 6 hours 3. Optimized MV^* * Defined by the presence of, positive end-expiratory pressure ≥ 10cmH2O and tidal volume of 6mL/kg of predicted weight. 4. Age >18 years	1. Pregnant women 2. BMI > 45 3. Chronic respiratory failure 4. Indication for VA-ECMO 5. History of HIT 6. Advanced cancer 7. Dying patients 8. Coma after cardiac arrest 9. Nonreversible neurologic injury 10. Palliative patients	60-day mortality of 35% (44/124 patients) in the ECMO group and 46% (57/125 patients) in the control group (RR: 0.76; 95%CI 0.55 -1.04; p = 0.09)	The ECMO group had a higher incidence of severe thrombocytopenia and bleeding requiring transfusion. The ECMO group had a lower incidence of IS, lower need for renal replacement therapy, and reduction of tidal volume, plateau pressure and drive pressure	Early interruption of the study due to futility Slow recruitment rate High crossover rate (28%) from the control group to the ECMO group due to refractory hypoxemia Greater failure of treatment at 60 days in the control group
Peek et al.⁽²2 Peek GJ, Mugford M, Tiruvoipati R, Wilson A, Allen E, Thalanany MM, Hibbert CL, Truesdale A, Clemens F, Cooper N, Firmin RK, Elbourne D; CESAR trialcollaboration. 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(9698):1351-63. Erratum in Lancet. 2009;374(9698):1330.⁾	180	Multicenter, randomized, controlled clinical trial	1. Age from 18 - 65 years 2. Severe but potentially reversible respiratory failure 3. Murray score ≥ 3.0 4. Uncompensated hypercapnia 5. Optimized MV	1. PIP > 30cmH₂O 2. FiO₂ > 80% 3. Time of MV ≥ 7 days 4. Intracranial bleeding 5. Contraindication to heparinization 6. Limitation of support	6-month mortality after randomization or before hospital discharge of 37% (33/90) in the ECMO group and 53% (46/87) in the control group (RR: 0.69; 95%CI 0.05-0.97, p = 0.03)	The transfer of patients with severe but potentially reversible respiratory failure to a reference center in ECMO proved to be cost-effective and reduce mortality	Control group does not have standardization of MV parameters Of the 90 patients randomized to receive ECMO, 22 patients did not use the device
Morris et al.⁽³3 Morris AH, Wallace CJ, Menlove RL, Clemmer TP, Orme JF Jr, Weaver LK, 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. Erratum in: Am J Respir Crit Care Med 1994;149(3 Pt 1):838.⁾	40	Dual-center, randomized, controlled clinical trial	1. PaO₂ < 50mmHg for 2 hours with FiO₂ = 100%, PEEP > 5 and PaCO₂ of 30 - 45 or PaO₂ < 50mmHg for 12 hours with FiO₂ = 60%, PEEP ≥ 5cmH₂O and PaCO₂ of 30 - 45 2. Optimized MV	1. Contraindication to anticoagulants 2. POAP > 25mmHg 3. Time of MV> 21 days 4. Severe, irreversible and without treatment prospective systemic disease.	30-day survival of 33% (7/21) in the ECMO group and 42% (8/19) in the control group (p = 0.8)	Does not recommend the use of ECMO in patients with ARDS	Small sample size High mortality rate (62% of patients died) Technical limitations inherent to the clinical trial period Nonprotective MV in both groups
Zapol et al.⁽⁴4 Zapol WM, Snider MT, Hill JD, Fallat RJ, Bartlett RH, Edmunds LH, et al. Extracorporeal membrane oxygenation in severe acute respiratory failure. A randomized prospective study. JAMA. 1979;242(20):2193-6.⁾	90	Multicenter, randomized, controlled clinical trial	1. PaO₂ < 50 mm Hg, for more than 2 hours with FiO₂ 100% and PEEP ≥ 5cmH₂O OR PaO₂ < 50 mm Hg, for more than 12 hours with FiO₂ = 60% and PEEP ≥ 5cmH₂O	1. Age from 12 to 65 years old 2. Pulmonary lesion time > 21 days 3. PWP > 25mmHg 4. Severe, irreversible and incurable systemic disease.	30-day survival of 9.5% (4/42) in the ECMO group and 8.3% (4/48) in the control group (no significant difference)	ECMO was able to provide respiratory support, but did not increase the survival in patients with severe ARDS	Mortality in both groups greater than 90% Technical limitations inherent to the clinical trial period Nonprotective MV in both groups

Author	N	Design	Inclusion criteria	Exclusion criteria	Primary outcome	Main findings	Conclusion
Dangers et al.⁽⁵5 Dangers L, Bréchot N, Schmidt M, Lebreton G, Hékimian G, Nieszkowska A, et al. Extracorporeal Membrane oxygenation for acute decompensated heart failure. Crit Care Med. 2017;45(8):1359-66.⁾	105	Retrospective analysis, single center	Patients who used VA-ECMO due to cardiogenic shock with dilated cardiomyopathy	Refractory cardiogenic shock due to complications of acute heart disease (myocardial infarction and myocarditis) Patients who used VV-ECMO	Description of characteristics, outcomes and risk factors associated with worse outcomes in patients on VA-ECMO due to cardiogenic shock	One-year survival of 42% One-year survival of patients with pre-VA-ECMO SOFA < 7 was 52%. One-year survival of patients with pre-VA-ECMO SOFA > 13 of 17% 67% of patients used IABP in combination with VA-ECMO.	VA-ECMO as a bridge to left ventricular assist device or heart transplantation should be considered in patients with cardiogenic shock VA-ECMO is best indicated in patients with SOFA < 11
Rastan et al.⁽⁶6 Rastan AJ, Dege A, Mohr M, Doll N, Falk V, Walther T, et al. Early and late outcomes of 517 consecutive adult patients treated with extracorporeal membrane oxygenation for refractory postcardiotomy cardiogenic shock. J Thorac Cardiovasc Surg. 2010;139(2):302-11, 311.e1.⁾	517	Observational prospective study	Patients who used VA-ECMO for refractory cardiogenic shock after cardiotomy	Not specified	Identification of risk factors associated with hospital outcomes and long-term outcomes	Six-month survival of 17.6% One-year survival of 16.5% Five-year survival of 13.7% Age > 70 years, diabetes, renal failure prior to surgery, obesity, lactate > 4 mmol/L are risk factors for in-hospital mortality	VA-ECMO is an acceptable option for patients with refractory cardiogenic shock after cardiotomy
Chen et al.⁽⁷7 Chen YS, Lin JW, Yu HY, Ko WJ, Jerng JS, Chang WT, et al. Cardiopulmonary resuscitation with assisted extracorporeal life-support versus conventional cardiopulmonary resuscitation in adults with in-hospital cardiac arrest: an observational study and propensity analysis. Lancet. 2008;372(9638):554-61.⁾	172	Observational prospective study, single center. Matching performed with propensity score	Intrahospital cardiac arrest Age between 18 and 75 years Cardiac arrest lasting > 10 minutes	Previous irreversible neurological disease Terminal stage cancer Uncontrolled bleeding of traumatic origin	Survival to hospital discharge in the ECMO group of 28.8% (17/59) and 12.3% (14/113) in the control group (log-rank p < 0.0001)	Return to spontaneous circulation was higher in the ECMO group. One-year survival in the ECMO group was 18.6% (11/59) One-year survival in the control group was 9.7% (11/113).	VA-ECMO in in-hospital cardiac arrest increased survival and improved neurological outcomes compared to conventional CPR
Combes et al.⁽⁸8 Combes A, Leprince P, Luyt CE, Bonnet N, Trouillet JL, Léger P, et al. Outcomes and long-term quality-of-life of patients supported by extracorporeal membrane oxygenation for refractory cardiogenic shock. Crit Care Med. 2008;36(5):1404-11.⁾	81	Retrospective study	Patients who used VA-ECMO for refractory cardiogenic shock	Patient using VV-ECMO	Identification of early and independent predictors of ECMO failure and description of the outcome of patients on ECMO support during ICU stay	Variables associated with increased mortality: onset of ECMO during cardiac arrest, severe hepatic or renal dysfunction and female sex ECMO due to fulminant myocarditis was associated with better outcomes	VA-ECMO in patients with refractory cardiogenic shock is effective in rescue in 40% patients Survival in the ICU in the ECMO group was 42% (34/81).
Pagani et al.⁽⁹9 Pagani FD, Aaronson KD, Swaniker F, Bartlett RH. The use of extracorporeal life support in adult patients with primary cardiac failure as a bridge to implantable left ventricular assist device. Ann Thorac Surg. 2001;71(3 Suppl):S77-81; discussion S82-5.⁾	33	Not specified	Absence of contraindication to heart transplantation Age < 66 years Refractory cardiogenic shock Severe hemodynamic instability	Need for VA-ECMO after transplant failure Elective and planned use of VA-ECMO for coronary angioplasty	Evaluation of the use of ECMO as a bridge to LVAD and subsequent transplantation in selected high-risk patients	Small sample size VA-ECMO is effective in the initial stabilization of patients with refractory cardiogenic shock, but maintenance of VA-ECMO is associated with a high rate of complications The cost of VA-ECMO compared to the LVAD was lower but had a higher incidence of complications	The initial stabilization of patients with refractory cardiogenic shock with VA-ECMO as a bridge to LVAD or heart transplantation is associated with better outcomes at 1 year.

Exams	When to collect	Therapeutic target	Considerations
ACT	Immediately after cannulation of ECMO	Initially, between 180 and 220 seconds. After collection of test, anticoagulation adjustment should be guided by aPTT or anti-Xa activity.	Easy to perform, can be performed at the bedside Result available quickly It allows the initial adjustment of heparin infusion
aPTT	Daily. It can be collected more than once per day, especially in cases of adjustment of heparin infusion.	Keep between 40 and 55 seconds	Adequate management of anticoagulation is essential to avoid complications such as system coagulation and intracranial hemorrhage.
Anti-Xa activity	Alternative to the aPTT. It can be collected more than once per day, especially in cases of adjustment of heparin infusion.	Keep between 0.2 and 0.3IU/mm	Adequate management of anticoagulation is essential to avoid complications such as system coagulation and intracranial hemorrhage.
Platelets	Daily. It can be collected more than once per day, especially in cases of bleeding.	Ideally kept greater than 100,000 cells per mm³	Platelets are an essential component of hemostasis and in the prevention of hemorrhagic complications.
Hemoglobin	Daily. It can be collected more than once per day, especially in cases of bleeding.	Ideally kept greater than 8.0 g/dL	Hemoglobin is a key component of oxygen transport.
D-Dimer	Daily. It can be collected more than once per day	Not applicable	Sudden elevation of D-dimer level is strongly indicative of clot formation, predicting failure of the ECMO system.
SvcO₂	Daily	Ideally maintained greater than 70%, especially in VA-ECMO.	It allows for the adjustment of VA-ECMO flow.
PaCO₂	Daily	Ideally, it was maintained close to 40mmHg, especially in VV-ECMO.	Allows for the adjustment of the fresh gas flow rate Patients with PaCO₂ > 50mmHg should be subjected to slow and gradual reduction (not to exceed reduction values greater than 10mmHg per hour).

[1] Corresponding author: Thiago Domingos Corrêa, Unidade de Terapia Intensiva Adulto, Hospital Israelita Albert Einstein, Avenida Albert Einstein, 627/701, 5º andar, Zip code: 05651-901 - São Paulo (SP), Brazil, E-mail: thiago.correa@einstein.br

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Extracorporeal membrane oxygenation: a literature review

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