The Use of ECMO in Patients with Cardiopulmonary Failure Due to COVID-19

Quick Takes

  • V-V ECMO should be considered for patients with refractory ARDS due to COVID-19.
  • V-A ECMO should be considered for patients with cardiogenic shock due to COVID-19.
  • Patients should be selected for ECMO based on the best chance for long-term survival.

Introduction
SARS-CoV-2, the virus which causes COVID-19, primarily attacks the lungs and causes acute hypoxemic respiratory failure in a subset of patients. Large case series from China and New York suggest that 5 – 14% of patients require intensive care and 2 – 20% will require invasive mechanical ventilation.1-4 Nearly all of these patients will have the acute respiratory distress syndrome (ARDS) and thus require lung-protective ventilation (LPV).5,6 Severe hypoxemia may be improved with the prone position, positive end-expiratory pressure (PEEP) optimization, neuromuscular blockade and inhaled pulmonary vasodilators.5-7 Patients with refractory hypoxemia or hypercarbia as well as patients with right ventricular failure resulting from hypercarbia, acidemia or hypoxic pulmonary vasoconstriction may benefit from extracorporeal life support (ECLS) through venovenous (V-V) extracorporeal membrane oxygenation (ECMO).6,8-10 In addition, a small subset of COVID-19 patients may suffer from cardiogenic shock or massive pulmonary embolism and may be considered for venoarterial (V-A) ECMO.11

V-V ECMO involves removing a portion of venous blood and pushing it through a "membrane lung" which fully oxygenates the blood and removes carbon dioxide through counter-flow of a sweep gas, then returning that blood to the right atrium (Figures 1 and 2). Replacing the function of the lungs allows for "resting" ventilator settings to provide the lungs time to heal without further ventilator-induced damage.

Figure 1

Figure 1
Figure 1: Graphical depiction of V-V ECMO, where blood is drained from the femoral vein above the diaphragm and returned to the right atrium. Image used with permission from CollectedMed, LLC.

Figure 2

Figure 2
Figure 2: Graphical depiction of V-V ECMO, where central venous blood is drained and oxygenated blood is returned to the right atrium, which then moves across the tricuspid valve. Image used with permission from CollectedMed, LLC.

V-A ECMO involves removing a portion of the venous blood and pushing it through a membrane lung then returning it to the distal-aorta to distribute through the arterial circulation. This results in partial cardiopulmonary bypass thus supplementing the reduced cardiac output of the failing heart with oxygenated blood (Figure 3).

Figure 3

Figure 3
Figure 3: Graphical depiction of V-A ECMO, where central venous blood is drained and oxygenated blood is returned to the arterial system. Image used with permission from CollectedMed, LLC.

ECMO as a treatment for viral pneumonia causing severe ARDS
The best data for ECMO as a treatment for respiratory failure in viral pneumonias comes from H1N1 influenza pneumonia. A systematic review and meta-analysis including 494 patients who received ECMO (94% V-V) found overall mortality of 37% (compared to 46% for all-comers with severe ARDS in a recent large epidemiological study12) with a median duration for ECMO of 10 days.13 A retrospective analysis of patients with respiratory failure caused by the Middle East Respiratory Syndrome coronavirus (MERS CoV) compared survival in 17 patients who received V-V ECMO compared to 18 managed with conventional therapy and found lower mortality (65% compared to 100%) in the group receiving ECMO.14 The most recent randomized controlled trial of ECMO for severe ARDS included 21% of patients with viral pneumonia in the ECMO arm and 16% of patients with viral pneumonia in the control group. The survival rate of 65% in the ECMO arm did not represent a statistically significant difference from the control arm, though a Bayesian analysis suggests there may be a benefit to ECMO.8,9

ECMO use for COVID-19
The cannulation and management of patients on ECMO is a labor-, equipment- and cost-intensive process, and the decision to do so should not be taken lightly. In all cases and in particular in locations where caseloads and intensive care unit (ICU) occupancy is rising, ECMO should be reserved for cases refractory to the best traditional ARDS and cardiogenic shock management and with the best chance of survival. ECMO can only support the lungs and heart, and patients with chronic systemic disease and irreversible multi-system organ failure are less likely to benefit. Patients being considered for ECMO should be transferred to ECMO centers for management.15

Epidemiology
The Extracorporeal Life Support Organization (ELSO) maintains a live dashboard of all reported patients treated with ECMO for COVID-19 (as a public service). As of this writing, ELSO reports that 1,468 patients with confirmed COVID-19 have been placed on ECMO, 801 of whom have been discharged from the hospital, with 56% surviving.16,17 The majority of patients (91%) have been supported by V-V and 4% of patients have been supported by V-A. Patients who have completed their ECMO run have had a median duration of 12 days on ECMO.17 Data from the EuroELSO Survey on COVID-19 ECMO Use18 and the international COVID-19 Critical Care Consortium are not yet published.19 Smaller case series report widely variable survival rates (0-69%), and most were published during ongoing ECMO therapy for multiple patients within the cohort and thus unable to report final outcomes.20,21

V-V ECMO as a treatment for respiratory failure caused by COVID-19
Patient selection for ECMO is critical. Traditional ARDS therapies (LPV, neuromuscular blockade for significant ventilator dyssynchrony, patient proning, inhaled pulmonary vasodilators) should be maximized prior to initiating ECMO. Early transport to ECMO centers should be considered if PaO2/FiO2 is <100 mmHg despite these supportive measures.15

The ELSO COVID-19 Interim Guidelines give the following indications for V-V ECMO:15

  • PaO2/FiO2 <60 mmHg for >6 hr or <50 mmHg for >3 hr
              and/or
  • pH <7.2 with CO2 >80 mmHg for >6hr (while targeting plateau pressure <30 cm H2O)

V-A ECMO as a treatment for cardiogenic shock caused by COVID-19
COVID-19 is primarily a respiratory disease, but does have cardiovascular manifestations as well and can occasionally be complicated by cardiogenic shock.11,22 COVID-19 has been associated with myocarditis, septic or stress cardiomyopathy, acute coronary syndrome as a result of a potential hypercoagulable state as well as pulmonary embolism.11,22 Indications for V-A ECMO in the setting of cardiogenic shock from COVID-19 should not differ from indications in other settings.17,23 V-A ECMO should be initiated prior to the development of irreversible multi-organ failure.15

Occasionally patients on V-V ECMO for respiratory failure will develop cardiogenic shock and require V-A support, and can be transitioned to venovenoarterial (V-VA) ECMO.15 V-VA ECMO is a hybrid configuration combining both V-V and V-A support. It utilizes a single venous drainage cannula and splits the return blood between the venous return cannula of V-V ECMO (internal jugular or femoral vein) and the arterial return cannulae of V-A ECMO (femoral artery). Indication:15

  • Refractory cardiogenic shock with persistent tissue hypoperfusion (systolic blood pressure <90 mmHg, cardiac index <2.2 L/min/m2 while on norepinephrine >0.5mcg/kg/min, dobutamine 20 mcg/kg/min or equivalent)

Contraindications for ECMO
As stated above, ECMO is resource-intensive, and contra-indications should become stricter as hospital capacities tighten. The most recent guidelines for the care of COVID-19 patients released by ELSO recommend different thresholds for ECMO based on hospital system capacity (Figure 2 of the cited reference).15 For systems within "conventional capacity," ECMO should be offered to selected COVID-19 patients as discussed above as well as for usual non-COVID-19 indications. There are two tiers of contingency capacity. Tier 1 includes systems running at expanded capacity and ECMO should be triaged to maximize the resource: benefit ratio. ECMO should be used judiciously for non-COVID-19 indications. Tier 2 includes systems with expanded capacity which is near saturation, and systems should utilize restrictive ECMO criteria for COVID-19 and non-COVID-19 indications. Non-COVID-19 patients with a better chance of survival should be prioritized, and V-A ECMO should not be offered. In crisis capacity, resources should be concentrated on usual care and ECMO may no longer be appropriate or feasible.

For systems running at contingency capacity Tier 1, the ELSO guideline list of potential contraindications can be found in Table 1. In general, ECMO should be avoided in patients with significant pre-existing co-morbidities, uncontrolled bleeding, inability to be anticoagulated or accept blood products, and should have a reasonable chance of long-term survival after resolution of COVID-19.15

Table 1: Contraindications for ECMO in systems functioning in contingency capacity Tier 1 (adapted from Shekar 2020)15

Relative contra-indications
Age ≥65
Body mass index ≥40
Immunocompromised
No legal medical decision-maker available
Advanced chronic underlying systolic heart failure
High-dose vasopressor requirement if not under consideration for V-A or V-VA ECMO
Absolute contra-indications
Advanced age
Clinical Frailty Scale Category ≥3
Mechanical ventilation >10 days
Significant underlying comorbidities:
      Chronic Kidney Disease (CKD) ≥III
      Cirrhosis
      Dementia
      Neurologic disease without potential for recovery
      Disseminated malignancy
      Advanced lung disease
      Uncontrolled diabetes with chronic end-organ dysfunction
      Severe deconditioning
      Protein-calorie malnutrition
      Severe peripheral vascular disease
      Pre-existing life-limiting condition
      Non-ambulatory or unable to perform activities
Severe multi-organ failure
Severe acute neurologic injury
Uncontrolled bleeding
Contraindications to anticoagulation
Inability to accept blood products
Ongoing cardiopulmonary resuscitation

Discontinuing ECMO
The possibility of discontinuing ECMO for futility should be discussed with the family prior to cannulation.17,24 The absence of hope for healthy survival should be considered as an indication for withdrawing ECMO, and is demonstrated by severe brain damage, severe irreversible multi-organ failure, or absence of heart or lung recovery without a durable option for replacement (ventricular assist device or transplant). The optimal timing for determining absence of recovery will vary by center, but no cardiac function for 3-5 days on V-A ECMO would meet the definition of futility in many ECMO centers.24 Establishing futility in pulmonary recovery for patients on V-V ECMO is challenging. A definition of futility after 2-3 weeks of no lung function has been challenged in recent years after observation of favorable outcomes after prolonged ECMO runs for patients with ARDS.25

Conclusion
COVID-19 related cardiopulmonary failure such as ARDS and cardiogenic shock or massive pulmonary embolism can be successfully supported with ECMO. Judicious patient selection is important to enable maximal benefit and optimized outcomes with this limited resource during a pandemic.

References

  1. Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020;382:1708-20.
  2. Huang R, Zhu L, Xue L, et al. Clinical findings of patients with coronavirus disease 2019 in Jiangsu province, China: a retrospective, multi-center study. PLoS Negl Trop Dis. 2020;14:e0008280.
  3. Liang WH, Guan WJ, Li CC, et al. Clinical characteristics and outcomes of hospitalised patients with COVID-19 treated in Hubei (epicentre) and outside Hubei (non-epicentre): a nationwide analysis of China. Eur Respir J 2020;55:2000562.
  4. Richardson S, Hirsch JS, Narasimhan M, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA 2020;323:2052-9.
  5. Thompson BT, Chambers RC, Liu KD. Acute respiratory distress syndrome. N Engl J Med 2017;377:1904-5.
  6. Papazian L, Aubron C, Brochard L, et al. Formal guidelines: management of acute respiratory distress syndrome. Ann Intensive Care 2019;9:69.
  7. Gallo de Moraes A, El-Yafawi R, Oeckler RA. Early neuromuscular blockade in the acute respiratory distress syndrome. N Engl J Med 2019;381:787.
  8. Combes A, Slutsky AS, Brodie D. ECMO for severe acute respiratory distress syndrome. N Engl J Med 2018;379:1091-2.
  9. Goligher EC, Tomlinson G, Hajage D, et al. Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome and posterior probability of mortality benefit in a post hoc Bayesian analysis of a randomized clinical trial. JAMA 2018;320:2251-9.
  10. Bunge JJH, Caliskan K, Gommers D, Reis Miranda D. Right ventricular dysfunction during acute respiratory distress syndrome and veno-venous extracorporeal membrane oxygenation. J Thorac Dis 2018;10:S674-82.
  11. Chow J, Alhussaini A, Calvillo-Argüelles O, Billia F, Luk A. Cardiovascular collapse in COVID-19 infection: the role of veno-arterial extracorporeal membrane oxygenation (VA-ECMO). CJC Open 2020;2:273-77.
  12. Bellani G, Laffey JG, Pham T, et al. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA 2016;315:788-800.
  13. Sukhal S, Sethi J, Ganesh M, Villablanca PA, Malhotra AK, Ramakrishna H. Extracorporeal membrane oxygenation in severe influenza infection with respiratory failure: a systematic review and meta-analysis. Ann Card Anaesth 2017;20:14-21.
  14. Alshahrani MS, Sindi A, Alshamsi F, et al. Extracorporeal membrane oxygenation for severe Middle East respiratory syndrome coronavirus. Ann Intensive Care 2018;8:3.
  15. Shekar K, Badulak J, Peek G, et al. Extracorporeal Life Support Organization COVID-19 interim guidelines. ASAIO J 2020;Apr 29 [Epub ahead of print].
  16. Extracorporeal Life Support Organization (ELSO website). 2020. Available at: www.elso.org. Accessed 6/16/2020.
  17. ECMO in Covid-19 (ELSO website). 2020. Available at: https://www.elso.org/Registry/FullCOVID19RegistryDashboard.aspx. Accessed 6/16/2020.
  18. EuroELSO. EuroELSO Survey on ECMO use in Adult Patients with COVID-19 in Europe (ELSO website). 2020. Available at: https://www.euroelso.net/covid-19/covid-19-survey/. Accessed 07/01/2020.
  19. Li Bassi G, Suen J, Barnett AG, et al. The COVID-19 Critical Care Consortium observational study: design and rationale of a prospective, international, multicenter, observational study (medRxiv website). 2020. Available at: https://www.medrxiv.org/content/10.1101/2020.05.29.20115253v1. Accessed 6/16/2020.  
  20. Takeda S. Nationwide system to centralize decisions around extracorporeal membranous oxygenation use for severe COVID-19 pneumonia in Japan. Acute Med Surg 2020;7:e510.
  21. Yang X, Cai S, Luo Y, et al. Extracorporeal membrane oxygenation for coronavirus disease 2019-induced acute respiratory distress syndrome: a multicenter descriptive study. Crit Care Med 2020;May 18 [Epub ahead of print].
  22. Fried JA, Ramasubbu K, Bhatt R, et al. The variety of cardiovascular presentations of COVID-19. Circulation 2020;141:1930-6.
  23. ELSO Adult Cardiac Failure Supplement to the ELSO General Guidelines (ELSO website). 2013. Available at: https://www.elso.org/Portals/0/IGD/Archive/FileManager/e76ef78eabcusersshyerdocumentselsoguidelinesforadultcardiacfailure1.3.pdf. Accessed 6/16/2020.
  24. ELSO Guidelines for Cardiopulmonary Extracorporeal Life Support (ELSO website). 2017. Available at: https://www.elso.org/Portals/0/ELSO%20Guidelines%20For%20Adult%20Respiratory%20Failure%201_4.pdf. Accessed 6/16/2020.
  25. Rosenberg AA, Haft JW, Bartlett R, et al. Prolonged duration ECMO for ARDS: futility, native lung recovery, or transplantation? ASAIO J 2013;59:642-50.

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure

Keywords: Heart Failure, Extracorporeal Membrane Oxygenation, Respiratory Distress Syndrome, Adult, Shock, Cardiogenic, COVID-19, severe acute respiratory syndrome coronavirus 2, Coronavirus, Prone Position, Respiration, Artificial, Neuromuscular Blockade, SARS Virus, Vasoconstriction, Vasodilator Agents, Hypercapnia, Carbon Dioxide, Pneumonia, Viral, Oxygen, Influenza A Virus, H1N1 Subtype, Cardiopulmonary Bypass, Retrospective Studies, Survival Rate, Bayes Theorem, Oxygenators, Cardiac Output, Low, Influenza, Human, Control Groups


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