key: cord-0781210-zwu1h60j
authors: Kon, Zachary N.; Smith, Deane E.; Chang, Stephanie H.; Goldenberg, Ronald M.; Angel, Luis F.; Carillo, Julius A.; Geraci, Travis C.; Cerfolio, Robert J.; Montgomery, Robert A.; Moazami, Nader; Galloway, Aubrey C.
title: Extracorporeal Membrane Oxygenation Support in Severe COVID-19
date: 2020-07-17
journal: Ann Thorac Surg
DOI: 10.1016/j.athoracsur.2020.07.002
sha: f61ab08c8ac9ffeca09b9f1a956d064e66c879f9
doc_id: 781210
cord_uid: zwu1h60j

Abstract: Background Coronavirus disease 2019 (Covid-19) remains a worldwide pandemic with a high mortality rate among patients requiring mechanical ventilation. The limited data that exists regarding the utility of extracorporeal membrane oxygenation (ECMO) in these critically ill patients shows poor overall outcomes. This paper describes our institutional practice regarding the application and management of ECMO support for patients with Covid-19 and reports promising early outcomes. Methods All critically ill patients with confirmed Covid-19 evaluated for ECMO support from March 10th, 2020-April 24th, 2020 were retrospectively reviewed. Patients were selected for ECMO support based on a PaO2/FiO2 (P/F) ratio<150 mmHg OR pH<7.25 with a pCO2>60 mmHg with no life-limiting comorbidities. Patients were cannulated at bedside and were managed with protective lung ventilation, early tracheostomy, bronchoscopies and proning as clinically indicated. Results Of 321 patients intubated for Covid-19, 77 (24%) patients were evaluated for ECMO support with 27 (8.4%) patients placed on ECMO. All patients were placed on veno-venous ECMO. Current survival is 96.3%, with only one mortality to date in over 350 days of total ECMO support. Thirteen patients (48.1%) remain on ECMO support, while 13 patients (48.1%) have been successfully decannulated. Seven patients (25.9%) have been discharged from the hospital. Six patients (22.2%) remain in the hospital of which four are on room-air. No healthcare workers that participated in ECMO cannulation developed symptoms of or tested positive for Covid-19. Conclusions The early outcomes presented here suggest that the judicious use of ECMO support in severe Covid-19 may be clinically beneficial.

Coronarvirus disease 2019 (COVID-19) results from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Approximately fifteen to twenty percent of hospitalized patients with COVID-19 develop a severe respiratory distress syndrome requiring endotracheal intubation, and the mortality rate in these patients is extremely high (50-90%) [1] [2] [3] [4] [5] .

The World Health Organization declared COVID-19 a pandemic on March 11 th , 2020 [6] . The number of people with this disease has increased exponentially since that time, with over 2.8 million cases and 190,000 deaths reported worldwide [7] The literature regarding the use of extracorporeal membrane oxygenation (ECMO) support in COVID-19 patients is scarce and most reports have involved only a small number of patients with poor outcomes. A pooled analysis of 17 patients, reported a 94.1% mortality rate [4] , and another study of 12 patients reported an early mortality rate of 42% with 33% of the surviving patients still on ECMO and 25% decannulated but remaining hospitalized [8] . Based on these data and anecdotal reports from Europe and China [9] , there is skepticism among physicians regarding the effectiveness of ECMO use in severe COVID-19.

However, previous reports with the use of ECMO in influenza [10] and other typical etiologies of adult respiratory distress syndrome (ARDS) [11, 12] were more promising. Given the paucity of data on the use of ECMO in COVID-19 and theoretical advantages that it might offer in this population, our institution has continued the judicious use of ECMO support for patients with COVID-19. The hypothesis of this study is that patient and lung recovery with the use of ECMO in severe COVID-19 is achievable, and a nihilistic approach to these patients is unwarranted. This report describes our experience with this approach during the surge phase of COVID-19 in New York City.

This is a retrospective analysis of all patients admitted to New York University Langone Health (NYULH) Manhattan campus from March 10 th , 2020 to April 24 th , 2020 with COVID-19 and severe respiratory failure requiring mechanical ventilation that were evaluated for ECMO support. COVID-19 was diagnosed by nasal pharyngeal swab for reverse transcriptase polymerase chain reaction (rtPCR) assay in all patients. The NYULH institutional review board approved this human subjects study (IRB #: i20-00611) and data were collected from direct chart review.

A multi-disciplinary team consisting of a cardiothoracic surgeon, critical care physician, and pulmonologist evaluated all patients referred for ECMO. Entry and inclusion criteria were based on the arterial partial pressure of oxygen (PaO 2 ) to fraction of inspired oxygen (FiO 2 ) ratio (P/F ratio), arterial blood gas, ventilator settings, patient functional status and comorbidities, and hemodynamic status. ECMO support was only offered to patients with a P/F ratio<150 mmHg OR a pH<7.25 with an arterial partial pressure of carbon dioxide (pCO 2 )>60 mmHg. Patients undergoing active cardiopulmonary resuscitation were not considered candidates for ECMO support. Additionally, patients with confirmed neurologic injury, known malignancy with poor prognosis, multisystem organ failure, with the exception of acute kidney injury during the current hospitalization, and age > 65 years were not deemed appropriate ECMO candidates. All patients deemed appropriate for further support underwent veno-venous (VV)-ECMO as the initial cannulation strategy, regardless of hemodynamic status or vasopressor requirement.

All patients placed on VV-ECMO were cannulated in the intensive care unit (ICU) at the patient's bedside. The primary cannulation strategy was via a percutaneous right femoral venous drainage cannula and right internal jugular (IJ) venous return cannula. Only if this access was not attainable was alternate access pursued. All personnel wore full personal protection equipment (PPE) per institutional policies (hair cover, N95 mask, face shield, gown, and two layers of gloves) upon entering the room. Two cardiothoracic surgeons with extensive experience in ECMO were present for each cannulation, with one cannulating the neck and one cannulating the femoral vein concurrently to minimize overall procedure and exposure time.

Ultrasound guidance was used for all cannulation access.

Ventilation/Oxygenation: All patients were managed with pressure control ventilation with peak inspiratory pressure (PIP)<25 mmHg, positive end-expiratory pressure (PEEP) 10-14 mmHg, respiratory rate≤16 breaths/minute, and FiO 2 ≤0.40. Ventilator support was not increased beyond these thresholds for persistent hypoxia, which was tolerated if no evidence of organ injury was present. ECMO circuit flow was titrated to oxygenation needs but did not exceed revolutions per minute (RPM) thresholds for possible hemolysis. In cases where persistent hypoxia could not be corrected by circuit flow red blood cell transfusion thresholds were modified to achieve adequate tissue perfusion [13] . Conversely, flow was maintained above 3 LPM to avoid oxygenator thrombus formation. Oxygenator FiO 2 was maintained at 1.0 for the entirety of support. pCO 2 management was controlled using the ECMO circuit by varying the sweep gas flow rate for a goal pCO 2 <45 mmHg, and mechanical ventilation was not altered.

When the sweep gas flow rate was less than 0.5 LPM, the gas flow was disconnected for 2 hours, with a repeat arterial blood gas. For patients with a pCO 2 <45 mmHg and P/F ratio>200 on two sequential clamp trials greater than 24 hours apart, they were deemed appropriate for ECMO decannulation. This was performed at bedside in all cases.

Tracheostomy/Airway Management: With the goal of decreasing sedation requirements and improving pulmonary toilet, early tracheostomy was planned within three days of ECMO cannulation. Broncho-alveolar lavage (BAL) was performed on every patient shortly after cannulation to identify potential co-infection that would alter treatment and to clear secretions.

Subsequent toilet bronchoscopies were performed as clinically indicated.

Anticoagulation: Therapeutic anticoagulation with an intravenous heparin infusion was initiated on every patient with a goal anti-factor Xa level>0.15 IU/mL and partial thromboplastin time (PTT)<70 seconds based on our previously published data [14] . Patients who developed thrombocytopenia were evaluated for heparin-induced thrombocytopenia (HIT) and transitioned to a therapeutic intravenous bivalirudin infusion with goal PTT of 40-60 seconds. HIT positive patients had their heparin coated systems exchanged for non-heparin coated systems.

Sedation/Paralytics: In the early part of the series, patients were sedated to achieve a Richmond agitation-sedation scale score of -4 to prevent dyssynchrony with mechanical ventilation, and many patients required pharmacologic paralysis. As the series progressed, more aggressive paralytic and sedation weans were initiated after tracheostomy placement.

After the initial nine cases, pharmacologic paralysis was terminated upon the initiation of ECMO support for all subsequent patients.

Prone positioning: While initial patients on ECMO were not routinely placed in the prone position, care strategy evolved to selectively prone patients as clinically indicated based on oxygenation and imaging. Patients were manually proned with a team consisting of anesthesiologists, a perfusionist, ICU nurses, and a respiratory therapist. No proning beds were used.

COVID-19 Targeted Therapy: On the basis of an interim institutional guidance protocol, all patients received azithromycin/hydroxychloroquine therapy for five days. No specific COVID-19 therapies were added post-cannulation, but they were continued if previously planned (Supplemental Table 1 ). However, selective use of moderate dose steroids was added for patients with persistent or up trending inflammatory clinical markers in the absence of obvious co-infection.

The primary outcome for this study was survival and lung recovery as defined by weaning off ECMO, mechanical ventilation and supplemental oxygen. Secondary outcomes were freedom from ECMO associated complications and COVID-19 infection among healthcare providers from patient transmission.

From March 10 th , 2020 to April 24 th , 2020, >1900 confirmed COVID-19 patients were admitted to NYULH Manhattan campus. Four-hundred twelve patients were admitted to the ICU, and 321 patients required endotracheal intubation. Seventy-seven patients were evaluated for ECMO during that time period. Twenty-seven patients met our patient selection criteria and fifty patients were deemed not to be appropriate candidates for ECMO support. Four patients were declined because they were undergoing active cardiopulmonary resuscitation (Figure 1) . 

All patients were placed on VV-ECMO and were cannulated at the bedside in the ICU without fluoroscopic equipment. Ultrasound was used for access of both the femoral vein and right IJ vein in all cases. Right IJ and right femoral venous cannulation was achieved in 25 patients (93%); one patient with a history of hemodialysis and kidney transplant had an occluded right IJ vein and required placement of the return cannula in the contralateral femoral vein. In another patient, we were unable to confirm appropriate wire position from the right femoral vein, so the drainage cannula was placed via the left femoral vein (Supplemental Table   3 ). No vascular injuries or major bleeding complications related to cannulation occurred. Mean total in-room time for cannulation was 21 ± 5 minutes.

To date, the primary outcome was observed in 11 (41%) patients who have been weaned from ECMO support, mechanical ventilation and supplemental oxygen. Two additional patients have been weaned and decannulated from ECMO support but remain on mechanical ventilation with modest settings. Seven (26%) patients have been discharged from the hospital ( Figure 2 ). Post-decannulation survival is 100% to date. Thirteen (48%) patients remain on ECMO support. One patient (4%) has died on ECMO support. This patient had shown significant lung recovery and was approaching decannulation, but acutely suffered a pulseless electrical activity arrest from unknown etiology. The median time on ECMO for all patients was 11 (IQR:10-14) days (as of 4/24/2020), with a median time of 11 (IQR:10-14) days on ECMO for all patients that were decannulated ( Table 2, Supplemental Table 4 ). 

The ECMO team included four cannulating physicians and 16 perfusionists that participated across the 27 bedside cannulations. To date, none of these 20 team members have developed any symptoms of fever, general malaise, cough, shortness of breath and/or have tested positive for COVID-19. Seventeen (85%) of these team members have agreed to testing and all have been negative via nasal pharyngeal swab for rtPCR assay.

While COVID-19 spreads across the globe, healthcare systems continue to be overwhelmed with critically ill patients that require ICU care and mechanical ventilation. Many of these intubated patients will have progression of the disease that leads to a fatal outcome. In a recent report of 5,700 patients hospitalized with COVID-19 from another New York City Health System, the mortality rate of patients who required intubation was 88.1% [5] . However, for a select portion of these patients who remain critically ill despite optimal medical therapy, ECMO support appears to have a valuable role in preventing mortality. Our experience differs from other published data which suggested that ECMO is of limited value for patients with COVID-19.

Although still early in many of these patients' clinical courses, these initial outcomes are encouraging with an overall current survival of 96%, with nearly half of the patients already weaned from ECMO support, mechanical ventilation and supplemental oxygen. Furthermore, a significant number of these patients have been discharged from the hospital.

The reason for the increased early survival observed in this study is likely multifactorial.

An established ECMO program was already in place with the infrastructure and expertise to care for patients with complex disease. Our screening process for the use of ECMO involves a team of physicians from multiple sub-specialties as well as specific selection criteria similar to those outlined by the Extracorporeal Life Support Organization (ELSO) recommendations for ECMO use patients with COVID-19 [15] . Only patients with a previously normal functional status and no pre-existing life-threatening medical comorbidities were placed on ECMO. After initiation of ECMO, our specialized multidisciplinary team of cardiothoracic surgeons, intensivists, and pulmonologists managed the care of these patients.

All patients received the same treatments as patients with traditional etiologies of ARDS, and this was the overarching theme of their care. Protective lung ventilation strategies with low inspiratory pressures and low FiO 2 were used for every patient to prevent ventilator associated lung injury. In addition, patients that would benefit from proning due to continued hypoxemia on full ECMO support were manually proned.

Tracheostomies were performed early in all patients using a novel percutaneous technique that minimized aerosolization [16] , with a potentially decreased risk of viral transmission to health care providers. The routine use of tracheostomy allowed for better airway secretion management and ultimate ventilator weaning post-ECMO decannulation. Early tracheostomies also facilitated faster weaning of sedation and paralytics, which allowed some patients to participate with physical therapy and sit in a chair while on ECMO.

Additionally, toilet bronchoscopies were performed commonly in these patients as clinically indicated. The addition of bronchoscopies and BAL helped diagnose the presence of concurrent infection. The global rate of superimposed bacterial and fungal pneumonia in COVID-19 patients is unknown, as BAL is not routinely performed due to fear of increasing the risk of viral transmission to healthcare workers. To mitigate this concern, the ventilator was placed on standby to reduce the risk of aerosolization during bronchoscopies. The combination of these unique strategies likely contributed to our promising early outcomes.

Another important finding is that our technique appears to be safe for our healthcare providers. All providers who participated in the cannulation of ECMO patients remain COVID-19 negative based on symptoms or testing. This is likely the result of a combination of the full PPE used by all healthcare providers, and an ECMO cannulation strategy designed to minimize the amount of time spent in the room for the providers. All ICU rooms at our institution are also single-bed negative pressure rooms. Of note, those providers that performed tracheostomies, bronchoscopies and BAL also all remain COVID-19 negative [16] . pre-discharge. ECMO: Extracorporeal membrane oxygenation.

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