In March of 2020, Brigham and Women’s Hospital purchased four additional extracorporeal membrane oxygenation (ECMO) machines to prepare for a possible surge of COVID-19. It wasn’t yet clear if ECMO could support critically ill COVID-19 patients, but early reports from China had shown promise.

The first wave of patients with COVID-19 arrived at the Brigham in late March. With more machines in place, the Brigham could offer ECMO support to 14 patients at a time. Many of the most critically ill patients were put on ventilators, and 13 patients transitioned to ECMO. Due to thoughtful and timely deployment, 70 percent of the patients who received ECMO made full recoveries.

“We considered ECMO as a support modality for COVID-positive patients who suffered from respiratory failure that was refractory to all standard ventilatory management,” said Antonio Coppolino, III, MD, a thoracic surgeon of The Lung Center at Brigham and Women’s Hospital. “In close collaboration with our vigilant ICU staff, the ECMO team successfully bridged the majority of these critically ill patients to recovery.”

ECMO Supports Respiratory Recovery by Resting the Lungs

ECMO functions by alleviating the work of the lungs when they are damaged. To do this, the machine pumps blood out of the body, oxygenates it and removes excess carbon dioxide, and then returns the blood to the body.

Prolonged mechanical ventilation can cause lung damage, however. While it can be mitigated with lung-protective settings or prone positioning, damage from extended mechanical ventilation poses a significant risk, in particular for COVID-19 patients experiencing long-term respiratory failure.

“ECMO gives the lungs a period of rest and allows for respiratory recovery until the patient can be weaned back to standard ventilator modes,” said Dr. Coppolino. “ECMO also decreases our need for extreme ventilator settings, which can be injurious.”

Determining How ECMO Can Support COVID-19 Patients

Early in the pandemic, many hospitals across the country were conservative with ECMO while they determined how useful the technology would be in the context of a new virus. While ECMO has been helpful in the past when treating viral diseases, such as H1N1, COVID-19 was so new that it wasn’t clear how patients would respond to the therapy.

“Based on our prior experience with viral pneumonias and organ failure, we decided to support these patients with ECMO in hopes of recovering them,” said Daniel Rinewalt, MD, a cardiac surgeon at the Brigham. “For some illnesses, patients are unlikely to recover on ECMO once they go into multiorgan failure. But with viral illnesses, we had previously found that it’s reasonable to be aggressive and support all the organs.”

Dr. Rinewalt noted that COVID-19 patients were able to fully recover on ECMO even if they were sick for over a month. The Brigham’s experience suggests that ECMO could play an expanded role in patients with COVID-19 and respiratory failure going forward.

“We found that critically ill patients—often on long-term ventilation with progressive renal dysfunction—were surviving and discharged when placed on ECMO,” said Dr. Coppolino. “ECMO was a critical support modality in patients who otherwise would not have survived due to their advanced disease.”

Dr. Coppolino added that mounting an effective ECMO response, during the COVID-19 pandemic, in particular, required a strong multidisciplinary effort across specialties.

“At the Brigham, there was a massive multidisciplinary effort to deal with the problems that COVID-19 patients presented with, ranging from respiratory and cardiovascular to hematologic to renal issues,” said Dr. Coppolino. “Successfully bridging these patients on ECMO took a heroic team effort across many different subspecialties.”

ECMO Can Support Patients with Cardiac Failure

At the Brigham, ECMO was used in instances of cardiac failure, which has been reported in some COVID-19 patients. ECMO configurations can be converted in real-time to support the heart (veno-arterial), lung (veno-venous), or both (veno-arterio-venous) as required. For veno-arterial ECMO, it’s recommended that some respiratory failure is also present to consider using ECMO as opposed to other forms of mechanical support.

“Some patients arrived with heart and lung failure, while others arrived with respiratory failure and then proceeded to heart failure,” said Dr. Rinewalt. “We used ECMO to support these patients.”

Patients with COVID-19 who went into heart failure presented unique challenges, added Dr. Rinewalt. Many patients experiencing organ failure were young and otherwise healthy, so their bodies responded with septic-like physiology and high heart rate.

“We had to slow these patients’ abnormally fast heart rates with beta blockers so the ECMO circuit could adequately oxygenate enough of the overall circulating volume,” said Dr. Rinewalt. “That’s not something we normally have to do.”

Patients with COVID-19 also presented with more blood clots, which required management while the patients were on ECMO. Despite these challenges, the use of ECMO was able to bridge patients with multiorgan failure to complete recovery.

Using ECMO Early Can Help Mitigate Lung Damage

As a life-support modality, ECMO should be neither a first nor last resort. Traditional approaches should be tried first. These include prone positioning, pulmonary vasodilation and lung-protective ventilation. But if these methods don’t lead to improvement, then it’s essential to move to ECMO as soon as possible.

“ECMO must be used at the right time, before irreversible lung injury,” said Nirmal S. Sharma, MD, co-director of the Lung Transplantation Program at the Brigham. “Intense mechanical ventilation can augment lung injury and using ECMO helped de-intensify mechanical ventilatory support and mitigate further lung damage in most patients.”

Since ECMO is a resource-intensive therapy, it requires careful deliberation before use. Clinicians must balance several factors when deciding which patients are likely to benefit from ECMO. These include the patient’s age, underlying health conditions, the duration of mechanical ventilation and extent of lung damage. The World Health Organization recommends transferring patients to ECMO in cases of refractory hypoxemia.

The Brigham’s Guidelines for Using ECMO in COVID-19 Patients

At the Brigham, Drs. Sharma, Coppolino, Rinewalt and others created a set of guidelines to decide which COVID-positive patients may benefit from ECMO. These guidelines are part of broader COVID-19 protocols developed at the Brigham. Based on these guidelines, ECMO is suggested for patients showing no trend toward improvement, as well as the following indications:

• PaO2:FiO2 ratio is less than 80 mmHg for more than 6 hours, despite optimal management methods in place (see full guidelines for more detail)
• Pleural pressure is higher than 30 cm H2O on lung-protective ventilation
• pH is less than 7.2 for more than 3 hours
• PaCO2 is more than 80 mm Hg for more than 3 hours

Contraindications include, but are not limited to:

• Multiple organ failure (excluding cardiopulmonary)
• Inability to tolerate anticoagulation for initiation of therapy
• Use of mechanical ventilation for 10 days or longer (7 days if on high ventilator
• settings)
• Anticipated life expectancy is less than 6 months
• Significant baseline comorbidities

In March of 2020, Raghu R. Seethala, MD, the medical director of the Brigham’s ECMO mechanical support service, and Steven P. Keller, MD, PhD, a pulmonologist and critical care physician at the Brigham, published an earlier version of the Brigham’s ECMO guidelines in the Annals of the American Thoracic Society. An international group of ECMO providers recently released a longer consensus document on the use of ECMO for COVID-19. These guidelines continue to evolve as doctors learn more about the disease.

The Brigham’s Collaboration with Hospitals and ECMO Centers

Throughout the COVID-19 pandemic, the Brigham’s ECMO teams have shared their acquired knowledge with several hospitals that are now managing influxes of patients. This includes the recommendation to apply ECMO earlier in the disease process.

“There’s a learning phase to ECMO,” said Dr. Sharma. “For instance, we’ve learned that COVID-19 patients may have a cytokine storm because of the body’s massive inflammatory response to the virus. This makes supporting patients on ECMO challenging because their inflammatory state makes their demand for oxygen so high. You have to fine-tune your ECMO circuit to support these needs.”

Dr. Sharma encourages ECMO programs to reach out to the Brigham for guidance. In addition to consultation, the Brigham also plans to expand its ECMO program with a new travel program to serve the Greater Boston Area.

“In this program, Brigham providers will go to other hospitals with patients who have respiratory failure refractory to standard ventilation, and we will put them on ECMO,” said Dr. Coppolino. “Then we can transport them back to the Brigham for complex care.”

To learn more about the Brigham’s use of ECMO during COVID-19, please contact Nirmal Sharma at nsharma21@bwh.harvard.edu.