Prolonged Prone Ventilation Decreases COVID-19 Mortality

Research at Massachusetts General Hospital recently demonstrated the safety and efficacy of prolonged prone positioning of patients with COVID-19 who required mechanical ventilation.

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"Early in the pandemic, we did not know which therapies would improve mortality in COVID-19 patients requiring mechanical ventilation," says Peggy Lai, MD, MPH, a physician-scientist in the Division of Pulmonary and Critical Care Medicine at Mass General. "This presented a unique opportunity to study existing therapies for similar disease processes, such as acute respiratory distress syndrome (ARDS), under conditions that allowed for an in-depth assessment of whether more effective methods exist."

Addressing Ventilator-induced Lung Injury

Approximately 5% of COVID-19 patients develop ARDS, which is associated with 30% mortality. These patients require admission to the intensive care unit (ICU) and treatment with mechanical ventilation. "A common misconception is that people with ARDS and COVID-19 die from a lack of oxygen," says Dr. Lai. "However, studies show that mortality is a consequence of multiple organ failure resulting from ventilator induced lung injury (VILI)."

The mainstay of therapy for ARDS is low tidal-volume ventilation, also known as lung protective ventilation. This approach reduces the rates of VILI and improves mortality in patients with ARDS.

Orientation of the lungs according to patient position (supine or prone) contributes to the effectiveness and safety of lung protective ventilation. Patients with ARDS accumulate fluid in the bases of the lungs, which are both the largest area and most important for gas exchange. This accumulated fluid subsequently reduces the available space for the lung to inflate during breathing, limiting appropriate oxygenation and gas exchange. Mechanical ventilation under these conditions can result in increased pressure in those areas, increasing the rates of VILI and driving an inappropriate immune response that can ultimately lead to organ failure.

PROSEVA, a randomized controlled trial published in The New England Journal of Medicine in 2013, compared outcomes between two groups of patients with severe ARDS who were under mechanical ventilation:

• Group 1 patients underwent ventilation in a prone position for at least 16 hours/day alternating with a supine position on a daily basis (intermittent supination)
• Group 2 patients underwent ventilation in a supine position only

Patients in Group 1 had significant improvements in mortality after 28-days (16.0% vs. 32.8%, respectively) and 90-days (23.6% vs. 41.0%, respectively). Subsequent studies reported that improved outcomes only occurred in patients undergoing proning for more than 12 hours per day. This raises the intriguing possibility that prolonging the duration of proning may improve mortality further; however, studies comparing the intermittent strategy from the PROSEVA trial with a prolonged approach have not been undertaken.

"In a given year pre-pandemic, only 5% to 10% of patients admitted to the Mass General ICU might have ARDS, with even fewer meeting the criteria for proning to support mechanical ventilation," explains Daniel Okin, MD, PhD, attending physician in the Division of Pulmonary and Critical Care Medicine at Mass General and the first author of the study. "Therefore, there were few opportunities for observational studies or prospective trials to assess different proning strategies."

Capitalizing on a Unique Opportunity

The pandemic created a unique opportunity to study ventilation techniques. It has always been known that turning a patient from prone to supine could be associated with worsening respiratory status, however there was never an opportunity to study whether this was associated with a difference in mortality.

"During the first wave of the pandemic, the absence of effective pharmacologic treatments for intubated COVID-19 patients prompted individual physicians to heavily utilize prolonged proning as a possible solution," Dr. Okin says. "The dramatic improvement in a patient's respiratory status after proning led some physicians to gradually extend the period a patient stayed in that position. In prolonged proning, the patient was not returned to a supine position on a daily basis but rather left proned until there was sustained clinical improvement. This variation in physician practice created an opportunity to study how duration of prone position affects mortality."

The focused presentation of the disease also proved beneficial to the research. "ARDS is the end physiologic syndrome that occurs due to a variety of processes, which can complicate treatment decisions," adds Dr. Okin. "However, because COVID patients displayed a uniform presentation, we were able to observe that prone positioning directly addressed the symptoms and helped support patient recovery while minimizing injuries related to intubation and ventilation."

Their observations during the pandemic, published in Chest, demonstrated not only the efficacy of prone position ventilation (PPV) in COVID-19 patients, but also the safety of prolonged PPV. Drs. Lai and Okin found that COVID-19 patients receiving prolonged PPV (24 or more hours) demonstrated significantly reduced 30- and 90-day all-cause mortality relative to patients receiving intermittent PPV (approximately 16 hours).

Although appropriate randomized controlled trials are necessary, Dr. Okin is encouraged by the findings that prolonged PPV is safe and associated with decreased mortality in patients with respiratory failure. "The data support prolonged PPV as a safe intervention and its strong association with improved outcomes."

Saving Lives Through Teamwork and Collaboration

The effectiveness of prolonged PPV resulted in its widespread adoption at Mass General based on the clear benefits to patients. As a result, Dr. Lai notes that performing a similar observational study would likely not be possible at this point, because finding a separate group of patients undergoing intermittent supination for study purposes would prove difficult.

Dr. Okin adds that being at Mass General during this period was particularly advantageous.

"A particular strength of our study is that it includes patients from academic and community hospitals—including Salem Hospital and Newton-Wellesley Hospital—increasing the likelihood that our findings will be generalizable to all hospital settings."

The potential importance of the findings is underscored by the hundreds of hours volunteered by physicians, residents, fellows, nurses, and respiratory therapists who performed chart reviews from the study period to make publication of the manuscript possible. "This method changed practice patterns at Mass General because everybody was determined to find a way to treat COVID patients successfully," Dr. Lai says. "These efforts demonstrate the incredible spirit of the people who work at these hospitals and their desire to provide the best possible care."

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