Improved survival in intubated patients with COVID-19 with longer prone positioning

Key takeaways:

• Patients intubated for COVID-19 were less likely to die when in prone positioning for prolonged periods.
• Facial edema was more prevalent in prolonged pronation, although total complications were the same.

Prolonged prone position ventilation for 24 hours or more was linked to less death at 30 and 90 days in COVID-19 patients on mechanical ventilation, according to study results published in CHEST.

Daniel Okin

“The key findings of our study are that prolonged proning is a safe and effective way to reduce mortality for patients intubated for COVID-19,” Daniel Okin, MD, PhD, instructor in medicine at Harvard Medical School and pulmonary physician-scientist at Massachusetts General Hospital, told Healio.

In a multicenter retrospective cohort study, Okin and colleagues evaluated 267 patients (median age, 62 years; 64.4% men; 55.4% white) intubated for severe COVID-19 and receiving prone position ventilation between March 11, 2020, and May 31, 2020, to determine if prolonged prone position ventilation (≥ 24 hours) showed better 30-day all-cause mortality rates than intermittent prone position ventilation (~ 16 hours with daily supination). They also compared 90-day all-cause mortality and complications associated with prone positioning between the two pronation lengths.

Researchers controlled for possible treatment selection bias with inverse probability treatment weights.

Within the total cohort, 157 patients received prolonged prone position ventilation, whereas 110 received intermittent prone position ventilation.

For the first prone session, researchers observed a median length of 40 hours in the prolonged group and 17 hours in the intermittent group (P < .001). This extended amount of time in the prolonged group was also observed when assessing median cumulative time in prone position (68 hours vs. 48 hours; P < .001).

Outcomes

In terms of mortality, researchers found lower rates in those receiving prolonged pronation than in those receiving intermittent pronation at 30 days (25.5% vs. 34.9%; adjusted HR = 0.475; 95% CI, 0.336-0.67) and at 90 days (29.3% vs. 37.7%; aHR = 0.638; 95% CI, 0.461-0.883) Adjusted HRs were calculated with multivariable Weibull survival models.

The mortality benefits of prolonged prone ventilation extended to patients with PaO₂/FIO₂ less than or equal to 150 mm Hg before pronation (30-day aHR = 0.357; 95% CI, 0.213-0.597; 90-day rates aHR = 0.562; 95% CI, 0.357-0.884). Both findings on mortality were surprising, Okin told Healio.

“As this is a retrospective study, we initially expected that patients who were left prone for greater than 24 hours would be substantially sicker and more likely to die,” Okin said. “As such, we were surprised by the magnitude of the reduction in mortality associated with prolonged proning.”

Another benefit of prolonged prone position ventilation is the associated reduction in the number of pronation and supination events. The median number of these events was one (95% CI, 1-2) in the prolonged group, whereas it was three (95% CI, 1-4) in the intermittent group, according to researchers.

“We suggest that reducing the number of pronation and supination events may decrease strain on the healthcare system in event of another COVID-19 surge or other viral respiratory illness triggered pandemic,” Okin told Healio.

Notably, researchers observed that the prolonged group did not contrast from the intermittent group when evaluating hospital length of stay, ICU length of stay and ventilator-free days at day 28.

Researchers found that 48.3% of patients experienced a prone-related complication and that there was no difference in overall burden based on prone strategy. There were more instances of facial edema found with prolonged pronation (15.3% vs. 6.4%; P = .04) but less peri-proning hypotension (1.3% vs. 7.3%; P = .03) than intermittent ventilation.

Future studies

Even though this study is from the early days of COVID-19, Okin told Healio that the results most likely do not change when thinking about different COVID-19 variants or treatments.

“Thankfully, treatments like Paxlovid and vaccines reduce the chances someone will develop severe COVID-19,” he said. “However, if someone were to require intubation for COVID-19, it is likely that prolonged prone ventilation will continue to be safe and efficacious regardless of prior treatment or COVID strain.

“Our work is the first to suggest that lengthening the duration a patient is placed prone for COVID-19 is associated with improved outcomes compared to an intermittent strategy,” Okin added. “An important next step will be the design of a randomized controlled trial of prolonged prone ventilation for COVID-19. Future studies will also need to evaluate whether our finding is generalizable to other causes of respiratory failure treated with intubation.”

This study by Okin and colleagues speaks to the importance of prolonged prone positioning in patients with severe COVID-19, according to an accompanying editorial by Savino Spadaro, MD, PhD, of the department of translational medicine at University of Ferrara in Ferrara, Italy, and colleagues.

“We believe that the clinical benefit coming from this study is that we should place these patients in prone positioning and keep them in prone positioning for a long time,” Spadaro and colleagues wrote. “According to our experience, many clinicians realized that prolonged prone positioning was a good strategy in patients with COVID-19 ARDS, but it is extremely encouraging now to know that we were right!”

Notably, Spadaro and colleagues wrote that there are some gaps in this study that should be investigated further, including if patients on prolonged ventilation would benefit from specific ventilatory settings and if these results can be found across various COVID-19 phenotypes.

Reference:

• Spadaro S, et al. CHEST. 2023;doi:10.1016/j.chest.2022.12.002.

For more information:

Daniel Okin, MD, PhD, can be reached at dokin@mgh.harvard.edu.