The PaO2/FiO2 ratio is an integral component to diagnose ARDS. It is one of the key parameters in the Berlin criteria.(24) The severity of the disease can be based on the ratio starting from 200-300 mmHg as mild, 100-200 as moderate, and <100 as severe conditions. Furthermore, some cohort studies linked the mortality percentage with PaO2/FiO2 levels, thus, making it become a valuable diagnostic, prognostic and clinical management tool.(25) Several studies have proven that prone position helped improve the ventilation-perfusion ratio due to expansion of the collapsed dorsal lung, reduction of the pleural pressure gradient and resulted in more homogenous distribution of the lung stress and strain.(23, 26) The PROSEVA study concluded that the 28-day mortality for severe ARDS patients assigned to prone position group was 16% and the unadjusted 90-day mortality was 23.6% compared to those in supine position, which were 32.8% and 41% respectively.(27) Since the pandemic began large numbers of hospitalized COVID-19 patients fulfilled the criteria of ARDS, which required invasive mechanical ventilation and a high level of patient care.(2, 6, 17) Numerous studies recommended prone positioning to help improve oxygenation and decrease work of breathing. This study demonstrated that COVID-19 patients with ARDS were associated with a higher PaO2/FiO2 ratio in the prone position group compared to supine position group. The findings of this meta-analysis parallel to prior studies, suggesting that prone positioning may improve oxygenation of injured lungs. The included articles were all cohorts, as there are no randomised controlled trials (RCTs) studies available, and were quality assessed using NOS which seven of the studies had a low risk of bias. However, the heterogeneity was substantial and the funnel plot suggested publication bias.
Additionally, this review also examined PaCO2 levels between the two groups and found that there was no significant association between the prone position with PaCO2 level, and that was not parallel to the prior studies.(27–31) Altered ventilation-perfusion ratio is a fundamental cause of abnormal gas exchange, which a low ratio induces hypoxemia and a high ratio induces hypercapnia.(28) Under normal physiology, PaCO2 is the primary control for air exchange, specifically for the minute ventilation or amount of air exchanged in the lungs per minute.(26, 29) It is responsible for affecting the pH, if there is an increase in PaCO2 then the pH will decrease and increase minute ventilation. Whereas, a decrease in PaCO2 will increase pH and decrease minute ventilation.(27, 30) A study conducted in 2003 by Gattinoni et al showed a reduction of PaCO2 level in ARDS patients in response to prone position. It stated that prone positioning reduced areas of distended lungs and the physiological dead-space, therefore it reduced shunts and resulted in reduction in PaCO2.(31) We included four cohort studies with low risk of bias to measure the outcome in PaCO2 level, and found the heterogeneity was extensive. The possible mechanism that proning did not significantly affect the level of PaCO2 was prone position using pressure-controlled ventilation would have a reduction of the chest wall compliance that reduced the tidal volume and minute ventilation.(32) Furthermore, prone position using volume-controlled ventilation would have the increased pleural pressure that reduced the venous return and affected the regional perfusion and increased the dead space.(32) Langer and colleague called it the CO2-non responders.(22)
Two articles mentioned mortality, Weiss et al showed 55% and Langer et al showed 40.4% of patients died in their study. Furthermore, Langer et al compared mortality between prone position versus supine position group, and reported that 112/409 patient’s death (28%) in the supine position group.(22, 23) However, the significance was not calculated by the author.
Langer et al compared ICU length of stay between the groups. For ICU length of stay, prone position patients had a significantly longer median of 16 days (Interquartile range 11–28) compared to median 12 days (Interquartile range 7–21) for the supine position group. This result supported other studies suggesting that prone positioning had longer time to death and in parallel to the beneficial changes of physiological parameters such as PaO2/FiO2 ratio.(33–36) The mechanical ventilation duration was also significantly longer in prone position group compared to supine position group.(21) The result might represent that prone positioning was applied as a salvage procedure on ARDS patients with more severe conditions. One other included study mentioned ICU length of stay with an average of 50.4 days.(22) However, Mittermaier et al did not compare between prone position and supine position. The study analysed 23 samples and divided into 3 subgroups, one of which prone position analysis. There were overlapping of samples between the subgroups, therefore, no direct comparison of prone position and supine position can be made. Thus, analysis of results from Langer and Mittermaier could not be performed.
This review focused on comparing the benefit of prone position in intubated COVID-19 patients with ARDS. All trials included in this review were observational studies in nature, while RCT studies were not yet available. Other limitations were the high degree in heterogeneity, risk of publication bias, no standardized prone position protocol, and the certainty of the measured outcome was very low.