Prone Positioning in ARDS

Prone Positioning in ARDS

Written by – Dr Jose Chacko 

Edited By – Dr Swapnil Pawar

Prone positioning was first proposed in the 1970s as a method to improve gas exchange in ARDS. Subsequent observations of dramatic improvement in oxygenation with simple patient rotation motivated the next several decades of research. During COVID -19 pandemic, the debate on the utility of proning has been resurfaced.

Ventilation heterogeneity

In ARDS, widespread edema occurs leading to an increase in the weight of the lung. The dependent areas of the lung are compressed by the weight of the overlying, non-dependent areas of the lung, due to gravitational effect. This results in the collapse of the dependent areas of the lung as air are “squeezed out”. 

The lung assumes the shape of a cone with the apex directed ventrally and the base directed dorsally. If a line is drawn halfway between the apex and the base of the cone, there will be a relatively larger mass at the bottom half of the cone. Similarly, the lung mass is higher in the dorsal compared to ventral areas. In the supine position, gravity dictates that the relatively larger lung mass located in the dorsal areas undergo compression collapse. In contrast, in the prone position, the dorsal areas of the lung become non-dependent and are relatively free from gravitational effect and compression by the overlying lung. This results in the larger, dorsal lung mass being released from compression effect in the prone position. Thus, the distribution of ventilation becomes more uniform in the prone position.¹ 

Given the conical shape of the lung, in the supine position, approximately 20% of the lung mass is located above the heart, compared to 50% below.² Thus, a larger lung mass is subjected to compression by the heart. In contrast, on assuming the prone position, the larger part of the lung lies above the heart and relieved from compression by the weight of the heart. This phenomenon contributes to more homogenous ventilation.³

In the supine position, the posterior wall of the chest being in contract with the surface is relatively rigid with little movement. Compliance is determined by the anterior chest wall and the diaphragm. On turning prone, the posterior wall becomes non-dependent and more mobile; however, the posterior wall is less compliant compared to the anterior wall. This leads to increased air movement and recruitment of the ventral areas of the lung, resulting in a more uniform distribution of ventilation.⁴ 

In the supine position, the ventral regions of the lung, which constitutes the apex of the lung cone are relatively free to expand as it aligns with the shape of the anterior chest wall, allowing better ventilation of these areas. Gravitational forces also preferentially redistribute ventilation to the ventral regions. However, in the prone position, while the ventral areas of the lung remain free to expand and align with the chest wall, gravitational forces lead to better ventilation of the dorsal, non-dependent lung. Thus the forces that dictate ventilation are more balanced in the prone position, allowing more uniform ventilation of different regions of the lung.

In the supine position, the intra-abdominal pressure exceeds the intrathoracic pressure; this phenomenon is exacerbated by obesity.⁵ The compressive effect of high intrabdominal is higher in the dorsal and inferior areas of the lung. The adverse impact of weight and pressure generated by the abdominal contents on the thoracic cavity is attenuated in the prone position, leading to better ventilation of the dorsal and inferior areas of the lung.⁶

Overall, a more homogenous distribution of ventilation occurs in the prone position. More homogenous ventilation leads to a more uniform distribution of transpulmonary pressures, resulting in reduced lung stress.⁷

Perfusion heterogeneity

Gravitational effects may seem to favour increased blood flow to the ventral areas of the lung in the prone position. However, it has been clearly demonstrated in experimental⁸ and human studies,⁹ that regardless of posture, perfusion is always higher in the dorsal regions of the lung. The perfusion bias to the dorsal lung regions regardless of posture is related to the unique vascular geometry of the lung. Thus, although the gravitational effect tends to redistribute perfusion ventrally, vascular geometry ensures preserved blood flow to the dorsal areas of the lung in the prone position.³ The net result is a more homogenous distribution of perfusion in the prone compared to the supine position.

What is the evidence? 

In one of the early randomized controlled trials on the efficacy of the prone position, Gattinoni et al. studied 304 patients.¹⁰ Patients were placed prone for 6 hours or more daily, for 10 days. The PaO₂/FiO₂ ratio was significantly higher in the prone group; however, the relative risk of death was not different between groups at the end of the study period, at ICU discharge, and at 6 months. The low tidal volume strategy was not established practice during the study period; the mean baseline tidal volume was more than 650 ml in both groups. Besides, the study was stopped prematurely as recruitment slowed down over time. Although this study did not show improved mortality overall, on post-hoc analysis, a significantly lower 10-day mortality was observed with prone ventilation in the quartile with the lowest PaO₂/FiO₂ ratios. This seminal study paved the way for further investigation of the possible clinical benefits of prone ventilation among severely hypoxemic patients.

A French study conducted during the same period enrolled 791 patients with acute respiratory failure with a PaO₂/FiO₂ ratio of less than 300 mm Hg.¹¹ Prone positioning was carried out for at least 8 hours daily. The primary endpoint, the 28-day mortality was similar between the prone and supine groups (32.4% vs. 31.5%, p=0.74). There was no significant difference in the secondary endpoints, including the 90-day mortality, duration of mechanical ventilation, or the incidence of ventilator-associated pneumonia. Similar to the study by Gattinoni et al., the PaO₂/FiO₂ ratio was significantly higher with prone ventilation. Adverse events, including pressure sores, endobronchial intubation, and tube blocks were more common in the prone group. This study also demonstrated improvement in oxygenation with prone positioning, which did not translate to improved survival.

The Spanish study by Mancebo et al. represented a breakthrough, with the use of lower tidal volumes compared to the previous two studies and an extended duration of prone ventilation.¹² Plateau pressures employed were also lower in this study, with increasing awareness of the beneficial effects of a lung-protective ventilation strategy.  Sixty patients with severe ARDS were randomized to supine and 76 to prone ventilation. Prone ventilation was carried out for an average of 17 hours per day for a mean duration of 10.1 ± 10.3 days. Although not statistically significant, lower ICU mortality was observed among patients who underwent prone ventilation (43% vs. 58%, p=0.12). On multivariate analysis, independent risk factors for mortality included randomization to the supine position, the simplified acute physiology score II (SAPS II) at baseline and the time interval between the diagnosis of ARDS and study inclusion. Similar to previous studies, the authors observed a significantly higher PaO₂/FiO₂ ratio in patients who were prone ventilated. This study suggested that an extended duration of prone ventilation combined with a lung-protective strategy may improve survival in patients with severe ARDS.

Subsequently, Taccone et al. studied the clinical efficacy of prone ventilation among patients with moderate (PaO₂/FiO₂ 100–200 mm Hg) and severe (PaO₂/FiO₂ <100 mm Hg) hypoxemia in The Prone-Supine II Study.¹³ In the intervention arm, prone ventilation was carried out for 18 ± 4 hours per day (n=174) while in the control group, supine ventilation was carried out (n = 168). The overall mortality rate was similar between groups at 28 days and 6 months. Although not statistically significant, there was a trend towards lower mortality 28 days and 6 months in the subgroup of patients with severe hypoxemia. This study set the background for further investigation of the clinical efficacy for prone ventilation among patients with severe hypoxemia. 

The landmark PROSEVA trial unequivocally confirmed improved survival with prone ventilation among severely hypoxemic patients (PaO₂/FiO₂ ration <150 mmHg, FiO₂ ≥0.6, PEEP ≥5 cm H₂O).¹⁴ This study included 466 patients were from 26 ICUs in France and one in Spain. Two hundred and thirty-seven patients underwent prone ventilation while 229 patients were ventilated in the supine position. The mean duration of prone ventilation was 17±3 hours per session; the average number of sessions was 4±4 per patient.  The unadjusted 28-day mortality, the primary endpoint, was significantly lower with prone ventilation [16% vs. 32.8%; hazard ratio: 0.39 (0.25–0.63); p <0.001)]. The 90-day mortality was also significantly lower in the prone ventilated group. Improved survival was observed with prone ventilation after adjusting for baseline SOFA scores. Successful extubation at 90 days was significantly higher in patients who were prone ventilated; furthermore, ventilation-free days at 28 and 90 days were also significantly higher with prone ventilation. Besides, patients who were prone ventilated required less rescue therapy including the use of extracorporeal membrane oxygenation and administration of inhaled nitric oxide.

Several meta-analyses have evaluated the clinical efficacy of prone ventilation.  In a meta-analysis of eight randomized trials, Munshi et al. reported lower mortality with prone ventilation in severe ARDS, especially when the duration of prone ventilation was more than 12 hours.¹⁵ A network meta-analysis including 25 trials evaluated several ventilatory interventions among patients with moderate to severe ARDS who were ventilated with a lung-protective strategy. In this report, prone ventilation was associated with a significantly lower 28-day mortality (risk ratio: 0.69, 95% CI: 0.48–0.99).¹⁶

Summary –

There is sufficient evidence in favour of Prone positioning in ARDS.

The use of prone positioning should be considered in 3 situations –

1. Severe ARDS – P/F ratio < 150 mm Hg
2. Along with lung protective ventilation strategy
3. Only when proning >12 hours is feasible.

Prone positioning should be considered early in the course of disease process and in every patient before considering V-V ECMO.