How does prone ventilation help? What is the evidence?

Mechanical ventilation in the prone position has been employed for more than four decades to treat severe hypoxemia in acute respiratory failure. In a report from 1976, Piehl and Roberts described the use of prone ventilation in five patients using a special type of bed that could rotate the patient through 180 degrees.1 The authors reported a mean increase in PaO2 by 47±16 mm Hg when all ventilatory parameters were held constant. It was also observed that children with severe cystic fibrosis often positioned themselves on their hands and knees to ease breathing efforts.2 Ventilation in the prone position became more widespread over the next two decades with the recognition of the non-homogenous nature of the diseased lung in acute respiratory distress syndrome (ARDS) and the concept of the “baby lung”.3 Let us look at the mechanism behind the beneficial effects of prone ventilation on lung and chest wall mechanics and improvement in ventilation/perfusion matching. 

How does prone ventilation result in more homogenous ventilation?  

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 collapse of the dependent areas of the lung as air is “squeezed out”.  

Difference in lung mass between dorsal and ventral regions 

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, a relatively larger lung mass (75%) exists at the bottom, dorsal half of the cone compared to the ventral half (25%). 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 the compression effect in the prone position. Thus, the distribution of ventilation becomes more uniform in the prone position.4 (Figure 1)

Figure 1. Imagine a line drawn halfway between the apex and the base of the lung cone. The dorsal half constitutes 75% and the ventral half 25% of the lung mass. When supine, gravitational effects result in collapse of the larger, dorsal lung mass. When prone, the dorsal areas of the lung are non-dependent and freed from gravitational effect and compression by the overlying lung, with a more homogenous distribution of ventilation   

Compression effect exerted by the heart 

Considering 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.5 Thus, a larger lung mass is subjected to compression by the heart in the supine position. In contrast, on assuming the prone position, the larger part of the lung lies above the heart and is relieved from compression by the weight of the heart. This phenomenon also contributes to more homogenous ventilation in the prone position.6

Difference in compliance between the ventral and dorsal chest wall 

In the supine position, the posterior wall of the chest is in contract with the surface; thus, it is relatively rigid with reduced 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.7  

The shape of the lung and the chest wall 

In the supine position, the ventral regions of the lung, which constitute the apex of the lung cone, is relatively free to expand as it aligns with the more spherical 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, elimination of 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. 

Effect of intra-abdominal pressure 

In the supine position, the intra-abdominal pressure exceeds the intrathoracic pressure; this phenomenon is exacerbated by obesity.8 The compressive effect of intrabdominal pressure 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.9

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.10

Does the prone position result in a more homogenous distribution of lung perfusion? 

Gravitational effects may seem to favor increased blood flow to the ventral areas of the lung in the prone position. However, it has been clearly demonstrated in experimental11 and human studies,12 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.6 The net result is a more homogenous distribution of perfusion in the prone compared to the supine position. The dorsal areas of the lung are better ventilated, while perfusion is maintained to these areas, thus, augmenting     ventilation/perfusion matching. 

What is the evidence?  

Let us consider the major randomized controlled trials (RCT) that evaluated the physiological effects and clinical efficacy of the prone position in hypoxemic patients on mechanical ventilation. 

In one of the early RCTs on the efficacy of ventilation in the prone position, Gattinoni et al. studied 304 patients.13 Patients were placed prone for 6 hours or more daily, for 10 days. The PaO2/FiOratio 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 had not been established as 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/FiOratios. 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/FiOratio of less than 300 mm Hg.14 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/FiOratios were 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.15 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/FiOratio 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/FiO100–200 mm Hg) and severe (PaO2/FiO<100 mm Hg) hypoxemia in the Prone-Supine II Study.16 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 at 28 days and 6 month in the subgroup of patients with severe hypoxemia. This study set the background for further investigation of the clinical efficacy of prone ventilation among patients with severe hypoxemia.  

The landmark PROSEVA trial unequivocally confirmed improved survival with prone ventilation among severely hypoxemic patients (PaO2/FiOratio <150 mmHg, FiO2 ≥0.6, and PEEP ≥5 cm H2O).17 This study included 466 patients were from 26 ICUs in France and one in Spain. Prone ventilation was carried out in 237 patients, 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 a lower mortality with prone ventilation in severe ARDS, especially when the duration of prone ventilation was more than 12 hours.18 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).19

The bottom line 

  • Prone positioning results in improved ventilation to the dorsal areas of the lung, which represent a larger tissue mass.
  • In the prone position, perfusion to the dorsal areas of the lung is maintained by the unique vascular geometry of the lung that overrides gravitational effects.
  • A more homogenous distribution of ventilation and perfusion results in more optimal ventilation/perfusion matching in the prone compared to the supine position.
  • Early RCTs that evaluated the clinical efficacy of prone ventilation were carried out during the period when the lung-protective strategy was not in common practice; although these studies revealed improved oxygenation on assuming the prone position, no beneficial effect was observed in clinical outcomes.  
  • Later studies that carried out prone ventilation for extended periods, combined with low tidal volume ventilation and limitation of plateau pressures revealed a trend towards improved survival. 
  • The PROSEVA trial conclusively demonstrated improved survival in patients who were severely hypoxic with a PaO2/FiOratio <150 mmHg with extended use of prone ventilation combined with a lung-protective strategy.
  • Most patients with severe ARDS should undergo a trial of prone ventilation prior to consideration of extracorporeal therapies.  

References

1.         Piehl MA, Brown RS. Use of extreme position changes in acute respiratory failure. Crit Care Med. 1976;4(1):13-14. doi:10.1097/00003246-197601000-00003

2.         Mellins RB. Pulmonary Physiotherapy in the Pediatric Age Group. Am Rev Respir Dis. 1974;110(6P2):137-142. doi:10.1164/arrd.1974.110.6P2.137

3.         Gattinoni L, Pesenti A, Avalli L, Rossi F, Bombino M. Pressure-volume curve of total respiratory system in acute respiratory failure. Computed tomographic scan study. Am Rev Respir Dis. 1987;136(3):730-736. doi:10.1164/ajrccm/136.3.730

4.         Gattinoni L, Busana M, Giosa L, Macrì M, Quintel M. Prone Positioning in Acute Respiratory Distress Syndrome. Semin Respir Crit Care Med. 2019;40(01):094-100. doi:10.1055/s-0039-1685180

5.         Gattinoni L, Pelosi P, Vitale G, Pesenti A, D’Andrea L, Mascheroni D. Body position changes redistribute lung computed-tomographic density in patients with acute respiratory failure. Anesthesiology. 1991;74(1):15-23. doi:10.1097/00000542-199101000-00004

6.         Johnson NJ, Luks AM, Glenny RW. Gas Exchange in the Prone Posture. Respir Care. 2017;62(8):1097-1110. doi:10.4187/respcare.05512

7.         Pelosi P, Tubiolo D, Mascheroni D, et al. Effects of the Prone Position on Respiratory Mechanics and Gas Exchange during Acute Lung Injury. Am J Respir Crit Care Med. 1998;157(2):387-393. doi:10.1164/ajrccm.157.2.97-04023

8.         Chiumello D, Cressoni M, Racagni M, et al. Effects of thoraco-pelvic supports during prone position in patients with acute lung injury/acute respiratory distress syndrome: a physiological study. Crit Care. 2006;10(3):R87. doi:10.1186/cc4933

9.         Mure M, Glenny RW, Domino KB, Hlastala MP. Pulmonary gas exchange improves in the prone position with abdominal distension. Am J Respir Crit Care Med. 1998;157(6 Pt 1):1785-1790. doi:10.1164/ajrccm.157.6.9711104

10.       Protti A, Cressoni M, Santini A, et al. Lung Stress and Strain during Mechanical Ventilation: Any Safe Threshold? Am J Respir Crit Care Med. 2011;183(10):1354-1362. doi:10.1164/rccm.201010-1757OC

11.       Wiener CM, Kirk W, Albert RK. Prone position reverses gravitational distribution of perfusion in dog lungs with oleic acid-induced injury. J Appl Physiol Bethesda Md 1985. 1990;68(4):1386-1392. doi:10.1152/jappl.1990.68.4.1386

12.       Nyrén S, Mure M, Jacobsson H, Larsson SA, Lindahl SG. Pulmonary perfusion is more uniform in the prone than in the supine position: scintigraphy in healthy humans. J Appl Physiol Bethesda Md 1985. 1999;86(4):1135-1141. doi:10.1152/jappl.1999.86.4.1135

13.       Luciano G, Gianni T, Antonio P, et al. Effect of Prone Positioning on the Survival of Patients with Acute Respiratory Failure. N Engl J Med. Published online 2001:6.

14.       Guerin C, Gaillard S, Lemasson S, et al. Effects of Systematic Prone Positioning in Hypoxemic Acute Respiratory Failure: A Randomized Controlled Trial. JAMA. 2004;292(19):2379. doi:10.1001/jama.292.19.2379

15.       Mancebo J, Fernández R, Blanch L, et al. A Multicenter Trial of Prolonged Prone Ventilation in Severe Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. 2006;173(11):1233-1239. doi:10.1164/rccm.200503-353OC

16.       Prone Positioning in Patients With Moderate and Severe Acute Respiratory Distress Syndrome: A Randomized Controlled Trial. :8.

17.       Guérin C, Reignier J, Richard J-C, et al. Prone Positioning in Severe Acute Respiratory Distress Syndrome. N Engl J Med. 2013;368(23):2159-2168. doi:10.1056/NEJMoa1214103

18.       Munshi L, Del Sorbo L, Adhikari NKJ, et al. Prone Position for Acute Respiratory Distress Syndrome. A Systematic Review and Meta-Analysis. Ann Am Thorac Soc. 2017;14(Supplement_4):S280-S288. doi:10.1513/AnnalsATS.201704-343OT

19.       Aoyama H, Uchida K, Aoyama K, et al. Assessment of Therapeutic Interventions and Lung Protective Ventilation in Patients With Moderate to Severe Acute Respiratory Distress Syndrome: A Systematic Review and Network Meta-analysis. JAMA Netw Open. 2019;2(7):e198116. doi:10.1001/jamanetworkopen.2019.8116

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