Distribution of aerated, poorly aerated, and non-aerated lung regions at end expiration (a and c) and end inspiration (b and d) in supine and in prone position. The springs are the elastance shown for the lung and the chest wall. Panels (e and f) display the distribution of lung perfusion in supine and in prone position. See text for further explanation
The prediction of oxygenation improvement with prone position is difficult. CT scan studies failed to demonstrate a correlation between the improvement in oxygenation in prone and the amount of consolidated areas  or the potential of lung recruitment  in the supine position. One of the single predictors of oxygenation improvement with proning has been shown as the chest wall compliance (CCW) in the supine position and its reduction in the prone position .
6.2.2 Respiratory Mechanics
The increase in CCW in the prone position , which has also been documented by other authors [8, 18], partly results from an increase in abdominal pressure . However, whether or not abdomen is supported in the prone position does not change the effect on either oxygenation or end-expiratory lung volume . If we assume a decrease in CCW in the prone position from the supine position, the absence of change in the compliance of the respiratory system (CRS) should indicate a concomitant increase in lung compliance (CL). By contrast a decrease in CRS should herald an increase in CL and, hence, a net lung recruitment. Interestingly, across the trials the impact of the prone positioning on CRS was not similar. In the trial by Mancebo et al. , CRS has been found decreasing with proning, while no significant change has been observed in the PROSEVA trial . Two CT scan studies demonstrated alveolar recruitment in the prone position as compared to the supine position in patients taken as own control [22, 23]. This result was more likely focal as compared to diffuse loss of aeration in one study . In the other CT scan study, alveolar recruitment was observed regardless the patient had a low or a high potential of recruitability in the supine position . This finding of prone position-induced lung recruitment would indicate that higher PEEP should be set in prone position than in the supine position. A recent study showed that actually the clinicians did not use as much PEEP as they should have in the prone position . The level of PEEP in the prone position is still an open question for two reasons. First, an experimental study in pigs concluded that prone position had same effect as PEEP of 7 cmH2O would have on oxygenation by investigating various combinations of PEEP and position . Second, using lower PEEP may have hemodynamic benefits, as discussed below. Furthermore, it has been suggested that the strongest predictor of mortality in ARDS patients is the driving pressure of the respiratory system, well above CRS, tidal volume, or plateau pressure . As prone position may affect CRS due to its effect on CCW, it is not clear whether same results may be relevant for the use of proning. By computing the trans-pulmonary driving pressure from the data of a recent trial, the following results deserve mention . Between patients in whom PEEP was set from esophageal pressure as compared to those receiving PEEP set from a PEEP/FiO2 table, the mean value of trans-pulmonary driving pressure was 10.6 and 10.5 cmH2O, respectively. At day 3 after randomization, these values averaged 7.3 and 8.7 cmH2O, respectively. The reduction of trans-pulmonary driving pressure was significantly higher in the esophageal pressure group than in the control group and significantly greater in survivors than in non-survivors (personal communication with D Talmor).
6.2.3 Lung Protection from VILI
Protecting the lung from VILI is the main goal of mechanical ventilation. There are several lines of evidence to support that prone position can achieve this objective. The abovementioned CT scan studies showed that not only prone position could promote lung recruitment but also reduce hyperinflation [22, 23]. However, only higher PEEP used in the prone position was able to minimize cycling opening and closure during tidal breath, the so-called atelectrauma . The lung concentration of pro-inflammatory cytokines was found reduced in prone as compared to supine position in ARDS patients . The overall stress and strain is reduced in prone position in ARDS patients . Experimental studies found that prone position reduced VILI due to high tidal volume and made it more homogeneously distributed throughout the lung in dogs , increased the time required to double elastance of the respiratory system as compared to supine position in rats , modulated the expression of a kinase strongly involved in VILI in rats , and attenuated VILI due to injurious ventilation in mice deficient for this kinase . Therefore, there is a strong background for VILI prevention by using prone position. The likely mechanism for this to occur is by making the lung distribution of tidal volume, and hence the strain more homogenous, and by minimizing the compression of the lung by its own weight and also that of the heart. It should be made clear from the onset that VILI was not assessed in the trials that investigated the effect of prone position on patient outcome as we shall discuss below. That means that the mechanics by which prone position improves survival in ARDS patients should stem from these beneficial physiological effects.
6.3 Patient Outcome
Five large trials (Table 6.1) have been performed over the last 15 years comparing prone position to supine position, and the results on patient survival can be summarized as follows. First, the mortality was significantly only reduced in patients with the highest severity of hypoxemia (PaO2/FiO2 <100 mmHg) as demonstrated in a patients’ data meta-analysis . Second, this was confirmed in a single trial in select ARDS patients with moderate to severe ARDS (PaO2/FiO2 <150 mmHg and PEEP of 5 cmH2O or more and FiO2 of 0.6 or more at the time of inclusion) after a 12–24-h stabilization period. Third, subsequent meta-analysis suggested that benefit of proning on survival was associated with length of proning sessions, lung protective ventilation, and intensity of hypoxemia .
Main characteristics of five large multicenter prospective randomized trials comparing prone to supine position in ARDS patients
Trial (first author and acronym)
Gattinoni PS I 
Guérin DDDV 
Taccone PS II 
Guérin PROSEVA 
n patients (SP/PP groups)
% of ARDS (SP/PP groups)
PaO2/FiO2 (mmHg) at the time of randomization
Tidal volume (mL/kg) at the time of randomization
PEEP at the time of randomization (cmH2O)
PP session duration (average hours per session)
Mortality (SP/PP groups) (%)
6.3.2 Why Survival Goes Up with the Prone Position in the Most Severely Hypoxemic Patients?
As discussed previously, the physiologic beneficial effects of prone positioning should explain its effect on survival. However, the cause to effect relationship between them is not so clear in particular regarding oxygenation.
Even though there is no doubt that oxygenation was found better in the prone as compared to the supine group, the fact that better survival results from better oxygenation is not supported by the analysis of the data. In the PROSEVA trial , the patients in each group were split into four quartiles of PaO2/FiO2 ratio at the time of randomization. The benefit of proning was present at every quartile. Furthermore, the magnitude of change in oxygenation during the first proning session was not associated with a better survival . This result is in line with previous studies [37, 38]. Therefore, even though prone positioning may prevent death from life-threatening hypoxemia, and in this way proning can be seen as a rescue therapy, this mechanism is not the main factor to explain survival improvement with this procedure.
VILI prevention is the second candidate for explaining survival improvement with prone. Even though it is highly likely, it has not been directly demonstrated in the trials because these did not include any assessment of VILI.
The hemodynamic effects may be a mechanism of better survival with prone that has not receive much attention. The use of proning in the early experience regularly showed lack of hemodynamic worsening contrary to the well-known deleterious effects of higher PEEP. In the PROSEVA trial, there was a greater number of days where patient was not in shock, i.e., 2 days greater for the prone group as compared to the supine group . Recently, prone position was associated with an even increase in cardiac output in those patients who were preload dependent in the supine position . By increasing abdominal pressure, prone position may push the stressed intravascular volume into the right atrium in patients with reserve of preload. Interestingly in this study, the improvement of oxygenation in prone was less important in those patients with the increased cardiac index than in those with no change (with no preload reserve). This may be explained by the increased intrapulmonary shunt resulting from the increased cardiac index as originally demonstrated by Dantzker . As important, proning has a beneficial impact on the right ventricle function , and this may explain survival benefit with this strategy. The right ventricle function can be impaired as a result from an acute increase in afterload due to different contributing factors that are working in ARDS, like hypoxemia, hypercapnia, overdistension . This culminates into the acute cor pulmonale (ACP) and acute right ventricle failure. ACP has been found to occur in 22% of ARDS patients and is a predictor of worst outcome . Earlier, Vieillard-Baron by using transesophageal echocardiography found that prone position reverted acute cor pulmonale in ARDS patients . Very recently a multicenter observational study in ICUs in France over a large cohort of ARDS patients confirmed these findings and found that ACP was an independent predictor of death . Interestingly in this cohort, prone position was an independent factor associated with better survival. By allowing lower PEEP, and hence minimizing the risk of overdisetnsion as previously discussed, and by improving oxygenation, prone position could prevent ACP occurrence and could be a strategy for the clinicians facing ACP in association with inhaled nitric oxide and dobutamine [41, 42]. This real preventive and curative effect of ACP by using prone position should be tested prospectively in trials, and, as a whole, the hemodynamic effects of prone position deserve further studies.
Finally, prevention of ventilator-associated pneumonia (VAP) could be a mechanism by which prone position reduces mortality. Prone position may reduce VAP by enhancing respiratory secretion removal. However, the attributable mortality of VAP is low, in particular in ARDS patients . Indeed, a post hoc analysis of the PROSEVA trial found that prone position was not associated with a reduction in VAP .
6.4 Clinical Practice
In daily practice the rate of use of prone position is still limited (Table 6.2). The most recent data, not published as yet, from the large observational international Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) study found that prone position was used in 7% of ARDS patients and in 14% of those with severe ARDS. It is likely that the risk of complications, like vascular line kinking or withdrawal and endotracheal tube obstruction or removal, are barriers that restraint the caregivers from performing prone positioning more frequently. It should be noted that in the PROSEVA trial, the rate of these complications was not significantly different between the two groups contrary to previous trials. This may reflect the fact that centers that participated in this trial have used prone positioning for many years and were able to provide with a safe procedure. Another concern is the pressure sores that occurred more frequently in the prone than in the supine position , which should deserve innovative preventive means.
Rate of use of prone position in ARDS patients
Trial acronym or first author
Randomized controlled trials
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