Prone Positioning Controversies in the ICU

2015 - 2 April – Clinical Controversies
Claude Guérin, MD, PhD
In this article, a world-renowned expert discusses the efficacy of prone positioning.


The prone position has been used for decades in patients with the acute respiratory distress syndrome (ARDS). Early clinical experience reported the frequent and sometimes dramatic improvement in oxygenation in these patients who, by definition, are severely hypoxemic. These results contributed to viewing prone positioning as a rescue therapy to be utilized—not necessarily early—in the treatment course of ARDS. Pathophysiological studies found that oxygenation improvement resulted from a reduction in intrapulmonary shunt due to better ventilation in the dorsal lung regions that continued to receive most of the blood flow in the prone position. Randomized controlled trials demonstrated that the chance for better oxygenation was significantly higher in the prone group compared to the supine group.
 
As prevention of ventilator-induced lung injury (VILI) was recognized as a major goal of mechanical ventilation, the role of prone positioning was then regarded in light of its capability to prevent/minimize/delay VILI. Several lines of evidence strongly suggested that the prone position prevented VILI. In normal dogs, Broccard et al(1) demonstrated a significant reduction of VILI induced by high tidal volume ventilation together with a homogenization of the distribution of VILI throughout the lungs. Prone positioning in rodents was associated with a significant increase in the time required to double the elastance of the respiratory system during high tidal volume mechanical ventilation.(2) In another study, the prone position modulated both activation and expression of a kinase strongly involved in VILI,(3) and mice deficient for that kinase were highly susceptible to VILI, which was prevented by proning. Mutoh et al(4) found that the pleural pressure—and hence the transpulmonary pressure ventral-to-dorsal gradient—was narrowed and more homogenously distributed in lung-injured pigs placed in the prone position. This suggested less stress throughout the lungs for the same tidal volume and pressure at the airway opening. In surfactant-depleted sheep, Richter et al(5) reported that the distribution of intrapulmonary shunt was made homogeneous in the prone position compared to the supine position; in particular, the large intrapulmonary shunt in the dorsal caudal lung regions was markedly reduced. Computed tomography scan studies in ARDS patients consistently found that the prone position decreased hyperinflation and promoted lung recruitment.(6,7) Furthermore, this effect was observed in patients with a high or a low potential for recruitment in the supine position in response to a given change in airway pressure, though the reduction in tidal opening and closure of the small airways (i.e., the reduction in tidal recruitment that is thought to be beneficial) with the prone position was primarily observed in patients with a high potential of recruitment in the supine position and under high positive end-expiratory pressure (i.e., PEEP of 15 cm H2O) in the prone position.(7)
 
All of these physiological effects are beneficial. The next step is to determine whether physiologic benefits translate into patient outcome benefits. After the completion of five large randomized controlled trials,(8-12) the answer to this issue should be yes—but in selected ARDS patients with no contraindication to prone positioning and for intensive care unit teams with expertise in the procedure. Two meta-analyses(13,14) consistently found that prone positioning significantly increased survival in ARDS patients with a PaO2/FIO2 ratio less than 100 mm Hg at the time of inclusion in the trial. No difference in survival was observed for the less severely hypoxemic patients or the entire population. This led experts to recommend use of prone positioning in severe ARDS patients(15) according to the new Berlin definition for ARDS.(16)
 
The PROSEVA multicenter randomized controlled trial was performed in selected ARDS patients.(12) Patients were included if they met severity criteria (PaO2/FIO2 <150 mm Hg with PEEP ≥5 cm H2O, FIO2 ≥0.6 and tidal volume 6 mL/kg predicted body weight) within 12 to 24 hours after the ARDS diagnosis. Several exclusion criteria were applied. Some pertained to contraindication to prone positioning, others to the design of the trial, such as patients receiving extracorporeal life support, having a lung transplant, having severe chronic respiratory failure requiring oxygen therapy or noninvasive ventilation, or having received noninvasive mechanical ventilation for more than 24 hours. Strict mechanical ventilation guidelines were applied in both groups, and in particular, low tidal volume was well maintained over time. The selection of PEEP was based on the PEEP/FIO2 table of the ARDSnet trial.(17) The prone positioning sessions were prolonged and scheduled to span at least 16 consecutive hours. In the supine group, the patients were not allowed to cross over, except for life-threatening hypoxemia. Neuromuscular blocking agents were used in both groups. The main outcome was mortality of any cause at day 28: 16% in the prone group and 32.8% in the supine group, a difference that persisted at day 90. Controlling for unbalance between groups at the time of randomization (lower sepsis-related organ failure assessment score and rate of use of vasopressors in the prone group), the difference in mortality remained. The meta-analyses performed after the publication of the PROSEVA trial confirmed the significant increase in survival with prone positioning.(18-20)
 
Some controversy may remain regarding the use of prone positioning. The first argument frequently leveled against it is the expertise that it requires. This is true, but at some point, even current experts had to familiarize themselves with the procedure. Furthermore, higher mortality in the prone group has never been documented. If expertise is truly an issue, patients could be referred to centers with the appropriate experience in prone positioning. The role of expertise is shown by the lack of difference in serious adverse events, in particular those related to airways, in the PROSEVA trial, which enrolled centers with expertise in repositioning. The second argument is that rather low PEEP was used in the PROSEVA trial. Experts recommend using higher PEEP in moderate to severe ARDS. However, no single trial found lower mortality with high PEEP, even though one individual meta-analysis found this.(21) So what is the best PEEP strategy, as the trials included in the meta-analysis used either a PEEP/FIO2 table or aimed at increased lung recruitment? Prone positioning may recruit the lung with no change in pressure at the airway opening and may act as a PEEP of 7 cm H2O as suggested by early experimental data.(22) Finally, provided that prone positioning is beneficial through a reduction in VILI, this effect has no direct link with oxygenation response. Furthermore, it is claimed that hypoxemia is no longer the leading cause of death in ARDS, but rather multiple organ failure.
 
Taking all these results together, prone positioning should be recommended in ARDS patients early and for long sessions when severity criteria (critical threshold ranges for PaO2/FIO2 between 100 and 150 mm Hg) are met, no contraindication exists and the patient center has the appropriate expertise.
 
References:

1. Broccard A, Shapiro RS, Schmitz LL, Adams AB, Nahum A, Marini JJ. Prone positioning attenuates and redistributes ventilator-induced lung injury in dogs. Crit Care Med. 2000;28:295-303.
2. Valenza F, Guglielmi M, Maffioletti M, et al. Prone position delays the progression of ventilator-induced lung injury in rats: does lung strain distribution play a role? Crit Care Med. 2005;33:361-367.
3. Park MS, He Q, Edwards MG, et al. Mitogen-activated protein kinase phosphatase-1 modulates regional effects of injurious mechanical ventilation in rodent lungs. Am J Respir Crit Care Med. 2012;186:72-81.
4. Mutoh T, Guest RJ, Lamm WJ, Albert RK. Prone position alters the effect of volume overload on regional pleural pressures and improves hypoxemia in pigs in vivo. Am Rev Respir Dis. 1992;146:300-306.
5. Richter T, Bellani G, Scott Harris R, et al. Effect of prone position on regional shunt, aeration, and perfusion in experimental acute lung injury. Am J Respir Crit Care Med. 2005;172:480-487.
6. Galiatsou E, Kostanti E, Svarna E, et al. Prone position augments recruitment and prevents alveolar overinflation in acute lung injury. Am J Respir Crit Care Med. 2006;174:187-197.
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8. Guérin C, Gaillard S, Lemasson S, et al. Effects of systematic prone positioning in hypoxemic acute respiratory failure: a randomized controlled trial. JAMA. 2004;292:2379–2387.
9.  Mancebo J, Fernandez 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;173:1233–1239.
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11.  Gattinoni L, Tognoni G, Pesenti A, et al. Effect of prone positioning on the survival of patients with acute respiratory failure. N Engl J Med. 2001;345:568–573.
12. Guerin C, Reignier J, Richard JC, et al. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med. 2013;368:2159-2168.
13. Sud S, Friedrich JO, Taccone P, et al. Prone ventilation reduces mortality in patients with acute respiratory failure and severe hypoxemia: systematic review and meta-analysis. Intensive Care Med. 2010;36:585-599.
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15. Ferguson ND, Fan E, Camporota L, et al. The Berlin definition of ARDS: an expanded rationale, justification, and supplementary material. Intensive Care Med. 2012;38:1573-1582.
16. Ranieri VM, Rubenfeld GD, Thompson BT, et al. Acute Respiratory Distress Syndrome: the Berlin Definition. JAMA. 2012;307:E1-E8.
17. ARDSnet. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med. 2000;342:1301-1308.
18. Sud S, Friedrich JO, Adhikari NK, et al. Effect of prone positioning during mechanical ventilation on mortality among patients with acute respiratory distress syndrome: a systematic review and meta-analysis. CMAJ. 2014;186:E381-E390.
19. Beitler JR, Shaefi S, Montesi SB, et al. Prone positioning reduces mortality from acute respiratory distress syndrome in the low tidal volume era: a meta-analysis. Intensive Care Med. 2014;40:332-341.
20. Lee JM, Bae W, Lee YL, Cho Y-J. The efficacy and safety of prone positional ventilation in acute respiratory distress syndrome: updated study-level meta-analysis of 11 randomized controlled trials. Crit Care Med. 2014;42:1252-1262.
21. Briel M, Meade M, Mercat A, et al. Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis. JAMA. 2010;303:865-873.
22. Cakar N, der Kloot TV, Youngblood M, Adams A, Nahum A. Oxygenation response to a recruitment maneuver during supine and prone positions in an oleic acid-induced lung injury model. Am J Respir Crit Care Med. 2000; 161:1949-1956.