Prone Position for Acute Respiratory Distress Syndrome

Prone Position for Acute Respiratory Distress Syndrome A Systematic Review and Meta-Analysis

Laveena Munshi(1), Lorenzo Del Sorbo(1), Neill K. J. Adhikari(2), Carol L. Hodgson(3), Hannah Wunsch(4), Maureen O. Meade(5), Elizabeth Uleryk(6), Jordi Mancebo(7), Antonio Pesenti(8), V. Marco Ranieri(9), and Eddy Fan(1)

(1) Interdepartmental Division of Critical Care Medicine, Toronto General Hospital, Toronto, Ontario, Canada; (2) Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; (3) Monash University, Melbourne, Victoria, Australia; (4) Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada; (5) McMaster University, Hamilton, Ontario, Canada; (6) Hospital for Sick Children, Toronto, Ontario, Canada; (7) University of Montreal, Montreal, Quebec, Canada; (8) Universita degli Studi di Milano, Milan, Italy; and (9) Policlinico Umberto I, Universit a “La Sapienza” Roma, Rome, Italy

Abstract

Rationale: The application of prone positioning for acute respiratory distress syndrome (ARDS) has evolved, with recent trials focusing on patients with more severe ARDS, and applying prone ventilation for more prolonged periods.

Objectives: This review evaluates the effect of prone positioning on 28-day mortality (primary outcome) compared with conventional mechanical ventilation in the supine position for adults with ARDS.

Methods: We updated the literature search from a systematic review published in 2010, searching MEDLINE, EMBASE, and CENTRAL (through to August 2016). We included randomized, controlled trials (RCTs) comparing prone to supine positioning in mechanically ventilated adults with ARDS, and conducted sensitivity analyses to explore the effects of duration of prone ventilation, concurrent lung-protective ventilation and ARDS severity. Secondary outcomes included PaO2/FIO2 ratio on Day4 and an evaluation of adverse events. Meta-analyses used random effects models. Methodologic quality of the RCTs was evaluated using the Cochrane risk of bias instrument, and methodologic quality of the overall body of evidence was evaluated using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) guidelines.

Results: Eight RCTs fulfilled entry criteria, and included 2,129 patients (1,093 [51%] proned). Meta-analysis revealed no difference in mortality (risk ratio [RR], 0.84; 95% confidence interval [CI], 0.68- 1.04), but subgroup analyses found lower mortality with 12 hours or greater duration prone (five trials; RR, 0.74; 95% CI, 0.56-0.99) and for patients with moderate to severe ARDS (five trials; RR, 0.74; 95% CI,0.56-0.99).PaO2/FIO2 ratio on Day4 for all patients was significantly higher in the prone positioning group (mean difference, 23.5; 95% CI, 12.4-34.5). Prone positioning was associated with higher rates of endotracheal tube obstruction and pressure sores. Risk of bias was low across the trials.

Conclusions: Prone positioning is likely to reduce mortality among patients with severe ARDS when applied for at least 12 hours daily.

Keywords: critical care; prone position; intensive care units; adult respiratory distress syndrome; systematic review

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Question 1

When applied for a longer daily duration, prone positioning appears to provide more benefit to patients that are:

The primary meta-analysis did not demonstrate a mortality difference, but a priori subgroup analyses demonstrated lower mortality when prone positioning was applied for 12 hours or longer per day and in studies including moderate to severe ARDS.Prone positioning appears to benefit more hypoxemic patients with ARDS, and particularly when applied for a longer daily duration. Those with the most severe lung injury have the greatest physiologic rationale for benefits from prone positioning, due to more severe and heterogeneous lung injury and greater ventilation-perfusion heterogeneity in the dependent lung zones while supine.

Question 2

Application of prone positioning yielded the greatest benefit in studies in which it was applied for:

Placing a patient in the prone position facilitates recruitment and decreases heterogeneity of compliance, which improves oxygenation and minimizes injurious ventilation. Application of prone positioning yielded the greatest benefit in studies in which it was applied for 12 hours or longer per day. This is not surprising, as a decrease in ventilator-induced lung injury is likely the mechanism by which prone positioning decreases mortality, and longer periods of prone ventilation means less injury.

Question 3

In the cohort of studies with reduced tidal volume, prone positioning in patients significantly reduced which of the following?

The difference in results may arise from the time point of the mortality assessment (their trial included mortality at the longest available follow-up) or differences in trial selection (one trial did not focus primarily on ARDS and two trials combined prone positioning with high-frequency oscillation). Sud and colleagues included 11 trials and found a significantly reduced mortality favoring prone positioning in the cohort of studies with reduced tidal volume (RR, 0.74, 95% CI, 0.59-0.95; I2, 29%). The difference found in their results can be attributed to three additional studies, and the fact that the mortality time point chosen was obtained at the longest period of follow-up.

Question 4

Prone positioning was associated with higher rates of pressure sores and one of the following:

Secondary outcomes included PaO2/FIO2 ratio on Day 4 and an evaluation of adverse events. Prone positioning was associated with higher rates of endotracheal tube obstruction and pressure sores. Early trials persistently demonstrated improved oxygenation.

Question 5

Placing a patient in the prone position facilitates recruitment and decreases heterogeneity of compliance, which minimizes injurious ventilation and improves:

Those with the most severe lung injury have the greatest physiologic rationale for benefits from prone positioning, due to more severe and heterogeneous lung injury and greater ventilation-perfusion heterogeneity in the dependent lung zones while supine. Placing a patient in the prone position facilitates recruitment and decreases heterogeneity of compliance, which improves oxygenation and minimizes injurious ventilation (24). Application of prone positioning yielded the greatest benefit in studies in which it was applied for 12 hours or longer per day.