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Prone Positioning for Acute Respiratory Distress Syndrome in Adults

No survival benefit

Benefits in NNT

No one was helped (no death or ventilator-associated pneumonia was prevented; similar length of stay on the ventilator, in the intensive care unit, and in the hospital)
No one was helped

Harms in NNT

8
1 in 8 were harmed (pressure sores)
16
1 in 16 were harmed (tracheal tube obstruction)
8
11.6% higher risk of pressure sores
16
6.2% higher risk of tracheal tube obstruction
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Source

Bloomfield R, Noble DW, Sudlow A. Prone position for acute respiratory failure in adults. Cochrane Database of Systematic Reviews. 2015;:CD008095.

Study Population: 2165 participants enrolled in randomized controlled trials comparing mechanical ventilation in the conventional supine or semi-recumbent position compared with mechanical ventilation in the prone position in adults with acute respiratory distress syndrome.

Efficacy Endpoints

Mortality (short and long term); ventilator-associated pneumonia; days on a ventilator, in intensive care unit, and in hospital

Harm Endpoints

Adverse events (pressure sores, tracheal tube obstruction, tracheal tube displacement, pneumothorax, arrhythmia)

Narrative

Acute respiratory distress syndrome (ARDS) is a type of acute diffuse, inflammatory lung injury leading to increased pulmonary vascular permeability and loss of aerated lung tissue. Clinically this process manifests as hypoxemia, radiographic opacities, increased physiologic dead space and decreased lung compliance.1 It is a common disease process affecting as many as 10% of intensive care unit (ICU) admissions, resulting in an overall mortality approaching 35%.2

Treatment strategies recommended by multiple guidelines are largely directed at improving alveolar recruitment and decreasing ventilator induced lung injury (VILI).3, 4, 5 One of these strategies involves mechanical ventilation of patients affected with ARDS in the prone position (proning) in order to both increase oxygenation and decrease lung injury. Physiologically, this is explained by recruitment of dorsal alveoli to improve ventilation-perfusion mismatch by partially alleviating cardiac and abdominal compression of these lung units. Additionally, it is postulated that less strain is applied to lung parenchyma as recruitment of alveoli allows for a more homogenous distribution of tidal volume during respiration.6 Furthermore, some believe that this positioning allows for improvement of postural drainage of the lungs and limits pooling of oropharyngeal secretions above the endotracheal tube cuff, possibly decreasing incidence of ventilator-associated pneumonia (VAP).7

Results
The meta-analysis discussed here assessed the benefits of prone positioning during mechanical ventilation for hypoxemic respiratory failure using a primary outcome of short-term (described as within 10-30 days or in ICU) mortality or longer-term (described as >30 days or hospital) mortality. The meta-analysis analyzed 2165 patients from 9 randomized controlled trials (RCTs). The publications spanned from 1997 to 2013. Overall, the meta-analysis showed no significant mortality benefit (short or long term) with using prone positioning during mechanical ventilation (low-quality evidence).8 Prone positioning also did not reduce the risk of ventilatorassociated pneumonia, days on ventilator, length of hospital or ICU stays (no statistically significant difference).

Mechanical ventilation in prone position was associated with increased risk of pressure sores (relative risk [RR]: 1.37, 95%CI, 1.05 to 1.79; absolute risk difference [ARD]: 11.6%; Numberneeded-to-harm [NNH]: 8) and tracheal tube obstruction (RR: 1.78, 95%CI, 1.22 to 2.60; ARD: 6.2%; NNH:16). Prone positioning did not increase the risk of tracheal tube displacement or pneumothorax. However, it was associated with a reduced risk of arrhythmias (including cardiac arrest). Although in this meta-analysis the primary outcomes showed no benefit from mechanical ventilation in prone position, the pre-planned subgroup analyses demonstrated improved longterm mortality (>30 days) in certain subgroups of patients. The subgroup analyses here included duration of daily ventilation while in prone position >16hrs/day (RR: 0.77, 95% CI, 0.61 to 0.99; ARD: 11%; NNT: 9), early enrollment and initiation of ventilation in prone position within 48 hours (RR: 0.75, 95% CI, 0.59 to 0.94; ARD: 12%; NNT: 9), severe hypoxia defined by the ratio of partial pressure of oxygen to percentage fraction of inspired oxygen (P/F ratio) <150 mmHg (RR: 0.77, 95% CI, 0.65 to 0.92; ARD: 12%, NNT: 9), and tidal volume of 6-8 cc/kg received based on ideal body weight (RR: 0.73, 95% CI, 0.55 to 0.96; ARD: 12%; NNT: 9).

Mechanical ventilation in prone position was associated with increased risk of pressure sores (relative risk [RR]: 1.37, 95%CI, 1.05 to 1.79; absolute risk difference [ARD]: 11.6%; Numberneeded-to-harm [NNH]: 8) and tracheal tube obstruction (RR: 1.78, 95%CI, 1.22 to 2.60; ARD: 6.2%; NNH:16). Prone positioning did not increase the risk of tracheal tube displacement or pneumothorax. However, it was associated with a reduced risk of arrhythmias (including cardiac arrest). Although in this meta-analysis the primary outcomes showed no benefit from mechanical ventilation in prone position, the pre-planned subgroup analyses demonstrated improved longterm mortality (>30 days) in certain subgroups of patients. The subgroup analyses here included duration of daily ventilation while in prone position >16hrs/day (RR: 0.77, 95% CI, 0.61 to 0.99; ARD: 11%; NNT: 9), early enrollment and initiation of ventilation in prone position within 48 hours (RR: 0.75, 95% CI, 0.59 to 0.94; ARD: 12%; NNT: 9), severe hypoxia defined by the ratio of partial pressure of oxygen to percentage fraction of inspired oxygen (P/F ratio) <150 mmHg (RR: 0.77, 95% CI, 0.65 to 0.92; ARD: 12%, NNT: 9), and tidal volume of 6-8 cc/kg received based on ideal body weight (RR: 0.73, 95% CI, 0.55 to 0.96; ARD: 12%; NNT: 9).

Caveats

The quality of evidence for primary outcome of short- and long-term mortality was rated low by the meta-analysis due to several biases and inconsistencies. While, the meta-analysis rated the quality of evidence for the subgroup analyses as moderate quality, it is important to note that the mortality benefits in the subgroups were more likely skewed by one RCT. The most recent RCT (Guerin, 2013)9 was the only trial to note a mortality benefit for prone positioning over standard supine mechanical ventilation. The impact of this RCT on the meta-analysis was demonstrated by the fact that the heterogeneity of the primary analyses changed from moderate-to-high (I2 :60%) to low (I2 : 0%) when this RCT was removed from the analysis.

The heterogeneity introduced by the most recent RCT may be related to the fact that this trial better reflects current practices with regards to treatment of ARDS. Within the span of publications included in this meta-analysis, two major events occurred with regards to ARDS definition and treatment. With the publication of the ARMA trial10 in 2000, ventilator strategies would be significantly affected in an attempt to prevent VILI using lower tidal volumes and place a limit on plateau pressures. Furthermore, the Berlin definition11 (published in 2012) improved on prior definitions of ARDS, thus allowing for better characterization and prediction of mortality in patients. This is shown as Guerin, 2013 utilizes the most restrictive tidal volumes (based on ideal body weight) and recruited the greatest number of severely hypoxemic (P/F ratio <150 mmHg) patients.

Additionally, on careful review of the individual studies, many of them are notable for a high crossover rate between supine and prone ventilation groups with several studies showing 10- 20% crossover between groups. Such errors can reduce the estimated treatment effect when using an intention to treat analysis, thus leading to type 2 error.12

In summary, prone positioning during mechanical ventilation in adults with acute respiratory failure does not offer any survival benefits. The existing evidence indicates that certain subgroups of patients may benefit from this intervention. These subgroups are listed in several guidelines and protocols3, 4, 5 as they suggest that the benefits of proning are only applicable for a small subset of ARDS patients. Future high quality RCTs focusing on these specific subgroups could better delineate which patients are better candidates for this intervention. Because of the lack of overall survival benefit for all ARDS patients, we have assigned a color recommendation of red (no benefit) to this intervention.

The original manuscript was published in Academic Emergency Medicine as part of the partnership between TheNNT.com and AEM.

Author

Walter Valesky, MD; Lillian Chow, MD
Supervising Editor: Shahriar Zehtabchi, MD

Published/Updated

February 14, 2020

References:

Fan E, Brodie D, Slutsky A. Acute respiratory distress syndrome advances in diagnosis and treatment. JAMA. 2018;319:698-710.
Bellani G, Laffey JG, Pham T, et al. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA. 2016;315:788-800.
Griffiths MJD, McAuley DF, Perkins GD, et al. Guidelines on the management of acute respiratory distress syndrome. BMJ Open Respir Res. 2019;6:e000420.
Papazian L, Aubron C, Brochard L, et al. Formal guidelines: Management of acute respiratory distress syndrome. Ann Intensive Care. 2019;9:69.
Fan E, Del Sorbo L, Goligher EC, et al. An official American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine clinical practice guideline: Mechanical ventilation in adult patients with acute respiratory distress syndrome. Am J Respir Crit Care Med. 2017;195:1253-63.
Dickinson S, Park PK, Napolitano LM. Prone-positioning therapy in ARDS. Crit Care Clin. 2011;27:511-23.
Kallet RH. A comprehensive review of prone position in ARDS. Respiratory Care. 2015;60:1660-87.
Bloomfield R, Noble DW, Sudlow A. Prone position for acute respiratory failure in adults. Cochrane Database of Systematic Reviews. 2015;:CD008095.
Guérin C, Reignier J, Richard JC, et al. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med. 2013;368:2159-68.
Acute Respiratory Distress Syndrome Network, Brower RG, Matthay MA, et al. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342:1301-8.
ARDS Definition Task Force, Ranieri VM, Rubenfeld GD, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307:2526-33.
Yelland LN, Sullivan TR, Voysey M, Lee KJ, Cook JA, Forbes AB. Applying the intention-totreat principle in practice: Guidance on handling randomisation errors. Clin Trials. 2015;12:418-23.

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