Respiration/Ventilation
Prone positioning in hypoxemic respiratory failure: Meta-analysis of randomized controlled trials

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Abstract

Purpose

Prone positioning is used to improve oxygenation in patients with hypoxemic respiratory failure (HRF). However, its role in clinical practice is not yet clearly defined. The aim of this meta-analysis was to assess the effect of prone positioning on relevant clinical outcomes, such as intensive care unit (ICU) and hospital mortality, days of mechanical ventilation, length of stay, incidence of ventilator-associated pneumonia (VAP) and pneumothorax, and associated complications.

Methods

We used literature search of MEDLINE, Current Contents, and Cochrane Central Register of Controlled Trials. We focused only on randomized controlled trials reporting clinical outcomes in adult patients with HRF. Four trials met our inclusion criteria, including 662 patients randomized to prone ventilation and 609 patients to supine ventilation.

Results

The pooled odds ratio (OR) for the ICU mortality in the intention-to-treat analysis was 0.97 (95% confidence interval [CI], 0.77-1.22), for the comparison between prone and supine ventilated patients. Interestingly, the pooled OR for the ICU mortality in the selected group of the more severely ill patients favored prone positioning (OR, 0.34; 95% CI, 0.18-0.66). The duration of mechanical ventilation and the incidence of pneumothorax were not different between the 2 groups. The incidence of VAP was lower but not statistically significant in patients treated with prone positioning (OR, 0.81; 95% CI, 0.61-1.10). However, prone positioning was associated with a higher risk of pressure sores (OR, 1.49; 95% CI, 1.17-1.89) and a trend for more complications related to the endotracheal tube (OR, 1.30; 95% CI, 0.94-1.80).

Conclusions

Despite the inherent limitations of the meta-analytic approach, it seems that prone positioning has no discernible effect on mortality in patients with HRF. It may decrease the incidence of VAP at the expense of more pressure sores and complications related to the endotracheal tube. However, a subgroup of the most severely ill patients may benefit most from this intervention.

Introduction

The acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are common and fatal diseases that represent a major public health problem [1]. Even though ARDS-associated mortality has been shown to be decreasing over the last 2 decades [2], it still remains higher than 30% [1], [3]. A recently published review of the studies reporting epidemiologic data on ARDS and ALI estimated their incidence to be approximately 20 to 75 cases per 100 000 person-years [4]. Another study [5] showed that among patients requiring mechanical ventilation for more than 24 hours, 5 patients have hypoxemic respiratory failure (HRF) for every one who is actually diagnosed with ARDS/ALI. This leaves a large, yet poorly characterized group of patients who contribute to the rising cost of healthcare.

Despite recent advances in the elucidation of the mechanisms of ALI and promising results from animal models, all pharmacologic approaches in the treatment of ARDS have been proven ineffective [6], with glucocorticoids representing the most recently proven unsuccessful intervention [7]. Thus, the only therapy so far showing a clear survival benefit (9% absolute decrease in mortality) remains the lung-protective ventilation strategy in which low tidal volume mechanical ventilation of 6 mL/kg is applied instead of the traditionally used tidal volume of greater than 10 mL/kg [8].

Prone positioning was initially shown to improve oxygenation in mechanically ventilated patients with hypoxemic acute respiratory failure more than 30 years ago [9], [10]. Over the last few years, numerous studies have shown that ventilation in the prone position improves oxygenation, sometimes dramatically, in approximately 70% of the patients [11]. Even though most clinical experience with the prone positioning has been derived from mechanically ventilated patients with ARDS/ALI, oxygenation improvement has been shown in a number of respiratory illnesses, such as hydrostatic/cardiogenic pulmonary edema [12], chronic obstructive pulmonary disease [13], [14], and postoperative hypoxemia [15]. Prone positioning has even been used in awake nonintubated patients with HRF to avoid mechanical ventilation [16]. The beneficial effects of prone positioning on gas exchange seem to stem from the recruitment of posterior atelectatic lung units [17] and increase of the end-expiratory lung volume [18], improvement of respiratory mechanics [18], [19], decrease of ventilation-perfusion mismatch [20], decrease of lungs' compression by the heart [21], attenuation of ventilator-induced lung injury (VILI) [22], [23], and facilitation of secretions, drainage [13].

Despite the undisputed improvement in oxygenation and lung mechanics attained by prone ventilation, normalizing physiologic variables in acute illness and applying physiologically sound treatments may not be sufficient [8], [24] and may even be harmful [25]. Although prone positioning is frequently used in the management of adult patients with HRF, it constantly sparks emotional responses and debates among critical care specialists [26], because the intensive care community is in equipoise regarding its actual clinical benefits. Although there have been reviews in the literature on this issue, they are mostly narrative [11], [27]. Thus, we decided to systematically review, assess, and synthesize the available evidence from studies that compared prone with supine positioning in terms of mortality and other important clinical outcomes among adult patients with HRF.

Section snippets

Methods

This article was prepared in accordance with the QUOROM statement [28].

Search results and trial characteristics

In Fig. 1, we present a flow diagram describing in detail the selection process applied to identify the pool of RCTs included in the meta-analysis. We identified 53 published clinical trials including patients with HRF that were treated in the prone position. From these, 10 trials were excluded because of inappropriate study design, that is, they were retrospective, not controlled, or not randomized clinical trials (1, 5, and 4 trials, respectively). In addition, 3 studies were excluded because

Discussion

The purpose of our study was to compare the effect of prone and supine mechanical ventilation on mortality and other relevant secondary clinical outcomes among patients with HRF, irrespective of changes in gas exchange and lung mechanics. Our main finding is that the evidence from randomized controlled trials does not support any benefit in mortality from the implementation of prone positioning ventilation in the broad group of hypoxemic patients. However, there is evidence that prone

Conclusions

The available evidence does not support a beneficiary effect of prone positioning on mortality among the broad group of patients with HRF, but a positive mortality effect in patients with severe ARDS cannot be excluded. In addition, our data show that ventilation in the prone position may lower the incidence of VAP at the expense of an increased incidence of pressure sores and, probably, complications related to the position of the ETT.

It is conceivable that negative trial results cannot deter

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