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

Eddy Fan, Lorenzo Del Sorbo, Ewan C. Goligher, Carol L. Hodgson, Laveena Munshi, Allan J. Walkey, Neill K. J. Adhikari, Marcelo B. P. Amato, Richard Branson, Roy G. Brower, Niall D. Ferguson, Ognjen Gajic, Luciano Gattinoni, Dean Hess, Jordi Mancebo, Maureen O. Meade, Daniel F. McAuley, Antonio Pesenti, V. Marco Ranieri, Gordon D. Rubenfeld, Eileen Rubin, Maureen Seckel, Arthur S. Slutsky, Daniel Talmor, B. Taylor Thompson, Hannah Wunsch, Elizabeth Uleryk, Jan Brozek, and Laurent J. Brochard; on behalf of the American Thoracic Society, European Society of Intensive Care Medicine, and Society of Critical Care Medicine

Abstract

Background: This document provides evidence-based clinical practice guidelines on the use of mechanical ventilation in adult patients with acute respiratory distress syndrome (ARDS).

Methods: A multidisciplinary panel conducted systematic reviews and metaanalyses of the relevant research and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations.

Results: For all patients with ARDS, the recommendation is strong for mechanical ventilation using lower tidal volumes (4-8 ml/kg predicted bodyweight) and lower inspiratory pressures (plateau pressure, 30 cm H2O) (moderate confidence in effect estimates). For patients with severe ARDS, the recommendation is strong for prone positioning for more than 12 h/d (moderate confidence in effect estimates). For patients with moderate or severeARDS, the recommendation is strong against routine use of high-frequency oscillatory ventilation (high confidence in effect estimates) and conditional for higher positive end-expiratory pressure (moderate confidence in effect estimates) and recruitment maneuvers (low confidence in effect estimates). Additional evidence is necessary to make a definitive recommendation for or against the use of extracorporeal membrane oxygenation in patients with severe ARDS.

Conclusions: The panel formulated and provided the rationale for recommendations on selected ventilatory interventions for adult patients with ARDS. Clinicians managing patients with ARDS should personalize decisions for their patients, particularly regarding the conditional recommendations in this guideline.

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Question 1

Which of the following exacerbates lung injury during mechanical ventilation by reducing the size of the lung available for tidal ventilation and by amplifying the stress in alveolar units subjected to cyclic tidal recruitment and derecruitment?

Mechanical ventilation itself can cause and potentiate lung injury and may contribute to nonpulmonary organ failure and mortality in patients with ARDS. This insight led to the design and evaluation of ventilatory strategies aimed at mitigating VILI.

Question 2

Sensitivity analysis that also included trials of a protocolized LTV/high PEEP cointervention showed:

Meta-regression showed a significant inverse association between larger tidal volume gradient (i.e., difference in tidal volume between LTV and control groups) and the relative risk of mortality associated with LTV (P = 0.002); trials with larger tidal volume gradients showed lower mortality risk with LTV. Sensitivity analysis that also included trials of a protocolized LTV/high PEEP cointervention showed significantly reduced mortality with LTV (nine studies, 1,629 patients; RR, 0.80; 95% CI, 0.66-0.98). Compared with trials without a high PEEP cointervention, LTV/high PEEP was associated with a greater mortality benefit (RR, 0.58; 95% CI, 0.41-0.82; P = 0.05 for interaction).

Question 3

Mechanical ventilation in the prone position has been evaluated as a strategy to enhance lung recruitment and which of the following:

Mechanical ventilation in the prone position has been evaluated as a strategy to enhance oxygenation and lung recruitment in ARDS. The mechanisms by which prone positioning may benefit patients with ARDS undergoing mechanical ventilation include improving ventilation-perfusion matching, increasing end-expiratory lung volume, and decreasing VILI by more uniform distribution of tidal volume through lung recruitment and alterations in chest wall mechanics.

Question 4

We recommend that adult patients with severe ARDS receive prone positioning for more than:

We recommend that adult patients with severe ARDS receive prone positioning for more than 12 hours per day (strong recommendation, moderate-high confidence in effect estimates).

Question 5

By simultaneously recruiting collapsed lung units and minimizing tidal stress and strain, which ventilation method offers a theoretically attractive mode of lung protection?

High-frequency oscillatory ventilation (HFOV) uses novel mechanisms of alveolar ventilation, permitting the delivery of very small tidal volumes at higher mean airway pressures. By simultaneously recruiting collapsed lung units and minimizing tidal stress and strain, HFOV offers a theoretically attractive mode of lung protection. HFOV requires specialized expertise, and patients must be heavily sedated to prevent tidal inspiratory efforts. The overall impact of HFOV on patient outcomes in ARDS was controversial.

Question 6

For patients in the HFOV group versus the control group, what was the difference in mortality rates?

Our primary analysis excluded trials that used cointerventions (e.g., higher PEEP) or did not mandate LTV in the control group. For our primary analysis, there was no significant difference in mortality for patients in the HFOV versus control group (three studies, 1,371 patients; RR, 1.14; 95% CI, 0.88-1.48; high confidence). When considering all six RCTs, there also was no significant difference in mortality between groups (six studies, 1,705 patients; RR, 0.94; 95% CI, 0.71-1.24; low confidence).

Question 7

Prone positioning was significantly associated with higher rates of which of the following:

Moreover, the committee considered a patient-level metaanalysis of four earlier RCTs demonstrating lower mortality in patients with severe ARDS at baseline, with subsequent confirmation of this finding in the PROSEVA (Proning Severe ARDS Patients) trial (mean 6 baseline PaO2/FIO2, 100 6 30 in the prone group). Prone positioning was significantly associated with higher rates of endotracheal tube obstruction (three studies, 1,594 patients; RR, 1.76; 95% CI, 1.24-2.50; moderate confidence) and pressure sores (three studies, 1,109 patients; RR, 1.22; 95% CI, 1.06-1.41; high confidence). There was no significant difference in barotrauma between groups (four studies, 988 patients; RR, 0.77; 95% CI, 0.48-1.24; moderate confidence).

Question 8

For patients with moderate or severe ARDS, what level of PEEP should they be receiving?

The best method to set PEEP in patients with ARDS remains uncertain. Given the lack of consistent efficacy when PEEP is adjusted according to oxygenation, other methods based on lung mechanics or imaging have been proposed and require evaluation in future studies. Individualizing PEEP titration by targeting the transpulmonary plateau pressure is an alternative strategy.

Question 9

Which of these exacerbates lung injury during mechanical ventilation by reducing the size of the lung available for tidal ventilation and by amplifying stress at the interface between atelectatic and aerated lung and in alveolar units subjected to cyclic tidal recruitment and derecruitment?

Patients with ARDS have dependent atelectasis due in part to increased lung weight from interstitial and alveolar edema. Atelectasis exacerbates lung injury during mechanical ventilation by reducing the size of the lung available for tidal ventilation and by amplifying stress at the interface between atelectatic and aerated lung and in alveolar units subjected to cyclic tidal recruitment and derecruitment. Both higher PEEP and lung RMs can reduce atelectasis and increase end-expiratory lung volume.

Question 10

In the study, at 24 hours, recruitment maneuvers reduced the need for rescue therapy and were associated with improvement of:

There was no evidence of heterogeneity (P = 0.21) despite a higher PEEP cointervention used in five of six trials. Recruitment maneuvers (RMs) were also associated with higher oxygenation (PaO2/FIO2 ratio) at 24 hours (six studies, 1,400 patients; 52 mm Hg higher; 95% CI, 23-81; low confidence) and reduced the need for rescue therapy (two studies, 1,003 patients; RR, 0.64; 95% CI, 0.35-0.93; moderate confidence). RMs were not significantly associated with barotrauma (four studies, 1,293 patients; RR, 0.84; 95% CI, 0.46-1.55; low confidence) and rates of hemodynamic compromise (three studies, 330 patients; RR, 1.30; 95% CI, 0.92-1.83).