By Eric Walter, MD, MSc

Pulmonary and Critical Care Medicine, Northwest Permanente and Kaiser Sunnyside Medical Center, Portland, OR

Dr. Walter reports no financial relationships relevant to this field of study.

SYNOPSIS: This article provides a collaborative, evidence-based guideline for mechanical ventilation in acute respiratory distress syndrome.

SOURCE: 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;195:1253-1263.

Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure. Patients with ARDS frequently need respiratory support with mechanical ventilation. While it can be life-saving, mechanical ventilation itself can cause and exacerbate lung injury. Over the past 20 years, numerous ventilator management strategies have been evaluated in an attempt to determine how to best provide respiratory support while preventing or minimizing additional lung injury. Representatives from the American Thoracic Society, the European Society of Intensive Care Medicine, and the Society of Critical Care Medicine reviewed this literature and developed a clinical practice guideline with recommendations for ARDS treatment strategies. Recommendations were classified as either strong or conditional. The authors used the phrases “we recommend” when discussing strong recommendations and “we suggest” when discussing conditional recommendations. The authors reviewed six specific ARDS treatment strategies (see Table 1).

The recommendation for low tidal volume (LTV) ventilation was based on nine randomized, controlled trials (RCTs) comparing LTV and traditional tidal volumes (mean tidal volume 6.8 ± 1.2 mL/kg predicted body weight (PBW) vs. 11.4 ± 1.1 mL/kg PBW, respectively). In the seven studies that compared LTV and traditional tidal volumes without any other interventions, such as high positive end-expiratory pressure (PEEP), there was no difference in mortality (relative risk [RR], 0.87; 95% confidence interval [CI], 0.70-1.080). However, a sensitivity analysis, including trials with LTV and protocolized PEEP, showed reduced mortality (RR, 0.80; 95% CI, 0.66-0.98). Furthermore, there was a significant inverse association between tidal volume gradient (difference in tidal volume between LTV and control groups) and mortality.

Among all ARDS patients, prone positioning was not associated with a reduction in mortality (RR, 0.84; 95% CI, 0.60-1.04). However, subgroup analyses in many studies and one RCT showed a significant reduction in mortality for patients placed in prone positioning for > 12 hours (RR, 0.74; 95% CI, 0.56-0.99) and patients with moderate or severe ARDS (RR, 0.74; 95% CI, 0.54-0.99). Thus, prone positioning for > 12 hours per day was recommended for patients with severe ARDS.

Higher PEEP and recruitment maneuvers were suggested rather than recommended. There was a recommendation against the use of high-frequency oscillatory ventilation based primarily on results from two RCTs that showed either no benefit or significant harm. Not enough data were available to make a recommendation for or against the use of extracorporeal membrane oxygenation. This guideline did not address the use of different modes of mechanical ventilation or neuromuscular blockade.

COMMENTARY

To best understand how to interpret this guideline, it is helpful to understand how it was developed. The authors used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. The GRADE system attempts to rate the quality of evidence across studies by both estimating a treatment effect (i.e., does the RR show benefit or harm) and assessing the confidence one can have in the treatment effect. Higher quality evidence allows for more confidence that the estimated treatment is true. Low-quality evidence may provide an estimated treatment effect but the confidence this treatment effect is true is lower. The GRADE system also bases the strength of a recommendation not solely on the evidence but on four concepts: balance of desirable and undesirable effects, quality of the evidence, values and preferences, and resource implications.

For example, the authors concluded there was only moderate quality of evidence for LTV ventilation (the primary analysis was not statistically significant). Therefore, the confidence that LTV ventilation is associated with lower mortality is not as high as it could be. If the quality of evidence was only moderate, then why was LTV ventilation given a strong recommendation? The authors evaluated other concepts and not just the evidence alone. The balance of desirable and undesirable effects seemed weighted for LTV ventilation. The point estimate of 0.87 suggests a 13% reduction in mortality and the CI suggests that the reduction in mortality could be as high as a 30% (albeit with the possibility of up to an 8% increase in mortality). Furthermore, the authors assessed there was moderate confidence that undesirable outcomes (adverse events due to LTV) are not severe and avoiding these outcomes is not highly valued, while the outcome of reduced mortality is highly desirable. The authors addressed the potential adverse outcomes of ventilator dysynchrony, patient discomfort, and potential need for increased sedation. To address this, they recommended an initial tidal volume of 6 mL/kg PBW, but if needed, LTV can be increased up to 8 mL/kg PBW, as carried out in the original landmark trial. Prone positioning was recommended based on moderate-high confidence in the moderate treatment effect on a highly desirable outcome (mortality). However, the strong recommendation for prone positioning was not unanimous. Dissenting committee members noted that undesirable effects of prone positioning can be severe and that the data were weighted heavily by a single trial. As opposed to the recommendation for prone positioning, recruitment maneuvers and higher PEEP only were suggested. This was primarily due to lower confidence of smaller treatment effects. With respect to recruitment maneuvers, there was some evidence of harm, so caution was suggested when recruitment maneuvers are used in patients with hypovolemia or shock.

This guideline helps synthesize decades of ARDS research in a systematic fashion and provide easy-to-interpret recommendations. These recommendations should not be considered all-encompassing, as all patients are unique. Recommendations will help guide clinicians, but the authors were right to note that clinicians should personalize decisions for all patients. This was noted to be most important for the conditional recommendations.

Table 1. Recommended Treatment Strategies for Acute Respiratory Distress Syndrome

Treatment Strategy

GRADE Recommendation

Author’s
Terminology

Low tidal volume ventilation

Strong recommendation for

Recommended

Prone positioning in severe acute respiratory distress syndrome

Strong recommendation for

Recommended

Higher positive end-expiratory pressure in moderate or severe acute respiratory distress syndrome

Conditional recommendation for

Suggested

Recruitment maneuvers

Conditional recommendation for

Suggested

High-frequency oscillatory ventilation

Strong recommendation against

Not recommended

Extracorporeal membrane oxygenation

Insufficient evidence

Insufficient evidence