Positive End-Expiratory Pressure Levels in Adult Patients With Acute Lung Injury and Acute Respiratory Distress Syndrome

Abstract

What are the benefits and harms of high versus low levels of positive end-expiratory pressure (PEEP) in adults with acute lung injury and acute respiratory distress syndrome (ARDS)?Acute lung injury generally refers to acute respiratory insufficiency with decreased lung compliance leading to tachypnea and cyanosis.1 A life-threatening form of acute lung injury, ARDS, is classified according to the degree of hypoxemia based on the ratio of Pao2 to fraction of inspired oxygen, ranging from mild at 200 to severe at less than or equal to 100. Acute respiratory distress syndrome is common in the intensive care unit setting and is associated with significant morbidity and mortality.2 One study examining the epidemiology of ARDS across several countries found that approximately 10% of all patients admitted to the intensive care unit and 23% of all patients requiring mechanical ventilation developed ARDS.3Even though research has been conducted on ARDS for many years, treatment options directed at the underlying causes are still limited. Therefore, supportive mechanical ventilation remains a key component of the management plan.2 Mechanical ventilation, however, comes with its own risks of lung injury and can lead to increased morbidity and mortality.2 A common strategy to help protect against lung injury is inclusion of PEEP among the ventilator settings. Positive end-expiratory pressure refers to alveolar pressure that is kept higher than atmospheric pressure at the end of expiration to prevent alveolar damage or collapse, maintain sufficient oxygenation, and prevent overall lung injury.2 Positive end-expiratory pressure also has potential adverse effects, including reduced cardiac output, increased pulmonary vascular resistance, alveolar overdistension, and even lung injury.4Given that PEEP has both potential benefits and harms, practices related to its use vary, and there is no consensus on optimal levels of PEEP for patients with ARDS. Some studies have indicated that higher PEEP levels can prevent alveolar collapse and lung injury, whereas others, especially those focusing on patients with mild lung injury, have shown that higher PEEP levels can lead to complications including circulatory insufficiency and alveolar overdistension.5 The first version of this systematic review, conducted in 2013, did not show any statistically significant differences between the use of high versus low PEEP in patients with ARDS.6As new evidence on a topic becomes available, however, updates are necessary to account for the results that the new evidence presents. In addition, the continued variation in practice regarding the use of high versus low PEEP for patients with ARDS warrants an updated review of studies.This summary is based on an update to a previously published systematic review conducted in 2013.6 This update, conducted by Cruz et al7 in 2021, included 10 randomized controlled trials (6 from the previous systematic review plus 4 new ones) comprising a total of 3851 adult participants. The primary outcome of this review was mortality before hospital discharge. Secondary outcomes were oxygen efficiency, barotrauma, and ventilator-free days.Cruz et al7 independently assessed the risk of bias for each study, including selection, performance, detection, attrition, reporting, and publication biases. They resolved any disagreements by reviewing the data together and through discussion. The authors used risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, with 95% CIs used as measures of treatment effect for various comparisons. They used the internationally approved Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to determine the certainty of evidence—high, moderate, low, or very low—for each outcome8: Moderate-certainty evidence indicated that there was little to no difference in the number of patients who died by their receipt of high versus low levels of PEEP (RR, 0.97; 95% CI, 0.90-1.04; P = .39; I2 = 15%; 7 studies, 3640 participants). The moderate-certainty level was chosen because there was clinical heterogeneity among the studies, with the included patients having varying levels of disease severity.Oxygen efficiency was defined as improvement in oxygenation assessed by ratio of Pao2 to fraction of inspired oxygen on the first, third, and seventh days (seventh-day analysis included here). Moderate-certainty evidence indicated improvement in oxygenation up to the seventh day among participants who had high levels of PEEP (MD, 28.52; 95% CI, 20.82-36.21; P < .001; I2 = 0%; 5 studies, 1611 participants). The moderate-certainty level was chosen because of clinical heterogeneity.Low-certainty evidence indicated little to no difference in the number of participants with barotrauma by high versus low levels of PEEP (RR, 1.00; 95% CI, 0.64-1.57; P = .98; I2 = 63%; 9 studies, 3791 participants). The low-certainty level was chosen because of clinical and statistical heterogeneity.Ventilator-free days was defined as the number of days free of mechanical ventilation in patients who were successfully weaned from mechanical ventilation within 28 days. Low-certainty evidence indicated little to no difference in the number of ventilator-free days by high versus low levels of PEEP (MD, 0.45; 95% CI, –2.02 to 2.92; P = .72; I2 = 81%; 3 studies, 1654 participants). The low-certainty level was chosen because of clinical and statistical heterogeneity.This systematic review indicated that in patients with ARDS, there was no significant benefit to hospital mortality with the use of high levels of PEEP compared with low levels. The review also indicated that oxygenation improved on the first, third, and seventh days with high levels of PEEP compared with low levels and that high levels of PEEP were not associated with barotrauma or more ventilator-free days. Although the authors noted clinical heterogeneity, with the included studies using different definitions of ARDS and having variations in how high PEEP was titrated, the findings are comparable to other research findings. However, the heterogeneity of the included studies precludes drawing strong conclusions regarding the use of high versus low levels of PEEP for patients with ARDS. Newer approaches are being explored that focus on more individualized ways of using PEEP and mechanical ventilation in patients with ARDS, and future studies may provide additional guidance.9The evidence from this systematic review may affect the decisions of clinical care teams in creating treatment plans for patients in this population. An important part of the role of nurses caring for critically ill patients is advocating for the best evidence-based treatment. We must always consider the best available evidence and understand the feasibility, appropriateness, meaningfulness, and effectiveness of any intervention to determine whether it is the most suitable intervention to implement in a particular individual context.