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Lung Recruitment and Titrated PEEP in Moderate to Severe ARDS: Is the Door Closing on the Open Lung?

Mechanical ventilation is critical for the survival of many patients with the acute respiratory distress syndrome (ARDS) but can also cause ventilator-induced lung injury (VILI). One form of VILI occurs when the lungs exhale to relatively low volumes and airway pressures. This may cause injurious tidal closing and reopening of small bronchioles and alveoli or excessive stress at the margins between aerated and atelectatic airspaces.1,2 In animal studies, positive end-expiratory pressure (PEEP) reduced or prevented VILI from exhalation to low volumes and pressures.1,3-5 PEEP can also recruit some previously atelectatic or fluidfilled lung regions, allowing more of the lung to be available for inflation during inspiration. This could reduce VILI from overdistention of an otherwise reduced amount of aerated lung. In some early studies, the levels of PEEP that were applied for lung-protection exceeded the levels that most clinicians use when managing patients with ARDS. This led to recommendations to use higher PEEP in patients with ARDS to minimize low volume and low pressure VILI and hopefully to improve clinical outcomes. The “open lung approach” (OLA) aims to achieve high levels of lung aeration in patients with ARDS by first conducting recruitment maneuvers (RMs) to reverse atelectasis and then applying high levels of PEEP to keep recruited alveoli open.6 Recruitment maneuvers typically involve a ventilatory approach that transiently increases pulmonary airway pressure to reopen recruitable lung areas. For example, an RM can be conducted by raising inspiratory airway pressures to 50 cm of water for 1 or 2 minutes. However, 3 large randomized clinical trials of higher PEEP and RMs in patients with ARDS and a PaO2/FIO2 ratio of 300 or less did not demonstrate significant reductions in mortality.7-9 An individual patient data meta-analysis of these 3 clinical trials suggested that higher PEEP reduced mortality in patients with more severe hypoxemia (PaO2/FIO2 ≤200), but this finding has not been tested in clinical trials.10 A recent pilot trial of the OLA involved 200 patients and used more aggressive RMs and higher levels of PEEP than in the 3 earlier trials.11 Arterial oxygenation improved and driving pressures decreased in the OLA group compared with the control group in which RMs were not conducted and PEEP was set according to the ARDS Network lower PEEP/FIO2 table. There were small but nonsignificant differences in mortality and ventilatorfree days that favored the OLA group, but the trial was not large enough to analyze these outcomes.11 In this issue of JAMA, the Writing Group for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) Investigators12 report the results of a large randomized clinical trial that was conducted in 120 intensive care units in 9 countries and compared patients treated with the OLA (n = 501) with those managed with conventional PEEP (n = 509). As in the recent pilot OLA trial, patients in this trial had moderate to severe ARDS (PaO2/FIO2 ≤200). To reduce VILI from overdistention in both study groups, the target tidal volume was 6 mL/kg of predicted body weight with inspiratory plateau pressures of 30 cm H2O or less, consistent with the National Institutes of Health (NIH) ARDS Network protocol.13 Patients in the OLA study group received RMs with PEEP as high as 45 cm H2O and peak airway pressures as high as 60 cm H2O. These were followed immediately by a decremental PEEP titration to identify the PEEP at which lung compliance was maximal, presumably representing the best balance between recruitment and overdistention. The control group used the NIH ARDS Network lower PEEP/FIO2 table without RMs.7 As the authors report, the OLA was associated with a significantly higher 28-day mortality and 6-month mortality (55.3% vs 49.3% and 65.3% vs 59.9%, respectively). A small but statistically significant difference in ventilator-free days favored the control group (5.3 days in the OLA group vs 6.4 days in the control group), and there was a higher rate of barotrauma among patients in the OLA group (5.6%) than among those in the control group (1.6%). The difference in mean levels of PEEP between the OLA and the control group in the study by the ART investigators was only 3 to 4 cm H2O over the first 7 days. The lung-protection that results from these differences in PEEP is probably small. Also, the difference between study groups in driving pressure over the first 3 days was less than 2 cm H2O. Because tidal volumes were similar in the 2 study groups, the differences in driving pressure reflect primarily the differences in volumes of aerated lung. The small differences in driving pressures suggest that the OLA protocol did not result in much recruitment. Additionally, higher PEEP in the OLA group may have caused more overdistention, which would tend to increase driving pressures, offsetting the decreases that might have resulted from additional recruitment of aerated lung. The mean PEEP in the control group of the ART investigators’ trial was approximately 3 cm H2O higher than the mean PEEP levels in the control groups of the other 3 large clinical Related article Opinion