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By Richard Kallet, MS, RRT, FCCM
Director of Quality Assurance, Respiratory Care Services, Department of Anesthesia, San Francisco General Hospital
Mr. Kallet reports he is a major stockholder in the Asthma & Allergy Prevention Company, and receives grant/research support from Nihon Kohden.
SOURCE: Cavalcanti AB, et al. Effect of lung recruitment and titrated positive end-expiratory pressure (PEEP) vs low PEEP on mortality in patients with acute respiratory distress syndrome: A randomized clinical trial. JAMA 2017;318:1335-1345.
The authors of this multinational, prospective, randomized, controlled trial enrolled more than 1,000 subjects with moderate to severe acute respiratory distress syndrome (ARDS) within 72 hours of onset. These patients received either 1) an open lung ventilation (OLV) strategy in which a neuromuscular blockade was administered, followed by a lung recruitment maneuver (RM) with incremental positive end-expiratory pressure (PEEP) levels titrated to the best respiratory-system static compliance, or 2) a conventional low-PEEP lung-protective ventilation (LPV) strategy. Patients had to be hemodynamically stable and without evidence of barotrauma.
At baseline, there was no difference between treatment arms in terms of demographics, illness severity, comorbidities, pulmonary mechanics, gas exchange, or in achieved LPV goals. Sixty-two percent of subjects demonstrated a pulmonary source of ARDS and 67% exhibited septic shock. Of those randomized to OLV, 96% received an initial RM, and 78% received an RM following the PEEP decrement trial. Approximately 63% of subjects required no further RMs vs. 9% who required three or more maneuvers during the trial. On the first two study days, mean PEEP levels were approximately 4 cm H2O higher in the OLV vs. low-PEEP groups (16.2 vs. 12.0 and 14.2 vs. 10.5 cm H2O, respectively). Mean plateau and driving pressures were significantly higher in the OLV group, yet both variables were well within accepted LPV boundaries for each group. Mortality in the OLV group was significantly higher at both day 28 and at six months compared to the control low-PEEP group (55.3 vs. 49.3% and 65.3 vs. 59.9%, respectively). The OLV group experienced slightly fewer ventilator-free days than the conventional low-PEEP group; however, both intensive care and hospital lengths of stay were not different.
ARDS presenting with severe hypoxemia refractory to high PEEP levels often reflects the contribution of enormous compressive forces emanating from reduced chest wall compliance. Over several decades, mounting evidence suggests that inspiratory pressures between 40-60 cm H2O are necessary to fully recruit dorsal-caudal regions and reverse intractable hypoxemia. While the mechanical foundation for a recruitment maneuver is sound, its application in ARDS has remained uncertain given both the heterogeneous nature of lung injury and the inability to ascertain the amount of potentially recruitable lung vs. consolidated lung. Moreover, the degree to which atelectrauma contributes to lung injury and mortality risk in ARDS has (up to this point) remained unanswered.
Clearly, the Cavalcanti et al study indicates that an open lung ventilation strategy with recruitment maneuvers and higher PEEP should not be used routinely in the management of ARDS. Nonetheless, more in-depth analysis of the study results is needed to determine how OLV should be used going forward. At this juncture, it would be unwise to reject the use of RM in ARDS categorically. First, 63% of subjects received only two RMs, the duration of which was a total of eight minutes at plateau pressures of 40-60 cm H2O at a safe driving pressure. Given what is known about ventilator-induced lung injury, it’s implausible that such brief exposure could affect mortality that profoundly.
What is plausible is that the 46 patients who received three or more RMs may have been harmed. Subjects requiring repeated RMs may have been less recruitable and more susceptible to aggravating a proinflammatory state in a study sample characterized by pulmonary ARDS and septic shock. This would include regional lung overdistension, the possibility of bacterial translocation, and repeated gastrointestinal ischemia/reperfusion injury.1,2 The higher mean PEEP levels in the OLV group would not explain the increased mortality, as it was only 3-4 cm H2O above the conventional low-PEEP group. In contrast, differences in mean PEEP in three previous major LPV studies (ALVEOLI, EXPRESS, LOVS) was 6-8 cm H2O. A similar relationship existed for higher mean plateau and driving pressures in those studies compared to the ART study.
What can we reasonably conclude at this juncture? The OLV strategy is not necessary for managing the vast majority of ARDS cases, and atelectrauma is unlikely to be a mortality driver when LPV incorporates reasonable levels of PEEP early in the acute phase (e.g., ~12-16 cm H2O). However, there exists a small subset of ARDS where these levels of PEEP and other ancillary therapies are insufficient. These situations are likely restricted to cases of severe lung injury complicated by markedly reduced chest wall compliance that necessitate the OLV strategy as a temporizing measure to stabilize oxygenation and reduce long-term exposure to hyperoxia. Unfortunately, given that these cases represent such a small minority of ARDS, we will never see an adequately powered study to provide conclusive evidence in a timely manner.
Financial Disclosure: Hospital Medicine Alert’s Physician Editor, Kenneth P. Steinberg, MD, Peer Reviewer Rachael Safyan, MD, Editor Jesse Saffron, Editor Jill Drachenberg, and Editorial Group Manager Terrey L. Hatcher report no relevant relationship related to the material presented in this issue.