How Much PEEP in Acute Lung Injury
Authors: Gordon D. Rubenfeld
Journal: JAMA (2010)

ACUTE LUNG INJURY (ALI) IS A COMMON, LETHAL, AND complex syndrome. Estimates of attributable mortality from ALI or its more severe form, acute respiratory distress syndrome (ARDS), in the United States place it above asthma and human immunodeficiency virus infection as a cause of death. The current mortality of 35% associated with ALI is roughly 3-fold higher than that associated with ST-segment elevation myocardial infarction. Most of the salient features of ARDS, including the therapeutic use of positive end-expiratory pressure (PEEP), were described by Ashbaugh et al in their classic description of the syndrome: “ventilation without positive end-expiratory pressure resulted in immediate hypoxaemia. . . . Collapsed alveoli require greater pressures for reopening, thus explaining the notable loss of compliance. Positive end-expiratory pressure would theoretically prevent complete collapse and improve oxygenation by maintaining alveolar ventilation.” Ashbaugh et al thought that mechanical ventilation merely prevented hypoxemic death, thereby providing clinicians with time to treat the underlying cause of ARDS. However, recent research has focused on the degree to which mechanical ventilation is injurious, depending on how it is applied, by causing inflammation and multiple organ failure. There is little disagreement about the principles of mechanical ventilation in patients with ALI: a PEEP sufficient to recruit collapsed lung areas should be used while delivering small tidal volumes to protect the uninjured lung from overdistention. These basic concepts do not provide any of the details required to manage the care of patients at the bedside. Although the use of PEEP is a simple physiological intervention, it has potentially deleterious effects on right and left ventricular function, pulmonary vascular resistance, and thoracic compliance, leading to unpredictable effects on gas exchange and hemodynamics in individual patients. Airway pressures necessary to recruit collapsed lung areas can improve oxygenation but also can overdistend normal areas of pulmonary parenchyma, worsen inflammation, and reduce cardiac output. Therefore, identifying the optimal PEEP to use in ALI has been the focus of a substantial amount of clinical investigation. Many strategies exist: clinicians can increase PEEP to achieve the maximal improvement in oxygenation, sacrificing overdistention of normal alveoli; balance oxygenation benefits against cardiac output or blood pressure; use pressure-volume curves or dynamic stress indices to identify a trade-off point of lung recruitment; or use sophisticated imaging techniques to assess how much lung has been opened. However, in clinical practice, patients with ALI do not appear to benefit from any of these strategies. Large cohorts of patients receiving mechanical ventilation show that patients with ALI, ARDS, acute respiratory failure that is neither ALI nor ARDS, and patients with chronic obstructive pulmonary disease all receive, on average, about 8 cm H2O of PEEP. Current practice may reflect the lack of evidence demonstrating a patient-centered outcome benefit of any specific approach to titrating PEEP. Four recent clinical trials address the question of “How much PEEP in acute lung injury?”: ALVEOLI, LOVS, EXPRESS, and EPVENT. All of these investigations were designed to measure the benefits of a protocolized higher PEEP strategy in a broad range of patients with ALI receiving tidal volumes thought to be protective. The protocols tested were related only in that they delivered approximately 14.5 to 18 cm H2O of PEEP on day 1 to patients in the intervention groups. The usual set of explanations were invoked to interpret the results of high-quality, wellconceived, but statistically negative trials; ie, the wrong patients were enrolled; too few patients were enrolled because of overly optimistic projections of the effect of PEEP on mortality; and unlucky randomization led to sicker patients in the intervention groups and to investigators not using the right approach to setting PEEP. In this issue of JAMA, a meta-analysis of individualpatient data by Briel and colleagues addresses 3 of these 4 important limitations. Using primary data from the actual trials, the authors demonstrated that, after adjusting for individual patient covariates, higher PEEP was associated with