Refining Ventilatory Treatment for Acute Lung Injury and Acute Respiratory Distress Syndrome

Abstract

ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS) IS the clinical manifestation of inflammatory lung edema originating from a variety of insults. Since its first description 40 years ago, the mainstays of management have been institution of mechanical ventilation to ventilate the incompliant lungs, inspired oxygen for hypoxemia, and when hypoxemia is severe, the addition of positive end-expiratory pressure (PEEP) to increase end-expiration lung volume, which facilitates O2 gas exchange. Early on, physicians recognized that the high intrathoracic pressures of mechanical ventilation caused parenchymal stress or rupture, known as barotrauma. However, it took several years to identify the local injury resulting from intratidal opening and closing of parts of the lung (atelectrauma) and the inflammatory reaction of the lung to nonphysiological stress (biotrauma). Subsequently computed tomographic scanning showed that the lung fraction open to gas exchange in ARDS is small, equivalent in size to that of a young child (baby lung model). This observation provided the anatomical basis for the concept of volutrauma, focused on the excessive strain within the baby lung induced by tidal ventilation. Taken together, these multiple potentially damaging factors are now called ventilatorinduced lung injury (VILI). In the last decade, prevention of VILI through gentle lung treatment, by adjusting either tidal volume or PEEP, has become the major goal of mechanical ventilatory support not just for ARDS but for the broader population of patients with acute lung injury (ALI). With regard to tidal volume, this line of reasoning and research was most conclusively supported by the National Heart, Lung, and Blood Institute ARDS Network trial demonstrating an improvement in survival for patients with ALI or ARDS who were ventilated with low tidal volumes (6 mL/kg of predicted body weight) compared with those ventilated with higher tidal volumes (12 mL/kg of predicted body weight). Although many argued that the tidal volume in the control group might have been higher than existing practice, the tidal volume in the interventional group marked a stark departure from usual care and has resulted in a dramatic change in the approach to tidal volume setting for ALI and ARDS. The optimal PEEP strategy, however, has remained unresolved. Evidence from animal studies suggested that higher PEEP (in the range of 10-15 cm H2O) could prevent VILI. Thus, many clinicians were surprised when the first large randomized clinical trial comparing higher levels of PEEP with lower levels of PEEP in patients with ALI and ARDS, the National Heart, Lung, and Blood Institute’s ARDS Network Assessment of Low Tidal Volume and Elevated EndExpiratory Lung Volume to Obviate Lung Injury (ALVEOLI) study, was stopped for futility. In this issue of the JAMA, 2 new large international randomized trials examining the effects of PEEP on outcome in patients with ALI and ARDS are presented. In the Lung Open Ventilation (LOV) trial, the level of PEEP administered, either lower or higher, was selected according to an oxygenation scale conceptually similar to the one used in the previous ALVEOLI study. In the Expiratory Pressure (Express) trial, PEEP selection was based on a more subtle and refined approach, using bedside assessment of lung mechanics instead of gas exchange. This method identified a minimal distention strategy (lower level of PEEP) and an increased recruitment strategy (higher level of PEEP). Despite the different criteria used for PEEP selection, the PEEP levels tested were similar in the 2 studies. In the LOV study, mean PEEP levels on day 1 were 15.6 cm H2O and 10.1 cm H2O, and the subsequent hospital mortality rates were 36.4% and 40.4%. In the Express study, mean PEEP levels on day 1 were 15.8 cm H2O and 8.4 cm H2O, and the