The value of positive end-expiratory pressure and Fio₂ criteria in the definition of the acute respiratory distress syndrome

Abstract

Objectives: The criteria that define acute lung injury and the acute respiratory distress syndrome include PaO₂/Fio₂ but not positive end-expiratory pressure or Fio2. PaO2/Fio2 ratios of some patients increase substantially after mechanical ventilation with positive end-expiratory pressure of 5-10 cm H₂O, and the mortality of these patients may be lower than those whose PaO₂/Fio₂ratios remain <200. Also, PaO₂/Fio₂ may increase when Fio2 is raised from moderate to high levels, suggesting that patients with similar PaO₂/Fio₂ ratios but different Fio₂ levels have different risks of mortality. The primary purpose of this study was to assess the value of adding baseline positive end-expiratory pressure and Fio₂ to PaO₂/Fio₂ for predicting mortality of acute lung injury/acute respiratory distress syndrome patients enrolled in Acute Respiratory Distress Syndrome Network clinical trials. We also assessed effects of two study interventions on clinical outcomes in subsets of patients with mild and severe hypoxemia as defined by PaO₂/Fio₂.

Design: Analysis of baseline physiologic data and outcomes of patients previously enrolled in clinical trials conducted by the National Institutes of Health Acute Respiratory Distress Syndrome Network.

Setting: Intensive care units of 40 hospitals in North America.

Patients: Two thousand three hundred and twelve patients with acute lung injury/acute respiratory distress syndrome.

Interventions: None.

Measurements and main results: Only 1.3% of patients enrolled in Acute Respiratory Distress Syndrome Network trials had baseline positive end-expiratory pressure < 5 cm H₂O, and 50% had baseline positive end-expiratory pressure ≥10 cm H₂O. Baseline PaO₂/Fio₂ predicted mortality, but after controlling for PaO₂/Fio₂, baseline positive end-expiratory pressure did not predict mortality. In contrast, after controlling for baseline PaO₂/Fio₂, baseline Fio₂ did predict mortality. Effects of two study interventions (lower tidal volumes and fluid-conservative hemodynamic management) were similar in mild and severe hypoxemia subsets as defined by PaO₂/Fio₂ ratios.

Conclusion: At Acute Respiratory Distress Syndrome Network hospitals, the addition of baseline positive end-expiratory pressure would not have increased the value of PaO₂/Fio₂ for predicting mortality of acute lung injury/acute respiratory distress syndrome patients. In contrast, the addition of baseline Fio2 to PaO₂/Fio₂ could be used to identify subsets of patients with low or high mortality.

Figure 1

Frequency distribution of baseline PEEP. Numbers over bars indicate numbers of patients at each level of PEEP and percentages of all patients.

Figure 2

Relationship of baseline PEEP to baseline FiO₂. The width of each bar is proportional to the number of patients at each PEEP-FiO₂ combination. Red bars indicate median PEEP levels at each of the FiO₂ ranges.

Figure 3

Effects on mortality of tidal volume reduction in mild and severe hypoxemia subsets in the ARDS Network clinical trial of mechanical ventilation with traditional versus lower tidal volumes (2). Effects of tidal volume reduction were not significantly different in the mild and severe hypoxemia subsets. Mortality rates in the lower and higher tidal volume study groups are represented by the light bars and dark bars, respectively. Values in parentheses are standard deviations.

Figure 4

Effects on ventilator-free days of fluid-conservative versus fluid-liberal hemodynamic management in mild and severe hypoxemia subsets of the ARDS Network clinical trial of hemodynamic management strategies (4). Effects of hemodynamic management strategy were not significantly different in the mild and severe hypoxemia subsets. Ventilator-free days in the fluid-conservative and fluid-liberal study groups are represented by the light bars and dark bars, respectively. Values in parentheses are standard deviations.

Figure 5

Frequency distributions of PaO₂/FiO₂ ratio at baseline (light bars) and on the first day after enrollment (dark bars) in the ARDS Network clinical trial of mechanical ventilation with lower versus higher PEEP (3). Left: Higher PEEP study group. Right: Lower PEEP study group.