Positive End-Expiratory Pressure Lower Than the ARDS Network Protocol Is Associated with Higher Pediatric Acute Respiratory Distress Syndrome Mortality

Abstract

Rationale: The ARDS Network (ARDSNet) used a positive end-expiratory pressure (PEEP)/Fi_O2 model in many studies. In general, pediatric intensivists use less PEEP and higher Fi_O2 than this model.

Objectives: To evaluate whether children managed with PEEP lower than recommended by the ARDSNet PEEP/Fi_O2 model had higher mortality.

Methods: This was a multicenter, retrospective analysis of patients with pediatric acute respiratory distress syndrome (PARDS) managed without a formal PEEP/Fi_O2 protocol. Four distinct datasets were combined for analysis. We extracted time-matched PEEP/Fi_O2 values, calculating the difference between PEEP level and the ARDSNet-recommended PEEP level for a given Fi_O2. We analyzed the median difference over the first 24 hours of PARDS diagnosis against ICU mortality and adjusted for confounding variables, effect modifiers, or factors that may have affected the propensity to use lower PEEP.

Measurements and main results: Of the 1,134 patients with PARDS, 26.6% were managed with lower PEEP relative to the amount of Fi_O2 recommended by the ARDSNet protocol. Patients managed with lower PEEP experienced higher mortality than those who were managed with PEEP levels in line with or higher than recommended by the protocol (P < 0.001). After adjustment for hypoxemia, inotropes, comorbidities, severity of illness, ventilator settings, nitric oxide, and dataset, PEEP lower than recommended by the protocol remained independently associated with higher mortality (odds ratio, 2.05; 95% confidence interval, 1.32-3.17). Findings were similar after propensity-based covariate adjustment (odds ratio, 2.00; 95% confidence interval, 1.24-3.22).

Conclusions: Patients with PARDS managed with lower PEEP relative to Fi_O2 than recommended by the ARDSNet model had higher mortality. Clinical trials targeting PEEP management in PARDS are needed.

Keywords: ARDS Network; acute lung injury; acute respiratory distress syndrome; pediatrics; positive end expiratory pressure.

Figure 1.

All pediatric acute respiratory distress syndrome (PARDS) positive end-expiratory pressure (PEEP)/Fi_O2 combinations. Actual PEEP values as a function of actual Fi_O2 levels (median [bar] and interquartile range [box]) for all patients with PARDS for the first day of mechanical ventilation after PARDS diagnosis. The superimposed line represents the ARDS Network protocol target combinations of PEEP/Fi_O2. In general, clinicians used more PEEP than recommended when Fi_O2 was less than 0.4 and used less PEEP than recommended when Fi_O2 was more than 0.5. Median PEEP level did not exceed 10 cm H₂O, regardless of Fi_O2.

Figure 2.

Unadjusted pediatric acute respiratory distress syndrome (PARDS) mortality as a function of positive end-expiratory pressure (PEEP) discordance from the ARDS Network (ARDSNet) PEEP/Fi_O2 protocol for all patients, and stratified by initial Pa_O2/Fi_O2 (PF) ratio group. Total N = 1,134 with 18.6% mortality. Total number of patients with PARDS in each PEEP range is represented by the bars, and ICU mortality (with SE) is represented by the squares. (A) All patients with PARDS. There was approximately an even split between patients managed with PEEP below protocol, per protocol, and above protocol. PEEP lower than recommended by the ARDSNet protocol for a given Fi_O2 was associated with higher mortality. The lowest mortality occurred when PEEP was 1 to 4 cm H₂O above protocol. (B) PF 200 to 300; (C) PF 100 to 200; (D) PF less than or equal to 100. The general trend that mortality is higher for those with PEEP lower than protocol is consistent across all initial PF subgroups. As initial PF ratio worsens, the number of patients managed with PEEP lower than protocol increases.

Figure 3.

Survival curves for patients on positive end-expiratory pressure (PEEP) lower than recommended by the protocol versus PEEP in line or higher than recommended by the protocol for a given Fi_O2, stratified by initial Pa_O2/Fi_O2 (PF) ratio. (A) All patients; (B) PF 200 to 300; (C) PF 100 to 200; (D) PF less than or equal to 100. For all patients, use of PEEP lower than recommended by the protocol for a given Fi_O2 was associated with higher mortality (P < 0.0001). When subgrouping by initial PF ratio, the trends were consistent, but only statistically significant for PF between 100 and 200 (PF < 100, P = 0.3; PF 100–200, P = 0.004; PF 200–300, P = 0.4). PARDS = pediatric acute respiratory distress syndrome.

Figure 4.

Positive end-expiratory pressure (PEEP) distribution for Children’s Hospital of Philadelphia (CHOP) (blue, top) versus Children’s Hospital Los Angeles (CHLA) (orange, bottom). There is a relatively normal distribution of PEEP in the CHOP dataset, which is shifted slightly to the right when Fi_O2 is increased over 0.5 (top right). In contrast, CHLA data have more variability in PEEP, which is retained, although shifted to the right, when Fi_O2 is increased over 0.5 (bottom right). obs = observations.

Figure 5.

Differences in ventilator strategy on Day 1 of acute respiratory distress syndrome (ARDS) between Children’s Hospital of Philadelphia (CHOP) and Children’s Hospital Los Angeles (CHLA), stratified by Pa_O2/Fi_O2 (PF) ratio 24 hours after pediatric ARDS (PARDS) diagnosis. All variables are scaled to a maximum value of 1 for each variable, to highlight relative differences between datasets. Actual values for these parameters can be found in Tables 4 and E4. The individual squares and diamonds represent the median value for the dataset for a given variable. (A) For all patients, CHOP generally used a higher mean airway pressure (PAW), higher positive end-expiratory pressure (PEEP), and slightly lower Fi_O2 than CHLA, with slightly higher PF ratio and oxygenation index (OI), and similar driving pressure and Vt. (B and C) For patients with PF ratio (B) 200 to 300 or (C) 100 to 200, PAW and PEEP are higher at CHOP than CHLA. (D) For those with PF less than or equal to 100, PAW, PEEP, OI, and PF ratio are similar between datasets, although Fi_O2, Vt, and driving pressure are slightly higher at CHOP.