The design of future pediatric mechanical ventilation trials for acute lung injury

Abstract

Pediatric practitioners face unique challenges when attempting to translate or adapt adult-derived evidence regarding ventilation practices for acute lung injury or acute respiratory distress syndrome into pediatric practice. Fortunately or unfortunately, there appears to be selective adoption of adult practices for pediatric mechanical ventilation, many of which pose considerable challenges or uncertainty when translated to pediatrics. These differences, combined with heterogeneous management strategies within pediatric critical care, can complicate clinical practice and make designing robust clinical trials in pediatric acute respiratory failure particularly difficult. These issues surround the lack of explicit ventilator protocols in pediatrics, either computer or paper based; differences in modes of conventional ventilation and perceived marked differences in the approach to high-frequency oscillatory ventilation; challenges with patient recruitment; the shortcomings of the definition of acute lung injury and acute respiratory distress syndrome; the more reliable yet still somewhat unpredictable relationship between lung injury severity and outcome; and the reliance on potentially biased surrogate outcome measures, such as ventilator-free days, for all pediatric trials. The purpose of this review is to highlight these challenges, discuss pertinent work that has begun to address them, and propose potential solutions or future investigations that may help facilitate comprehensive trials on pediatric mechanical ventilation and define clinical practice standards.

Figure 1.

Distribution of Vt in ml/kg of actual body weight from 75 patients with acute lung injury/acute respiratory distress syndrome across 59 pediatric intensive care units in Europe and North America. There was significant variability in management, with Vt available on less than half of the 165 patients. Pediatric intensivists embraced a “low” Vt (median, 7 ml/kg; interquartile range, 6–9) strategy. Reprinted by permission from Reference .

Figure 2.

Vt based on lung disease severity, using a lung-protective pressure-control strategy. As lung injury severity increases (as measured by increasing lung injury score), Vt is naturally limited, with patients with the most severe lung injury achieving median Vt just under 6 ml/kg. Data expressed as median, interquartile range, and actual range. Reprinted by permission from Reference .

Figure 3.

Oxygenation index before initiation of high-frequency oscillatory ventilation (HFOV), shortly after initiation, and then 24 hours later. Data presented as median and interquartile range (IQR). Overall difference by Kruskal-Wallis analysis of variance, P = 0.009. Multiple comparisons by mean ranks. Pre and 24-hour post P = 0.67. Unpublished data from a single institution (Children's Hospital Los Angeles). HFOV implemented at a median of 3.5 (IQR, 1.25–7.5) days into mechanical ventilation for acute hypoxemic respiratory failure.

Figure 4.

For 6,017 charted ventilator settings from 402 children with acute hypoxemic respiratory failure, Fi_O2 was changed 1,869 times. When practitioners change Fi_O2 they frequently make changes at intervals of 0.05, both for increases and decreases of Fi_O2. This is in contrast to the Acute Respiratory Distress Syndrome Network protocol, which implements changes in Fi_O2 at intervals of 0.1. Reprinted with permission from Reference .

Figure 5.

Measurement from a 4.0-kg infant with a cuffed endotracheal tube in pressure-control mode with tube compensation active. On the left, flow-volume measurements are made at the ventilator with compensation for tubing compliance. There is “overshoot” of flow measurements causing volumes to be larger and giving the expiratory portion of the flow-volume curve (below the horizontal axis) a pattern of obstructive airways disease. Vt is 12.3 ml/kg. On the right, measurements are made at the endotracheal tube connector within a minute of the left panel. Here, the flows and volumes are much lower with Vt now one-third at 4.1 ml/kg. The flow pattern on the expiratory limb now resembles that of normal airways. ETT = endotracheal tube; VTE = exhaled tidal volume.

Figure 6.

Mortality stratified by time-weighted average oxygenation index (OI) on the first day of mechanical ventilation after meeting criteria for acute lung injury (n = 156 children). Note the stepwise increase in mortality as oxygenation index increases. Unpublished data from a single institution (Children's Hospital Los Angeles).