Exogenous surfactant may improve oxygenation but not mortality in adult patients with acute lung injury/acute respiratory distress syndrome: a meta-analysis of 9 clinical trials

Abstract

Objective: To evaluate whether exogenous surfactant therapy may be useful in adult patients with acute lung injury or acute respiratory distress syndrome, using a meta-analysis of published clinical trials.

Design: A comprehensive literature search was performed to identify all randomized clinical trials examining the effects of the treatment of acute lung injury/acute respiratory distress syndrome with exogenous surfactant in adults. The primary outcome measurement was mortality 28 or 30 days after randomization. Secondary outcome measurements included a change in the ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen in the first 24 hours or after 120 hours, the number of ventilation-free days, and any adverse effects. The meta-analysis was performed using the Review Manager 5.0.0 system.

Participants: Randomized clinical trials.

Intervention: Meta-analysis of 9 trials.

Measurements and main results: Nine trials involving 2,575 patients were included in the meta-analysis. The analysis showed that treatment with exogenous pulmonary surfactant does not decrease mortality significantly. There was a significant effect of exogenous surfactant treatment on the change in the partial pressure of arterial oxygen/fraction of inspired oxygen ratio in the first 24 hours but this was lost by 120 hours. The duration of ventilation trended lower in surfactant-treated patients but this was not significant. In addition, surfactant-treated patients had a significantly higher risk of adverse effects.

Conclusions: An exogenous surfactant may improve oxygenation over the first 24 hours after administration. However, treatment does not improve mortality and oxygenation over ≥120 hours after administration and results in a high rate of adverse effects. Therefore, the present data suggest that an exogenous surfactant cannot be considered an effective adjunctive therapy in patients with acute lung injury/acute respiratory distress syndrome.

Fig 1

Trial selection flowchart indicates the process used for selecting relevant randomized clinical trials included in the present meta-analysis.

Fig 2

Pulmonary surfactant and mortality at 28 or 30 days with odds ratios and 95% confidence intervals. The size of the data markers (squares) is approximately proportional to the statistical weight of each trial. CI, confidence interval; M-H, Mantel-Haenszel.

Fig 3

Pulmonary surfactant and mortality at 28 or 30 days with odds ratios and 95% confidence intervals for mortality and surface protein with intratracheal delivery methods (top), direct lung injury (middle), and protein C (bottom). The size of the data markers (squares) is approximately proportional to the statistical weight of each trial. CI, confidence interval; M-H, Mantel-Haenszel.

Fig 4

Pulmonary surfactant and mean difference in the change of the ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen during 24 hours with mean differences and 95% confidence intervals. The size of the data markers (squares) is approximately proportional to the statistical weight of each trial. CI, confidence interval; IV, inverse variance; SD, standard deviation.

Fig 5

Pulmonary surfactant and rate of adverse effect with odds ratios and 95% confidence intervals. Rates of adverse effects related to treatment (top) and severe complications (bottom) are presented. The size of the data markers (squares) is approximately proportional to the statistical weight of each trial. CI, confidence interval; M-H, Mantel-Haenszel.