Exogenous pulmonary surfactant for the treatment of adult patients with acute respiratory distress syndrome: results of a meta-analysis

Abstract

Introduction: The purpose of this study was to perform a systematic review and meta-analysis of exogenous surfactant administration to assess whether this therapy may be useful in adult patients with acute respiratory distress syndrome.

Methods: We performed a computerized literature search from 1966 to December 2005 to identify randomized clinical trials. The primary outcome measure was mortality 28-30 days after randomization. Secondary outcome measures included a change in oxygenation (PaO2:FiO2 ratio), the number of ventilation-free days, and the mean duration of ventilation. Meta-analysis was performed using the inverse variance method.

Results: Two hundred and fifty-one articles were identified. Five studies met our inclusion criteria. Treatment with pulmonary surfactant was not associated with reduced mortality compared with the control group (odds ratio 0.97; 95% confidence interval (CI) 0.73, 1.30). Subgroup analysis revealed no difference between surfactant containing surface protein or not - the pooled odds ratio for mortality was 0.87 (95% CI 0.48, 1.58) for trials using surface protein and the odds ratio was 1.08 (95% CI 0.72, 1.64) for trials without surface protein. The mean difference in change in the PaO2:FiO2 ratio was not significant (P = 0.11). There was a trend for improved oxygenation in the surfactant group (pooled mean change 13.18 mmHg, standard error 8.23 mmHg; 95% CI -2.95, 29.32). The number of ventilation-free days and the mean duration of ventilation could not undergo pooled analysis due to a lack of sufficient data.

Conclusion: Exogenous surfactant may improve oxygenation but has not been shown to improve mortality. Currently, exogenous surfactant cannot be considered an effective adjunctive therapy in acute respiratory distress syndrome.

Figure 1

Forest plot of mortality. This Forest plot represents the odds ratio (OR) (95% confidence interval) for 28-day to 30-day mortality in patients treated with surfactant compared with controls. OR < 1 indicates that treatment with surfactant was associated with a reduction in mortality compared with the control group, while OR > 1 indicates an increase in mortality with surfactant therapy. Areas of boxes are proportional to the respective study weight within the corresponding pooled analysis (see also weight values on the right). Eur-SA, European–South African trial; NA, North American trial.

Figure 2

Forest plot of the PaO₂:FiO₂ ratio. This Forest plot represents the mean difference in the change in the PaO₂:FiO₂ ratio (mmHg) of surfactant compared with controls. A positive value (i.e. right of 0) indicates that treatment with surfactant resulted in improved oxygenation at 24 hours compared with controls. Areas of boxes are proportional to the respective study weight within the corresponding pooled analysis (see also weight values on the right). Eur-SA, European–South African trial; NA, North American trial.