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

Critical Care, Mar 2006

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.

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

Warren J Davidson 2 Del Dorscheid 1 2 Roger Spragg 0 Michael Schulzer 2 Edwin Mak 2 Najib T Ayas 1 2 3 Corresponding author: Warren J Davidson 0 University of California at San Diego, California , USA 1 Intensive Care Unit Providence Healthcare , Vancouver, British Columbia , Canada 2 Department of Medicine University of British Columbia , Vancouver, British Columbia , Canada 3 Centre for Clinical Epidemiology and Evaluation, Vancouver Coastal Health Research Institute , Vancouver, British Columbia , Canada 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. Metaanalysis was performed using the inverse variance method. - Introduction Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in the intensive care unit. Patients with ARDS exhibit an intense inflammatory reaction centered in the lung parenchyma, resulting in alveolar flooding and collapse, in reduced lung compliance, in increased work of breathing, and in severe impairments in gas exchange [1-4]. Patients with ARDS have an inhospital mortality rate ranging from 34% to 60% [5]. Treatment of patients with ARDS is largely supportive, and includes mechanical ventilation with low tidal volumes [6], positive end expiratory pressure to open collapsed alveoli [7], supplemental oxygen, and supportive care of other organ system failures. Given the high mortality rate of patients with ARDS, other therapies are clearly needed. Administration of exogenous pulmonary surfactant is an adjunctive therapy that may help adult patients with ARDS. Pulmonary surfactant is produced by type II alveolar cells and is composed of two major fractions: phospholipids (90%) and surfactant-specific proteins (10%). Surfactant decreases alveolar surface tension, thereby preventing alveolar collapse and allowing efficient gas exchange at low transpulmonary pressures. Furthermore, surfactant has important roles in host immune defense, through both specific and nonspecific mechanisms [8]. Patients with ARDS show injury to the alveolar epithelial barrier with consequent surfactant dysfunction. Indeed, surfactant recovered from bronchoalveolar lavage fluid from ARDS patients has alterations of the phospholipid and fatty acid profile, has decreased levels of surfactant-specific proteins, and has impaired surface-tension-lowering properties. Causes of this impairment include the inhibition of surfactant function by protein-rich edema fluid, by surfactant lipid peroxidation, and by surfactant protein degradation [1,9]. Given these abnormalities, administration of exogenous pulmonary surfactant has been considered a possible treatment option in adult patients with ARDS [8]. The purpose of this study was to perform a systematic review and meta-analysis of exogenous surfactant administration to assess whether this therapy, as currently administered, may be useful in adult patients with ARDS. Materials and methods Study identification We performed a computerized search to identify articles that compared treatment with exogenous pulmonary surfactant against the usual therapy for patients diagnosed with ARDS. For our analysis, we only included studies that were randomized controlled clinical trials, that compared the use of exogenous pulmonary surfactant to an appropriate control group (defined as patients receiving standard therapy with or without a placebo), that evaluated mortality and/or pulmonary physiological parameters, and that used objective documentation of ARDS using accepted criteria at the time of the individual study publication. Abstracts, case reports, editorials, nonhuman studies, and nonEnglish studies were excluded. We performed a computerized literature search of MEDLINE (1966December 2005), EMBASE (1980December 2005), Cochrane Database of Systematic Reviews (1996December 2005), Cochrane controlled trials register (1996December 2005), and the Database of Abstracts and Reviews of Effects (1994December 2005) to identify clinical studies and systematic reviews. We conducted the search for human studies using the following combination of exploded medical subject headings and text words: ('adult respiratory distress syndrome' or 'acute respiratory distress syndrome' or 'ARDS') and ('pulmonary surfactant' or 'lung surfactant') and ('adult'). The reference lists of all articles selected were then hand-searched for additional citations missed in the search. Study selection Two authors (WJD, NTA) independently reviewed the (...truncated)


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Warren J Davidson, Del Dorscheid, Roger Spragg, Michael Schulzer, Edwin Mak, Najib T Ayas. Exogenous pulmonary surfactant for the treatment of adult patients with acute respiratory distress syndrome: results of a meta-analysis, Critical Care, 2006, pp. R41, 10, DOI: 10.1186/cc4851