venticute and Respiratory-Distress-Syndrome

Studies to date have shown no survival benefit for the use of exogenous surfactant to treat patients with the ARDS. To identify specific patient subgroups for future study, we performed an exploratory post hoc analysis of clinical trials of recombinant surfactant protein-C (rSP-C) surfactant (Venticute; Nycomed GmbH; Konstanz, Germany).. We performed a pooled analysis of all five multicenter studies in which patients with ARDS due to various predisposing events were treated with rSP-C surfactant. Patients received either usual care (n = 266) or usual care plus up to four intratracheal doses (50 mg/kg) of rSP-C surfactant (n = 266). Factors influencing the study end points were analyzed using descriptive statistics, analysis of covariance, and logistic regression models.. ARDS was most often associated with pneumonia or aspiration, sepsis, and trauma or surgery. For the overall patient population, treatment with rSP-C surfactant significantly improved oxygenation (p = 0.002) but had no effect on mortality (32.6%). Multivariate analysis showed age and acute physiology and chronic health evaluation (APACHE) II score to be the strongest predictors of mortality. In the subgroup of patients with severe ARDS due to pneumonia or aspiration, surfactant treatment was associated with markedly improved oxygenation (p = 0.0008) and improved survival (p = 0.018).. rSP-C surfactant improved oxygenation in patients with ARDS irrespective of the predisposition. Post hoc evidence of reduced mortality associated with surfactant treatment was obtained in patients with severe respiratory insufficiency due to pneumonia or aspiration. Those patients are the focus of a current randomized, blinded, clinical trial with rSP-C surfactant.

Topics: Adult; Aged; Female; Humans; Instillation, Drug; Male; Middle Aged; Pulmonary Surfactants; Recombinant Proteins; Respiratory Distress Syndrome; Trachea; Treatment Outcome

The pharmaceutical application of exogenous natural pulmonary surfactant preparations has shown its efficiency in the therapeutical treatment of infants with Respiratory Distress Syndrome. At the same time, the use of these preparations in patients with Acute Respiratory Distress Syndrome, although not still an effective therapy, shows promising results. The analysis of composition, structure and surface activity of some of the different natural surfactant preparations available today for clinical use reveals important differences, a fact that opens horizons in the optimization of new effective formulations in the treatment of the Acute Respiratory Distress Syndrome. The purpose of this review is to carry out an updating of the current models interpreting the role of the main components of pulmonary surfactant as a reference to evaluate the biochemical composition of the preparations of exogenous natural pulmonary surfactant currently in use and their apparent pharmacological effect.

Topics: Animals; Humans; Intercellular Signaling Peptides and Proteins; Peptides; Pulmonary Surfactants; Recombinant Proteins; Respiratory Distress Syndrome

Extensive biochemical and biophysical changes of the pulmonary surfactant system occur in the acute respiratory distress syndrome (ARDS).. The effect of intrabronchial administration of a recombinant surfactant protein C-based surfactant preparation (Venticute) on gas exchange, surfactant composition and function was investigated in 31 patients with ARDS in a randomised controlled phase I/II clinical pilot trial. Bronchoalveolar lavage fluids for surfactant analysis were obtained 3 h before and 48 and 120 h after the first surfactant application. Potentially deleterious effects of surfactant neutral lipids in patients with ARDS were also identified.. Before treatment all patients had marked abnormalities in the surfactant phospholipid and protein composition. In response to surfactant treatment, gas exchange improved and surfactant phospholipid and protein content were almost normalised. Alveolar surface activity was dramatically impaired before treatment and only partially improved after surfactant administration. Further analysis of the bronchoalveolar lavage fluids revealed a twofold increase in neutral lipid content and altered neutral lipid profile in patients with ARDS compared with healthy controls. These differences persisted even after administration of large amounts of Venticute. Supplementation of Venticute or natural surfactant with a synthetic neutral lipid preparation, mimicking the profile in ARDS, caused a dose-dependent deterioration of surface activity in vitro.. Intrabronchial surfactant treatment improves gas exchange in ARDS, but the efficacy may be limited by increased concentration and altered neutral lipid profile in surfactant under these conditions.

Topics: Adult; Bronchoalveolar Lavage Fluid; Fatty Acids; Female; Humans; Lipids; Male; Middle Aged; Phospholipids; Pulmonary Alveoli; Pulmonary Gas Exchange; Pulmonary Surfactants; Recombinant Proteins; Respiratory Distress Syndrome

Topics: Drug Administration Schedule; Humans; Pulmonary Surfactants; Recombinant Proteins; Respiratory Distress Syndrome