Key Point

In a post hoc pooled analysis of clinical trials, evidence suggests that recombinant surfactant protein-C surfactant may reduce mortality in patients with direct ARDS (ie, severe respiratory insufficiency due to pneumonia or aspiration).

Not only can recombinant surfactant protein-C (rSP-C) surfactant improve oxygenation in all ARDS patients, said researchers in the October Chest, it may also reduce mortality in the subset of patients with severe direct ARDS—that is, patients with severe respiratory insufficiency due to pneumonia or aspiration of gastric contents.

Previous studies have not shown a survival benefit of surfactant therapy; however, those meta-analyses varied widely in surfactant preparations, patient populations, and protocols, the researchers noted. The current investigation, a post hoc pooled analysis of five multicenter randomized trials with similar study protocols, exclusively examined use of rSP-C surfactant; the German company Nycomed GmbH sponsored the trials and supplied the study medication.

“The aim of this analysis was to identify patients who are the most likely to benefit from surfactant therapy by accounting for all variability … and thereby to gain a strategic direction for future clinical study design and evaluations.” To this end, Friedemann J. H. Taut, MD, of Nycomed in Konstanz, Germany, and colleagues assessed 28-day mortality, oxygenation, and ventilator-free days to day 28.

In each of the five trials examined, intubated and mechanically ventilated patients were randomly assigned to receive either usual care with no surfactant or as many as four intratracheal doses of rSP-C surfactant per 24-hour period, with each dose consisting of 1 mg of rSP-C and 50 mg of phospholipid per kilogram of lean body weight.

Patient characteristics and the predisposing events for ARDS—including sepsis syndrome, pneumonia, trauma/surgery, witnessed aspiration, multiple blood transfusions, and pancreatitis—were similar between groups, as were the overall mortality rates (34.0% and 31.3% in the rSP-C surfactant and usual care groups, respectively). Among the treatment groups, the individual predisposing events did not appear to affect mortality rates, nor did treatment decrease mortality among the group of patients with severe ARDS (ie, a baseline fraction of inspired oxygen of ≥ 0.7). For patients with severe direct ARDS, treatment with rSP-C was significantly associated with reduced mortality (odds ratio, 0.30).

Multivariate analysis showed a direct link between mortality and age, APACHE II score, PEEP, and presence of pneumonia or direct ARDS, and an indirect link between mortality and BMI. Consistent with prior research, patients in the rSP-C surfactant groups had more improved oxygenation than those in the usual care groups.

“Indirect ARDS is thought to be characterized by primary vascular and interstitial disease processes,” the researchers surmised, “whereas direct ARDS may be more related to an initial injury of the alveolar environment, leading to alveolar edema containing inflammatory agents that can inactivate and/or destroy surfactant.” They also noted that patients with direct ARDS may benefit most from surfactant treatment because they have lower pulmonary compliance than those with indirect lung injury, and surfactant has been shown to increase pulmonary compliance and alveolar recruitment.

—Adriene Marshall

Suggested Reading
Taut FJH, Rippin G, Schenk P, et al. A search for subgroups of patients with ARDS who may benefit from surfactant replacement therapy: a pooled analysis of five studies with recombinant surfactant protein-C surfactant (Venticute). Chest. 2008;134(4):724-732.

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