Acute Lung Injury in Critically Ill Patients: Actin-Scavenger Gelsolin Signals Prolonged Respiratory Failure

BACKGROUND: Gelsolin is an actin-scavenger controlling the tissue damage from actin in the blood. Gelsolin levels in circulation drops when tissue damage and corresponding actin release is pronounced due to catabolic conditions. The purpose of this study was to determine if low plasma gelsolin independently predicts a reduced chance of weaning from ventilator-demanding respiratory failure in critically ill patients within 28 days from admission. RESULTS: This cohort study included 746 critically ill patients with ventilator-demanding respiratory failure from the randomized clinical trial, “Procalcitonin And Survival Study (PASS).” Primary end point was successful weaning from mechanical ventilation within 28 days. We used multivariable Cox regression adjusted for age, sepsis, PaO(2)/FiO(2) ratio and other known and suspected predictors of persistent respiratory failure. Follow-up was complete. For medical patients, baseline-gelsolin below the 25th percentile independently predicted a 40% lower chance of successful weaning within 28 days (HR 0.60, 95% CI 0.46–0.79, P = 0.0002); among surgical patients this end point was not predicted. Low gelsolin levels predicted chance of being “alive and out of intensive care at day 14” for both medical and surgical patients (HR 0.69, 95% CI 0.54–0.89, P = 0.004). Gelsolin levels did not predict 28 day mortality for surgical or medical patients. CONCLUSIONS: Low levels of serum gelsolin independently predict a decreased chance of successful weaning from ventilator within 28 days among medical intensive care patients. This finding has implications for identifying patients who need individualized intervention early in intensive care course to prevent unfavorable lung prognosis in acute respiratory failure. TRIAL REGISTRATION: This is a substudy to the PASS, Clinicaltrials.gov ID: NCT00271752, first registered January 1, 2006.