Nebulised heparin is associated with fewer days of mechanical ventilation in critically ill patients: a randomised controlled trial

INTRODUCTION: Prolonged mechanical ventilation has the potential to aggravate or initiate pulmonary inflammation and cause lung damage through fibrin deposition. Heparin may reduce pulmonary inflammation and fibrin deposition. We therefore assessed whether nebulised heparin improved lung function in patients expected to require prolonged mechanical ventilation. METHODS: Fifty patients expected to require mechanical ventilation for more than 48 hours were enrolled in a double-blind randomised placebo-controlled trial of nebulised heparin (25,000 U) or placebo (normal saline) 4 or 6 hourly, depending on patient height. The study drug was continued while the patient remained ventilated to a maximum of 14 days from randomisation. RESULTS: Nebulised heparin was not associated with a significant improvement in the primary end-point, the average daily partial pressure of oxygen to inspired fraction of oxygen ratio while mechanically ventilated, but was associated with improvement in the secondary end-point ventilator free days amongst survivors at day 28 (22.6 4.0 versus 18.0 7.1, treatment difference 4.6 days, 95% CI 0.9 to 8.3, P = 0.02). Heparin administration was not associated with any increase in adverse events. CONCLUSIONS: Nebulised heparin was associated with fewer days of mechanical ventilation in critically ill patients expected to require prolonged mechanical ventilation. Further trials are required to confirm these findings. Trial registration: The Australian Clinical Trials Registry (ACTR-12608000121369