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

Barry Dixon1*, Marcus J Schultz2, Roger Smith1, James B Fink3, John D Santamaria1 and Duncan J Campbell45

Author Affiliations

1 Department of Intensive Care, St. Vincent's Hospital, 41 Victoria Parade, Fitzroy, Melbourne, Victoria, 3065, Australia

2 Department of Intensive Care Medicine & Laboratory of Experimental Intensive Care and Anesthesiology, The Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands

3 Division of Respiratory Therapy, School of Health Professions, College of Health and Human Sciences, Georgia State University, 424 One Park Place South, Atlanta, GA 30302-4019, USA

4 St. Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, Melbourne, Victoria, 3065, Australia

5 Department of Medicine, The University of Melbourne, Clinical Sciences Building, 29 Regent Street, Fitzroy, Melbourne, Victoria, 3065, Australia

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Critical Care 2010, 14:R180  doi:10.1186/cc9286

Published: 11 October 2010

Abstract

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 nebulized 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 randomized placebo-controlled trial of nebulized 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 randomization.

Results

Nebulized 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

Nebulized 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).