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Nebulized Heparin in Burn Patients with Inhalation Trauma—Safety and Feasibility

Sciprofile linkGerie J. Glas, Sciprofile linkJanneke Horn, Sciprofile linkJan M. Binnekade, Sciprofile linkMarkus W. Hollmann, Sciprofile linkJan Muller, Sciprofile linkBerry Cleffken, Sciprofile linkKirsten Colpaert, Sciprofile linkBarry Dixon, Sciprofile linkNicole P. Juffermans, Sciprofile linkPaul Knape, Sciprofile linkMarcel Levi, Sciprofile linkBert G. Loef, Sciprofile linkDavid P. Mackie, Sciprofile linkManu L. N. G. Malbrain, Sciprofile linkBenedikt Preckel, Sciprofile linkAuke C. Reidinga, Sciprofile linkK.F. Van Der Sluijs, Sciprofile linkMarcus J. Schultz
Published: 25 March 2020
 by  MDPI
Journal of Clinical Medicine , Volume 9; doi:10.3390/jcm9040894

Abstract: Background: Pulmonary hypercoagulopathy is intrinsic to inhalation trauma. Nebulized heparin could theoretically be beneficial in patients with inhalation injury, but current data are conflicting. We aimed to investigate the safety, feasibility, and effectiveness of nebulized heparin. Methods: International multicenter, double-blind, placebo-controlled randomized clinical trial in specialized burn care centers. Adult patients with inhalation trauma received nebulizations of unfractionated heparin (25,000 international unit (IU), 5 mL) or placebo (0.9% NaCl, 5 mL) every four hours for 14 days or until extubation. The primary outcome was the number of ventilator-free days at day 28 post-admission. Here, we report on the secondary outcomes related to safety and feasibility. Results: The study was prematurely stopped after inclusion of 13 patients (heparin N = 7, placebo N = 6) due to low recruitment and high costs associated with the trial medication. Therefore, no analyses on effectiveness were performed. In the heparin group, serious respiratory problems occurred due to saturation of the expiratory filter following nebulizations. In total, 129 out of 427 scheduled nebulizations were withheld in the heparin group (in 3 patients) and 45 out of 299 scheduled nebulizations were withheld in the placebo group (in 2 patients). Blood-stained sputum or expected increased bleeding risks were the most frequent reasons to withhold nebulizations. Conclusion: In this prematurely stopped trial, we encountered important safety and feasibility issues related to frequent heparin nebulizations in burn patients with inhalation trauma. This should be taken into account when heparin nebulizations are considered in these patients.
Keywords: safety / Heparin / Burn / Nebulization / Inhalation Trauma

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