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

• Main Authors: Gerie J. Glas, Janneke Horn, Jan M. Binnekade, Markus W. Hollmann, Jan Muller, Berry Cleffken, Kirsten Colpaert, Barry Dixon, Nicole P. Juffermans, Paul Knape, Marcel M. Levi, Bert G. Loef, David P. Mackie, Manu L.N.G. Malbrain, Benedikt Preckel, Auke C. Reidinga, K.F. van der Sluijs, Marcus J. Schultz
• Format: Article
• Language: English
• Published: MDPI AG 2020-03-01
• Series: Journal of Clinical Medicine
• Subjects: burn; inhalation trauma; heparin; nebulization; safety
• Online Access: https://www.mdpi.com/2077-0383/9/4/894

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 <i>N</i> = 7, placebo <i>N</i> = 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.