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Open AccessArticle

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

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Laboratory of Experimental Intensive Care and Anesthesiology (L·E·I·C·A), Amsterdam University Medical Centers, 1105 AZ Amsterdam, The Netherlands
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Department of Anesthesiology, Amsterdam University Medical Centers, 1105 AZ Amsterdam, The Netherlands
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Department of Intensive Care, Amsterdam University Medical Centers, 1105 AZ Amsterdam, The Netherlands
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Department of Intensive Care, University Hospital Gasthuisberg, 3000 Leuven, Belgium
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Department of Intensive Care, Maasstad Hospital, 3079 DZ Rotterdam, The Netherlands
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Department of Intensive Care, Ghent University Hospital, 9000 Ghent, Belgium
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Department of Intensive Care, St Vincent’s Hospital, Melbourne 3065, Australia
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Department of Intensive Care, Red Cross Hospital, 1942 LE Beverwijk, The Netherlands
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Department of Vascular Medicine, Amsterdam University Medical Centers, 1105 AZ Amsterdam, The Netherlands
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Department of Intensive Care, Martini Hospital, 9728 NT Groningen, The Netherlands
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Department of Intensive Care and Faculty of Medicine and Pharmacy, University Hospital Brussels, Jette, Belgium and Free University of Brussels, 1090 Brussels, Belgium
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2020, 9(4), 894; https://doi.org/10.3390/jcm9040894 (registering DOI)
Received: 12 March 2020 / Accepted: 20 March 2020 / Published: 25 March 2020
(This article belongs to the Special Issue Anesthesia for the High-Risk Patient)
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: burn; inhalation trauma; heparin; nebulization; safety burn; inhalation trauma; heparin; nebulization; safety
MDPI and ACS Style

Glas, G.J.; Horn, J.; Binnekade, J.M.; Hollmann, M.W.; Muller, J.; Cleffken, B.; Colpaert, K.; Dixon, B.; Juffermans, N.P.; Knape, P.; Levi, M.M.; Loef, B.G.; Mackie, D.P.; Malbrain, M.L.; Preckel, B.; Reidinga, A.C.; van der Sluijs, K.; Schultz, M.J. Nebulized Heparin in Burn Patients with Inhalation Trauma—Safety and Feasibility. J. Clin. Med. 2020, 9, 894.

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