Is Inhaled Heparin a Viable Therapeutic Option in Inhalation Injury?

Abstract

Inhalation injury is a major cause of morbidity and mortality in patients with burns. Presence of airways injury adds to the need of fluid supplementation, increases risk of pulmonary complications. Due to many mechanisms involved in pathophysiology the treatment is complex. Among them the formation of fibrin casts inside airways constitutes a prominent element. The material residing in tracheobronchial tree causes ventilation-perfusion mismatch, complicates mechanical ventilation, provides a medium for bacterial growth. Many studies of animal models and single centre human studies investigated inhaled anticoagulation regimens employing heparin in management of inhalation injury. Simultaneously safety, especially in connection with possible bleeding risk, was the subject of research. The results suggest positive impact on treatment results, with low risk of side effects. This paper revise the available clinical data on inhaled heparin use in patients with burns.

Elucidating the Interactions Between Heparin/Heparan Sulfate and SARS-CoV-2-Related Proteins—An Important Strategy for Developing Novel Therapeutics for the COVID-19 Pandemic

“…Apart from its anti-coagulant effects, a retrospective cohort study found that IL-6 levels were significantly reduced while the percentage of lymphocytes was remarkably increased in the hospitalized COVID-19 treated with LMWH in comparison to the non-LMWH-treated group (Shi et al, 2020b), demonstrating the anti-inflammatory activity of the drug. In addition to the systemic administration, local application of heparin/LMWH through intranasal or inhalation route have also been reported for the treatment of lung diseases and inhalation injury (Yildiz-Pekoz and Ozsoy, 2017;Zielinski et al, 2019). Considering the antiviral activities of heparin/LMWH, along with data suggesting that the nasal epithelium is a portal for initial infection and transmission, Tandon et al suggested that intranasal administration of UFH may be an effective and safe prophylactic treatment SARS-CoV-2 transmission.…”

Japanese Society for Burn Injuries (JSBI) Clinical Practice Guidelines for Management of Burn Care (3rd Edition)

“…No references were used as evidence. A systematic review examining the effects of heparin inhalation on inhalation injury was reported in 2019; 2 this SR included six observational studies and one RCT, of which two observational studies showed reduced mortality with heparin inhalation, two observational studies showed reduced lung injury score, and one observational study reported shortening of the mechanical ventilation period. The RCT comparing inhaled doses of different heparins reported lower lung injury scores in the high dose (10,000 units every 2 h) group than in the low dose (5,000 units every 2 h) group.…”

“…An observational study included in the above systematic review reported that heparin inhalation increased the risk of pneumonia 2 . A protocol of inhaling 5,000 or 10,000 units of heparin every 2 or 4 h has not been shown to increase bleeding complications, but it may prolong activated partial thromboplastin time (APTT) and prothrombin time (PT), and its recommended to monitor these parameters 2 . In one RCT, 25,000 units of heparin was inhaled by the treatment group every 4 h, and the study was suspended after 13 cases were registered 3 .…”

“…Acute lung injury due to inhalation injury is associated with poor prognosis of burn patients 1 . In inhalation injury, the inflammation increases vascular permeability of the tracheal and bronchial mucosa, resulting in the formation of a pseudomembrane of exudate mixed with fibrin, blood clots, and necrotic tissue.…”

“…An SR examining the effects of combined use of heparin and N‐acetylcysteine inhalation on inhalation injury was published in 2019. This SR included six observational studies, two of which showed reduced mortality, two showed reduced lung injury score, and three reported shortening of the mechanical ventilation period in the treatment group 1,2 …”