Safety and potential anticoagulant effects of nebulised heparin in burns patients with inhalational injury at Singapore General Hospital Burns Centre
Introduction
Inhalation lung injury (ILI) is a leading cause of death in burns patients. In a recent multivariate analysis done at our burn centre from 2003 to 2005, ILI was found to significantly increase mortality rate from 4.5% to 50.0% [1]. The presence of ILI in burns patients is found to be associated with an increased incidence of pulmonary complications. A study by Hollingsed et al. showed that patients with ILI had a 73% incidence of respiratory failure (hypoxemia, prolonged ventilator support or multiple pulmonary infections) and a 20% incidence of acute respiratory distress syndrome (ARDS) [2]. These respiratory complications often exacerbate the clinical outcome and prognosis of burns patients [3], [4]. As such, effective respiratory management forms the corner stone in improving patients’ outcomes [5].
Heparin is an endogenous glycosaminoglycan (GAG) that was found to have multiple therapeutic effects in burns. Parenteral and topical application studies on GAGs revealed anticoagulative, anti-inflammatory and neoangiogenic properties [6]. The benefits of heparin in ILI have been shown in multiple studies. From burn animal models and human autopsies, ILI is generally believed to cause pathologic alteration which results in airway obstruction, pulmonary oedema, decreased pulmonary compliance and ventilation–perfusion mismatch [5], [7], [8], [9]. Administration of nebulised heparin combined with N-acetylcysteine (NAC) has shown to be able to reduce tracheobronchial cast formation and pulmonary oedema in smoke inhalation injury [6]. Desai et al. [10] have reported that heparin nebulisation in combination with NAC were able to decrease reintubation rates, incidence of atelectasis and mortality in paediatric burns patients. The combined efficacy of nebulised heparin, NAC and salbutamol in ILI was also demonstrated in a recent study conducted on adult burns patients with smoke inhalation injury and high acute physiology and chronic health evaluation (APACHE)-III scores [7]. In this group of patients, a reduction in lung injury scores was observed during the first week of treatment with the nebulised heparin, NAC and salbutamol protocol.
Nebulised heparin, NAC and salbutamol protocol was introduced in SGH Burns Centre in 2006. While the benefits of heparin have been illustrated in several studies, data on the safe use of nebulised heparin are limited [11], [12]. As with any therapeutic intervention, it is essential to weigh the benefits against the potential risks. Heparin, as an anticoagulant, is known to be capable of causing bleeding. However, the safety on the use of the nebulised form of heparin for burns patients with ILI is not well established. In this study, we investigated the safety and potential anticoagulant effects of nebulised heparin in burns patients with ILI.
Section snippets
Methodology
This study was a retrospective study with historical control. The study protocol was approved by the SingHealth Centralised Institutional Review Board.
Patient characteristics
63 patients and 104 patients were admitted to BICU from the year of 2001 to 2005 and 2006 to 2009, respectively. From the year of 2001 to 2009, a total of 167 patients were admitted to BICU (Fig. 1). Of which, 92 were not eligible for inclusion due to either absence of inhalational injury or they were not placed on mechanical ventilation. Eleven patients were excluded from the study as they were anticoagulated with enoxaparin upon admission and 1 patient was excluded as he was on warfarin prior
Discussion
The beneficial effects of heparin nebulisation in ILI, particularly when combined with mucolytics or antithrombin, were demonstrated in numerous studies [7], [10], [14], [15]. However, safety data on the use of nebulised heparin in the burns patient cohort is inadequate [11], [12]. As the airways and alveoli are capable of absorbing drugs delivered through the inhalation route and that heparin is able to increase the risk of bleeding, there may be a risk of systemic complications with the use
Conclusion
Findings from this study did not suggest any clinically significant increase in bleeding risk associated with nebulised heparin. When the therapeutic range of antithrombotic therapy was used as a gauge in the absence of established guideline available for nebulised heparin in burn patients with ILI, the coagulation indices were found to be in the clinically acceptable range. Our study suggested that nebulised heparin was not found to potentiate the risk of bleeding in burns patients with ILI.
Conflicts of interest
The authors declared that they have no potential conflicts of interest.
Acknowledgement
We would like to thank Ms. Stephanie Fook, biostatistician, for her advice on the statistical analysis of this study and the colleagues at Health Information Management System for tracing the casenotes of patients involved in this study.
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