Citation Information :
Ghiasi F, Sadeghian M, Emami M, Kiaie B, Mousavi S. A pilot study of nebulized heparin for prevention of ventilator induced lung injury: Comparative effects with an inhaled corticosteroid. Indian J Crit Care Med 2017; 21 (10):634-639.
Background: Ventilator-induced lung injury (VILI) is a side effect of mechanical ventilation. Lung inflammation and pulmonary activation of coagulation are induced by mechanical stress. Clinical and preclinical studies show that heparin possesses anti-inflammatory properties. Therefore, we assessed the effects of nebulized heparin in VILI.
Methods: Sixty critically ill adult patients who require mechanical ventilation for more than 48 h were included in this prospective, nonrandomized controlled study. Patients received nebulized heparin (10,000 U every 6 h) for 5 days. The matched control group received nebulized budesonide as routine practice in our center. This study assessed changes in partial pressure of oxygen to inspired fraction of oxygen ratio (PaO2/FiO2) and rapid shallow breathing index (RSBI) during the study as primary endpoints.
Results: The average daily PaO2/FiO2ratio was not statistically significant between both groups (187 ± 11.6 vs. 171 ± 11.6, P = 0.35). The RSBI also did not differ between groups (P = 0.58). Heparin administration was associated with a higher number of ventilator-free days among survivors but not significantly (7.7 ± 10.6 vs. 5.1 ± 8, 95% confidence interval − 2.2–7.5, P = 0.28). Successful weaning from mechanical ventilation was higher in the heparin group (P = 0.42). We did not observe any serious or increased adverse effects from nebulized heparin.
Conclusion: The results of this study show that the overall effectiveness of nebulized heparin is at least as comparable with a potent corticosteroid (budesonide). Heparin could be a safe and effective modality for patients who at risk of VILI.
Cabrera-Benítez NE, Valladares F, García-Hernández S, Ramos-Nuez Á, Martín-Barrasa JL, Martínez-Saavedra MT, et al. Altered profile of circulating endothelial-derived microparticles in ventilator-induced lung injury. Crit Care Med 2015;43:e551-9.
Hughes KT, Beasley MB. Pulmonary manifestations of acute lung injury: More than just diffuse alveolar damage. Arch Pathol Lab Med 2017;141:916-22.
Rasmussen BS, Maltesen RG, Pedersen S, Kristensen SR. Early coagulation activation precedes the development of acute lung injury after cardiac surgery. Thromb Res 2016;139:82-4.
Bowler SD, Smith SM, Lavercombe PS. Heparin inhibits the immediate response to antigen in the skin and lungs of allergic subjects. Am Rev Respir Dis 1993;147:160-3.
Bissonnette EY, Tremblay GM, Turmel V, Pirotte B, Reboud-Ravaux M. Coumarinic derivatives show anti-inflammatory effects on alveolar macrophages, but their anti-elastase activity is essential to reduce lung inflammation in vivo. Int Immunopharmacol 2009;9:49-54.
Hofstra JJ, Vlaar AP, Cornet AD, Dixon B, Roelofs JJ, Choi G, et al. Nebulized anticoagulants limit pulmonary coagulopathy, but not inflammation, in a model of experimental lung injury. J Aerosol Med Pulm Drug Deliv 2010;23:105-11.
Tuinman PR, Dixon B, Levi M, Juffermans NP, Schultz MJ. Nebulized anticoagulants for acute lung injury - A systematic review of preclinical and clinical investigations. Crit Care 2012;16:R70.
Young E. The anti-inflammatory effects of heparin and related compounds. Thromb Res 2008;122:743-52.
Ludwig RJ. Therapeutic use of heparin beyond anticoagulation. Curr Drug Discov Technol 2009;6:281-9.
Mousavi S, Moradi M, Khorshidahmad T, Motamedi M. Anti-inflammatory effects of heparin and its derivatives: A Systematic review. Adv Pharmacol Sci 2015;2015:507151.
Poterucha TJ, Libby P, Goldhaber SZ. More than an anticoagulant: Do heparins have direct anti-inflammatory effects? Thromb Haemost 2017;117:437-44.
Mohammad RS, El-Maraghi SK, El-Sorougi WM, Sabri SM, Mohammad MF. Role of nebulized heparin inhalation on mechanically ventilated critically ill patients. Egypt J Bronchology 2016;10:179.
Fan E, Villar J, Slutsky AS. Novel approaches to minimize ventilator-induced lung injury. BMC Med 2013;11:85.
Köhler D. Aerosolized heparin. J Aerosol Med 1994;7:307-14.
Bendstrup KE, Newhouse MT, Pedersen OF, Jensen JI. Characterization of heparin aerosols generated in jet and ultrasonic nebulizers. J Aerosol Med 1999;12:17-25.
Dixon B, Schultz MJ, Hofstra JJ, Campbell DJ, Santamaria JD. Nebulized heparin reduces levels of pulmonary coagulation activation in acute lung injury. Crit Care 2010;14:445.
Dixon B, Schultz MJ, Smith R, Fink JB, Santamaria JD, Campbell DJ, et al. Nebulized heparin is associated with fewer days of mechanical ventilation in critically ill patients: A randomized controlled trial. Crit Care 2010;14:R180.
Wilson MR, Takata M. Inflammatory mechanisms of ventilator-induced lung injury: A time to stop and think? Anaesthesia 2013;68:175-8.
Tang BM, Craig JC, Eslick GD, Seppelt I, McLean AS. Use of corticosteroids in acute lung injury and acute respiratory distress syndrome: A systematic review and meta-analysis. Crit Care Med 2009;37:1594-603.
Festic E, Carr GE, Cartin-Ceba R, Hinds RF, Banner-Goodspeed V, Bansal V, et al. Randomized clinical trial of a combination of an inhaled corticosteroid and beta agonist in patients at risk of developing the acute respiratory distress syndrome. Crit Care Med 2017;45:798-805.
Ju YN, Yu KJ, Wang GN. Budesonide ameliorates lung injury induced by large volume ventilation. BMC Pulm Med 2016;16:90.
Glas GJ, Serpa Neto A, Horn J, Cochran A, Dixon B, Elamin EM, et al. Nebulized heparin for patients under mechanical ventilation: An individual patient data meta-analysis. Ann Intensive Care 2016;6:33.
Dixon B, Santamaria JD, Campbell DJ. A phase 1 trial of nebulised heparin in acute lung injury. Crit Care 2008;12:R64.