A pilot study of nebulized heparin for prevention of ventilator induced lung injury: Comparative effects with an inhaled corticosteroid

Abstract

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/FiO2 ratio 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.

Nebulized heparin and salbutamol versus salbutamol alone in acute exacerbations of chronic obstructive pulmonary disease requiring mechanical ventilation: a double-blind randomized controlled trial

“…Based on such results, the research team decided to adjust the treatment protocol to add enoxaparin SC as a prophylaxis against thromboembolic complications and to withhold heparin nebulisation if APTT increased more than double the normal or serious bleeding occurred. Our results correlated well with all the studies done on the nebulized heparin regarding the absence of any bleeding hazards in response to its usage [ 8 , 10 , 14 , 23 – 25 , 27 , 28 ].…”

“…Moreover, inhalational heparin has anti-asthmatic properties as confirmed by different clinical models of bronchial asthma [ 8 , 21 ] and inpatients with smoke inhalational injuries [ 8 , 9 , 21 , 22 ]. Heparin nebulization also improved oxygenation and increased the VFDs in critically ill mechanically ventilated patients and was found to be comparable to a nebulized corticosteroid (budesonide) in decreasing the risk of ventilator-induced lung injury [ 14 , 23 ], highlighting its anti-inflammatory effect. Subcutaneous low-molecular-weight heparin also improved the pulmonary functions and decreased the days of MV among AECOPD ventilated patients [ 24 , 25 ].…”

Viral Coagulopathy in Patients With COVID-19: Treatment and Care

“… 35 – 37 A pilot study of nebulized UFH for the prevention of ventilator-induced lung injury has been reported. 38 Inhaled prophylactic UFH has also been shown to be effective for the prevention and management of pneumonia and ventilated intensive care unit patients. A phase 1 trial of nebulized heparin in acute lung injury demonstrated better outcomes in heparin-treated groups.…”

Anticoagulant therapy in acute respiratory distress syndrome

“…No convincing benefit of heparin nebulization was found under mechanical ventilation (74) or for prophylaxis for pneumonia patients receiving mechanical ventilation (75,76). In 16 patients with ventilator-induced lung injury, heparin was nebulized proving safety and increasing the number of ventilator-free days (77).…”