Influence of Nebulized Unfractionated Heparin and N-Acetylcysteine in Acute Lung Injury After Smoke Inhalation Injury

Abstract

To determine whether the combination of aerosolized unfractionated heparin and N-acetylcystine reduces 28-days mortality and lung injury scores (LISs) in adult patients with smoke inhalation injury requiring mechanical ventilation. The study was a single-center retrospective study with historical control. The authors included 30 mechanically ventilated adult subjects who were admitted within 48 hours of their bronchoscopy confirmed smoke inhalation injury over a 5-year period. The experimental group was treated with nebulized heparin sulfate, N-acetylcystine, and albuterol sulfate. Controls received ventilation support and albuterol sulfate. The authors calculated acute physiology and chronic health evaluation (APACHE)-III scores on admission in addition to daily LIS for 7 days. The experimental group was divided into five APACHE-III subgroups and matched with inhalation lung injury patients in the historical control group. There was no significant difference in initial APACHE-III scores or LISs between groups (alpha = 0.05) upon entry to the study. The experimental group showed significant improvement in LISs, respiratory resistance and compliance measurements, and hypoxia scores as compared with controls throughout the duration of the study. There was a statistically significant survival benefit in the experimental group that was most pronounced in patients with APACHE-III scores >35. Survival for the control vs experimental group was 0.5714 +/- 0.1497 vs 0.9375 +/- 0.0605, respectively, (risk ratio -0.0055; 95% confidence interval -0.0314-0.0204; hazard ratio 1.003; number needed to treat 2.7). The use of aerosolized unfractionated heparin and N-acetylcystine attenuates lung injury and the progression of acute respiratory distress syndrome in ventilated adult patients with acute lung injury following smoke inhalation.

Nebulized anticoagulants in lung injury in critically ill patients—an updated systematic review of preclinical and clinical studies

“…Nebulized heparin was associated with physiologic improvements, but the physiologic endpoints varied widely. Nebulized heparin was associated with shorter duration of ventilatory support in two trials (50,55), and with reduced mortality in two trials (50,52), both retrospective trials using historical controls. Nebulization of heparin did neither affect systemic coagulation nor resulted in more systemic bleedings (53,55).…”

Acute Lung Injury: Prevention May Be the Best Medicine

“…Aerosolized unfractionated heparin and N-acetylcysteine attenuate lung injury in mechanically ventilated adult patients after smoke inhalation. 43,44 Other anti-inflammatory and anti-oxidant agents, such as curcumin, are also under investigation for ALI prevention. 45,46 Additionally, ␤ 2 adrenoreceptor agonists have been evaluated for their effects on lung vascular permeability and pro-surfactant effects.…”

Is inhaled prophylactic heparin useful for prevention and management of pneumonia in ventilated ICU patients?

“…[4] Clinical applications have been reported in airway burns [5] and respiratory conditions where there is a significant sputum production or airway inflammation. [6] With these therapeutic effects, the potential role of UFH in preventing and treating lung infections including ventilator-associated pneumonia (VAP) remains insufficiently investigated.…”

“…Some studies recommend the use of inhaled heparin to resolve airway burns but definitive trials are yet to be published. [5] This study had several limitations. Despite being small, there were no significant trends in the incidence of VAP or VAC, pneumonia resolution or effects on airway colonization or airway secretions to justify continued recruitment to the a priori sample size.…”

“…[37] It is possible that a higher dose is required but a pragmatic decision was made to use dosages consistent with other airway inflammatory diseases where some benefit of inhaled heparin has been noted. [2] , [3], [4], [5], [6] Importantly, the majority of patients were recruited from a single center.…”