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.

Objective Inhaled anticoagulation regimens are increasingly being employed to manage smoke inhalation-associated acute lung injury (SI-ALI). We systematically reviewed published and unpublished pre-clinical and clinical trial data to elucidate the effects of these regimens on lung injury severity, airway obstruction, ventilation, oxygenation, pulmonary infections, bleeding complications, and survival. Data Sources PubMed, Scopus, EMBASE, and Web of Science were searched to identify relevant published studies. Relevant unpublished studies were identified by searching the Australian and New Zealand Clinical Trials Registry, World Health Organization International Clinical Trials Registry Platform, Cochrane Library, ClinicalTrials.gov, MINDCULL.com, Current Controlled Trials, and Google. Study Selection Inclusion criteria were any pre-clinical or clinical study in which (1) animals or subjects experienced smoke inhalation exposure, (2) were treated with nebulized or aerosolized anticoagulation regimens including heparin, heparinoids, antithrombins, or fibrinolytics (e.g., tissue plasminogen activator), (3) a control and/or sham group was described for pre-clinical studies, (4) and a concurrent or historical control group described for clinical studies. Exclusion criteria were (1) the absence of a group treated with a nebulized or aerosolized anticoagulation regimen, (2) the absence of a control or sham group, and (3) case reports. Data Extraction 99 potentially relevant references were identified. 27 references met inclusion criteria including 19 pre-clinical references reporting 18 studies, and 8 clinical references reporting 5 clinical studies. Data Synthesis A systematic review of the literature is provided. Both clinical and methodological diversity precluded combining these studies in a meta-analysis. Conclusions The high mortality associated with SI-ALI results from airway damage, mucosal dysfunction, neutrophil infiltration, airway coagulopathy with cast formation, ventilation-perfusion mismatching with shunt and barotrauma. Inhaled anticoagulation regimens in both pre-clinical and clinical studies improve survival and decrease morbidity without altering systemic markers of clotting and anticoagulation. In some preclinical and clinical studies, inhaled anticoagulants were associated with a favorable effect on survival. This approach appears sufficiently promising to merit a well-designed prospective study to validate its use in patients with severe SI-ALI requiring mechanical ventilation.

T-cell-specific immunologic changes occur after major injury. Identification of those TH1/TH2 cytokine profiles associated with worse prognosis may one day allow clinicians to risk stratify injured patients and identify those at increased risk of developing SIRS, sepsis, MOF, and deep venous thrombosis. Immune-targeted therapies may eventually serve as effective treatments in the acute setting to decrease morbidity and mortality, and to improve the management and prognosis of those patients at risk for developing postinjury complications.