Does a Nebulized Heparin/N-acetylcysteine Protocol Improve Outcomes in Adult Smoke Inhalation?

Smoke inhalation continues to be a major source of morbidity and mortality in burn patients, increasing the likelihood of mortality by as much as 25% despite the many advances in burn care over the past decades.1 Although inhalation injury is not uncommon among patients with burns, there remains no standard for its diagnosis, scoring, and subsequent treatment, which makes it difficult to evaluate the results of studies and treatments.2 For these reasons, inhalation injury was designated a top 10 research priority at the 2007 American Burn Association (ABA) Consensus Conference.3 Smoke inhalation occurs through a variety of mechanisms, including thermal injury to the respiratory tract mucosa; however, the exact mechanism of what occurs following smoke inhalation injury is not clearly understood. Studies have shown that airway edema combined with obstructive casts produced from cellular debris, fibrin clots, polymorphonuclear leukocytes, mucus, and mucin B5 cause the airway obstruction contributing to pulmonary failure.4 Inhalation injury leads to the destruction of the ciliated epithelium that lines the tracheobronchial tree and impairs surfactant production, ultimately leading to a proinflammatory cytokine cascade, altering capillary membrane integrity and exacerbating pulmonary edema.5 Neutrophils and mucus casts can cause upper-airway obstruction, contributing to pulmonary failure. Hollingsed et al6 found that patients with inhalation injury had a 73% incidence of respiratory failure (hypoxemia, multiple pulmonary infections, or prolonged ventilator support) and a 20% incidence of acute respiratory distress syndrome (ARDS). Heparin and N-acetylcysteine nebulization treatment in combination with albuterol has potential efficacy in inhalation injury based initially on results from animal models and clinical studies in children. The primary mechanism is thought to be a combination of mucolysis by the N-acetylcysteine component, bronchodilation by the albuterol, and inhibition of fibrin clot formation within the airways by the anticoagulant heparin. Herndon and Traber’s7 laboratory reported the effects of aerosolized recombinant human antithrombin and heparin in an ovine model of acute lung injury induced by smoke inhalation and cutaneous flame burn. The results of this study strongly suggest that aerosolized recombinant human antithrombin and heparin in combination may be a novel therapeutic approach for airway management of burn victims with smoke inhalation injury. Desai et al8 have previously demonstrated that nebulized heparin/N-acetylcysteine is associated with reduced mortality in burned children with inhalation injury (n = 47), without significant side effects. The Holt9 group found no clinical benefit using a similar protocol in a treated group consisting of both children and adults (n = 62). Miller et al4 described the effect of a protocol with alternating nebulized N-acetylcysteine and 10,000 U of heparin as attenuating lung injury and the progression of ARDS in ventilated adult patients (n = 30) with acute lung injury. We therefore hypothesized that aerosolized anticoagulant may benefit adult burn patients with inhalation injury and implemented a nebulized heparin/N-acetylcysteine/albuterol (HNA) protocol at our burn center in 2011; this study details the clinical results of this protocol.