SYSTEMATIC REVIEW Wound Healing and Infection in Surgery: The Pathophysiological Impact of Smoking, Smoking Cessation, and Nicotine Replacement Therapy A Systematic Review

Objective: The aim was to clarify how smoking and nicotine affects wound healing processes and to establish if smoking cessation and nicotine replacement therapy reverse the mechanisms involved. Background: Smoking is a recognized risk factor for healing complications after surgery, but the pathophysiological mechanisms remain largely unknown. Methods: Pathophysiological studies addressing smoking and wound healing were identified through electronic databases (PubMed, EMBASE) and by hand-search of articles’ bibliography. Of the 1460 citations identified, 325 articles were retained following title and abstract reviews. In total, 177 articles were included and systematically reviewed. Results: Smoking decreases tissue oxygenation and aerobe metabolism temporarily. The inflammatory healing response is attenuated by a reduced inflammatory cell chemotactic responsiveness, migratory function, and oxidative bactericidal mechanisms. In addition, the release of proteolytic enzymes and inhibitors is imbalanced. The proliferative response is impaired by a reduced fibroblast migration and proliferation in addition to a downregulated collagen synthesis and deposition. Smoking cessation restores tissue oxygenation and metabolism rapidly. Inflammatory cell response is reversed in part within 4 weeks, whereas the proliferative response remains impaired. Nicotine does not affect tissue microenvironment, but appears to impair inflammation and stimulate proliferation. Conclusions: Smoking has a transient effect on the tissue microenvironment and a prolonged effect on inflammatory and reparative cell functions leading to delayed healing and complications. Smoking cessation restores the tissue microenvironment rapidly and the inflammatory cellular functions within 4 weeks, but the proliferative response remain impaired. Nicotine and nicotine replacement drugs seem to attenuate inflammation and enhance proliferation but the effect appears to be marginal.