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Wound Healing and Infection in Surgery: The Pathophysiological Impact of Smoking, Smoking Cessation, and Nicotine Replacement TherapyA Systematic Review

Sørensen, Lars Tue MD

doi: 10.1097/SLA.0b013e31824f632d
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.

Smoking has a temporary effect on tissue microenvironment and it modulates the inflammatory and proliferative response leading to surgical site infections and impaired healing. Nicotine appears to have a marginal effect on tissue oxygenation, inflammation, and proliferation. Smoking cessation reverses inflammation within 4 weeks, but not proliferation, which remain attenuated.

From the Copenhagen Wound Healing Center and Department of Surgery K, Bispebjerg Hospital, University of Copenhagen, Denmark.

Reprints: Lars Tue Sørensen MD, Department of Surgery, Bispebjerg Hospital, DK-2400 Copenhagen, Denmark. E-mail:

Disclosure: This study has been supported by Bispebjerg Hospital Research Foundation, Niels and Desiree Yde Foundation, San Cataldo Foundation, Danish Physicians' Insurance Association of 1891, and Danish Society for Tobacco Research.

© 2012 Lippincott Williams & Wilkins, Inc.