The nonspecific inflammatory response to injury

Purpose: The role of the nonspecific inflammatory response in causing injury related to surgery has become bet ter understood over the last decade. There are complex interactions between neutrophils, cytokines-and nitric oxide metabolites that may cause organ injury following surgery. The purpose of this review is to summarize some of the processes causing injury through these nonspecific pathways. Methods: A review of the medical and anaesthetic literature related to inflammation, neutrophils and pro-inflammatory cytokines were performed using Medline, Bibliographies of relevant articles were searched and additional articles were then selected and reviewed. Results: Pro-inflammatory cytokines, such as tumour necrosis factor, are released in response to a variety of noxious stimuli (e.g. burns, sepsis, or CABG surgery). These cytokines cause activation of neutrophils with increased up-regulation of adhesion complexes on neutrophils and vascular endothelium. Nitric oxide synthase activity is also increased with a resultant increased production of nitric oxide. The Increased nitric oxide concentration in the presence of superoxide free radicals secreted by activated neutrophils forms peroxynitrite, a more reactive and toxic molecule. Once this process is initiated, diffuse organ injury can result, Although some information related to specific anaesthetics is available, firm recommendations related to clinical practice cannot be made. Conclusions: There is a complex interplay of inflammatory mediators that can cause injury. Although specific clinical applications for manipulating these pathways are not yet generally available, this area holds promise to develop new techniques to improve outcomes following surgery.