Effect of inhaled and intravenous lidocaine on inflammatory reaction in endotoxaemic rats.

Background and objective Systemically administered lidocaine has been shown to have anti-inflammatory properties. Inhalation is an attractive way of application because of high pulmonary compound concentrations and potentially fewer systemic side effects. The aim of this study was to clarify whether inhaled or, likewise, intravenous lidocaine can attenuate the inflammatory response in a model of experimental endotoxaemia in the rat. Methods Animals randomly received (nine animals in each group) lidocaine, either aerosolized 4 mg kg(-1) (Lid(Ae4.0)) and 0.4 mg kg(-1) (Lid(Ae0.4)) or 4 mg kg(-1) intravenously (Lid(iv)) before intravenous injection of 5 mg kg(-1) lipopolysaccharide (LPS). Administration of lidocaine was repeated after 2 h. Additional control animals were observed either without (sham) or with the infusion of LPS. Following 5 h of experimental endotoxaemia, the concentrations of tumour necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta) and IL-6 were measured in bronchoalveolar lavage fluid and blood plasma. Release of nitrite in ex-vivo cultured alveolar macrophages was measured by Griess assay. Results Bronchoalveolar lavage fluid levels of IL-1 beta and TNF alpha in Lid(Ae4.0) (IL-1 beta, -47%; TNF alpha, -41%; P< 0.05) and Lid(iv) (IL-1 beta, -55%; TNF alpha, -54%; P<0.05) but not in Lid(Ae0.4) were significantly lower than in LPS. Plasma cytokine levelswere not attenuated. Nitrite was found to be significantly reduced in Lid(Ae4.0) (-46%), Lid(Ae0.4) (-39%) and Lid(iv) (-41%) when compared with LPS (P<0.05, respectively). Conclusion Pretreatment of enclotoxaemic rats either with Lid(Ae4.0) or with Lid(iv) attenuated the levels of proinflarnmatory mediators in bronchoalveolar lavage fluid. Plasma cytokine levels were not affected. Nebulized lidocaine (0.4 mg kg(-1)) inhibited the nitrite release but did not affect the cytokine levels. Eur J Anaesthesiol 27:53-60 (C) 2010 European Society of Anaesthesiology.