ORIGINAL ARTICLE Influence of high dose tumescent local anaesthesia with prilocaine on systemic interleukin (IL)-6, IL-8 and tumour necrosis factor-a MD Schmittner, †, * ,1 J Faulhaber, ‡,1 B Kemler, † W Koenen, ‡ JO Thumfart, § C Weiss, – M Neumaier, § GC Beck † † Department of Anaesthesiology and Surgical Intensive Care Medicine, ‡ Department of Dermatology, Venereology and Allergology, § Institute for Clinical Chemistry , and – Department of Medical Statistics and Biomathematics, University Medical Center Mannheim, Ruprecht-Karls-University of Heidelberg, Mannheim, Germany *Correspondence: MD Schmittner. E-mail: marc.schmittner@umm.de Abstract Background and objective Tumescent local anaesthesia (TLA) with high prilocaine doses leads to formation of methemoglobin (MHb) which is known to be a potent activator of pro-inflammatory endothelial cell response in vitro. As TLA is widely used for large dermatological resections, the aim of this study was to investigate the effects of high prilocaine doses on the systemic inflammatory response in vivo and its clinical relevance. Methods This prospective study examines the influence of MHb on serum interleukin (IL)-6, IL-8 and tumour necrosis tumour necrosis (TNF)-a levels up to 72 h after application of TLA with prilocaine in doses higher than 600 mg. Results A total of 30 patients received prilocaine in a median dose of 1500 mg (range: 880–4160 mg) for large resections. Peak prilocaine serum concentration was reached 4 h (0.72 ± 0.07 lg ⁄ mL), the maximum concentration of MHb (7.43 ± 0.87%) and IL-6 (28.4 ± 4.1 U ⁄ L) 12 h after TLA application. TNF-a and IL-8 release were not found significantly increased. Three patients developed MHb concentrations >15%. Conclusions This clinical study shows for the first time that a high prilocaine serum concentration leads in vivo to elevated systemic levels of IL-6 but not of IL-8 and TNF-a because of initial high MHb levels. Because of possible and unpredictable high MHb concentrations, TLA should only be performed with prilocaine in doses of 2.5 mg ⁄ kg. In general, new solutions of TLA are necessary to achieve adequate anaesthesia for large dermatological resections to decrease the risk of methemoglobinaemia. Received: 15 October 2009; Accepted: 15 February 2010 Keywords anaesthetic techniques, cytokines, dermatological surgery, methemoglobin, prilocaine, tumescent local anaesthesia Conflict of interest None declared. Introduction Tumescent local anaesthesia (TLA) is an anaesthesia technique where high fluid volumes containing diluted local anaesthetics are infused subcutaneously. Initially used to facilitate liposuction, 1 TLA is carried out for plastic, dermatological and proctological surgery also in ambulatory settings. 2–4 Reports of adverse side- effects after liposuction in TLA with lidocaine made prilocaine to become the preferred substance. 5 Prilocaine is an amide-type local anaesthetic with an extremely high distribution volume. However, prilocaine is known as a trigger for methemoglobinaemia by its metabolites o-toluidine and nitrosotoluidine. 6,7 Although an upper limit of 2.5 mg ⁄ kg prilocaine was recently recommended, some authors reported the use of up to 43 mg ⁄ kg. 8–10 Thus, elevated methemoglobin (MHb) serum levels are presumable, especially in extended resections in dermatological surgery, when large amounts of TLA are applied. 11 There is a high interindividual vari- ability in the amount of MHb formed for any given dose of prilo- caine administered but MHb is more likely to happen with higher doses. 12 This effect may also be potentiated by other oxidative drugs. 8 The production of MHb has clinical consequences: it causes a shift of the oxygen-dissociation curve to the left, 13 it can result in respiratory failure 14 and a variety of physically symptoms. 1 These authors contributed equally to this work. ª 2010 The Authors JEADV 2010, 24, 1400–1405 Journal of the European Academy of Dermatology and Venereology ª 2010 European Academy of Dermatology and Venereology DOI: 10.1111/j.1468-3083.2010.03653.x JEADV