title: Influence of high dose tumescent local anaesthesia with prilocaine on systemic interleukin (IL)-6, IL-8 and tumour necrosis factor-α.
abstract: 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)-α 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 μg/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-α 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-α 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.
authors.affiliation: Department of Anaesthesiology and Surgical Intensive Care Medicine, University Medical Center Mannheim, Ruprecht-Karls-University of Heidelberg, Mannheim, Germany. marc.schmittner@umm.de
authors.forename: M D
authors.initials: MD
authors.lastname: Schmittner
authors.forename: J
authors.initials: J
authors.lastname: Faulhaber
authors.forename: B
authors.initials: B
authors.lastname: Kemler
authors.forename: W
authors.initials: W
authors.lastname: Koenen
authors.forename: J O
authors.initials: JO
authors.lastname: Thumfart
authors.forename: C
authors.initials: C
authors.lastname: Weiss
authors.forename: M
authors.initials: M
authors.lastname: Neumaier
authors.forename: G C
authors.initials: GC
authors.lastname: Beck
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D016209:Interleukin-8 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011318:Prilocaine / Q000008:administration & dosage* / Q000097:blood; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D055815:Young Adult
chemical_list: D000779:Anesthetics, Local; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D011318:Prilocaine; D002097:C-Reactive Protein