title: Ropivacaine, Interleukin-6 and Tumor Necrosis Factor Alpha Plasma Levels during Intermittent Epidural and Continuous Wound Infusion of Ropivacaine for Analgesia after Hysterectomy or Myomectomy: An Observational Study.
abstract: OBJECTIVE
  The concentration-time profile of the long-acting local anesthetic ropivacaine after epidural (EP) administration at fixed time intervals or continuous subcutaneous (SC) infusion has not been fully evaluated. The objective of this work was to determine total plasma concentrations of ropivacaine and changes in cytokine interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels during EP and SC.
  
  
  METHODS
  In this prospective randomized controlled trial, 18 patients undergoing abdominal hysterectomy or myomectomy were randomly selected to receive ropivacaine either every 6 h via an EP catheter or by continuous wound infusion along the skin incision, after a bolus dose, for 48 h. Total plasma ropivacaine concentrations were measured before the bolus and 2, 4, 8, 24, 48, and 50 h after the bolus using high-performance liquid chromatography-UV and IL-6 and TNF-α levels were measured at 0, 8 and 24 h with ELISA and analyzed statistically.
  
  
  RESULTS
  During EP, mean ± SD ropivacaine concentrations were relatively stable up to 50 h postoperatively, that is, 239 ± 89 ng/ml, while during SC, initial concentrations between 2 and 8 h were comparatively lower (101.5 ± 42.9 ng/ml) than 24-50 h concentrations (437.1 ± 206 ng/ml). An increase in IL-6 levels was noted between 0 and 24 h during EP and SC, but TNF-α levels increased slightly, between 0 and 24 h, only during EP.
  
  
  CONCLUSIONS
  Ropivacaine plasma concentrations with both EP and SC were found to be safe throughout the administration time interval. IL-6 levels increased during the same time interval, while TNF levels varied only slightly.
authors.affiliation: Laboratory of Biopharmaceutics and Pharmacokinetics, Department of Pharmacy, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Sophia L
authors.initials: SL
authors.lastname: Markantonis
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Melemeni
authors.forename: Marina
authors.initials: M
authors.lastname: Markidou
authors.forename: Stefania Irene
authors.initials: SI
authors.lastname: Haikali
authors.forename: Vangelis
authors.initials: V
authors.lastname: Karalis
authors.forename: Argyro
authors.initials: A
authors.lastname: Fassoulaki
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008875:Middle Aged; D000577:Amides / Q000008:administration & dosage / Q000097:blood; D015360:Analgesia, Epidural / Q000379:methods; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000097:blood; D015415:Biomarkers / Q000097:blood; D007044:Hysterectomy / Q000009:adverse effects; D015850:Interleukin-6 / Q000097:blood; D010149:Postoperative Pain / Q000097:blood / Q000517:prevention & control; D011446:Prospective Studies; D000077212:Ropivacaine; D000072836:Surgical Wound / Q000097:blood / Q000188:drug therapy; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D063186:Uterine Myomectomy / Q000009:adverse effects
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6; D000077212:Ropivacaine; D014409:Tumor Necrosis Factor-alpha