title: Preoperative high-dose steroid administration attenuates the surgical stress response following liver resection: results of a prospective randomized study.
abstract: OBJECTIVE
  Major abdominal surgery such as liver resection is associated with an excessive hyperinflammatory response and transient immunosuppression. We investigated the immunomodulating effect of preoperative pulse administration of high-dose methylprednisolone in patients undergoing hepatic resection without pedicle clamping.
  
  
  METHODS
  Twenty patients who underwent hepatic resection were randomized into two groups: a steroid group (n = 10), in which patients were given 30 mg/kg per body weight (BW) methylprednisolone intravenously, and a control group (n = 10), in which patients received a placebo (sodium chloride) infusion. The main outcome parameter to assess systemic stress was the serum plasma level of interleukin-6 (IL-6). To evaluate cell-mediated immune function, human leukocyte antigen-DR (HLA-DR) expression on peripheral blood monocytes and lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha) release by peripheral monocytes was measured. Other investigated serum parameters included C-reactive protein (CRP), total bilirubin, alanine aminotransferase (ALT), prothrombin time (PT)-INR, and cytokines such as IL-8 and IL-10 and TNF-alpha. Postoperative convalescence, complication rate, and length of hospital stay were compared between the groups.
  
  
  RESULTS
  Postoperative plasma concentrations of IL-6 (days 1 and 2), IL-8 (days 2 and 3), and CRP (days 1-4) were significantly lower in the steroid than in the control group. The total bilirubin concentration was significantly lower on day 6 in the steroid than in the control group. Four hours after surgery, LPS-induced TNF-alpha secretion was significantly reduced in the steroid group, but it increased rapidly during the following days. HLA-DR, ALT, and PT-INR levels were not different between the two groups. The postoperative hospital stay in the steroid group was significantly lower compared to that in the control group (mean, 10.5 days versus 14.8 days; P < 0.05). No differences were found in the convalescence score or postoperative complication rate.
  
  
  CONCLUSIONS
  Intravenous methylprednisolone administration before hepatic resection significantly reduced systemic inflammatory cytokine release. No adverse effect on immunity was noted due to the methylprednisolone. We found no significant difference in the convalescence score, but a significantly shorter hospital stay in the steroid group. Further studies with more patients are needed to elucidate the clinical impact of preoperative steroid bolus therapy in liver surgery.
authors.affiliation: Department of General-, Visceral- and Transplantation Surgery, University Medicine Berlin, Charité Campus Virchow Clinic, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Sven C
authors.initials: SC
authors.lastname: Schmidt
authors.forename: Susanne
authors.initials: S
authors.lastname: Hamann
authors.forename: Jan M
authors.initials: JM
authors.lastname: Langrehr
authors.forename: Conny
authors.initials: C
authors.lastname: Höflich
authors.forename: Jens
authors.initials: J
authors.lastname: Mittler
authors.forename: Dictmar
authors.initials: D
authors.lastname: Jacob
authors.forename: Peter
authors.initials: P
authors.lastname: Neuhaus
mesh_terms: D000368:Aged; D002097:C-Reactive Protein / Q000032:analysis; D003289:Convalescence; D016207:Cytokines / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000009:adverse effects; D006684:HLA-DR Antigens / Q000097:blood; D006498:Hepatectomy / Q000009:adverse effects*; D006801:Humans; D008111:Liver Function Tests; D008297:Male; D008776:Methylprednisolone Hemisuccinate / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D011183:Postoperative Complications / Q000097:blood / Q000517:prevention & control*; D011292:Premedication; D011446:Prospective Studies; D018746:Systemic Inflammatory Response Syndrome / Q000517:prevention & control*; D013997:Time Factors
chemical_list: D016207:Cytokines; D005938:Glucocorticoids; D006684:HLA-DR Antigens; D008776:Methylprednisolone Hemisuccinate; D002097:C-Reactive Protein