title: Detrimental effects of high-dose methylprednisolone sodium succinate on serum concentrations of hepatic and renal function indicators in severe sepsis and septic shock. The Methylprednisolone Severe Sepsis Study Group.
abstract: OBJECTIVE
  To evaluate the effects of high-dose methylprednisolone sodium succinate on biochemical markers of hepatic and renal function in patients with severe sepsis and septic shock.
  
  
  METHODS
  Retrospective analysis of serial serum chemistries in 382 patients who were entered prospectively into a randomized, placebo-controlled, double-blind clinical trial of high-dose methylprednisolone or placebo in the sepsis syndrome.
  
  
  METHODS
  The original study was conducted at 19 academic centers.
  
  
  METHODS
  Adult patients in severe sepsis or septic shock who met the study entry criteria, which included a clinically defined source of infection and signs of systemic sepsis, were enrolled into the study. Three hundred eighty-two patients were evaluated.
  
  
  METHODS
  Patients received either methylprednisolone (30 mg/kg) or placebo by iv infusion every 6 hrs for four doses. Hemodynamic variables and serum concentrations of creatinine, urea nitrogen, bilirubin, and aspartate aminotransferase (AST) were recorded on entering the study, at 12 and 24 hrs, and at 3, 7, and 14 days after the first infusion of methylprednisolone or placebo. These data were analyzed retrospectively.
  
  
  METHODS
  Hemodynamic and biochemical data were analyzed to determine whether or not hepatic and renal function in the sepsis syndrome had been influenced by methylprednisolone treatment.
  
  
  RESULTS
  Differences between methylprednisolone and placebo in hemodynamic variables, the occurrence rate of shock and recovery from shock, mortality rates and serum concentrations of creatinine and AST were not statistically significant. At 12 and 24 hrs, and at 3 and 7 days after the first drug infusion (of methylprednisolone or placebo), blood urea nitrogen was increased from baseline values in a significantly (p < .01) greater proportion of the methylprednisolone-treated patients compared with placebo-treated patients. The frequency of increased serum bilirubin concentrations was significantly (p < .01) greater among methylprednisolone patients vs. the placebo group at 12 and 24 hrs.
  
  
  CONCLUSIONS
  The frequency of acutely increased blood urea nitrogen and bilirubin concentrations in severe sepsis was increased significantly with high-dose methylprednisolone therapy. Similar frequencies of circulatory shock in the study groups excluded differences in global perfusion as a cause of this phenomenon. Possible adverse effects of pharmacologic concentrations of methylprednisolone in critically ill patients should be considered in planning treatment.
authors.affiliation: Department of Surgery, Cooper Hospital/University Medical Center, Camden, NJ 08103.
authors.forename: G J
authors.initials: GJ
authors.lastname: Slotman
authors.forename: C J
authors.initials: CJ
authors.lastname: Fisher
authors.forename: R C
authors.initials: RC
authors.lastname: Bone
authors.forename: T P
authors.initials: TP
authors.lastname: Clemmer
authors.forename: C A
authors.initials: CA
authors.lastname: Metz
mesh_terms: D001219:Aspartate Aminotransferases / Q000097:blood*; D001424:Bacterial Infections / Q000097:blood*; D001663:Bilirubin / Q000097:blood*; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood*; D004311:Double-Blind Method; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D007677:Kidney Function Tests; D008111:Liver Function Tests; D008776:Methylprednisolone Hemisuccinate / Q000009:adverse effects*; D012189:Retrospective Studies; D012772:Shock, Septic / Q000097:blood*
chemical_list: D008776:Methylprednisolone Hemisuccinate; D003404:Creatinine; D001219:Aspartate Aminotransferases; D001663:Bilirubin