title: Randomized, double-blind, placebo-controlled trial of granulocyte colony-stimulating factor in patients with septic shock.
abstract: OBJECTIVE
  To investigate the effect of early administration of granulocyte colony-stimulating factor (G-CSF) on hospital mortality in nonneutropenic patients with septic shock, excluding patients with melioidosis.
  
  
  METHODS
  A randomized, placebo-controlled, double-blinded clinical trial.
  
  
  METHODS
  Adult patients with septic shock admitted to the Royal Darwin Hospital Intensive Care Unit.
  
  
  METHODS
  Patients were randomized to receive G-CSF or placebo intravenously daily for 10 days, in addition to routine management of septic shock.
  
  
  METHODS
  Primary outcome was hospital mortality. Secondary outcomes included intensive care unit mortality, intensive care unit and hospital length of stay, ventilator hours, and time to resolution of shock. Patient comorbidities, baseline and daily physiology, and organ function were collected.
  
  
  RESULTS
  Of 166 patients enrolled, 83 were allocated to receive G-CSF (81 included in analysis) and 83 were allocated to receive placebo. At baseline, 30% of patients had diabetes, 18% were known to have renal impairment or failure, and 38% had a history of hazardous alcohol use. The two groups had similar comorbidities at baseline and a similar severity of illness. The in-hospital mortality was 27% in the G-CSF group and 25% in the placebo group. Secondary end points were not different between groups. There was a higher rate of new organ failure in G-CSF-treated patients than placebo-treated patients (50% vs. 33%, p = .03), most of which was accounted for by new liver dysfunction (11% vs. 1%, p = .007). There was no significant difference in the proportion of patients with troponin I of >0.08 mg/L (78% vs. 66%, p = .09), and the prevalence of acute myocardial infarction (6% vs. 4%, p = .55) was not different during the study. The median peak troponin I level was higher in the G-CSF group (0.5 vs. 0.14 mg/L, p = .007), but baseline levels were not available.
  
  
  CONCLUSIONS
  G-CSF does not improve outcomes in patients with septic shock, excluding melioidosis. Increased hepatic dysfunction and higher peak troponin levels in patients receiving G-CSF have not been reported in previous clinical trials and warrant further investigation.
authors.affiliation: Intensive Care, Royal Darwin Hospital, Darwin, Australia. dianne.stephens@nt.gov.au
authors.forename: Dianne P
authors.initials: DP
authors.lastname: Stephens
authors.forename: Jane H
authors.initials: JH
authors.lastname: Thomas
authors.forename: Alisa
authors.initials: A
authors.lastname: Higgins
authors.forename: Michael
authors.initials: M
authors.lastname: Bailey
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Anstey
authors.forename: Bart J
authors.initials: BJ
authors.lastname: Currie
authors.forename: Allen C
authors.initials: AC
authors.lastname: Cheng
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D003422:Critical Care; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D017052:Hospital Mortality; D006801:Humans; D007902:Length of Stay; D000078224:Lenograstim; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012772:Shock, Septic / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000078224:Lenograstim