title: Procalcitonin-guided interventions against infections to increase early appropriate antibiotics and improve survival in the intensive care unit: a randomized trial.
abstract: OBJECTIVE
  For patients in intensive care units, sepsis is a common and potentially deadly complication and prompt initiation of appropriate antimicrobial therapy improves prognosis. The objective of this trial was to determine whether a strategy of antimicrobial spectrum escalation, guided by daily measurements of the biomarker procalcitonin, could reduce the time to appropriate therapy, thus improving survival.
  
  
  METHODS
  Randomized controlled open-label trial.
  
  
  METHODS
  Nine multidisciplinary intensive care units across Denmark.
  
  
  METHODS
  A total of 1,200 critically ill patients were included after meeting the following eligibility requirements: expected intensive care unit stay of ≥ 24 hrs, nonpregnant, judged to not be harmed by blood sampling, bilirubin <40 mg/dL, and triglycerides <1000 mg/dL (not suspensive).
  
  
  METHODS
  : Patients were randomized either to the "standard-of-care-only arm," receiving treatment according to the current international guidelines and blinded to procalcitonin levels, or to the "procalcitonin arm," in which current guidelines were supplemented with a drug-escalation algorithm and intensified diagnostics based on daily procalcitonin measurements.
  
  
  RESULTS
  The primary end point was death from any cause at day 28; this occurred for 31.5% (190 of 604) patients in the procalcitonin arm and for 32.0% (191 of 596) patients in the standard-of-care-only arm (absolute risk reduction, 0.6%; 95% confidence interval [CI] -4.7% to 5.9%). Length of stay in the intensive care unit was increased by one day (p = .004) in the procalcitonin arm, the rate of mechanical ventilation per day in the intensive care unit increased 4.9% (95% CI, 3.0-6.7%), and the relative risk of days with estimated glomerular filtration rate <60 mL/min/1.73 m was 1.21 (95% CI, 1.15-1.27).
  
  
  CONCLUSIONS
  Procalcitonin-guided antimicrobial escalation in the intensive care unit did not improve survival and did lead to organ-related harm and prolonged admission to the intensive care unit. The procalcitonin strategy like the one used in this trial cannot be recommended.
authors.affiliation: Copenhagen HIV Programme, University of Copenhagen, Copenhagen, Denmark. juj@cphiv.dk
authors.forename: Jens U
authors.initials: JU
authors.lastname: Jensen
authors.forename: Lars
authors.initials: L
authors.lastname: Hein
authors.forename: Bettina
authors.initials: B
authors.lastname: Lundgren
authors.forename: Morten H
authors.initials: MH
authors.lastname: Bestle
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Mohr
authors.forename: Mads H
authors.initials: MH
authors.lastname: Andersen
authors.forename: Klaus J
authors.initials: KJ
authors.lastname: Thornberg
authors.forename: Jesper
authors.initials: J
authors.lastname: Løken
authors.forename: Morten
authors.initials: M
authors.lastname: Steensen
authors.forename: Zoe
authors.initials: Z
authors.lastname: Fox
authors.forename: Hamid
authors.initials: H
authors.lastname: Tousi
authors.forename: Peter
authors.initials: P
authors.lastname: Søe-Jensen
authors.forename: Anne Ø
authors.initials: AØ
authors.lastname: Lauritsen
authors.forename: Ditte
authors.initials: D
authors.lastname: Strange
authors.forename: Pernille L
authors.initials: PL
authors.lastname: Petersen
authors.forename: Nanna
authors.initials: N
authors.lastname: Reiter
authors.forename: Søren
authors.initials: S
authors.lastname: Hestad
authors.forename: Katrin
authors.initials: K
authors.lastname: Thormar
authors.forename: Paul
authors.initials: P
authors.lastname: Fjeldborg
authors.forename: Kim M
authors.initials: KM
authors.lastname: Larsen
authors.forename: Niels E
authors.initials: NE
authors.lastname: Drenck
authors.forename: Christian
authors.initials: C
authors.lastname: Ostergaard
authors.forename: Jesper
authors.initials: J
authors.lastname: Kjær
authors.forename: Jesper
authors.initials: J
authors.lastname: Grarup
authors.forename: Jens D
authors.initials: JD
authors.lastname: Lundgren
mesh_terms: D000368:Aged; D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002116:Calcitonin / Q000097:blood*; D015740:Calcitonin Gene-Related Peptide; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007362:Intensive Care Units; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D011498:Protein Precursors / Q000097:blood*; D012121:Respiration, Artificial; D018805:Sepsis / Q000517:prevention & control*; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D015415:Biomarkers; C000606589:CALCA protein, human; D011498:Protein Precursors; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide