• Jens U Jensen, Lars Hein, Bettina Lundgren, Morten H Bestle, Thomas T Mohr, Mads H Andersen, Klaus J Thornberg, Jesper Løken, Morten Steensen, Zoe Fox, Hamid Tousi, Peter Søe-Jensen, Anne Ø Lauritsen, Ditte Strange, Pernille L Petersen, Nanna Reiter, Søren Hestad, Katrin Thormar, Paul Fjeldborg, Kim M Larsen, Niels E Drenck, Christian Ostergaard, Jesper Kjær, Jesper Grarup, Jens D Lundgren, and Procalcitonin And Survival Study (PASS) Group.
• Copenhagen HIV Programme, University of Copenhagen, Copenhagen, Denmark. juj@cphiv.dk
• Crit. Care Med.. 2011 Sep 1;39(9):2048-58.

ObjectiveFor 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.DesignRandomized controlled open-label trial.SettingNine multidisciplinary intensive care units across Denmark.PatientsA 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).Interventions: 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.Measurements And Main ResultsThe 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).ConclusionsProcalcitonin-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.

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