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Procalcitonin-guided interventions against infections to increase early appropriate antibiotics and improve survival in the intensive care unit: A randomized trial*

Jensen, Jens U. MD, PhD; Hein, Lars MD; Lundgren, Bettina MD, DMSc; Bestle, Morten H. MD, PhD; Mohr, Thomas T. MD, PhD; Andersen, Mads H. MD; Thornberg, Klaus J. MD; Løken, Jesper MD; Steensen, Morten MD; Fox, Zoe MD, PhD; Tousi, Hamid MD; Søe-Jensen, Peter MD; Lauritsen, Anne Ø MD; Strange, Ditte MD; Petersen, Pernille L. MD; Reiter, Nanna MD; Hestad, Søren MD; Thormar, Katrin MD; Fjeldborg, Paul MD; Larsen, Kim M. MD; Drenck, Niels E. MD; Østergaard, Christian MD, PhD, DMSc; Kjær, Jesper MSc; Grarup, Jesper DVM; Lundgren, Jens D. MD, DMSc

doi: 10.1097/CCM.0b013e31821e8791
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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.

Design: Randomized controlled open-label trial.

Setting: Nine multidisciplinary intensive care units across Denmark.

Patients: 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).

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 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 m2 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.


From the Copenhagen HIV Programme (JUJ, ZF, JK, JG, JDL), University of Copenhagen, Copenhagen, Denmark; the Departments of Clinical Microbiology (JUJ, BL) and Anaesthesia and Intensive Care (JL, MS), Copenhagen University Hospital, Hvidovre, Denmark; the Department of Anaesthesia and Intensive Care (LH, AØL, DS, PLP), Copenhagen University Hospital, Glostrup, Denmark; the Department of Anaesthesia and Intensive Care (LH, MHB, SH), Copenhagen University Hospital, Hillerød, Denmark; the Department of Anaesthesia and Intensive Care (TTM, KJT, KT), Copenhagen University Hospital, Gentofte, Denmark; the Department of Anaesthesia and Intensive Care (MHA, PF), Aarhus University Hospital, Skejby, Denmark; Royal Free Hospital (ZF), University College London, London, UK; the Departments of Anaesthesia and Intensive Care (HT, PSJ) and Clinical Microbiology (CØ), Copenhagen University Hospital, Herlev, Denmark; the Department of Anaesthesia and Intensive Care (NED, NR), Copenhagen University Hospital, Roskilde, Denmark; the Department of Anaesthesia and Intensive Care (KML), Aarhus University Hospital, Aarhus, Denmark; and the Department of Infectious Diseases (JDL), Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

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This study was funded, in part, by the Danish State, the Lundbeck Foundation, the Toyota Foundation, the A.P. Møller Foundation, the Horboe Foundation, and the Capitol Region of Denmark.

Dr. Jensen received speaker fee and travel reimbursement from Brahms Diagnostica and received an unrestricted grant for the organization for sample transport and analysis. The remaining authors have not disclosed any potential conflicts of interest.

Clinical trial registered with (NCT00271752).

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© 2011 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins