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

TY - JOUR

T1 - Procalcitonin-guided interventions against infections to increase early appropriate antibiotics and improve survival in the intensive care unit: a randomized trial

AU - Jensen, Jens U

AU - Hein, Lars

AU - Lundgren, Bettina

AU - Bestle, Morten H

AU - Mohr, Thomas T

AU - Andersen, Mads H

AU - Thornberg, Klaus J

AU - Løken, Jesper

AU - Steensen, Morten

AU - Fox, Zoe

AU - Tousi, Hamid

AU - Søe-Jensen, Peter

AU - Lauritsen, Anne Ø

AU - Strange, Ditte

AU - Petersen, Pernille L

AU - Reiter, Nanna

AU - Hestad, Søren

AU - Thormar, Katrin

AU - Fjeldborg, Paul

AU - Larsen, Kim M

AU - Drenck, Niels E

AU - Ostergaard, Christian

AU - Kjær, Jesper

AU - Grarup, Jesper

AU - Lundgren, Jens D

AU - Procalcitonin And Survival Study (PASS) Group

AU - Pedersen, Lars Møller

PY - 2011/9/1

Y1 - 2011/9/1

N2 - 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 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.

AB - 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 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.

KW - Aged

KW - Algorithms

KW - Anti-Bacterial Agents

KW - Biological Markers

KW - Calcitonin

KW - Female

KW - Hospital Mortality

KW - Humans

KW - Intensive Care Units

KW - Length of Stay

KW - Male

KW - Middle Aged

KW - Protein Precursors

KW - Respiration, Artificial

KW - Sepsis

KW - Time Factors

U2 - 10.1097/ccm.0b013e31821e8791

DO - 10.1097/ccm.0b013e31821e8791

M3 - Journal article

SN - 0090-3493

VL - 39

SP - 2048

EP - 2058

JO - Critical Care Medicine

JF - Critical Care Medicine

IS - 9

ER -