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

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.

The Procalcitonin And Survival Study (PASS) - a randomised multi-center investigator-initiated trial to investigate whether daily measurements biomarker Procalcitonin and pro-active diagnostic and therapeutic responses to abnormal Procalcitonin levels, can improve survival in intensive care unit patients. Calculated sample size (target population): 1000 patients.

BACKGROUND: Sepsis and complications to sepsis are major causes of mortality in critically ill patients. Rapid treatment of sepsis is of crucial importance for survival of patients. The infectious status of the critically ill patient is often difficult to assess because symptoms cannot be expressed and signs may present atypically. The established biological markers of inflammation (leucocytes, C-reactive protein) may often be influenced by other parameters than infection, and may be unacceptably slowly released after progression of an infection. At the same time, lack of a relevant antimicrobial therapy in an early course of infection may be fatal for the patient. Specific and rapid markers of bacterial infection have been sought for use in these patients. METHODS: Multi-centre randomized controlled interventional trial. Powered for superiority and non-inferiority on all measured end points. Complies with, "Good Clinical Practice" (ICH-GCP Guideline (CPMP/ICH/135/95, Directive 2001/20/EC)). Inclusion: 1) Age > or = 18 years of age, 2) Admitted to the participating intensive care units, 3) Signed written informed consent.Exclusion: 1) Known hyper-bilirubinaemia. or hypertriglyceridaemia, 2) Likely that safety is compromised by blood sampling, 3) Pregnant or breast feeding. Computerized Randomisation: Two arms (1:1), n = 500 per arm: Arm 1: standard of care. Arm 2: standard of care and Procalcitonin guided diagnostics and treatment of infection. Primary Trial Objective: To address whether daily Procalcitonin measurements and immediate diagnostic and therapeutic response on day-to-day changes in procalcitonin can reduce the mortality of critically ill patients. DISCUSSION: For the first time ever, a mortality-endpoint, large scale randomized controlled trial with a biomarker-guided strategy compared to the best standard of care, is conducted in an Intensive care setting. Results will, with a high statistical power answer the question: Can the survival of critically ill patients be improved by actively using biomarker procalcitonin in the treatment of infections? 700 critically ill patients are currently included of 1000 planned (June 2008). Two interim analyses have been passed without any safety or futility issues, and the third interim analysis is soon to take place. Trial registration number at clinicaltrials.gov: Id. nr.: NCT00271752).

[Measurement of intraabdominal pressure and abdominal compartment syndrome in surgical and intensive care units]. / Måling af intraabdominalt tryk og abdominalt kompartmentsyndrom på kirurgiske og intensiv terapi-afdelinger.

INTRODUCTION: Over the past number of years, there has been an increasing interest in the pathophysiological phenomena intraabdominal hypertension (IAH) and abdominal compartment syndrome (ACS). Foreign studies have shown considerably national differences in the interpretation of the two phenomena. The purpose of this questionnaire study was to survey which group of patients is examined for IAH and ACS, how the examination is carried out and how the two conditions are treated in surgical and intensive care units in Denmark. MATERIALS AND METHODS: A questionnaire was sent to all relevant surgical and intensive care units in Denmark. RESULTS: The response rate was 81%. 74% intensive care units and 31% surgical wards measured IAP. 100% used the intravesical method. International guidelines were followed in 11% of surgical wards and 18% of the intensive care units regarding how often IAP should be measured and 44%/ 32% regarding at what IAP level surgical intervention should be considered. 78% of the wards and 79% of the intensive care units that measured IAP had celiotomy as a treatment modality. There were major differences between both surgical wards and intensive care units regarding which group of patients should have IAP measured. CONCLUSION: Considering the differences in clinical practice and the discrepancy to international guidelines interdisciplinary national guideline might contribute to a more uniform evaluation and treatment of patients with IAH or ACS.