Continuous EEG Monitoring in a Consecutive Patient Cohort with Sepsis and Delirium.

BACKGROUND: Delirium is common during sepsis, although under-recognized. We aimed to assess the value of continuous electroencephalography (cEEG) to aid in the diagnosis of delirium in septic patients. METHODS: We prospectively evaluated 102 consecutive patients in a medical intensive care unit (ICU), who had sepsis or septic shock, without evidence of acute primary central nervous system disease. We initiated cEEG recording immediately after identification. The median cEEG time per patient was 44 h (interquartile range 21-99 h). A total of 6723 h of cEEG recordings were examined. The Confusion Assessment Method for the ICU (CAM-ICU) was administered six times daily to identify delirium. We analyzed the correlation between cEEG and delirium using 1252 two-minute EEG sequences recorded simultaneously with the CAM-ICU scorings. RESULTS: Of the 102 included patients, 66 (65%) had at least one delirium episode during their ICU stay, 30 (29%) remained delirium-free, and 6 (6%) were not assessable due to deep sedation or coma. The absence of delirium was independently associated with preserved high-frequency beta activity (> 13 Hz) (P < 10-7) and cEEG reactivity (P < 0.001). Delirium was associated with preponderance of low-frequency cEEG activity and absence of high-frequency cEEG activity. Sporadic periodic cEEG discharges occurred in 15 patients, 13 of whom were delirious. No patient showed clinical or electrographic evidence of non-convulsive status epilepticus. CONCLUSIONS: Our findings indicate that cEEG can help distinguish septic patients with delirium from non-delirious patients.

Invasive Candida infections and the harm from antibacterial drugs in critically ill patients: data from a randomized, controlled trial to determine the role of ciprofloxacin, piperacillin-tazobactam, meropenem, and cefuroxime.

OBJECTIVE: Use of antibiotics in critically ill patients may increase the risk of invasive Candida infection. The objective of this study was to determine whether increased exposure to antibiotics is associated with increased prevalence of invasive Candida infection. DESIGN: Substudy using data from a randomized controlled trial, the Procalcitonin And Survival Study 2006-2010. SETTING: Nine multidisciplinary ICUs across Denmark. PATIENTS: A total of 1,200 critically ill patients. INTERVENTION: Patients were randomly allocated to either a "high exposure" antibiotic therapy (intervention arm, n = 604) or a "standard exposure" guided by current guidelines (n = 596). MEASUREMENTS AND MAIN RESULTS: Seventy-four patients met the endpoint, "invasive Candida infection," 40 in the high exposure arm and 34 in standard exposure arm (relative risk = 1.2; 95% CI, 0.7-1.8; p = 0.52). Among medical patients in the high exposure arm, the use of ciprofloxacin and piperacillin/tazobactam was 51% and 75% higher than in the standard exposure arm; no difference in antibiotic exposure was observed between the randomized arms in surgical patients. Among medical intensive care patients, invasive Candida infection was more frequent in the high exposure arm (6.2%; 27/437) than in standard exposure arm (3.3%; 14/424) (hazard ratio = 1.9; 95% CI, 1.0-3.6; p = 0.05). Ciprofloxacin used at study entry independently predicted invasive Candida infection (adjusted hazard ratio = 2.1 [1.1-4.1]); the risk gradually increased with duration of ciprofloxacin therapy: six of 384 in patients not exposed (1.6%), eight of 212 (3.8%) when used for 1-2 days (hazard ratio = 2.5; 95% CI, 0.9-7.3), and 31 of 493 (6.3%) when used for 3 days (hazard ratio = 3.8; 95% CI, 1.6-9.3; p = 0.002). Patients with any ciprofloxacin-containing antibiotic regimen the first 3 days in the trial had a higher risk of invasive Candida infection than did patients on any antibiotic regimen not containing ciprofloxacin (unadjusted hazard ratio = 3.7; 95% CI, 1.6-8.7; p = 0.003; adjusted hazard ratio, 3.4; 95% CI, 1.4-8.0; p = 0.006). CONCLUSIONS: High exposure to antibiotics is associated to increased risk of invasive Candida infection in medical intensive care patients. Patients with ciprofloxacin-containing regimens had higher risk of invasive Candida infection. Other antibiotics, such as meropenem, piperacillin/tazobactam, and cefuroxime, were not associated with such a risk.

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).

[Acute normovolemic hemodilution combined with inhibition of fibrinolysis and use of cell saver in total hip arthroplasty]. / Akut normovolaemisk haemodilution kombineret med fibrinolyseinhibition og brug af "cellsaver" under indsaettelse af total hoftealloplastik.

INTRODUCTION: Transfusion with homologous blood is not without costs for the recipient: An increased risk of postoperative infections must be anticipated, and the risk of transfusion-transmitted viral infections is of growing concern. This has increased the interest for methods which can reduce the need for intraoperative blood transfusion. The goal of this study was to determine if acute normovolemic hemodilution combined with fibrinolytic inhibition and the use of cell saver can reduce the need for homologous blood transfusion in total hip arthroplasty compared to the cellsaver technique alone. MATERIAL AND METHODS: 145 patients undergoing total hip arthroplasty in spinal anesthesia were included in the study. They were all operated by the same surgeon. In group A (N = 64) only the cell saver was used, whereas in group B (N = 81) it was combined with acute normovolemic hemodilution and use of the fibrinolytic inhibitor tranexamic acid. RESULTS: The total blood loss and the need for homologous blood transfusion were significantly smaller in group B than in group A. DISCUSSION: Although the cell saving technique is effective in total hip arthroplasty, this study demonstrates that a further reduction of blood loss and homologous blood transfusion can be achieved by combining the method with acute normovolemic hemodilution and pharmacological inhibition of fibrinolysis.