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 requirementsexpected 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.
ObjectivesTo explore whether a strategy of more intensive antibiotic therapy leads to emergence or prolongation of renal failure in intensive care patients.DesignSecondary analysis from a randomised ...antibiotic strategy trial (the Procalcitonin And Survival Study). The randomised arms were conserved from the primary trial for the main analysis.SettingNine mixed surgical/medical intensive care units across Denmark.Participants1200 adult intensive care patients, 18+ years, expected to stay +24 h. Exclusion criteria: bilirubin >40 mg/dl, triglycerides >1000 mg/dl, increased risk from blood sampling, pregnant/breast feeding and psychiatric patients.InterventionsPatients were randomised to guideline-based therapy (‘standard-exposure’ arm) or to guideline-based therapy supplemented with antibiotic escalation whenever procalcitonin increased on daily measurements (‘high-exposure’ arm).Main outcome measuresPrimary end point: estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2. Secondary end points: (1) delta eGFR after starting/stopping a drug and (2) RIFLE criterion Risk ‘R’, Injury ‘I’ and Failure ‘F’. Analysis was by intention to treat.Results28-day mortality was 31.8% and comparable (Jensen et al, Crit Care Med 2011). A total of 3672/7634 (48.1%) study days during follow-up in the high-exposure versus 3016/6949 (43.4%) in the ‘standard-exposure arm were spent with eGFR <60 ml/min/1.73 m2, p<0.001. In a multiple effects model, 3 piperacillin/tazobactam was identified as causing the lowest rate of renal recovery of all antibiotics used: 1.0 ml/min/1.73 m2/24 h while exposed to this drug (95% CI 0.7 to 1.3 ml/min/1.73 m2/24 h) vs meropenem: 2.9 ml/min/1.73 m2/24 h (2.5 to 3.3 ml/min/1.73 m2/24 h)); after discontinuing piperacillin/tazobactam, the renal recovery rate increased: 2.7 ml/min/1.73 m2/24 h (2.3 to 3.1 ml/min/1.73 m2 /24 h)). eGFR <60 ml/min/1.73 m2 in the two groups at entry and at last day of follow-up was 57% versus 55% and 41% versus 39%, respectively.ConclusionsPiperacillin/tazobactam was identified as a cause of delayed renal recovery in critically ill patients. This nephrotoxicity was not observed when using other beta-lactam antibiotics.Trial registrationClinicalTrials.gov identifier: NCT00271752.
The long‐term effect of cisplatin on renal function was studied in a follow‐up investigation, 16 to 52 months after chemotherapy in 22 patients with disseminated nonseminomatous testicular cancer. ...The median cumulated cisplatin dose was 452 mg/in2 (range, 275–650 mg/m2). Prehydration with isotonic saline secured diuresis above 100 ml/hour. GFR (glomerular filtration rate: 51Cr‐EDTA clearance) fell by 12.5% (median, P < 0.01) compared with the pretreatment level. Effective renal plasma flow (125I‐hippuran clearance) was estimated to be likewise reduced. The serum creatinine level rose 8 μmol/1 (median, P < 0.05) during the treatment period with no further rise afterwards. Serum magnesium and urinary excretion of beta‐2‐microglobulin were normal. The results indicate a moderate and permanent reduction in GFR with no signs of long‐term tubular defects in patients treated with cisplatin.
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.
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.
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).
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A method by which 51Cr-EDTA plasma clearance is determined from a single capillary blood sample (Clsc) was studied in 52 children less than 1 year old. The Clsc is calculated as the ratio between the ...injected dose and the total area under a transformed monoexponential function. The monoexponential curve is determined from the plasma activity 120 min after i.v. single injection of 51Cr-EDTA and a hypothetical initial activity calculated as the injected dose divided by the distribution space of 51Cr-EDTA. The distribution space was estimated from the body surface area. The rate constant of the monoexponential function is transformed by an empirically determined factor to make the area under the curve identical to the area under the true plasma disappearance curve. The Clsc was compared with 51Cr-EDTA plasma clearance (range 18-146 ml/min/1.73 m2) determined by a standard method from five capillary blood samples (CI). The regression of CI on Clsc did not differ from the line of identity, the SD being 5.9 ml/min/1.73 m2. In advanced renal failure the one-sample method is very sensitive to inaccuracies in the distribution space estimate and, accordingly, this method should be used only when the clearance value is predicted higher than 30 ml/min/1.73 m2.
The effect of propranolol on renal haemodynamics was studied in nine patients with arterial hypertension and moderate to severe chronic renal failure. A reduction of the renal function in this type ...of patient might have clinical consequence. The patients, whose glomerular filtration rate (GFR) ranged between 17 ml/min/1.73 m2 and 71 ml/min/1.73 m2, were studied during three 4-week periods with alternately placebo, propranolol (40 mg b.i.d.) and placebo treatment. The GFR and the effective renal plasma flow (ERPF) were determined as the plasma clearance of 51Cr-EDTA and 125I-hippurane. The GFR fell on the average 7% (95% confidence limits: 1-12%) during propranolol treatment, and the fall was reversible. No changes were found in ERPF. In conclusion, propranolol treatment in this type of patient causes a modest and reversible fall of GFR.
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