Hydroxyethyl starch (HES) corrected is widely used for fluid resuscitation in intensive care units (ICUs), but its safety and efficacy have not been established in patients with severe sepsis.
In ...this multicenter, parallel-group, blinded trial, we randomly assigned patients with severe sepsis to fluid resuscitation in the ICU with either 6% HES 130/0.42 (Tetraspan) or Ringer's acetate at a dose of up to 33 ml per kilogram of ideal body weight per day. The primary outcome measure was either death or end-stage kidney failure (dependence on dialysis) at 90 days after randomization.
Of the 804 patients who underwent randomization, 798 were included in the modified intention-to-treat population. The two intervention groups had similar baseline characteristics. At 90 days after randomization, 201 of 398 patients (51%) assigned to HES 130/0.42 had died, as compared with 172 of 400 patients (43%) assigned to Ringer's acetate (relative risk, 1.17; 95% confidence interval CI, 1.01 to 1.36; P=0.03); 1 patient in each group had end-stage kidney failure. In the 90-day period, 87 patients (22%) assigned to HES 130/0.42 were treated with renal-replacement therapy versus 65 patients (16%) assigned to Ringer's acetate (relative risk, 1.35; 95% CI, 1.01 to 1.80; P=0.04), and 38 patients (10%) and 25 patients (6%), respectively, had severe bleeding (relative risk, 1.52; 95% CI, 0.94 to 2.48; P=0.09). The results were supported by multivariate analyses, with adjustment for known risk factors for death or acute kidney injury at baseline.
Patients with severe sepsis assigned to fluid resuscitation with HES 130/0.42 had an increased risk of death at day 90 and were more likely to require renal-replacement therapy, as compared with those receiving Ringer's acetate. (Funded by the Danish Research Council and others; 6S ClinicalTrials.gov number, NCT00962156.).
In this study, patients with severe sepsis were assigned to fluid resuscitation with starch (HES 130/0.4) or Ringer's acetate. The starch group had an increased risk of death at day 90 and increased ...use of renal-replacement therapy, as compared with the Ringer's acetate group.
Intravenous fluids are the mainstay of treatment for patients with hypovolemia due to severe sepsis. Colloid solutions are used to obtain rapid and lasting circulatory stabilization, but there are limited data to support this practice.
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The Surviving Sepsis Campaign guidelines recommend the use of either colloids or crystalloids,
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but high-molecular-weight hydroxyethyl starch (HES) may cause acute kidney failure in patients with severe sepsis, as observed in two randomized trials.
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,
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Those trials had substantial limitations, and participants received HES solutions with a molecular weight of 200 kD and a substitution ratio (the number of hydroxyethyl groups per glucose molecule) of . . .
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.
In a randomized trial comparing the proton-pump inhibitor pantoprazole with placebo in the ICU, there was no significant difference in the rate of death at 90 days or in a combined end point of ...clinically meaningful events, which included gastrointestinal bleeding and pneumonia.
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).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Flexible endoscopes have been well established for diagnostic and therapeutic interventions in critically ill patients. The purpose of this study was to compare the utility between the novel aScope 4 ...Broncho and the standard bronchoscope in a non-interventional study.
In a prospective multicentre study, we evaluated the aScope 4 Broncho for different clinical indications involving an endoscopy procedure. We compared the acceptability of and preference for the novel Ambu® aScope™ 4 Broncho (Ambu® A/S, Ballerup, Denmark) with that of the customary flexible endoscope (reusable or single-use) normally used at each of the study centres.
A total of 176 aScope 4 Broncho-aided interventions were evaluated, and the primary finding of the study was that the aScope 4 Broncho was preferred over customary devices for both diagnostic/therapeutic bronchoscopy (58% preference, P < 0.001), awake intubation with a flexible endoscope (65% preference, P = 0.0026), and pooled data (59%, P < 0.001).
Possible reasons for the higher acceptability of and preference for the aScope 4 Broncho are the manoeuvrability of the scope and the optimised visualisation during tracheal intubation or of the bronchial system. Because of these benefits, any encountered risks may be reduced in patients undergoing bronchoscopic procedures, including in critically ill and presurgical/medical patients.
NCT03294213. Registered: September 26, 2017.
•Flexible endoscopy is a common diagnostic and essential therapeutic technique in critical care patients or used for difficult airway.•In this multicentre study we investigated the novel aScope 4 Broncho single-use video-endoscope in 176 patients, undergoing awake video-optical intubation or bronchoscopy.•The aim of the study was the comparison of the preference of each intervention, based on the physician’s memory of their standard endoscope.•The primary finding of the study was that the aScope 4 Broncho was preferred over standard methods for both bronchoscopy and intubation.•The improved technical features (e.g. image quality, bending angle with 180° ante-/reflection) of the aScope 4 Broncho may have led to the results.
Mannan-binding lectin (MBL) is a member of the innate immune system, and MBL-deficiency affects 10-15% of Caucasians. With development of a plasma-derived MBL, substitution has become a therapeutic ...option in diseases associated with MBL insufficiency. The pharmacokinetics of injected MBL is weakly described, particularly in patients with infectious diseases. The pharmacokinetic profile of MBL following administration of 0.08 mg/kg to 20 healthy MBL-deficient volunteers and 0.2 mg/kg to 2 patients with Staphylococcus aureus septicaemia was established. In the volunteers, the maximal concentration was 2849 µg/l; the mean half-life (T1/2) was 69.6 h (14.6-114.9 h). The normalized clearance was 9×10−6 l/min×kg, and the mean residence time was 82 h. In the patients the serum-MBL versus time curves were similar to those in the volunteers, and T1/2 values were 36 and 40 h. In conclusion, MBL is distributed into a median volume of 3.4 l similar to the plasma volume, and the elimination in septicaemic patients was within the range of the controls. Due to the large individual variation in T1/2, we recommend that MBL therapy, with respect to dose and infusion intervals, is based on the chosen therapeutic target (≥1000 µg/l) and MBL serum determinations following the first infusion.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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