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Doripenem dosing recommendations for critically ill patients receiving continuous renal replacement therapy.

ABSTRACT: Doripenem dosing regimens for patients receiving continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodiafiltration (CVVHDF) were devised based on an established efficacy criterion (free plasma doripenem concentrations above the minimum inhibitory concentration [fT > MIC] of 1?mg/L for ?35% of the dosing interval) while maintaining exposure below that with the highest studied dose of 1000?mg infused over 1 hour every 8 hours in healthy subjects. Simulations were utilized to assure ?90% probability of achieving the efficacy criterion with the recommended doripenem regimens. Inflated intersubject variability of 40% (coefficient of variation) was used for pharmacokinetic parameters (representative of clinical variation) and nonrenal clearance was doubled to account for potential changes with acute renal insufficiency. Results indicate that a reduction in doripenem dose will be needed for critically ill patients receiving CVVH or CVVHDF. This work was conducted to fulfill a health authority request and resulted in the addition of dosing recommendations to the Doribax Summary of Product Characteristics.

SUBMITTER: Samtani MN

PROVIDER: S-EPMC3409546 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Doripenem dosing recommendations for critically ill patients receiving continuous renal replacement therapy.

Samtani Mahesh N MN Vaccaro Nicole N Cirillo Iolanda I Matzke Gary R GR Redman Rebecca R Nandy Partha P

ISRN pharmacology 20120719

Doripenem dosing regimens for patients receiving continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodiafiltration (CVVHDF) were devised based on an established efficacy criterion (free plasma doripenem concentrations above the minimum inhibitory concentration [fT > MIC] of 1 mg/L for ≥35% of the dosing interval) while maintaining exposure below that with the highest studied dose of 1000 mg infused over 1 hour every 8 hours in healthy subjects. Simulations were utilized to ...[more]

PMID: 22888451

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Project description:Rationale & objectiveClinical practice guidelines recommend delivering a continuous renal replacement therapy (CRRT) dose of 20 to 25mL/kg/h. However, practice patterns nationwide are highly variable; this inconsistent prescribing may lead to errors in medication dosing and increase rates of electrolyte and acid-base abnormalities. We describe an initiative to standardize CRRT practice patterns and reduce dosing variability.Study designQuality improvement study.Setting & participantsAdult patients treated with CRRT at the University of Colorado Hospital between January 2016 and October 2017.Quality improvement activitiesAn assessment of the magnitude of the variability in CRRT dosing and the following specific interventions were implemented during the course of 1 year: (1) modification of the electronic medical record (EMR) to include calculated average 24-hour dose in real time, (2) modification of the CRRT procedure note to include comments on dosing, (3) modification of the CRRT order set to display calculations, and (4) yearly educational sessions for renal fellows outlining CRRT-specific dosing targets.OutcomesThe primary outcome was weekly percentage of CRRT treatments with an average delivered daily dose of 20 to 25mL/kg/h. Process and balancing outcomes included CRRT flowsheet accuracy, documentation of rates of delivered dose, and nursing satisfaction.Analytical approachRates of weekly CRRT dosing in compliance with national guidelines were determined and used to create run charts showing compliance rates before and after the quality improvement interventions.ResultsAmong 837 treatments before the intervention, 279 (33%) daily CRRT sessions achieved an average dose of 20 to 25mL/kg/h. Following implementation of interventions, 631 of 952 (66%) treatments achieved this goal. Week-to-week variation in dosing was significantly reduced.LimitationsA single-center study generating data that may not be generalizable to institutions with different CRRT nursing models or different EMR systems.ConclusionsChanges to the EMR and documentation templates and education of CRRT providers about dosing were associated with doubling of the rate of appropriate CRRT dosing and reduction in dosing variability.

Project description:BackgroundFluid overload is associated with morbidity and mortality in patients receiving renal replacement therapy (RRT). We aimed to explore whether fluid overload at initiation of RRT was independently associated with mortality and whether changes in cumulative fluid balance during RRT were associated with outcome.MethodsWe retrospectively analysed the data of patients who were admitted to the multidisciplinary adult intensive care unit (ICU) in a tertiary care centre in the UK between 2012 and 2015 and received continuous RRT (CRRT) for acute kidney injury for at least 24?h. We collected baseline demographics, body mass index (BMI), comorbidities, severity of illness, laboratory parameters at CRRT initiation, daily cumulative fluid balance (FB), daily prescribed FB target, fluid bolus and diuretic administration and outcomes. The day of the lowest cumulative FB during CRRT was identified as nadir FB.ResultsEight hundred twenty patients were analysed (median age 65?years; 49% female). At CRRT initiation, the median cumulative FB was +?1772?ml; 89 patients (10.9%) had a cumulative FB?>?10% body weight (BW). Hospital survivors had a significantly lower cumulative FB at CRRT initiation compared to patients who died (1495 versus 2184?ml; p <?0.001). In the 7?days after CRRT initiation, hospital survivors had a significant decline in cumulative FB (mean decrease 473?ml per day, p <?0.001) whilst there was no significant change in cumulative FB in non-survivors (mean decrease 112?ml per day, p =?0.188). Higher severity of illness at CRRT initiation, shorter duration of CRRT, the number of days without a prescribed FB target and need for higher doses of noradrenaline were independent risk factors for not reaching a FB nadir during CRRT. Multivariable analysis showed that older age, lower BMI, higher severity of illness, need for higher doses of noradrenaline and smaller reductions in cumulative FB during CRRT were independent risk factors for ICU and hospital mortality. Cumulative FB at CRRT initiation was not independently associated with mortality.ConclusionIn adult patients receiving CRRT, a decrease in cumulative FB was independently associated with lower mortality. Fluid overload and need for vasopressor support at CRRT initiation were not independently associated with mortality after correction for severity of illness.

Project description:Background: Overfeeding can lead to multiple metabolic and clinical complications and has been associated with increased mortality in the critically ill. Continuous venovenous hemofiltration (CVVH) represents a potential source of calories that is poorly recognized and may contribute to overfeeding complications.Objective: We aimed to quantify the systemic caloric contribution of acid-citrate-dextrose regional anticoagulation and dextrose-containing replacement fluids in the CVVH circuit.Design: This was a prospective study in 10 critically ill adult patients who received CVVH from April 2014 to June 2014. Serial pre- and postfilter blood samples (n = 4 each) were drawn and analyzed for glucose and citrate concentrations on each of 2 consecutive days.Results: Participants included 5 men and 5 women with a mean ± SEM age of 61 ± 4 y (range: 42-84 y) and body mass index (in kg/m2) of 28 ± 2 (range: 18.3-36.2). There was generally good agreement between data on the 2 study days (CV: 7-11%). Mean ± SEM pre- and postfilter venous plasma glucose concentrations in the aggregate group were 152 ± 10 and 178 ± 9 mg/dL, respectively. Net glucose uptake from the CVVH circuit was 54 ± 5 mg/min and provided 295 ± 28 kcal/d. Prefilter plasma glucose concentrations were higher in patients with diabetes (n = 5) than in those without diabetes (168 ± 12 compared with 140 ± 14 mg/dL; P < 0.05); however, net glucose uptake was similar (46 ± 8 compared with 61 ± 6 mg/min; P = 0.15). Mean ± SEM pre- and postfilter venous plasma citrate concentrations were 1 ± 0.1 and 3.1 ± 0.2 mmol/L, respectively. Net citrate uptake from the CVVH circuit was 60 ± 2 mg/min and provided 218 ± 8 kcal/d.Conclusions: During CVVH there was a substantial net uptake of both glucose and citrate that delivered exogenous energy and provided ∼512 kcal/d. Failure to account for this source of calories in critically ill patients receiving nutrition on CVVH may result in overfeeding.

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Doripenem dosing recommendations for critically ill patients receiving continuous renal replacement therapy.

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Doripenem dosing recommendations for critically ill patients receiving continuous renal replacement therapy.

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