Drug Dosing During Intermittent Hemodialysis and Continuous Renal Replacement Therapy

Veltri, Michael A.; Neu, Alicia M.; Fivush, Barbara A.; Parekh, Rulan S.; Furth, Susan L.

doi:10.2165/00148581-200406010-00004

Cited by 69 publications

(38 citation statements)

References 87 publications

(20 reference statements)

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“…19 ). Veltri et al recommended an initial dose of 10-15 mg/kg parenterally followed by vancomycin concentrations monitoring in septic patients treated with CRRT in all modes 21 . The initial median daily dose of vancomycin in our group of patients was 20.0 mg/kg (8.3 to 43.8) with a loading dose of 1.0 g, maintenance dose was based on vancomycin serum concentrations.…”

Section: Discussionmentioning

confidence: 99%

Vancomycin pharmacokinetics during high-volume continuous venovenous hemofiltration in critically ill septic patients

Petejová¹,

Martínek²,

Zahálková³

et al. 2014

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Aims.To assess the influence of continuous venovenous hemofiltration (CVVH) at a filtration rate of 45 mL/kg/h on vancomycin pharmacokinetics in critically ill septic patients with acute kidney injury (AKI). Methods. Seventeen adult septic patients with acute kidney injury treated with CVVH and vancomycin were included. All patients received first dose of 1.0 g intravenously followed by 1.0 g/12 h if not adjusted. In sixteen patients vancomycin was introduced on the day of the start of CRRT therapy. Blood samples and ultrafiltrates were obtained before and 0.5, 1, 6 and 12 h after vancomycin administration. Results. On the first day, the median total vancomycin clearance (Cl tot ) was 0.89 mL/min/kg (range 0.31 -2.16). CRRT clearance accounted for around 50-60% of the total clearance of vancomycin found in a population with normal renal function (0.97 mL/min/kg). Vancomycin serum concentrations after the first dose were below the required target of 10 mg/L as early as 6 h in 10 patients, AUC 0-24 /MIC ≥ 400 ratio was achieved in 10 patients on the first day. Conclusions. CVVH at a filtration rate of 45 mL/kg/h leads to high and rapid extracorporeal removal of vancomycin in critically ill patients. Due to the rapid change in patient clinical status it was impossible to predict a fixed dosage regimen. We recommend blood sampling as early as 6 h after first vancomycin dose with maintenance dose based on vancomycin serum level monitoring.

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Section: Discussionmentioning

confidence: 99%

Vancomycin pharmacokinetics during high-volume continuous venovenous hemofiltration in critically ill septic patients

Petejová¹,

Martínek²,

Zahálková³

et al. 2014

BIOMED PAP

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“…Dose modifications of CTX might therefore be required, particularly because the bactericidal action of CTX is time dependent, which is why the dosing interval and frequency should result in plasma concentrations that remain above the targeted level for as long as possible. For CTX, this targeted level is commonly set at 4 mg/liter, which is 4ϫ the MIC against Enterobacteriaceae (9, 10).For CTX, regimes of 1,000 mg twice daily, 2,000 mg twice daily, or 1,000 mg four times daily have all been recommended in patients with severe renal failure (11,12). However, during continuous renal replacement therapy, the pharmacokinetics may appear completely different compared to intermittent hemodialysis.…”

mentioning

confidence: 99%

“…For CTX, regimes of 1,000 mg twice daily, 2,000 mg twice daily, or 1,000 mg four times daily have all been recommended in patients with severe renal failure (11,12). However, during continuous renal replacement therapy, the pharmacokinetics may appear completely different compared to intermittent hemodialysis.…”

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confidence: 99%

Pilot Study of the Pharmacokinetics of Cefotaxime in Critically Ill Patients with Acute Kidney Injury Treated with Continuous Renal Replacement Therapy

Koedijk

Valk-Swinkels

Rijpstra

et al. 2016

Antimicrob Agents Chemother

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h The objective of this study was to describe the pharmacokinetics of cefotaxime (CTX) in critically ill patients with acute kidney injury (AKI) when treated with continuous renal replacement therapy (CRRT) in the intensive care unit (ICU). This single-center prospective observational pilot study was performed among ICU-patients with AKI receiving >48 h concomitant CRRT and CTX. CTX was administered intravenously 1,000 mg (bolus) every 6 h for 4 days. CRRT was performed as continuous venovenous hemofiltration (CVVH). Plasma concentrations of CTX and its active metabolite desacetylcefotaxime (DAC) were measured during CVVH treatment. CTX plasma levels and patient data were used to construct concentration-time curves. By using this data, the duration of plasma levels above 4 mg/liter (four times the MIC) was calculated and analyzed. Twenty-seven patients were included. The median CTX peak level was 55 mg/liter (range, 19 to 98 mg/liter), the median CTX trough level was 12 mg/liter (range, 0.8 to 37 mg/liter), and the median DAC plasma level was 15 mg/liter (range, 1.5 to 48 mg/liter). Five patients (19%) had CTX plasma levels below 4 mg/liter at certain time points during treatment. In at least 83% of the time any patient was treated with CTX, the CTX plasma level stayed above 4 mg/liter. A dosing regimen of 1,000 mg of CTX given four times daily is likely to achieve adequate plasma levels in patients with AKI treated with CVVH. Dose reduction might be a risk for suboptimal treatment. Nosocomial infections are frequently acquired in the intensive care unit (ICU), leading to an increase in morbidity and mortality in patients (1). Systemic antibiotics are used to treat these infections. Also in our ICU, patients are treated to prevent colonization and subsequent infections by selective decontamination of the digestive tract (SDD) (2-4). Widely used systemic agents are broad-spectrum parenteral cephalosporins such as cefotaxime (CTX). CTX is a ␤-lactam antibiotic that has antimicrobial activity against potential pathogenic microorganisms such as Staphylococcus aureus, Streptococcus pneumoniae, and Enterobacteriaceae (5). After administration, CTX undergoes hydrolysis by esterases available in plasma and the liver to form its active metabolite, desacetylcefotaxime (DAC), which is further metabolized into inactive compounds (6). CTX and DAC have half-lives of 1.1 and 1.3 h, respectively, and are mainly excreted in the urine (7).Since CTX is mainly cleared by the kidneys, acute kidney injury (AKI) may alter its excretion and pharmacokinetic parameters (8). Subsequently, supporting a patients impaired renal function with renal replacement therapy can again significantly alter the elimination of the drugs. Continuous renal replacement therapy (CRRT) substitutes for renal function by effectively removing solutes from the blood. The extracorporeal clearance is especially relevant for drugs with a dominant renal clearance and results in unpredictable pharmacokinetics (8). Dose modifications of CTX might therefore be required...

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“…Overall this means that the management of drug therapy in children is not necessarily informed by reviewing adult data. Anecdotal evidence suggests that many paediatricians use the anuric dose, extrapolate from IHD doses or simply prescribe the full dose when prescribing for children on CRRT [61]. It is important that future studies of drug disposition during CRRT include children, as this would allow for more specific recommendations for drug dosing in paediatric patients.…”

Section: Special Populations: Paediatric Considerationsmentioning

confidence: 99%

Drug Dosing in Continuous Renal Replacement Therapy (CRRT)

Gallagher

Murray

2016

Core Concepts in Dialysis and Continuous Therapies

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Drug Dosing During Intermittent Hemodialysis and Continuous Renal Replacement Therapy

Cited by 69 publications

References 87 publications

Vancomycin pharmacokinetics during high-volume continuous venovenous hemofiltration in critically ill septic patients

Vancomycin pharmacokinetics during high-volume continuous venovenous hemofiltration in critically ill septic patients

Pilot Study of the Pharmacokinetics of Cefotaxime in Critically Ill Patients with Acute Kidney Injury Treated with Continuous Renal Replacement Therapy

Drug Dosing in Continuous Renal Replacement Therapy (CRRT)

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