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Continuous Renal Replacement Therapy01:30

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Drug Dosing in Renal Diseases: Dose Adjustments Based on Drug Clearance and Elimination Rate Constant01:25

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In patients with renal disease, dosage adjustments are necessary to maintain therapeutic plasma drug concentrations and prevent toxicity or subtherapeutic exposure. Renal impairment alters drug pharmacokinetics, especially in conditions like uremia, where changes such as prolonged elimination half-life and altered apparent volume of distribution can significantly affect drug disposition. These changes require careful modification of the dosing regimen to achieve the desired clinical...
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Extracorporeal Removal of Drugs: Continuous Renal Replacement Therapy01:26

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Continuous Renal Replacement Therapy (CRRT) is an essential intervention for patients experiencing severe kidney dysfunction. This therapy offers a continuous mechanism for removing fluids and toxins from the bloodstream, leveraging the patient’s blood pressure to facilitate filtration through a specialized filter. This method contrasts with intermittent dialysis, providing a gentler and more consistent removal of waste products and excess fluid, which is particularly beneficial in...
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Intermittent intravenous (IV) infusion is a method of drug administration where medications are delivered over short infusion periods followed by intervals of no drug delivery. This approach helps to prevent sustained high drug concentrations in the bloodstream, reducing the risk of adverse effects associated with prolonged exposure. Unlike continuous infusion, steady-state concentrations may not be achieved during a single dosing cycle but can be reached through repeated...
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Gentamicin, an aminoglycoside antibiotic, is commonly administered via intermittent intravenous infusion to treat severe infections. An intermittent one-hour infusion of gentamicin, administered at eight-hour intervals, allows for precise control of plasma drug concentrations, minimizing toxicity while ensuring therapeutic efficacy. Pharmacokinetic principles govern the dynamics of plasma concentrations and can be mathematically described using specific equations.The plasma drug concentration...
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Antibiotic Dosing in Continuous Renal Replacement Therapy.

Alexander R Shaw1, Bruce A Mueller1

  • 1Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, MI.

Advances in Chronic Kidney Disease
|August 6, 2017
PubMed
Summary
This summary is machine-generated.

Appropriate antibiotic dosing in sepsis is challenging with continuous renal replacement therapy (CRRT). This study found most standard antibiotic doses achieve target concentrations with CRRT effluent flow rates of 20 or 35 mL/kg/h.

Keywords:
Acute kidney injuryAntibioticsPharmacodynamicsPharmacokineticsRenal replacement therapy

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Area of Science:

  • Pharmacology
  • Nephrology
  • Critical Care Medicine

Background:

  • Optimizing antibiotic dosing is crucial for sepsis patients, especially those on continuous renal replacement therapy (CRRT).
  • Lack of CRRT standardization leads to variable antibiotic exposure and potentially suboptimal treatment.
  • Understanding the impact of CRRT effluent flow rate on antibiotic concentrations is essential.

Purpose of the Study:

  • To evaluate if CRRT effluent flow rate affects achieving adequate antibiotic concentrations using standard dosing.
  • To assess the impact of varying effluent flow rates on pharmacodynamic target attainment for key antibiotics.

Main Methods:

  • Utilized Monte Carlo simulations with 5000 virtual patients per antibiotic.
  • Modeled pharmacokinetic parameters for cefepime, ceftazidime, levofloxacin, meropenem, piperacillin, and tazobactam.
  • Simulated CRRT effluent flow rates at Kidney Disease: Improving Global Outcomes (KDIGO) extremes (20 and 35 mL/kg/h) over 72 hours.

Main Results:

  • Most conventional antibiotic dosing regimens achieved acceptable pharmacodynamic target attainment rates.
  • This held true for both 20 mL/kg/h and 35 mL/kg/h effluent flow rates.
  • Levofloxacin was an exception, with some regimens not reaching target attainment.

Conclusions:

  • Conventional antibiotic dosing generally ensures adequate drug exposure in sepsis patients on CRRT.
  • Effluent flow rates within KDIGO guidelines (20-35 mL/kg/h) are unlikely to compromise target attainment for most tested antibiotics.
  • Further optimization may be needed for specific antibiotics like levofloxacin in CRRT settings.