Altered aminoglycoside pharmacokinetics in the critically ill
M J Beckhouse1, I M Whyte, P L Byth
1Discipline of Clinical Pharmacology, Faculty of Medicine, University of Newcastle.
Anaesthesia and Intensive Care
|November 1, 1988
Summary
Critically ill patients receiving aminoglycoside antibiotics for gram-negative sepsis often require higher doses due to larger volumes of distribution (Vd). Standard dosing is not recommended due to significant Vd variability.
Area of Science:
- Pharmacology
- Critical Care Medicine
- Infectious Diseases
Background:
- Aminoglycosides are crucial for treating gram-negative sepsis.
- Patient variability in drug response necessitates individualized dosing strategies.
Purpose of the Study:
- To investigate the pharmacokinetic variability of aminoglycosides in critically ill patients.
- To determine optimal dosing regimens for achieving therapeutic aminoglycoside concentrations.
Main Methods:
- Prospective study of 49 intensive care unit patients receiving aminoglycosides.
- Pharmacokinetic analysis using a one-compartment model from three post-dose serum levels.
- Volume of distribution (Vd) changes assessed during therapy and post-discharge.
Main Results:
- Mean aminoglycoside dose was 7 mg/kg/day, with a range of 2-12 mg/kg/day.
- 60% of patients exhibited >20% change in Vd during therapy, often associated with fever and confirmed infection.
- Post-discharge, mean Vd decreased significantly from 0.24 to 0.18 l/kg (P < 0.02).
Conclusions:
- Critically ill patients often have larger Vd, potentially requiring higher aminoglycoside doses.
- Significant Vd variations underscore the inadequacy of standard dosing or nomograms.
- Individualized pharmacokinetic monitoring is essential for optimizing aminoglycoside therapy in sepsis.
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