Abstract
Objective
Population pharmacokinetic analysis and pharmacodynamic profile of propofol/alfentanil infusions for sedation and analgesia of intensive care unit patients for up to 24 h.
Design
Institutional Review Board-approved prospective clinical trial.
Setting
The ten-bed intensive care unit of an university hospital.
Patients
18 consecutive patients (ten men/eight women; age: 17–73 years, mean 51.6±16.7 years, SD; body weight: 60–110 kg, meand 82.9±11.2 kg. SD) requiring mechanical ventilation and prolonged sedation/analgesia after major surgery or trauma.
Interventions
Plasma propofol and alfentanil concentrations were measured at regular intervals during the long-term drug infusion using a high-performance liquid chromatography (propofol) and radioimmunoassay (alfentanil) analysis. The depth of sedation was controlled by monitoring a two-lead online EEG. Thus, drug application was computer controlled via a closed-loop EEG median-frequency feedback system.
Results
ICU long-term infusion population pharmacokinetics (open three-compartment model) revealed for propofol: central compartment distribution volume (V1): 31.2±5.3 l; steady-state distribution volume (Vdss): 499±173 l; total clearance (Cltot): 1001−±150 ml/min; redistribution half-life (t1/2γ): 90±23 min; elimination half-life (t1/2β): 558±218 minutes. For alfentanil: V1: 31.9±10.1 l; Vdss: 124±41 l; Cltot: 345±70 ml/min; t1/2γ: 36±15 min; t1/2β: 275±94 min, respectively.
Conclusions
The population pharmacokinetic analysis of propofol/alfentanil for ICU sedation therapy revealed increased volumes of drug distribution and decreased elimination characteristics as compared to pharmacokinetic data from short-term infusions in surgical patients. This can be attributed in part to altered distribution/redistribution processes and/or drug elimination under the condition of ICU therapy. No significant drug accumulation was observed. For future long-term sedation and analgesia of ICU patients with propofol/alfentanil, this altered pharmacokinetic behaviour should be taken into consideration to allow a more individualized and safer dosing of this drug combination.
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Frenkel, C., Schüttler, J., Ihmsen, H. et al. Pharmacokinetics and pharmacodynamics of propofol/alfentanil infusions for sedation in ICU patients. Intensive Care Med 21, 981–988 (1995). https://doi.org/10.1007/BF01700659
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DOI: https://doi.org/10.1007/BF01700659