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Published on: August 30, 2018

Phenytoin loading doses in adult critical care patients: does current practice achieve adequate drug levels?

M T Putt1, A A Udy, P Jarrett

  • 1Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.

Anaesthesia and Intensive Care
|August 28, 2013
PubMed

Insights

Phenytoin dosing in intensive care units (ICUs) often leads to suboptimal free concentrations. Lower weight-adjusted loading doses are linked to inadequate therapeutic drug levels in critically ill patients.

Area of Science:

  • Pharmacology and Critical Care Medicine

Background:

  • Phenytoin is crucial for seizure management in critically ill patients.
  • Current phenytoin dosing practices in Australasian intensive care units (ICUs) lack prior investigation.
  • Optimizing phenytoin therapy requires understanding factors influencing serum concentrations.

Purpose of the Study:

  • To evaluate the adequacy of current phenytoin dosing based on free and total serum concentrations.
  • To identify predictors of achieving therapeutic phenytoin concentrations.
  • To assess the accuracy of predictive equations for estimating free phenytoin levels in ICUs.

Main Methods:

  • Prospective study of 53 critically ill patients receiving phenytoin loading doses in a tertiary ICU.
  • Serum samples collected pre-dose to measure free and total phenytoin concentrations via high-performance liquid chromatography.
  • Suboptimal free concentrations defined as <1 mg/l.

Main Results:

  • Nearly half of patients (49%) experienced suboptimal trough free phenytoin concentrations.
  • Patients with suboptimal concentrations received significantly lower weight-adjusted loading doses (12.8 vs 16.3 mg/kg).
  • Higher weight-adjusted doses, increased albumin, and non-seizure indications correlated with adequate concentrations.

Conclusions:

  • Phenytoin dosing in critically ill patients presents significant challenges.
  • Lower per-kilogram loading doses are strongly associated with subtherapeutic free phenytoin levels.
  • Weight-adjusted dosing, albumin levels, and indication are key factors for optimizing phenytoin therapy.

Keywords:
dosingphenytointherapeutic drug monitoring

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