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Phenytoin dosing and serum concentrations in paediatric patients requiring 20 mg/kg intravenous loading
  1. Joe D Piper1,
  2. Daniel B Hawcutt2,
  3. George K Verghese1,
  4. Stefan Spinty1,
  5. Paul Newland3,
  6. Richard Appleton1,2
  1. 1Department of Neurology, Alder Hey Children's Hospital, Liverpool, UK
  2. 2Department of Women's and Children's Health, University of Liverpool, Liverpool, UK
  3. 3Department of Clinical Chemistry, Alder Hey Children's Hospital, Liverpool, UK
  1. Correspondence to Dr Richard Appleton, Alder Hey Children's Hospital, Eaton Road, Liverpool L12 2AP, UK; Richard.Appleton{at}Alderhey.nhs.uk

Abstract

Introduction Phenytoin has complex pharmacokinetics. The intravenous loading dose of phenytoin for children in status epilepticus has recently been increased from 18 to 20 mg/kg. There are no data on the clinical effectiveness and safety of this new dose.

Methods The use of intravenous loading doses of phenytoin was audited over 27 months to evaluate the pharmacokinetic, clinical and toxic effects of the new dose in clinical practice. Serum phenytoin concentrations were compared with dose (weight-adjusted) and time.

Results Serum phenytoin concentrations were measured on 48 occasions from 41 children (39 retrospective and 9 prospective), of which 24 were within 60–180 (median 105) minutes following completion of infusion of the loading dose. Use of estimated weights meant patients received between 15.5 and 27.5 mg/kg (78% to 138% expected dose). Supra-therapeutic serum concentrations >20 µg/mL were present in 5/24 (20.1%) (after doses based on actual weight in three and estimated weight in two patients). Three adverse effects consistent with phenytoin toxicity were noted in children with supra-therapeutic concentrations. Two errors in dose prescriptions were found.

Conclusions The majority of serum phenytoin concentrations were in the therapeutic range. Estimating weight in children for the 20 mg/kg intravenous loading dose of phenytoin is often clinically necessary but inaccurate, resulting in up to 138% of the expected and recommended dose in this cohort.

  • Pharmacology
  • Neurology
  • Accident & Emergency
  • Therapeutics
  • Audit

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