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

Putt, M. T., Udy, A. A., Jarrett, P., Martin, J., Hennig, S., Salmon, N., Lipman, J. and Roberts, J. A. (2013) Phenytoin loading doses in adult critical care patients: does current practice achieve adequate drug levels?. Anaesthesia and Intensive Care, 41 5: 602-609.

Author Putt, M. T.
Udy, A. A.
Jarrett, P.
Martin, J.
Hennig, S.
Salmon, N.
Lipman, J.
Roberts, J. A.
Title Phenytoin loading doses in adult critical care patients: does current practice achieve adequate drug levels?
Journal name Anaesthesia and Intensive Care   Check publisher's open access policy
ISSN 0310-057X
1448-0271
Publication date 2013-09
Year available 2013
Sub-type Article (original research)
Open Access Status
Volume 41
Issue 5
Start page 602
End page 609
Total pages 8
Place of publication Edgecliff, N.S.W., Australia
Publisher Australian Society of Anaesthetists
Collection year 2014
Language eng
Formatted abstract
Phenytoin is regularly employed in the critically ill for prophylaxis against or treatment of seizure disorders.
No prior studies have examined current dosing practices in an Australasian intensive care unit (ICU) setting.
The aims of this study were to: a) describe the adequacy of contemporary dosing in respect to free and
total serum phenytoin concentrations; b) identify factors associated with therapeutic drug concentrations; and
c) examine the accuracy of predictive equations that estimate free concentrations in this setting. All patients
receiving a loading dose of phenytoin in a tertiary-level ICU were eligible for enrolment; 53 patients were
enrolled in the study. Serum samples to determine free and total phenytoin concentrations (measured by
high performance liquid chromatography) were then drawn prior to the following dose. Free concentrations
below the recommended target (<1 mg/l) were considered as suboptimal. The most common indication
for phenytoin loading was traumatic brain injury (49%) and the mean administered dose was 14.5 (3.66)
mg/kg. Twenty-six patients (49%) had suboptimal trough free concentrations, although this subgroup was
significantly heavier and therefore received a lower per kilogram dose (12.8 [3.1] vs 16.3 [3.4] mg/kg, P=0.001).
In multivariate analysis, larger weight adjusted doses (P=0.018), higher albumin concentration (P=0.034) and
receiving phenytoin for an indication other than seizure (P=0.035), were associated with a greater likelihood
of adequate concentrations. In conclusion, phenytoin dosing remains complex in critically ill patients, although
lower per kilogram loading doses are strongly associated with free concentrations below the desired target.
Keyword Therapeutic drug monitoring
Dosing
Phenytoin
Intravenous Phenytoin
Status Epilepticus
Protein binding
Management
Epilepsy
System
Nonmem
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
School of Pharmacy Publications
 
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