Abstracts

RATIONALE: Fosphenytoin (FOS) offers the alternative of intramuscular (IM) administration to achieve therapeutic phenytoin (PHT) plasma concentrations. In addition to convenience in patients with limited intravenous (IV) access, minimal changes in blood pressure (BP) and heart rate (HR) with IM FOS suggest it may be advantageous in patients at risk for cardiovascular (CV) complications from IV PHT or FOS. The purpose of this study was to evaluate the CV effects following IM FOS loading doses in patients with or without existing cardiac problems.
METHODS: Medical records for adult patients in the Neurosurgical ICU or step-down unit receiving IM FOS doses of [gte]500 mg phenytoin equivalents (PE) between October 1996 and April 2000 were reviewed. Demographic and clinical data for 3 days before and after IM FOS were abstracted. Serial BP and HR were collected until 3 hours postdose and changes from baseline assessed by analysis of variance.
RESULTS: Data on 53 patients, 32 males and 21 females, aged 17 - 82 yr (mean 49 yr) were analyzed. Indications for FOS were seizure prophylaxis for craniotomy (26%), intracranial hemorrhage (26%), or brain neoplasms (32%). Doses ranged from 500-2000 mg PE (mean 974 mg PE). Loading doses were given as 2 IM injections (5-20 ml each) in 6 patients and as a single injection in 47 patients (10-40 ml). Injection site was gluteus in 61.5%, vastus lateralis in 30.8% and deltoid in 7.7%. No signs of irritation at injection site were noted in any patients. Mean BP and HR did not significantly (p[gt]0.1) change from baseline (mean: 127/65 and 82) at 30 (117/62 and 77), 60 (128/65 and 82), 120 (124/63 and 81), and 180 (120/66 and 80) minutes after IM FOS. When BP and HR in patients with existing cardiac disease (n=31) and patients older than 60 yr (n=14) were analyzed separately, the changes from baseline remained clinically and statistically insignificant (p[gt]0.1) at 30 to 180 minutes postdose in both subgroups. Decrease of [gt]20 mmHg in systolic or [gt]10 mmHg in diastolic BP occurred in 12 patients, all of whom had existing cardiac disease and were receiving antihypertensives or pressors. These changes were not clinically significant and no interventions or changes in doses of pressors or vasodilators were required. No significant changes were seen in PR, QRS and QT intervals in patients with pre and postdose ECG data.
CONCLUSIONS: IM FOS provides a safe and well-tolerated alternative for administration of PHT loading doses, including those patients at risk for CV complications with IV PHT and FOS (i.e., the elderly or patients with existing cardiac disease).
Support: unrestricted educational grant from Pfizer.