Abstract 471 Poster Session III, Monday, 5/3 (poster 190)

Introduction: Reports that standard doses should be increased are flawed since the doses given and the amount of flush infused were not standardized in these studies. We compared the drug levels and pharmacodynamics of fosphenytoin and phenytoin given via the intraosseous and intravenous route in standard doses.

Methods: Piglets (30-40kg) were anesthetized, intubated, mechanically ventilated and placed on a Gross Model 7E Polygraph (Gross Instrument Co, Quincy, Massachusetts). A central venous flow direct catheter and an arterial catheter were placed for monitoring blood pressure and arterial blood sampling. A peripheral intravenous line and intraosseous needle (15 gauge Sur Fast Cook Inc.) was inserted for drug infusions. Forty animals (10 per group) were randomly assigned for intravenous and intraosseous phenytoin and fosphenytoin infusions. Phenytoin (20mg/kg) was infused over 20 minutes and fosphenytoin (20 mg PE/kg) over 7 minutes. All infusions were followed by 5ml normal saline flush (as done clinically). Blood samples (3 mls) for drug levels were then drawn before infusion (base line) and at 0, 5, 10, 15, 20, 30, 40, 50, 60 and 75 minutes following the completion of the infusion. Free and total phenytoin levels were assessed by Fluorescent Polarization Immunoassay Technique. Repeated measures Analysis of Variance (ANOVA) was used to evaluate statistical significance (p <.05).

Results: Phenytoin levels were undetected at baseline. Free (10-20mcg/ml) and total (80-110 mcg/ml) were well above therapeutic range (free 1-2mcg/ml and total 10-20 mcg/ml) post infusion in fosphenytoin groups as compared to phenytoin. From 20-75 minutes, all groups had free and total levels within therapeutic range. Significant differences in values were seen in free phenytoin at 0-10 minutes (p<0.05) and total phenytoin at 0-20 minutes (p<0.05) between intraosseous phenytoin and fosphenytoin. Similarly, differences were seen when intravenous phenytoin and fosphenytoin groups were compared. There was no significant difference in heart rate and blood pressure between groups.

Conclusion: There is no need to adjust standard drug doses of phenytoin when given via the intraosseous route if followed by adequate flush of 5ml. The initial high levels of phenytoin in the in the fosphenytoin groups are of concern since neurological toxic effects may occur at these levels. Slower infusion rates may be needed for fosphenytoin to avoid toxic levels.

Funded by Nemours Children's Foundation