Abstracts

Introduction of IV VPA has allowed its use when oral administration is not feasible. However, the recommended administration rate of 20 mg/minute does not facilitate its use in emergent situations. We present data on safety of IV administration of loading doses (20 or 30mg/kg) of undiluted VPA at 10mg/kg/min. Patients meeting inclusion criteria were enrolled in this prospective study. Patients in status epilepticus, with hepatic dysfunction, allergy to VPA or lamotrigine therapy were excluded.
VPA loading doses of 20 or 30mg/kg were administered undiluted via peripheral IV at 10mg/kg/min. Local tolerance was evaluated using the pain scale (0-10). Blood pressure (MAP), heart rate (HR), respiratory rate (RR), and electrocardiogram (EKG) were monitored every 2.5 minutes for the first 20 minutes, then at 30, 45 and 60 minutes post-infusion. Level of consciousness (LOC) was evaluated prior to and 60 minutes post-infusion using the NIH Stroke Scale-LOC tool. Total and unbound VPA levels were measured at baseline, 30, 60 minutes, and then 4 hours post-infusion.
Repeated measures ANOVA was used to evaluate the influence of VPA dose on cardiovascular parameters. Seventeen patients (10 men) were enrolled with eight patients receiving 20mg/kg and nine 30 mg/kg loading doses of VPA. There were no differences in age, gender distribution, or weight between the 2 dose groups.
Patients tolerated the infusion well. Most reports were of minor or no intolerance. Three patients reported severe pain (score [gt]7/10) and two severe cold sensation/numbness (score [gt]7/10). This intolerance was transient, did not require slowing infusion, [amp] resolved spontaneously in all patients within 3 minutes. There was no difference in duration of intolerance by dose (p=0.24).
[underline]Systemic Tolerance: [/underline]The cardiovascular tolerance of rapid infusion was good with no significant alteration in LOC, EKG or respiratory parameters. Since the heart rate (HR) in patients receiving 20 mg/kg was higher than those receiving 30 mg/kg at baseline (p=0.002), the repeated measures model ANOVA considered baseline HR and MAP as predictor variables.
Neither time of HR measurement or dose had a significant affect on HR (p[gt]0.50).
Both time of MAP measurement and dose had a significant effect on MAP (p[lt]0.05). MAP was lower by 2.86 mmHg [95% CI 0.105, 5.63] for patients receiving 30mg/kg dose than for those receiving 20-mg/kg doses. Although this finding is statistically significant, its clinical significance is equivocal.
Both free [amp] total VPA concentrations were significanlty higher in the 30mg/kg dose group than in the 20 mg/kg group at 30 [amp] 60 minutes(p[lt]0.0001) but not at 4 hours. Administration of loading doses (20 or 30 mg/kg) of undiluted VPA at 10 mg/kg/min is well tolerated with expected peak concentrations over 100mcg/ml. (Supported in part by Abbott Laboratories under FDA IND# 62165.)