VPA is a short-chain fatty acid possessing anticon- vulsant activity, although ...
patients who did not respond to primary therapies, usu- ... Academy of Neurology.
PROCEEDINGS
OUTCOME OF STATUS EPILEPTICUS TREATED WITH INTRAVENOUS VALPROIC ACID* — Dean K. Naritoku, MD
ABSTRACT A retrospective chart review of 32 patients treated with intravenous valproic acid (IV VPA) for status epilepticus (SE) was conducted to determine the effectiveness of the regimen. The endpoint was cessation of convulsive seizures identified by electrography or clinical observation. Overall, the study suggested that IV VPA is a useful adjunct for SE. However, outcomes for overt convulsive SE are dependent on the rapidity of treatment. (Advanced Studies in Medicine 2001;1(7):279–280)
alproic acid (VPA) has been reported to be effective in the treatment of status epilepticus (SE) when administered orally or rectally.1 Intravenous (IV) administration potentially expands the utility of VPA in SE, but experience with this formulation is limited. VPA is a short-chain fatty acid possessing anticonvulsant activity, although its exact mechanism is not known.2 In SE, VPA has been reported to have few adverse reactions, and to be slower and longer acting
V
Correspondence to Dean K. Naritoku, MD, Associate Professor of Neurology and Pharmacology, Department of Neurology, P.O. Box 19637, Springfield, IL 62791-9637. *This article is based in part on a presentation given by Dr. Naritoku at the 53rd Annual Meeting of the American Academy of Neurology.
Advanced Studies in Medicine
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than benzodiazepines, but faster and shorter acting than phenytoin and phenobarbital.1 Some published studies report the use of IV VPA in SE patients.3-5 To further analyze this regimen, a retrospective review of 32 patients treated with IV VPA for SE was conducted. Convulsive SE was classified as simple partial (SPSE), complex partial (CPSE), overt convulsive (OCSE), and subtle convulsive (SCSE). The endpoint was cessation of convulsive seizures identified by electrography or clinical observation. As can be expected, patient age varied according to seizure type. Those with status epilepticus had a median age of 68.5 years, and those with complex partial and simple partial SE had a median age of about 45. Although the etiologies varied among patients, the majority developed SE as a result of anoxia (Table 1). Predictably, the duration of SE prior to valproic acid therapy did differ slightly, depending on the SE classification. In overt convulsive patients, the mean duration of SE was found to be approximately 20 hours. Patients who had SCSE had a mean duration of approximately 40 hours prior to therapy. IV VPA was used primarily for patients who did not respond to primary therapies, usually a benzodiazepine and a phos-phenytoin. For some, IV VPA was started in place of phenobarbital as a result of a shortage of that drug a few years ago. In 3 patients with unstable cardiac status, IV VPA was used as a primary therapy because it has been shown to be well tolerated in cardiac patients who may be using additional agents such as benzodiazepine or phos-phenytoin. The mean number of drugs administered to patients prior to IV VPA was 2 for patients with CPSE and 1.5 for patients with SPSE. The mean IV VPA dose administered was 25.0 ± 7.9 mg/kg, with resulting serum levels of 80.1 ± 39.5 mg/L. Postinfusion levels averaged approxi-
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Table 1. Etiologies of Status Epilepticus
Postanoxia
8
CNS infection
5
Epilepsy exacerbation
5
Metabolic encephalopathy
5
Subdural hematoma
3
CVA
3
Hypertensive encephalopathy
1
Unknown
3
CNS = central nervous system; CVA = cardiovascular accident.
Figure. Control of Status Epilepticus by Type of Status
mately 80 mg/L across all groups. Control was 100% in patients with SPSE. In the other groups, approximately 40% of patients were controlled (Figure). Time to control varied significantly across groups (Table 2). The mean time to seizure control in the OCSE group was 0.5 ± 0.3 hours for responders, and greater than or equal to 20 hours in the SCSE group (P = 0.048). Within the OCSE group a striking difference was seen in duration of SE prior to treatment between responders (2.8 ± 2.2 hours) and nonresponders (30.0 ± 34.7 hours; P = 0.02). Thus, patients who responded to IV VPA tended to be treated much earlier in the course of SE. Significant differences were not seen in IV VPA dose received, or level achieved, between responders and nonresponders. Adverse events linked to IV VPA include 1 case of hyperammonemia. No patients showed significant hypotension or cardiac arrhythmia, including several patients with baseline hypotension or cardiac disease. All patients were highly morbid, many with do not resuscitate orders, and some died of causes apparently unrelated to VPA use. Overall, the study suggests that IV VPA is a useful adjunct for SE and that outcomes in OCSE are dependent on rapidity of treatment, as is the case with other anticonvulsive agents.
REFERENCES SE = status epilepticus; OCSE = overt convulsive status epilepticus; SCSE = subtle convulsive status epilepticus; CPSE = complex partial status epilepticus; SPSE = simple partial status epilepticus.
Table 2.Time to Control After VPA
OCSE 0.5 ± 0.3 hr SCSE 20.3 ± 24.6 hr
P = 0.048*
CPSE 6.2 ± 10.2 hr SPSE 0.5 ± 0.3 hr SE = status epilepticus; OCSE = overt convulsive status epilepticus; SCSE = subtle convulsive status epilepticus; CPSE = complex partial status epilepticus; SPSE = simple partial status epilepticus; VPA = valproic acid. *Kruskall-Wallace test
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1. Yamamoto LG, Yim GK. The role of intravenous valproic acid in status epilepticus. Pediatr Emerg Care. 2000; 16(4):296-298. 2. Naritoku DK, Mueed S. Intravenous loading of valproate for epilepsy. Clin Neuropharmacol. 1999;22(2):102-106. 3. Giroud M, Gras D, Esconsse A, et al. Use of injectable valproic acid in status epilepticus-a split study. Drug Invest. 1993;5(3):154-159. 4. Hovinga CA, Chicella MF, Rose DF, et al. Use of intravenous valproate in three pediatric patients with nonconvulsive and convulsive status epilepticus. Ann Pharmacother. 1999;33:579-584. 5. Lowe MR, DeToledo JC, Villavizza N, et al. Efficacy, safety, and tolerability of fast I.V. loading of valproate in patients with seizures and status epilepticus [abstract]. Epilepsia. 1998;39(suppl 6):235.
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