Status epilepticus valproate

Misra UK, Kalita J, Patel R. Sodium valproate vs phenytoin in status epilepticus A pilot study. Neurology 2006 67 340-342. 

Phenobarbital is still used for the management of partial seizures, generalized tonic-clonic seizures and for the control of status epilepticus. However because of its low therapeutic index and the possibility of dependence, phenobarbital has largely been displaced by other anticonvulsants. For newborns phenobarbital is often the drug of first choice. If given together with sodium valproate the metabolism of phenobarbital may be inhibited while in combination with carbamazepine the serum concentrations of carbamazepine will be reduced due to enzyme induction by phenobarbital. 

Yu KT, Mills S, Thompson N, Cunanan C. Safety and efficacy of intravenous valproate in pediatric status epilepticus and acute repetitive seizures. Epilepsia 2003 44(5) 724-6. 

Phenobarbital Enhances phasic GABAa receptor responses reduces excitatory synaptic responses Nearly complete absorption not significantly bound to plasma proteins peak concentrations in Vi to 4 h no active metabolites tjy2 varies from 75 to 125 h Generalized tonic-clonic seizures, partial seizures, myoclonic seizures, generalized seizures, neonatal seizures, status epilepticus Toxicity Sedation, cognitive issues, ataxia, hyperactivity Interactions Valproate, carbamazepine, felbamate, phenytoin, cyclosporine, felodipine, lamotrigine, nifedipine, nimodipine, steroids, theophylline, verapamil, others... 

A 10-year-old child had status epilepticus controlled with a combination of valproate, oxcarbazepine, and 48 hours of propofol infusion in a dose of 5.5 mg/kg/ hour. After weaning from propofol, a classic ketogenic diet was instituted in an attempt to provide long-term control of the seizures. A day later status epilepticus recurred and propofol was restarted at a rate of 6-9 mg/ kg/hour to suppress seizure activity (the diet, valproate, and oxcarbazepine were also continued). Shortly thereafter, he developed the classical constellation of malignant ventricular arrhythmias, hyperlipidemia, rhabdomyolysis, lactic acidosis, and biventricular cardiac failure. He did not survive. 

Convulsions. Sodium valproate orally is preferred as it is effective for a wide range of seizure disorders (for status epilepticus see p. 417). 

Antiepilepsy drugs continued medication is essential to avoid status epilepticus. Drugs must be given parenterally (e.g. phenytoin, sodium valproate) or by rectum (e.g. carbamazepine) until the patient can absorb enterally. 

In an 11-year-old girl who was treated with intravenous valproate (30 mg/kg over 1 hour) for status epilepticus, the blood pressure fell from 130/80 mmHg to 70/ 55 mmHg after about 40 minutes of infusion. Her seizures stopped, but her blood pressure fluctuated for several hours between 90/60 mmHg and 60/30 mmHg, requiring intravenous fluids and pressor therapy. Endotracheal intubation was also performed and she eventually recovered. 

In a study of intravenous valproate in status epilepticus, three of 19 patients (ages and dosages not specified) developed a rise in serum lipase activity above 4000 lU/ ml within 1-3 weeks (86) one of these developed overt exudative pancreatitis. Based on these data, it may be prudent to monitor serum lipase when using intravenous valproate. 

Hovinga CA, Chicella MF, Rose DF, et al. Use of intravenous valproate in three pediatric patients with nonconvulsive or convulsive status epilepticus. Ann Pharmacother 1999 33 579-584. 

The concurrent administration of valproate and clonazepam rarely has been associated with the development of absence status epilepticus. 

Amitriptyline and nortriptyline plasma levels can be increased by sodium valproate and valpromide, but in contrast, an isolated report attributes a paradoxical rise in serum desipramine levels to the withdrawal of valproic acid. Valproate pharmacokinetics may be moderately affected by amitriptyline. Status epilepticus has been attributed to elevated clomipramine levels in a patient taking valproic acid. 

Brandt, C, Gastens, AM, Sun, M, Hausknecht, M, Loscher, W (2006) Treatment with valproate after status epilepticus effect on neuronal damage, epileptogenesis, and behavioral alterations in rats. Neuropharmacology, 51 789-804. 

Valproate toxicity after intravenous administration and recommendations for its use in status epilepticus have been reviewed [303 ]. 

In a retrospective chart review in 137 children, mean age 8 years who had received an infusion of valproate, average dose 31 mg/kg/day for a mean duration of 7.8 days, for status epilepticus or repetitive seizures, in prophylactic use for brain operations, or in when oral administration was not feasible, there was an allergic reaction (rash) in 1 patient [308 ]. The common adverse reactions to valproate (nausea, stomach irritation, increased appetite, and dizziness) were seen in 30 patients, but they... 

Ertapenem In two cases there was marked induction of valproate metabolism by ertapenem [349 ]. The first was a 47-year-old woman whose valproate concentrations rose after ertapenem withdrawal from <1 to 34 mg/1. The second was a 72-year-old woman with status epilepticus whose valproate concentrations continued to increase for several days after ertapenem withdrawal. 

Kwan SY. The role of intravenous valproate in convulsive status epilepticus in the future. Acta Neurol Taiwan 2010 19(2) 78-81. 

A 4-year-old previously healthy girl presented with new-onset seizures associated with fevers, headache, and malaise. She developed status epilepticus resistant to intravenous tenzodiaz-epines, fosphenytoin, levetiracetam, valproate, pentobarbital, and ketamine. An initial MRI brain scan was unremarkable. Isoflurane was begun, and an MRI scan 14 days later showed hyperintense T2 signals in the cerebellar vermis and cerebellar hemispheres. The isoflurane concentration was reduced to 0.5% and a further scan after 31 days of isoflurane therapy showed improvement in the signal abnormalities. Her isoflurane exposure was 1382% concentration-hours/1257 MAC-hours. She remained minimally conscious. 

Phenytoin and valproate Phenytoin ( = 25) by infusion and intravenous valproate ( = 49) have been compared in status epilepticus or acute repetitive seizures in 74 patients [241 ]. There were no adverse effects with valproate but three patients who received phenytoin had adverse effects cardiac dysrhythmias, vertigo, and hyponatremia). 

The effect of intravenous valproate when given for the treatment of status epilepticus has been studied in small retrospective case series. 

In 32 patients who received intravenous valproate for status epilepticus as first or second line therapy there were no serious cardiovascular complications the only adverse events reported were initial leukocytosis and hypotension [401 ]. 

In a prospective study of 48 patients with status epilepticus refractory to benzodiazepines, intravenous valproate (30 mg/ kg, 6 mg/kg per hour was not associated with systemic or local adverse effects [402 ]. 

In a comparison of intravenous valproate n = 49) and phenytoin infusion n = 25) in 74 patients with status epilepticus or acute repetitive seizures, the two drugs were equally effective but there were adverse effects in none of those given valproate and in three of those who were given phenytoin (cardiac dysrhythmia, vertigo, and hyponatremia) [241 ]. 

Tiamkao S, Sawanyawisuth K. Predictors and prognosis of status epilepticus treated with intravenous sodium valproate. Epileptic Disord 2009 11(3) 228-31. 

Chen L, Feng P, Wang J, Liu L, Zhou D. Intravenous sodium valproate in mainland China for the treatment of diazepam refractory convulsive status epilepticus. J Clin Neurosci 2009 16(4) 524-6. 

Brigo F, Storti M, Del Felice A, Fiaschi A, Bongiovanni LG. IV Valproate in generalized convulsive status epilepticus a systematic review. Eur J Neurol September 2012 19(9) 1180-91. 

Malamiri RA, Ghaempanah M, Khosroshahi N, Nikkhah A, Bavarian B, Ashrafi MR. Efficacy and safety of intravenous sodium valproate versus phenobarbital in controlling convulsive status epilepticus and acute prolonged convulsive seizures in children a randomised trial. Eur J Paediatr Neurol September 2012 16(5) 536-41. 

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