Valproate, overdose

Valproate overdose results in increasing sedation, confusion, and ultimately, coma. The patient may also manifest hyperreflexia or hyporeflexia, seizures, respiratory suppression, and supraventricular tachycardia. Treatment should include gastric lavage, electrocardiographic monitoring, treatment of emergent seizures, and respiratory support. 

Stelman GS, Woerpel RW, Sherard ES. Treatment of accidental sodium valproate overdose with an opiate antagonist [Letter]. Ann Neurol 1979 6 274. 

A beneficial effect of high-flux hemodialysis without hemo-perfusion has been described in valproate overdose (126). 

After a valproate overdose a 27-year-old man developed seizures, hypernatremia, respiratory failure, metabolic acidosis, liver failure, and bone marrow depression (125). His plasma valproic acid concentration was 1414 pg/ml. Treatment with hemodialysis was effective in enhancing valproic acid clearance, while hemoperfu-sion was relatively less effective, because of saturation of the column. Overall, the half-Ufe of the drug was reduced from over 20 hours before treatment to less than 3 hours during hemodialysis/hemoperfusion drug removal was probably favored by saturation of drug binding to plasma proteins, which resulted in a low unbound fraction (32% at the start of treatment). He was comatose for 5 days but recovered fully thereafter. 

Continuous venovenous hemodiafiltra-tion has been proposed for treating valproate overdose [356" ]. 

Drug overdose Valproate overdose can mimic brain death [403 ]. 

Two identical cases of life-threatening valproate overdose which were treated with two different approaches have been described [412 ]. One patient was treated with supportive therapy alone until cerebral edema and seizures developed the other was treated with immediate extended hemodialysis followed by high-volume hemodiaffltration. The first patient remained critically ill with high valproate and ammonia concentrations, seizures, and life-threatening cerebral edema. The second patient s valproate and ammonia concentrations rapidly fell with hemodialysis and hemodiafiltration and he improved rapidly. 

In another patient severe valproate overdose associated with a serum valproate concentration of 1320 mg/1 resulted in coma... 

The advantages of using carnitine in patients with valproate overdose or valproate-induced hepatotoxicity and hyper-ammonemic encephalopathy have been discussed [414 ]. Carnitine supplementation may increase the beta-oxidation of valproate, thereby limiting cytosolic omega-oxidation and the production of toxic metabolites that are involved in liver toxicity and ammonia accumulation. 

Licari E, Calzavacca P, Warrillow SJ, Bellomo R. life-threatening sodium valproate overdose a comparison of two approaches to treatment. Crit Care Med 2009 37(12) 3161. ... 

Mestrovic J, Filipovic T, Polic B, Stricevic L, Omazic A, Kuzmanic-Samija R, Markic J. Life-threatening valproate overdose successfully treated with haemodialysis. Arh Hig Rada Toksi-kol 2008 59(4) 295-8. 

Adverse effects are most commonly manifest as acute pancreatitis. The strongest association is with alcohol abuse. High plasma calcium, including that caused by hypervitaminosis D, and parenteral nutrition also increase the risk. Corticosteroids, didanosine, azathoipurine, diuretics (including thiazides and frusemide), sodium valproate, mesalazine and paracetamol (in overdose) have also been causally related. 

Activated charcoal Carbamazepine Lamotrigine Phenobarbital Phenytoin Valproate With some drugs can be exploited to reduce drug concentrations in overdose Sequestration in the gastrointestinal tract... 

A 55-year-old woman taking lamotrigine and valproate for partial epilepsy took an overdose of lamotrigine and... 

Three patients who took overdoses of valpromide presented with no sjmptoms or only moderate ones and serum valproate concentrations below or within the usual target range in two cases more than 3 hours after ingestion (127). However, there was marked deterioration more than 10 hours after ingestion, when serum valproate concentrations were in the toxic range. 

Valproate has a wide therapeutic rauge, so toxicity from overdoses is uucorumou. Sigus of overdose iuclude coma, visual hallucinations, deep sleep, and heart block. Hemodialysis can be used to remove unbound valproic acid in overdose situations. ... 

A. Severe valproate-induced hepatotoxicity, hyperammonemia, coma, or acute valproic acid overdose. Early intervention with iV (rather than orai)... 

Drug overdose In a study of 9809 consecutive adults and adolescents with self-poisoning during a 6-month period, there were 474 with non-benzodiazepine antiepileptic drug intoxication [103. The most frequent motivation was intentional intoxication (95.3%). There was no association between antiepileptic drug intoxication and a history of parasuidde, sex, age, or occupation. The most frequent drug involved was carbamazepine ( = 117), followed by phenobarbital ( =77) and sodium valproate ( = 51). 

Drug overdose A 38-year-old man with alcoholism and a history of drug abuse attempted suicide with valproate and developed a... 

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