Valproate-Induced Coma: Case Report and Literature Review

Duarte, Jacinto; Macías, S.; Coria, F; Fernández, Enrique J.; Clavería, Luis Erick

doi:10.1177/106002809302700510

Cited by 70 publications

(69 citation statements)

References 23 publications

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“…VHE sometimes occurs with normal liver enzyme serum levels and hepatic function (2,3). It can occur immediately after large loading doses of VPA or more insidiously over time, often in a level-or dose-related fashion (2,4).…”

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confidence: 99%

Serum and CSF Glutamine Levels in Valproate‐related Hyperammonemic Encephalopathy

et al. 2002

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Summary:Purpose: To investigate ammonia and glutamine levels in valproate (VPA)-related hyperammonemic encephalopathy (VHE).Methods: We reviewed the medical records and EEG recordings of seven adults diagnosed with VHE.Results: Venous ammonia levels were elevated in five (71%) of the seven patients. Elevated serum or cerebrospinal fluid (CSF) glutamine levels were found in four (80%) of five cases tested, including two who had normal ammonia levels. Initial behavioral signs included violent outbursts in three patients, paranoid ideation severe enough to require restraint in two cases, and milder abnormalities in two instances. The severity of encephalopathy was not related to any particular serum VPA level. In four patients serum VPA levels did not exceed 100 g/ml, and in one case, VHE developed after taking only one 250-mg dose. Symptoms eventually cleared after reducing the dose of, or discontinuing, VPA. Liver-function tests were normal. Each of six patients tested had EEG findings that supported the diagnosis of VHE and excluded nonconvulsive status epilepticus. The rate of normalization of one patient's serum glutamine level and the EEGs of two cases correlated better with the timing of their delayed clinical recovery than did the more rapid rate of decline of the serum ammonia levels. Conclusions: Serum or CSF glutamine levels are initially elevated in a majority of patients with suspected VHE, sometimes in the absence of hyperammonemia. Glutamine levels may be useful adjunctive laboratory tests for the diagnosis of VHE.

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confidence: 99%

Serum and CSF Glutamine Levels in Valproate‐related Hyperammonemic Encephalopathy

et al. 2002

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“…Aunque controvertido, el rango terapéutico se encuentra comprendido entre 50 y 100 µg/ml 66 . El 90% está unido a proteínas plasmáticas, aunque esta relación es dependiente de la concentración sérica, siendo del 81,5% para niveles de 130 mg/ml y de tan solo el 35% cuando se superan los 300 µg/ml 67 .…”

Section: Farmacocinética Y Farmacodinamiaunclassified

Intoxicaciones medicamentosas (II): Analgésicos y anticonvulsivantes

Munné

Banuelos

Izura

et al. 2003

Anales Sis San Navarra

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RESUMENEn este segundo capítulo sobre Intoxicaciones Medicamentosas Agudas abordamos dos grupos de sustancias de enorme trascendencia desde el punto de vista de su uso y morbimortalidad. Dentro del grupo de los anagésicos-antiinflamatorios desarrollamos el paracetamol y los salicilatos, de enorme disponibilidad para la población. En cuanto a los anticonvulsivantes, aunque están poco implicados en el conjunto de las intoxicaciones medicamentosas agudas, sus efectos pueden ser graves. Nos ceñimos a cuatro fármacos: ácido valproico, fenobarbital, carbamacepina, y fenitoína. Finalmente dedicamos un apartado a la isoniacida, fármaco que, con el rebrote de la tuberculosis, presenta interés toxicológico.Palabras clave. Intoxicación aguda. Paracetamol. Anticonvulsivantes. Fenitoína. Isoniacida. ABSTRACTIn this second chapter on Acute Drugs Poisoning we deal with two groups of substances of great transcendence from the point of view of their use and morbidity/mortality. Within the group of analgesic-antiinflammatory drugs we consider paracetamol and the salicylates, which are easily available to the population. With respect to the anticonvulsants, although they are barely involved in the ensemble of acute drug poisonings, their effects can be serious. We concentrate on four drugs: valproic acid, phenobarbitol, carbamacepine, and phenytoin. Finally, a section is dedicated to isoniazid, a drug that, with the renewed incidence of tuberculosis, is of toxicological interest.

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“…Although the incidence of hyperammonemia associated with hepatic encephalopathy is over 90% in the United States, elevated serum ammonia can be seen in patients therapeutically taking VPA or after a VPA overdose without any evidence of hepatic injury or failure [30,42,64,65]. Duarte et al reported a case of a 46-year-old woman who developed isolated hyperammonemia without any evidence of hepatic failure after being started on the drug [33]. VPA can cause elevation of serum ammonia by various, distinct pathways.…”

Section: What Occurs With Valproic Acid Toxicity?mentioning

confidence: 99%

“…In rat models, the metabolite 4-en-VPA causes microvesicular steatosis in the liver [62]. The concomitant use of phenobarbital therapy with VPA has been shown to induce the cytosolic -oxidation pathway and further increase the risk of hepatoxicity [33,63].…”

Section: What Occurs With Valproic Acid Toxicity?mentioning

confidence: 99%

“…Although these latter metabolites have a minor role, they can be highly toxic in patients on chronic therapeutic dosing or after an acute overdose. 4-en-VPA has been incriminated in the development of cerebral edema, hepatotoxicty, and hyperammonemia [8,19,29,[31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48].…”

Section: How Is Valproic Acid Metabolized?mentioning

confidence: 99%

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Case files of the Children’s Hospital of Michigan Regional Poison Control Center: The use of carnitine for the management of acute valproic acid toxicity

Katiyar

Aaron

2007

J. Med. Toxicol.

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A 28-year-old African-American male was found unresponsive outside of his girlfriend's house around 7 o'clock in the morning. He spent the night at the girlfriend's house and was last witnessed to be awake about 12 hours earlier. The girlfriend and her family were unable to awaken the patient and called emergency medical services (EMS). There was no history of headache, dizziness, fever, chills, nausea, vomiting, seizures, trauma, depressive thoughts, or suicidal ideation. When EMS arrived, they administered 6 mg of naloxone intramuscularly without effect, and the patient was transported to the emergency department (ED).After arriving in the ED, the cardiac monitor displayed a narrow-complex rhythm with a rate of 85-90 per minute. His initial vital signs were: heart rate 91/min; blood pressure 148/80 mmHg; respiratory rate 24/min; temperature 35.1°C (95.1°F) rectally; and pulse oximetry 100% on non-rebreather face mask oxygen. A fingerstick glucose determination was 106 mg/dL.Physical examination revealed a well developed, well nourished individual who was obtunded and unresponsive. His pupils were 2 mm, unreactive to light, and without nystagmus. He had diffuse bilateral wheezing, regular heart rate without any murmurs, and decreased bowel sounds. The patient had warm skin with good distal pulses in all extremities and no cyanosis, erythema, or edema. There was no clonus or hyperreflexia, and the gag reflex was intact.His past medical history was only pertinent for an old gunshot wound to the head. He developed a seizure disorder and was taking divalproex, 500 mg BID. Reportedly, he was allergic to carbamazepine and phenytoin. The patient smoked cigarettes, but the family stated that he had no history of alcohol or illicit drug use.A 12-lead electrocardiogram showed a sinus rhythm with a rate of 92 bpm, a PR interval of 134 msec, a QRS duration of 90 msec, and a QTc of 601 msec. A head CT and chest radiograph were unremarkable. Laboratory tests were obtained.

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Valproate-Induced Coma: Case Report and Literature Review

Cited by 70 publications

References 23 publications

Serum and CSF Glutamine Levels in Valproate‐related Hyperammonemic Encephalopathy

Serum and CSF Glutamine Levels in Valproate‐related Hyperammonemic Encephalopathy

Intoxicaciones medicamentosas (II): Analgésicos y anticonvulsivantes

Case files of the Children’s Hospital of Michigan Regional Poison Control Center: The use of carnitine for the management of acute valproic acid toxicity

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