Valproic acid
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Hyperammonaemic encephalopathy: 3 case reports Three patients developed hyperammonaemic encephalopathy while receiving seizure prophylaxis with valproic acid during inpatient treatment for drug dependence; all patients received valproic acid 250mg in the morning, and 500mg in the evening. A 51-year-old woman, who was hospitalised for benzodiazepine and diamorphine [heroin] abuse and dependence, started receiving tapering doses of lorazepam and buprenorphine/naloxone, as well as valproic acid. On hospital day (HD) 3, she reported visual hallucinations of 2 days duration; haloperidol was added to her treatment regimen. She reported dizziness, and auditory and visual hallucinations on HD 4. Lorazepam was withdrawn, chlordiazepoxide was started, and haloperidol was increased. Her ammonia level was found to be 65; valproic acid was subsequently stopped, and she commenced lactulose. The following day, her hallucinations were resolving, and her ammonia level had decreased. No further hallucinations were reported from HD 6, and she was discharged on oxcarbazepine. A 49-year-old woman with a history of anxiety and panic disorder started receiving lorazepam and valproic acid for treatment of benzodiazepine and alcohol dependence. She developed agitation, confusion, and an unsteady gait on HD 2, and reported visual and auditory hallucinations. She became completely delusional and disorientated on HD 3, and her ammonia level was 50. Valproic acid was withdrawn, and she commenced treatment with lactulose. Her ammonia level subsequently normalised, and she had completely recovered by HD 9. She was discharged after finishing her lorazepam taper, but intended to resume use after discharge. A 47-year-old man with a long history of polysubstance abuse started receiving buprenorphine/naloxone and lorazepam for benzodiazepine and opiate dependence, with the addition of valproic acid on HD 2. He developed sudden-onset guaiac positive emesis, epigastric distress, abdominal distention, and decrease in his oxygen saturation on HD 3. Telemetry was performed, and he refused further use of valproic acid. Confusion, dysarthria and agitation developed on HD 4, and his ammonia level was 41. His mental status had resolved by HD 5, and he proceeded with detoxification. Author comment: "This case series illustrates the risk of hyperammoneic encephalopathy associated with the use of valproic acid during inpatient acute detoxification from benzodiazepine withdrawal." Starer J, et al. Hyperammoneic encephalopathy, valproic acid, and benzodiazepine withdrawal: A case series. American Journal of Drug and Alcohol Abuse 36: 98-101, No. 2, Mar 2010. Available from: URL: http:// 803017967 dx.doi.org/10.3109/00952991003674804 - USA
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Reactions 29 May 2010 No. 1303
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