Psychosomatics 49:82-83, January-February 2008
doi: 10.1176/appi.psy.49.1.82
© 2008 Academy of Psychosomatic Medicine
Severe Acute Hyperammonemia After Brief Exposure to Valproate
Aubrey L. Eubanks, M.D.,
Betzabel Aguirre, B.S., and
James A. Bourgeois, O.D., M.D.
Received January 16, 2007; revised February 1, 2007; accepted February 20, 2007. From the Dept. of Psychiatry and Behavioral Sciences, Univ. of California, Davis Medical Center, Sacramento CA. Send correspondence and reprint requests to James A. Bourgeois, O.D., M.D., Dept. of Psychiatry and Behavioral Sciences, Univ. of California, Davis Medical Center, 2230 Stockton Blvd., Sacramento CA 95817. e-mail: james.bourgeois{at}ucdmc.ucdavis.edu
© 2008 The Academy of Psychosomatic Medicine
|
ABSTRACT
|
The authors describe a case of acute hyperammonemia after the addition of valproate to the medication regimen of a patient on multiple psychotropic medications. The patient presented with acute mental-status changes consistent with delirium. With prompt intervention and supportive care, her delirium quickly cleared.
|
INTRODUCTION
|
The patient was a 33-year-old woman with history of bipolar disorder, posttraumatic stress disorder, substance dependence, and borderline personality disorder, who was admitted to a university medical center because of altered mental status. She had been discharged from a psychiatric facility 2 days before her emergency presentation. She was started on divalproex sodium 1,500 mg po qhs the day before her discharge from the psychiatric facility. This was in addition to her regular psychotropic medications of clonazepam 0.5 mg tid, venlafaxine-XR 225 mg qA.M., mirtazapine 15 mg qhs, bupropion-SR 300 mg qA.M., and hydroxyzine 50 mg q 4 h. She had been staying at a residential crisis facility, and attendants had noted her to be lethargic.
Rescue personnel found her to be minimally responsive. In the Emergency Department, her initial ammonia level was 283 mcmol/L (reference range: 2–30), and valproate serum level was 120 mg/L (reference range: 50–100). AST/AST/alkaline phosphatase/bilirubin were all normal. Initial albumin was 2.9 g/dL (reference range: 3.4–4.8). Complete blood count, urinalysis, urine culture, and renal panel were normal. Urine toxicology screen revealed only benzodiazepines. A CT of the head was unremarkable. All psychotropic medications were withheld. She received carnitine 3 g IV and then was started on carnitine 990 mg tid and lactulose 30 cc q6h. Within several hours of emergency treatment and after a decrease in her ammonia level, her mental status improved. She was seen by the psychosomatic medicine team several hours later. At that time, she had full level of consciousness. Speech was spontaneous and fluent. Her mood was described as "tired," and affect was restricted and dysphoric. Thought process was organized and linear. Thought content revealed no current suicidal/homicidal ideation or psychosis. Her Mini-Mental State Exam score was 25.
She remained in stable condition. Her ammonia level was monitored closely and, 6 hours after admission, had decreased to 41, then rose to 66 on the next day (Hospital Day 2), at which time the lactulose dose was increased to 45 cc q 6h. Her ammonia level fell to 30 on Hospital Day 3, and to 25 on Hospital Day 4, the day of her discharge. Her valproate level fell to <10 by her day of discharge. Lactulose was decreased back to 30 cc q 6h on the day of discharge. Both carnitine and lactulose were continued for 3 additional days after her discharge.
|
Discussion
|
Although usually well tolerated, valproate is known to be associated with a number of side effects, including hepatotoxicity, tremor, thrombocytopenia, polycystic ovarian disease, pancreatitis, and teratogenicity. A more unusual but dangerous side effect of valproate is acute hyperammonemia. The mechanism by which this occurs is thought to involve valproate (VPA)-induced carnitine deficiency and inhibition of carbamyl-phosphate-synthetase, thus impairing the conversion of ammonia to urea. It has also been reported that valproate can increase the transport of glutamine across the mitochondrial membrane in the kidney, thus increasing the production of ammonia.1
Clinical signs include mental-status changes and delirium. Acute hyperammonemia is an emergency for which immediate steps must be taken to minimize permanent brain damage.2 When mental-status changes are observed in patients receiving valproate, liver-associated enzymes and ammonia levels should be assessed. LoVecchio et al.3 describe how L-carnitine administration given to patients with VPA overdoses yielded a positive response. Vossler et al.4 described seven patients with VPA-induced encephalopathy, five of whom had elevated ammonia levels. Cerebrospinal fluid glutamine levels were also monitored and observed to be elevated in 80% of the patients, providing evidence of a proposed mechanism of VPA-induced hyperammonemia. Similarly, Latour et al.5 described a case series of six patients with severe epilepsy who were co-prescribed VPA and topiramate, with an exacerbation of hyperammonemia noted. The association of VPA and encephalopathy is also seen in a case series in which Gerstner et al.6 reported 19 new cases in Germany.
Psychiatrists and other physicians are reminded of the risk for hyperammonemia with valproate and of the need for proper laboratory monitoring of these patients. Such monitoring must include not only liver-associated enzymes and monitoring of valproate levels, but also ammonia-level determination. With prompt intervention and supportive care, including carnitine rescue therapy, mental-status changes and risk of permanent brain damage can be minimized.
|
REFERENCES
|
- Lokrantz C-M, Erikson B, Rosen I, et al: Hyperammonemic encephalopathy induced by a combination of valproate and pivmecillinam. Acta Neurol Scand 2004; 109:297–301[CrossRef][Medline]
- Verrotti A, Trotta D, Morgese G, et al: Valproate-induced hyperammonemic encephalopathy. Metab Brain Dis 2002; 17:367–373[CrossRef][Medline]
- LoVecchio F, Shriki J, Samaddar R: L-carnitine was safely administered in the setting of valproate toxicity. Am J Emerg Med 2005; 23:321–322[CrossRef][Medline]
- Vossler DG, Wilensky AJ, Cawthon DF, et al: Serum and CSF glutamine levels in valproate-related hyperammonemic encephalopathy. Epilepsia 2002; 43:154–159[CrossRef][Medline]
- Latour P, Arnaud B, Polard E, et al: Drug-induced encephalopathy in six epileptic patients: topiramate? valproate? or both? Hum Psychopharmacol Clin Exp 2004; 19:193–203[CrossRef]
- Gerstener T, Buesing D, Longin E, et al: Valproic acid-induced encephalopathy: 19 new cases in Germany from 1994 to 2003: a side effect associated with VPA therapy not only in young children. J Seizure 2006; 15:443–448[CrossRef]
Get information about faster international access.
Privacy Policy
Copyright © 2008
Academy of Psychosomatic Medicine.
All rights reserved.
Home
| Search
| Current Issue
| Past Issues
| Subscribe
| All APPI Journals
| Help
| Contact Us
|
TOP
ABSTRACT
INTRODUCTION
