CARBAMAZEPINE-ASSOCIATED HYPERAMMONEMIC ENCEPHALOPATHY (HE)

Abstract

SESSION TITLE: Drug-Induced Lung Injury and DiseaseSESSION TYPE: Rapid Fire Case ReportsPRESENTED ON: 10/18/2022 01:35 pm - 02:35 pmINTRODUCTION: Hyperammonemia is a metabolic condition associated with elevated ammonia, a potent neurotoxin. Drug-induced hyperammonemia typically results from interference with the urea cycle or enhancement of renal release of ammonia into the systemic circulation [1].CASE PRESENTATION: A 61-year-old female with a past medical history of bipolar disorder and schizophrenia was brought to our hospital due to altered mentation. Her home medications included carbamazepine, risperidone and trazodone. Glascow coma score was 3. She was intubated to secure the airway. Computed tomography of the head was negative for any acute abnormality. Labs were significant for leukocytosis and Ammonia of 301 mcmol/L (reference [REF] 11-35). Carbamazepine level was 4.7 mcg/ml (REF 4-10). Urine drug screen was negative. Urine culture was positive for >100,000 cfu/ml of E. Coli. Chronic hepatitis panel was negative. Ultrasound of the abdomen showed normal contour of the liver. Transthoracic echo was normal. The patient was admitted to the intensive care unit with diagnoses of HE, acute respiratory failure and urinary tract infection. She was sedated with dexmedetomidine and started on Piperacillin/Tazobactam and lactulose 20g. Rifaxamin was later added. Her home medications were held. A 1 hour followed by a 24-hour electroencephalogram showed no evidence of seizure activity but findings of severe diffuse encephalopathy. Brain magnetic resonance imaging (MRI) findings were consistent with acute HE. Ammonia level normalized after 5 days of treatment after which sedation was discontinued and the patient was extubated with return to baseline mentation and neurologic function. Carbamazepine was concluded to be the likely cause for her hyperammonemia.DISCUSSION: Medications associated with hyperammonemia include valproic acid (VA), fluorouracil, salicylates and rarely carbamazepine. Carbamazepine is an anticonvulsant with antineuralgic and antidepressive properties. There are a few case reports that associate carbamazepine with hyperammonemia, the mechanism of of which is unknown, although postulated to be similar to that of VA; through inhibition of glutamate uptake by astrocytes [2]. Hyperammonemia mainly presents with neurologic signs and symptoms. Clinical signs usually occur at concentrations >60 µmol/L. Diagnosis involves measurement of serum ammonia levels and clinical assessment of cognitive status. MRI findings characteristic of HE include symmetrical signal abnormalities in insular and cingulate cortices [3]. No EEG findings are specific to HE but the presence of triphasic waves is suggestive.CONCLUSIONS: Carbamazepine is associated with hyperammonemia even in patients with therapeutic levels. Management involves prompt diagnosis of hyperammonemia, exclusion of other causes, lowering ammonia and discontinuation of the offending agent. Further studies are needed to better assess the association of carbamazepine with HE.Reference #1: Upadhyay R, Bleck TP, Busl KM. Hyperammonemia: What Urea-lly Need to Know: Case Report of Severe Noncirrhotic Hyperammonemic Encephalopathy and Review of the Literature. Case Rep Med. 2016;2016:8512721. doi: 10.1155/2016/8512721. Epub 2016 Sep 21. PMID: 27738433; PMCID: PMC5050374.Reference #2: Verrotti A, Trotta D, Morgese G, Chiarelli F. Valproate-induced hyperammonemic encephalopathy. Metab Brain Dis. 2002 Dec;17(4):367-73. doi: 10.1023/a:1021918104127. PMID: 12602513.Reference #3: Reis E, Coolen T, Lolli V. MRI Findings in Acute Hyperammonemic Encephalopathy: Three Cases of Different Etiologies: Teaching Point: To recognize MRI findings in acute hyperammonemic encephalopathy. J Belg Soc Radiol. 2020 Jan 30;104(1):9. doi: 10.5334/jbsr.2017. PMID: 32025625; PMCID: PMC6993592.DISCLOSURES: No relevant relationships by Rami Al-AyyubiNo relevant relationships by ahmad hamdan SESSION TITLE: Drug-Induced Lung Injury and Disease SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 01:35 pm - 02:35 pm INTRODUCTION: Hyperammonemia is a metabolic condition associated with elevated ammonia, a potent neurotoxin. Drug-induced hyperammonemia typically results from interference with the urea cycle or enhancement of renal release of ammonia into the systemic circulation [1]. CASE PRESENTATION: A 61-year-old female with a past medical history of bipolar disorder and schizophrenia was brought to our hospital due to altered mentation. Her home medications included carbamazepine, risperidone and trazodone. Glascow coma score was 3. She was intubated to secure the airway. Computed tomography of the head was negative for any acute abnormality. Labs were significant for leukocytosis and Ammonia of 301 mcmol/L (reference [REF] 11-35). Carbamazepine level was 4.7 mcg/ml (REF 4-10). Urine drug screen was negative. Urine culture was positive for >100,000 cfu/ml of E. Coli. Chronic hepatitis panel was negative. Ultrasound of the abdomen showed normal contour of the liver. Transthoracic echo was normal. The patient was admitted to the intensive care unit with diagnoses of HE, acute respiratory failure and urinary tract infection. She was sedated with dexmedetomidine and started on Piperacillin/Tazobactam and lactulose 20g. Rifaxamin was later added. Her home medications were held. A 1 hour followed by a 24-hour electroencephalogram showed no evidence of seizure activity but findings of severe diffuse encephalopathy. Brain magnetic resonance imaging (MRI) findings were consistent with acute HE. Ammonia level normalized after 5 days of treatment after which sedation was discontinued and the patient was extubated with return to baseline mentation and neurologic function. Carbamazepine was concluded to be the likely cause for her hyperammonemia. DISCUSSION: Medications associated with hyperammonemia include valproic acid (VA), fluorouracil, salicylates and rarely carbamazepine. Carbamazepine is an anticonvulsant with antineuralgic and antidepressive properties. There are a few case reports that associate carbamazepine with hyperammonemia, the mechanism of of which is unknown, although postulated to be similar to that of VA; through inhibition of glutamate uptake by astrocytes [2]. Hyperammonemia mainly presents with neurologic signs and symptoms. Clinical signs usually occur at concentrations >60 µmol/L. Diagnosis involves measurement of serum ammonia levels and clinical assessment of cognitive status. MRI findings characteristic of HE include symmetrical signal abnormalities in insular and cingulate cortices [3]. No EEG findings are specific to HE but the presence of triphasic waves is suggestive. CONCLUSIONS: Carbamazepine is associated with hyperammonemia even in patients with therapeutic levels. Management involves prompt diagnosis of hyperammonemia, exclusion of other causes, lowering ammonia and discontinuation of the offending agent. Further studies are needed to better assess the association of carbamazepine with HE. Reference #1: Upadhyay R, Bleck TP, Busl KM. Hyperammonemia: What Urea-lly Need to Know: Case Report of Severe Noncirrhotic Hyperammonemic Encephalopathy and Review of the Literature. Case Rep Med. 2016;2016:8512721. doi: 10.1155/2016/8512721. Epub 2016 Sep 21. PMID: 27738433; PMCID: PMC5050374. Reference #2: Verrotti A, Trotta D, Morgese G, Chiarelli F. Valproate-induced hyperammonemic encephalopathy. Metab Brain Dis. 2002 Dec;17(4):367-73. doi: 10.1023/a:1021918104127. PMID: 12602513. Reference #3: Reis E, Coolen T, Lolli V. MRI Findings in Acute Hyperammonemic Encephalopathy: Three Cases of Different Etiologies: Teaching Point: To recognize MRI findings in acute hyperammonemic encephalopathy. J Belg Soc Radiol. 2020 Jan 30;104(1):9. doi: 10.5334/jbsr.2017. PMID: 32025625; PMCID: PMC6993592. DISCLOSURES: No relevant relationships by Rami Al-Ayyubi No relevant relationships by ahmad hamdan