Hyperammonemia In Patients Research Articles

Postoperative hyperammonemic encephalopathy due to unexpected constipation in a patient with hyperornithinemia-hyperammonemia-homocitrullinuria syndrome: a case report

BackgroundHyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is a rare autosomal recessive urea cycle disorder associated with a high risk of exacerbation of hyperammonemia during the perioperative period. Here, we describe an adult patient with HHH syndrome who developed hyperammonemic encephalopathy secondary to postoperative constipation.Case presentationA 52-year-old patient with HHH syndrome underwent intrathecal baclofen pump insertion for lower limb spasticity under general anesthesia. The surgery was uneventful, without any increase in serum ammonia levels. However, after surgery, he was constipated, and on postoperative day (POD) 3, he fell into a coma with an exacerbation of hyperammonemia (894 µg/dL). After administering a glycerin enema, he defecated, leading to a rapid decrease in serum ammonia levels to 165 µg/dL. He regained consciousness, and serum ammonia levels remained stable as long as he defecated.ConclusionsWe suggest strict management of defecation during the perioperative period to prevent hyperammonemia in patients with HHH syndrome.

Clinical significance and possibilities for correction of hyperammonemia in patients with atrial fibrillation

Clinical significance and possibilities for correction of hyperammonemia in patients with atrial fibrillation

Diagnostic and Prognostic Value of Hyperammonemia in Patients with Liver Cirrhosis, Hepatic Encephalopathy, and Sarcopenia (Experts’ Agreement)

Introduction. In cirrhotic patients, hyperammonemia develops due to impaired ammonia detoxification and portosystemic blood shunting and is most commonly associated with hepatic encephalopathy and sarcopenia. Currently, there are questions regarding the diagnosis of hyperammonemia and the effect of ammonia-lowering therapy on disease outcomes.Materials and methods. The Russian Scientific Liver Society selected a panel of seven experts in liver cirrhosis research and management of patients with this disease to make reasoned statements and recommendations on the issue of diagnostic and prognostic value of hyperammonemia in patients with liver cirrhosis, hepatic encephalopathy and sarcopenia.Results. The Delphi panel identified the most relevant topics, in the form of PICO questions (patient or population, intervention, comparison, outcome). The Delphi panel made six questions relevant to clinical practice and gave reasoned answers, framed as ‘clinical practice recommendations and statements’ with evidence-based comments. The questions and statements were based on the search and critical analysis of medical literature by keywords in Englishand Russian-language databases. The formulated questions could be combined into four categories: hepatic encephalopathy, sarcopenia, hyperammonemia, and ammonia-lowering therapy.Conclusions. The results of the experts' work are directly relevant to the quality management of patients with liver cirrhosis, and their recommendations and statements can be used in clinical practice.

Hyperammonemia in patients with stable angina pectoris and nonalcoholic fatty liver disease at the steatosis stage

The aim. To assess the severity of hyperammoniemia in patients with non-alcoholic fatty liver disease at the steatosis stage in conditions of comorbidity with stable angina. Research materials and methods. During the clinical trial, three groups of patients with stable angina were formed. Group I (n = 43) consisted of patients with NAFLD at the stage of hepatic steatosis in combination with obesity and a stable form of CHD. Group II (n = 41) - patients with NAFLD at the stage of hepatic steatosis against the background of normal body weight and stable CHD. Group III (control) (n = 42) - patients with stable angina without NAFLD, with normal body weight. The results of laboratory examination (clinical and biochemical blood tests, lipidograms, insulin levels (calculated by HOMA-IR), glycosylated hemoglobin (HbAlc)) were evaluated; non-invasive markers for the diagnosis of liver injury. Hyperammonemia was evaluated by quantitative rapid ammonia analysis using a Pocket Chem TM BA PA-4140 analyzer. All patients underwent ultrasound of the liver using Philips Epiq 5 (USA). Results. In all patients with stable angina (group I and II), the diagnosis of non-alcoholic fatty liver disease, steatosis stage, was confirmed. The lipid profile of patients in Groups I and II showed more significant hypertriglyceridemia compared to those in the control group, with no statistical difference in Groups I and II. The mean ammonium level in patients with NAFLD in combination with stable CHD (group I, II) was above the threshold and was 87 (57-127.5) and 79 (57-97) μmol/L, respectively, and did not differ significantly (p > 0.05). In patients of group III (without liver disease), the mean values of ammonia in the blood were in the target range. According to the results of correlation analysis, we established the relationship of ammonium with liver enzymes, calculated steatosis indices and basic metabolic indicators. Conclusion. Patients with non-alcoholic fatty liver disease in the steatosis stage with a combination of stable angina have more severe hyperammonemia compared to patients with stable CHD without concomitant liver injury.

Hyperammonemia in patients on Valproic Acid therapy in a tertiary care hospital of Karachi

Hyperammonemia in patients on Valproic Acid therapy in a tertiary care hospital of Karachi

Results of a multicenter prospective observational study “Clinical significance of hyperammonemia in patients with post-Covid syndrome (LIRA - COVID)”: efficacy of L-ornithine L-aspartate

Epidemiological data suggests that approximately 10-65% of patients with mild to moderate COVID-19 have persistent symptoms already after an acute infection, which may last for six months or more. Previous clinical studies have shown that similar symptoms may also occur in the liver. Russian scientists have studied the phenomenon of hyperammonemia in the acute phase of COVID-19, but the problem of elevated blood ammonia levels in post - COVID syndrome has not been studied before. One possible option for the correction of hyperammonemia is the L-ornithine - L-aspartate (LOLA) preparation. The aim of the study was to investigate the manifestation of hyperammonemia in post - COVID syndrome and the possibility of its correction by using LOLA. Eighty-three patients (mean age 51.71 ± 12.82) with post-COVID syndrome, attention and memory impairment, chronic fatigue, hyperammonemia, 2-fold increase of alanine transaminase (ALT) and aspartate transaminase (AST) levels were included into multicenter, prospective observational study. L-ornithine-L-aspartate (LOLA) was given (3 g 3 times per day orally) for 4 weeks to correct hyperammonemia. Patients were accessed by the number connection test (NCT), fatigue evaluation test, measurement of ammonia and ALT, AST levels at baseline, and after 4 weeks. At week 4 the ammonia level was significantly decreased in 81 patients (97.6%). Time (sec) to complete the NCT was 49,43 ± 15,85 vs 64.67 ± 24.95 at baseline (p<0.001). Before treatment, the majority of patients had stage 1 hepatic encephalopathy (HE) - 50.6% and stage 1-2 (intermediate) HE - 30.1%, stage 2 HE - 10.9%, stage 3 HE - 2.4%. After LOLA treatment, the distribution changed: 41% of patients had no HE, 36.1% had stage 1 of HE, 22.9% had stage 1-2 (intermediate) of HE, and stage 2 and 3 of HE was no longer defined. The mean score in fatigue evaluation test was 46,27 ± 10.0 vs 64,71 ± 19,18 at baseline (p<0.001). ALT and AST levels were 47,83 ± 38,21 units/l vs 95,75 ± 68.99 units/l at baseline and 40,10 ± 35,97 units/l vs 78,51 ± 90,90 units/l at baseline respectively (p<0.001). This study showed that the inclusion of LOLA in a dose of 3 g 3 times a day for 4 weeks was associated with significant improvement in the objective and subjective outcomes in patients with post-COVID syndrome.

The effect of induced hyperammonaemia on sleep and melanopsin-mediated pupillary light response in patients with liver cirrhosis: A single-blinded randomized crossover trial.

Sleep disturbances are related to hepatic encephalopathy and hyperammonaemia in patients with cirrhosis. The circadian rhythm is regulated by light stimulation of the retina via melanopsin-containing ganglion cells. The study aimed to investigate whether induced hyperammonaemia affects the pupillary light response and sleep efficiency in patients with cirrhosis. The study was a single-blinded crossover trial including nine patients with cirrhosis. Sleep was evaluated by Pittsburgh Sleep Quality Index (PSQI) and monitored for twelve nights with wrist accelerometers and sleep diaries. On two experimental days, separated by one week, patients were randomized to ingest either an oral amino acid challenge (AAC) or an isocaloric glucose solution (GS). We measured pupillary light response, capillary ammonia, the Karolinska Sleepiness Scale (KSS), and two neuropsychological tests on both experimental days. The patients had poor self-assessed sleep quality. The amino acid challenge led to a significant increase in capillary ammonia and KSS. The time spent in bed sleeping after AAC was longer and with a reduced movement index compared to baseline but not different from GS. We found no difference in the pupillary light response or neuropsychiatric tests when comparing the effect of AAC with GS. Patients with cirrhosis had impaired sleep quality. Induced hyperammonaemia led to increased sleepiness but had no acute effect on pupillary light response or the neuropsychiatric tests. Registration number: NCT04771104.

Risk factors and outcome of hyperammonaemia in people with epilepsy

BackgroundHyperammonaemia is a recognised complication of antiseizure treatment but risk factors leading to individual patient susceptibility and outcome remain unclear.ObjectiveTo identify risk factors for hyperammonaemia and investigate the impact of its management on clinical outcomes.MethodsWe carried out a retrospective observational study of adults with epilepsy who had ammonia tested over a 3-year period. Hyperammonaemia was defined as ammonia level > 35 μmol/L. Patients were classified into two groups: hyperammonaemic and non-hyperammonaemic. Association analyses and linear regression analysis were used to identify risk factors for hyperammonaemia.ResultsWe reviewed 1002 ammonia requests in total and identified 76 people with epilepsy who had ammonia concentration measured, including 26 with repeated measurements. 59/76 (78%) were found to have hyperammonaemia. There was borderline statistical significance of hyperammonaemia being less common in patients with an established monogenic/metabolic condition than in those with structural or cryptogenic epilepsy (P = 0.05). Drug resistance, exposure to stiripentol and oxcarbazepine were identified as risk factors for hyperammonaemia. We found a dose-dependent association between valproate and hyperammonaemia (P = 0.033). Clinical symptoms were reported in 22/59 (37%) of the hyperammonaemic group. Improved clinical outcomes with concurrent decrease in ammonia concentration were seen in 60% of patients following treatment adjustment.ConclusionsDrug resistance and exposure to stiripentol, oxcarbazepine or high-dose valproate are associated with an increased risk of hyperammonaemia. Clinicians should consider symptoms related to hyperammonaemia in patients on high-dose valproate or multiple antiseizure treatments. Prompt identification of hyperammonaemia and subsequent treatment adjustments can lead to improved clinical outcomes.

Pharmacokinetics/pharmacodynamics of L-ornithine phenylacetate in overt hepatic encephalopathy and the effect of plasma ammonia concentration reduction on clinical outcomes.

Hepatic encephalopathy (HE) is a serious neurocognitive complication of liver dysfunction, often associated with elevated plasma ammonia. Ornithine phenylacetate (OP), a potent ammonia scavenger, is being evaluated for the treatment of acute/overt HE. The pharmacokinetics and pharmacodynamics of OP in patients with HE were characterized in this phase IIb study (NCT01966419). Adult patients hospitalized with an overt HE episode, cirrhosis, and plasma ammonia above the upper limit of normal (ULN) who failed to improve after 48 hours’ standard care were randomly assigned to continuous intravenous OP (10, 15, or 20 g/day, based on Child–Turcotte–Pugh score) or matching placebo for 5 days. Plasma levels of ornithine and phenylacetic acid (PAA) and plasma/urinary levels of phenylacetylglutamine (PAGN) (primary metabolite of PAA) were regularly assessed; plasma ammonia level was the primary pharmacodynamic variable. PAA demonstrated dose‐dependent pharmacokinetics; ornithine and PAGN levels increased with dose. PAGN urinary excretion represented ~50%–60% of administered PAA across all doses. Mean reduction in plasma ammonia with OP at 3 hours postinfusion was significantly greater versus placebo (p = 0.014); and time to achieve plasma ammonia less than or equal to the ULN was significantly reduced (p = 0.028). Achievement of clinical response based on HE stage was associated with a greater reduction in mean plasma ammonia level (p = 0.009). OP effects on plasma ammonia were consistent with its proposed mechanism of action as a primary ammonia scavenger, with a significant association between reduced plasma ammonia and improvement in HE stage. OP should be further evaluated as a promising treatment for hyperammonemia in patients with overt HE.

Long-term effectiveness of carglumic acid in patients with propionic acidemia (PA) and methylmalonic acidemia (MMA): a randomized clinical trial

BackgroundPropionic acidemia (PA) and methylmalonic acidemia (MMA) are rare, autosomal recessive inborn errors of metabolism that require life-long medical treatment. The trial aimed to evaluate the effectiveness of the administration of carglumic acid with the standard treatment compared to the standard treatment alone in the management of these organic acidemias.MethodsThe study was a prospective, multicenter, randomized, parallel-group, open-label, controlled clinical trial. Patients aged ≤ 15 years with confirmed PA and MMA were included in the study. Patients were followed up for two years. The primary outcome was the number of emergency room (ER) admissions because of hyperammonemia. Secondary outcomes included plasma ammonia levels over time, time to the first episode of hyperammonemia, biomarkers, and differences in the duration of hospital stay.ResultsThirty-eight patients were included in the study. On the primary efficacy endpoint, a mean of 6.31 ER admissions was observed for the carglumic acid arm, compared with 12.76 for standard treatment, with a significant difference between the groups (p = 0.0095). Of the secondary outcomes, the only significant differences were in glycine and free carnitine levels.ConclusionUsing carglumic acid in addition to standard treatment over the long term significantly reduces the number of ER admissions because of hyperammonemia in patients with PA and MMA.

The Role of Helicobacter Pylori Eradication on the Pathogenesis of Minimal Hepatic Encephalopathy in Egyptian Patients with Liver Cirrhosis

Abstract Background Hepatic Encephalopathy (HE) is defined as alteration of mental state in the absence of other causes of encephalopathy due to liver failure and/or abnormal shunting of blood from portal to systemic circulation often accompanied by elevated blood ammonia. Objectives The aim of this study was to determine the relation between the Helicobacter pylori infectionand minimal hepatic encephalopathy (MHE) in cirrhotic patients and to assess the outcome after treatment of H. pylori. Patients and Methods This study was can•ied out at Egyptian Railway Medical Centre at the in-patients section at Gastroenterology and Hepatology Medicine Department with chronic liver disease who agreed to participate in the study. After performing the psychometric tests the patients were allocated in one of the two groups according to test results: Group I: consisted of 30 consecutive patients who have chronic liver disease and presented with evidence of Minimal hepatic encephalopathy (MHE), as recognized by positive psychometric tests, Group Il: included 30 consecutive patients who presented with chronic liver disease and did not have Minimal hepatic encephalopathy, as confirmed by negative psychometric test. Results In this study a significant reduction was found in blood ammonia levels in MHE and non- MHE after triple-drug anti-H. pylori treatment (p &amp;lt; 0.001). This reduction was more marked in patients with MHE group compared to non-MHE group with % improvement in ammonia level 26.1 ± 8.36 umol/L and 17.79 ± 7.308 for MHE and non-MHE respectively. This finding indicates that H. pylori may contribute to the development of hyperammonemia in patients with liver disease and MHE. The role of H. pylori in the pathogenesis of hyperammonemia has been shown in previous studies which showed a reduction in blood ammonia levels after eradication of H.pylori infection. Conclusion Helicobacter Pylori infection was more prevalent in patients with MHE than without MHE. Serum arnrnonia levels were significantly higher in MHE patients than without MHE and even higher in H.pylori positive patients than without H.pylori infection. Helicobacter Pylori eradication treatment significantly improves ammonia levels, results of psychometric tests and improves manifestations of MHE.

Hyperammonemia in patients receiving valproic acid in the hospital setting: A retrospective review.

IntroductionValproic acid (VPA) is widely used for the treatment of epilepsy, migraine, and a variety of psychiatric conditions. The reported incidences of hyperammonemia induced by VPA use is variable. The purpose of this study is to evaluate the incidence of VPA-induced hyperammonemia in the general adult inpatient population.MethodsAdult patients who received at least 1 dose of VPA and derivatives between June 1, 2017 to December 31, 2017 were included. Patients were excluded if they did not have VPA administered during their inpatient stay or if they had elevated ammonia levels (>33 μmol/L) prior to initiation of VPA. Patients with a confirmed diagnosis of liver cirrhosis were also excluded. The primary endpoint was the incidence of hyperammonemia. Secondary outcomes included symptoms of hyperammonemia, diagnosis of VPA-induced hyperammonemia, and treatment of VPA-induced hyperammonemia.ResultsA total of 162 patients were included in this study. A total of 33 (20.4%) patients were identified as having the primary outcome of hyperammonemia; 26 (16.0%) patients had symptoms of hyperammonemia, and 13 (8.0%) patients were diagnosed with VPA-induced hyperammonemia. Treatment modalities included administration of lactulose, levocarnitine, discontinuing VPA, or decreasing the VPA dose.DiscussionThe administration of VPA in the general adult inpatient population resulted in a 20.4% incidence of hyperammonemia, with a lower rate of diagnosed VPA-induced hyperammonemia. Clinicians should be encouraged to obtain ammonia levels in patients receiving VPA if symptoms of altered mental status or encephalopathy develop.

Computational extraction and analysis of de-identified medical records to characterize hyperammonemia in patients with fibrolamellar carcinoma (FLC).

e16169 Background: Rare cancers including FLC make up 25% of adult tumors, but are difficult to study due to low incidence and incomplete case identification. FLC occurs in adolescents and young adults without liver dysfunction. Hyperammonemia has been frequently reported in FLC patients, but is poorly understood. Methods: Data from three clinical trials allowed us to establish the incidence of hyperammonemia (serum ammonia value &gt; 75 µmol/L) in FLC. In these studies, FLC patients received everolimus, estrogen deprivation therapy (EDT) with leuprolide + letrozole or everolimus + EDT (Oncologist. 2020 25(11):925-e1603), ENMD-2076 (Oncologist. 2020 25(12):e1837-e1845), or neratinib (J Clin Oncol 39, 2021 (suppl 3; abstr 310); ammonia was tested prospectively in the latter two studies. To assess impacts of cancer therapy or liver dysfunction, we studied hyperammonemia in FLC and non-FLC patients at UCSF in parallel. Using Natural Language Processing (NLP) of pathology reports and oncology notes from &gt; 2300 liver cancer patients from the last 12 years of UCSF records, we identified a cohort of patients with FLC, contrasting their laboratory data to all UCSF patients with ammonia testing for the last 10 years. We used leiden clustering and umap dimensionality reduction to contrast FLC and other patients to assess the clinical context of hyperammonemia. Results: Data from the 3 trials showed hyperammonemia in 10 of 32 (31.3%) FLC patients during study participation, independent of the therapy received. These patients exhibited hyperammonemia with varying levels, and at different points in their treatment. NLP identified 37 patients with FLC ( &lt; 0.1% of liver cancer patients), with 33% showing hyperammonemia. Across all UCSF patients, we found 24,000 independent visits where ammonia was tested, with &gt; 2400 demonstrating hyperammonemia. Using leidan clustering on all encounters with ammonia &gt; 75 µmol/L, we found distinct subsets of hyperammonemia corresponding to known metabolic and physiologic processes (e.g., fulminant liver failure, tumor lysis syndrome, etc). FLC patients clustered separately from hepatocellular carcinoma patients with hyperammonemic encephalopathy due to cirrhosis. Conclusions: NLP of large EMRs is a valuable tool to study FLC, a rare cancer. Herein, we have defined hyperammonemia as a frequent event in FLC, not directly linked to hepatic dysfunction or individual therapies. Further investigation may determine whether hyperammonemia is related to FLC tumor biology.

Risk factors of mFOLFOX6-induced hyperammonemia in patients with colorectal cancer: an observational study.

FOLFOX therapy, a standard treatment for colorectal cancer (CRC), causes a rare, but serious adverse event, hyperammonemia. However, the risk factors of hyperammonemia remain unknown. We examined 74 patients who received mFOLFOX6 therapy with or without biologics for CRC between April 2013 and March 2018 in Yaizu City Hospital. Clinicopathological factors were retrospectively reviewed in association with hyperammonemia, and risk factors of hyperammonemia during mFOLFOX6 therapy were analyzed in 32 patients with the available data. Seven patients developed hyperammonemia, with onset exclusively on day 2 or 3 in the first cycle of therapy. They were treated with branched chain amino acid administration and hydration; however, one patient with stage G4 chronic kidney disease (CKD) died. By multivariate analysis, estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 was independently associated with hyperammonemia during FOLFOX therapy (odds ratio: 9.0, p = 0.040). Reduced eGFR is considered a risk factor of developing hyperammonemia during FOLFOX therapy. Serum ammonia levels should be monitored especially during the first cycle of FOLFOX therapy in patients with CKD stage G3 or higher.

Hyperammonemia in Patients With Status Epilepticus Treated With or Without Valproic Acid.

Hyperammonemia is a common side effect of valproic acid (VPA) and can occur after generalized seizures, but the clinical significance is unclear. The aim of this study was to better understand the clinical practice and utility of ammonia testing in status epilepticus (SE) treated with or without VPA. Charts of adult patients with SE from St. Mary's Hospital Intensive Care Units (ICUs) (Mayo Clinic, Rochester, MN) from 2011 to 2016 were reviewed. Clinical factors were compared between patients who had ammonia checked versus those who did not, and those with normal ammonia versus hyperammonemia (>50 µg/dL). Charts were reviewed to determine if hyperammonemia changed clinical management and if it was felt to be symptomatic. There were 304 patients identified: 94 received VPA, 142 had ammonia checked and receiving VPA was associated with ammonia testing (P<0.001). Hyperammonemia was identified in 32 and associated with younger age, being in a non-neurological intensive care unit, and liver disease, but was not statistically associated with VPA. Only one patient had valproate-induced hyperammonemic encephalopathy; however, many patients received treatment for hyperammonemia such as lactulose, levocarnitine, or VPA dose reductions. This study demonstrated variability in ammonia testing and management changes in SE but does not support the routine monitoring of ammonia levels and showed that hyperammonemic encephalopathy was rare in this clinical setting.

Long-term N-carbamylglutamate treatment of hyperammonemia in patients with classic organic acidemias

BackgroundClassic organic acidurias (OAs) usually characterized by recurrent episodes of acidemia, ketonuria, and hyperammonemia leading to coma and even death if left untreated. Acute hyperammonemia episodes can be treated effectively with N-carbamylglutamate (NCG). The effect of the long-term efficacy of N-carbamylglutamate is little known. Material-MethodsThis retrospective study was conducted at Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Pediatric Nutrition and Metabolism Clinic between January 2012 to January 2018. Patients with classic OAs were enrolled in the study. Patients' ammonia levels, hospitalization needs, hyperammonemia episodes, and management of hyperammonemia were recorded. NCG usage for more than consecutively 15 days was considered as a long-term treatment. ResultsTwenty-one patients, consisting of eleven patients with methylmalonic acidemia (MMA) and ten patients with propionic acidemia (PA) were eligible for the study. N-carbamylglutamate was used as ammonia scavenger for a total of 484 months with a median period of 23 months (min-max: 3–51 months) in all patients. A significant decrease in plasma ammonia levels was detected during long term NCG treatment (55.31 ± 13.762 μmol/L) in comparison with pre NCG treatment period (69.64 ± 17.828 μmol/L) (p = 0.021). Hospitalization required hyperammonemia episodes decreased with NCG treatment (p = 0.013). In addition, hyperammonemia episodes were also successfully treated with NCG (p = 0.000). Mean initial and final ammonia levels at the time of hyperammonemia episodes were 142 ± 46.495 μmol/L and 42.739 ± 12.120 μmol/L, respectively. The average NCG dosage was 85 mg/kg/day (range 12.5–250 mg/kg/day). No apparent side effects were observed. ConclusionN-Carbamylglutamate may be deemed an effective and safe treatment modality in the chronic management of hyperammonemia in patients with PA and MMA.

Prognosis of Patients with Sepsis and Non-Hepatic Hyperammonemia: A Cohort Study.

BackgroundHyperammonemia has been reported in some critically ill patients with sepsis who do not have hepatic failure. A significant proportion of patients with non-hepatic hyperammonemia have underlying sepsis, but the association between non-hepatic hyperammonemia and prognosis is unclear.Material/MethodsInformation about patients with sepsis and non-hepatic hyperammonemia was retrieved from the Medical Information Mart for Intensive Care-III database. Survival rates were analyzed using the Kaplan-Meier method. Multivariate logistic regression models were employed to identify prognostic factors. Receiver operating characteristic (ROC) curve analysis was used to measure the predictive ability of ammonia in terms of patient mortality.ResultsA total of 265 patients with sepsis were enrolled in this study. Compared with the non-hyperammonemia group, the patients with hyperammonemia had significantly higher rates of hospital (59.8% vs. 43.0%, P=0.007), 30-day (47.7% vs. 34.8%, P=0.036), 90-day (61.7% vs. 43.7%, P=0.004), and 1-year mortality (67.3% vs. 49.4%, P=0.004). In the survival analysis, hyperammonemia was associated with these outcomes. Serum ammonia level was an independent predictor of hospital mortality. The area under the ROC curve for the ammonia levels had poor discriminative capacity. The hyperammonemia group also had significantly lower Glasgow Coma Scale scores (P=0.020) and higher incidences of delirium (15.9% vs. 8.2%, P=0.034) and encephalopathy (37.4% vs. 19.6%, P=0.001). Intestinal infection and urinary tract infection with organisms such as Escherichia coli may be risk factors for hyperammonemia in patients who have sepsis.ConclusionsHigher ammonia levels are associated with poorer prognosis in patients with sepsis. Ammonia also may be associated with sepsis-associated encephalopathy. Therefore, we recommend that serum ammonia levels be measured in patients who are suspected of having sepsis.

Changes in the Body Composition and Nutritional Status after Long-term Rifaximin Therapy for Hyperammonemia in Japanese Patients with Hepatic Encephalopathy.

Objective Rifaximin has become available for treating hyperammonemia in patients with hepatic encephalopathy. This study analyzed the changes in the body composition and nutritional status after long-term rifaximin therapy. Methods Twenty-one patients who underwent rifaximin therapy at 1,200 mg/day for more than 24 weeks were evaluated for the changes in the controlling nutritional status (CONUT) scores for the nutritional assessment, albumin-bilirubin (ALBI) scores for the liver function assessment, and skeletal muscle index (SMI) for the body composition assessment. Results There were 17 men and 4 women, with a mean age of 67.14±8.32 years. Eleven cases had a portosystemic shunt (52.3%), and 10 had hepatocellular carcinoma (47.6%). The Child-Pugh class was A in 9 cases (42.9%), B in 9 cases (42.9%), and C in 3 cases (14.2%). The blood ammonia levels in the rifaximin group improved significantly upon rifaximin therapy, from 124.76±28.68 μg/dL at baseline to 47.00±14.43 μg/dL after 2 weeks (p<0.001) and 49.81±15.02 μg/dL after 24 weeks (p<0.001). The CONUT scores improved significantly during rifaximin therapy, from 6.47±3.25 at baseline to 3.33±2.65 after 24 weeks (p=0.0007). The ALBI scores also improved significantly from -0.39±1.89 at baseline to -2.20±0.55 after 24 weeks (p=0.0002). The SMI scores showed that the body composition had been maintained in response to rifaximin therapy (50.20±7.67 at baseline and 51.29±7.62 after 24 weeks). Conclusion Rifaximin administration for hepatic encephalopathy improved the CONUT and ALBI scores. It may have a secondary effect on the improvement in the nutritional status and hepatic reserve.

S3271 Blame It on the Alcohol...or Not?

INTRODUCTION: Hyperammonemia (HA) can cause cerebral edema and brain herniation leading to coma or death, making it a common cause to be considered in patients who present with altered mental status (AMS). However, the etiology of hyperammonemia must be determined to guide treatment. While alcohol-related liver disease is one of the most common causes of liver cirrhosis, there are many other causes of cirrhosis that can also lead to hyperammonemia. We aim to study whether the etiology of cirrhosis plays a role in the severity of hyperammonemia in patients who present with AMS. METHODS: We performed a retrospective chart review of 190 patients seen at community hospital between July to August 2019 with an ICD-10 code of altered mental status (R41.82), hepatic failure without coma (K72.90) and cirrhosis of liver (K74.60). Data points included history/etiology of cirrhosis, history of alcohol abuse, AMS, and ammonia level on presentation. HA was defined as an ammonia level > 45 µmol/L. Patients were separated by the etiology of cirrhosis with alcohol in one group and other etiologies, including autoimmune hepatitis, non-alcoholic steatohepatitis (NASH), and viral hepatitis leading malignancy, and unknown etiology, in another group. We compared the average ammonia level for each group. RESULTS: Out of a total 190 patients who met criteria, 143 presented with ammonia levels >45 µmol/L. Out of this cohort, 52% had cirrhosis due to alcohol, and 48% had cirrhosis due to other causes. The average ammonia level for patients who presented with hyperammonemia with a history of alcoholic cirrhosis and cirrhosis due to other etiologies were 139µmol/L and 110 µmol/L, respectively. CONCLUSION: Alcohol-related liver disease is one of the most common causes of liver cirrhosis, but there are many other etiologies for liver cirrhosis. Hyperammonemia is known to be associated with increasing severity of liver cirrhosis. Whether the etiology of liver cirrhosis plays a role in the level of hyperammonemia that a patient presents with is unknown. This study found that patients with cirrhosis due to alcohol-related liver disease presented with a higher level of hyperammonemia on average compared to those with other etiologies of cirrhosis. However, the significance of determining the etiology of liver cirrhosis and its relation to diagnosing and management of hyperammonemia is yet to be determined. Limitations included the exclusion of other causes of hyperammonemia and being a single-center retrospective study.

Association Between the Serum Carnitine Level and Ammonia and Valproic Acid Levels in Patients with Bipolar Disorder.

Valproic acid (VPA) is not only an antiepileptic drug but also a mood stabilizer for patients with bipolar disorder. Long-term VPA therapy can cause carnitine deficiency, which may result in an increase in the blood ammonia level, in patients with epilepsy. However, information about this effect in patients with bipolar disorder is limited. The aim of this study was to investigate the associations between the serum VPA level and the carnitine and ammonia levels in psychiatric adult patients with epilepsy. The subjects were 182 consecutive Japanese adult patients (mean age 54.3 ± 19.5 years) diagnosed with bipolar disorder and treated with VPA. The serum VPA level, carnitine fraction, and plasma ammonia level were measured. Furthermore, the free carnitine and acylcarnitine fractions were measured using an enzyme cycling method. Sixty-nine patients (38%) had a low free carnitine level. There were significant differences in sex, height, VPA dose, serum VPA level, total carnitine level, acylcarnitine level, and acylcarnitine/free carnitine ratio between patients with a low free carnitine level and those with a normal range of free carnitine. The simple and multiple regression analyses revealed that the VPA dose and the serum VPA level were inversely and significantly correlated with the free carnitine level. The plasma ammonia level was correlated with the VPA dose, serum VPA level, and acylcarnitine level but not with the free carnitine level. These findings suggest that carnitine deficiency is associated with the VPA dose and the serum VPA level in patients with bipolar disorder. However, it is unlikely that carnitine deficiency is associated with hyperammonemia in patients with bipolar disorder.