Non-hepatic Hyperammonemia Research Articles

NHH promotes Sepsis-associated Encephalopathy with the expression of AQP4 in astrocytes through the gut-brain Axis.

Sepsis-associated encephalopathy (SAE) is a significant cause of mortality in patients with sepsis. Despite extensive research, its exact cause remains unclear. Our previous research indicated a relationship between non-hepatic hyperammonemia (NHH) and SAE. This study aimed to investigate the relationship between NHH and SAE and the potential mechanisms causing cognitive impairment. In the in vivo experimental results, there were no significant abnormalities in the livers of mice with moderate cecal ligation and perforation (CLP); however, ammonia levels were elevated in the hippocampal tissue and serum. The ELISA study suggest that fecal microbiota transplantation in CLP mice can reduce ammonia levels.Reduction in ammonia levels improved cognitive dysfunction and neurological impairment in CLP mice through behavioral, neuroimaging, and molecular biology studies. Further studies have shown that ammonia enters the brain to regulate the expression of aquaporins-4 (AQP4) in astrocytes, which may be the mechanism underlying brain dysfunction in CLP mice. The results of the in vitro experiments showed that ammonia up-regulated AQP4 expression in astrocytes, resulting in astrocyte damage. The results of this study suggest that ammonia up-regulates astrocyte AQP4 expression through the gut-brain axis, which may be a potential mechanism for the occurrence of SAE.

Nonhepatic Hyperammonemia Secondary to Escherichia coli Urinary Tract Infection

Nonhepatic Hyperammonemia Secondary to Escherichia coli Urinary Tract Infection

Non-hepatic Hyperammonemia with Loading Dose of Perampanel in a Case of CNS Lupus Presenting with Non-Convulsive Status Epilepticus

Non-hepatic Hyperammonemia with Loading Dose of Perampanel in a Case of CNS Lupus Presenting with Non-Convulsive Status Epilepticus

A Case of Rising Serum Ammonia Associated with Early Detection of Antibiotic Resistant Pseudomonas Aeruginosa Pneumonia

Background: Hyperammonemia is frequently encountered in critical illness as a consequence of liver failure, but Nonhepatic Hyperammonemia (NHHA) can also occur in pathologies causing ammonia overproduction or inappropriate ammonia clearance. Sepsis-associated hyperammonemia is a subset of NHHA associated with urease producing infections causing ammonia overproduction. Case Description: We report an unusual case of sepsis-associated NHHA secondary to multi-drug resistant Pseudomonas aeruginosa pneumonia in a 50-year-old critically ill man who was admitted to the intensive care unit for cardiogenic shock, respiratory failure, and hepatic failure secondary to myocardial infarction with papillary muscle rupture. He subsequently developed P. aeruginosa pneumonia and was treated empirically with piperacillin/tazobactam and subsequently meropenem as guided by culture data. The patient’s serum ammonia concentration was incidentally trended to stratify risk for cerebral edema. Eight days into his pneumonia treatment course, the patient’s serum ammonia level abruptly doubled despite improving hepatic function, which prompted switching the P. aeruginosa treatment from meropenem to ciprofloxacin. Bronchial washings later revealed that the P. aeruginosa had acquired resistance to meropenem. The patient subsequently demonstrated clinical improvement and also had a downward trend in the serum ammonia concentration. Another trend of hyperammonemia without worsening hepatic function later in his hospital course correlated with P. aeruginosa infection with acquired resistance to ciprofloxacin, and which improved with the addition of inhaled tobramycin to the antibiotic regimen. Conclusions: In sepsis-associated NHHA, the serum ammonia trend may be a useful adjunct marker to indicate treatment response and provide an early indication of antibiotic treatment resistance.

Relationship between Nonhepatic Serum Ammonia Levels and Sepsis-Associated Encephalopathy: A Retrospective Cohort Study.

Nonhepatic hyperammonemia often occurs in patients with sepsis. Ammonia plays an essential role in the occurrence of hepatic encephalopathy. However, the relationship between nonhepatic serum ammonia levels and sepsis-associated encephalopathy (SAE) remains unclear. Thus, we aimed to evaluate the association between serum ammonia levels and patients with SAE. Data of critically ill adults with sepsis who were admitted to the intensive care unit were retrieved from the Medical Information Mart for Intensive Care IV (MIMIC IV) between 2008 and 2019 and retrospectively analyzed. Data of patients with sepsis patients and serum ammonia not related to acute or chronic liver disease were not included. Data from 720 patients with sepsis were included. SAE was found to have a high incidence (64.6%). After adjusting for other risk factors, a serum ammonia level of ≥45 μmol/L (odds ratio (OR): 3.508, 95% confidence interval (CI): 2.336-5.269, p < 0.001) was found to be an independent risk factor for patients with SAE; moreover, as the serum ammonia level increased, the hospital mortality of SAE gradually increased in a certain range (serum ammonia <150 μmol/L). Serum ammonia levels of ≥45 μmol/L were associated with higher Simplified Acute Physiology Score II and Sequential Organ Failure Assessment (SOFA) scores in patients with SAE. Besides, our study found that patients with SAE used opioid analgesics (OR:3.433, 95% CI: 1.360-8.669, p = 0.009) and the SOFA scores of patients with SAE (OR: 1.126, 95% CI: 1.062-1.194, p < 0.001) were significantly higher than those without SAE. Nonhepatic serum ammonia levels of ≥45 μmol/L evidently increased the incidence of SAE. Serum ammonia levels should be closely monitored in patients with sepsis.

Pearls & Oy-sters: Status Epilepticus and Cerebral Edema From Hyperammonemia Due to Disseminated Ureaplasma and Mycoplasma Species.

Nonhepatic hyperammonemia syndrome is a rare cause of neurologic dysfunction and cerebral edema and has most commonly been reported in posttransplant patients. Only recently has opportunistic infection with Ureaplasma species and Mycoplasma hominis been found to be key to the pathogenesis. We describe the cases of 3 immunosuppressed patients who developed hyperammonemia syndrome with new-onset refractory status epilepticus and diffuse cerebral edema. PCR was positive for M hominis in 1 patient and Ureaplasma parvum in the other 2. Despite early diagnostic suspicion and aggressive management with empirical antibiotics, seizure control, hypertonic saline, and ammonia elimination, none of our patients survived this life-threatening infection. Nonhepatic hyperammonemia and new-onset seizures can be presenting features of disseminated Ureaplasma species and M hominis infections in posttransplant patients. Immunosuppression in the absence of organ transplantation is likely sufficient to trigger this entity, as was the case in our third patient. When suspected, empiric combination antibiotics should be used due to high likelihood of resistance. The diagnostic test of choice is PCR. Patients with hyperammonemia syndrome associated with these infections typically have a poor prognosis. Early recognition and aggressive multimodal interventions may be key to ameliorating the high mortality and severe neurologic sequelae from this entity.

Non-hepatic Hyperammonemia: A Potential Therapeutic Target for Sepsis-associated Encephalopathy.

Sepsis-Associated Encephalopathy (SAE) is a common complication in the acute phase of sepsis, and patients who develop SAE have a higher mortality rate, longer hospital stay, and worse quality of life than other sepsis patients. Although the incidence of SAE is as high as 70% in sepsis patients, no effective treatment is available for this condition. To develop an effective treatment for SAE, it is vital to explore its pathogenesis. It is known that hyperammonemia is a possible factor in the pathogenesis of hepatic encephalopathy as ammonia is a potent neurotoxin. Furthermore, our previous studies indicate that non-hepatic hyperammonemia seems to occur more often in sepsis patients; it was also found that >50% of sepsis patients with non-hepatic hyperammonemia exhibited encephalopathy and delirium. Substatistical analyses indicate that non-hepatic hyperammonemia is an independent risk factor for SAE. This study updates the definition, clinical manifestations, and diagnosis of SAE; it also investigates the possible treatment options available for non-hepatic hyperammonemia in patients with sepsis and the mechanisms by which non-hepatic hyperammonemia causes encephalopathy.

Author response: Undifferentiated non-hepatic hyperammonemia in the ICU: Diagnosis and management

Author response: Undifferentiated non-hepatic hyperammonemia in the ICU: Diagnosis and management

Undifferentiated non-hepatic hyperammonemia in the ICU: Diagnosis and management.

Hyperammonemia occurs frequently in the critically ill but is largely confined to patients with hepatic dysfunction or failure. Non-hepatic hyperammonemia (NHHA) is far less common but can be a harbinger of life-threatening diagnoses that warrant timely identification and, sometimes, empiric therapy to prevent seizures, status epilepticus, cerebral edema, coma and death; in children, permanent cognitive impairment can result. Subsets of patients are at particular risk for developing NHHA, including the organ transplant recipient. Unique etiologies include rare infections, such as with Ureaplasma species, and unmasked inborn errors of metabolism, like urea cycle disorders, must be considered in the critically ill. Early recognition and empiric therapy, including directed therapies towards these rare etiologies, is crucial to prevent catastrophic demise. We review the etiologies of NHHA and highlight the first presentation of it associated with a concurrent Ureaplasma urealyticum and Mycoplasma hominis infection in a previously healthy individual with polytrauma. Based on this clinical review, a diagnostic and treatment algorithm to identify and manage NHHA is proposed.

Prognostic value of serum ammonia in critical patients with non-hepatic disease: A prospective, observational, multicenter study.

Non-hepatic hyperammonemia can damage the central nervous system (CNS), and possible prognostic factors are lacking. This study aimed to investigate the prognostic and risk factors for patients admitted to the intensive care unit (ICU). This prospective, observational, multicenter study was conducted between November and December 2019 at 11 ICUs in the Chinese Heilongjiang province. Changes in blood ammonia level during and after ICU admission were continuously monitored and expressed as the high level (H-), mean level (M-), and initial level (I-) of ammonia. The risk factors of poor prognosis were investigated by conducting univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curve analysis was conducted to compare the predictive ability of Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE-II) score, lactic acid, total bilirubin (TBil), and M-ammonia. A total of 1060 patients were included in this study, of which 707 (67%) had a favorable prognosis and 353 (33%) had a poor prognosis. As shown by univariate models, a poor prognosis was associated with elevated serum levels of lactic acid, TBil, and ammonia (P < 0.05) and pathologic scores from three assessments: APACHE-II, Glasgow Coma Scale (GCS), and Sequential Organ Failure Assessment (SOFA). Multivariate analysis revealed that circulating mean ammonia levels in ICU patients were independently associated with a poor prognosis (odds ratio [OR] = 1.73, 95% confidence interval [CI]: 1.07-2.80, P = 0.02). However, the APACHE-II score (area under the curve [AUC]: 0.714, sensitivity: 0.86, specificity: 0.68, P < 0.001) remained the most predictive factor for patient prognosis by ROC analysis. Elevated serum levels of ammonia in the blood were independently prognostic for ICU patients without liver disease.

Epidemiology, Clinical Presentation and Treatment of Non-Hepatic Hyperammonemia in ICU COVID-19 Patients.

(1) Background: Although COVID-19 is largely a respiratory disease, it is actually a systemic disease that has a wide range of effects that are not yet fully known. The aim of this study was to determine the incidence, predictors and outcome of non-hepatic hyperammonemia (NHH) in COVID-19 in intensive care unit (ICU); (2) Methods: This is a 3-month prospective observational study in a third-level COVID-19 hospital. The authors collected demographic, clinical, severity score and outcome data. Logistic regression analyses were performed to identify predictors of NHH; (3) Results: 156 COVID-19 patients were admitted to the ICU. The incidence of NHH was 12.2% (19 patients). The univariate analysis showed that invasive mechanical ventilation had a 6.6-fold higher risk (OR 6.66, 95% CI 0.86–51.6, p = 0.039) for NHH, while in the multiple regression analysis, there was a 7-fold higher risk for NHH—but it was not statistically significant (OR 7.1, 95% CI 0.90–56.4, p = 0.062). Demographics, clinical characteristics and mortality in the ICU at 28 days did not show a significant association with NHH. (4) Conclusions: The incidence of NHH in ICU COVID-19 patients was not low. NHH did not appear to significantly increase mortality, and all patients with non-hepatic hyperammonemia were successfully treated without further complications. However, the pathogenesis of NHH in ICU patients with COVID-19 remains a topic to be explored with further research.

Impact of non-hepatic hyperammonemia on mortality in intensive care unit patients: a retrospective cohort study.

Background/AimsThe effect of hyperammonemia on the mortality in patients with liver cirrhosis is well documented. However, little is known about the impact of hyperammonemia on mortality among intensive care unit patients without hepatic disease. We aimed to investigate factors associated with non-hepatic hyperammonemia among intensive care unit patients and to evaluate the factors related to the 7- and 90-day mortality.MethodsBetween February 2016 and February 2020, 948 patients without hepatic disease who had 972 episodes of admission to the intensive care unit were retrospectively enrolled and classified as hyperammonemia grades 0 (≤ 80 μg/dL; 585 [60.2%]), 1 (≤ 160 μg/dL; 291 [29.9%]), 2 (≤ 240 μg/dL; 55 [5.7%]), and 3 (> 240 μg/dL; 41 [4.2%]). Factors associated with hyperammonemia and the 7- and 90-day mortality were evaluated by multivariate logistic regression analysis and Cox regression analysis, respectively. Kaplan-Meier survival curves for the 7- and 90-day mortality were constructed.ResultsThe independent risk factors for hyperammonemia were male sex (odds ratio, 1.517), age (0.984/year), acute brain failure (2.467), acute kidney injury (1.437), prothrombin time-international normalized ratio (2.272/unit), and albumin (0.694/g/dL). The 90-day mortality rate in the entire cohort was 24.3% and gradually increased with increasing hyperammonemia grade at admission (17.9%, 28.2%, 43.6%, and 61.0% in patients with grades 0, 1, 2, and 3, respectively). Additionally, non-hepatic hyperammonemia was an independent predictor of the 90-day mortality in intensive care unit patients.ConclusionsNon-hepatic hyperammonemia is common (39.8%) and associated with the 90-day mortality among intensive care unit patients.

Analysis of clinical prognosis in patients with non-hepatic hyperammonemia.

The aim of this study was to evaluate the association of non-hepatic hyperammonemia (NHH) with the prognosis of critically ill patients with NHH.According to the serum ammonia level, the patients with NHH (n = 498) were retrieved by us. The risk factors of the mortality with NHH patients were investigated by conducting univariate and multivariate logistic regression analyses. A nomogram to predict the risk of hospital mortality was constructed. Receiver operating characteristic curve (ROC) analysis was conducted to compare nomogram (ammonia into a prognostic model, P1) with the simplified acute physiology II (SAPSII) and quick sequential organ failure assessment (qSOFA).Five independent factors for the mortality in patients with NHH were identified, including age, platelets, bun, hemoglobin, and ammonia. Models P1 using ammonia showed good prediction power. The AUROC of P1 (AUROC, 0.755 [95% CI, 0.713–0.796]) was higher than that of qSOFA (AUROC, 0.500 [95% CI, 0.449–0.551]), and SAPS II (AUROC, 0.703[95% CI, 0.658–0.748]).Ammonia was an independent prognostic predictor of mortality for NHH patients. We developed a nomogram that can predict hospital mortality with patients. Nomogram had superior discriminative power to qSOFA and SAPS II, indicating that the nomogram may have clinical utility.

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.

Prognostic Role of Ammonia in Critical Care Patients Without Known Hepatic Disease.

Background and Aims: Hyperammonemia usually develops because of hepatic disease, but it may occur in patients with non-hepatic hyperammonemia (NHH). But, studies on the prognosis and possible risk factors of this disorder are lacking. The aim of this study was to find possible prognostic and risk factors for NHH in critically ill patients.Methods: Data were extracted from MIMIC III Database. Survival was analyzed by the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify prognostic factors.Results: Valproic acid, carbamazepine, corticosteroids, recent orthopedic surgery, epilepsy, disorders of urea cycle metabolism, and obesity were found to be risk factors for NHH. Patients in the hyperammonemia group had a higher 30 day mortality than those in the non-hyperammonemia group. After final regression analysis, ammonia was found to be independent predictors of mortality.Conclusion: Ammonia was an independent prognostic predictor of 30 day mortality for critical care patients without liver disease.

A Cross-Sectional Survey on Nonhepatic Hyperglycemia in Intensive Care Unit, Heilongjiang Province, China

Introduction: The importance of blood ammonia detection and nonhepatic hyperammonemia (NHH) in the treatment and prognosis of patients has been neglected clinically. The purpose of this study was to evaluate the etiology, diagnosis, treatment, and prognosis of NHH in intensive care unit adults in Heilongjiang province, China. To solve this problem, we designed a provincial-level survey of severe adult NHH, including its etiology, risk factors, incidence, prognosis, and treatment strategies. Methods: The present study refers to a cross-sectional survey of the whole province, involving five cities in Heilongjiang province. All patients who met the inclusion criteria were eligible to apply to participate in the study, which included baseline demographics, clinical presentation, and follow-up related to diagnosis and treatment. Results: The total number of patients to be recruited in this study was estimated to reach 759. All patients who met the inclusion criteria were eligible to apply to participate in the study, which included baseline demographics, clinical presentation, and follow-up related to diagnosis and treatment. Conclusion: This study is expected to provide a theoretical basis for the development of more scientific and standardized NHH diagnosis and treatment methods. Ethics and Dissemination: Ethical approval was obtained from the ethics committee of The Second Affiliated Hospital of Harbin Medical University (registration number KY2019-184). The findings of this review will be communicated through peer-reviewed publications and scientific presentations. Trial Registration Number: ChiCTR1900026632.

A CASE OF RECURRENT ENCEPHALOPATHY IN A GASTRIC BYPASS PATIENT

SESSION TITLE: Critical Care Complications SESSION TYPE: Med Student/Res Case Report PRESENTED ON: 10/22/2019 3:45 PM - 4:45 PM INTRODUCTION: Hyperammonemia (HA) is a common cause of altered mental status (AMS) typically due to severe liver disease or drug therapy in the adult population. In certain patient populations new enzyme deficiencies should be considered especially urea acid cycle disorders. We present a case of AMS secondary to an acquired enzyme deficiency. CASE PRESENTATION: A 40 year old woman presented with recurrent AMS and worsening generalized weakness over 1 month. She had a history of a Roux-en-Y bypass, with multiple hospitalizations since then for malnutrition, nausea, vomiting, weakness, HA and recurrent AMS. On admission, ammonia was 103 despite home lactulose use, AST/ALT 35/35, AP 142 with normal bilirubin. She was alert, oriented, anicteric, lacked cirrhotic stigmata, had mild dysarthria, profound weakness, without focal deficits. A few days later she was intubated for a low GCS. Liver function minimally changed with maximum AST 87, ALT 82, AP 222, and T. Bili 2.4. Vitamin B12 was over 1800, thiamine 1290, ceruloplasmin 7, A1AT normal, hepatitis panel and ANA negative; ammonia peaked at 234. Despite later removing sedation, neurologic status remained poor. Brain MRI showed no acute changes, abdominal ultrasound revealed mild intrahepatic ductal dilation, and EEG showed triphasic waves. Alternative explanations were then considered and a urine orotic acid level was elevated confirming OTC deficiency. Arginine and Ammonul were started well as continuous renal replacement therapy. Transfer was arranged to another hospital specializing in OTC deficiency. DISCUSSION: Neurologic complications of bariatric surgery (BS) are uncommon and often related to vitamin B12 and folate deficiencies. Intermittent encephalopathy associated with recurrent HA should raise the suspicion of urea cycle disorders following BS. HA has been reported in case studies after these surgeries and some have been attributed to acquired OTC deficiency in the setting of a heterozygous enzyme deficiency. As a result they are asymptomatic until after BS when their nutritional status changes and they are now in a catabolic state. While most OTC deficiencies are diagnosed in childhood, this case emphasizes the importance of considering intrinsic enzyme deficiencies in patients with unexplainable AMS and HA without severe liver disease in adults. Cases that are identified early have a better chance of survival but unfortunately the mortality rate is often high. CONCLUSIONS: In light of an increasing number of patients undergoing BS, rare side effects including acquired enzyme deficiencies can have significant adverse outcomes for those patients. Urea cycle disorders should be thought of as an etiology of HA in the absence of liver disease in this population. Reference #1: Acharya, Gyanendra et al. “Fatal Nonhepatic Hyperammonemia in ICU Setting: A Rare but Serious Complication following Bariatric Surgery” Case Reports in Critical Care vol. 2016 (2016): 8531591. DISCLOSURES: No relevant relationships by Ibrahim Ismail-Sayed, source=Web Response No relevant relationships by Kathleen Twomey, source=Web Response No relevant relationships by Margaret Wojnar, source=Web Response

Analysis of cerebral blood flow and intracranial hypertension in critical patients with non-hepatic hyperammonemia.

Hyperammonemia in adults is generally associated with cerebral edema, decreased cerebral metabolism, and increased cerebral blood flow. The aim of this study was to evaluate the association between non-hepatic hyperammonemia and intracranial hypertension assessed by Doppler flowmetry and measurement of the optic nerve sheath. A prospective cohort study in critically ill patients hospitalized in intensive care units of a University Hospital between March 2015 and February 2016. Clinical data and severity scores were collected and the Glasgow coma scale was recorded. Serial serum ammonia dosages were performed in all study patients. Transcranial Doppler evaluation was carried out for the first 50 consecutive results of each stratum of ammonemia: normal (<35μmol/L), mild hyperammonemia (≥35μmol/L and < 50μmol/L), moderate hyperammonemia (≥50μmol/L and < 100μmol/L), and severe hyperammonemia (≥100μmol/L). The measurement of the optic nerve sheath was performed at the same time as the Doppler examination if the patient scored less than 8 on the Glasgow coma scale. There was no difference in flow velocity in the cerebral arteries between patients with and without hyperammonemia. Patients with hyperammonemia presented longer ICU stay. Optic nerve sheath thickness was higher in the group with severe hyperammonemia and this group presented an association with intracranial hypertension. Higher mortality was observed in the severe hyperammonemia group. There was an association between severe hyperammonemia and signs of intracranial hypertension. No correlation was found between ammonia levels and cerebral blood flow velocity through the Doppler examination.

Valproate Induced Hyperammonemic Encephalopathy in a Patient with Phenytoin Toxicity: A Case Report

Valproate is an antiepileptic drug which is commonly used for the treatment of focal and/or generalized epilepsy and mood disorders. Valproate is one of the safest first line antiepileptic drug, but like any other drug, it has adverse effects such as nausea, vomiting, drowsiness, tremors, alopecia, menstrual irregularities, polycystic ovarian disease, hepatotoxicity, pancreatitis, thrombocytopenia and rarely hyperammonemia etc. We have reported a case of 22-years-old female of idiopathic generalized epilepsy admitted with eptoin toxicity and subsequently she developed valproate induced non-hepatic hyperammonemia encephalopathy during her hospital stay. Valproate was withheld immediately, and her symptoms resolved after 48 hours.

Hyperammonemic Encephalopahty Can Result from a Duodenal Switch

A 41-year-old female had inadequate weight loss 2 years after a vertical sleeve gastrectomy. 1 year prior to presentation, she underwent revision to a duodenal switch with formation of a duodeno-ileal anastomosis. At presentation she had evidence for protein-calorie malnutrition. She denied alcohol use; total parenteral nutrition (TPN) was initiated. Upper endoscopy revealed a normal esophagus and post-operative changes of sleeve gastrectomy with duodenal switch; a nasoileal tube was placed to begin enteral nutrition. On day 9, the patient was moved to the intensive care unit after onset of catatonia and unresponsiveness. On exam, she had no signs of chronic liver disease. Her INR was 1.4, platelet count 237 and had minimal elevations of serum ALT and AST. She had no evidence for metabolic acidosis (AGAP-8 and lactic acid-1.1). CT scan of the head was unremarkable. There was no deficiency of vitamin B12, folate, copper, or zinc, but she had hyperammonemia with a blood level of 223 mcg/dl. The differential diagnosis for non-hepatic hyperammonemia includes medications, hyperalimentation, infections with urease producing bacteria, surgical-induced nutritional deficiency, and errors of metabolism. Other potential explanations were excluded for this patient. She was started on a protein restriction of 40 grams/day, lactulose enemas and high dose intravenous thiamine. She had a decrease in her serum ammonia levels with improvement in her mental status. A 24-hour urine collection revealed an elevated orotic acid level (2.9 mmol/mol Cr) supporting Ornithine Transcarbamylase Deficiency. She underwent revision of her ileo-ileostomy, and the common channel was increased in length. On day 30, TPN was discontinued. She was discharged on a protein limited diet and oral lactulose. This exceedingly rare phenomenon with similar presentations has been described previously involving predominantly female patients developing an often fatal hyperammonemic encephalopathy after gastric bypass surgery, which in some patients was up to 28 years post-operatively. The exact mechanism remains unclear, but this disorder is believed to involve unmasking of inborn errors of urea metabolism after bariatic surgery, the most common of which is Ornithine Transcarbamylase Deficiency. This case report demonstrates that this disorder can also occur after duodenal switch. Gastroenterologists need to be aware of this disorder due to the number of patients undergoing bariatric surgery.