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

Zhao, Lina; Walline, Joseph Harold; Gao, Yanxia; Lu, Xin; Yu, Shiyuan; Ge, Zengzheng; Zhu, Huadong; Li, Yang

doi:10.3389/fmed.2020.589825

Cited by 11 publications

(13 citation statements)

References 34 publications

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“…A retrospective analysis of a multicenter database demonstrated some common metabolic disturbances and acute renal failure as potentially modifiable factors contributing to SAE ( 13 ). Another study from our center found that nonhepatic hyperammonemia occurred more often in patients with SAE ( 30 ), and this may be a potential therapeutic target for SAE ( 31 ).…”

Section: Discussionmentioning

confidence: 89%

Clinical Phenotypes of Sepsis-Associated Encephalopathy: A Retrospective Cohort Study

Lu¹,

Qin²,

Walline³

et al. 2023

Shock

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Background: Sepsis-associated encephalopathy (SAE) is a dysfunction of the central nervous system experienced during sepsis with variable clinical and pathophysiologic features. We sought to identify distinct SAE phenotypes in relation to clinical outcomes. Methods: The Medical Information Mart for Intensive Care IV (MIMIC-IV) database and the eICU database were used to conduct a retrospective cohort study. Adult sepsis patients were included and SAE was defined as having a Glasgow Coma Scale (GCS) score ˂15 or delirium. The following our clinical phenotypes were defined as: ischemic-hypoxic, metabolic, mixed (ischemic-hypoxic and metabolic), and unclassified. The primary outcome was in-hospital mortality. Results:The study enrolled 4,120 sepsis patients, 2,239 from MIMIC-IV (including 1,489 patients with SAE, 67%), and 1,881 from eICU (1,291, 69%). For the SAE cohort, 2,780 patients in total were enrolled (median age, 67 years; interquartile range, 56-76.8; 1,589 (57%) were male; median GCS score was 12 [8-14]; median Sequential Organ Failure Assessment score was 6 [4-9]). The SAE phenotype distributions between the MIMIC-IV and eICU cohorts were as follows (39% vs. 35% ischemic-hypoxic, P = 0.043; 38% vs. 40% metabolic, P = 0.239; 15% vs. 15% mixed, P = 0.972; 38% vs. 40% unclassified, P = 0.471). For the overall cohort, the in-hospital mortality for patients with ischemic-hypoxic, metabolic, mixed, or unclassified phenotypes was 33.9% (95% confidence interval, 0.3-0.37), 28.4% (0.26-0.31), 41.5% (0.37-0.46), and 14.2% (0.12-0.16), respectively. In the multivariable logistic analysis, the mixed phenotype was associated with the highest risk of in-hospital mortality after adjusting for age, sex, GCS, and modified Sequential Organ Failure Assessment score (adjusted odds ratio, 2.11; 95% confidence interval, 1.67-2.67; P < 0.001). Conclusions: Four SAE phenotypes had different clinical outcomes. The mixed phenotype had the worst outcomes. Further understanding of these phenotypes in sepsis may improve trial design and targeted SAE management. KEYWORDS-Sepsis-associated encephalopathy; clinical phenotype; large observational database; cohort study ABBREVIATIONS-ALTalanine transaminase; ASTaspartate transaminase; CIconfidence interval; GCS -Glasgow Coma Scale; ICUintensive care unit; IQRinterquartile range; LOSlength of stay; MIMIC-IV -Medical Information Mart for Intensive Care IV; ORodds ratio; RRTrenal replacement therapy; SAEsepsis-associated encephalopathy; SDstandard deviation; SOFA -Sequential Organ Failure Assessment; SpO 2pulse oximetry

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Section: Discussionmentioning

confidence: 89%

Clinical Phenotypes of Sepsis-Associated Encephalopathy: A Retrospective Cohort Study

Lu¹,

Qin²,

Walline³

et al. 2023

Shock

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“…Acquired diseases can be further divided into hyperammonemia because of hepatic and nonhepatic causes. Congenital disorders associated with enzyme defects include UCDs, organic acidosis, congenital lactic acidosis, fatty acid oxidation defects, and dibasic amino acid deficiency ( Savy et al, 2018 ; Zhao et al, 2020 ). Ammonia is normally produced in the large and small intestines, where it is carried to the liver and converted into urea via the urea cycle.…”

Section: Discussionmentioning

confidence: 99%

“…In congenital metabolic disorders including hyperammonemia, secondary ammonia formation occurs when there is a defect in ammonia-detoxifying enzymes [e.g., in urea cycle disorders (UCDs)] or when there is liver damage (e.g., in cirrhosis) ( Savy et al, 2018 ; Zhao et al, 2020 ). Consequently, this process leads to the accumulation of ammonia (a toxic metabolite), which enters the portosystemic circulation.…”

Section: Introductionmentioning

confidence: 99%

Engineered Probiotics for the Management of Congenital Metabolic Diseases: A Systematic Review

Barati,

Mosharkesh,

Tahmassian

et al. 2024

Prev. Nutr. Food Sci.

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Engineered probiotics (EPs) can be used to treat/manage chronic and congenital diseases. However, to the best of our knowledge, no systematic review has evaluated the effects of EPs on congenital metabolic disorders in murine models and human subjects. Thus, the present study systematically reviewed interventional studies that assessed the effects of EPs on congenital metabolic disorders. PubMed, Web of Science, and Scopus databases were searched up to February 2023 to retrieve related publications. Seventy-six articles were obtained in the primary step. After screening the titles/abstracts based on the inclusion and exclusion criteria, 11 papers were included. Finally, only seven articles were included after performing full-text evaluation. The included articles evaluated the effects of EPs on managing phenylketonuria (PKU, n=4) and hyperammonemia (n=3). Moreover, these studies examined mice and/or rats (n=6), monkeys (n=1), and humans (n=2). Studies on EPs and hyperammonemia revealed that some wild strains such as Lactobacillus plantarum have an innate ammonia-hyper-consuming potential; thus, there was no need to manipulate them. However, manipulation is needed to obtain a phenylalanine-metabolizing strain. In conclusion, EPs can be used to manage or treat congenital metabolic diseases including PKU.

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“…( 25 (30,31) In the present research, we examined whether there could be differences in the different prognosis between distinct types of diseases (e.g., Sepsis, Kidney failure), and no signi cant differences were identi ed, consistent with previously reported results in severity of hyperammonemia. (17) This may be attributed to the diverse and complicated etiology of NHH, which indicating the prognosis. Overall energy expenditure and severity of disease are the key factors contributing to the occurrence of NHH.…”

Section: Discussionmentioning

confidence: 99%

“…(14)(15)(16) Two recent retrospective studies demonstrated that serum ammonia status was an independent prognostic predictor of mortality for NHH patients. (7,17) Speci cally, proactive monitoring of blood ammonia levels for the prompt detection of, and early intervention against, NHH may improve the prognosis of critically ill patients.…”

Section: Introductionmentioning

confidence: 99%

Prognostic Value of Serum Ammonia in Critical Patients with Non-Hepatic Disease : A Prospective, Observational, Multicenter Study

Li¹,

Yao²,

Li³

et al. 2021

Preprint

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Background: 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).Methods: 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, 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 curve (ROC) analysis was conducted to compare predictive ability of APACHE-II score, lactic acid, TBil, M-ammonia.Results: 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, GCS, and SOFA. Multivariate analysis revealed that circulating mean ammonia levels in ICU patients were independently associated with a poor prognosis (OR=1.73, 95% CI: 1.07-2.80, P=0.02). However, the APACHE-II score (AUC: 0.714, sensitivity: 0.86, specificity: 0.68, P <0.001) remained the most predictive factor for patient prognosis by ROC analysis.Conclusions: Elevated serum levels of ammonia in the blood were independently prognostic for ICU patients without liver disease.Trial registration: ChiCTR1900026632. Registered 16 October 2014.

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

Cited by 11 publications

References 34 publications

Clinical Phenotypes of Sepsis-Associated Encephalopathy: A Retrospective Cohort Study

Clinical Phenotypes of Sepsis-Associated Encephalopathy: A Retrospective Cohort Study

Engineered Probiotics for the Management of Congenital Metabolic Diseases: A Systematic Review

Prognostic Value of Serum Ammonia in Critical Patients with Non-Hepatic Disease : A Prospective, Observational, Multicenter Study

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