@article{ae04337e4fc3464188bc37a5cb393c63,
title = "Serum osmolality, cerebrospinal fluid specific gravity and overt hepatic encephalopathy severity in patients with liver failure",
abstract = "Background and Aims: Hepatic encephalopathy (HE) is a leading contributor to morbidity in liver disease. While hyperammonaemia plays a key role, the mechanisms of cerebral toxicity are unclear. We hypothesized that serum hyperosmolality contributes to HE during acute (ALF) and acute-on-chronic liver failure (ACLF) through mechanisms that affect the water and solute composition of the cerebral environment. Methods: We performed a retrospective analysis of serum osmolality, cerebral spinal fluid (CSF) solute density (specific gravity, determined from computed tomography attenuation) and clinical HE severity (Glasgow Coma Score [GCS]) at the time of intensive care admission in a prospectively identified cohort of liver failure patients with overt HE. Results: Seventy-three patients (39 ALF and 34 ACLF) were included, of whom 28 (38%) were comatose. Serum osmolality (303.9 ± 15.4 mOsm/kg) was elevated despite normal serum sodium (136.6 ± 6.3 mEq/L). Increased osmolality was independently associated with more severe encephalopathy (ordinal adjusted OR 0.26 [95% CI 0.22, 0.31] for higher GCS per standard deviation increase in osmolality) and lower CSF-specific gravity (linear adjusted β = −0.039 [95% CI −0.069, −0.009] Hounsfield unit per 1 mOsm/kg). Conclusions: In the context of related research, these data suggest that hyperosmolality increases brain exposure to metabolic toxins by blood-brain barrier alteration and may be a unique therapeutic target.",
keywords = "acute liver failure, acute-on-chronic liver failure, hepatic encephalopathy, neuroimaging, osmolality, specific gravity",
author = "Liotta, {Eric M.} and Karvellas, {Constantine J.} and Minjee Kim and Ayush Batra and Andrew Naidech and Shyam Prabhakaran and Sorond, {Farzaneh A.} and Kimberly, {W. Taylor} and Maas, {Matthew B.}",
note = "Funding Information: Dr. Liotta received support from the National Institutes of Health grants KL2TR001424 and L30 NS098427. Dr. Maas received support from National Institutes of Health grants K23 NS092975. Research reported in this publication was supported, in part, by the National Institutes of Health's National Center for Advancing Translational Sciences grant UL1 TR000150. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Agency for Healthcare Research and Quality. The funding agencies had no role in the study design; in the collection, analysis and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication. Funding Information: Dr. Liotta received support from the National Institutes of Health grants KL2TR001424 and L30 NS098427. Dr. Maas received support from National Institutes of Health grants K23 NS092975. Research reported in this publication was supported, in part, by the National Institutes of Health's National Center for Advancing Translational Sciences grant UL1 TR000150. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Agency for Healthcare Research and Quality. The funding agencies had no role in the study design; in the collection, analysis and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication. 2 2 Publisher Copyright: {\textcopyright} 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd",
year = "2020",
month = aug,
day = "1",
doi = "10.1111/liv.14400",
language = "English (US)",
volume = "40",
pages = "1977--1986",
journal = "Liver International",
issn = "1478-3223",
publisher = "Wiley-Blackwell",
number = "8",
}