Osmotic Shifts, Cerebral Edema, and Neurologic Deterioration in Severe Hepatic Encephalopathy

Objectives: We sought to determine the effect of acute electrolyte and osmolar shifts on brain volume and neurologic function in patients with liver failure and severe hepatic encephalopathy. Design: Retrospective analysis of brain CT scans and clinical data. Setting: Tertiary care hospital ICUs. Patients: Patients with acute or acute-on-chronic liver failure and severe hepatic encephalopathy. Interventions: Clinically indicated CT scans and serum laboratory studies. Measurements and Main Results: Change in intracranial cerebrospinal fluid volume between sequential CT scans was measured as a biomarker of acute brain volume change. Corresponding changes in serum osmolality, chemistry measurements, and Glasgow Coma Scale were determined. Associations with cerebrospinal fluid volume change and Glasgow Coma Scale change for initial volume change assessments were identified by Spearman's correlations (rs) and regression models. Consistency of associations with repeated assessments was evaluated using generalized estimating equations. Forty patients were included. Median baseline osmolality was elevated (310 mOsm/Kg [296–321 mOsm/Kg]) whereas sodium was normal (137 mEq/L [134–142 mEq/L]). Median initial osmolality change was 9 mOsm/kg (5–17 mOsm/kg). Neuroimaging consistent with increased brain volume occurred in 27 initial assessments (68%). Cerebrospinal fluid volume change was more strongly correlated with osmolality (r = 0.70; p = 4 × 10–7) than sodium (r = 0.28; p = 0.08) change. Osmolality change was independently associated with Glasgow Coma Scale change (p = 1 × 10–5) and cerebrospinal fluid volume change (p = 2.7 × 10–5) in initial assessments and in generalized estimating equations using all 103 available assessments. Conclusions: Acute decline in osmolality was associated with brain swelling and neurologic deterioration in severe hepatic encephalopathy. Minimizing osmolality decline may avoid neurologic deterioration. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/29S62lw). Dr. Liotta contributed to study conception and design; data acquisition, analysis, and interpretation; drafted the article and revised it critically for important intellectual content; approved the final article draft; and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Dr. Liotta had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Dr. Liotta takes responsibility for the integrity of the work as a whole. Dr. Romanova contributed to data acquisition and analysis, critically revised the article for important intellectual content, approved the final article draft, and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Dr. Lizza contributed to data acquisition, critically revised the article for important intellectual content, approved the final article draft, and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Dr. Rasmussen-Torvik contributed to study design; data analysis and interpretation; revised the article critically for important intellectual content; approved the final article draft; and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Dr. Rasmussen-Torvik also provided statistical consultation and review. Dr. Kim contributed to data interpretation, critically revised the article for important intellectual content, approved the final article draft, and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Dr. Francis contributed to data acquisition, critically revised the article for important intellectual content, approved the final article draft, and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Dr. Sangha contributed to data acquisition, critically revised the article for important intellectual content, approved the final article draft, and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Dr. Carroll contributed to study design, data interpretation, critically revised the article for important intellectual content, approved the final article draft, and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Drs. Ganger, Ladner, and Prabhakaran contributed to study conception, data interpretation, critically revised the article for important intellectual content, approved the final article draft, and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Dr. Naidech and Maas contributed to study conception and design, data interpretation, critically revised the article for important intellectual content, approved the final article draft, and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Dr. Paparello contributed to data interpretation, critically revised the article for important intellectual content, approved the final article draft, and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Dr. Sorond contributed to study conception, data interpretation, critically revised the article for important intellectual content, approved the final article draft, and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Supported, in part, by the National Institutes of Health's National Center for Advancing Translational Sciences, Grant Number KL2TR001424, and the National Institutes of Health, Grant Number L30 NS098427 and by departmental funding from the Ken & Ruth Davee Department of Neurology in the Northwestern University Feinberg School of Medicine. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Drs. Liotta, Rasmussen-Torvik, Sorond, and Maas received support for article research from the National Institutes of Health (NIH). Dr. Liotta is supported by a KL2 career development grant awarded through the Northwestern University Clinical and Translational Sciences Institute. Dr. Liotta's institution received funding from NIH's National Center for Advancing Translational Sciences and the NIH's National Center for Advancing Translational Sciences, Grant Number KL2TR001424; he received funding from the NIH, Northwestern University, and NIH Grant Number L30 NS098427; and he disclosed that his institution received grant support from Placement of AoRTic TraNscathetER Valves II Trial (Edwards Lifesciences), TranScatheter Aortic Valve RepLacement System U.S. Feasibility Trial (Direct Flow Medical), and SAGE-547 Clinical Trial (SAGE therapeutics) for his work on those clinical trials. Dr. Ganger received funding from Abbvie, Gilead, and Merck. Dr. Naidech's institution received funding from the Agency for Healthcare Research and Quality, K18 HS023437. Dr. Maas' institution received funding from the NIH. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: eric.liotta@northwestern.edu Copyright © by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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