Association of Hyponatremia on Mortality in Cryptococcal Meningitis: A Prospective Cohort
Author:
Tugume Lillian1, Fieberg Ann2, Ssebambulidde Kenneth1, Nuwagira Edwin3, Williams Darlisha A12, Mpoza Edward1, Rutakingirwa Morris K1, Kagimu Enoch1, Kasibante John1, Nsangi Laura1, Jjunju Samuel1, Musubire Abdu K12, Muzoora Conrad3, Lawrence David S45, Rhein Joshua12, Meya David B126, Hullsiek Kathy Huppler2ORCID, Boulware David R7ORCID, Abassi Mahsa17ORCID, Rhein Joshua, Kiggundu Reuben, Akampurira Andrew, Kirumira Paul, Francis Ndyetukira Jane, Ahimbisibwe Cynthia, Kugonza Florence, Namuju Carolyne, Sadiq Alisat, Kiiza Kandole Tadeo, Luggya Tony, Kaboggoza Julian, Laker Eva, Namudde Alice, Lofgren Sarah, Kwizera Richard, Rwomushana Irene, Ssemusu Mike, Rukundo Joan, Mwesigye James, Nielsen Kirsten, Stadelman Anna, Bangdiwala Ananta S., Lawrence David, Youssouf Nabila,
Affiliation:
1. Infectious Diseases Institute, College of Health Sciences, Makerere University , Kampala , Uganda 2. Department of Biostatistics, University of Minnesota , Minneapolis, Minnesota , USA 3. Department of Internal Medicine, Mbarara University of Science and Technology , Mbarara , Uganda 4. Clinical Research Department, London School of Hygiene and Tropical Medicine , London , United Kingdom 5. Botswana Harvard AIDS Institute Partnership , Gaborone , Botswana 6. School of Medicine, College of Health Sciences, Makerere University , Kampala , Uganda 7. Division of Infectious Diseases, Department of Medicine, University of Minnesota , Minneapolis, Minnesota , USA
Abstract
Abstract
Background
Sodium abnormalities are frequent in central nervous system infections and may be caused by cerebral salt wasting, syndrome of inappropriate antidiuretic hormone secretion, or medication adverse events. In cryptococcal meningitis (CM), the prevalence of baseline hyponatremia and whether hyponatremia adversely impacts survival is unknown.
Methods
We conducted a secondary analysis of data from 2 randomized trials of human immunodeficiency virus–infected adult Ugandans with CM. We grouped serum sodium into 3 categories: <125, 125–129, and 130–145 mmol/L. We assessed whether baseline sodium abnormalities were associated with clinical characteristics and survival.
Results
Of 816 participants with CM, 741 (91%) had a baseline sodium measurement available: 121 (16%) had grade 3–4 hyponatremia (<125 mmol/L), 194 (26%) had grade 2 hyponatremia (125–129 mmol/L), and 426 (57%) had a baseline sodium of 130–145 mmol/L. Hyponatremia (<125 mmol/L) was associated with higher initial cerebrospinal fluid (CSF) quantitative culture burden (P < .001), higher initial CSF opening pressure (P < .01), lower baseline Glasgow Coma Scale score (P < .01), and a higher percentage of baseline seizures (P = .03). Serum sodium <125 mmol/L was associated with increased 2-week mortality in unadjusted and adjusted survival analyses (adjusted hazard ratio, 1.87 [95% confidence interval, 1.26–2.79]; P < .01) compared to those with sodium 130–145 mmol/L.
Conclusions
Hyponatremia is common in CM and is associated with excess mortality. A standardized management approach to correctly diagnose and correct hyponatremia in CM needs to be developed and tested.
Funder
National Institute of Neurologic Diseases and Stroke National Institutes of Health Fogarty International Center National Institute of Allergy and Infectious Diseases United Kingdom (UK) Medical Research Council European and Developing Countries Clinical Trials Partnership Swedish International Development Cooperation Agency Wellcome Trust UK Medical Research Council
Publisher
Oxford University Press (OUP)
Subject
Infectious Diseases,Oncology
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