Association of Hyponatremia on Mortality in Cryptococcal Meningitis: A Prospective Cohort

The Adjunctive Sertraline for HIV-Associated Cryptococcal Meningitis (ASTRO-CM) Team

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


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.

Original languageEnglish (US)
Article numberofac301
JournalOpen Forum Infectious Diseases
Issue number7
StatePublished - Jul 1 2022

Bibliographical note

Funding Information:
This work was supported by the National Institute of Neurologic Diseases and Stroke (grant numbers R01NS086312 and K23NS122601); the National Institutes of Health through the Fogarty International Center (grant numbers K43TW010718 and R25TW009345); the National Institute of Allergy and Infectious Diseases (award number T32AI055433); the United Kingdom (UK) Medical Research Council and Wellcome Trust (award number MR/M007413/1); the European and Developing Countries Clinical Trials Partnership; the Swedish International Development Cooperation Agency; and the Wellcome Trust/UK Medical Research Council/UK Aid Joint Global Health Trials.

Publisher Copyright:
© 2022 The Author(s).


  • cryptococcal meningitis
  • hyponatremia
  • mortality
  • prognostic marker
  • sodium

PubMed: MeSH publication types

  • Journal Article


Dive into the research topics of 'Association of Hyponatremia on Mortality in Cryptococcal Meningitis: A Prospective Cohort'. Together they form a unique fingerprint.

Cite this