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

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

doi:10.1093/ofid/ofac301

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

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

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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.

Original language	English (US)
Article number	ofac301
Journal	Open Forum Infectious Diseases
Volume	9
Issue number	7
DOIs	https://doi.org/10.1093/ofid/ofac301
State	Published - 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).

Keywords

cryptococcal meningitis
hyponatremia
mortality
prognostic marker
sodium

PubMed: MeSH publication types

Journal Article

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/ofid/ofac301

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@article{763f7382cacc4c98984c673bb057f208,

title = "Association of Hyponatremia on Mortality in Cryptococcal Meningitis: A Prospective Cohort",

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.",

keywords = "cryptococcal meningitis, hyponatremia, mortality, prognostic marker, sodium",

author = "{The Adjunctive Sertraline for HIV-Associated Cryptococcal Meningitis (ASTRO-CM) Team} and Lillian Tugume and Ann Fieberg and Kenneth Ssebambulidde and Edwin Nuwagira and Williams, {Darlisha A.} and Edward Mpoza and Rutakingirwa, {Morris K.} and Enoch Kagimu and John Kasibante and Laura Nsangi and Samuel Jjunju and Musubire, {Abdu K.} and Conrad Muzoora and Lawrence, {David S.} and Joshua Rhein and Meya, {David B.} and Hullsiek, {Kathy Huppler} and Boulware, {David R.} and Mahsa Abassiand",

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: {\textcopyright} 2022 The Author(s).",

year = "2022",

month = jul,

day = "1",

doi = "10.1093/ofid/ofac301",

language = "English (US)",

volume = "9",

journal = "Open Forum Infectious Diseases",

issn = "2328-8957",

publisher = "Oxford University Press",

number = "7",

}

TY - JOUR

T1 - Association of Hyponatremia on Mortality in Cryptococcal Meningitis

T2 - A Prospective Cohort

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

AU - Tugume, Lillian

AU - Fieberg, Ann

AU - Ssebambulidde, Kenneth

AU - Nuwagira, Edwin

AU - Williams, Darlisha A.

AU - Mpoza, Edward

AU - Rutakingirwa, Morris K.

AU - Kagimu, Enoch

AU - Kasibante, John

AU - Nsangi, Laura

AU - Jjunju, Samuel

AU - Musubire, Abdu K.

AU - Muzoora, Conrad

AU - Lawrence, David S.

AU - Rhein, Joshua

AU - Meya, David B.

AU - Hullsiek, Kathy Huppler

AU - Boulware, David R.

AU - Abassiand, Mahsa

N1 - 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).

PY - 2022/7/1

Y1 - 2022/7/1

N2 - 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.

AB - 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.

KW - cryptococcal meningitis

KW - hyponatremia

KW - mortality

KW - prognostic marker

KW - sodium

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U2 - 10.1093/ofid/ofac301

DO - 10.1093/ofid/ofac301

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AN - SCOPUS:85136260261

SN - 2328-8957

VL - 9

JO - Open Forum Infectious Diseases

JF - Open Forum Infectious Diseases

IS - 7

M1 - ofac301

ER -

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

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

UN SDGs

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