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

Abstract

Background Sodium abnormalities are frequent in CNS infections and may be caused by cerebral salt wasting, syndrome of inappropriate antidiuretic hormone secretion (SIADH), or medication adverse events. In cryptococcal meningitis, the prevalence of baseline hyponatremia and whether hyponatremia adversely impacts survival is unknown. Methods We conducted a secondary analysis of data from two randomized trials of HIV-infected adult Ugandans with cryptococcal meningitis. 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 cryptococcal meningitis, 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 CSF quantitative culture burden (P < .001), higher initial CSF opening pressure (P < 0.01), lower baseline Glasgow Coma Score (P < 0.01), 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 of 1.87 (95%CI, 1.26 to 2.79; p < 0.01) compared to those with sodium 130-145 mmol/L. Conclusions Hyponatremia is common in cryptococcal meningitis and is associated with excess mortality. A standardized management approach to correctly diagnose and correct hyponatremia in cryptococcal meningitis needs to be developed and tested.

Hyponatremia as a Predictor of Cryptococcal Meningitis and Death Among Asymptomatic Persons With HIV and Cryptococcal Antigenemia

“…Hyponatremia is common in tuberculous meningitis (TBM) and prognosticates increased mortality in persons coinfected with human immunodeficiency virus (HIV) and TBM [ 7–9 ]. In a study of patients with HIV-associated cryptococcal meningitis, 42% presented with hyponatremia (sodium <130 mmol/L), and severe hyponatremia (sodium <125 mmol/L) was an independent predictor of 2-week mortality [ 10 ].…”

Missed Opportunities in the Diagnosis of Tuberculosis Meningitis

“…Therefore, we explored hyponatremia during the index admission separately, because this is the most common electrolyte abnormality in hospitalized patients and a well known complication of TBM due to cerebral salt wasting or syndrome of inappropriate antidiuretic hormone, described in approximately half the patients with TBM [ 28 , 29 ]. Hyponatremia was independently associated with 90-day mortality in our study, and it is also a known risk factor associated with in-hospital death in other CNS infections such as cryptococcal meningitis [ 30 ].…”

Cryptococcal meningitis

“…However, ancillary support for patients with cryptococcal meningitis has an important survival benefit and is multi-modality. Severe baseline hyponatremia (with serum sodium levels of <125 mmol/L) occurs in up to 15% of patients with cryptococcal meningitis and this complication is associated with a doubling in 2-week mortality and 30-day mortality risks 192 . The development of hyponatremia in patients with cryptococcal meningitis is likely to be a multifactorial insult, in which raised intracranial pressures (ICP), high quantitative cryptococcal cultures, and seizures, leading to either the syndrome of inappropriate antidiuretic hormone secretion (SIADH) or cerebral salt wasting (CSW).…”

“…An objective assessment of impaired consciousness resulting in a Glasgow Coma Scale score (GCS) that is lower than 15 at diagnosis is a strong independent predictor for acute mortality, therefore management of altered mental status is likely to further improve survival. Baseline GCS <15 is associated with a five-fold increase in the probability of death 39 and is linked to increased ICP, seizures, hyponatremia, and elevated CSF lactate (> 5 mmol/L) [192][193][194][195] . Seizures are common in patients with cryptococcal meningitis, occurring in 28% of the cases, and associated with a higher 10-week mortality risk 194 .…”