The cause, treatment and outcome of hyponatraemia associated with tuberculous meningitis: An observational study nested within two clinical trials of corticosteroids

OBJECTIVES: To characterize tuberculous meningitis (TBM)-associated hyponatraemia and better understand its causality, progression, and influence on treatment outcomes. METHODS: 208 Vietnamese adults with TBM, consecutively enrolled into two trials of adjunctive dexamethasone (ACT-HIV:NCT03092817; LAST-ACT:NCT03100786), had at least one measurement of plasma sodium, urinary sodium, serum osmolality, or urine osmolality during treatment. Fluid status was assessed by fluid balance and inferior vena cava ultrasound. TBM severity and clinical endpoints by 12 months were recorded. RESULTS: 176/190 (92.6%) participants with plasma sodium measured at presentation had hyponatraemia, with lower sodium associated with more severe TBM, and increased CSF inflammation. Pre-defined causality criteria applied to 34 participants with complete data suggested 7/34 (20.6%) had cerebral salt wasting (CSW) and 27/34 (79.4%) had the syndrome of inappropriate anti-diuretic hormone (SIADH). Dexamethasone therapy (vs. placebo) was associated with higher plasma sodium during the first 30 days, irrespective of baseline plasma sodium, however these associations did not reach statistical significance. During treatment, lower plasma sodium and higher 24-hour urinary outputs strongly predicted death and neurological events at 3 and 12 months. CONCLUSIONS: Hyponatraemia was strongly associated with more severe TBM and intracerebral inflammation. Persistent hyponatraemia and increasing urinary output during treatment associate with worse clinical outcomes.