Classifying Hypotonic Hyponatremia by Projected Treatment Effects - A Quantitative 3-Dimensional Framework

Abstract

The diagnostic algorithms currently used for hypotonic hyponatremia focus primarily on impaired urinary dilution and often neglect the influence of free water intake and solute excretion. We hypothesized that, in each case of hypotonic hyponatremia different pathophysiological mechanisms play a role simultaneously. Using clinical data of the previous observational Co-Med study, we defined each case of hypotonic hyponatremia concurrently in 3 dimensions as follows: (i) high net free water intake (HNFWI), (ii) impaired dilution of the urine (IDU), and (iii) low nonelectrolyte solute excretion (LNESE). For each dimension, a "standard delta sodium" (sdna) was calculated reflecting the expected difference to the serum sodium concentration, that would result from changing a dimension to a specific and equivalent target level. Results from 279 patients were used for this analysis. With target levels of free water intake and urine osmolality at the fifth percentile, and nonelectrolyte solute excretion at the 95th percentile, median (interquartile range) sdna values were 7.1 (4.8-10.2) for HNFWI, 11.8 (7.0-18.6) for IDU and 2.6 (1.6-4.2) mmol/l per 24 hours for LNESE. Sdna results in individual patients were highest with IDU in 68.5%, HNFWI in 30.8% and 0.7% with LNESE. At an sdna-level of at least 4mmol/l per 24 hours, the prevalence of HNFWI was 78.9%, IDU 87.1%, and LNESE 26.5%. 77.5% of patients had 2 or all 3 mechanisms present. Hyponatremia was mostly multifactorial in subgroups according to classic categories of hyponatremia and typical comorbidities as well. Hypotonic hyponatremia can be quantitatively defined by 3 dimensions. Most cases should be considered multifactorial.