Altered consciousness mediates the effect of hypernatremia, but not hyponatremia, on mortality among patients observed in the ICU

Abstract Purpose: Dysnatremias - hypernatremia and hyponatremia - may be associated with mortality through their impact on altered consciousness. We examined the mediating effect of decreased consciousness on the relationship between dysnatremia and mortality. Methods: Among 195,568 critically ill patients in the United States contained in the eICU database, we categorized serum sodium into bands of 5mEq/L. Using causal mediation analysis, we compared bands in the hypernatremia and hyponatremia ranges to a reference band of 135-139mEq/L to determine the proportion of mortality mediated by decreased consciousness as determined by the Glasgow Coma Score (GCS). Results: Both hyponatremia (OR [95%CI] for bands: <120mEq/L: 1.58 [1.26-1.97]; 120-<125mEq/L: 1.92 [1.64-2.25]; 125-<130mEq/L: 1.76 [1.60-1.93]; 130-<135mEq/L: 1.32 [1.24-1.41]) and hypernatremia (OR [95%CI] for bands: 140-<145mEq/L: 1.12 [1.05-1.19]; 145-<150mEq/L: 1.89 [1.70-2.11]; ≥150mEq/L: 1.86 [1.57-2.19]) were significantly associated with increased mortality. GCS mediated the effect of hypernatremia on mortality risk (Proportion mediated [95%CI]: 140-144mEq/L: 0.38 [0.23 to 0.89]; 145-149mEq/L: 0.27 [0.22 to 0.34]; ≥150mEq/L: 0.53 [0.41 to 0.81]) but not hyponatremia (proportion mediated 95%CI upper bound <0.05 for all bands). Conclusion: Decreased consciousness mediates the association between increased mortality and hypernatremia, but not hyponatremia. Further studies are needed to explore neurologic mechanisms and directionality in this relationship.