Correction of hyponatremia and osmotic demyelinating syndrome: have we neglected to think intracellularly?

Osmotic demyelination syndrome (ODS) is a complication generally associated with overly rapid correction of hyponatremia. Traditionally, nephrologists have been trained to focus solely on limiting the correction rate. However, there is accumulating evidence to suggest that the prevention of ODS is beyond achieving slow correction rates. We (1) reviewed the literature for glial intracellular protective alterations during hyperosmolar stress, a state presumed equivalent to the rapid correction of hyponatremia, and (2) analyzed all available hyponatremia-associated ODS cases from PubMed for possible contributing factors including correction rates and concurrent metabolic disturbances involving hypokalemia, hypophosphatemia, hypomagnesemia, and/or hypoglycemia. In response to acute hyperosmolar stress, glial cells undergo immediate extracellular free water shift, followed by active intracellular Na+, K+ and amino acid uptake, and eventual idiogenic osmoles synthesis. At minimum, protective mechanisms require K+, Mg2+, phosphate, amino acids, and glucose. There were 158 cases of hyponatremia-associated ODS where both correction rates and other metabolic factors were documented. Compared with the rapid correction group (> 0.5 mmol/L/h), the slow correction group (a parts per thousand currency sign0.5 mmol/L/h) had a greater number of cases with concurrent hypokalemia (49.4 vs. 33.3 %, p = 0.04), and a greater number of cases with any concurrent metabolic derangements (55.8 vs. 38.3 %, p = 0.03). Glial cell minimizes volume changes and injury in response to hyperosmolar stress via mobilization and/or utilization of various electrolytes and metabolic factors. The prevention of ODS likely requires both minimization of correction rate and optimization of intracellular response during the correction phase when a sufficient supply of various factors is necessary.