TREATMENT Hypernatremia
The underlying cause of hypernatremia should be withdrawn or corrected, be it drugs, hyperglycemia, hypercalcemia, hypokalemia, or diarrhea. The approach to the correction of hypernatremia is outlined in Table 49-3. It is imperative to correct hypernatremia slowly to avoid cerebral edema, typically replacing the calculated free water deficit over 48 h. Notably, the plasma Na+ concentration should be corrected by no >10 mM/d, which may take longer than 48 h in patients with severe hypernatremia (>160 mM). A rare exception is patients with acute hypernatremia (<48 h) due to sodium loading, who can safely be corrected rapidly at a rate of 1 mM/h.
Water should ideally be administered by mouth or by nasogastric tube, as the most direct way to provide free water, i.e., water without electrolytes. Alternatively, patients can receive free water in dextrose-containing IV solutions, such as 5% dextrose (D5W); blood glucose should be monitored in case hyperglycemia occurs. Depending on the history, blood pressure, or clinical volume status, it may be appropriate to initially treat with hypotonic saline solutions (1/4 or 1/2 normal saline); normal saline is usually inappropriate in the absence of very severe hypernatremia, where normal saline is proportionally more hypotonic relative to plasma, or frank hypotension. Calculation of urinary electrolyte-free water clearance (Table 49-3) is required to estimate daily, ongoing loss of free water in patients with NDI or central DI, which should be replenished daily.
Additional therapy may be feasible in specific cases. Patients with central DI should respond to the administration of intravenous, intranasal, or oral DDAVP. Patients with NDI due to lithium may reduce their polyuria with amiloride (2.5–10 mg/d), which decreases entry of lithium into principal cells by inhibiting ENaC (see above); in practice, however, most patients with lithium-associated DI are able to compensate for their polyuria by simply increasing their daily water intake. Thiazides may reduce polyuria due to NDI, ostensibly by inducing hypovolemia and increasing proximal tubular water reabsorption. Occasionally, nonsteroidal anti-inflammatory drugs (NSAIDs) have been used to treat polyuria associated with NDI, reducing the negative effect of intrarenal prostaglandins on urinary concentrating mechanisms; however, this assumes the risks of NSAID-associated gastric and/or renal toxicity. Furthermore, it must be emphasized that thiazides, amiloride, and NSAIDs are only appropriate for chronic management of polyuria from NDI and have no role in the acute management of associated hypernatremia, where the focus is on replacing free water deficits and ongoing free water loss.