Complications and Management of Hyponatremia

Richard H. Sterns; Stephen M. Silver


Curr Opin Nephrol Hypertens. 2016;25(2):114-119. 

In This Article

Treatment of Severe Hyponatremia

Clinicians should respond promptly to the immediate dangers posed by acute hyponatremia, while remaining mindful of potential iatrogenic injury when more sustained hyponatremia is corrected too rapidly.[4,31–33] Exercise-associated hyponatremia is one of the more common causes of acute hyponatremia. Once thought to be a complication of competitive running, symptomatic hyponatremia has been recognized in a wider spectrum of activities, causing fatalities in football players, military recruits, and hikers.[34] The common thread is intake of water and sports drinks in excess of body fluid losses.[34,35] A consensus conference recommended that athletes with signs or symptoms of encephalopathy should be treated with up to 300 ml of 3% saline given as repeated 100 ml bolus infusions, enough to rapidly correct hyponatremia by 2–5 mEq/l.[34] Similar regimens have been recommended for other causes of symptomatic acute hyponatremia, including postoperative hyponatremia, and self-induced water intoxication associated with psychosis and use of the illegal recreational drug, 3,4-methylenedioxy-methamphetamine, popularly known as "Ecstasy".[4,31–33,36–38] Larger increases can sometimes be tolerated, but there is no evidence that they are needed. Correction by 4–6 mEq/l is sufficient to reverse impending herniation; larger increases offer no advantage and can be harmful to patients with chronic hyponatremia.[4,31,33,38,39]

Isotonic saline should not be used to treat symptomatic hyponatremia or hyponatremia associated with intracranial disease. If vasopressin levels are high, and the urine is concentrated, all administered sodium can be excreted in a small volume of urine so that the volume of fluid administered exceeds the volume of urine excreted; the resulting net positive water balance exacerbates hyponatremia.[4,38] Such a sequence, known as 'desalination' is common in postoperative SIADH and subarachnoid hemorrhage. In these settings, large volumes of isotonic saline are often given and the resulting hypervolemia promotes urinary sodium excretion despite a low serum sodium.[4] Desalination associated with subarachnoid hemorrhage is sometimes called 'cerebral salt wasting,' a label implying sodium loss despite hypovolemia, rather than natriuresis because of volume expansion, as occurs in SIADH. With no gold standard to define volume depletion, it is difficult to distinguish between SIADH and cerebral salt wasting.[40] Such a distinction is unnecessary; given the dire consequences of worsening hyponatremia, patients with intracranial disease should corrected with hypertonic saline. This is usually given intravenously (i.v.) as a 3% solution, but a single case report demonstrated that hourly doses of 1 g of NaCl orally, equivalent to 35 ml/h of 3% saline, can be effective.[41]

A recent prospective study of 100 patients with subarachnoid hemorrhage identified 49 who became hyponatremic; the cause determined by clinical examination, fluid balance, and vasopressin and natriuretic peptide levels, was SIADH in 71.4%, hypotonic fluids in 10.2%, hypovolemia without salt wasting in 10.2%, and no cases of cerebral salt wasting.[42] Notably, acute glucocorticoid insufficiency was identified in 8.2% of patients; their hyponatremia rapidly responded to steroid replacement.

Most hyponatremia is chronic, developing over 48 h or more, and should be presumed to be chronic when the duration is unknown. Experts agree that large increases in serum sodium (10 mEq/l in 24 h or 18 mEq/l in 48 h) should be avoided in all chronically hyponatremic patients (some would set the limit at 8 mEq/l/day), and, in patients with serum sodium 105 mEq/l or less, hypokalemia, alcoholism, liver disease, and malnutrition (conditions increasing the risk of ODS), correction should not exceed 4–6 mEq/l/day.[4,31–33,36–38] It can be difficult to avoid excessive correction, because the cause of hyponatremia is often reversible, and inadvertent overcorrection is common;[33,39,40,43] once the cause is eliminated (by stopping medication, volume repletion, cortisol replacement, or the passage of time), physiological suppression of vasopressin secretion provokes a water diuresis that can correct hyponatremia by more than 2 mEq/l/h. In hypokalemic patients, potassium replacement, given orally or as a 400 mM i.v. solution, will also increase the serum sodium.

Desmopressin (a synthetic vasopressin analogue) has been used to avoid iatrogenic injury from overcorrection of chronic hyponatremia. Three strategies have been described: 'proactive', where desmopressin is administered based on the presenting serum sodium (<125 mEq/l) and the perceived risk of overcorrection before any correction has occurred; 'reactive', where desmopressin is administered in response to a change in serum sodium or increase in urine output, indicating that excessive correction is likely to occur; and 'rescue', where desmopressin is administered after correction has already exceeded accepted limits, or neurological complications of overcorrection have developed, to stabilize or relower the serum sodium.[44] Desmopressin-induced hyponatremia is one example of a reversible cause; if desmopressin is discontinued, the resulting water diuresis can cause permanent brain damage if water losses are not replaced.[45] Rather than discontinuing desmopressin, it can be continued to prevent urinary water losses, concurrently administering 3% saline to slowly correct hyponatremia. The same strategy has been shown to be effective for other causes of reversible hyponatremia.[4,38,46] A review of the literature concluded that this proactive strategy is more likely to avoid excessive correction, particularly in patients at high risk of developing ODS.[44]