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Management of hyponatremia: Providing treatment and avoiding harm

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NEXT, FIND THE APPROPRIATE RATE OF CORRECTION

After the initial serious signs or symptoms have been addressed with hypertonic saline, management should focus on limiting the rate of correction in patients with chronic hyponatremia or hyponatremia of unknown duration.

Animal studies and retrospective human studies have suggested certain guidelines on the appropriate pace and magnitude of correction during treatment of hyponatremia to avoid osmotic demyelination syndrome.2

Clinicians must not attempt to correct the serum sodium to “normal” values. Although patients with acute hyponatremia may tolerate complete correction, there is little evidence that raising the serum sodium concentration acutely by more than 5 to 8 mmol/L is advantageous. Therefore, correction should be judicious in all patients.

Appropriate rates of correction

A recent expert consensus panel suggested that the serum sodium level be raised by no more than 10 to 12 mmol/L during the first 24 hours of treatment, and by less than 18 mmol/L over 48 hours.2

Patients with chronic hyponatremia and signs or symptoms of cerebral edema should have their sodium level raised at an even slower rate—some recommend less than 10 mmol/L in the first 24 hours.10 Aggressive initial correction at the rate of 1.5 to 2 mmol/hour for the first 3 to 4 hours with 3% saline is indicated until serious symptoms (seizure, obtundation) resolve, but correction beyond 10 to 12 mmol/L in the first 24 hours should be avoided. Hypertonic saline therapy should usually be discontinued well before the serum sodium level has risen this much, to avoid a continuing rise in the sodium level after the infusion has stopped.

While hypertonic saline is being infused, serum sodium levels should be checked every 1 to 2 hours. In a study in 56 patients with severe hyponatremia (serum sodium ≤ 105 mmol/L),11 no neurologic complications were observed in patients with chronic hyponatremia whose serum sodium was corrected by less than 12 mmol/L in 24 hours or by less than 18 mmol/L in 48 hours or in whom the average rate of correction to a serum sodium of 120 mmol/L was less than or equal to 0.55 mmol/L per hour.

If the serum sodium concentration has been overcorrected

Desmopressin is effective in preventing and reversing inadvertent overcorrection of hyponatremia. 12 In one study, desmopressin lowered the sodium concentration by 2 to 9 mmol/L in 14 of 20 patients. None of the patients developed any serious adverse consequences.

In addition, intravenous water (dextrose 5%) can be given alone or in combination with desmopressin to prevent or reverse an excessive increase in serum sodium.13 Such therapy may be considered in patients who continue to excrete hypotonic urine and have already reached a serum sodium concentration that meets or exceeds the recommended rate or magnitude of change.

Formulas for estimating the rate of correction

Various formulas have been devised for estimating the change in serum sodium concentration during treatment of hyponatremia.14

The Adrogué-Madias formula, one of the most commonly used, gives an estimate of how much the serum sodium concentration will rise when 1 L of various intravenous fluids is given (Table 5).15 This formula also accounts for the increase in serum sodium that takes place during concomitant correction of hypokalemia with potassium. Recently, however, a retrospective study16 found that this formula underestimated the change in serum sodium in 23 (74.2%) of 31 patients with hyponatremia treated with hypertonic saline.

An alternative is the Barsoum-Levine equation, which takes into account ongoing urinary losses. Although it is more cumbersome to calculate, it may be more precise.17

Alternatively, in patients without hypovolemia, the clinician can calculate the amount of urinary excretion of free water required to achieve a specific target serum sodium and then measure hourly urinary water excretion during aquaresis induced by furosemide (Lasix).8 Although more physiologic, this method can be clinically cumbersome, requiring timely handling of urine specimens, accurate recording of urine output, and rapid reporting of laboratory results.

Ultimately, these methods serve only as estimates of the change in serum sodium and do not replace careful monitoring of electrolytes (every 1 to 2 hours during acute therapy) and fastidious assessment for clinical signs or symptoms of osmotic demyelination syndrome.

PATIENTS WITH HYPONATREMIA AND NO SERIOUS SIGNS OR SYMPTOMS

General approach

Hyponatremic patients without serious signs or symptoms of cerebral edema do not require urgent therapy to raise the serum sodium.

Patients with chronic asymptomatic hyponatremia are commonly encountered in clinical practice. As a result of cerebral adaptation, they can appear to have no symptoms despite serum sodium levels as low as 115 to 120 mmol/L. However, even if they have no serious signs or symptoms of cerebral edema, some patients may complain of fatigue, lethargy, nausea, gait abnormalities, and muscle cramps and have evidence of milder forms of neurocognitive impairment.18

In a recent case-control study,18 elderly patients with chronic hyponatremia (mean serum sodium concentration 126 ± 5 mmol/L) were more likely to present to the hospital with falls compared with age-matched controls. Further analysis suggested these patients had marked impairments in gait and attention, which improved in some as the serum sodium increased.

Another recent study19 reported that mild hyponatremia (mean serum sodium concentration 132 mmol/L) was independently associated with the risk of fracture, even after adjustment for known osteoporotic risk factors.

Even when there is no need for acute therapy to raise the serum sodium level, the clinician should scrutinize the medical regimen and available clinical data to rule out reversible causes of water excess. These may include ongoing administration of hypotonic fluids (eg, parenteral nutrition or dextrose 5% to “keep the vein open”) or of medications that cause inappropriate release of ADH (eg, selective serotonin reuptake inhibitors) or that impair water excretion (eg, nonsteroidal anti-inflammatory drugs). The clinician should also search for an underlying diagnosis that predisposes to water retention, such as hypothyroidism, adrenal insufficiency, congestive heart failure, or hepatic or renal failure. If hyponatremia is due to endocrine disease, correction of hypothyroidism or adrenal insufficiency should result in water excretion and improvement in the serum sodium.

If the cause of the hyponatremia is not immediately apparent, treatment can be started on the basis of assessment of the patient’s extracellular fluid volume status using clinical examination and supplementary laboratory data such as the serum uric acid concentration and urinary sodium concentration.3Table 3 outlines general treatment options for hypoosmolar hyponatremia according to extracellular fluid volume status.

Of note, physical examination alone has poor sensitivity and specificity in assessing extracellular fluid volume status in patients with hyponatremia.20,21 This highlights the importance of spot measurements of urine sodium and serum uric acid and, when appropriate, isotonic intravenous saline challenge to detect occult hypovolemia.

In general, patients with euvolemia are treated with fluid restriction, and patients with hypovolemia are given isotonic saline. Patients with hypervolemia can be difficult to treat, but in general they are prescribed both sodium and fluid restriction. Loop diuretics can be given to promote excretion of water and sodium. Thiazide diuretics are avoided, as they impair urinary dilution and worsen hyponatremia. Attempts should be made to optimize the treatment of the underlying hypervolemic disorder (congestive heart failure, cirrhosis, advanced renal failure). Vasopressin receptor antagonists can also be used in selected cases of hypervolemic or euvolemic hyponatremia (see discussion below).

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