Review: Syndrome of inappropriate antidiuresis

The New England Journal of Medicine features a review of the syndrome of inappropriate antidiuresis (SIAD), beginning with a case vignette, a discussion of the clinical problem, diagnosis, evidence supporting various treatment strategies, and ends with the authors' clinical recommendations on the management of the case.

The review notes that the only definitive treatment of SIAD is elimination of its underlying cause; the most important factors dictating management are the severity of the hyponatraemia, its duration, and the presence or absence of symptoms.

The aim of treating symptomatic patients with severe hyponatraemia known to have developed acutely (within 48 hours) is to increase serum sodium level by 1-2mmol/L/h by infusing 3% saline; concomitant furosemide is recommended by some, though others advise avoiding it, or reserving it for patients with extracellular-fluid volume expansion. In addition, the magnitude of correction during the first 24 hours should be no more than 8-10 mmol/L, and no more than 18-25 mmol/L during the first 48 hours, even when the hyponatraemia is acute. An increase in serum sodium levels of < 10 mmol/L is usually sufficient to reduce symptoms and prevent complications.

Most cases of hyponatraemia of long or unclear duration are chronic and minimally symptomatic. Unlike those with acute hyponatraemia, these patients have a documented risk of osmotic demyelination if serum sodium is corrected by more than 12 mmol/L over 24 hours; this disorder begins with lethargy and affective changes (generally after initial improvement of neurological symptoms with treatment), followed by mutism or dysarthria, spastic quadriparesis, and pseudobulbar palsy. To balance the risks of chronic hyponatraemia vs risks of rapid correction, many authorities recommend a modest rate of correction (increase in serum sodium 0.5-1.0 mmol/L/h), using lower rates of saline infusion for patients with symptomatic hyponatraemia of unknown duration. Many limit correction to 8 mmol/L over 24 hours and 18 mmol/l over 48 hours; close monitoring of the rate of correction (every 2 to 3 hours) is recommended to avoid overcorrection.

Asymptomatic patients with chronic hyponatraemia have a low risk of serious neurological problems, but are at risk of osmotic demyelination with rapid correction. Oral intake of urea (30 g per day) is effective but is poorly tolerated; demeclocycline (300 to 600 mg BD) reduces urinary osmolality and increases serum sodium levels, but its effects can be variable and it can cause nephrotoxicity, whilst lithium is no longer recommended.

A new therapeutic option for SIAD is conivaptan, a vasopressin-receptor antagonist approved by the FDA in 2007 for IV treatment of hypervolaemic hyponatraemia; drugs in development include the oral selective vasopressin V2 receptor antagonists tolvaptan and satavaptan.

Other topics discussed include reversal of osmotic demyelination that develops during the treatment of hyponatraemia, differentiating SIAD from Cerebral Salt Wasting, a syndrome of hyponatraemia and extracellular-fluid volume depletion in patients with insults to the CNS, and the prevention of postoperative hyponatraemia.

N Engl J Med 2007; 356: 2064-72 (link to extract).