management of SIADH

Last reviewed 07/2022

Seek expert advice.

• correction of acute symptomatic hyponatraemia is best accomplished with hypertonic (3%) saline given via continuous infusion
  • this is because patients with euvolaemic hypo-osmolality such as SIADH will not respond to isotonic saline
  • intravenous furosemide 20 to 40 mg should be used to treat volume overload, in some cases anticipatorily in patients with known cardiovascular disease
  • regardless of the initial rate of correction chosen, acute treatment should be interrupted once any of three end points is reached (1):
    • (1) the patient's symptoms are abolished
    • (2) a safe serum [Na+] level (generally >=120 mmol/L) is achieved;
    • or (3) a total magnitude of correction of 18 mmol/L is achieved
  • serum [Na+] levels must be carefully monitored at frequent intervals (preferably every 2 hours, but at least every 4 hours) during the active phases of treatment in order to adjust therapy so that the correction stays within these limits
    • it is only necessary and appropriate to correct the serum [Na+] acutely to a safe range rather than completely to normal levels
• treatment of chronic hyponatraemia
  • for most other cases of mild-to-moderate SIADH, fluid restriction represents the least toxic therapy, and has generally been the treatment of choice
    • (1) all fluids, not only water, must be included in the restriction
    • (2) the degree of restriction required depends on urine output plus insensible fluid loss (generally discretionary, ie, nonfood, fluids should be limited to 500 mL/day below the average daily urine volume);
    • (3) several days of restriction are usually necessary before a significant increase in plasma osmolality occurs;
    • (4) only fluid, not sodium, should be restricted - because of the ongoing natriuresis, patients with chronic SIADH often have a negative total body sodium balance and therefore should be maintained on relatively high NaCI intake unless otherwise contraindicated
    • if there is failure of significant fluid restriction after several days of confirmed negative fluid balance
      • reconsider other possible causes, including solute depletion and clinically unapparent hypovolaemia
    • at the time that fluid restriction is first initiated, any drugs known to be associated with SIADH should be discontinued or changed
  • fluid restriction should generally be tried as the initial therapy, with pharmacologic intervention reserved for refractory cases where the degree of fluid restriction required to avoid hypo-osmolality is so severe that the patient is unable, or unwilling, to maintain it
  • pharmacologic intervention should also be avoided initially in patients with SIADH that is secondary to tumours, because successful treatment of the underlying malignant lesion often eliminates or reduces the inappropriate arginine vasopressin (AVP) secretion
  • preferred drug is the tetracycline derivative demeclocycline
    • causes a nephrogenic form of diabetes insipidus, thereby decreasing urine concentration even in the presence of high plasma AVP levels
    • treatment must be continued for several days to achieve maximal diuretic effects; consequently, one should wait 3 to 4 days before deciding to increase the dose
    • demeclocycline can cause reversible azotaemia and sometimes nephrotoxicity, especially in patients with cirrhosis
    • other agents, such as lithium, have similar renal effects - however has inconsistent results and significant side effects and toxicities
    • urea has also been described as an alternative mode of treatment for SIADH as well as for other hyponatremic disorders

Reference:

• (1) hyponatraemia Treatment Guidelines 2007: Expert Panel Recommendations.American Journal of Medicine 2007; 120 (11);S1:S1-S21.