Hyponatremia must be managed with care, especially in patients with chronic severe illness, due to the unpredictable nature of tolvaptan to raise serum sodium levels.
Hyponatremia is one of the most commonly occurring electrolyte abnormalities, reported in up to 22% of hospitalized patients. Although there are several treatment options available to clinicians, including vasopressin antagonists like tolvaptan, patients with hyponatremia must be managed carefully, as rapid overcorrection of serum sodium levels can result in neurologic complications such as osmotic demyelination syndrome (ODS).
The authors of the case report “Unpredictable Nature of Tolvaptan in Treatment of Hypervolemic Hyponatremia: Case Review on Role of Vaptans,” published in Case Reports in Endocrinology, noted that treatment of hyponatremia “depends on several factors, including the cause, overall volume status of the patient, severity of hyponatremic symptoms, and duration of hyponatremia at presentation.” They wrote that although vasopressin antagonists like tolvaptan seem “promising for the treatment of euvolemic and hypervolemic hyponatremia in heart failure,” their use requires careful dosing and monitoring to avoid the complications associated with overly rapid sodium correction.
In this case report, they analyzed the role of vasopressin antagonists in the treatment of hyponatremia and examined “the need for daily dosing of tolvaptan and the monitoring of serum sodium levels to avoid rapid overcorrection,” which can result in ODS.
In patients with heart failure, treatment options for hyponatremia (defined here as serum sodium levels < 135 mmol/L) such as “water restriction or the use of hypertonic saline with loop diuretics” have been shown to have limited efficacy. The use of vasopressin antagonists such as tolvaptan and conivaptan has been shown to increase sodium levels effectively and improve outcomes in patients. However, the authors noted that “safety in terms of overcorrecting sodium levels with daily doses of 15—60 mg of tolvaptan is still debatable.”
They wrote on these and other issues raised by the case of a 51-year-old man with a history of coronary artery disease and peripheral vascular disease who was admitted to the hospital with chronic hypervolemic hyponatremia and subsequently developed acute hypernatremia and osmotic demyelination syndrome “due to administration of tolvaptan and diuretics.”
On admission, the patient had “a B type natriuretic peptide level of 3458, sodium of 122 mmol/L, potassium of 5.2 mmol/L, and blood urea nitrogen/creatinine ratio of 39/1.5.” Initial treatment with “aggressive dieresis” produced no increase in serum sodium levels after six days, so the patient was also given tolvaptan 15 mg. One day after the initial tolvaptan dose, the patient’s serum sodium had increased to 126 mmol/L. After a second tolvaptan dose, the patient’s serum sodium had rapidly increased from 142 mmol/L to 159 mmol/L to 167 mmol/L, at which point tolvaptan treatment was stopped.
The authors reported that at this point the patient “developed signs of osmotic demyelination syndrome which failed to resolve after rapid correction with hypotonic fluids and desmopressin and was transferred to the medical intensive care unit for further management of hypernatremia.”
In their discussion of this case, the authors wrote that “overly rapid correction of hyponatremia (eg, >12 mEq/L/24 hours) with tolvaptan can cause osmotic demyelination resulting in dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma, and death.” To mitigate against the development of ODS, recommendations call for slow correction of serum sodium (less than 12 mmol/L/day).
Additional recommendations highlighted in the article include:
In their conclusion, the authors said this case “tells us that severe chronic hyponatremia must be managed with extreme care especially in patients with chronic debilitating illness due to the unpredictable nature of tolvaptan to raise serum sodium levels.” Tolvaptan should be administered after checking serum sodium levels each day and it should not be started as a standing order while initiating treatment.