Hyponatremia is one of the most commonly encountered electrolyte abnormalities occurring in up to 22% of hospitalized patients. Hyponatremia usually reflects excess water retention relative to sodium rather than sodium deficiency. Volume status and serum osmolality are essential to determine etiology. Treatment depends on several factors, including the cause, overall volume status of the patient, severity of hyponatremic symptoms, and duration of hyponatremia at presentation. Vasopressin antagonists like tolvaptan seem promising for the treatment of euvolemic and hypervolemic hyponatremia in heart failure. Low sodium concentrations cause cerebral edema, but the overly rapid sodium correction can also lead to iatrogenic cerebral osmotic demyelination syndrome. Demyelination may occur days after sodium correction or initial neurologic recovery from hyponatremia. The following case report analyzes the role of vasopressin antagonists in the treatment of hyponatremia and the need for daily dosing of tolvaptan and the monitoring of serum sodium levels to avoid rapid overcorrection which can result in osmotic demyelination syndrome (ODS).
Hyponatremia which is defined as serum sodium levels less than 135 mmol/L is often encountered in patients with heart failure. Patients with heart failure develop hyponatremia due to the activation of neurohormonal system leading to decrease in sodium levels. Treatment options for hyponatremia in heart failure, such as water restriction or the use of hypertonic saline with loop diuretics, have limited efficacy. AVP-receptor antagonists increase sodium levels effectively and their use has proven to be effective in correcting sodium levels and improving the outcome of these patients. However, their safety in terms of overcorrecting sodium levels with daily doses of 15–60 mg of tolvaptan is still debatable. Rapid correction of sodium levels in chronic hyponatremia patients has been shown to cause hypernatremia and osmotic demyelination syndrome (ODS) with grave consequences.
We report a case of a 51-year-old male who was admitted with chronic hypervolemic hyponatremia. He developed acute hypernatremia and osmotic demyelination syndrome due to administration of tolvaptan and diuretics. We raise the question of dosing of vasopressin antagonists only after checking daily sodium levels and monitoring urine output.
A 51-year-old male with past medical history of coronary artery disease and peripheral vascular disease presented to the hospital with progressive shortness of breath and bilateral pedal edema. 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. Echocardiogram showed global hypokinesis with an ejection fraction of 10–15%. (Relevant lab values are shown in Table
Trend of pertinent clinical and laboratory data.
Day | Sodium (mEq/L) | Urine output (mL) | Tolvaptan (mg) |
---|---|---|---|
1 | 122 | 2250 | — |
2 | 123 | 2300 | — |
3 | 124 | 2300 | — |
4 | 123 | 2000 | — |
5 | 121 | 2200 | — |
6 | 126 | 7460 | 15 |
7 | 142 | 11950 | 15 |
8 | 167 | 10500 | 30 |
9 | 187 | 4500 | 30 |
10 | 181 | 3800 | — |
Effect of tolvaptan on serum sodium levels.
Effect of tolvaptan on serum sodium and urine output. The dotted rectangle shows the exposure to Tolvaptan from day 6 to day 9.
Hyponatremia is defined as a plasma Na+ concentration <135 mmol/L. This disorder is always almost the result of an increase in circulating AVP and/or increased renal sensitivity to AVP, combined with an intake of free water. Hyponatremia usually reflects the retention of excessive water relative to sodium rather than sodium deficiency alone [
Arginine vasopressin (AVP) is a neuropeptide hormone synthesized in the nuclei of the hypothalamus in neuronal cell bodies and released from the posterior pituitary into the bloodstream. AVP has two different receptor subtypes: V1 and V2 [
Overly rapid correction of hyponatremia (e.g., >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. In susceptible patients, including those with severe malnutrition, alcoholism or advanced liver disease, slower rates of correction may be advisable. Osmotic demyelination syndrome is a serious neurologic disorder which in the well-adjusted intracellular environment becomes relatively hypotonic, with rapid or complete restoration of extracellular osmolality. Water then flows from the intracellular to the extracellular compartment, causing cell volume collapse. In the CNS this can cause a demyelinating lesion [
The present 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. In most hospital settings, warfarin dosing happens after checking daily prothrombin time. Similarly tolvaptan should be administered after checking serum sodium levels for that day and it should not be started as a standing order while initiating treatment.
The authors declare that there is no conflict of interests regarding the publication of the paper.