Hyponatremia and heart failure: the overlooked piece of the puzzle

An 83-year-old woman was admitted to our hospital with complaints of dyspnea and bilateral lower extremity edema. The admission electrocardiogram showed atrial fibrillation with a heart rate of 80 beats/min. An echocardiogram showed a left ventricular ejection fraction of 50% and grade 3 diastolic dysfunction. The patient was initially continued on her outpatient medical regimen (aspirin, digoxin, irbesartan/hydrochlorothiazide, gliclazide, acarbose, and alendronate sodium), except for the fact that aspirin, gliclazide, acarbose, and digoxin were withheld and insulin, enoxaparin sodium, and intravenous furosemide were started. After her physical signs (edema, inspiratory crackles, and wheezing) and symptoms were resolved, she was discharged from the hospital on irbesartan/hydrochlorothiazide 150/12.5 mg 1×1, furosemide 40 mg 1×1, rivaroxaban 15 mg 1×1, metoprolol 50 mg 2×1, and insulin.

Three days after hospital discharge, she presented to the emergency department with malaise, fatigue, and slurred speech. Her initial vital signs were within normal limits. Laboratory results revealed 2 mg/dL of creatinine, 117 mmol/L of sodium, 5.8 mmol/L of potassium, 89 mmol/L of chloride, 8.9 mg/ dL of calcium, 4.2 g/dL of albumin, and 256 mg/dL of glucose. The other calculated parameters were as follows: corrected serum sodium, 120.7 mmol/L; measured serum osmolality, 276 mOsm/kg (reference range 275-295 mOsm/kg); and effective serum osmolarity, 274 mOsm/kg. Her urine sodium concentration was 26 mmol/L and specific gravity was 1.011. Arterial blood gas analysis revealed pH of 7.407, PaCO2 of 35 mm Hg, and Pa02 of 79.3 mm Hg.

What is the possible cause of hyponatremia, and how it should be treated?

a) Pseudohyponatremia, no treatment

b) Hypertonic hyponatremia, intravenous fluid therapy

c) Thiazide induced hyponatremia, cessation of drug

d) Drug induced hyponatremia+hypotonic hyponatremia, fluid restriction+drug cessation

e) Hypovolemic hyponatremia, intravenous fluid therapy

Answer: D. Drug induced hyponatremia+hypotonic hypontremia, fluid restriction+drug cessation

Hyponatremia may occur with a high, low, or normal serum osmolality. Pseudohyponatremia is an artifact of measurement as a result of interference between abnormally high concentrations of lipids or proteins and sodium. In pseudohyponatremia, the serum osmolality is usually normal (1).

In hypertonic hyponatremia, the serum osmolality is more than 295 mOsm/kg. Hypertonic hyponatremia occurs when the plasma contains an osmotically active substance such as mannitol or excess glucose. The serum Na concentration falls approximately by 1.6 mEq/L for every 100 mg/dL rise in the serum glucose concentration above the normal concentration (1).

Hypovolemic hyponatremia is associated with a deficit in serum sodium and total body water. Sodium loss is more prominent than water loss. As sodium deficits can be due to renal or extrarenal losses, urine sodium may be <30 mmol/L or >30 mmol/L, respectively (2).

In chronic heart failure, the incidence of hyponatremia is approximately 20-30%, and loop diuretics have less potential for causing hyponatremia than thiazides (2). In our patient, we considered hypotonic hyponatremia (effective serum osmolarity< 275 mOsm/kg, urine sodium concentration<30 mmol/L, and high urine osmolality>1.003) as a consequence of water retention. Despite fluid restriction, ultrafiltration, and intravenous diuretic therapy, hyponatremia did not resolve. After reviewing the relevant literature, we did not find any possible offending drug other than thiazide or loop diuretics that could be associated with hyponatremia. However, according to 4766 reports from the FDA and social media, 4619 people reported having side effects when taking rivaroxaban. Among them, 8 (0.17%) had hyponatremia (3). As in our case, hyponatremia was found among those who take rivaroxaban, especially for those who are females, more than 60 years old, have been taking the drug for <1 month, also take medication hydrochlorothiazide, and have atrial fibrillation/flutter. After the cessation of rivaroxaban, serum sodium levels continuously increased, and the patient was discharged from the hospital with a serum sodium level of 136 mmol/L. At the two-week followup, her serum sodium level was 138 mmol/L.

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©Copyright 2015 by Turkish Society of Cardiology - Available online at www.anatoljcardiol.com

DOI:10.5152/AnatolJCardiol.2015.6743

References

Reference

1. Buffington MA, Abreo K. Hyponatremia: A Review. J Intensive Care Med 2015 Jan 14. Epub ahead of print. [CrossRef]

2. Verbrugge FH, Steels P, Grieten L, Nijst P, Tang WH, Mullens W. Hyponatremia in acute decompensated heart failure: depletion versus dilution. J Am Coll Cardiol 2015; 65: 480-92. [CrossRef]

3. Could Xarelto cause hyponatremia. Available from. http://ehealthme.com/ ds/xarelto/hyponatremia. [last accessed on 2015 Sep 4]