hyponatremia associated with medication and RTA

The patient presented with decompensated heart failure causing both cardiogenic shock and pulmonary edema. Over the course of the patient’s ICU stay, she improved with diuresis; however, she has developed hyponatremia and hyperkalemia. Although a number of conditions can cause these electrolyte abnormalities, it is prudent to review the patient’s medications to ensure medications are not causing or contributing to the problem.

All of the medications listed are associated with the development of hyponatremia. Unfractionated heparin is a known inhibitor of aldosterone production by the zona glomerulosa of the adrenal glands. Heparin has been associated with the development of both hyponatremia and hyperkalemia, most commonly seen within 1 to 3 days of initiation. Of note, the patient has also developed nonanion gap acidosis, which should raise suspicion for a renal tubular acidosis (11 RTA) that can be seen in the setting of aldosterone deficiency.

Vasopressin via continuous IV infusion is a medication commonly used in adults who are critically ill to increase BP via stimulation of arginine vasopressin 1A receptors in the vasculature. However exogenous vasopressin also can stimulate arginine vasopressin type 2 receptors in the kidney, resulting in a concentration of the urine via increased free water reabsorption. Use of vasopressin in the setting of shock has been associated with the development of new hyponatremia; however, it is not associated with the development of hyperkalemia, and the rate of hyponatremia in adults who are critically ill may be as low as 0.3%, as seen in the Vasopressin and Septic Shock Trial.

Many advances have been made in the care of patients with heart failure over the past decade, including the use of sodium-glucose cotransporter 2 (SGLT-2) inhibiting medications such as empagliflozin to decrease the risk of hospitalization and cardiovascular death. SGLT-2 inhibitors decrease the reabsorption of sodium and glucose in the proximal tubules, increasing sodium excretion. SGLT-2 inhibitors are only rarely associated with hyponatremia and seem to be protective against the development of hyperkalemia.

Thiazide diuretics, such as chlorothiazide, inhibit the sodium-chloride cotransporter in the renal distal convoluted tubule, which decreases sodium reabsorption. These types of diuretics can cause hyponatremia and hypokalemia rather than hyperkalemia as seen in this case.12345

Footnotes

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  3. Norman NE, Sneed AM, Brown C, et al. Heparin-induced hyponatremia. Ann Pharmacother. 2004;38(3):404-407. PubMed ↩

  4. Oster JR, Singer I, Fishman LM. Heparin-induced aldosterone suppression and hyperkalemia. Am J Med. 1995;98(6):575-586. PubMed ↩

  5. Wilcox CS. Antihypertensive and renal mechanisms of SGLT2 (sodium-glucose linked transporter 2) inhibitors. Hypertension. 2020;75(4):894-901. PubMed ↩