Demetra Tsapepas1, Mariana Chiles2, Revekka Babayev2, Maya K Rao2, Manasvi Jaitly3, David Salerno4, Sumit Mohan5. 1. Department of Pharmacy, New York-Presbyterian Hospital, Columbia University Medical Center, New York, NY; Division of Abdominal Transplantation, Department of Surgery, Columbia University, New York, NY. 2. Division of Nephrology, Department of Medicine, Columbia University, New York, NY. 3. Department of Medicine, Claxton Hepburn Medical Center, Ogdensburg, NY. 4. Department of Pharmacy, New York-Presbyterian Hospital, Columbia University Medical Center, New York, NY. 5. Division of Nephrology, Department of Medicine, Columbia University, New York, NY; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY. Electronic address: sm2206@cumc.columbia.edu.
Abstract
BACKGROUND: Trimethoprim-sulfamethoxazole (TMP-SMX) is a commonly prescribed antibiotic used at high doses for treatment of pneumocystis pneumonia and other infections. Trimethoprim is structurally related to the potassium-sparing diuretic amiloride and has been associated with hyperkalemia and hyponatremia through blocking of epithelial sodium channels in the distal nephron. The incidence of hyponatremia in hospitalized patients treated with high-dose TMP-SMX is unknown. METHODS: We performed a single-center retrospective chart review of all hospitalized patients who received high-dose TMP-SMX (n = 235) from January 2012 to July 2014. Patients with congestive heart failure, cirrhosis, estimated glomerular filtration rate <30 mL/min/1.73 m2, baseline hyponatremia, and those on other medications associated with hyponatremia were excluded. Hyponatremia was defined as a serum sodium level <136 mEq/L. RESULTS: Analysis was restricted to 76 unique patients who received more than 8 mg/kg/d of TMP for ≥3 days. Mean starting serum sodium at time of TMP-SMX initiation was 138.4 ± 2.1 mEq/L. Fifty-five patients (72.3%) developed hyponatremia while on therapy, of which 43.6% (n = 24) were cases of serum sodium <130 mEq/L. Mean sodium at the time of nadir was 131.6 ± 5.1 mEq/L. Hyponatremia was noted, on average, 5.5 days after initiation of therapy, with more severe hyponatremia development among African American patients. Urine sodium concentrations were available for 40.0% (22/55) of incident hyponatremia cases, with mean urinary sodium of 104.8 ± 55.9 mEq/L. Hyponatremia often resolved within 3 weeks of drug discontinuation. CONCLUSIONS: There is a high incidence (72.3%) of hyponatremia associated with the use of high-dose TMP-SMX among hospitalized patients. This is an overlooked and potentially reversible cause of hyponatremia.
BACKGROUND:Trimethoprim-sulfamethoxazole (TMP-SMX) is a commonly prescribed antibiotic used at high doses for treatment of pneumocystis pneumonia and other infections. Trimethoprim is structurally related to the potassium-sparing diuretic amiloride and has been associated with hyperkalemia and hyponatremia through blocking of epithelial sodium channels in the distal nephron. The incidence of hyponatremia in hospitalized patients treated with high-dose TMP-SMX is unknown. METHODS: We performed a single-center retrospective chart review of all hospitalized patients who received high-dose TMP-SMX (n = 235) from January 2012 to July 2014. Patients with congestive heart failure, cirrhosis, estimated glomerular filtration rate <30 mL/min/1.73 m2, baseline hyponatremia, and those on other medications associated with hyponatremia were excluded. Hyponatremia was defined as a serum sodium level <136 mEq/L. RESULTS: Analysis was restricted to 76 unique patients who received more than 8 mg/kg/d of TMP for ≥3 days. Mean starting serum sodium at time of TMP-SMX initiation was 138.4 ± 2.1 mEq/L. Fifty-five patients (72.3%) developed hyponatremia while on therapy, of which 43.6% (n = 24) were cases of serum sodium <130 mEq/L. Mean sodium at the time of nadir was 131.6 ± 5.1 mEq/L. Hyponatremia was noted, on average, 5.5 days after initiation of therapy, with more severe hyponatremia development among African American patients. Urine sodium concentrations were available for 40.0% (22/55) of incident hyponatremia cases, with mean urinary sodium of 104.8 ± 55.9 mEq/L. Hyponatremia often resolved within 3 weeks of drug discontinuation. CONCLUSIONS: There is a high incidence (72.3%) of hyponatremia associated with the use of high-dose TMP-SMX among hospitalized patients. This is an overlooked and potentially reversible cause of hyponatremia.
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