Journals | Policy | Permission

Journal of Medical Cases

Case Report

Volume 5, Number 5, May 2014, pages 283-284

Severe Symptomatic Hyponatremia Induced by Trimethoprim-Sulfamethoxazole

Hyponatremia secondary to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is an uncommon complication of treatment with trimethoprim-sulfamethoxazole (TMP-SMX). TMP-SMX acts as a K-sparing diuretic, if this is the case, hyponatremia would be inevitable [1, 2]. Estimation of the occurrence of hyponatremia during TMP-SMX is 26.4%, which is more frequent than reported previously [3, 4]. The risk of hyponatremia seems to be greatest in elderly population, other comorbidities and is dose dependent [5, 6]. I described a case of an 88-year-old female who presents with malaise and confusion caused by TMP-SMX induced hyponatremia due to SIADH.

This is an 88-year-old female presented to the emergency department with a 24-h history of malaise and progressive confusion. Three days prior to this admission, she had been started on TMP-SMX 800/160 mg twice a day for an urinary tract infection. The daughter reported that she became progressively confused and had difficulty performing simple tasks.

She has history of essential hypertension treated with lisinopril 10 mg daily, coronary artery disease on metoprolol 25 mg BID. The week before previous to her admission, she was feeling dizzy and with nauseas and was found to have an UTI, she was started on TMP-SMX and the day before to be hospitalized she had a follow-up at the adult primary care clinic where her sodium level was found to be normal 142 mmol/L (136 - 145 mmol/L). Upon admission she was afebril but confuse with normal vital signs. She appeared euvolemic, with no signs of dehydration or congestion. Neurologic examination was normal except for general debilitation. Significant laboratory findings included sodium of 123 mmol/L (136 - 145 mmol/L), potassium of 4.2 mmol/L (3.5 - 4.5 mmol/L), chloride 100 mg/dL (98 - 106 mmol/L), blood urea nitrogen of 19 mg/dL (6 - 19 mg/dL), creatinine 1 mg/dL µmol/L (0.6 - 1.2 mg/dL), glucose of 106 mg/dL (70 - 100 mg/dL), a uric acid of 5 mg/dL (< 7 mg/dL) and a serum osmolarity of 256 mOsm/ L (285 - 295 mOsm/L). Urine sodium and urine osmolarity were elevated, 136 mEq/L, and 470 mosm/L, respectively. A CT of the head was normal. An AM cortisol level, thyroid-stimulating hormone (TSH) and free thyroxine levels were within normal limits. A TMP-SMX pill count confirmed compliance with the drug regimen without evidence of overdose.

The criteria for the syndrome of inappropriate secretion of ADH were fulfilled and other causes of SIADH were excluded.

On the day of admission, TMP-SMX was discontinued and the patient was treated with 1 L of intravenous 0.9% sodium chloride and ceftriaxone for UTI. Approximately 24 h after admission the patient’s serum sodium decreased to 122 mmol/L (136 - 145 mmol/L) and fluids were restricted to 1,200 mL/day. Her mental status improved over the next 48 h and she was discharged 4 days after her admission with a sodium level of 137 mmol/L (136 - 145 mmol/L).

A follow-up sodium after 7 days of her discharge was 140 mmol/L.

The present case reported emphasized the need for greater awareness of the development of this serious and potentially fatal complication in association with TMP-SMX therapy. This case has shown that the onset of TMP-SMX induced hyponatremia or SIADH ranges from the first days after the therapy has been started. Potential risk factors for SIADH due to TMP-SMX included advanced age, concomitant use of medications known to cause SIADH or hyponatremia, and possibly, higher TMP-SMX doses. Therefore, a high level of suspicion, close monitoring of serum sodium concentration particularly in elderly patients pretreatment may reduce the incidence of this serious and likely, rare, adverse effect.

1. Velazquez H, Perazella MA, Wright FS, Ellison DH. Renal mechanism of trimethoprim-induced hyperkalemia. Ann Intern Med. 1993;119(4):296-301.
   doi pubmed
2. Mori H, Kuroda Y, Imamura S, Toyoda A, Yoshida I, Kawakami M, Tabei K. Hyponatremia and/or hyperkalemia in patients treated with the standard dose of trimethoprim-sulfamethoxazole. Intern Med. 2003;42(8):665-669.
   doi pubmed
3. Jick H, Derby LE. A large population-based follow-up study of trimethoprim-sulfamethoxazole, trimethoprim, and cephalexin for uncommon serious drug toxicity. Pharmacotherapy. 1995;15(4):428-432.
   pubmed
4. Smilack JD. Trimethoprim-sulfamethoxazole. Mayo Clin Proc. 1999;74(7):730-734.
   doi pubmed
5. Eiam-Ong S, Kurtzman NA, Sabatini S. Studies on the mechanism of trimethoprim-induced hyperkalemia. Kidney Int. 1996;49(5):1372-1378.
   doi pubmed
6. Fonseca PD, Moura TF, Ferreira KT. The effect of trimethoprim on sodium transport across the frog skin epithelium. Eur J Pharmacol. 1991;207(4):337-343.
   doi

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Journal of Medical Cases is published by Elmer Press Inc.