Hyponatremia With Intravenous Sulfamethoxazole/Trimethoprim in Children

Ann Pharmacother. 2020 Apr;54(4):351-358. doi: 10.1177/1060028019887919. Epub 2019 Nov 6.

Abstract

Background: Intravenous (IV) sulfamethoxazole/trimethoprim (SMX/TMP) has been associated with hyponatremia in adults. Objective: The primary objective was to identify the number of patients with a serum sodium <135 mEq/L. Secondary objectives between the hyponatremic versus nonhyponatremic groups included demographic comparisons, median serum sodium concentrations, SMX/TMP cumulative dose, number of diuretics, and other medications causing hyponatremia. Methods: This was a retrospective study of children <18 years receiving IV SMP/TMX. Comparisons were conducted via Mann-Whitney-Wilcoxon and Mantel-Haenszel χ2 tests with an a priori P value <0.05. Results: Sixty-one patients received 66 total courses; 20 courses (30.3%) were associated with hyponatremia with a decrease in the median nadir serum sodium concentration of 133 and 138 mEq/L in the hyponatremic and nonhyponatremic groups, respectively (P<0.001). The median age (interquartile range) was lower in the hyponatremic versus nonhyponatremic group, but this was not statistically significant: 0.6 (0.1-5.5) versus 3.9 (0.3-11.0) years; P=0.077. There was no significant difference in the median cumulative dose (mg/kg) between groups; P=0.104. In addition, there was a significant difference in the number of children in the hyponatremic versus nonhyponatremic groups receiving diuretics (16 [80.0%] vs 23 [50.0%], P=0.023) and other medications that cause hyponatremia (7 [35.0%] vs 5 [10.9%], P=0.034), respectively. Furosemide was noted to be the medication most associated with hyponatremia. Conclusion and Relevance: Approximately one-third administered IV SMX/TMP developed hyponatremia. Concomitant furosemide administration was one of the most common risk factors. Clinicians should be aware of this potential adverse event when initiating IV SMX/TMP in children.

Keywords: child; hyponatremia; sulfamethoxazole; trimethoprim.

MeSH terms

  • Administration, Intravenous
  • Adult
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / adverse effects*
  • Anti-Bacterial Agents / therapeutic use
  • Child
  • Child, Preschool
  • Dose-Response Relationship, Drug
  • Female
  • Furosemide / administration & dosage
  • Furosemide / adverse effects
  • Furosemide / therapeutic use
  • Humans
  • Hyponatremia / chemically induced*
  • Hyponatremia / epidemiology
  • Infant
  • Male
  • Retrospective Studies
  • Trimethoprim, Sulfamethoxazole Drug Combination / administration & dosage
  • Trimethoprim, Sulfamethoxazole Drug Combination / adverse effects*
  • Trimethoprim, Sulfamethoxazole Drug Combination / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Furosemide
  • Trimethoprim, Sulfamethoxazole Drug Combination