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Hyperkalemia in Hospitalized Patients Treated with Trimethoprim-Sulfamethoxazole

Rajendran Alappan, MD; Mark A. Perazella, MD; and Gregory K. Buller, MD
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From St. Mary's Hospital, Waterbury, Connecticut, and Yale University School of Medicine, New Haven, Connecticut. Acknowledgments: The authors thank Richard Spierto, John Concato, MD, Mary Kinney, and Ali Abu-Alfa, MD, for technical support. Requests for Reprints: Mark A. Perazella, MD, Section of Nephrology, Department of Medicine, Yale University School of Medicine, LMP2071, 333 Cedar Street, New Haven, CT 06510. Current Author Addresses: Dr. Alappan: Yale Primary Care Program, Department of Medicine, St. Mary's Hospital, 56 Franklin Street, Waterbury, CT 06706.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1996;124(3):316-320. doi:10.7326/0003-4819-124-3-199602010-00006
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Objective: To determine the effect of standard-dose trimethoprim-sulfamethoxazole on serum potassium concentration in hospitalized patients.

Design: Prospective chart review.

Setting: Community-based teaching hospital.

Patients: 105 patients with various infections were hospitalized and treated. Eighty patients treated with standard-dose trimethoprim-sulfamethoxazole (trimethoprim, less than equals 320 mg/d; sulfamethoxazole, less than equals 1600 mg/d) composed the treatment group; 25 patients treated with other antibiotic agents served as the control group.

Measurements: Serum sodium, potassium, and chloride concentrations; serum carbon dioxide content; anion gap; blood urea nitrogen level; and serum creatinine level.

Results: The serum potassium concentration in the treatment group (mean ±SD) was 3.89 ± 0.46 mmol/L (95% CI, 3.79 to 3.99 mmol/L), and it increased by 1.21 mmol/L (CI, 1.09 to 1.32 mmol/L) 4.6 ± 2.2 days after trimethoprim-sulfamethoxazole therapy was initiated. Blood urea nitrogen levels increased from 7.92 ± 5.7 mmol/L (CI, 6.67 to 9.16 mmol/L) to 9.2 ± 5.8 mmol/L (CI, 7.9 to 10.5 mmol/L), and serum creatinine levels increased from 102.5 ± 49.5 µmol/L (CI, 91.4 to 113.6 µmol/L) to 126.1 ± 70.7 µmol/L (CI, 110.3 to 141.9 µmol/L). Patients with a serum creatinine level of 106 µmol/L (1.2 mg/dL) or more developed a higher peak potassium concentration (5.37 ± 0.59 mmol/L [CI, 5.15 to 5.59 mmol/L]) than patients with a serum creatinine level of less than 106 µmol/L (4.95 ± 0.48 mmol/L [CI, 4.80 to 5.08 mmol/L]). Patients with diabetes had a slightly higher peak potassium concentration (5.14 ± 0.45 mmol/L [CI, 4.93 to 5.35 mmol/L]) than did patients without diabetes (5.08 ± 0.59 mmol/L [CI, 4.93 to 5.23 mmol/L]), but the difference was not statistically significant. The serum potassium concentration in the control group was 4.33 ± 0.45 mmol/L (CI, 4.15 to 4.51 mmol/L), and it decreased nonsignificantly over 5 days of therapy.

Conclusions: Standard-dose trimethoprim-sulfamethoxazole therapy used to treat various infections leads to an increase in serum potassium concentration. A peak serum potassium concentration greater than 5.0 mmol/L developed in 62.5% of patients; severe hyperkalemia (peak serum potassium concentration more than equals 5.5 mmol/L) occurred in 21.2% of patients. Patients treated with standard-dose trimethoprim-sulfamethoxazole should be monitored closely for the development of hyperkalemia, especially if they have concurrent renal insufficiency (serum creatinine level more than equals 106 µmol/L).


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Figure 2.
Peak serum potassium concentrations (mean ± SE) in the various subgroups of patients treated with trimethoprim-sulfamethoxazole.n

A statistically significant peak potassium concentration was seen only in patients with a baseline serum creatinine level of 106 µmol/L (1.2 mg/dL) or more, regardless of the presence or absence of diabetes mellitus. Cr = creatinine; K+ = potassium; = number of patients.

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Grahic Jump Location
Figure 1.
Baseline and peak daily serum potassium concentrations (mean ± SE) between the group treated with trimethoprim-sulfamethoxazole (TMP-SMX) and the control group.nPP

A statistically significant increase in potassium concentration occurred in the treatment group. K+ = potassium; = number of patients. * < 0.01; ** < 0.05.

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