HDCN Article Review/Hyperlink

Alappan R, Perazella MA, Buller GK

Hyperkalemia in hospitalized patients treated with trimethoprim-sulfamethoxazole

Ann Intern Med (Feb) 124:316-320 1996

Trimethoprim-Sulfamethoxazole is frequently prescribed because of its spectrum of antimicrobial activity and low cost. Hyperkalemia is a well known result of high dose trimethoprim therapy in patient with acquired immune deficiency syndrome. A few cases of hyperkalemia have been reported in patients taking standard doses of trimethoprim-sulfamethoxazole. Alappan and colleagues did a prospective chart review of 105 patients with various infections. Eighty patients treated with standard doses of trimethoprim-sulfamethoxazole were the treatment group and 25 patients treated with other antibiotics constituted the control group. They found that patients treated with trimethoprim-sulfamethoxazole had significantly higher serum potassium concentrations than those treated with other antibiotics. Surprisingly, more than 60 % treated with trimethoprim-sulfamethoxazole developed a serum potassium greater than 5 mmol/L. More than 20 % had serum potassium measurements greater than 5.5 mmol/L. Peak serum potassium concentrations occurred after 4 days of treatment with trimethoprim-sulfamethoxazole. Decreased renal function was the only clinical variable associated with the effect. The authors postulate that the structural similarity of trimethoprim to the potassium-sparing diuretic, amiloride, is responsible for an amiloride like effect on distal tubular potassium reabsorption.

Comment: This paper reports an important adverse drug event. Although the potential for hyperkalemia in patients treated with high dose trimethoprim is well known, the frequent incidence of this phenomenon in hospitalized patients treated with usual doses of trimethoprim- sulfamethoxazole is surprising. Potentially life threatening hyperkalemia could result in patients taking other drugs known to increase the serum potassium, such as nonsteroidal anti-inflammatory drugs and angiotensin converting enzyme inhibitors. Further, renal insufficiency and Type IV renal tubular acidosis could enhance the hyperkalemia. Clinicians should recognize this drug induced electrolyte abnormality and use trimethoprim-sulfamethoxazole with caution in these high risk patients. (George R. Aronoff, M.D., University of Louisville, KY)