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)