Trimethoprim-associated hyperkalaemia: a systematic review and meta-analysis.

INTRODUCTION: Trimethoprim is structurally similar to potassium-sparing diuretics and may induce hyperkalaemia. The prevalence and the factors that predispose to trimethoprim-associated hyperkalaemia have never been extensively addressed. METHODS: A literature search with no date or language limits was carried out using the National Library of Medicine, Embase and Web of Science in March and repeated during August 2021. The principles underlying the Economic and Social Research Council guidance on the conduct of synthesis and the PRISMA guidelines were employed. For the analysis, we retained reports including ≥10 subjects on treatment with trimethoprim, which addressed the possible occurrence of hyperkalaemia. RESULTS: Eighteen reports were retained for the final analysis. The pooled prevalence of potassium value >5.0 mmol/L, >5.5 mmol/L and >6.0 mmol/L or symptomatic, was, respectively, 22%, 10% and 0.2%. The analysis disclosed that the risk of trimethoprim-associated hyperkalaemia is dose-related and enhanced by drugs with known hyperkalaemic potential including potassium-sparing diuretics, renin-angiotensin-aldosterone system inhibitors, ß-blockers and non-steroidal anti-inflammatory agents. Poor kidney function also increased the tendency towards hyperkalaemia. The time to onset of hyperkalaemia was generally 1 week or less after starting trimethoprim. CONCLUSIONS: The present analysis documents the hyperkalaemic potential of trimethoprim, a widely prescribed drug that was introduced more than 50 years ago. Clinicians must recognize patients at risk of trimethoprim-associated hyperkalaemia.

Trimethoprim-associated electrolyte and acid-base abnormalities.

INTRODUCTION: The antimicrobial trimethoprim is structurally related to potassium-sparing diuretics and may consequently lead to derangements in electrolyte and acid-base balance. Since no report so far analyzed the literature documenting individual cases with electrolyte and acid-base derangements induced by trimethoprim, a systematic review was carried out. EVIDENCE ACQUISITION: We retained 53 reports documenting 68 cases (42 males and 26 females 23 to 96 years of age) of electrolyte or acid-base derangements occurring on trimethoprim for about 5 days. EVIDENCE SYNTHESIS: One hundred five electrolyte imbalances were detected in the 68 patients: hyperkalemia (>5.0 mmol/L) in 62 (91%), hyponatremia (<135 mmol/L) in 29 (43%) and metabolic acidosis (pH<7.38 and bicarbonate <19 mmol/L) in 14 (21%) cases. Following possible predisposing factors for electrolyte and acid-base abnormalities were found in 54 (79%) patients: high-dose trimethoprim, comedication with drugs that have been associated with electrolyte and acid-base derangements, preexisting kidney disease, age ≥80 years and diabetes mellitus. CONCLUSIONS: High-dose trimethoprim, comedicated with drugs that have been associated with electrolyte and acid-base derangements, poor kidney function, age ≥80 years and diabetes mellitus predispose to trimethoprim-associated electrolyte and acid-base abnormalities. Clinicians must recognize patients at risk, possibly avoid drug combinations that may worsen the problem and monitor the laboratory values.