Treatment with azithromycin or respiratory fluoroquinolones is associated with increased risks of sudden cardiac death in patients on hemodialysis, particularly when the serum-to-dialysate potassium gradient is large.
According to the 2007-2017 US Renal Data System, 113,516 azithromycin and 103,493 amoxicillin treatment episodes occurred in 89,379 patients receiving hemodialysis. The risk for sudden cardiac death within 14 days was a significant 68% higher with azithromycin vs amoxicillin treatment, Jennifer E. Flythe, MD, MPH, of the University of North Carolina Kidney Center in Chapel Hill, North Carolina, and colleagues reported in Kidney Medicine. The larger the potassium gradient during hemodialysis, the higher the risks. A serum-to-dialysate potassium gradient of 3 mEq/L or more was significantly associated with a 2.2-fold increased risk for sudden cardiac death, whereas a gradient of less than 3 mEq/L was significantly associated with a 1.4-fold increased risk.
Similar cardiac risks were found with respiratory fluoroquinolones. Investigators compared 65,959 levofloxacin/moxifloxacin and 103,776 amoxicillin treatment episodes in 79,449 patients on hemodialysis. The risk for sudden cardiac death within 14 days was a significant 72% higher with respiratory fluoroquinolones compared with amoxicillin, the investigators reported. Sudden cardiac death risks were increased 2.2- and 1.5-fold when potassium gradients were 3 mEq/L or higher and lower than 3 mEq/L, respectively.
Azithromycin, levofloxacin, and moxifloxacin prolong the QT interval, whereas amoxicillin does not, Dr Flythe’s team explained. Use of these QT-prolonging antibiotics adds to the risks patients already have due to disordered potassium homeostasis. They noted that rapid and excessive potassium removal during dialysis can lead to large shifts linked to EKG risk markers for cardiac arrest, including QT interval prolongation and QT dispersion.
Both lower dialysate potassium concentrations and higher serum potassium levels can contribute to higher serum-to-dialysate potassium gradient levels, Dr Flythe’s team explained. Hyperkalemia has a known association with sudden death, so clinicians should aim to reduce elevated serum potassium levels, such as with potassium-binding agents, they suggested. Clinicians should also avoid dialysate potassium less than 2 mEq/L while patients are being treated with QT-prolonging antibiotics.
“Selecting antibiotics that do not prolong the QT interval when appropriate and minimizing the potassium gradient during the course of QT-prolonging antibiotic therapy may be an important steps to reducing the already high risk of SCD borne by patients receiving maintenance hemodialysis,” the investigators wrote.
In an accompanying editorial, Jonathan S. Chávez-Iñiguez, MSc, MD, of Hospital Civil de Guadalajara Fray Antonio Alcalde in Guadalajara, Mexico, and Jochen G. Raimann, MD, MPH, PhD, of Renal Research Institute in New York, New York, noted that sudden cardiac death is the most frequent cause of death in patients treated with dialysis, and occurs most frequently toward the end of the long interdialytic interval. The current study lacked information on which dialysis day sudden cardiac death occurred, which is a limitation.
“A review of electrocardiograms before the use of drugs that may prolong the QT interval is advised to identify patients with preexisting borderline or prolonged QT-intervals,” the editorialists wrote. “Furthermore, individualization of dialysate composition, particularly of the potassium concentration, should be considered as an approach to mitigate large dialysate-to-potassium gradients, while providing adequate treatment for hyperkalemia.”
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Pun PH, Assimon MM, Wang L, et al. QT-prolonging antibiotics, serum-to-dialysate potassium gradient, and risk of sudden cardiac death among patients receiving maintenance hemodialysis. Kidney Med. 15;5(5):100618. doi:10.1016/j.xkme.2023.100618
Chávez-Iñiguez JS, Raimann JG. Individualization of serum-to-dialysate potassium concentrations to reduce the risk of sudden cardiac death conferred by QT-prolonging antibiotics in patients receiving hemodialysis. Kidney Med. Published online April 11, 2023. doi:10.1016/j.xkme.2023.100638