Cargando…

QT-Prolonging Antibiotics, Serum-to-Dialysate Potassium Gradient, and Risk of Sudden Cardiac Death Among Patients Receiving Maintenance Hemodialysis

RATIONALE & OBJECTIVE: Treatment with certain QT interval-prolonging antibiotics is associated with a higher risk of sudden cardiac death among individuals with hemodialysis-dependent kidney failure. Concurrent exposure to large serum-to-dialysate potassium gradients, which promote large potassi...

Descripción completa

Detalles Bibliográficos
Autores principales: Pun, Patrick H., Assimon, Magdalene M., Wang, Lily, Al-Khatib, Sana M., Brookhart, M. Alan, Weber, David J., Winkelmayer, Wolfgang C., Flythe, Jennifer E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10127135/
https://www.ncbi.nlm.nih.gov/pubmed/37113163
http://dx.doi.org/10.1016/j.xkme.2023.100618
_version_ 1785030400499777536
author Pun, Patrick H.
Assimon, Magdalene M.
Wang, Lily
Al-Khatib, Sana M.
Brookhart, M. Alan
Weber, David J.
Winkelmayer, Wolfgang C.
Flythe, Jennifer E.
author_facet Pun, Patrick H.
Assimon, Magdalene M.
Wang, Lily
Al-Khatib, Sana M.
Brookhart, M. Alan
Weber, David J.
Winkelmayer, Wolfgang C.
Flythe, Jennifer E.
author_sort Pun, Patrick H.
collection PubMed
description RATIONALE & OBJECTIVE: Treatment with certain QT interval-prolonging antibiotics is associated with a higher risk of sudden cardiac death among individuals with hemodialysis-dependent kidney failure. Concurrent exposure to large serum-to-dialysate potassium gradients, which promote large potassium shifts, may augment the proarrhythmic effects of these medications. The primary objective of this study was to examine whether the serum-to-dialysate gradient modifies the cardiac safety of azithromycin, and separately, levofloxacin/moxifloxacin. STUDY DESIGN: Retrospective observational cohort study using a new-user study design. SETTING & POPULATION: Adult in-center hemodialysis patients with Medicare coverage in the US Renal Data System (2007-2017). EXPOSURE: Initiation of azithromycin (or levofloxacin/moxifloxacin) as compared to amoxicillin-based antibiotics (exposure). Serum-to-dialysate potassium gradient (effect modifier). Individual patients could contribute multiple study antibiotic treatment episodes to the analyses. OUTCOMES: Sudden cardiac death (14 days). ANALYTICAL APPROACH: Inverse probability of treatment-weighted survival models to estimate HRs and robust 95% CIs. RESULTS: The azithromycin versus amoxicillin-based antibiotic cohort included 89,379 unique patients with 113,516 azithromycin and 103,493 amoxicillin-based treatment episodes. Azithromycin versus amoxicillin-based antibiotic treatment was associated with a higher risk of sudden cardiac death overall, HR, 1.68; 95% CI, 1.31-2.16. The risk was numerically higher when the baseline serum-to-dialysate potassium gradient was ≥3 mEq/L compared with <3 mEq/L (HR, 2.22; 95% CI, 1.46-3.40 vs HR, 1.43; 95% CI. 1.04-1.96, P(interaction) = 0.07). Analogous analyses in a respiratory fluoroquinolone (levofloxacin/moxifloxacin) versus amoxicillin-based antibiotic cohort with 79,449 unique patients and 65,959 respiratory fluoroquinolone and 103,776 amoxicillin-based treatment episodes yielded similar results. LIMITATIONS: Residual confounding. CONCLUSIONS: Although treatment with azithromycin and, separately, respiratory fluoroquinolones were each associated with a heightened risk of sudden cardiac death, this risk was augmented in the setting of larger serum-to-dialysate potassium gradients. Minimizing the potassium gradient may be an approach to reduce the cardiac risk of these antibiotics.
format Online
Article
Text
id pubmed-10127135
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-101271352023-04-26 QT-Prolonging Antibiotics, Serum-to-Dialysate Potassium Gradient, and Risk of Sudden Cardiac Death Among Patients Receiving Maintenance Hemodialysis Pun, Patrick H. Assimon, Magdalene M. Wang, Lily Al-Khatib, Sana M. Brookhart, M. Alan Weber, David J. Winkelmayer, Wolfgang C. Flythe, Jennifer E. Kidney Med Original Research RATIONALE & OBJECTIVE: Treatment with certain QT interval-prolonging antibiotics is associated with a higher risk of sudden cardiac death among individuals with hemodialysis-dependent kidney failure. Concurrent exposure to large serum-to-dialysate potassium gradients, which promote large potassium shifts, may augment the proarrhythmic effects of these medications. The primary objective of this study was to examine whether the serum-to-dialysate gradient modifies the cardiac safety of azithromycin, and separately, levofloxacin/moxifloxacin. STUDY DESIGN: Retrospective observational cohort study using a new-user study design. SETTING & POPULATION: Adult in-center hemodialysis patients with Medicare coverage in the US Renal Data System (2007-2017). EXPOSURE: Initiation of azithromycin (or levofloxacin/moxifloxacin) as compared to amoxicillin-based antibiotics (exposure). Serum-to-dialysate potassium gradient (effect modifier). Individual patients could contribute multiple study antibiotic treatment episodes to the analyses. OUTCOMES: Sudden cardiac death (14 days). ANALYTICAL APPROACH: Inverse probability of treatment-weighted survival models to estimate HRs and robust 95% CIs. RESULTS: The azithromycin versus amoxicillin-based antibiotic cohort included 89,379 unique patients with 113,516 azithromycin and 103,493 amoxicillin-based treatment episodes. Azithromycin versus amoxicillin-based antibiotic treatment was associated with a higher risk of sudden cardiac death overall, HR, 1.68; 95% CI, 1.31-2.16. The risk was numerically higher when the baseline serum-to-dialysate potassium gradient was ≥3 mEq/L compared with <3 mEq/L (HR, 2.22; 95% CI, 1.46-3.40 vs HR, 1.43; 95% CI. 1.04-1.96, P(interaction) = 0.07). Analogous analyses in a respiratory fluoroquinolone (levofloxacin/moxifloxacin) versus amoxicillin-based antibiotic cohort with 79,449 unique patients and 65,959 respiratory fluoroquinolone and 103,776 amoxicillin-based treatment episodes yielded similar results. LIMITATIONS: Residual confounding. CONCLUSIONS: Although treatment with azithromycin and, separately, respiratory fluoroquinolones were each associated with a heightened risk of sudden cardiac death, this risk was augmented in the setting of larger serum-to-dialysate potassium gradients. Minimizing the potassium gradient may be an approach to reduce the cardiac risk of these antibiotics. Elsevier 2023-02-15 /pmc/articles/PMC10127135/ /pubmed/37113163 http://dx.doi.org/10.1016/j.xkme.2023.100618 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Research
Pun, Patrick H.
Assimon, Magdalene M.
Wang, Lily
Al-Khatib, Sana M.
Brookhart, M. Alan
Weber, David J.
Winkelmayer, Wolfgang C.
Flythe, Jennifer E.
QT-Prolonging Antibiotics, Serum-to-Dialysate Potassium Gradient, and Risk of Sudden Cardiac Death Among Patients Receiving Maintenance Hemodialysis
title QT-Prolonging Antibiotics, Serum-to-Dialysate Potassium Gradient, and Risk of Sudden Cardiac Death Among Patients Receiving Maintenance Hemodialysis
title_full QT-Prolonging Antibiotics, Serum-to-Dialysate Potassium Gradient, and Risk of Sudden Cardiac Death Among Patients Receiving Maintenance Hemodialysis
title_fullStr QT-Prolonging Antibiotics, Serum-to-Dialysate Potassium Gradient, and Risk of Sudden Cardiac Death Among Patients Receiving Maintenance Hemodialysis
title_full_unstemmed QT-Prolonging Antibiotics, Serum-to-Dialysate Potassium Gradient, and Risk of Sudden Cardiac Death Among Patients Receiving Maintenance Hemodialysis
title_short QT-Prolonging Antibiotics, Serum-to-Dialysate Potassium Gradient, and Risk of Sudden Cardiac Death Among Patients Receiving Maintenance Hemodialysis
title_sort qt-prolonging antibiotics, serum-to-dialysate potassium gradient, and risk of sudden cardiac death among patients receiving maintenance hemodialysis
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10127135/
https://www.ncbi.nlm.nih.gov/pubmed/37113163
http://dx.doi.org/10.1016/j.xkme.2023.100618
work_keys_str_mv AT punpatrickh qtprolongingantibioticsserumtodialysatepotassiumgradientandriskofsuddencardiacdeathamongpatientsreceivingmaintenancehemodialysis
AT assimonmagdalenem qtprolongingantibioticsserumtodialysatepotassiumgradientandriskofsuddencardiacdeathamongpatientsreceivingmaintenancehemodialysis
AT wanglily qtprolongingantibioticsserumtodialysatepotassiumgradientandriskofsuddencardiacdeathamongpatientsreceivingmaintenancehemodialysis
AT alkhatibsanam qtprolongingantibioticsserumtodialysatepotassiumgradientandriskofsuddencardiacdeathamongpatientsreceivingmaintenancehemodialysis
AT brookhartmalan qtprolongingantibioticsserumtodialysatepotassiumgradientandriskofsuddencardiacdeathamongpatientsreceivingmaintenancehemodialysis
AT weberdavidj qtprolongingantibioticsserumtodialysatepotassiumgradientandriskofsuddencardiacdeathamongpatientsreceivingmaintenancehemodialysis
AT winkelmayerwolfgangc qtprolongingantibioticsserumtodialysatepotassiumgradientandriskofsuddencardiacdeathamongpatientsreceivingmaintenancehemodialysis
AT flythejennifere qtprolongingantibioticsserumtodialysatepotassiumgradientandriskofsuddencardiacdeathamongpatientsreceivingmaintenancehemodialysis