Independent correlates of vancomycin steady-state trough concentration among patients undergoing combined CABG and valve surgery: observational findings for intra-aortic balloon pump support
- 1Henan Key Laboratory of Individualized Drug Therapy for Cardiovascular Diseases, Department of Pharmacy, Fuwai Central China Cardiovascular Hospital, Central China Fuwai Hospital of Zhengzhou University, Zhengzhou, China
- 2Department of Cardiac Surgery Intensive Care Unit, Fuwai Central China Cardiovascular Hospital, Central China Fuwai Hospital of Zhengzhou University, Zhengzhou, China
- 3Department of Cardiology, Big Data Center for Cardiovascular Disease, Fuwai Central China Cardiovascular Hospital, Central China Fuwai Hospital of Zhengzhou University, Zhengzhou, China
Abstract
Background: Patients undergoing coronary artery bypass grafting (CABG) combined with valve surgery represent a high-risk surgical population with substantial perioperative hemodynamic disturbances and highly variable organ function, leading to high variability in vancomycin pharmacokinetics. Conventional vancomycin dosing solely on renal function frequently fails to achieve target trough concentrations in this complex subgroup. This study aimed to identify independent correlates c of vancomycin steady-state trough concentrations (Css-min), and to report observational findings for intra-aortic balloon pump (IABP) support, to inform individualized therapeutic drug monitoring.
Methods: A single-center retrospective observational study enrolled adult patients undergoing combined CABG and valve surgery from January 2018 to October 2024. Clinical data and vancomycin TDM records were extracted from electronic medical records. Vancomycin Css-min was detected by enzyme-multiplied immunoassay technique. Generalized Estimating Equations (GEE) accounting for within-patient repeated TDM measurements were used to identify clinical correlates of Css-min. IABP support was pre-specified and force-entered into the multivariable model based on clinical observations and pathophysiological reasoning, independent of univariate screening results. We performed a sensitivity analysis for patients with at least one TDM within postoperative day 7, prespecified interaction tests for effect modification, and binary logistic-GEE for the supratherapeutic endpoint (Css-min > 20 mg/L). A two-tailed P < 0.05 was set as statistical significance.
Results: A total of 283 eligible patients with 473 valid Css-min measurements were included. Multivariate GEE demonstrated that categorical vancomycin dosing regimen, age, ventilator dependence ≥96 h, continuous renal replacement therapy (CRRT), IABP support, serum creatinine (Scr), and serum urea nitrogen (SUN) were positively associated with higher geometric-mean Css-min. Associations remained largely consistent in the sensitivity-analysis subgroup of patients with at least one early-phase TDM within postoperative day 7. A significant CRRT-by-postoperative-time interaction was detected, indicating that the influence of CRRT on vancomycin exposure varied across different postoperative phases. Of note, the association signal linking IABP to supratherapeutic trough concentrations (Css-min>20 mg/L) was modest and requires cautious interpretation.
Conclusion: Multiple clinical factors jointly affect vancomycin steady-state trough concentrations in patients undergoing combined CABG and valve surgery, including dosing regimen, age, renal biomarkers, and critical-care supportive interventions such as IABP, CRRT and prolonged mechanical ventilation. IABP support represents an intriguing observational signal; this finding remains hypothesis-generating and requires prospective external validation before it can guide formal dose-adjustment strategies. Individualized vancomycin management for this population should comprehensively integrate hemodynamic support measures and laboratory indices rather than depend merely on renal-function markers. This study focuses on clinically accessible trough concentration monitoring rather than constructing complex pharmacokinetic models, which is more in line with real-world clinical practice.
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BibTeX
@article{shao2026independent,
title = {{Independent correlates of vancomycin steady-state trough concentration among patients undergoing combined CABG and valve surgery: observational findings for intra-aortic balloon pump support}},
author = {Bei-bei Shao and Tao Feng and Ji-cheng Jiang and Wen-lu Xing and Ming Ni and Lu-lu Li and Chao Liu and Shu-ping Meng and Yong-cheng Ma and Ai-feng Wang},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1888382},
url = {https://doi.org/10.3389/fphar.2026.1888382},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Independent correlates of vancomycin steady-state trough concentration among patients undergoing combined CABG and valve surgery: observational findings for intra-aortic balloon pump support
AU - Bei-bei Shao
AU - Tao Feng
AU - Ji-cheng Jiang
AU - Wen-lu Xing
AU - Ming Ni
AU - Lu-lu Li
AU - Chao Liu
AU - Shu-ping Meng
AU - Yong-cheng Ma
AU - Ai-feng Wang
PY - 2026
DA - 2026/10/12
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1888382
UR - https://doi.org/10.3389/fphar.2026.1888382
AB - Background: Patients undergoing coronary artery bypass grafting (CABG) combined with valve surgery represent a high-risk surgical population with substantial perioperative hemodynamic disturbances and highly variable organ function, leading to high variability in vancomycin pharmacokinetics. Conventional vancomycin dosing solely on renal function frequently fails to achieve target trough concentrations in this complex subgroup. This study aimed to identify independent correlates c of vancomycin steady-state trough concentrations (Css-min), and to report observational findings for intra-aortic balloon pump (IABP) support, to inform individualized therapeutic drug monitoring. Methods: A single-center retrospective observational study enrolled adult patients undergoing combined CABG and valve surgery from January 2018 to October 2024. Clinical data and vancomycin TDM records were extracted from electronic medical records. Vancomycin Css-min was detected by enzyme-multiplied immunoassay technique. Generalized Estimating Equations (GEE) accounting for within-patient repeated TDM measurements were used to identify clinical correlates of Css-min. IABP support was pre-specified and force-entered into the multivariable model based on clinical observations and pathophysiological reasoning, independent of univariate screening results. We performed a sensitivity analysis for patients with at least one TDM within postoperative day 7, prespecified interaction tests for effect modification, and binary logistic-GEE for the supratherapeutic endpoint (Css-min > 20 mg/L). A two-tailed P < 0.05 was set as statistical significance. Results: A total of 283 eligible patients with 473 valid Css-min measurements were included. Multivariate GEE demonstrated that categorical vancomycin dosing regimen, age, ventilator dependence ≥96 h, continuous renal replacement therapy (CRRT), IABP support, serum creatinine (Scr), and serum urea nitrogen (SUN) were positively associated with higher geometric-mean Css-min. Associations remained largely consistent in the sensitivity-analysis subgroup of patients with at least one early-phase TDM within postoperative day 7. A significant CRRT-by-postoperative-time interaction was detected, indicating that the influence of CRRT on vancomycin exposure varied across different postoperative phases. Of note, the association signal linking IABP to supratherapeutic trough concentrations (Css-min>20 mg/L) was modest and requires cautious interpretation. Conclusion: Multiple clinical factors jointly affect vancomycin steady-state trough concentrations in patients undergoing combined CABG and valve surgery, including dosing regimen, age, renal biomarkers, and critical-care supportive interventions such as IABP, CRRT and prolonged mechanical ventilation. IABP support represents an intriguing observational signal; this finding remains hypothesis-generating and requires prospective external validation before it can guide formal dose-adjustment strategies. Individualized vancomycin management for this population should comprehensively integrate hemodynamic support measures and laboratory indices rather than depend merely on renal-function markers. This study focuses on clinically accessible trough concentration monitoring rather than constructing complex pharmacokinetic models, which is more in line with real-world clinical practice.
SN - 1663-9812
ER -