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Milrinone exhibits a sigmoidal relationship between plasma concentrations and the percent increase of cardiac index, with no additional hemodynamic benefit above 500 ng/ml. Milrinone may accumulate in renal dysfunction and increase arrhythmic risk in a concentration dependent manner. We hypothesized that heart failure (HF) patients with renal dysfunction would have elevated steady-state milrinone concentrations.
29 patients on continuous milrinone infusion at the time of plasma collection were enrolled in the Vanderbilt Heart Registry. Creatinine clearance (CrCl) was used to stratify patients into four groups: Group 1 (CrCl >60ml/min), Group 2 (CrCl 60-30 ml/min), Group 3 (CrCl <30 ml/min), and Group 4 (hemodialysis). Plasma milrinone concentration was determined by liquid chromatography-mass spectrometry. Hemodynamic and arrhythmic effects were compared to a pre-milrinone baseline.
All patients (76% male; 39% ischemic cardiomyopathy) had stage D HF and an implanted cardiac defibrillator (ICD). There was no difference in the mean infusion rates (0.391 + 0.08 mcg/kg/min) (p=0.14) between groups. Of 8 post-milrinone ventricular tachycardia episodes requiring defibrillation, 6 occurred in Group 4 patients.
Milrinone concentrations are markedly elevated in renal dysfunction. Quantification of milrinone concentrations may identify those at highest risk of ventricular arrhythmias.
|Group 1 (n=14)||Group 2 (n=10)||Group 3 (n=3)||Group 4 (n=2)|
|Milrinone (ng/ml)||451+ 243||591 + 293||1,575 + 962||6,252 + 4,409b|
|CI increasea||24% + 25%||44% + 45%||50% + 14%||15% + 35%|
Data as mean + SD
bp<0.05 vs all groups
Poster Sessions, Expo North
Sunday, March 10, 2013, 9:45 a.m.-10:30 a.m.
Session Title: Heart Failure: Pharmacologic Therapy
Abstract Category: 17. Heart Failure: Therapy
Presentation Number: 1223-300
- 2013 American College of Cardiology Foundation