Elevation of plasma milrinone concentrations in stage D heart failure associated with renal dysfunction.

Cox ZL, Calcutt MW, Morrison TB, Akers WS, Davis MB, Lenihan DJ
J Cardiovasc Pharmacol Ther. 2013 18 (5): 433-8

PMID: 23695773 · DOI:10.1177/1074248413489773

PURPOSE - To determine steady state milrinone concentrations in patients with stage D heart failure (HF) with and without renal dysfunction

METHODS - We retrospectively identified patients with stage D HF at a single medical center on continuous milrinonein fusion at the time of plasma collection for entry into a research registry database. Milrinone was prescribed and titrated to improve hemodynamic and clinical status by a cardiologist. Plasma samples were obtained at steady state milrinone concentrations. Patients were stratified by creatinine clearance (CrCl) into 4 groups: group 1 (CrCl >60 mL/min), group 2 (CrCl 60-30 mL/min), group 3 (CrCl <30 mL/min), and group 4 (intermittent hemodialysis). Retrospective chart review was performed to quantify the post milrinone hemodynamic changes by cardiac catheterization and electrophysiologic changes by implantable cardiac defibrillator (ICD) interrogation.

RESULTS - A total of 29 patients were identified: group 1 (n=14), group 2 (n=10), group 3(n=3), and group 4 (n = 2). The mean infusion rate (0.391+0.08 mg/kg/min) did not differ between groups (P=0.14). The mean milrinone concentration was 451+243 ng/mL in group 1, 591+293 ng/mL in group 2, 1575+962 ng/mL in group 3, and 6252+4409 ng/mL in group 4 (P<0.05 compared to groups 1). There was no difference in post milrinone hemodynamic improvements between the groups (P=0.41). The ICD interrogation revealed limited comparisons, but 6 of the 8 post milrinone ventricular tachycardia episodes requiring defibrillation occurred in group 4 patients.

CONCLUSION - Patients with stage D HF having severe renal dysfunction have elevated milrinone concentrations. Future studies of milrinone concentrations are warranted to investigate the potential risk of life-threatening arrhythmias and potential dosing regimens in renal dysfunction.

MeSH Terms (18)

Adult Aged Cardiac Catheterization Cardiotonic Agents Creatinine Defibrillators, Implantable Female Heart Failure Hemodynamics Humans Kidney Diseases Male Middle Aged Milrinone Renal Dialysis Retrospective Studies Severity of Illness Index Tachycardia, Ventricular

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