title: Elevation of plasma milrinone concentrations in stage D heart failure associated with renal dysfunction.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacy Practice, Lipscomb University College of Pharmacy, Nashville, TN 37204, USA. zachary.l.cox@vanderbilt.edu
authors.forename: Zachary L
authors.initials: ZL
authors.lastname: Cox
authors.forename: Marion W
authors.initials: MW
authors.lastname: Calcutt
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Morrison
authors.forename: Wendell S
authors.initials: WS
authors.lastname: Akers
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Davis
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Lenihan
mesh_terms: D000328:Adult; D000368:Aged; D006328:Cardiac Catheterization; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003404:Creatinine / Q000097:blood / Q000652:urine; D017147:Defibrillators, Implantable; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006439:Hemodynamics; D006801:Humans; D007674:Kidney Diseases / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D020105:Milrinone / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006435:Renal Dialysis; D012189:Retrospective Studies; D012720:Severity of Illness Index; D017180:Tachycardia, Ventricular
chemical_list: D002316:Cardiotonic Agents; D003404:Creatinine; D020105:Milrinone