Inhaled Milrinone After Left Ventricular Assist Device Implantation

J Card Fail. 2015 Oct;21(10):792-7. doi: 10.1016/j.cardfail.2015.04.011. Epub 2015 Apr 29.

Abstract

Background: Proven strategies to reduce right ventricular (RV) dysfunction after continuous-flow left ventricular assist device (CF-LVAD) implantation are lacking. We sought to evaluate the tolerability, feasibility, efficacy, and pharmacokinetics of inhaled milrinone (iMil) delivery after CF-LVAD implantation.

Methods and results: We prospectively evaluated fixed-dose nebulized iMil delivered into a ventilator circuit for 24 hours in 10 postoperative CF-LVAD (Heartmate-II) patients. Tolerability (arrhythmias, hypotension, and hypersensitivity reaction), efficacy (hemodynamics), pharmacokinetics (plasma milrinone levels), and cost data were collected.Mean age was 56 ± 9 years, 90% were male, and mean INTERMACS profile was 2.5 ± 0.8. No new atrial arrhythmia events occurred, although 3 (30%) ventricular tachycardia (1 nonsustained, 2 sustained) events occurred. Sustained hypotension, drug hypersensitivity, death, or need for right ventricular assist device were not observed. Invasive mean pulmonary arterial pressure from baseline to during iMil therapy was improved (P = .017). Mean plasma milrinone levels (ng/mL) at baseline, and 1, 4, 8, 12, and 24 hours were 74.2 ± 35.4, 111.3 ± 70.9, 135.9 ± 41.5, 205.0 ± 86.7, 176.8 ± 61.3 187.6 ± 105.5, respectively. Reduced institutional cost was observed when iMil was compared with nitric oxide therapy over 24 hours ($165.29 vs $1,944.00, respectively).

Conclusions: iMil delivery after CF-LVAD implantation was well tolerated, feasible, and demonstrated favorable hemodynamic, pharmacokinetic, and cost profiles. iMil therapy warrants further study in larger clinical trials.

Keywords: Phosphodiesterase inhibitor; left ventricular assist device; nebulization; right ventricular dysfunction.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Administration, Inhalation
  • Aged
  • Cost-Benefit Analysis
  • Female
  • Heart Failure / diagnosis
  • Heart Failure / drug therapy*
  • Heart Failure / surgery*
  • Heart Ventricles
  • Heart-Assist Devices / trends*
  • Hemodynamics / drug effects
  • Hemodynamics / physiology
  • Humans
  • Male
  • Middle Aged
  • Milrinone / administration & dosage*
  • Milrinone / economics
  • Postoperative Care / economics
  • Postoperative Care / methods
  • Treatment Outcome
  • Vasodilator Agents / administration & dosage
  • Vasodilator Agents / economics
  • Ventricular Dysfunction, Right / prevention & control

Substances

  • Vasodilator Agents
  • Milrinone