Disposition of milrinone in patients after cardiac surgery

Abstract

We have evaluated the disposition of milrinone in seven patients with low cardiac output after elective cardiac surgery involving cardiopulmonary bypass. Patients received a loading dose of milrinone 50 micrograms kg-1 given over 10 min followed immediately by an infusion of 0.5 microgram kg-1 min-1, continued for a minimum of 5 h. Plasma concentrations of milrinone were measured at designated intervals during the infusion and for 6 h after its termination, by high pressure liquid chromatography. Concentrations greater than 100 ng ml-1 were produced in all patients within 2 min of starting the loading dose and were maintained for the duration of the infusion. Volume of distribution, clearance and terminal half-life were similar to those found in patients with chronic cardiac failure.

Population Pharmacokinetics of Milrinone in Infants, Children, and Adolescents

“…Plasma concentrations of albumin in particular could affect estimates of V given the moderate degree of binding of milrinone to this protein . Unfortunately, we did not have access to plasma albumin concentrations in these opportunistically collected data to assess its effect on milrinone V. Our estimate of CL scaled to a 70‐kg WT (15.9 L/h) falls within the wide range of adult estimates (18 L/h in healthy volunteers, 9.1 L/h in patients with congestive heart failure, 1.4 L/h in patients with congestive heart failure, and CrCl <30 mL/min) and is similar to prior pediatric estimates . In a study of 19 children 0 to 13 years of age (3.5‐40 kg WT) recovering from cardiac surgery, milrinone CL was estimated at 24 L/h/70 kg using a 2‐compartment PK model .…”

“…8,9 Unfortunately, we did not have access to plasma albumin concentrations in these opportunistically collected data to assess its effect on milrinone V. Our estimate of CL scaled to a 70-kg WT (15.9 L/h) falls within the wide range of adult estimates (18 L/h in healthy volunteers, 9.1 L/h in patients with congestive heart failure, 1.4 L/h in patients with congestive heart failure, and CrCl <30 mL/min) and is similar to prior pediatric estimates. [10][11][12]33 In a study of 19 children 0 to 13 years of age (3.5-40 kg WT) recovering from cardiac surgery, milrinone CL was estimated at 24 L/h/70 kg using a 2-compartment PK model. 34 In a more recent 2-compartment PopPK model developed in infants <12 months of age who received milrinone after cardiac surgery, milrinone CL was estimated at 7.91 L/h/70 kg.…”

“…Elimination CL is significantly reduced in adults with moderate to severe renal impairment and an estimated creatinine clearance (CrCl) between 30 and 80 mL/min, including those with congestive heart failure. [10][11][12] Plasma concentrations associated with therapeutic effects in adults range from 100 to 300 ng/mL. 13,14 Higher concentrations (>500 ng/mL) are associated with toxicity, primarily systemic hypotension resulting from excessive vasodilation.…”

Pilot study of milrinone for low systemic blood flow in very preterm infants

“…On the other hand, milrinone was accumulating above the target range by 24 hours when the cardiovascular system is normally recovering spontaneously. This is probably due to the longer half-life in the preterm infant, which at 10 hours was longer than 1.47 to 3.15 hours in children 7,13 and 1 to 1.69 hours in healthy adults 20,21 This may also explain the higher rate of hypotension seen at 0.5 g/kg per minute. We used population pharmacokinetic modeling to design a regimen that fits our therapeutic goal.…”

Grundsätze der Katecholamintherapie

“…Bei Milrinon, dem wirksamsten PDE-Hemmer, beträgt der empfohlene Bolus 50 g/kg, verabreicht über 10 Minuten, und die Infusionsrate 0,375 ± 0,75 g/kg´min [119]. Ein Nachteil der PDE-Hemmer ist die im Vergleich zu Katecholaminen deutlich schlechtere Steuerbarkeit.…”