title: Hemodynamic effects of i.v. milrinone lactate in pediatric patients with septic shock. A prospective, double-blinded, randomized, placebo-controlled, interventional study.
abstract: OBJECTIVE
  To determine the hemodynamic effects of i.v. milrinone lactate in pediatric patients with nonhyperdynamic septic shock. Specifically we tested the hypothesis that i.v. milrinone would increase cardiac index by 20% and decrease systemic vascular resistance index by 20% during a 2-h study period.
  
  
  METHODS
  Prospective, double-blinded, randomized, placebo-controlled, descriptive, interventional study.
  
  
  METHODS
  Twenty-six-bed pediatric ICU at Children's Medical Center of Dallas and a 10-bed pediatric trauma ICU at Parkland Memorial Hospital.
  
  
  METHODS
  Twelve patients (age range, 9 months to 15 years) with nonhyperdynamic septic shock despite administration of catecholamines (cardiac index [CI] normal [3.5 to 5.5 L/min/m2] or low [< or =3.5 L/min/m2]; systemic vascular resistance index [SVRI] normal [800 to 1,600 dyne.s.cm5/m2] or high [> or =1,600 dyne.s.cm5/m2]; and pulmonary capillary wedge pressure [PCWP] normal [8 to 12 mm Hg] or higher) with clinical signs of poor perfusion were enrolled, randomized, and treated in a blinded fashion with i.v. milrinone and placebo.
  
  
  METHODS
  Patients were randomized into two groups. Group A received a loading dose of 50 micrograms/kg i.v. of milrinone followed by a continuous i.v. infusion of 0.5 microgram/kg/min while group B received an equal volume loading dose and continuous infusion of placebo. After 2 h, group A received an equal-volume loading dose followed by a continuous infusion of placebo while the milrinone infusion continued, while group B received a 50 micrograms/kg loading dose of milrinone followed by a continuous infusion of 0.5 microgram/kg/min while the placebo infusion remained. Outcome variable were measured at baseline, 0.5, 1.0, 2.0, 2.5, 3.0, and 4.0 h. Echocardiographic measurements were taken at baseline, hour 2, and hour 4 in all subjects. No changes in other inotropic or mechanical ventilatory support were allowed during the study period.
  
  
  RESULTS
  Milrinone significantly increased CI, stroke volume index (SVI), right and left ventricular stroke work index, and oxygen delivery (Do2) at 0.5, 1.0, and 2.0 h postloading dose (p < 0.05) while significantly decreasing SVRI, pulmonary vascular resistance index, and mean pulmonary arterial pressure at 0.5, 1.0, and 2.0 h postloading dose (p < 0.05). No clinically or statistically significant changes in heart rate, systolic and diastolic BP, mean systemic arterial pressure, or PCWP were observed during milrinone treatment compared to placebo.
  
  
  CONCLUSIONS
  CI, SVI, and Do2 significantly increased while SVRI significantly decreased when compared to placebo after i.v. administration of milrinone to pediatric patients with nonhyperdynamic septic shock. No adverse effects were observed. In a volume-resuscitated pediatric patient with septic shock, when administered in addition to catecholamines, milrinone will improve cardiovascular function.
authors.affiliation: Divisions of Pediatric Critical Care, University of Texas Southwestern Medical Center (Children's Medical Center of Dallas and Parkland Memorial Hospital), USA 75235-9063.
authors.forename: P
authors.initials: P
authors.lastname: Barton
authors.forename: J
authors.initials: J
authors.lastname: Garcia
authors.forename: A
authors.initials: A
authors.lastname: Kouatli
authors.forename: L
authors.initials: L
authors.lastname: Kitchen
authors.forename: A
authors.initials: A
authors.lastname: Zorka
authors.forename: C
authors.initials: C
authors.lastname: Lindsay
authors.forename: S
authors.initials: S
authors.lastname: Lawless
authors.forename: B
authors.initials: B
authors.lastname: Giroir
mesh_terms: D000293:Adolescent; D002302:Cardiac Output / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D008297:Male; D020105:Milrinone; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage*; D011446:Prospective Studies; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D011728:Pyridones / Q000008:administration & dosage*; D012772:Shock, Septic / Q000188:drug therapy* / Q000503:physiopathology; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D010726:Phosphodiesterase Inhibitors; D011728:Pyridones; D020105:Milrinone