HEMODYNAMIC-EFFECTS OF IV MILRINONE LACTATE IN PEDIATRIC-PATIENTS WITH SEPTIC SHOCK - A PROSPECTIVE, DOUBLE-BLINDED, RANDOMIZED, PLACEBO-CONTROLLED, INTERVENTIONAL STUDY

Study objective: To determine the hemodynamic effects of IV milrinone lactate in pediatric patients with nonhyperdynamic septic shock. Speci fically we tested the hypothesis that IV milrinone would increase card iac index by 20% and decrease systemic vascular resistance index by 20 % during a 2-h study period. Design: Prospective, double-blinded, rand omized, placebo-controlled, descriptive, interventional study. Setting : Twenty-six-bed pediatric ICU at Children's Medical Center of Dallas and a 10-bed pediatric trauma ICU at Parkland Memorial Hospital. Patie nts/participants: Twelve patients (age range, 9 months to 15 years) wi th nonhyperdynamic septic shock despite administration of catecholamin es (cardiac index [CI] normal [3.5 to 5.5 L/min/m(2)] or low [less tha n or equal to 3.5 L/min/m(2)]; systemic vascular resistance index [SVR I] normal [800 to 1,600 dyne-s-cm(5)/m(2)] or high [greater than or eq ual to 1,600 dyne-s-cm(5)/m(2)]; and pulmonary capillary wedge pressur e [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 IV milrinone and placebo. Interventions: Patients were randomize d into two groups. Group A received a loading dose of 50 mu g/kg IV of milrinone followed by a continuous IV infusion of 0.5 mu g/kg/min whi le group B received an equal volume loading dose and continuous infusi on of placebo. After 2 h, group A received an equal-volume loading dos e followed by a continuous infusion of placebo while the milrinone inf usion continued, while group B received a 50 mu g/kg loading dose of m ilrinone followed by a continuous infusion of 0.5 mu g/kg/min while th e placebo infusion remained. Outcome variables were measured at baseli ne, 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 change s in other inotropic or mechanical ventilator) support were allowed du ring the study period. Measurements and main results: Milrinone signif icantly increased CI, stroke volume index (SVI), right and left ventri cular stroke work index, and oxygen delivery (Do(2)) at 0.5, 1.0, and 2.0 h postloading dose (p<0.05) while significantly decreasing SVRI, p ulmonary vascular resistance index, and mean pulmonary arterial pressu re 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 diastoli c BP, mean systemic arterial pressure, or PCWP were observed during mi lrinone treatment compared to placebo. Conclusions: CI, SVI, and Do(2) significantly increased while SVRI significantly decreased when compa red to placebo after IV administration of milrinone to pediatric patie nts with nonhyperdynamic septic shock. No adverse effects mere observe d. In a volume-resuscitated pediatric patient with septic shock, when administered in addition to catecholamines, milrinone will improve car diovascular function.