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Evaluate effects and safety of nesiritide (Natrecor, Scios Inc) human B-type natriuretic peptide, in neonates with heart failure.Seventeen neonates, not responding to conventional therapy, treated with nesiritide were retrospectively reviewed.Average age 16 ± 8 days; weight 3.2 ± 0.6 kg. Fifteen treated with concomitant inotropic therapy; all with diuretics. Twelve received loading dose; followed by continuous infusions of 0.005 mcg/kg/min (2); 0.01 mcg/kg/min (12); 0.02 mcg/kg/min (3). Length of therapy 5 ± 4 days. No change in heart rate or blood pressure between baseline, 1 hour or 24 hours of nesiritide infusion. Decrease central venous pressure (CVP) 24 hours after infusion (p =0.03). Ins-out ratio improved in 29%. No difference in pre and post therapy BUN and creatinine (Cr). 18% had hypotension requiring intervention.Nesiritide use in neonates may improve hemodynamics as demonstrated by reduction in CVP. All patients tolerated bolus dosing, however, transient hypotension occurred in 18% of neonates with continuous infusion.