Exposure to repetitive painful experiences may significantly alter clinical& neurobehavioral outcomes in ventilated preterm neonates. Nine participating NICUs randomized 69 preterm neonates of 24-32 wks gestation to receive morphine (Mo), midazolam (Mi), or dextrose (Dex) infusions in a double-blind trial. Groups were similar for gestation, postnatal age, gender, birth weight, severity of illness (CRIB scores, Neonatal Medical Index), maternal variables including obstetric course & drug exposure.

Premature Infant Pain Profile (PIPP) scores decreased during Mo(8.1±2.3#) and Mi (9.2±3.1#) infusions compared to Dex infusion group (12.8±3.9#, p<0.001). Less neonates required additional analgesia during the Mo infusion vs. The Dex or Mi groups (p<0.05). Nonsignificant trends for increased weight gain, decreased duration of ventilator or oxygen therapy, and NICU stay occurred in the Mi & Mo groups vs. the Dex group. Poor outcomes (death, IVH grade III/IV, or PVL) occurred in 5% of the Mo group, 31.6% of the Mi group, & 31.3% of the Dex group. Neurobehavioral outcomes (NAPI exam cluster scores) at 36 wks post-conceptional age were similar in the three groups.Table

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# Mean (S.D.); *Number of patients; Mortality: p=0.07, IVH: X2=10.097, p=0.26; NAPI scores are average cluster scores from: motor development, alertness & orientation, irritability & crying, scarf sign, and popliteal angle. No significant differences.

This pilot trial suggests that morphine analgesia may decrease the neonatal responses to pain/stress and appears to reduce the incidence of poor outcomes in ventilated preterm neonates. These data need confirmation in a large multicenter trial.