OBJECTIVETo evaluate the effects of morphine infusion analgesia on behavioural and neuroendocrine stress response and short term outcome in ventilated neonates.

METHODSA randomized, double-blind clinical trial was conducted between August 2010 and April 2011 at the neonatal intensive care unit of Nanjing Children's Hospital Affiliated to Nanjing Medical University. A total of 46 ventilated preterm infants (≥ 32 weeks) and term infants were divided into 2 groups at random. Twenty-two infants in test group received a loading dose (100 µg/kg) of morphine (> 1 h) followed by a continuous infusion [10 µg/(kg·h)] for (70.05 ± 29.05) h, and 24 infants in control group received 5% glucose with the same infusion rate. (1) The ventilatory parameters [respiratory rate (R), frequence (f), peak inspiratory pressure (PIP), positive end expiratory pressure (PEEP), fraction of inspired oxygen (FiO2)], mean blood pressure (MBP) and heart rate (HR) before treatment, at 30 min, 2 h, 6 h, 12 h, 24 h, 48 h after treatment between two groups were compared. (2) Pain was measured by two assessment tools [neonatal pain, agitation and sedation scale (N-PASS) and COMFORT scale] at the same periods. (3) The ventilation duration, the time from withdrawal to extubation, the total oxygen-inhaled time, the side effects and the clinical outcomes [e.g., pulmonary hemorrhage, air leak, patent ductus arteriosus (PDA), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH)] between two groups were compared.

RESULTS(1) There were no significant differences in the different ventilatory parameters before and after treatment between two groups at different periods (P > 0.05). There was no significant difference in the average blood pressure of two groups at different periods, but the heart rate reduced at 24 - 48 h after treatment in test group with significant difference as compared to control group (t = -2.152 and -2.513, P < 0.05). (2) The N-PASS score and COMFORT score in test group were lower than that in control group at different time points 2 h after treatment (P < 0.05), especially 12 h after treatment (P < 0.01). (3) There were no significant differences in the ventilation duration, the time from withdrawal to extubation and the total oxygen time between two groups, and also in side effects, the incidence of IVH, white matter damage and the clinical outcomes.

CONCLUSIONContinuous infusion of morphine could relieve pain in ventilated neonates, reduce the stress response and promote the human-machine coordination, but the medication did not show any effects on neurobehavioral development and short term outcome.