Effect of morphine on cerebral activity of extremely premature infants

Background: Morphine is widely used for sedation in premature infants and may have long-term effects on neurodevelopmental outcome. Aims: To assess its effect on cerebral activity of extremely preterm infants. Methods: Retrospective study in infants less than 28 weeks of gestational age (GA), treated with morphine and monitored with amplitude integrated EEG (aEEG), that were assessed at baseline and 6 consecutive 2 h periods. At each period, the background activity score and presence of cycling were determined. Results: A total of 140 infants were included. Background aEEG activity score worsened in 40% of the infants by 6 h after morphine initiation and cycling, initially present in 70% of the infants, could be detected in only 10% after 10 h. On multivariable analysis, adjusted for baseline aEEG score and GA, the background activity decreased by 0.85 (95% confidence interval (CI): 0.74–0.97) immediately after morphine initiation, 0.72 (CI: 0.63–0.83) at 2 h later and on average by 0.64 (CI: 0.57–0.71) at each subsequent 2 h periods. The relative risk of cycling loss at 2 h and 4 h after morphine administration was 1.58 (CI: 1.15–2.16) and 3.37 (CI: 2.23–5.08), respectively. Conclusions: Continuous infusion of morphine in extremely preterm infants significantly depresses their cerebral activity soon after its commencement.