Intravenous morphine and topical tetracaine for treatment of pain in [corrected] neonates undergoing central line placement

There is limited evidence of the analgesic effectiveness of opioid analgesia or topical anesthesia during central line placement in neonates, and there are no previous studies of their relative effectiveness. To determine the effectiveness and safety of topical tetracaine, intravenous morphine, or tetracaine plus morphine for alleviating pain in ventilated neonates during central line placement. Randomized, double-blind, controlled trial enrolling 132 ventilated neonates (mean gestational age, 30.6 [SD, 4.6] weeks at study entry) and conducted between October 2000 and July 2005 in 2 neonatal intensive care units in Toronto, Ontario. Prior to central line insertion, neonates were randomly assigned to receive tetracaine (n = 42), morphine (n = 38), or both (n = 31); a separate nonrandomized group of 21 neonates receiving neither tetracaine nor morphine was used as a control group. The primary outcome measure was a pain score for the proportion of time neonates displayed facial grimacing (brow bulge) during different phases of the procedure (skin preparation, needle puncture, and recovery). In randomized neonates, safety assessments included blood pressure, ventilatory support, and local skin reactions. Compared with no treatment, pain scores were lower in the morphine and tetracaine-morphine groups during skin preparation (mean difference, -0.22; 95% confidence interval [CI], -0.4 to -0.04; P = .02 and -0.29; 95% CI, -0.49 to -0.09; P = .01, respectively), and needle puncture (mean difference, -0.35; 95% CI, -0.57 to -0.13; P = .003 and -0.47; 95% CI, -0.71 to -0.24; P