Intravenous Morphine and Topical Tetracaine for Treatment of Pain in Preterm Neonates Undergoing Central Line Placement
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CONTEXT: 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. OBJECTIVE: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. INTERVENTIONS: 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. MAIN OUTCOME MEASURES: 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. RESULTS: 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<.001, respectively), but pain scores did not differ statistically for tetracaine alone vs no treatment. Pain scores were lower for morphine and tetracaine-morphine vs tetracaine during the skin preparation phase and for tetracaine-morphine vs tetracaine during needle puncture. Compared with neonates without morphine, morphine-treated neonates required larger increases in ventilation rate in the first 12 hours (mean difference, 3.9/min; 95% CI, 1.3-6.5/min; P = .003). Local skin reactions occurred in 30% of neonates given tetracaine vs 0% for morphine (risk difference, 0.30; 95% CI, 0.19-0.41; P<.001). CONCLUSION: In this study of ventilated neonates undergoing central line placement, morphine and tetracaine plus morphine provided superior analgesia to tetracaine; however, morphine caused respiratory depression and tetracaine caused erythema.Clinical Trials Registration ClinicalTrials.gov Identifier: NCT00213200.