Taddio Anna, Lee Charlene, Yip Amelia, Parvez Boriana, McNamara Patrick J, Shah Vibhuti
Department of Pharmacy, The Hospital for Sick Children, Faculty of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario.
JAMA. 2006 Feb 15;295(7):793-800. doi: 10.1001/jama.295.7.793.
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.
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.
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<.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).
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.
关于新生儿中心静脉置管期间阿片类镇痛或局部麻醉的镇痛效果，证据有限，且此前尚无关于它们相对有效性的研究。
确定丁卡因局部用药、静脉注射吗啡或丁卡因加吗啡在通气新生儿中心静脉置管期间缓解疼痛的有效性和安全性。
设计、地点和参与者：随机、双盲、对照试验，纳入132例通气新生儿（研究开始时平均胎龄为30.6[标准差，4.6]周），于2000年10月至2005年7月在安大略省多伦多市的2个新生儿重症监护病房进行。
在中心静脉置管前，将新生儿随机分配接受丁卡因（n = 42）、吗啡（n = 38）或两者联合使用（n = 31）；另外一组21例未接受丁卡因和吗啡的新生儿作为非随机对照组。
主要结局指标是在操作的不同阶段（皮肤准备、针刺和恢复）新生儿出现面部 grimacing（眉弓隆起）的时间比例的疼痛评分。在随机分组的新生儿中，安全性评估包括血压、通气支持和局部皮肤反应。
与未治疗相比，吗啡组和丁卡因-吗啡组在皮肤准备阶段（平均差值，-0.22；95%置信区间[CI]，-0.4至-0.04；P = 0.02和-0.29；95%CI，-0.49至-0.09；P = 0.01）和针刺阶段（平均差值，-0.35；95%CI，-0.57至-0.13；P = 0.003和-0.47；95%CI，-0.71至-0.24；P<0.001）的疼痛评分较低，但单独使用丁卡因组与未治疗组的疼痛评分在统计学上无差异。在皮肤准备阶段，吗啡组和丁卡因-吗啡组的疼痛评分低于丁卡因组；在针刺阶段，丁卡因-吗啡组的疼痛评分低于丁卡因组。与未使用吗啡的新生儿相比，使用吗啡治疗的新生儿在最初12小时内通气率需要更大幅度的增加（平均差值，3.9/分钟；95%CI，1.3 - 6.5/分钟；P = 0.003）。30%接受丁卡因治疗的新生儿出现局部皮肤反应，而接受吗啡治疗的新生儿为0%（风险差值，0.30；95%CI，0.19 - 0.41；P<0.001）。
在这项对接受中心静脉置管的通气新生儿的研究中，吗啡和丁卡因加吗啡的镇痛效果优于丁卡因；然而，吗啡导致呼吸抑制，丁卡因导致红斑。临床试验注册ClinicalTrials.gov标识符：NCT00213200。
