Carbajal Ricardo, Lenclen Richard, Jugie Myriam, Paupe Alain, Barton Bruce A, Anand Kanwaljeet J S
Neonatal Intensive Care Unit, Poissy Saint Germain Hospital, Poissy, France.
Pediatrics. 2005 Jun;115(6):1494-500. doi: 10.1542/peds.2004-1425.
Morphine alleviates prolonged pain, reduces behavioral and hormonal stress responses induced by surgery among term neonates, and improves ventilator synchrony and sedation among ventilated preterm neonates, but its analgesic effects on the acute pain caused by invasive procedures remain unclear.
To investigate the analgesic efficacy of intravenously administered morphine on heel stick-induced acute pain among preterm neonates.
This study was nested within a prospective, randomized, double-blind, multicenter, placebo-controlled trial (the NEOPAIN Trial).
A tertiary-care NICU in a teaching hospital.
Forty-two preterm neonates undergoing ventilation.
Neonates were randomized to either the morphine (loading dose of 100 microg/kg, followed by infusions of 10-30 microg/kg per hour according to gestation, N = 21) or placebo (5% dextrose infusions, N = 21) group. Pain responses to 3 heel sticks were evaluated, ie, before the loading dose (T1), 2 to 3 hours after the loading dose (T2), and 20 to 28 hours after the loading dose (T3).
Pain was assessed with the Douleur Aiguë Nouveau-né (DAN) scale (behavioral pain scale) and the Premature Infant Pain Profile (PIPP) (multidimensional pain scale); plasma morphine levels were measured at T3.
Infants in the placebo and morphine groups had similar gestational ages (mean +/- SD: 27.2 +/- 1.7 vs 27.3 +/- 1.8 weeks) and birth weights (972 +/- 270 vs 947 +/- 269 g). Mean +/- SD DAN pain scores at T1, T2, and T3 were 4.8 +/- 4.0, 4.6 +/- 2.9, and 4.7 +/- 3.6, respectively, for the placebo group and 4.5 +/- 3.8, 4.4 +/- 3.7, and 3.1 +/- 3.4 for the morphine group. The within-group factor (pain at T1, T2, and T3) was not statistically different over time. The between-group analysis (infants receiving placebo versus those receiving morphine) showed no significant differences. Mean +/- SD PIPP pain scores at T1, T2, and T3 were 11.5 +/- 4.8, 11.1 +/- 3.7, and 9.1 +/- 4.0, respectively, for the placebo group and 10.0 +/- 3.6, 8.8 +/- 4.9, and 7.8 +/- 3.6 for the morphine group. The within-group factor was statistically different over time. The between-group analysis showed no significant differences. Mean +/- SD plasma morphine levels at T3 were 0.44 +/- 1.79 ng/mL and 63.36 +/- 33.35 ng/mL for the placebo and morphine groups, respectively. There was no correlation between plasma morphine levels and pain scores at T3 (DAN, R = -0.05; PIPP, R = -0.02).
Despite its routine use in the NICU, morphine given as a loading dose followed by continuous intravenous infusions does not appear to provide adequate analgesia for the acute pain caused by invasive procedures among ventilated preterm neonates.
吗啡可缓解持续性疼痛，减轻足月儿手术引起的行为和激素应激反应，并改善机械通气早产儿的通气同步性和镇静效果，但其对侵入性操作所致急性疼痛的镇痛作用尚不清楚。
探讨静脉注射吗啡对早产儿足跟采血所致急性疼痛的镇痛效果。
本研究嵌套于一项前瞻性、随机、双盲、多中心、安慰剂对照试验（NEOPAIN试验）。
一家教学医院的三级护理新生儿重症监护病房。
42例接受机械通气的早产儿。
将新生儿随机分为吗啡组（负荷剂量100μg/kg，随后根据孕周每小时输注10 - 30μg/kg，n = 21）或安慰剂组（5%葡萄糖输注，n = 21）。评估对3次足跟采血的疼痛反应，即负荷剂量前（T1）、负荷剂量后2至3小时（T2）和负荷剂量后20至28小时（T3）。
采用新生儿急性疼痛量表（DAN，行为疼痛量表）和早产儿疼痛量表（PIPP，多维疼痛量表）评估疼痛；在T3时测量血浆吗啡水平。
安慰剂组和吗啡组婴儿的孕周相似（平均±标准差：27.2±1.7 vs 27.3±1.8周），出生体重相近（972±270 vs 947±269 g）。安慰剂组在T1、T2和T3时的平均±标准差DAN疼痛评分分别为4.8±4.0、4.6±2.9和4.???±3.6，吗啡组分别为4.5±3.8、4.4±3.7和3.1±3.4。组内因素（T1、T2和T3时的疼痛）随时间无统计学差异。组间分析（接受安慰剂与接受吗啡的婴儿）无显著差异。安慰剂组在T1、T2和T3时的平均±标准差PIPP疼痛评分分别为11.5±4.8、11.1±3.7和9.1±4.0，吗啡组分别为10.0±3.6、8.8±4.9和7.8±3.6。组内因素随时间有统计学差异。组间分析无显著差异。安慰剂组和吗啡组在T3时的平均±标准差血浆吗啡水平分别为0.44±1.79 ng/mL和63.36±33.35 ng/mL。T3时血浆吗啡水平与疼痛评分之间无相关性（DAN，R = -0.05；PIPP，R = -0.02）。
尽管吗啡在新生儿重症监护病房常规使用，但负荷剂量后持续静脉输注吗啡似乎不能为机械通气早产儿侵入性操作所致急性疼痛提供充分镇痛。
