Analgesic efficacy and safety of morphine in the Procedural Pain in Premature Infants (Poppi) study: randomised placebo-controlled trial.
Analgesic efficacy and safety of morphine in the Procedural Pain in Premature Infants (Poppi) study: randomised placebo-controlled trial.
复制标题
DOI：
10.1016/s0140-6736(18)31813-0
复制
发表时间：
2018-12-15
期刊：
影响因子：
--
通讯作者：
Slater R
中科院分区：
文献类型：
--
作者：
Hartley C;Moultrie F;Hoskin A;Green G;Monk V;Bell JL;King AR;Buckle M;van der Vaart M;Gursul D;Goksan S;Juszczak E;Norman JE;Rogers R;Patel C;Adams E;Slater R
婴儿疼痛具有即时和长期影响，但由于缺乏循证止痛药而治疗不足。虽然吗啡常用于镇静通气婴儿，但其镇痛效果尚不清楚。我们的目的是确定口服吗啡是否可以为非通气早产儿急性手术疼痛提供有效和安全的镇痛。在这项单中心设盲试验中，在英国牛津John Radcliffe医院的31名婴儿使用基于网络的设施和最小化算法随机分配到100 μg/kg口服硫酸吗啡或安慰剂组，在临床要求的足跟穿刺和早产儿视网膜病变筛查检查前1小时，在同一场合。合格的婴儿是在小于32周的妊娠时早产或出生体重低于1501 g，并且在研究时胎龄为34-42周。共同主要结局指标为早产儿视网膜病变筛查后的早产儿疼痛特征修订（PIPP-R）评分和足跟兰辛后的毒性诱发脑活动程度。次要结局指标评估生理稳定性和安全性。本试验已在欧洲临床试验数据库中注册（编号2014-003237-25）。在2016年10月30日至2017年11月17日期间，15名婴儿被随机分配到吗啡组，16名婴儿被随机分配到安慰剂组;一名分配到安慰剂组的婴儿在监测开始前退出研究。超过了预定义的停止边界，由于吗啡的严重呼吸不良反应而停止了试验招募，但未提示镇痛疗效。两组之间的共同主要结局指标无显著差异。早产儿视网膜病变筛查后，吗啡组PIPP-R评分平均为11.1（SD 3.2），安慰剂组为10.5（3.4）（平均差异0.5，95%CI − 2.0至3.0; p= 0.66）。在足跟兰辛后，吗啡组和安慰剂组的伤害性诱发脑活动中位数分别为0.99（IQR 0.40 - 1.56）和0.75（0.33 - 1.22）（中位数差异0.25，95% CI − 0.16 - 0.80; p= 0.25）。对未通气早产儿口服吗啡（100 μg/kg）可能造成伤害，但无镇痛效果。我们不建议口服吗啡用于早产儿视网膜病变筛查，并强烈建议在考虑将其用于未通气早产儿的其他急性疼痛程序时应谨慎。Wellcome Trust和National Institute for Health Research。
Infant pain has immediate and long-term effects but is undertreated because of a paucity of evidence-based analgesics. Although morphine is often used to sedate ventilated infants, its analgesic efficacy is unclear. We aimed to establish whether oral morphine could provide effective and safe analgesia in non-ventilated premature infants for acute procedural pain. In this single-centre masked trial, 31 infants at the John Radcliffe Hospital, Oxford, UK, were randomly allocated using a web-based facility with a minimisation algorithm to either 100 μg/kg oral morphine sulphate or placebo 1 h before a clinically required heel lance and retinopathy of prematurity screening examination, on the same occasion. Eligible infants were born prematurely at less than 32 weeks' gestation or with a birthweight lower than 1501 g and had a gestational age of 34–42 weeks at the time of the study. The co-primary outcome measures were the Premature Infant Pain Profile–Revised (PIPP-R) score after retinopathy of prematurity screening and the magnitude of noxious-evoked brain activity after heel lancing. Secondary outcome measures assessed physiological stability and safety. This trial is registered with the European Clinical Trials Database (number 2014-003237-25). Between Oct 30, 2016, and Nov 17, 2017, 15 infants were randomly allocated to morphine and 16 to placebo; one infant assigned placebo was withdrawn from the study before monitoring began. The predefined stopping boundary was crossed, and trial recruitment stopped because of profound respiratory adverse effects of morphine without suggestion of analgesic efficacy. None of the co-primary outcome measures differed significantly between groups. PIPP-R score after retinopathy of prematurity screening was mean 11·1 (SD 3·2) with morphine and 10·5 (3·4) with placebo (mean difference 0·5, 95% CI −2·0 to 3·0; p=0·66). Noxious-evoked brain activity after heel lancing was median 0·99 (IQR 0·40–1·56) with morphine and 0·75 (0·33–1·22) with placebo (median difference 0·25, 95% CI −0·16 to 0·80; p=0·25). Administration of oral morphine (100 μg/kg) to non-ventilated premature infants has the potential for harm without analgesic efficacy. We do not recommend oral morphine for retinopathy of prematurity screening and strongly advise caution if considering its use for other acute painful procedures in non-ventilated premature infants. Wellcome Trust and National Institute for Health Research.