吗啡暴露与镰状细胞病血管闭塞性危象患儿的急性胸部综合征有关吗？一项为期6年的病例交叉研究。

Is morphine exposure associated with acute chest syndrome in children with vaso-occlusive crisis of sickle cell disease? A 6-year case-crossover study.

作者信息

Finkelstein Yaron, Schechter Tal, Garcia-Bournissen Facundo, Kirby Melanie, Nurmohamed Laila, Juurlink David N, Blanchette Victor, Koren Gideon

机构信息

Department of Pediatrics, The Hospital for Sick Children, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.

出版信息

Clin Ther. 2007 Dec;29(12):2738-43. doi: 10.1016/j.clinthera.2007.12.016.

DOI:10.1016/j.clinthera.2007.12.016

PMID:18201591

Abstract

BACKGROUND

Recurrent painful vaso-occlusive crises (VOC) are a hallmark of sickle cell disease (SCD), and narcotic analgesics are an effective component of therapy. However, the belief that these drugs can promote development of the acute chest syndrome (ACS) may lead to undertreatment of pain.

OBJECTIVE

The aim of this study was to explore the potential association between a dose-response effect of morphine exposure and the development of ACS in children with SCD who presented with VOC.

METHODS

A retrospective, self-matched, case-crossover design was used to study data from children with SCD who were treated with continuous-drip IV morphine (initial rate of 10 mug/kg . h) for VOC and subsequently developed ACS (index hospitalization) at a tertiary pediatric hospital in Toronto, Ontario, Canada, from April 1, 2000, to March 31, 2006. So that each child could serve as his or her own control for the analysis, a comparison hospitalization for VOC was identified for each child during which ACS did not develop (reference hospitalization). We determined the cumulative dose of morphine administered before ACS development (index interval) during the index hospitalization and the cumulative amount of morphine administered during the same time interval during the reference hospitalization (reference interval).

RESULTS

Seventeen children (13 girls, 4 boys; index hospitalization: mean [SD] age, 8.9 [4.0] years; mean [SD] weight, 30.9 [15.2] kg; reference hospitalization: mean [SD] age, 8.6 [3.4] years; mean [SD] weight, 27.3 [11.2] kg) with SCD who met all inclusion criteria were identified. There was no significant difference in the cumulative morphine dose (mean [SD] amount, 1.24 [0.60] mg/kg) during the index interval compared with the amount administered during the reference interval (mean [SD] amount, 1.44 [0.84] mg/kg).

CONCLUSION

Among these children with SCD who presented with VOC, the administration of morphine was not found to be associated with a dose-response effect on the risk for ACS.

摘要

背景

复发性疼痛性血管闭塞危象（VOC）是镰状细胞病（SCD）的一个标志，麻醉性镇痛药是治疗的有效组成部分。然而，认为这些药物会促进急性胸综合征（ACS）发展的观点可能导致疼痛治疗不足。

目的

本研究的目的是探讨吗啡暴露的剂量反应效应与出现VOC的SCD儿童发生ACS之间的潜在关联。

方法

采用回顾性、自身匹配、病例交叉设计，研究2000年4月1日至2006年3月31日在加拿大多伦多一家三级儿科医院接受持续静脉滴注吗啡（初始速率为10μg/kg·h）治疗VOC并随后发生ACS（索引住院）的SCD儿童的数据。为了使每个儿童都能作为自己分析的对照，为每个儿童确定一次未发生ACS的VOC对照住院（参考住院）。我们确定了索引住院期间ACS发生前给予的吗啡累积剂量（索引间隔）以及参考住院期间同一时间间隔内给予的吗啡累积量（参考间隔）。

结果

确定了17名符合所有纳入标准的SCD儿童（13名女孩，4名男孩；索引住院：平均[标准差]年龄，8.9[4.0]岁；平均[标准差]体重，30.9[15.2]kg；参考住院：平均[标准差]年龄，8.6[3.4]岁；平均[标准差]体重，27.3[11.2]kg）。与参考间隔期间给予的量（平均[标准差]量，1.44[0.84]mg/kg）相比，索引间隔期间的吗啡累积剂量（平均[标准差]量，1.24[0.60]mg/kg）无显著差异。