年龄及治疗相关因素对术后婴儿吗啡需求量、吗啡及其代谢产物血浆浓度的影响

Age- and therapy-related effects on morphine requirements and plasma concentrations of morphine and its metabolites in postoperative infants.

作者信息

Bouwmeester N J, van den Anker J N, Hop W C J, Anand K J S, Tibboel D

机构信息

Department of Anaesthesiology, Erasmus MC/Sophia, Dr Molewaterplein 60, NL-3015 GJ Rotterdam, the Netherlands.

出版信息

Br J Anaesth. 2003 May;90(5):642-52. doi: 10.1093/bja/aeg121.

DOI:10.1093/bja/aeg121

PMID:12697593

Abstract

BACKGROUND

To investigate clinical variables such as gestational age, sex, weight, the therapeutic regimens used and mechanical ventilation that might affect morphine requirements and plasma concentrations of morphine and its metabolites.

METHODS

In a double-blind study, neonates and infants stratified for age [group I 0-4 weeks (neonates), group II > or =4-26 weeks, group III > or =26-52 weeks, group IV > or =1-3 yr] admitted to the paediatric intensive care unit after abdominal or thoracic surgery received morphine 100 micro g kg(-1) after surgery, and were randomly assigned to either continuous morphine 10 micro g kg(-1) h(-1) or intermittent morphine boluses 30 micro g kg(-1) every 3 h. Pain was measured using the COMFORT behavioural scale and a visual analogue scale. Additional morphine was administered on guidance of the pain scores. Morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) plasma concentrations were measured before, directly after, and at 6, 12 and 24 h after surgery.

RESULTS

Multiple regression analysis of different variables revealed that age was the most important factor affecting morphine requirements and plasma morphine concentrations. Significantly fewer neonates required additional morphine doses compared with all other age groups (P<0.001). Method of morphine administration (intermittent vs continuous) had no significant influence on morphine requirements. Neonates had significantly higher plasma concentrations of morphine, M3G and M6G (all P<0.001), and significantly lower M6G/morphine ratio (P<0.03) than the older children. The M6G/M3G ratio was similar in all age groups.

CONCLUSIONS

Neonates have a narrower therapeutic window for postoperative morphine analgesia than older age groups, with no difference in the safety or effectiveness of intermittent doses compared with continuous infusions in any of these age groups. In infants >1 month of age, analgesia is achieved after morphine infusions ranging from 10.9 to 12.3 micro g kg(-1) h(-1) at plasma concentrations of <15 ng ml(-1).

摘要

背景

研究诸如胎龄、性别、体重、所用治疗方案及机械通气等可能影响吗啡需求量以及吗啡及其代谢产物血浆浓度的临床变量。

方法

在一项双盲研究中，因腹部或胸部手术后入住儿科重症监护病房的新生儿和婴儿按年龄分层[I组0 - 4周（新生儿），II组≥4 - 26周，III组≥26 - 52周，IV组≥1 - 3岁]，术后接受100μg/kg的吗啡，然后随机分为持续静脉输注吗啡10μg·kg⁻¹·h⁻¹或每3小时间断静脉推注吗啡30μg/kg。使用COMFORT行为量表和视觉模拟量表测量疼痛程度。根据疼痛评分指导追加吗啡。在手术前、术后即刻以及术后6、12和24小时测量吗啡、吗啡-3-葡萄糖醛酸苷（M3G）和吗啡-6-葡萄糖醛酸苷（M6G）的血浆浓度。

结果

对不同变量进行多元回归分析显示，年龄是影响吗啡需求量和血浆吗啡浓度的最重要因素。与所有其他年龄组相比，需要追加吗啡剂量的新生儿明显更少（P<0.001）。吗啡给药方式（间断与持续）对吗啡需求量无显著影响。新生儿的吗啡、M3G和M6G血浆浓度显著更高（均P<0.001），且M6G/吗啡比值显著更低（P<0.03），比大龄儿童低。所有年龄组的M6G/M3G比值相似。