Saarenmaa E, Neuvonen P J, Rosenberg P, Fellman V
Hospital for Children and Adolescents, the Department of Clinical Pharmacology, University of Helsinki, Finland.
Clin Pharmacol Ther. 2000 Aug;68(2):160-6. doi: 10.1067/mcp.2000.108947.
We sought to provide a rational basis for morphine administration in preterm infants in the immediate postnatal period by determining the clearance and evaluating the efficacy and adverse effects of a continuous infusion.
Morphine was infused for 2 to 4 days (140 microg/kg over 1 hour followed by 20 microg/kg/h) to 31 ventilator-treated newborn infants (gestational age, 24 to 41 weeks; birth weight, 765 to 4,015 g). Morphine, morphine-3-glucuronide, and morphine-6-glucuronide concentrations in serum were determined from arterial blood obtained at 2, 12, 24, 48, and 60 hours after the start of morphine infusion at a median postnatal age of 10 hours.
The mean +/- SD steady-state morphine concentration, 167 +/- 77 ng/mL, was achieved between 24 and 48 hours of infusion, and morphine-6-glucuronide and morphine-3-glucuronide concentrations did not reach steady state within 60 hours. Morphine clearance (range, 0.8 to 6.5 mL/min/kg) correlated significantly with gestational age (r = 0.60; P < .01) and birth weight (r = 0.55; P < .01). Pain relief did not correlate with the steady-state morphine concentration. However, significantly higher morphine concentrations were found in infants with decreased gastrointestinal motility (187 +/- 82 ng/mL) compared with those without (128 +/- 51 ng/mL; P < .05).
Morphine should be used with caution in prematurely born infants because of its low clearance, which correlates with gestational age.
通过测定清除率并评估持续输注的疗效和不良反应，为出生后即刻的早产儿吗啡给药提供合理依据。
对31例接受机械通气治疗的新生儿（胎龄24至41周；出生体重765至4015克）输注吗啡2至4天（1小时内输注140微克/千克，随后以20微克/千克/小时的速度输注）。在吗啡输注开始后2、12、24、48和60小时，从中位数出生后10小时的动脉血中测定血清中的吗啡、吗啡-3-葡萄糖醛酸苷和吗啡-6-葡萄糖醛酸苷浓度。
在输注24至48小时之间达到平均±标准差稳态吗啡浓度，即167±77纳克/毫升，而吗啡-6-葡萄糖醛酸苷和吗啡-3-葡萄糖醛酸苷浓度在60小时内未达到稳态。吗啡清除率（范围为0.8至6.5毫升/分钟/千克）与胎龄（r = 0.60；P <.01）和出生体重（r = 0.55；P <.01）显著相关。疼痛缓解与稳态吗啡浓度无关。然而，与胃肠道蠕动未减弱的婴儿（128±51纳克/毫升）相比，胃肠道蠕动减弱的婴儿（187±82纳克/毫升）的吗啡浓度显著更高（P <.05）。
由于吗啡清除率低且与胎龄相关，因此在早产儿中应谨慎使用。
