Hughes J, Gill A M, Mulhearn H, Powell E, Choonara I
Institute of Child Health, Alder Hey Children's Hospital, Liverpool, England.
Ann Pharmacother. 1996 Jan;30(1):27-30. doi: 10.1177/106002809603000104.
To determine the steady-state plasma concentrations of midazolam in critically ill infants and children.
Prospective uncontrolled study conducted over 18 months.
Regional pediatric intensive care unit in a children's hospital.
Thirty-eight infants and children, aged 1 month to 13 years, requiring midazolam as sedation during mechanical ventilation. The patients were divided into three age groups: (1) infants less than 12 months (n = 16); (2) children 1-2 years (n = 12); and (3) children aged 3 years and older (n = 10).
A single blood sample was collected once steady-state plasma concentrations of midazolam were achieved during a continuous intravenous infusion. Plasma clearance was calculated from the plasma concentrations and infusion rate.
The plasma clearance was higher in children aged 3 years and older (median plasma clearance 13.0 mL/min/kg) than in infants and children 1-2 years old (median plasma clearance 3.1 and 2.3 mL/min/kg, respectively) (Kruskal-Wallis analysis of variance, p < 0.01). The midazolam infusion rates were similar for the three groups studied (Kruskal-Wallis analysis of variance, p > 0.05). The plasma concentrations of midazolam were significantly lower in children 3 years and older (median plasma concentration 128 ng/mL) than in infants and children 1-2 years old (median plasma concentrations 395 and 790 ng/mL, respectively) (Kruskal-Wallis analysis of variance, p < 0.05).
The plasma clearance in children 3 years and older was higher than in infants and children up to 2 years old. There was considerable interindividual variation in the steady-state plasma concentrations of midazolam in critically ill infants and children.
测定危重症婴幼儿和儿童中咪达唑仑的稳态血浆浓度。
为期18个月的前瞻性非对照研究。
儿童医院的区域儿科重症监护病房。
38名年龄在1个月至13岁之间、在机械通气期间需要使用咪达唑仑进行镇静的婴幼儿和儿童。患者被分为三个年龄组：（1）小于12个月的婴儿（n = 16）；（2）1至2岁的儿童（n = 12）；（3）3岁及以上的儿童（n = 10）。
在持续静脉输注期间，一旦达到咪达唑仑的稳态血浆浓度，采集一份血样。根据血浆浓度和输注速率计算血浆清除率。
3岁及以上儿童的血浆清除率（血浆清除率中位数为13.0 mL/min/kg）高于1至2岁的婴幼儿和儿童（血浆清除率中位数分别为3.1和2.3 mL/min/kg）（Kruskal-Wallis方差分析，p < 0.01）。所研究的三组的咪达唑仑输注速率相似（Kruskal-Wallis方差分析，p > 0.05）。3岁及以上儿童的咪达唑仑血浆浓度（血浆浓度中位数为128 ng/mL）显著低于1至2岁的婴幼儿和儿童（血浆浓度中位数分别为395和790 ng/mL）（Kruskal-Wallis方差分析，p < 0.05）。
3岁及以上儿童的血浆清除率高于2岁及以下的婴幼儿和儿童。危重症婴幼儿和儿童中咪达唑仑的稳态血浆浓度存在相当大的个体差异。
