Department of Pediatrics, Erasmus Medical Center, Rotterdam, The Netherlands,
Clin Drug Investig. 2003;23(1):27-38. doi: 10.2165/00044011-200323010-00004.
The aim of this study was to evaluate the pharmacodynamics and safety of midazolam after intravenous infusion or oral administration in preterm infants. METHODS ]PATIENTS WERE RANDOMLY ASSIGNED TO INITIALLY RECEIVE MIDAZOLAM 0.1 MG/KG AS A 30-MINUTE INTRAVENOUS INFUSION OR AN ORAL BOLUS DOSE. IF PATIENTS STILL MET THE INCLUSION CRITERIA, THEY THEN RECEIVED MIDAZOLAM VIA THE ALTERNATE ROUTE (AFTER AN INTERVAL OF ≥72 HOURS). PHARMACODYNAMIC MEASUREMENTS CONSISTED OF A COMFORT® SCORE (A PREVIOUSLY VALIDATED SEDATION SCALE FOR PAEDIATRIC PATIENTS) AT BASELINE AND AT 0.5, 1, 2, 4 AND 6 HOURS POSTDOSE. MIDAZOLAM AND 1-OH-MIDAZOLAM CONCENTRATIONS WERE MEASURED AND VITAL SIGNS WERE RECORDED AT ALL PHARMACODYNAMIC MEASUREMENT TIMEPOINTS:
A total of 24 infants were enrolled of whom seven received both intravenous and oral midazolam, 13 received only intravenous midazolam, and four received only oral midazolam. Overall, mean COMFORT® scores decreased (i.e. sedation increased) significantly within 30 minutes after intravenous (p S 0.05) and within 1 hour after oral (p = 0.003) midazolam administration. In 45% of patients the COMFORT® scores decreased little or not at all after midazolam, which was similar after both oral and intravenous administration. The sedative response to midazolam did not differ after intravenous or oral administration. No relationship was found between overall COMFORT® scores or change in COMFORT® score from baseline and midazolam, 1-OH-midazolam, or midazolam plus 1-OH-midazolam concentrations. Diastolic blood pressure decreased significantly after intravenous (approximately 11%) but not after oral midazolam administration. No serious adverse events were reported.
Midazolam administered as a 30-minute intravenous infusion or oral bolus dose appears to be effective and well tolerated in a small majority of preterm infants. However, a considerable number of neonates do not appear to respond to midazolam. The lack of response may be due to the fact that patients truly experienced therapeutic failure and/or consequent to the inability of the COMFORT® score to adequately reflect sedation uniformly in sick preterm infants.
本研究旨在评估早产儿静脉输注或口服咪达唑仑后的药效学和安全性。
将患者随机分为初始接受咪达唑仑 0.1mg/kg 静脉输注 30 分钟或口服推注剂量。如果患者仍符合纳入标准，则在≥72 小时后通过另一种途径（静脉或口服）接受咪达唑仑。药效学测量包括在基线和给药后 0.5、1、2、4 和 6 小时使用舒适度评分（以前为儿科患者验证的镇静评分）。测量咪达唑仑和 1-OH-咪达唑仑浓度，并在所有药效学测量时间点记录生命体征。
共纳入 24 例婴儿，其中 7 例接受了咪达唑仑静脉和口服治疗，13 例仅接受了咪达唑仑静脉治疗，4 例仅接受了咪达唑仑口服治疗。总体而言，咪达唑仑静脉给药后 30 分钟内（p S 0.05）和口服后 1 小时内（p = 0.003），舒适度评分显著下降（即镇静作用增强）。在 45%的患者中，咪达唑仑后舒适度评分下降很少或根本没有下降，这与口服和静脉给药后相似。咪达唑仑的镇静反应在静脉和口服给药后没有差异。总体舒适度评分或舒适度评分从基线的变化与咪达唑仑、1-OH-咪达唑仑或咪达唑仑加 1-OH-咪达唑仑浓度之间均无相关性。静脉注射咪达唑仑后舒张压显著下降（约 11%），但口服咪达唑仑后无此现象。未报告严重不良事件。
咪达唑仑作为 30 分钟静脉输注或口服推注剂量，在小部分早产儿中似乎是有效且耐受良好的。然而，相当数量的新生儿似乎对咪达唑仑没有反应。这种无反应可能是由于患者确实经历了治疗失败，和/或舒适度评分无法在患有疾病的早产儿中均匀地反映镇静作用所致。
