Prins Sandra A, Van Dijk Monique, Van Leeuwen Pim, Searle Susan, Anderson Brian J, Tibboel Dick, Mathot Ron A A
Department of Pediatric Surgery, Erasmus MC, Sophia Children's Hospital, Rotterdam, The Netherlands.
Paediatr Anaesth. 2008 Jul;18(7):582-92. doi: 10.1111/j.1460-9592.2008.02619.x. Epub 2008 May 8.
The pharmacokinetics and analgesic effects of intravenous and rectal paracetamol were compared in nonventilated infants after craniofacial surgery in a double-blind placebo controlled study.
During surgery all infants (6 months-2 years) received a rectal loading dose of 40 mg.kg(-1) paracetamol 2 h before anticipated extubation. On admittance to the pediatric surgical ICU, the children were randomized to receive either a 15 min intravenous infusion of 40 mg.kg(-1) propacetamol, a prodrug of paracetamol, or 20 mg.kg(-1) paracetamol rectally every 6 h. A population pharmacokinetic analysis of the paracetamol plasma concentration time-profiles was undertaken using nonlinear mixed effects models. The visual analogue scale (VAS) (score 0-10 cm) and COMFORT Behavior scale (score 6-30) were used to monitor analgesia in the 24-h period following surgery.
Twelve infants received intravenous propacetamol and 14 paracetamol suppositories. Paracetamol pharmacokinetics were described according to a two-compartmental model with linear disposition. Pharmacokinetic parameters were standardized to a 70 kg person using allometric '1/4 power' models. Parameter estimates were: absorption half-life from the rectum 4.6 h, propacetamol hydrolysis half-life 0.028 h, clearance 12 l.h(-1).70 kg(-1), intercompartmental clearance 116 l.h(-1).70 kg(-1), central and peripheral volume of distribution 7.9 and 44 l.70 kg(-1), respectively. During the 24-h study period 22 infants exhibited VAS scores <4 cm, which was considered a cutoff point. On single occasions four patients, two in each group, exhibited a VAS score >/=4 cm. Nine patients in the rectal treatment group and three patients in the intravenous treatment group received midazolam for COMFORT-B scores exceeding 17 (P < 0.05).
Intravenous propacetamol proved to be more effective than rectal paracetamol in infants after craniofacial surgery. Midazolam was more frequently administered to patients receiving paracetamol suppositories, indicating that these children experienced more distress, possibly caused by pain.
在一项双盲安慰剂对照研究中，比较了颅面外科手术后未通气婴儿静脉注射和直肠给予对乙酰氨基酚的药代动力学及镇痛效果。
手术期间，所有婴儿（6个月至2岁）在预计拔管前2小时接受40mg·kg⁻¹对乙酰氨基酚的直肠负荷剂量。进入小儿外科重症监护病房后，将儿童随机分为两组，一组接受15分钟的静脉输注40mg·kg⁻¹丙帕他莫（对乙酰氨基酚的前体药物），另一组每6小时直肠给予20mg·kg⁻¹对乙酰氨基酚。使用非线性混合效应模型对乙酰氨基酚血浆浓度时间曲线进行群体药代动力学分析。在术后24小时内，使用视觉模拟评分法（VAS）（评分0 - 10cm）和舒适行为量表（评分6 - 30）监测镇痛效果。
12名婴儿接受静脉注射丙帕他莫，14名婴儿接受对乙酰氨基酚栓剂。对乙酰氨基酚的药代动力学根据具有线性处置的二室模型进行描述。使用异速生长“1/4幂”模型将药代动力学参数标准化为70kg的个体。参数估计值为：直肠吸收半衰期4.6小时，丙帕他莫水解半衰期0.028小时，清除率12L·h⁻¹·70kg⁻¹，室间清除率116L·h⁻¹·70kg⁻¹，中央室和外周室分布容积分别为7.9L和44L·70kg⁻¹。在24小时研究期间，22名婴儿的VAS评分<4cm，这被视为一个临界点。单次测量时，每组各有2名患者的VAS评分≥4cm。直肠治疗组有9名患者，静脉治疗组有3名患者因舒适行为量表 - B评分超过17而接受咪达唑仑治疗（P < 0.05）。
在颅面外科手术后的婴儿中，静脉注射丙帕他莫比直肠给予对乙酰氨基酚更有效。接受对乙酰氨基酚栓剂的患者更频繁地使用咪达唑仑，表明这些儿童经历了更多的痛苦，可能是由疼痛引起的。
