Hakim Mohammed, Anderson Brian J, Walia Hina, Tumin Dmitry, Michalsky Marc P, Syed Ahsan, Tobias Joseph D
Department of Anesthesiology & Pain Medicine, Nationwide Children's Hospital, Columbus, Ohio.
Department of Anesthesiology, University of Auckland, Auckland, New Zealand.
Paediatr Anaesth. 2019 Jan;29(1):20-26. doi: 10.1111/pan.13525. Epub 2018 Nov 28.
Intravenous acetaminophen is commonly administered as an adjunctive to opioids during major surgical procedures, but neither the correct pharmacokinetic size descriptor nor the dose is certain in severely obese adolescents undergoing bariatric surgery.
Adolescents, 14-20 years of age, with a body mass index (BMI) ≥95th percentile for age and sex or BMI ≥40 kg·m , presenting for laparoscopic or robotic assisted or vertical sleeve gastrectomy were administered intravenous acetaminophen (1000 mg) following completion of the surgical procedure. Venous blood was drawn for acetaminophen assay at eight time points, starting 15 minutes after completion of the infusion and up to 12 hours afterward. Time-concentration data profiles were analyzed using nonlinear mixed effects models. Parameter estimates were scaled to a 70-kg person using allometry. Normal fat mass was used to assess the impact of obesity on pharmacokinetic parameters.
The study cohort comprised 11 female patients, age 17 SD 2 years with a weight of 125 SD 19 kg and a mean BMI of 46 SD 5 kg·m . The plasma acetaminophen serum concentration was 17 (SD 4) μg·mL at 10-20 minutes after completion of the infusion and 5 (SD 6) μg·mL at 80-100 minutes. A two-compartment model, used to investigate pharmacokinetics, estimated clearance 10.6 (CV 72%) L·h·70 kg , intercompartment clearance 37.3 (CV 63%) L·h·70 kg , central volume of distribution 20.4 (CV 46%) L·70 kg , and peripheral volume of distribution 16.8 (CV 42%) L·70 kg . Clearance was best described using total body weight. Normal fat mass with a parameter that accounts for fat mass contribution (Ffat) of 0.88 best described volumes.
Current recommendations of acetaminophen to a maximum dose of 1000 mg resulted in serum concentrations below detection limits in all patients within 2 hours after administration. Dose is better predicted using total body mass with allometric scaling.
在大型外科手术期间，静脉注射对乙酰氨基酚通常作为阿片类药物的辅助用药，但对于接受减肥手术的严重肥胖青少年，正确的药代动力学大小描述符和剂量都不确定。
年龄在14 - 20岁、体重指数（BMI）处于年龄和性别的第95百分位数以上或BMI≥40kg·m²、拟行腹腔镜或机器人辅助或垂直袖状胃切除术的青少年，在手术结束后静脉注射对乙酰氨基酚（1000mg）。在输注完成后15分钟开始，直至12小时后的八个时间点采集静脉血进行对乙酰氨基酚检测。使用非线性混合效应模型分析时间 - 浓度数据曲线。参数估计值使用异速生长法按70kg的人进行缩放。使用正常脂肪量评估肥胖对药代动力学参数的影响。
研究队列包括11名女性患者，年龄17±2岁，体重125±1 kg，平均BMI为46±5kg·m²。输注完成后10 - 20分钟时血浆对乙酰氨基酚血清浓度为17（标准差4）μg·mL，80 - 100分钟时为5（标准差6）μg·mL。用于研究药代动力学的二室模型估计清除率为10.6（变异系数72%）L·h⁻¹·70kg⁻¹，室间清除率为37.3（变异系数63%）L·h⁻¹·70kg⁻¹，中央分布容积为20.4（变异系数46%）L·70kg⁻¹，外周分布容积为16.8（变异系数42%）L·70kg⁻¹。清除率用总体重描述最佳。正常脂肪量以及一个考虑脂肪量贡献（Ffat）为0.88的参数对容积描述最佳。
目前对乙酰氨基酚最大剂量为1000mg的推荐导致所有患者给药后2小时内血清浓度低于检测限。使用总体重和异速生长缩放能更好地预测剂量。
