Department of Anesthesia and Paediatrics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, MLC 2001, Cincinnati, OH, 45229, USA ; University of Cincinnati, Cincinnati, OH, USA.
Division of Pharmacology, Leiden/Amsterdam Center for Drug Research, Leiden, Netherlands.
BMC Anesthesiol. 2013 Apr 21;13:8. doi: 10.1186/1471-2253-13-8. eCollection 2013.
Poor characterization of propofol pharmacokinetics and pharmacodynamics in the morbidly obese (MO) pediatric population poses dosing challenges. This study was conducted to evaluate propofol total intravenous anesthesia (TIVA) in this population.
After IRB approval, a prospective study was conducted in 20 MO children and adolescents undergoing laparoscopic surgery under clinically titrated propofol TIVA. Propofol doses/infusion rates, hemodynamic variables, times to induction and emergence, and postoperative occurrence of respiratory adverse events (RAE) were recorded, along with intraoperative blinded Bispectral Index/BIS and postoperative Ramsay sedation scores (RSS). Study subjects completed awareness questionnaires on postoperative days 1 and 3. Propofol concentrations were obtained at predetermined intra- and post-operative time points.
Study subjects ranged 9 - 18 years (age) and 97 - 99.9% (BMI for age percentiles). Average percentage variability of hemodynamic parameters from baseline was ≈ 20%. Patients had consistently below target BIS values (BIS < 40 for >90% of maintenance phase), delayed emergence (25.8 ± 22 minutes), increased somnolence (RSS ≥ 4) in the first 30 minutes of recovery from anesthesia and 30% incidence of postoperative RAE, the odds for which increased by 14% per unit increase in BMI (p ≤ 0.05). Mean propofol concentration was 6.2 mg/L during maintenance and 1.8 mg/L during emergence from anesthesia.
Our findings indicate clinical overestimation of propofol requirements and highlight the challenges of clinically titrated propofol TIVA in MO adolescents. In this setting, it may be advantageous to titrate propofol to targeted BIS levels until more accurate weight-appropriate dosing regimens are developed, to minimize relative overdosing and its consequences.
病态肥胖（MO）儿科人群中丙泊酚药代动力学和药效学特征描述不佳，导致给药存在挑战。本研究旨在评估该人群中丙泊酚全凭静脉麻醉（TIVA）的效果。
在机构审查委员会（IRB）批准后，对 20 名接受腹腔镜手术的 MO 儿童和青少年进行了一项前瞻性研究，这些患者在临床滴定丙泊酚 TIVA 下进行手术。记录丙泊酚剂量/输注率、血流动力学变量、诱导和苏醒时间以及术后呼吸不良事件（RAE）的发生情况，同时记录术中盲法脑电双频指数（BIS）/BIS 和术后 Ramsay 镇静评分（RSS）。研究对象在术后第 1 天和第 3 天完成意识调查问卷。在预定的术中及术后时间点获取丙泊酚浓度。
研究对象的年龄范围为 9-18 岁，BMI 年龄百分位为 97-99.9%。与基线相比，血流动力学参数的平均百分比变化约为 20%。患者的 BIS 值始终低于目标值（维持阶段超过 90%的时间 BIS<40），苏醒延迟（25.8±22 分钟），麻醉恢复 30 分钟内镇静程度增加（RSS≥4），且 30%的患者发生术后 RAE，BMI 每增加一个单位，RAE 的发生几率增加 14%（p≤0.05）。维持阶段丙泊酚的平均浓度为 6.2mg/L，麻醉苏醒阶段丙泊酚的平均浓度为 1.8mg/L。
本研究结果表明，临床对丙泊酚需求的估计过高，并强调了在 MO 青少年中临床滴定丙泊酚 TIVA 的挑战。在这种情况下，将丙泊酚滴定至靶向 BIS 水平可能更有利，直到开发出更准确的、适合体重的给药方案，以尽量减少相对过量用药及其后果。
