评估单次芬太尼栓剂对儿童的镇痛效果:基于七氟醚全身麻醉期间痛觉水平指数的药代动力学和药效学分析。

IF 1.7 4区 医学 Q2 ANESTHESIOLOGY Pediatric Anesthesia Pub Date : 2024-12-01 Epub Date: 2024-10-04 DOI:10.1111/pan.15013
Francisco Cruzat, Mauricio Ibacache, Alejandro González, Juan Cristóbal Pedemonte, Víctor Contreras, Ady Giordano, Ignacio Cortínez
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引用次数: 0

摘要

背景:痛觉水平指数在估计成人的痛觉/反痛觉平衡方面显示出优势,但在儿童人群中的证据却很有限。目的:评估痛觉水平指数识别标准化痛觉刺激和芬太尼栓剂镇痛效果的能力。此外,研究七氟醚麻醉期间芬太尼与痛觉水平指数反应的药代动力学/药效学关系:研究对象为19名计划接受下腹部或泌尿科手术的儿童,年龄为5.3(4.1-6.7)岁。七氟醚麻醉和尾部阻滞后,在前臂进行四肢刺激(50 赫兹,60 毫安,5 秒)。静脉注射 2 μg/kg 芬太尼后,分别在 5 分钟、15 分钟和 30 分钟后进行三次类似的连续四联律刺激。比较了痛觉水平指数、心率、平均动脉压和双频谱指数在四肢刺激下的变化。利用芬太尼血浆浓度和痛觉水平指数数据,使用 NONMEM® 中的顺序建模方法建立了药代动力学/药效学模型:结果:在第一次四联刺激后,痛觉水平指数和心率与基线相比均有所上升(8 ± 7 vs. 19 ± 10;平均差(CI95)-12(-18--6)和 100 ± 10 vs. 102 ± 10;-2(-4--0.1)),而在给予芬太尼后则有所下降(19 ± 10 vs. 8 ± 8;12(5-18)和 102 ± 10 vs. 91 ± 11;11(7-16))。在随后的四联刺激中,心率保持不变,而痛觉水平指数在 15 分钟内逐渐增加到与使用芬太尼前相似的值。异速体重比例三室模型最能体现芬太尼的药代动力学特征。药代动力学/药效学模型分析显示,芬太尼血浆浓度与痛觉水平指数反应之间存在滞后现象,血浆效应部位平衡半衰期为 1.69 (0.4-2.9) 分钟。估计的芬太尼 C50 为 1.93 (0.73-4.2) 纳克/毫升:与传统的血流动力学变量相比,痛觉水平指数在七氟醚麻醉下的儿童不同芬太尼浓度时判别不同痛觉-反痛觉水平的能力更强。
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Assessment of the antinociceptive effect of a single fentanyl bolus dose in children: A pharmacokinetic and pharmacodynamic analysis based on the nociception level index during sevoflurane general anesthesia.

Background: The Nociception Level Index has shown benefits in estimating the nociception/antinociception balance in adults, but there is limited evidence in the pediatric population. Evaluating the index performance in children might provide valuable insights to guide opioid administration.

Aims: To evaluate the Nociception Level Index ability to identify a standardized nociceptive stimulus and the analgesic effect of a fentanyl bolus. Additionally, to characterize the pharmacokinetic/pharmacodynamic relationship of fentanyl with the Nociception Level Index response during sevoflurane anesthesia.

Methods: Nineteen children, 5.3 (4.1-6.7) years, scheduled for lower abdominal or urological surgery, were studied. After sevoflurane anesthesia and caudal block, a tetanic stimulus (50 Hz, 60 mA, 5 s) was performed in the forearm. Following the administration of fentanyl 2 μg/kg intravenous bolus, three similar consecutive tetanic stimuli were performed at 5-, 15-, and 30-min post-fentanyl administration. Changes in the Nociception Level Index, heart rate, mean arterial pressure, and bispectral index were compared in response to the tetanic stimuli. Fentanyl plasma concentrations and the Nociception Level Index data were used to elaborate a pharmacokinetic/pharmacodynamic model using a sequential modeling approach in NONMEM®.

Results: After the first tetanic stimulus, both the Nociception Level Index and the heart rate increased compared to baseline (8 ± 7 vs. 19 ± 10; mean difference (CI95) -12(-18--6) and 100 ± 10 vs. 102 ± 10; -2(-4--0.1)) and decrease following fentanyl administration (19 ± 10 vs. 8 ± 8; 12 (5-18) and 102 ± 10 vs. 91 ± 11; 11 (7-16)). In subsequent tetanic stimuli, heart rate remained unchanged, while the Nociception Level Index progressively increased within 15 min to values similar to those before fentanyl. An allometric weight-scaled, 3-compartment model best characterized the pharmacokinetic profile of fentanyl. The pharmacokinetic/pharmacodynamic modeling analysis revealed hysteresis between fentanyl plasma concentrations and the Nociception Level Index response, characterized by plasma effect-site equilibration half-time of 1.69 (0.4-2.9) min. The estimated fentanyl C50 was 1.93 (0.73-4.2) ng/mL.

Conclusion: The Nociception Level Index showed superior capability compared to traditional hemodynamic variables in discriminating different nociception-antinociception levels during varying fentanyl concentrations in children under sevoflurane anesthesia.

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来源期刊
Pediatric Anesthesia
Pediatric Anesthesia 医学-麻醉学
CiteScore
3.20
自引率
11.80%
发文量
222
审稿时长
3-8 weeks
期刊介绍: Devoted to the dissemination of research of interest and importance to practising anesthetists everywhere, the scientific and clinical content of Pediatric Anesthesia covers a wide selection of medical disciplines in all areas relevant to paediatric anaesthesia, pain management and peri-operative medicine. The International Editorial Board is supported by the Editorial Advisory Board and a team of Senior Advisors, to ensure that the journal is publishing the best work from the front line of research in the field. The journal publishes high-quality, relevant scientific and clinical research papers, reviews, commentaries, pro-con debates, historical vignettes, correspondence, case presentations and book reviews.
期刊最新文献
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