复合丙泊酚时奥赛利定用于亚临床肥胖患者双向内窥镜检查的半数有效剂量

doi:10.12092/j.issn.1009-2501.2026.04.008

中国临床药理学与治疗学 ›› 2026, Vol. 31 ›› Issue (4): 493-499.doi: 10.12092/j.issn.1009-2501.2026.04.008

复合丙泊酚时奥赛利定用于亚临床肥胖患者双向内窥镜检查的半数有效剂量

姬永久¹^,²(), 周素利¹, 杨斯淇¹, 涂映舟¹, 姜陈琦¹, 张冰缘³, 朱昌茂¹, 张琪¹, 杨春¹^,*(), 胡苏皖¹^,*()

1. 南京医科大学第一附属医院麻醉与围术期医学科，南京 210029，江苏
2. 淮安市第五人民医院麻醉科，淮安 223300，江苏
3. 南京医科大学附属泰州市人民医院麻醉科，泰州 225300，江苏

收稿日期:2025-06-24 修回日期:2025-07-31 出版日期:2026-04-26 发布日期:2026-04-30
通讯作者: 杨春,胡苏皖 E-mail:330729093@qq.com;chunyang@njmu.edu.cn;swhu@njmu.edu.cn
作者简介:姬永久，男，副主任医师，研究方向：临床麻醉与镇痛。E-mail：330729093@qq.com
基金资助:
吴阶平医学基金会临床科研专项资助基金（320.6750.2024-15-99；310.6750.2024-15-82；310.6750.2024-15-81；320.6750.2024-05-51）

Median effective dose of oliceridine as an adjunct to propofol sedation in patients with preclinical obesity undergoing same-visit bidirectional endoscopy

Yongjiu JI¹^,²(), Suli ZHOU¹, Siqi YANG¹, Yingzhou TU¹, Chenqi JIANG¹, Bingyuan ZHANG³, Changmao ZHU¹, Qi ZHANG¹, Chun YANG¹^,*(), Suwan HU¹^,*()

1. Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China
2. Department of Anesthesiology, Huai'an Fifth People's Hospital, Huai'an 223300, Jiangsu, China
3. Department of Anesthesiology, Taizhou People's Hospital Affiliated to Nanjing Medical University, Taizhou 225300, Jiangsu, China

Received:2025-06-24 Revised:2025-07-31 Online:2026-04-26 Published:2026-04-30
Contact: Chun YANG,Suwan HU E-mail:330729093@qq.com;chunyang@njmu.edu.cn;swhu@njmu.edu.cn

摘要/Abstract

摘要：

目的: 基于去脂体重，测定复合不同剂量丙泊酚时奥赛利定用于亚临床肥胖患者同次就诊双向内窥镜检查的半数有效剂量（ED₅₀）和95%有效剂量（ED₉₅），为该人群临床麻醉合理用药提供参考。方法: 纳入54例ASA分级Ⅱ或Ⅲ级的亚临床肥胖患者，随机接受丙泊酚2.0 mg/kg（P1组，n=28）或2.5 mg/kg（P2组，n=26）复合奥赛利定（起始剂量0.02 mg/kg，梯度±0.005 mg/kg）。以胃镜操作中呛咳或体动反应≥2级（需暂停操作或加深麻醉）为阳性反应，以阳性反应转阴性反应为交叉点，当出现7个交叉点时终止研究。采用Probit概率回归法计算ED值，监测血流动力学及不良事件。结果: 两组患者基线资料（性别、年龄、BMI、去脂体重等）无统计学差异。基于去脂体重，P1组奥赛利定的ED₅₀为0.037 mg/kg（95%CI: 0.033～0.042），ED₉₅为0.048 mg/kg（95%CI: 0.043～0.075）；P2组ED₅₀为0.012 mg/kg（95%CI: 0.004～0.016），ED₉₅为0.023 mg/kg（95%CI: 0.017～0.063）。丙泊酚剂量从2.0 mg/kg增至2.5 mg/kg使奥赛利定ED₅₀降低52.1%，ED₉₅降低67.6%（P<0.001）。P2组呼吸抑制（SpO₂<90%）发生率低于P1组（30.8% vs. 46.4%），心动过缓（11.5% vs. 0%）和低血压（15.4% vs. 3.6%）发生率较高，但差异无统计学意义。两组注射痛（25.0% vs. 26.9%）及苏醒/离院时间无统计学差异，均无恶心呕吐及离院后不良事件。结论: 奥赛利定与丙泊酚存在剂量协同效应。推荐基于去脂体重采用丙泊酚2.5 mg/kg复合奥赛利定0.023 mg/kg，该方案可减少奥赛利定用量及呼吸抑制风险，且恢复质量良好。

关键词: 奥赛利定, 丙泊酚, 亚临床肥胖, 双向内窥镜, 半数有效剂量

Abstract:

AIM: To determine the median effective dose (ED₅₀) and 95% effective dose (ED₉₅) of oliceridine based on lean body weight (LBW) when combined with different propofol doses for same-visit bidirectional endoscopy in patients with preclinical obesity. METHODS: Fifty-four ASA physical status II–III preclinical obesity patients were randomized to receive propofol 2.0 mg/kg LBW (Group P1, n=28) or 2.5 mg/kg LBW (Group P2, n=26) combined with oliceridine (initial dose 0.02 mg/kg LBW, adjusted in ±0.005 mg/kg LBW increments). A positive response was defined as coughing or body movement ≥ grade 2 during gastroscopy (requiring procedure suspension or anesthetic deepening). The study terminated after observing seven crossover points (positive-to-negative response transitions). ED values were calculated using Probit regression analysis. Hemodynamics and adverse events were recorded. RESULTS: Patient demographics (gender, age, BMI, LBW) showed no intergroup differences. Based on LBW, the ED₅₀ and ED₉₅ of oliceridine in Group P1 were 0.037 mg/kg (95%CI: 0.033–0.042) and 0.048 mg/kg (95%CI: 0.043–0.075), respectively; in Group P2, the ED₅₀ and ED₉₅ were 0.012 mg/kg (95%CI: 0.004–0.016) and 0.023 mg/kg (95%CI: 0.017–0.063), respectively. Increasing propofol from 2.0 mg/kg to 2.5 mg/kg reduced oliceridine ED₅₀ by 52.1% and ED₉₅ by 67.6% (P<0.001), indicating synergism. Group P2 had lower incidence of respiratory depression (SpO₂ <90%: 30.8% vs. 46.4%) but higher rates of bradycardia (11.5% vs. 0%) and hypotension (15.4% vs. 3.6%) (all P>0.05). Injection pain (P1: 25.0% vs. P2: 26.9%) and recovery/discharge times did not differ significantly. No nausea, vomiting, or post-discharge adverse events occurred in either group. CONCLUSION: Propofol and oliceridine exhibit dose-dependent synergism. For preclinical obesity patients, propofol 2.5 mg/kg LBW combined with oliceridine 0.023 mg/kg LBW is recommended, providing effective anesthesia with reduced oliceridine requirements, lower respiratory depression risk, and satisfactory recovery.

Key words: oliceridine, propofol, preclinical obesity, same-visit bidirectional endoscopy, median effective dose

中图分类号:

R614.2

姬永久, 周素利, 杨斯淇, 涂映舟, 姜陈琦, 张冰缘, 朱昌茂, 张琪, 杨春, 胡苏皖. 复合丙泊酚时奥赛利定用于亚临床肥胖患者双向内窥镜检查的半数有效剂量[J]. 中国临床药理学与治疗学, 2026, 31(4): 493-499.

Yongjiu JI, Suli ZHOU, Siqi YANG, Yingzhou TU, Chenqi JIANG, Bingyuan ZHANG, Changmao ZHU, Qi ZHANG, Chun YANG, Suwan HU. Median effective dose of oliceridine as an adjunct to propofol sedation in patients with preclinical obesity undergoing same-visit bidirectional endoscopy[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(4): 493-499.

图/表 6

参考文献 24

1	崔晓爽, 张二康, 夏洪莲, 等. 丙泊酚联合不同镇痛药物在肥胖患者胃肠镜检查中的应用比较[J]. 中国处方药, 2022, 20 (3): 177- 179. doi: 10.3969/j.issn.1671-945X.2022.03.074
2	朱昌茂, 谢力, 吴仔峰, 等. 偏向性μ-阿片受体激动剂奥赛利定的临床应用进展[J]. 中国临床药理学与治疗学, 2024, 29 (9): 1057- 1061.
3	Rubino F, Cummings DE, Eckel RH, et al. Definition and diagnostic criteria of clinical obesity[J]. Lancet Diabetes Endocrinol, 2025, 13 (3): 221- 262. doi: 10.1016/S2213-8587(24)00316-4
4	Wei CN, Deng JL, Dong JH, et al. The median effective dose of oxytocin needed to prevent uterine atony during cesarean delivery in elderly parturients[J]. Drug Des Devel Ther, 2020, 14, 5451- 5458. doi: 10.2147/DDDT.S258651
5	Janmahasatian S, Duffull SB, Ash S, et al. Quantification of lean bodyweight[J]. Clin Pharmacokinet, 2005, 44 (10): 1051- 1065. doi: 10.2165/00003088-200544100-00004
6	李红新, 肖海浩, 杨仁, 等. 环泊酚用于老年患者无痛纤维支气管镜检查的有效性及安全性[J]. 实用医学杂志, 2025, 41 (8): 1217- 1223. doi: 10.3969/j.issn.1006-5725.2025.08.019
7	李平乐, 杨智虎, 邢飞, 等. 肥胖因素对复合阿芬太尼时瑞马唑仑用于无痛胃镜检查术量效关系的影响[J]. 中华麻醉学杂志, 2022, 42 (6): 712- 715.
8	刘婷婷, 刘存明. 丙泊酚在克罗恩病患者无痛胃肠镜检查中的半数有效剂量[J]. 临床麻醉学杂志, 2023, 39 (6): 577- 581. doi: 10.12089/jca.2023.06.003
9	Oron AP, Souter MJ, Flournoy N. Understanding research methods: Up-and-down designs for dose-finding[J]. Anesthesiology, 2022, 137 (2): 137- 150. doi: 10.1097/ALN.0000000000004282
10	白雪, 罗昊, 黄雅莹, 等. 甲苯磺酸瑞马唑仑与丙泊酚在儿童无痛胃镜检查中的比较[J]. 实用医学杂志, 2023, 39 (19): 2529- 2533.
11	易强林, 莫怀忠, 胡慧, 等. 环泊酚与丙泊酚在老年患者无痛胃镜检查中的比较[J]. 临床麻醉学杂志, 2022, 38 (7): 712- 715. doi: 10.16662/j.cnki.1674-0742.2024.17.104
12	Von Thaer S, McVey J, Shelton J, et al. Obesity and anesthesia: challenges in the perioperative period[J]. Mo Med, 2024, 121 (2): 156- 163.
13	Taheri S. Clinical obesity: a look into the future[J]. Clin Obes, 2023, 13 (2): e12581. doi: 10.1111/cob.12581
14	邢文鑫, 张宗旺. 新型阿片类药物奥赛利定[J]. 国际麻醉学与复苏杂志, 2023, 44 (10): 1116- 1120. doi: 10.3760/cma.j.cn321761-20221214-00912
15	夏江燕, 陆新健, 袁静, 等. 丙泊酚复合阿片类药物在胃镜检查中的应用[J]. 临床麻醉学杂志, 2016, 32 (5): 464- 467.
16	刘力玮, 孔二亮, 李雨恒, 等. 艾司氯胺酮与舒芬太尼用于肥胖患者腹腔镜下胃袖状切除术麻醉诱导对术后疼痛影响的比较[J]. 实用医学杂志, 2024, 40 (17): 2454- 2459. doi: 10.3969/j.issn.1006-5725.2024.17.017
17	Zhao J, Zhang Y, Su G, et al. The median effective dose of ciprofol combined with a low-dose sufentanil for gastroscopy in obese or nonobese patients: a dose-finding study using Dixon's up-and-down method[J]. Front Pharmacol, 2025, 16, 1521715. doi: 10.3389/fphar.2025.1521715
18	Lyu S, Deng Q, Lin W, et al. Randomized controlled trial for anesthesia during gastroscopy: interactions between remimazolam and propofol in combination with sufentanil[J]. Int J Clin Pharm, 2023, 45 (4): 857- 863. doi: 10.1007/s11096-023-01568-y
19	孙搏, 付淑军, 陈桂良, 等. 药物相互作用研究在新药研发和审评决策中的应用[J]. 中国临床药理学与治疗学, 2021, 26 (10): 1095- 1102. doi: 10.12092/j.issn.1009-2501.2021.10.001
20	刘璐, 石雨菲, 何庆烽, 等. 群体模型分析方法评估基因多态性对药物PK/PD的影响[J]. 中国临床药理学与治疗学, 2023, 28 (11): 1275- 1282. doi: 10.12092/j.issn.1009-2501.2023.11.010
21	王泽宇, 颜娟. 阿片类药物与药物代谢酶基因多态性研究进展[J]. 药学研究, 2024, 43 (11): 1109- 1115, 1135.
22	Fossler MJ, Sadler BM, Farrell C, et al. Oliceridine (TRV130), a novel G protein-biased ligand at the μ‐opioid receptor, demonstrates a predictable relationship between plasma concentrations and pain relief. I: Development of a pharmacokinetic/pharmacodynamic model[J]. J Clin Pharmacol, 2018, 58 (6): 750- 761. doi: 10.1002/jcph.1076
23	Goudra B. Oliceridine-opioid of the 21^st century[J]. Saudi J Anaesth, 2022, 16 (1): 69- 75. doi: 10.4103/sja.sja_510_21
24	Brzezinski M, Hammer GB, Candiotti KA, et al. Low incidence of opioid‐induced respiratory depression observed with oliceridine regardless of age or body mass index: exploratory analysis from a phase 3 open‐label trial in postsurgical pain[J]. Pain Ther, 2021, 10 (1): 457‐473. doi: 10.1007/s40122-020-00232-x

Group	Sex (M/F)	ASA (Ⅱ/Ⅲ)	Age (years)	Oliceridine (mg)	TBW (kg)	LBW (kg)	BMI (kg/m²)	Propofol (mg)
P1 group (n=28)	21/7	18/10	46.5±11.2	2.1±0.5	84.4±11.2	58.9 (48.6,63.1)	28.9 (28.4,31.1)	195 (175,225)
P2 group (n=26)	15/11	20/6	45.6±11.2	0.7±0.3	82.4±8.9	58.2 (43.8,64.6)	28.5 (28.3,29.6)	215 (190,267.5)
x²/t/z	1.817	1.033	0.291	12.584	0.720	?0.580	?1.299	?1.448
P	0.250	0.379	0.773	＜0.001	0.474	0.562	0.194	0.148

Group	Sex (M/F)	ASA (Ⅱ/Ⅲ)	Age (years)	Oliceridine (mg)	TBW (kg)	LBW (kg)	BMI (kg/m²)	Propofol (mg)
P1 group (n=28)	21/7	18/10	46.5±11.2	2.1±0.5	84.4±11.2	58.9 (48.6,63.1)	28.9 (28.4,31.1)	195 (175,225)
P2 group (n=26)	15/11	20/6	45.6±11.2	0.7±0.3	82.4±8.9	58.2 (43.8,64.6)	28.5 (28.3,29.6)	215 (190,267.5)
x²/t/z	1.817	1.033	0.291	12.584	0.720	?0.580	?1.299	?1.448
P	0.250	0.379	0.773	＜0.001	0.474	0.562	0.194	0.148

Item	Time point	P1 group (n=13)	P2 group (n=14)	t/z	P
MAP (mmHg)	T0	110.2±11.4	109.1±14.9	0.226	0.823
	T1	85.9±9.1	89.1±11.7	?0.776	0.445
	T2	86.0±12.1	92.2±12.3	?1.318	0.199
	T3	87.1±8.8	93.8±13.7	?1.504	0.145
	T4	95.1±10.3	91.1±12.8	0.873	0.391
	T5	101.5±15.5	98.4±18.2	0.486	0.631
HR (bpm)	T0	78.9±10.7	75.9±12.0	0.680	0.503
	T1	81.1±7.8	81.6±8.4	?0.158	0.875
	T2	76.2±6.9	72.4±7.3	1.381	0.180
	T3	75.5±7.5	72.6±9.3	0.863	0.396
	T4	77.0±9.3	73.2±11.1	0.954	0.349
	T5	80.9±8.2	79.8±10.2	0.319	0.753
SpO₂ (%)	T0	98(97.5,100)	99.5(96.8,100)	?0.153	0.878
	T1	100(95,100)	100(99,100)	?1.457	0.145
	T2	98(96,99)	99(97.5,100)	?1.359	0.174
	T3	98(96,98.5)	99(97.5,100)	?1.797	0.072
	T4	96(94.5,98)	98(95.8,100)	?1.448	0.148
	T5	96(96,98.5)	96(94,97.3)	?0.812	0.417

Item	Time point	P1 group (n=13)	P2 group (n=14)	t/z	P
MAP (mmHg)	T0	110.2±11.4	109.1±14.9	0.226	0.823
	T1	85.9±9.1	89.1±11.7	?0.776	0.445
	T2	86.0±12.1	92.2±12.3	?1.318	0.199
	T3	87.1±8.8	93.8±13.7	?1.504	0.145
	T4	95.1±10.3	91.1±12.8	0.873	0.391
	T5	101.5±15.5	98.4±18.2	0.486	0.631
HR (bpm)	T0	78.9±10.7	75.9±12.0	0.680	0.503
	T1	81.1±7.8	81.6±8.4	?0.158	0.875
	T2	76.2±6.9	72.4±7.3	1.381	0.180
	T3	75.5±7.5	72.6±9.3	0.863	0.396
	T4	77.0±9.3	73.2±11.1	0.954	0.349
	T5	80.9±8.2	79.8±10.2	0.319	0.753
SpO₂ (%)	T0	98(97.5,100)	99.5(96.8,100)	?0.153	0.878
	T1	100(95,100)	100(99,100)	?1.457	0.145
	T2	98(96,99)	99(97.5,100)	?1.359	0.174
	T3	98(96,98.5)	99(97.5,100)	?1.797	0.072
	T4	96(94.5,98)	98(95.8,100)	?1.448	0.148
	T5	96(96,98.5)	96(94,97.3)	?0.812	0.417

Group	Injection pain	Nausea and vomiting	Hypotension	Bradycardia	Respiratory depression	PONV	Dizziness and falling
P1 group (n=28)	7(25)	0(0)	1(3.6)	0(0)	13(46.4)	1(3.6)	0(0)
P2 group (n=26)	7(26.9)	0(0)	4(15.4)	3(11.5)	8(30.8)	0(0)	0(0)
P	0.872	Untested	0.184	0.105	0.238	1.000	Untested

复合丙泊酚时奥赛利定用于亚临床肥胖患者双向内窥镜检查的半数有效剂量

Median effective dose of oliceridine as an adjunct to propofol sedation in patients with preclinical obesity undergoing same-visit bidirectional endoscopy

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 6

参考文献 24

相关文章 15

编辑推荐

Metrics

本文评价

Group	Time of examination (min)	Time of awakening (min)	Time of discharge (min)	Dizziness on awakening (VAS)	Dizziness prior to discharge (VAS)
P1 group (n=28)	16.6±4.7	19.1±6.3	9.5(8.0,13.5)	0(0,4.0)	0.5(0,2.0)
P2 group (n=26)	16.2±5.6	18.3±6.1	10.0(8.0,13.2)	0(0,3.3)	1.0(0,1.3)
t/z	0.316	0.431	?0.10	?0.46	?0.22
P	0.753	0.668	0.922	0.645	0.823

[1]	金晶星, 梅凤美, 赵金兵, 曾琼. 舒更葡糖钠复合格隆溴铵、新斯的明在术中神经电生理监测时逆转肌松作用的半数有效剂量[J]. 中国临床药理学与治疗学, 2025, 30(11): 1536-1540.
[2]	金宝伟, 王凯, 郭建荣. 丙泊酚对肿瘤生长和转移机制影响的研究进展[J]. 中国临床药理学与治疗学, 2024, 29(9): 1042-1048.
[3]	朱昌茂, 谢力, 吴仔峰, 王森, 张琪, 徐祥清, 杨春. 偏向性μ-阿片受体激动剂奥赛利定的临床应用进展[J]. 中国临床药理学与治疗学, 2024, 29(9): 1057-1061.
[4]	江宇, 侯文龙, 宗酉明. 模拟丙泊酚Marsh模式靶控输注瑞马唑仑在全麻诱导和维持的可行性研究[J]. 中国临床药理学与治疗学, 2024, 29(3): 310-315.
[5]	衡冰冰, 杨丹峰, 戴舒阳, 上官王宁. 丙泊酚对皮下注射氯喹所致瘙痒大鼠脊髓TRPV1和CB1受体的影响[J]. 中国临床药理学与治疗学, 2023, 28(10): 1101-1108.
[6]	郑红波, 姚文龙, 罗爱林, 周碧云. 瑞马唑仑复合丙泊酚在无痛内镜逆行胰胆管造影术中的应用[J]. 中国临床药理学与治疗学, 2023, 28(10): 1154-1160.
[7]	沈燕平, 殷利军, 庄文明, 严海雅. 艾司氯胺酮预防无痛人工流产术中丙泊酚注射痛的有效剂量[J]. 中国临床药理学与治疗学, 2022, 27(6): 660-664.
[8]	赵欣, 李丁, 吴安石. 基于视神经鞘直径与眼球横径比值评价丙泊酚与地氟醚对妇科腹腔镜手术患者颅内压的影响[J]. 中国临床药理学与治疗学, 2022, 27(12): 1408-1413.
[9]	杨沁岩, 黄立, 石岚, 欧媛媛, 黎国媛, 黄成勇. 复合布托啡诺时丙泊酚抑制宫腔镜手术患者体动的半数有效血浆靶浓度[J]. 中国临床药理学与治疗学, 2020, 25(9): 1033-1037.
[10]	杨璐，魏滨，张利萍，毕姗姗，卢炜. 应用响应曲面模型法研究丙泊酚与瑞芬太尼的最佳配伍剂量[J]. 中国临床药理学与治疗学, 2020, 25(4): 413-420.
[11]	周俊辉，孟宪慧. 序贯法测定羟考酮皮下注射用于Stanford A型主动脉夹层撕裂患者术前镇痛的半数有效剂量[J]. 中国临床药理学与治疗学, 2019, 24(8): 916-921.
[12]	衡冰冰，戴舒阳，杨丹峰，Beekoo Deepti，连庆泉，上官王宁. 丙泊酚对吗啡鞘内注射所致瘙痒大鼠脊髓内胃泌素释放肽受体的影响[J]. 中国临床药理学与治疗学, 2019, 24(7): 759-765.
[13]	徐文婷，杨丽勤，张忠楠，梁俊，江楠，蒋淼，郭文俊，汪萌芽. 丙泊酚成瘾大鼠的心理生理学特性[J]. 中国临床药理学与治疗学, 2019, 24(6): 608-614.
[14]	赵鹏程，徐丽丽，李艳玲. 右美托咪定联合靶控输注丙泊酚在肝癌射频消融治疗中的临床效果[J]. 中国临床药理学与治疗学, 2018, 23(6): 682-687.
[15]	赵鹏程，张超. 七氟醚联合丙泊酚对肝硬化患者术后肝肾功能及免疫功能的影响[J]. 中国临床药理学与治疗学, 2018, 23(11): 1276-1281.