Yao Yiyi,Zhu Yi,Chen Zheng,et al.Median effective dose of esketamine for preventing pain caused by an injection of propofol medium-chain triglyceride/long-chain triglyceride emulsion in school-age children[J].Journal of Clinical Pediatric Surgery,2024,(10):965-969.[doi:10.3760/cma.j.cn101785-202311038-012]
艾司氯胺酮注射减轻学龄期手术患儿丙泊酚中/长链脂肪乳注射痛的半数有效剂量研究
- Title:
- Median effective dose of esketamine for preventing pain caused by an injection of propofol medium-chain triglyceride/long-chain triglyceride emulsion in school-age children
- Keywords:
- Esketamine; Propofol Medium-Chain Triglyceride/Long-Chain Triglyceride Emulsion; Injection Pain; ED50; Surgical Procedures; Operative; Child
- 摘要:
- 目的 探讨艾司氯胺酮减轻学龄期患儿丙泊酚中/长链脂肪乳注射痛的半数有效剂量 (median effective dose, ED50)。方法 本研究为前瞻性研究, 选取2023年5月至2023年7月在湖南省儿童医院行全身麻醉手术的学龄期患儿26例作为研究对象, 年龄6~13岁, 美国麻醉医师协会分级Ⅰ~Ⅱ级。麻醉过程由2名麻醉医师完成, 第一名麻醉医师负责给药, 为每例患儿注射丙泊酚中/长链脂肪乳前预先注射艾司氯胺酮, 同时由另一名不知药物剂量的麻醉医师记录相关不良反应;根据Ambesh评分评估丙泊酚中/长链脂肪乳注射后患儿注射疼痛程度。根据改良序贯法对艾司氯胺酮剂量进行调整, 艾司氯胺酮初始剂量为0.2 mg/kg, 若Ambesh评分≤1分, 纳入有效组, 则下一例患儿艾司氯胺酮剂量减少0.02 mg/kg;若Ambesh评分＞1分, 纳入无效组, 则下一例患儿艾司氯胺酮剂量增加0.02 mg/kg。当出现7个交叉点(有效转为无效)时终止研究。采用Probit回归分析法计算艾司氯胺酮减轻学龄期患儿丙泊酚中/长链脂肪乳注射痛的ED50、95%有效剂量(95% effective dose, ED95)、99%有效剂量(99% effective dose, ED99)及各自的95%置信区间(confidence interval, CI)。结果 共26例患儿完成试验, 其中有效组14例, 无效组12例。艾司氯胺酮减轻学龄期患儿丙泊酚中/长链脂肪乳注射痛ED50为0.14 mg/kg, 95%CI(0.07~0.18 mg/kg);ED95为0.22 mg/kg, 95%CI(0.18~0.90 mg/kg);ED99为0.25 mg/kg, 95%CI(0.20~1.20 mg/kg)。结论 本研究初步证明预先注射艾司氯胺酮减轻学龄期儿童丙泊酚中/长链脂肪乳注射痛的ED50为0.14 mg/kg。
- Abstract:
- Objective To explore the half effective dose of esketamine in mitigating pain of propofol medium-chain triglyceride/long-chain triglyceride (MCT/LCT) emulsion injection in school-age children. Methods From May 2023 to July 2023, 26 school-age children aged 6-13 year with ASA grade I-II underwent operations under general anesthesia.Anesthesia was performed by two anesthesiologists.The first anesthesiologist injected esketamine before propofol MCT/LCT emulsion.At the same time, adverse reactions were recorded by another anesthesiologist not knowing the dosage of drug.Pain after an injection of propofol MCT/LCT emulsion was evaluated by Ambesh score.The dose of esketamine was adjusted according to the modified sequential method.The initial dose of esketamine was 0.2 mg/kg.If Ambesh score ≤1, effective group (n=14) was designated.The dose of esketamine in the next case dropped by 0.02 mg/kg.Conversely, if Ambesh score ＞1, ineffective group (n=12) was selected and the dose of esketamine in the next case was boosted by 0.02 mg/kg accordingly.Trial was terminated when there were seven intersections (effective to ineffective).ED50, ED95 and ED99 effects of esketamine on propofol MCT/LCT emulsion injection pain were calculated by Probit regression analysis. Results ED50 of esketamine in reducing propofol MCT/LCT emulsion injection pain in school-age children was 0.14 mg/kg (95%CI:0.07-0.18 mg/kg).ED95 was 0.22 mg/kg (95%CI:0.18-0.90 mg/kg) and ED99 0.25 mg/kg (95%CI:0.2-1.2 mg/kg). Conclusions ED50 of esketamine is 0.14 mg/kg in reducing propofol MCT/LCT emulsion injection pain in school-age children.
参考文献/References:
[1] Singla B, Malde AD.A prospective observational study of injection pain in children with medium plus long chain triglyceride and long chain triglyceride propofol premixed with lignocaine[J].Indian J Anaesth, 2018, 62(3):214-218.DOI:10.4103/ija.IJA_506_17.
[2] Cheng DB, Liu L, Hu Z.Prevention of anesthesia-induced injection pain of propofol in pediatric anesthesia[J].Pak J Med Sci, 2017, 33(3):752-756.DOI:10.12669/pjms.333.12026.
[3] Rochette A, Hocquet AF, Dadure C, et al.Avoiding propofol injection pain in children:a prospective, randomized, double-blinded, placebo-controlled study[J].Br J Anaesth, 2008, 101(3):390-394.DOI:10.1093/bja/aen169.
[4] Annetta MG, Iemma D, Garisto C, et al.Ketamine:new indications for an old drug[J].Curr Drug Targets, 2005, 6(7):789-794.DOI:10.2174/138945005774574533.
[5] Iwata M, Inoue S, Kawaguchi M, et al.Ketamine eliminates pr-opofol pain but does not affect hemodynamics during induction with double-lumen tubes[J].Journal of anesthesia, 2010, 24(1):31-37.DOI:10.1007/s00540-009-0833-5.
[6] Zhao GY, Guo Y, Bao SM, et al.Prevention of propofol-induced pain in children:pretreatment with small doses of ketamine[J].J Clin Anesth, 2012, 24(4):284-288.DOI:10.1016/j.jclinane.2011.08.013.
[7] Trimmel H, Helbok R, Staudinger T, et al.S(+)-ketamine:current trends in emergency and intensive care medicine[J].Wien Klin Wochenschr, 2018, 130(9/10):356-366.DOI:10.1007/s00508-017-1299-3.
[8] Fu DY, Wang DD, Li WX, et al.Pretreatment with low-dose esketamine for reduction of propofol injection pain:a randomized controlled trial[J].Pain Res Manag, 2022, 2022:4289905.DOI:10.1155/2022/4289905.
[9] Tan MY, Zhang CY, Zeng W, et al.Determining the effective dose of esketamine for mitigating pain during propofol injection by Dixon’s up-and-down method:a double-blind, prospective clinical study of drug dose response[J].BMC Anesthesiol, 2022, 22(1):368.DOI:10.1186/s12871-022-01914-z.
[10] 沈燕平, 殷利军, 庄文明, 等.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.DOI:10.12092/j.issn.1009-2501.2022.06.009. Shen YP, Yin LJ, Zhuang WM, et al.Effective dose of esketamine for preventing pain of propofol injection during painless abortion[J].Chin J Clin Pharmacol Ther, 2022, 27(6):660-664.DOI:10.12092/j.issn.1009-2501.2022.06.009.
[11] Beyaz SG, Eman A.Injection pain of propofol in children:a comparison of two formulations without added lidocaine[J].J Anaesthesiol Clin Pharmacol, 2012, 28(3):314-317.DOI:10.4103/0970-9185.98322.
[12] Tian SP, Zhang DS, Zhou W, et al.Median effective dose of lidocaine for the prevention of pain caused by the injection of propofol formulated with medium-and long-chain triglycerides based on lean body weight[J].Pain Med, 2021, 22(6):1246-1252.DOI:10.1093/pm/pnaa316.
[13] Guan XH, Jiao ZY, Gong XF, et al.Efficacy of pre-treatment with remimazolam on prevention of propofol-induced injection pain in patients undergoing abortion or curettage:a prospective, double-blinded, randomized and placebo-controlled clinical trial[J].Drug Des Devel Ther, 2021, 15:4551-4558.DOI:10.2147/DDDT.S334100.
[14] Kwak K, Kim J, Park S, et al.Reduction of pain on injection of propofol:combination of pretreatment of remifentanil and premixture of lidocaine with propofol[J].Eur J Anaesthesiol, 2007, 24(9):746-750.DOI:10.1017/S026502150600233X.
[15] 徐学武, 许文秀, 王宝宁, 等.丙泊酚复合不同浓度利多卡因预防注射痛的临床研究[J].临床麻醉学杂志, 2012, 28(4):378-380. Xu XW, Xu WX, Wang BN, et al.Prophylactic effect of lidocaine at different concentrations on propofoi-induced injection pain[J].J Clin Anesthesiol, 2012, 28(4):378-380.
[16] 张欢欢, 田航, 宋兴荣, 等.盐酸纳布啡对小儿胃镜检查中丙泊酚注射痛的影响[J].中华实用诊断与治疗杂志, 2018, 32(4):388-390.DOI:10.13507/j.issn.1674-3474.2018.04.024. Zhang HH, Tian H, Song XR, et al.Effect of nalbuphine on preventing propofol-induced pain in children undergoing gastroscopy[J].J Chin Pract Diagn Ther, 2018, 32(4):388-390.DOI:10.13507/j.issn.1674-3474.2018.04.024.
[17] 姚婧, 蔡英敏, 雷浩, 等.艾司氯胺酮减少丙泊酚注射痛的效果[J].临床麻醉学杂志, 2023, 39(11):1158-1162.DOI:10.12089/jca.2023.11.007. Yao J, Cai YM, Lei H, et al.Effect of esketamine in reducing the pain of propofol injection[J].J Clin Anesthesiol, 2023, 39(11):1158-1162.DOI:10.12089/jca.2023.11.007.
[18] Sun NCH, Wong AYC, Irwin MG.A comparison of pain on intravenous injection between two preparations of propofol[J].Anesth Analg, 2005, 101(3):675-678.DOI:10.1213/01.ANE.0000157564.91910.04.
[19] Allford MA, Mensah JA.Discomfort on injection:a comparison between two formulations of propofol[J].Eur J Anaesthesiol, 2006, 23(11):971-974.DOI:10.1017/S0265021506001049.
[20] 任燕伶, 邢飞, 周莉, 等.小剂量艾司氯胺酮对瑞芬太尼诱发患者术后痛觉过敏的影响[J].中华麻醉学杂志, 2023, 43(1):51-55.DOI:10.3760/cma.j.cn131073.20220919.00111. Ren YL, Xing F, Zhou L, et al.Effect of low-dose esketamine on remifentanil-induced postoperative hyperalgesia[J].Chin J Anesthesiol, 2023, 43(1):51-55.DOI:10.3760/cma.j.cn131073.20220919.00111.
[21] 唐玲, 肖婷, 杜真, 等.右旋氯胺酮用于小儿腹腔镜疝囊高位结扎术麻醉的有效性与安全性评价[J].临床小儿外科杂志, 2022, 21(8):758-763.DOI:10.3760/cma.j.cn101785-202110038-010. Tang L, Xiao T, Du Z, et al.Effectiveness and safety evaluations of s-ketamine during laparoscopic high ligation of hernia sac in children[J].DOI:10.3760/cma.j.cn101785-202110038-010.
[22] 万倩, 邸立超, 黄立宁.艾司氯胺酮用于围术期镇痛及其机制的研究进展[J].中华麻醉学杂志, 2023, 43(10):1272-1275.DOI:10.3760/cma.j.cn131073.20230426.01026. Wan Q, Di LC, Huang LN.Research advances of S-ketamine for perioperative analgesia and its mechanism[J].Chin J Anesthesiol, 2023, 43(10):1272-1275.DOI:10.3760/cma.j.cn131073.20230426.01026.
[23] 叶国妹, 陈依君.不同时间间隔艾司氯胺酮预先给药对小儿外科患者丙泊酚注射痛的影响[J].浙江临床医学, 2023, 25(7):1070-1071. Ye GM, Chen YJ.Effect of esketamine preadministration at different time intervals on propofol injection pain in pediatric surgical patients[J].Zhejiang Clin Med J, 2023, 25(7):1070-1071.
备注/Memo
收稿日期:2023-11-26。
基金项目:湖南省自然科学基金(2019JJ50294)
通讯作者:杜真,Email:meggyzhen@163.com