不同剂量艾司氯胺酮对胸腔镜下肺部分切除术患者瑞芬太尼诱发痛觉过敏的影响

doi:10.13481/j.1671-587X.20240526

摘要/Abstract

摘要：

目的比较不同剂量艾司氯胺酮对胸腔镜下肺部分切除术患者瑞芬太尼诱发的痛觉过敏（RIH）的预防作用，为多模式镇痛和术后快速康复提供依据。方法采用前瞻性、双盲、平行设计的随机对照试验（RCT），纳入行胸腔镜下肺部分切除术患者共107例，采用随机数字表法分为正常对照组、低剂量艾司氯胺酮组和高剂量艾司氯胺酮组。除外被剔除试验者和退出试验者，正常对照组纳入31例，低剂量艾司氯胺酮组33例，高剂量艾司氯胺酮组33例。低剂量艾司氯胺酮组患者麻醉诱导时静脉注射艾司氯胺酮0.25 mg·kg^－1（稀释至5 mL），高剂量艾司氯胺酮组患者麻醉诱导时静脉注射艾司氯胺酮0.50 mg·kg^－1（稀释至5 mL），正常对照组患者麻醉诱导时静脉注射生理盐水5 mL。记录各组患者不同时间点非优势手前臂及手术切口周围皮肤的机械痛阈值、数字评价量表（NRS）评分、Ramsay镇静评分、围术期镇痛药物用量及患者术后谵妄、恶心和呕吐等不良反应的发生情况。结果与正常对照组比较，低和高剂量艾司氯胺酮组患者术后手术切口周围皮肤的机械痛阈值升高（P<0.05）；与低剂量艾司氯胺酮组比较，高剂量艾司氯胺酮组患者拔管时间延长（P<0.05）；麻醉诱导给药2 min后，与正常对照组比较，低和高剂量艾司氯胺酮组患者平均动脉压（MAP）及心率（HR）升高（P<0.05），低和高剂量艾司氯胺酮组患者MAP和HR差异无统计学意义（P>0.05）；与正常对照组比较，高剂量艾司氯胺酮组患者幻觉和谵妄发生率升高（P<0.05），低剂量艾司氯胺酮组患者幻觉和谵妄发生率差异无统计学意义（P>0.05）；与低剂量艾司氯胺酮组比较，高剂量艾司氯胺酮组患者幻觉和谵妄发生率升高（P<0.05）。结论麻醉诱导时静脉注射0.25 mg·kg^－1艾司氯胺酮可提高胸腔镜下肺部分切除术患者的术后机械痛阈值，对RIH的预防效果较好且不增加围术期不良反应发生率。

关键词: 艾司氯胺酮, 瑞芬太尼, 痛觉过敏, 胸外科手术, 麻醉诱导

Abstract:

Objective To compare the preventive effects of different doses of esketamine on remifentanil-induced hyperalgesia （RIH） in the patients underwent thoracoscopic pnlmonary lobectomy， and to provide the basis for the multimodal analgesia and rapid postoperative recovery. Methods The prospective， double-blind，parallel-designed randomized controlled trial （RCT） were conducted， and 107 patients who underwent visual-assisted thoracoscopic pulmonary lobectomy were included. The patients were randomly divided into normal control group，low dose of esketamine group，and high dose of esketamine group using random number methods. Except the patients who were eliminated and those who dropped out of the study，there were 31 patients in normal control group，33 patients in low dose of esketamine group，and 33 patients in high dose of esketamine group.The patients in low dose of esketamine group were given the intravenous injection of 0.25 mg·kg^－1 esketamine （diluted to 5 mL） during anesthesia induction；the patients in high dose of esketamine group were given the intravenous injection of 0.50 mg·kg^－1 esketamine （diluted to 5 mL）， and the patients in normal control group were given 5 mL intravenous injection of saline. The mechanical pain thresholds of the non-dominant forearm skin and skin around the surgical incision at different time points， numeric rating scale （NRS） scores， Ramsay sedation scores， perioperative analgesic drug dosages， and the incidences of adverse reactions such as postoperative delirium， nausea， and vomiting of the patients in various groups were recorded. Results Compared with normal control group， the mechanical pain thresholds around the surgical incision skin of the patients in low and high doses of esketamine groups were increased （P<0.05）； compared with low dose of esketamine group， the extubation time of the patients in high dose of esketamine group was increased（P<0.05）. Two minutes after anesthesia induction administration， compared with normal control group， the mean arterial pressure（MAP） and heart rate（HR） of the patients in low and high doses of esketamine groups were increased （P<0.05）， but there were no significant differences in the MAP and HR of the patients between low dose of esketamine and high dose of esketamine group （P>0.05）；compared with normal control group， the incidences of hallucinations and delirium among the patients in high dose of esketamine group were increased （P<0.05）， while there were no significant differences in the incidences of above adverse reactions in low dose of esketamine group （P>0.05）； compared with low dose of esketamine group， the incidences of hallucinations and delirium among the patients in high dose of esketamine group were increased （P<0.05）. Conclusion Intravenous administration of esketamine with a dosage of 0.25 mg·kg^－1 during anesthesia induction improves the postoperative mechanical pain threshold of the patients undergoing thoracoscopic pulmonary lobectomy， which exhibits effective prevention of RIH without an increase in incidences of adverse reactions during the perioperative period.

Key words: Esketamine, Remifentanil, Hyperalgesia, Thoracic surgery, Anesthesia induction

中图分类号:

R614.2

王瑞琨,段宗生,张文文,王虎山. 不同剂量艾司氯胺酮对胸腔镜下肺部分切除术患者瑞芬太尼诱发痛觉过敏的影响[J]. 吉林大学学报(医学版), 2024, 50(5): 1406-1413.

Ruikun WANG,Zongsheng DUAN,Wenwen ZHANG,Hushan WANG. Effects of different doses of esketamine on remifentanil-induced hyperalgesia in patients underwent thoracoscopic pulmonary lobectomy[J]. Journal of Jilin University(Medicine Edition), 2024, 50(5): 1406-1413.

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Group	n	Gender (Male/female)	Age(year)	Weight(m/kg)	BMI(kg·m^－2)	ASA Classification (Ⅰ/Ⅱ)
Normal control	31	17/14	46.6±16.1	64.8±8.9	24.4±3.5	4/27
Esketamine
Low dose	33	18/15	49.5±16.7	67.1±10.2	25.0±3.4	4/29
High dose	33	15/18	48.1±16.5	66.1±7.5	25.5±3.6	5/28

Group	n	Surgery duration (t/min)	Anesthesia duration (t/min)	Extubation time (t/min)	PACU stay duration (t/min)
Normal control	31	92.76±14.68	101.25±15.80	10.12±1.62	56.50±6.25
Esketamine
Low dose	33	85.60±11.80	95.67±17.25	9.81±1.96	57.42±5.05
High dose	33	91.89±14.65	105.43±18.30	17.18±3.45^*△	56.63±5.85
F		2.567	2.664	91.69	0.246
P		0.080	0.080	<0.01	0.780
Group	n	Remifentanil usage (m/mg)	Sufentanil usage (m/μg)	Norepinephrine usage (m/mg)	Hydromorphone usage (m/mg)
Normal control	31	1.26±0.18	46.24±2.34	1.05±0.35	8.62±1.21
Esketamine
Low dose	33	1.35±0.24	42.17±2.97^*	0.53±0.28^*	6.21±1.10^*
High dose	33	1.27±0.14	43.45±2.01^*	0.48±0.22^*	5.93±1.05^*
F		2.162	4.425	38.33	55.18
P		0.120	0.020	<0.01	<0.01
^P<*0.05 vs normal control group;^△P<0.05 vs low dose of esketamine group.

Group	HR（beat·min^－1）
	T₀	T₁	T₂	T₃		T₀	T₁	T₂	T₃
Normal control	79.28±6.52	63.45±9.81^*	61.36±8.67^*	68.79±8.94	103.45±14.78		84.45±17.92^*	83.27±15.75^*	96.28±9.52
Esketamine Low dose	84.45±9.81	3.28±6.52^△	65.28±6.52	75.41±7.26	100.18±11.72		98.59±9.13^△	96.12±16.82	104.36±8.67
High dose	83.85±8.04	74.73±7.93^△	67.73±7.93	74.93±7.33	101.69±16.92		97.36±19.40^△	94.38±17.34	108.15±8.04
T₀ ：15 min before operation；T₁ ：20 min after induction administration；T₂：1 h during operation；T₃：30 min after extubation.^*P<0.05 compared with T₀； ^△P<0.05 compared with normal control group.

Group	n	Mechanical pain threshold non-dominant forearm
Group	n	1 d before operation	2 h after operation	6 h after operation	12 h after operation	24 h after operation	48 h after operation
Normal control	31	178.78±49.22	112.56±37.34	107.13±38.35^*	135.17±44.68	147.89±77.02	169.47±55.18
Esketamine
Low dose	33	167.91±37.34	179.24±47.76^△	138.79±48.27	27.28±43.34	157.52±60.78	159.08±43.33
High dose	33	171.32±73.34	199.16±58.98^*△	171.85±52.12	174.33±39.97	184.22±60.23	174.97±70.27
F		0.3189	27.110	15.320	11.450	2.611	0.652
P		0.73	<0.01	<0.01	<0.01	<0.01	<0.01
Group	n	Mechanical pain threshold around the surgical incision
Group	n	1 d before operation	2 h after operation	6 h after operation	12 h after operation	24 h after operation	48 h after operation
Normal control	31	170.81±61.57	109.06±39.31^*	89.93±47.42^*	102.18±54.99^*	117.89±48.24^*	123.57±46.88
Esketamine
Low dose	33	157.42±39.57	139.24±52.91^△	129.38±65.82^△	137.24±53.12^△	141.16±58.07	143.98±33.28
High dose	33	170.01±46.57	159.34±51.64^△	161.54±57.63^△	157.28±39.71^△	169.34±38.45^△	153.49±44.41
F		0.741	8.667	12.350	10.050	8.886	4.243
P		0.48	<0.01	<0.01	<0.01	<0.01	0.02

Group	n	NRS score
Group	n	2 h after operation	12 h after operation	24 h after operation	48 h after operation
Normal control	31	2.00（2.00,2.00）	1.00（0.00,1.00）	0.00（1.00,0.00）	0.00（0.00,0.00）
Esketamine
Low dose	33	2.00（1.00,2.00）	0.00（0.00,1.00）	0.00（0.00,0.00）	0.00（0.00,0.00）
High dose	33	2.00（0.0,2.000）	0.00（0.00,1.00）	0.00（0.00,0.00）	0.00（0.00,0.00）
P		0.58	1.00	1.00	1.00