右美托咪定持续输注对肿瘤细胞减灭术联合腹腔热灌注化疗患者乳酸代谢和术后康复的影响

doi:10.13481/j.1671-587X.20220526

摘要/Abstract

摘要：

目的探讨右美托咪定持续输注对择期行肿瘤细胞减灭术（CRS）联合腹腔热灌注化疗术（HIPEC）腹膜癌患者围术期应激反应、乳酸（Lac）清除率和术后康复的影响。方法收集60例全身麻醉下行CRS联合HIPEC腹膜癌患者的临床资料，筛选后剔除4例患者，分为对照组（常规麻醉）27例和右美托咪定组29例。所有患者常规全身麻醉，右美托咪定组患者同时给予右美托咪定；术中监测有创动脉压（ABP）和中心静脉压（CVP），测定心脏指数（CI），计算心率血压乘积（RPP），术中以每搏变异度（SVV）指导补液。记录手术前（T0）、HIPEC开始前（T1）、HIPEC结束后（T2）和手术结束后（T3）时平均动脉压（MAP）、心率（HR）、RPP、CVP及CI和血中Lac、碱剩余（BE）、血糖（Glu）和皮质醇水平，计算Lac清除率；记录2组患者术后3 d内并发症发生情况。结果循环相关指标，在T0时2组患者MAP、HR、RPP、CVP和CI比较差异无统计学意义（P>0.05）；在T1时，与对照组比较，右美托咪定组患者RPP减少（P<0.05）；在T2时，与对照组比较，右美托咪定组患者HR和CVP均明显降低（P<0.05），RPP减少（P<0.05）；在T3时，与对照组比较，右美托咪定组患者HR、MAP和CVP明显降低（P<0.05），RPP减少（P<0.05），2组患者CI比较差异无统计学意义（P>0.05）。血气及应激相关指标，在T0时，2组患者血中Lac、BE、Glu和皮质醇水平比较差异无统计学意义（P>0.05）；在T1和T2时，与对照组比较，右美托咪定组患者血中Lac、Glu和皮质醇水平降低（P<0.05），BE负值减少（P<0.05）。术后Lac水平和肝肾功能，在术后12 h（T4）、术后24 h（T5）、术后48 h（T6）和术后72 h（T7）时，与对照组比较，右美托咪定组患者Lac水平降低（P<0.05），Lac清除率明显升高（P<0.05）；T5和T7时右美托咪定组患者丙氨酸氨基转移酶（ALT）和天门冬氨酸氨基转移酶（AST）水平明显降低（P<0.05）。术后并发症发生情况，与对照组比较，术后3 d内右美托咪定组患者术后低血压、恶心呕吐、腹胀、寒战和睡眠障碍发生例数明显减少（P<0.05）。结论术中右美托咪定持续输注可降低腹膜癌患者围术期应激反应和Lac水平，减少术后并发症发生，促进患者术后康复。

关键词: 右美托咪定, 腹膜肿瘤, 热灌注化疗, 乳酸, 应激反应

Abstract:

Objective To investigate the effects of continuous infusion of dexmedetomidine on the perioperative stress response， lactate（Lac） clearance rate and postoperative rehabilitation of the patients with peritoneal cancer undergoing selective cytoreductive surgery（CRS） combined with hyperthermic intraperitoneal chemotherapy （HIPEC）. Methods The clinical data of 60 patients with peritoneal cancer underwent CRS combined with HIPEC under general anesthesia were collected.After screening，4 cases of patients were eliminated； the patients were divided into control group （general anesthesia）（27 patients） and dexmedetomidine group（29 patients）. All patients were subjected to general anesthesia，and the patients in dexmedetomidine group recieved dexmedetomidine at the same time. Intraoperative invasive arterial blood pressure （ABP） and central venous pressure （CVP） were monitored， cardiac index （CI） was measured， rate pressure product （RPP） were calculated， and intraoperative fluid replacement was guided by stroke volume variation （SVV）. Mean arterial pressure （MAP）， heart rate（HR）， RPP，CVP and CI were recorded before surgery （T0）， before the start of thermoperfusion chemotherapy （T1）， after thermoperfusion chemotherapy （T2）， and after surgery （T3），and the levels of Lac， base excess （BE），blood glucose （Glu） and cortisol in blood were calculated and Lac dearance rate was calculated. The postoperative complications within 3 d after surgery of the patients between two groups were recorded. Results There were no statistically significant differences in circulatory indicators such as MAP， HR，RPP， CVP and CI between two groups at T0 （P>0.05）.At T1，compared with control group，RPP of the patients in dexmedetomidine group was decreased（P<0.05）. At T2， compared with control group， HR and CVP of the patients in dexmedetomidine group were significantly decreased （P<0.05）， and RPP was decreased （P<0.05）.At T3，compared with control group，HR，MAP and CVP of the patients in dexmedetomidine group were significantly decreased （P<0.05），RPP was decreased （P<0.05）；there was no significant difference in CI between two groups （P>0.05）. At T0， there were no significant differences in the levels of Lac， BE， Glu and cortisol in blood of the patients between two groups （P>0.05）. At T1 and T2， compared with control group，the Lac， Glu and cortisol levels in blood of the patients in dexmedetomidine group were decreased （P<0.05）， and BE negative value was decreased （P<0.05）. At 12 h after surgery（T4）， 24 h after surgery（T5）， 48 h after surgery（T6） and 72 h after surgery（T7）， compared with control group，the Lac levels of the patients in dexmedetomidine group were decreased （P<0.05）， and the Lac clearance rates were significantly increased （P<0.05）；and the levels of alanine aminotrasferase（ALT） and aspartate aminotransferase（AST） were significantly decreased at T5 and T7 （P<0.05）.Compared with control group， the incidence cases of postoperative hypotension， nausea and vomiting， abdominal distention， chills and sleep disorders of the patients in dexmedetomidine group were significantly reduced at 3 d after surgery（P<0.05）. Conclusion Intraoperative dexmedetomidine continuous infusion can reduce the perioperative stress response and Lac levels， reduce the incidence of postoperative complications， and promote postoperative recovery in the patients with peritoneal cancer.

Key words: Dexmedetomidine, Peritoneal carcinoma, Hyperthermic intraperitoneal chemotherapy, Lacate, Stress response

中图分类号:

张静,王劭恒,刘鹏飞,关雷. 右美托咪定持续输注对肿瘤细胞减灭术联合腹腔热灌注化疗患者乳酸代谢和术后康复的影响[J]. 吉林大学学报(医学版), 2022, 48(5): 1305-1313.

Jing ZHANG,Shaoheng WANG,Pengfei LIU,Lei. GUAN. Effects of continuous infusion of dexmedetomidine on lactate metabolism and postoperative recovery in patients undergoing cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy[J]. Journal of Jilin University(Medicine Edition), 2022, 48(5): 1305-1313.

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参考文献 30

1	KITAI T. The role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal carcinomatosis： a systematic review including evidence from Japan［J］. Surg Today， 2021， 51（7）： 1085-1098.
2	MINARECI Y， TOSUN O A， SOZEN H，et al. A retrospective clinical analysis of hyperthermic intraperitoneal chemotherapy in gynecological cancers： technical details，tolerability， and efficacy［J］. Medeniyet Med J，2020，35（3）：202-211.
3	AUER R C， SIVAJOHANATHAN D， BIAGI J，et al. Indications for hyperthermic intraperitoneal chemotherapy with cytoreductive surgery： a systematic review［J］. Eur J Cancer，2020，127：76-95.
4	ZHU Y S， XIONG Y F， LUO F Q，et al. Dexmedetomidine protects rats from postoperative cognitive dysfunction via regulating the GABA_B R-mediated cAMP-PKA-CREB signaling pathway［J］. Neuropathology，2019，39（1）：30-38.
5	俞贝贝，赵国庆，宋知遥，等. 右美托咪定在病态肥胖患者减重手术中的应用研究进展［J］. 中国实验诊断学， 2021，25（1）： 147-150.
6	王琴，王辉. 右美托咪定的器官保护作用及其机制［J］. 医学综述，2019，25（9）： 1822-1826.
7	XU Y X， DU X X. Application of dexmedetomidine-assisted intravertebral anesthesia in hip replacement and its influence on T-lymphocyte subsets［J］. Exp Ther Med，2020， 20（2）： 1269-1276.
8	FERREIRA J. The theory is out there：the use of ALPHA-2 agonists in treatment of septic shock［J］. Shock，2018，49（4）： 358-363.
9	MIYAMOTO K， NAKASHIMA T， SHIMA N，et al. Effect of dexmedetomidine on lactate clearance in patients with septic shock：a subanalysis of a multicenter randomized controlled trial［J］. Shock，2018，50（2）： 162-166.
10	PAREDES A Z， GUZMAN-PRUNEDA F A， ABDEL-MISIH S，et al. Perioperative morbidity of gastrectomy during CRS-HIPEC：an ACS-NSQIP analysis［J］. J Surg Res，2019，241： 31-39.
11	CHEN J C， BEAL E W， HAYS J，et al. Outcomes of neoadjuvant chemotherapy before CRS-HIPEC for patients with appendiceal cancer［J］. J Surg Oncol， 2020， 122（3）： 388-398.
12	徐靓，严静，龚仕金，等. 感染性休克患者经皮氧分压与血乳酸的相关性［J］. 中华内科杂志， 2018， 57（11）： 841-843.
13	ANDERSEN L W. Lactate elevation during and after major cardiac surgery in adults： a review of etiology， prognostic value， and management［J］. Anesth Analg， 2017，125（3）： 743-752.
14	DESPLANQUE L， HAMAIDE-DEFROCOURT F， BERKIA I，et al. Lactate clearance in infants undergoing surgery for congenital heart disease［J］. Artif Organs，2019，43（1）：54-59.
15	KISHI K， ISHIDA K， MAKINO Y，et al. A simple way to measure glucose and lactate values during free flap head and neck reconstruction surgery［J］. J Oral Maxillofac Surg，2019，77（1）：226.e1-226.e9.
16	STEPHENS E H， EPTING C L， BACKER C L，et al. Hyperlactatemia： an update on postoperative lactate［J］. World J Pediatr Congenit Heart Surg，2020，11（3）：316-324.
17	WANG F， CATALINO M P， BI W L，et al. Postoperative day 1 morning cortisol value as a biomarker to predict long-term remission of cushing disease［J］. J Clin Endocrinol Metab， 2021，106（1）：e94-e102.
18	BOJAN M， DESPLANQUE L， ALBINNI S. Increased lactate load of older red blood cell preparations increases blood lactate concentrations in infants during cardiac surgery［J］. Paediatr Anaesth，2018，28（2）：185-186.
19	NALBANDIAN M， RADAK Z， TAKEDA M. Lactate metabolism and satellite cell fate［J］. Front Physiol，2020，11：610983.
20	ZWAAG J， RTER HORST， BLAŽENOVIC I，et al. Involvement of lactate and pyruvate in the anti-inflammatory effects exerted by voluntary activation of the sympathetic nervous system［J］. Metabolites，2020，10（4）：E148.
21	TORNERO-AGUILERA J F， CLEMENTE-SUÁREZV J. Effect of experience，equipment and fire actions in psychophysiological response and memory of soldiers in actual underground operations［J］. Int J Psychophysiol，2018，128：40-46.
22	SCARAVILLI V， DI GIROLAMO L， SCOTTI E，et al. Effects of sodium citrate， citric acid and lactic acid on human blood coagulation［J］. Perfusion，2018，33（7）：577-583.
23	张延卓，何绪雄，叶茂英，等. 右美托咪定神经保护作用机制的综述［J］. 中国继续医学教育，2021，13（9）：195-198.
24	陶广华，李卫，刘文值. 右美托咪定围术期应用的研究进展［J］. 中国药房，2017，28（5）： 706-710.
25	韦国温，卢炳益. 右美托咪定对脓毒症休克患者围术期血流动力学、乳酸清除率及肝肾功能的影响［J］. 广西医学，2020，42（10）：1219-1223.
26	孙英，贾莉莉，朱敏，等. 右美托咪定对亲体肝移植术婴儿术后肺损伤的影响［J］. 临床麻醉学杂志，2021，37（4）：367-371.
27	李海斌. 负荷剂量右美托咪定对肝移植受者术后24 h内MACE风险的影响［J］. 临床研究，2021，29（7）：89-90.
28	GARCÍACAMACHO C， MARÍN-PAZA J， LAGARES-FRANCO C，et al. Continuous ultrafiltration during extracorporeal circulation and its effect on lactatemia： a randomized controlled trial［J］.PLoS One，2020，15（11）：e0242411.
29	VELICKOVIC J， PALIBRK I， MILICIC B， et al. The association of early postoperative lactate levels with morbidity after elective major abdominal surgery［J］. Bosn J Basic Med Sci，2019， 19（1）：72-80.
30	GREENWOOD J C， JANG D H， HALLISEY S D，et al. Severe impairment of microcirculatory perfused vessel density is associated with postoperative lactate and acute organ injury after cardiac surgery［J］. J Cardiothorac Vasc Anesth，2021，35（1）：106-115.

Group	n	Gender			Age (year)	BMI （kg·m^－2）		ASA						Pre-operative Hb[ρ_B/（g·L^－1）]		Pre-operative albumin [ρ_B/（g·L^－1）]		Surgery time （t/min）
		Gender						Ⅰ	Ⅱ			Ⅲ
		Female	Male					Ⅰ	Ⅱ			Ⅲ
Control	27	15	12		46±6	22.7±3.4		6	15		6			118.25±13.22		34.71±3.33		541±112
Dexme- detomidine	29	18	11		45±7	23.1±3.7		9	12		8			120.62±17.41		35.13±3.84		535±126
t		0.252			0.773	0.421		1.151						0.512		0.424		0.194
P		0.621			0.453	0.675		0.564						0.611		0.673		0.854
Group	n	Bleeding （V/mL）		Crystal quantity（V/mL）			Colloidal quantity（V/mL）			Red blood cells（λ_B/U）			Plasma （V/mL）		Urine volume（V/mL）		Propofol （m/mg）		Remifentanil（m/mg）
Control	27	552±147		5 782±461			978±133			3.22±1.53			464±94		1 021±164		1 856±194		3.64±1.12
Dexme- detomidine	29	544±131		5 683±409			1 021±116			2.91±1.33			475±82		979±155		1 592±168^*		2.72±0.83^*
t		0.221		0.863			1.312			0.811			0.474		0.995		5.510		3.482
P		0.831		0.395			0.223			0.421			0.642		0.334		<0.001		0.011
^P*<0.05 compared with control group.

Group	n	MAP(P/mmHg)
Group	n	T0	T1	T2	T3
Control	27	82.73±6.72	81.53±6.84	76.82±6.85^△	85.53±7.22
Dexmedetomidine	29	82.23±8.95	82.32±6.64	77.51±7.24^△	80.34±7.82^*
Group	n	HR (beat·min^－1)
Group	n	T0	T1	T2	T3
Control	27	75.32±8.34	70.33±7.32	79.33±9.53^△	85.53±7.93^△
Dexmedetomidine	29	74.83±7.81	67.26±6.87^△	72.46±8.17^*	76.38±6.72^*
Group	n	CVP (P/mmHg)
Group	n	T0	T1	T2	T3
Control	27	5.91±1.43	7.13±1.56^△	8.82±1.76^△	8.55±1.86^△
Dexmedetomidine	29	6.15±1.56	6.92±1.34^△	7.67±1.23^*△	7.43±0.87^*△
Group	n	CI (L·min·m^－2）
Group	n	T0	T1	T2	T3
Control	27	3.92±0.32	3.74±0.66^△	3.59±0.63^△	4.12±0.57^△
Dexmedetomidine	29	4.03±0.36	3.83±0.78^△	3.52±0.73^△	3.95±0.82
Group	n	RPP
Group	n	T0	T1	T2	T3
Control	27	9 023±225	8 567±262^△	9 243±253	9 823±325^△
Dexmedetomidine	29	9 040±283	8 239±221^*△	8 579±219^*△	9 156±264^*

Group	n	Glu [c_B/(mmol·L^－1)]			BE [c_B/(mmol·L^－1)]
Group	n	T0	T1	T2	T0	T1	T2
Control	27	6.52±1.23	8.23±1.77^△	9.52±2.24^△	0.91±0.08	－1.22±0.08^△	－2.52±0.11^△
Dexmedetomidine	29	6.42±1.56	7.34±1.42^*△	8.17±1.93^*△	0.82±0.06	－0.34±0.05^*△	－1.76±0.08^*△
Group	n	Lac [c_B/(mmol·L^－1)]			Cortisol [c_B/(mmol·L^－1)]
Group	n	T0	T1	T2	T0	T1	T2
Control	27	0.90±0.08	1.30±0.08^△	2.50±0.12^△	221±28	276±45^△	294±59^△
Dexmedetomidine	29	0.80±0.06	0.90±0.08^*	1.80±0.09^*△	219±32	244±37^*	271±42^*△

Group	n	Lac[c_B/（mmol·L^－1）]
		T0	T4		T5		T6		T7
Control	27	0.90±0.08	3.43±0.15^△		3.14±0.15^△		2.73±0.16^△		1.92±0.15^△
Dexmedetomidine	29	0.80±0.06	2.92±0.17^*△		2.46±0.13^*△		1.85±0.11^*△		1.26±0.13^*△
Group	n	Lac clearance rate（η/%）
Group	n	T4		T5		T6		T7
Control	27	3.10±0.72		3.12±0.89		15.64±2.67		40.65±5.21
Dexmedetomidine	29	8.13±1.21^*		11.13±2.14^*		33.34±4.13^*		55.53±7.18^*
Group	n	ALT[λ_B/（U·L^－1）]
Group	n	T0		T5		T7
Control	27	32±16		68±27^△		46±15^△
Dexmedetomidine	29	31±14		41±11^*△		32±13^*
Group	n	AST[λ_B/（U·L^－1）]
Group	n	T0		T5		T7
Control	27	38±17		89±25^△		67±21^△
Dexmedetomidine	29	39±14		62±17^*△		44±18^*△

Group	n	Chills	Hypotension	Nausea and vomiting	Abdominal distension	Sleep disturbance	Fever	Surgical site infection	Pulmonary infection
Control	27	8	6	7	10	11	5	0	1
Dexmedetomidine	29	2^*	1^*	1^*	3^*	24^*	1	0	0
^*P<0.05 compared with control group.