术中使用小剂量右美托咪定对乳腺癌手术患者预后的影响

doi:10.3969/j.issn.1674-8115.2023.02.008

摘要/Abstract

摘要：

目的·探讨术中使用右美托咪定对乳腺癌患者手术后5年无复发生存率（recurrence-free survival，RFS）和总生存率（overall survival，OS）的影响。方法·回顾性分析2013年7月至2014年6月在上海交通大学医学院附属瑞金医院乳腺疾病诊治中心接受乳腺癌手术的患者，根据术中是否滴注0.7~0.8 μg/kg右美托咪定，分为右美组和对照组。采用倾向性评分匹配法校正组间混杂因素后，通过单因素和多因素分析调查影响乳腺癌手术患者预后生存的因素，进一步通过Kaplan-Meier生存曲线分析术中使用右美托咪定对乳腺癌手术后5年的RFS和OS的影响。结果·倾向性评分匹配前2组患者年龄、孕激素受体（progesterone receptor，PR）阳性比例、增殖细胞核抗原（Ki67）表达评分、美国麻醉医师协会（American Society of Anesthesiologists，ASA）分级、麻醉时长存在差异。倾向性评分匹配后共239对配对成功，匹配后2组患者的基线资料和围术期相关数据差异无统计学意义（P>0.05）。单因素分析发现年龄（P=0.032）、术后放射治疗（P=0.041）、Ki67评分（P=0.021）、肿瘤TMN分期（P=0.029）与术后5年OS显著相关。多因素分析结果显示，术后放射治疗、Ki67评分、肿瘤TMN分期与术后5年OS显著相关（P<0.05）。术中滴注小剂量右美托咪定不是影响术后5年OS的危险因素（P>0.05）。与对照组比较，右美组术后5年的RFS和OS无明显降低（P>0.05）。结论·术中使用小剂量（0.7~0.8 μg/kg）右美托咪定不影响乳腺癌手术患者术后5年RFS和OS，为肿瘤手术患者麻醉药物的合理选择提供了理论参考。更高剂量右美托咪定的作用需进行前瞻性的多中心随机对照研究进一步确认。

关键词: 右美托咪定, 乳腺癌, 总生存率, 无病生存率

Abstract:

Objective ·To investigate the influence of intraoperative dexmedetomidine infusion on the recurrence-free survival (RFS) and overall survival (OS) rate of patients undergoing breast cancer surgery. Methods ·A retrospective analysis was performed on patients who underwent breast cancer surgery at the Breast Disease Diagnosis and Treatment Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from July 2013 to June 2014. Patients were divided into dexmedetomidine group and control group according to whether dexmedetomidine was injected intraoperatively at 0.7?0.8 ìg/kg. After correcting the confounding factors between the two groups by using the propensity score matching method, the factors affecting the prognosis and survival of patients undertaking breast cancer surgery were investigated by univariate and multivariate analysis, and the Kaplan-Meier survival curve was further used to analyze the effect of intraoperative dexmedetomidine on RFS and OS after five years of breast cancer surgery. Results ·There were significant differences in age, progesterone receptor (PR) positive ratio, proliferating cell nuclear antigen (Ki67) expression score, American Society of Anesthesiologists (ASA) grade, and anesthesia duration between the two groups before propensity score matching. After propensity score matching, a total of 239 pairs were successfully matched, and there was no significant difference in baseline data and perioperative data between the two groups (P>0.05). Univariate analysis showed that age (P=0.032), postoperative radiotherapy (P=0.041), Ki67 score (P=0.021), and tumor TMN stage (P=0.029) were significantly correlated with postoperative five-year OS. The results of multivariate analysis showed that postoperative radiotherapy, Ki67 score, and tumor TMN stage were significantly correlated with postoperative five-year OS (P<0.05). Intraoperative low-dose dexmedetomidine infusion was not a risk factor for postoperative five-year OS (P>0.05). Compared with the control group, the five-year postoperative RFS and OS in dexmedetomidine group did not decrease significantly (P>0.05). Conclusion ·Intraoperative use of low dosage of dexmedetomidine (0.7?0.8 μg/kg) has no significant effect on RFS and OS in patients undergoing breast cancer surgery at five years postoperatively, providing theoretical reference for the rational selection of anesthetics for tumor patients. The effect of higher dosage of dexmedetomidine needs to be further confirmed by prospective multicenter randomized controlled studies.

Key words: dexmedetomidine, breast cancer, overall survival, recurrence-free survival

中图分类号:

R614.2

杨笑萱, 朱珊, 钱程, 储晓英. 术中使用小剂量右美托咪定对乳腺癌手术患者预后的影响[J]. 上海交通大学学报（医学版）, 2023, 43(2): 194-200.

YANG Xiaoxuan, ZHU Shan, QIAN Cheng, CHU Xiaoying. Effect of intraoperative use of low-dose dexmedetomidine on the prognosis of patients undergoing breast cancer surgery[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023, 43(2): 194-200.

图/表 4

参考文献 18

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Item	DEX group (n=385)	Control group (n=273)	P value
Age/year	54.5±0.6	52.1±0.7	0.004
BMI/(kg·m^-2)	23.2±0.2	23.3±0.2	0.002
Chemotherapy/n(%)	259 (67.3)	180 (65.9)	0.742
Radiotherapy/n(%)	176 (45.7)	127 (46.5)	0.871
Hormonal therapy/n(%)	236 (61.3)	177 (64.8)	0.365
ER+/n(%)	224 (58.2)	171 (62.6)	0.258
PR+/n(%)	155 (40.3)	140 (51.3)	0.011
HER2+/n(%)	94 (24.4)	61 (22.3)	0.576
Ki67/n(%)	209 (54.3)	151 (55.3)	0.812
ASA classification/n(%)			0.000
Ⅰ	206 (53.5)	91 (33.3)
Ⅱ	179 (46.5)	182 (66.7)
TMN stage/n(%)			0.937
0	50 (13.0)	31 (11.4)
Ⅰ	155 (40.3)	106 (38.8)
ⅡA	101 (26.2)	77 (28.2)
ⅡB	36 (9.3)	28 (10.3)
Ⅲ	43 (11.2)	31 (11.4)
Type of surgery/n(%)			0.891
Breast-conserving surgery	111 (28.8)	80 (29.3)
Mastectomy	274 (71.2)	193 (70.7)
Duration of anesthesia/min	64.8±1.1	61.1±0.9	0.023
Remifentanil/μg	707.7±17.2	692.6±19.6	0.563
Sufentanyl/μg	34.5±0.5	34.2±0.6	0.638
Propofol/mg	142.0±1.2	138.6±1.4	0.074
Cisatracurium/mg	19.7±0.2	19.4±0.3	0.301
Inhalable anesthetic/n(%)			0.169
Sevoflurane	183 (47.5)	115 (42.1)
Desflurane	202 (52.5)	158 (57.9)
VAS score when leaving PACU	0.6±0.0	0.6±0.0	0.342
Propensity score	0.31±0.08	0.25±0.06	0.006

Item	DEX group (n=385)	Control group (n=273)	P value
Age/year	54.5±0.6	52.1±0.7	0.004
BMI/(kg·m^-2)	23.2±0.2	23.3±0.2	0.002
Chemotherapy/n(%)	259 (67.3)	180 (65.9)	0.742
Radiotherapy/n(%)	176 (45.7)	127 (46.5)	0.871
Hormonal therapy/n(%)	236 (61.3)	177 (64.8)	0.365
ER+/n(%)	224 (58.2)	171 (62.6)	0.258
PR+/n(%)	155 (40.3)	140 (51.3)	0.011
HER2+/n(%)	94 (24.4)	61 (22.3)	0.576
Ki67/n(%)	209 (54.3)	151 (55.3)	0.812
ASA classification/n(%)			0.000
Ⅰ	206 (53.5)	91 (33.3)
Ⅱ	179 (46.5)	182 (66.7)
TMN stage/n(%)			0.937
0	50 (13.0)	31 (11.4)
Ⅰ	155 (40.3)	106 (38.8)
ⅡA	101 (26.2)	77 (28.2)
ⅡB	36 (9.3)	28 (10.3)
Ⅲ	43 (11.2)	31 (11.4)
Type of surgery/n(%)			0.891
Breast-conserving surgery	111 (28.8)	80 (29.3)
Mastectomy	274 (71.2)	193 (70.7)
Duration of anesthesia/min	64.8±1.1	61.1±0.9	0.023
Remifentanil/μg	707.7±17.2	692.6±19.6	0.563
Sufentanyl/μg	34.5±0.5	34.2±0.6	0.638
Propofol/mg	142.0±1.2	138.6±1.4	0.074
Cisatracurium/mg	19.7±0.2	19.4±0.3	0.301
Inhalable anesthetic/n(%)			0.169
Sevoflurane	183 (47.5)	115 (42.1)
Desflurane	202 (52.5)	158 (57.9)
VAS score when leaving PACU	0.6±0.0	0.6±0.0	0.342
Propensity score	0.31±0.08	0.25±0.06	0.006

Item	DEX group (n=239)	Control group (n=239)	P value
Age/year	54.3±0.8	52.9±0.8	0.212
BMI/(kg·m^-2)	23.1±0.2	23.0±0.2	0.681
Chemotherapy/n(%)	168 (70.3)	161 (67.4)	0.548
Radiotherapy/n(%)	119 (49.8)	108 (45.2)	0.357
Hormonal therapy/n(%)	116 (48.5)	109 (45.6)	0.582
ER+/n(%)	125 (52.3)	141 (59.0)	0.174
PR+/n(%)	158 (66.1)	140 (58.6)	0.113
HER2+/n(%)	60 (25.1)	58 (24.3)	0.916
Ki67/n(%)	129 (54.0)	141 (59.0)	0.308
ASA classification/n(%)			0.082
Ⅰ	109 (45.6)	129 (54.0)
Ⅱ	130 (54.4)	110 (46.0)
TMN stage/n(%)			0.531
0	24 (9.9)	21 (8.5)
Ⅰ	103 (43.3)	100 (41.9)
ⅡA	75 (31.2)	79 (33.1)
ⅡB	10 (4.3)	12 (5.1)
Ⅲ	27 (11.1)	27 (11.4)
Type of surgery/n(%)			0.176
Breast-conserving surgery	6 (25.8)	58 (24.3)
Mastectomy	177 (74.2)	181 (75.7)
Duration of anesthesia/min	64.6±1.3	62.2±1.0	0.162
Remifentanil/μg	680.5±20.7	704.7±21.6	0.416
Sufentanyl/μg	34.0±0.7	34.2±0.7	0.781
Propofol/mg	141.9±1.5	138.2±1.4	0.073
Cisatracurium/mg	19.4±0.3	19.1±0.3	0.367
Inhalable anesthetic/n(%)			0.564
Sevoflurane	83 (34.8)	76 (32.1)
Desflurane	156 (65.2)	163 (67.9)
VAS score when leaving PACU	0.6±0.0	0.7±0.1	0.125
Propensity score	0.29±0.07	0.30±0.06	0.331

Item	DEX group (n=239)	Control group (n=239)	P value
Age/year	54.3±0.8	52.9±0.8	0.212
BMI/(kg·m^-2)	23.1±0.2	23.0±0.2	0.681
Chemotherapy/n(%)	168 (70.3)	161 (67.4)	0.548
Radiotherapy/n(%)	119 (49.8)	108 (45.2)	0.357
Hormonal therapy/n(%)	116 (48.5)	109 (45.6)	0.582
ER+/n(%)	125 (52.3)	141 (59.0)	0.174
PR+/n(%)	158 (66.1)	140 (58.6)	0.113
HER2+/n(%)	60 (25.1)	58 (24.3)	0.916
Ki67/n(%)	129 (54.0)	141 (59.0)	0.308
ASA classification/n(%)			0.082
Ⅰ	109 (45.6)	129 (54.0)
Ⅱ	130 (54.4)	110 (46.0)
TMN stage/n(%)			0.531
0	24 (9.9)	21 (8.5)
Ⅰ	103 (43.3)	100 (41.9)
ⅡA	75 (31.2)	79 (33.1)
ⅡB	10 (4.3)	12 (5.1)
Ⅲ	27 (11.1)	27 (11.4)
Type of surgery/n(%)			0.176
Breast-conserving surgery	6 (25.8)	58 (24.3)
Mastectomy	177 (74.2)	181 (75.7)
Duration of anesthesia/min	64.6±1.3	62.2±1.0	0.162
Remifentanil/μg	680.5±20.7	704.7±21.6	0.416
Sufentanyl/μg	34.0±0.7	34.2±0.7	0.781
Propofol/mg	141.9±1.5	138.2±1.4	0.073
Cisatracurium/mg	19.4±0.3	19.1±0.3	0.367
Inhalable anesthetic/n(%)			0.564
Sevoflurane	83 (34.8)	76 (32.1)
Desflurane	156 (65.2)	163 (67.9)
VAS score when leaving PACU	0.6±0.0	0.7±0.1	0.125
Propensity score	0.29±0.07	0.30±0.06	0.331

Influencing factor	Univariate analysis		Multivariate analysis
Influencing factor	HR(95%CI)	P value	HR(95%CI)	P value
Age	1.02 (1.00, 1.03)	0.032	1.01 (0.99, 1.04)	0.062
BMI	1.01 (0.98, 1.03)	0.891	1.00 (0.99, 1.01)	0.603
Chemotherapy	0.98 (0.95, 1.00)	0.063	0.98 (0.95, 1.11)	0.062
Radiotherapy	0.54 (0.24, 1.47)	0.041	0.55 (0.26, 1.54)	0.033
Hormonal therapy	1.10 (0.56, 1.48)	0.732	0.93 (0.65, 1.33)	0.562
ER+	0.98 (0.45, 1.54)	0.087	1.12 (0.66, 1.69)	0.118
PR+	1.09 (0.53, 1.44)	0.228	1.22 (0.64, 1.73)	0.215
HER2+	1.02 (0.51, 1.49)	0.198	1.12 (0.58, 1.63)	0.115
Ki67	1.15 (1.01, 1.22)	0.021	1.13 (1.09, 1.18)	0.033
ASA classification	0.97 (0.95, 1.01)	0.067	1.01 (0.97, 1.04)	0.632
TMN stage		0.029		0.032
0	0.99 (0.95, 1.05)		1.25 (0.74, 2.09)
Ⅰ	1.15 (0.64, 1.71)		1.24 (0.46, 2.12)
ⅡA	1.09 (0.52, 1.51)		0.96 (0.62, 1.38)
ⅡB	1.16 (0.88, 1.23)		1.21 (1.01, 1.58)
Ⅲ	1.23 (0.74, 1.74)		1.26 (0.87, 1.84)
Type of surgery		0.781		0.593
Breast-conserving surgery	1.09 (0.84, 1.52)		1.08 (0.73, 1.59)
Mastectomy	0.98 (0.91, 1.15)		1.02 (0.79, 1.69)
Duration of anesthesia	1.02 (0.85, 1.36)	0.232	0.99 (0.69, 1.23)	0.312
Remifentanil	0.69 (0.34, 1.89)	0.538	0.74 (0.49, 1.09)	0.381
Sufentanyl	0.87 (0.39, 1.41)	0.667	0.98 (0.71, 1.29)	0.769
Propofol	1.01 (0.88, 1.29)	0.517	1.10 (0.89, 1.31)	0.487
Cisatracurium	1.05 (0.91, 1.25)	0.473	1.08 (0.88, 1.27)	0.388
Inhalable anesthetic	0.94 (0.73, 1.27)	0.081	0.92 (0.87, 1.08)	0.057
VAS score when leaving PACU	1.02 (0.81, 1.19)	0.790	1.10 (0.81, 1.19)	0.682
Dexmedetomidine	1.15 (0.62, 2.16)	0.626	1.17 (0.62, 2.20)	0.673