右美托咪啶对肝硬化患者围手术期消化功能的影响

doi:10.3877/cma.j.issn.1674-0793.2016.03.009

目的

探讨右美托咪啶对肝硬化患者行肝癌切除术后消化器官功能是否有保护作用。

方法

择期全麻下行肝癌切除术的肝硬化患者50例，年龄18~64岁，ASA分级Ⅱ或Ⅲ级。将患者随机分为右美托咪啶组（D组）和对照组（C组）。D组患者予右美托咪啶首量1 μg/kg，15 min静脉恒速泵注，续以0.3 μg·kg^-1·h^-1的速度持续泵注至手术结束。C组患者以同样方式泵注等量0.9%氯化钠溶液。麻醉前、肝癌切除后1 h、6 h、24 h及72 h取血样，测定血清二胺氯化酶（DAO）、D-乳酸（D-LAC）、天门冬氨酸转氨酶（AST）、丙氨酸转酶（ALT）、肿瘤坏死乳因子（TNF-α）、白细胞介素6（IL-6）、丙二醛（MDA）水平。

结果

两组患者围术期一般情况的比较差异无统计学意义。反映肠损伤的指标随着时间延长而升高，D组的DAO活性及D-乳酸水平在肝切除后较C组明显降低（P<0.05）；反映肝损伤的指标AST和ALT随着时间延长而升高，但D组低于C组（P<0.05）。D组的TNF-α和IL-6活性及MDA在肝切除后较C组明显降低（P<0.01）。

结论

右美托咪啶对肝硬化患者围术期消化器官功能有保护作用。

关键词: 右美托咪啶, 肝切除术, 肝硬化, 消化

Objective

To investigate the effect of dexmedetomidine on digestive functions after hepatectomy in patients with liver cirrhosis under general anesthesia.

Methods

In this prospective, randomized, double-blind investigation, fifty patients with liver cirrhosis undergoing elective hepatectomy were randomized into dexmedetomidine group and control group. General anesthesia was conducted with a target-controlled infusion of propofol at a plasma target concentration of 3-4 μg/ml, 3 μg/kg fentanyl, and 0.2 mg/kg cisatracurium. After tracheal intubation, anesthesia was maintained with a target-controlled infusion of propofol, remifentanil 0.1-0.3 μg·kg^-1·min^-1, and cisatracurium 5-10 mg boluses according to clinical needs. The dexmedetomidine group received a loading dose of 1 μg/kg dexmedetomidine over 15 min right after the intubation, then followed by a maintenance dose of 0.3 μg·kg^-1·h^-1 to the end of operation. In the control group, 0.9% sodium chloride was administered. Venous blood was collected at five time points: baseline (before surgery), 1, 6, 24, and 72 h after hepatectomy. The observation targets included the variables reflecting (1) intestinal injury: serum diamine oxidase (DAO) and D-lactic acid (LAC); (2) liver function: AST and ALT; (3) inflammatory response: TNF-α and IL-6; (4) oxidative stress: MDA.

Results

DAO activity and D-LAC levels were lower in the dexmedetomidine group than in the control group after liver reperfusion (P<0.05). Also, the biomarkers reflecting liver injury increased over time, but were lower in the dexmedetomidine group (P<0.05). And the variables reflecting inflammatory response and oxidative stress were lower in the dexmedetomidine group than in the control group after liver reperfusion (P<0.01).

Conclusions

Dexmedetomidine administered perioperatively attenuates intestinal and hepatic injury in patients with liver cirrhosis after hepatectomy under general anesthesia. The protective mechanism of dexmedetomidine against intestinal and hepatic injury has a close relationship with inhibition of systemic inflammatory response and oxidant stress.

Key words: Dexmedetomidine, Hepatectomy, Liver cirrhosis, Digestion

表1 两组肝硬化患者围手术期一般情况的比较

项目	C组	D组	统计值	P值
例数	25	25	?	?
年龄（ ± s，岁）	47.6±11.4	44.6±10.1	1.023^a	0.38
体重（ ± s，kg）	61.2±7.6	59.4±9.9	0.515^a	0.48
男∶女（例）	18∶7	19∶6	0.104^b	1.00
ASA（Ⅱ/Ⅲ，例）	15/10	17/8	0.347^b	1.00
麻醉时间（ ± s，min）	253±74.5	262.4±62.9	0.222^a	0.64
手术时间（ ± s，min）	193±64.2	218±54.9	2.296^a	0.14
失血量［M(Q)，ml］	600(425,800)	400(250,800)	1.327^c	0.25
尿量（ ± s，ml）	594±180	544±205	0.841^a	0.36

表1 两组肝硬化患者围手术期一般情况的比较

项目	C组	D组	统计值	P值
例数	25	25	?	?
年龄（ ± s，岁）	47.6±11.4	44.6±10.1	1.023^a	0.38
体重（ ± s，kg）	61.2±7.6	59.4±9.9	0.515^a	0.48
男∶女（例）	18∶7	19∶6	0.104^b	1.00
ASA（Ⅱ/Ⅲ，例）	15/10	17/8	0.347^b	1.00
麻醉时间（ ± s，min）	253±74.5	262.4±62.9	0.222^a	0.64
手术时间（ ± s，min）	193±64.2	218±54.9	2.296^a	0.14
失血量［M(Q)，ml］	600(425,800)	400(250,800)	1.327^c	0.25
尿量（ ± s，ml）	594±180	544±205	0.841^a	0.36

表2 两组肝硬化患者不同时间点肝脏及肠道血清标志物的变化

时间点	ALT(U/L)		AST(U/L)		DAO(U/mg)		D-LAC(mg/L)
时间点	C组	D组	C组	D组	C组	D组	C组	D组
麻醉前	29.5±5.46	29.8±9.83	34.2±14.95	41.6±20.24	8.2±2.46	7.1±2.03	3.5±0.36	2.4±0.43
术后1 h	39.9±10.83	37.1±10.99	132.3±66.31^c	91.9±46.09^ac	10.8±2.27	8.9±2.82^a	7.7±0.96^c	3.3±0.83^b
术后6 h	66.3±27.16^c	55.3±22.26^c	309.8±111.50^c	210.2±48.80^bc	13.8±4.39^c	9.9±3.26^bc	11.8±1.19^c	4.8±0.81^bc
术后24 h	298.6±157.67^c	169.9±57.34^bc	838.8±421.66^c	402.1±188.83^bc	13.7±3.81^c	9.5±3.03^bc	11.3±1.15^c	4.9±1.04^bc
术后72 h	179.8±76.88^c	83.6±31.89^bc	239.9±147.71^c	150.9±84.67^ac	10.7±5.16^c	9.1±3.33	8.8±1.07^c	3.8±0.62^b

表2 两组肝硬化患者不同时间点肝脏及肠道血清标志物的变化

时间点	ALT(U/L)		AST(U/L)		DAO(U/mg)		D-LAC(mg/L)
时间点	C组	D组	C组	D组	C组	D组	C组	D组
麻醉前	29.5±5.46	29.8±9.83	34.2±14.95	41.6±20.24	8.2±2.46	7.1±2.03	3.5±0.36	2.4±0.43
术后1 h	39.9±10.83	37.1±10.99	132.3±66.31^c	91.9±46.09^ac	10.8±2.27	8.9±2.82^a	7.7±0.96^c	3.3±0.83^b
术后6 h	66.3±27.16^c	55.3±22.26^c	309.8±111.50^c	210.2±48.80^bc	13.8±4.39^c	9.9±3.26^bc	11.8±1.19^c	4.8±0.81^bc
术后24 h	298.6±157.67^c	169.9±57.34^bc	838.8±421.66^c	402.1±188.83^bc	13.7±3.81^c	9.5±3.03^bc	11.3±1.15^c	4.9±1.04^bc
术后72 h	179.8±76.88^c	83.6±31.89^bc	239.9±147.71^c	150.9±84.67^ac	10.7±5.16^c	9.1±3.33	8.8±1.07^c	3.8±0.62^b

表3 两组肝硬化患者不同时间点全身炎性反应及氧化应激的变化

时间点	TNF-α(ng/L)		IL-6(U/ml)		MDA(μmol/L)
时间点	C组	D组	C组	D组	C组	D组
麻醉前	13.3±1.50	14.9±1.25	40.8±3.92	30.0±3.71	6.0±2.28	5.7±2.87
术后1 h	66.2±5.29^b	40.3±4.72^ab	79.3±8.10	63.1±9.26	14.3±3.70^b	9.8±4.99^ab
术后6 h	141.7±10.71^b	61.2±8.95^ab	210.1±19.29^b	102.3±10.38^ab	18.2±5.55^b	11.7±5.58^ab
术后24 h	94.2±8.78^b	58.8±6.76^ab	400.0±48.54^b	193.6±22.95^ab	13.6±5.47^b	10.9±4.65^b
术后72 h	15.3±1.87	13.6±1.64	111.4±8.59^b	81.2±6.21^ab	9.8±4.82^b	9.9±4.46^b

表3 两组肝硬化患者不同时间点全身炎性反应及氧化应激的变化

时间点	TNF-α(ng/L)		IL-6(U/ml)		MDA(μmol/L)
时间点	C组	D组	C组	D组	C组	D组
麻醉前	13.3±1.50	14.9±1.25	40.8±3.92	30.0±3.71	6.0±2.28	5.7±2.87
术后1 h	66.2±5.29^b	40.3±4.72^ab	79.3±8.10	63.1±9.26	14.3±3.70^b	9.8±4.99^ab
术后6 h	141.7±10.71^b	61.2±8.95^ab	210.1±19.29^b	102.3±10.38^ab	18.2±5.55^b	11.7±5.58^ab
术后24 h	94.2±8.78^b	58.8±6.76^ab	400.0±48.54^b	193.6±22.95^ab	13.6±5.47^b	10.9±4.65^b
术后72 h	15.3±1.87	13.6±1.64	111.4±8.59^b	81.2±6.21^ab	9.8±4.82^b	9.9±4.46^b

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Protective effects of dexmedetomidine on perioperative digestive function of patients with liver cir-rhosis

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Protective effects of dexmedetomidine on perioperative digestive function of patients with liver cir-rhosis