子宮切除術(shù)前給予右美托咪定對(duì)患者應(yīng)激和免疫功能的影響

劉紅梅，楊　莉

(河北省唐山市工人醫(yī)院麻醉科，河北 唐山 063000)

子宮切除術(shù)前給予右美托咪定對(duì)患者應(yīng)激和免疫功能的影響

劉紅梅，楊莉

(河北省唐山市工人醫(yī)院麻醉科，河北 唐山 063000)

目的：探討右美托咪定對(duì)子宮切除術(shù)患者應(yīng)激及免疫功能的影響，旨在為臨床麻醉用藥提供依據(jù)。方法：選取子宮肌瘤且需行擇期子宮切除術(shù)患者60例，ASA Ⅰ-Ⅱ級(jí)，依據(jù)預(yù)輸注藥物不同分為觀察組和對(duì)照組，每組30例，觀察組患者麻醉前給予負(fù)荷劑量右美托咪定靜脈泵注，劑量1 μg·kg-1，濃度4 mg·L-1，泵注時(shí)間10 min，對(duì)照組患者給予等量生理鹽水泵注。2組均在泵注10 min后開(kāi)始誘導(dǎo)，麻醉中2組患者均使用七氟醚和芬太尼維持；2組患者于入室前(T0)、手術(shù)2 h(T1)和術(shù)后拔管時(shí)(T2)采血，檢測(cè)血清皮質(zhì)醇(COR)和白細(xì)胞介素2(IL-2)濃度，并檢測(cè)血漿T 淋巴細(xì)胞亞群和 NK 細(xì)胞水平。結(jié)果：2組患者T0時(shí)血清COR和IL-2濃度比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)；2組患者T2時(shí)COR濃度明顯高于T0時(shí)(P<0.05)；觀察組T2時(shí)COR濃度明顯低于對(duì)照組(P<0.05)；隨手術(shù)時(shí)間延長(zhǎng)2組患者血清IL-2濃度呈下降趨勢(shì)，觀察組T2時(shí)血清IL-2濃度明顯高于對(duì)照組(P<0.05)；2組患者T0時(shí)CD3+、CD4+、CD8+、CD4+/ CD8+和NK水平比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)；2組患者各時(shí)間點(diǎn)CD8+水平比較差異均無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)；對(duì)照組患者T1和T2時(shí)CD3+、CD4+、CD4+/ CD8+及NK水平均明顯低于T0時(shí)(P<0.05)；觀察組T2時(shí)CD3+、CD4+、CD4+/ CD8+和NK水平均明顯高于對(duì)照組(P<0.05)。結(jié)論：右美托咪定輔助麻醉可減輕患者術(shù)后應(yīng)激反應(yīng)，降低麻醉及手術(shù)創(chuàng)傷對(duì)機(jī)體細(xì)胞免疫功能的影響，利于患者術(shù)后康復(fù)。

子宮切除術(shù)；右美托咪定；皮質(zhì)醇；白細(xì)胞介素2；T淋巴細(xì)胞亞群

子宮切除術(shù)是婦科常用的手術(shù)治療方案，療效明顯；但麻醉藥物的應(yīng)用及手術(shù)創(chuàng)傷均可對(duì)機(jī)體神經(jīng)內(nèi)分泌及免疫功能造成一定影響[1-3]。右美托咪定屬新型腎上腺素能α2受體激動(dòng)劑，具有高選擇性，鎮(zhèn)靜作用良好，對(duì)心血管系統(tǒng)影響小，已被廣泛應(yīng)用于臨床[4]。有研究[5]表明：右美托咪定具有抑制內(nèi)毒素導(dǎo)致的炎癥反應(yīng)作用。但右美托咪定對(duì)子宮切除術(shù)患者應(yīng)激及免疫功能的影響報(bào)道相對(duì)較少。為觀察右美托咪定對(duì)子宮切除術(shù)患者應(yīng)激及免疫功能的影響，本文作者選取本院收治的子宮肌瘤需行擇期子宮切除術(shù)患者，麻醉誘導(dǎo)前給予負(fù)荷劑量右美托咪定靜脈泵注，觀察其血清皮質(zhì)醇(COR)、白細(xì)胞介素2(IL-2)濃度、血漿T 淋巴細(xì)胞亞群及NK 細(xì)胞水平變化，旨在為臨床麻醉用藥提供依據(jù)。

1　資料與方法

1.1研究對(duì)象選取2013年1月—2014年1月本院收治的子宮肌瘤需擇期行子宮切除術(shù)患者60例，年齡40～65歲，平均年齡(56.0±9.1)歲，體質(zhì)量53～80 kg，平均體質(zhì)量(59.5±10.2) kg，ASAⅠ-Ⅱ級(jí)。納入標(biāo)準(zhǔn)：①術(shù)前確診為良性子宮肌瘤的患者； ②ASA Ⅰ-Ⅱ級(jí)；③患者術(shù)前近期未使用激素類藥物。排除標(biāo)準(zhǔn)：排除肝、腎功能異常、內(nèi)分泌疾病、代謝性疾病、自身免疫性疾病及感染發(fā)熱患者。所有患者術(shù)前均獲得患者及家屬同意并簽署知情同意書，并經(jīng)本院醫(yī)學(xué)倫理委員會(huì)批準(zhǔn)進(jìn)行觀察。60例手術(shù)患者依據(jù)術(shù)前預(yù)輸注藥物不同分為觀察組與對(duì)照組，每組各30例，2組患者年齡、體質(zhì)量分布比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)，具有可比性。

1.2麻醉方法2組患者術(shù)前2 h禁食、4 h禁飲，入室后常規(guī)開(kāi)放靜脈通路，并監(jiān)測(cè)心率、心電圖、無(wú)創(chuàng)舒張壓和收縮壓(SBP)。①麻醉誘導(dǎo)。觀察組患者麻醉前給予負(fù)荷劑量右美托咪定靜脈泵注，劑量1 μg·kg-1，濃度4 mg·L-1，泵注時(shí)間10 min，對(duì)照組患者給予等量生理鹽水泵注；2組均在泵注10 min后開(kāi)始誘導(dǎo)；方法：藥物泵注10 min后給予2 mg·kg-1異丙酚、0.08 mg·kg-1萬(wàn)可松、0.003 mg·kg-1芬太尼靜注；患者意識(shí)消失后，行經(jīng)口氣管插管、通氣，設(shè)定通氣頻率12～14 min-1，潮氣量6～8 mL·kg-1，吸呼比1∶2，氧流量2 L·min-1，呼氣末二氧化碳分壓(PETCO2)維持在35～45 mmHg。②麻醉維持。維持藥物使用0.5%～3.0%七氟醚，麻醉深度以生命體征平穩(wěn)，心率、血壓波動(dòng)于基礎(chǔ)值±20為宜，根據(jù)術(shù)中實(shí)際情況追加芬太尼；觀察組患者持續(xù)泵注右美托咪定，劑量0.5 μg·kg-1·h-1；為保證術(shù)中足夠的肌松，2組均按需給予維持劑量的萬(wàn)可松，術(shù)中給予6%中分子輕乙基淀粉注射液及0.9%的生理鹽水以維持血循環(huán)量，手術(shù)結(jié)束前5 min關(guān)閉右美托咪定泵注及SEV，術(shù)后待患者自主呼吸恢復(fù)，患者可喚醒后，清理呼吸道即可拔出氣管導(dǎo)管，使用面罩吸氧。

1.3觀察指標(biāo)2組患者于入室前(T0)、手術(shù)2 h(T1)、術(shù)后拔管時(shí)(T2)采集肘靜脈血，檢測(cè)血清COR、IL-2濃度，并使用FACSClibur 流式細(xì)胞儀(BD 公司， 美國(guó)) 檢測(cè)血T 淋巴細(xì)胞亞群和 NK 細(xì)胞水平。

2　結(jié)　果

2.12組患者不同時(shí)間點(diǎn)血清COR和IL-2濃度2組患者T0時(shí)血清COR和IL-2濃度比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)，T2時(shí)COR濃度明顯高于T0時(shí)(P<0.05)；觀察組患者T2時(shí)COR濃度明顯低于對(duì)照組(P<0.05)；隨手術(shù)時(shí)間延長(zhǎng)2組血清IL-2濃度呈下降趨勢(shì)，觀察組T2時(shí)患者血清IL-2濃度明顯高于對(duì)照組(P<0.05)。見(jiàn)表1。

2.22組患者不同時(shí)間點(diǎn)血清T淋巴細(xì)胞亞群和 NK 細(xì)胞水平2組患者T0時(shí)CD3+、CD4+、CD8+、CD4+/ CD8+和NK水平比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)；2組不同時(shí)間點(diǎn)CD8+水平比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)；對(duì)照組患者T1和T2時(shí)CD3+、CD4+、CD4+/ CD8+及NK水平均明顯低于T0時(shí)(P<0.05)；觀察組T2時(shí)CD3+、CD4+、CD4+/ CD8+和NK水平均明顯高于對(duì)照組(P<0.05)。見(jiàn)表2。

表1　不同時(shí)間點(diǎn)2組患者血清COR和IL-2濃度

*P<0.05 compared with T2;△P<0.05 compared with control group.

表2　不同時(shí)間點(diǎn)2組患者T細(xì)胞亞群和 NK 細(xì)胞水平

*P<0.05 compared with T0 ;△P<0.05 compared with control group.

3　討　論

子宮切除術(shù)是婦科臨床常用的治療術(shù)式，對(duì)子宮良、惡性疾病的治療均可獲得良好的療效[6]。隨著臨床研究的不斷深入，其臨床適應(yīng)證也不斷擴(kuò)大，但該術(shù)式存在操作時(shí)間長(zhǎng)和對(duì)患者創(chuàng)傷大的缺點(diǎn)，加之麻醉藥物的使用，均可對(duì)患者應(yīng)激反應(yīng)及免疫功能產(chǎn)生不同程度的影響，這不僅影響了患者的術(shù)后康復(fù)，亦給患者帶來(lái)不同程度的身心痛苦[7]。因此，如何降低麻醉藥物對(duì)患者術(shù)后應(yīng)激反應(yīng)及免疫功能的影響，已成為臨床亟待解決的問(wèn)題。

應(yīng)激反應(yīng)是機(jī)體受到創(chuàng)傷后發(fā)生的全身性非特異性反應(yīng)，主要表現(xiàn)為丘腦-垂體-腎上腺皮質(zhì)軸、交感-腎上腺髓質(zhì)軸和藍(lán)斑-去甲腎上腺素能神經(jīng)元的強(qiáng)烈反應(yīng)，其應(yīng)激強(qiáng)度與創(chuàng)傷程度呈正相關(guān)關(guān)系，如機(jī)體發(fā)生強(qiáng)烈應(yīng)激紊亂，則可導(dǎo)致嚴(yán)重繼發(fā)性損害[10]。因此，圍手術(shù)期有效調(diào)控機(jī)體應(yīng)激反應(yīng)，對(duì)患者預(yù)后意義重大。右美托咪定是近年來(lái)新研發(fā)的α2-腎上腺素受體激動(dòng)劑，鎮(zhèn)靜作用明顯，還具有減輕機(jī)體應(yīng)激反應(yīng)的效果[8-9]。COR是應(yīng)激反應(yīng)中的抑制性反饋調(diào)節(jié)因子，具有唯一性，亦是反映機(jī)體應(yīng)激反應(yīng)程度的敏感指標(biāo)，測(cè)定COR濃度可準(zhǔn)確地反映麻醉手術(shù)對(duì)患者應(yīng)激狀態(tài)的影響[11]。本研究中，觀察組患者T2時(shí)血清COR濃度明顯低于對(duì)照組，提示右美托咪定可有效降低子宮切除術(shù)患者應(yīng)激反應(yīng)，利于患者術(shù)后康復(fù)。有研究[11-14]表明：麻醉藥物的搭配與劑量對(duì)患者的免疫功能可產(chǎn)生不同影響，如何調(diào)配麻醉藥物已成為麻醉學(xué)術(shù)界研究的重要方向之一；另外，患者免疫功能的強(qiáng)弱對(duì)維護(hù)機(jī)體內(nèi)環(huán)境平衡及術(shù)后康復(fù)意義重大。IL-2是活化的T淋巴細(xì)胞產(chǎn)生的調(diào)節(jié)因子，具有促進(jìn)T細(xì)胞分析、增殖的作用，并可促進(jìn)B細(xì)胞分泌抗體，促進(jìn)機(jī)體防御感染[12，15]。同時(shí)，IL-2亦是維持T細(xì)胞及NK細(xì)胞正常功能的重要條件；因此，IL-2濃度檢測(cè)可準(zhǔn)確反映機(jī)體免疫功能狀況[16]。本研究中，觀察組患者T2時(shí)IL-2濃度明顯高于對(duì)照組，提示右美托咪定作為麻醉輔助用藥在短時(shí)間的手術(shù)中對(duì)患者IL-2水平無(wú)明顯抑制作用。有研究[17-18]證實(shí)：T 淋巴細(xì)胞亞群在細(xì)胞免疫過(guò)程中起主要作用，其中CD3+可反映細(xì)胞免疫總體水平，CD4+具有輔助其他細(xì)胞參與免疫應(yīng)答的作用，CD8+可抑制免疫細(xì)胞功能；而CD4+/CD8+可準(zhǔn)確反映機(jī)體免疫狀態(tài)，其比值降低，多提示機(jī)體免疫功能低下，預(yù)后不良；NK 細(xì)胞是免疫調(diào)節(jié)細(xì)胞，其活力高低亦可作為判斷疾病發(fā)展及轉(zhuǎn)歸的指標(biāo)。本研究中，對(duì)照組患者T2時(shí)除CD8+外，其余各項(xiàng)指標(biāo)均明顯下降，而觀察組患者各時(shí)間點(diǎn)下降幅度與T0時(shí)比較差異無(wú)統(tǒng)計(jì)學(xué)意義，表明右美托咪定可明顯減輕麻醉及手術(shù)對(duì)細(xì)胞免疫功能的影響，對(duì)患者術(shù)后康復(fù)起積極作用。

綜上所述，右美托咪定輔助麻醉可減輕子宮切除術(shù)患者術(shù)后應(yīng)激反應(yīng)，降低麻醉及手術(shù)刺激對(duì)機(jī)體細(xì)胞免疫功能的影響，利于患者術(shù)后康復(fù)。

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Influence of administration of dexmedetomidine before uterectomy in stress and immunologic function in patients

LIU Hongmei,YANG Li

(Department of Anesthesiology,Worker’s Hospital of Tanshan City,Hebei Province,Tangshan 063000,China)

ObjectiveTo explore the effect of dexmedetomidine on the stress and immunologic function in the patients undergoing uterectomy,and to provide an evidence for the medication in clinical anesthesia.MethodsA total of 60 hysteromyoma patients who needed uterectomy were selected. All the patients were in ASAⅠ-Ⅱlevel.The patients were divided into observation group (n=30) and control group (n=30) according to administration of different types of drugs.Before anesthesia,the patients in observation group were given dexmedetomidine (l μg·kg-1) with a concentration of 4 g·L-1for 10 min,while the patients in control group were given equal normal saline.The induction was performed 10 min after infusion pump.Sevoflurane and fentanyl were used for maintaining during the anesthesia.The blood samples of the patients in two groups before entering the operation room (T0),2 h after operation (T1),and extubation after operation (T2) were collected.The serum cortisol (COR) and interleukin-2 (IL-2) concentrations,plasma T lymphocyte subpopulations and NK levels were detected.ResultsThe differences of COR and IL-2 concentrations at T0 between two groups were not statistically significant (P>0.05).The COR concentrations at T2 in two groups were significantly higher than those at T0 (P<0.05).The COR concentration at T2 in observation group was significantly lower than that in control group (P<0.05).The serum IL-2 concentration was gradually decreased with the prolongation of time observation in two groups.The serum IL-2 concentration in observation group was significantly higher than that in control group (P<0.05).The differences of CD3+,CD4+,CD8+,CD4+/ CD8+,and NK levels at T0 between two groups were not statistically significant (P>0.05).The differences of CD8+level in each time point between two groups were not statistically significant (P>0.05).The CD3+,CD4+,CD4+/ CD8+,and NK levels at T1 and T2 in control group were significantly lower than those at T0 (P<0.05).The CD3+,CD4+,CD4+/ CD8+,and NK levels at T2 in observation group were significantly higher than those in control group (P<0.05).ConclusionDexmedetomidine assisting anesthesia can alleviate the postoperative stress reaction,and reduce the effect of anesthesia and operation wound on the cellular immune function.It is beneficial for the postoperative rehabilitation.

hysterectomy;dexmedetomidine; cortisol;interleukin-2; T lymphocyte subsets

1671-587Ⅹ(2015)06-1245-04

10.13481/j.1671-587x.20150628

2015-05-25

河北省科技廳科技發(fā)展項(xiàng)目資助課題(20091748)

劉紅梅(1972-)，女，河北省唐山市人，副主任醫(yī)師，醫(yī)學(xué)碩士，主要從事臨床麻醉方面的研究。

R614.2

A

網(wǎng)絡(luò)出版時(shí)間:2015-07-09 13:24

網(wǎng)絡(luò)出版地址: http://www.cnki.net/kcms/detail/22.1342.R.20150709.1324.001.html