[摘要] 目的 觀察右美托咪定對脊柱手術(shù)控制性降壓患者術(shù)后炎性因子水平的影響。 方法 60例擇期在全麻下擬行胸腰椎骨折減壓內(nèi)固定術(shù)的患者,隨機(jī)分為對照組(Sham組,n=30)和右美托咪定組(Dex組,n=30). 抽取麻醉誘導(dǎo)前30 min(T1)、氣管導(dǎo)管拔出即刻(T2)、術(shù)畢2 h(T3)、術(shù)畢6 h(T4)、術(shù)畢12 h(T5)、術(shù)畢24 h(T6)的外周靜脈血,測定C反應(yīng)蛋白(CRP)、白細(xì)胞介素-6(IL-6)和腫瘤壞死因子-α(TNF-α)水平。 結(jié)果 兩組患者的一般情況及術(shù)中各監(jiān)測指標(biāo)比較,差異無統(tǒng)計(jì)學(xué)意義(P>0.05);與Sham組比較,Dex組CRP、IL-6和TNF-α在T2-6各時點(diǎn)均降低,差異有統(tǒng)計(jì)學(xué)意義(P<0.05);與T1比較,Sham組中,CRP從T3時點(diǎn)開始升高, IL-6、TNF-α均從T2時點(diǎn)開始升高,在T4時點(diǎn)升至最高點(diǎn),T5時點(diǎn)開始下降;Dex組,CRP從T4時點(diǎn)開始升高,IL-6、TNF-α均從T3時點(diǎn)開始升高,在T4時點(diǎn)升至最高點(diǎn),T5時點(diǎn)開始下降,差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。 結(jié)論 右美托咪定用于脊柱手術(shù)控制性降壓安全可行,并且可以降低炎癥反應(yīng),提高安全性。
[關(guān)鍵詞] 脊柱手術(shù);右美托咪定;細(xì)胞因子;炎癥反應(yīng)
[中圖分類號] R614 [文獻(xiàn)標(biāo)識碼] B [文章編號] 1673-9701(2013)32-0116-02
Effect of deliberate hypotension of dexmedetomidine on inflammatory factors in patients undergoing surgery for spinal
WANG Hongwei1 FU Chunlan2 DING Ming2
1.Department of Anaesthesiology,Weifang Medical University, Weifang 261000, China; 2.Department of Anaesthesiology,The 89th Hospital of People's Liberation Army, Weifang 261000, China
[Abstract] Objective To investigate the effects of deliberate hypotension of dexmedetomidine on inflammatory factors in patients undergoing surgery for spinal. Methods A total of 60 patients who underwent decompression of thoracolumbar fracture fixation under general anesthesia were randomly divided into 2 groups,sham group(Sham group) and dexmedetomidine group(Dex group), 30 in each group. The cervical venous blood samples were obtained from the patient at 30 min before anesthesia induction (T1), when endotracheal tubewas removed (T2) and 2 h(T3)、6 h(T4)、12 h(T5)、24 h (T6) postoperation for determination of the expression of CPR,IL-6 and TNF-α. Results The difference of the general situation and the monitoring indicators of intraoperative between the patients of the two groups was not statistically significant(P>0.05); compared with sham group, CPR, IL-6 and TNF-α of Dex group were all lower at each time point of T2-T6, difference was statistically significant(P<0.05); compared with T1,CPR of sham group was bagan to rise from T3, IL-6 and TNF-α of sham group were bagan to rise from T2, and rosen to the highest at T4, bagan to decline at T5; CPR of Dex group was bagan to rise from T4, IL-6 and TNF-α of Dex group were bagan to rise from T3, and rosen to the highest at T4, bagan to decline at T5, difference was statistically significant (P<0.05). Conclusion Deliberate hypotension of dexmedetomidine in patients undergoing surgery for spinal is safe and feasible,and can reduce inflammation,improve security.
[Key words] Spinal surgery;Dexmedetomidine;Cytokines;Inflammation
脊柱區(qū)域的手術(shù)創(chuàng)傷大,出血多,不易止血,術(shù)中出血過多可致術(shù)野模糊,造成不必要的損傷,因此控制性降壓對此類手術(shù)來說是必須的。國外對Dex用于控制性降壓的研究[1]認(rèn)為,Dex可輔助丙泊酚和瑞芬太尼進(jìn)行術(shù)中控制性降壓,可提高患者血流動力學(xué)的穩(wěn)定性并明顯減少術(shù)中出血;但是Dex對于術(shù)中降壓后炎癥反應(yīng)影響的研究較少。本研究旨在觀察脊柱全麻手術(shù)中應(yīng)用右美托咪定對于術(shù)后炎癥反應(yīng)的影響。
1 資料與方法
1.1 一般資料
選擇全麻下行胸腰椎后路切開減壓內(nèi)固定術(shù)的患者60例,ASAⅠ~Ⅱ級,年齡40~60歲。隨機(jī)分成對照組(Sham組)和右美托咪定組(Dex組),每組30例。完善術(shù)前檢查。剔除標(biāo)準(zhǔn):①嚴(yán)重高血壓,有心、腦血管意外者;②出凝血功能異常者;③術(shù)前服用過鎮(zhèn)靜藥、干擾腎上腺功能或抗交感活性藥物者;④重要臟器功能不全者。
1.2 麻醉方法
患者入室后開通靜脈通路,連接多功能心電監(jiān)護(hù),常規(guī)監(jiān)測心電圖(ECG)、脈搏、血氧飽和度(SpO2)、心率(HR)和血壓(BP)。麻醉誘導(dǎo):兩組患者均采用快誘導(dǎo),經(jīng)口明視下氣管插管方法。具體操作如下:靜脈推注丙泊酚2 mg/kg、瑞芬太尼1 μg/kg,順式阿曲庫銨0.15 mg/kg;預(yù)充氧5 min后行氣管插管,確診氣管導(dǎo)管在指定位置后連接麻醉機(jī)行機(jī)械控制呼吸。呼吸機(jī)設(shè)置參數(shù)分別為:呼吸頻率13次/分,吸呼比1:2,設(shè)置潮氣量8 mL/kg,氧流量為1.5 L/min。麻醉維持:兩組均采用吸入麻醉,瑞芬太尼以0.25 μg/(kg·min)恒速泵注致術(shù)畢,吸入濃度為2%~3%的七氟醚至術(shù)畢前30 min,間斷靜脈注射順苯磺酸阿曲庫銨0.05 mg/kg維持肌松。所有患者于椎體完全暴露后開始降壓,Dex組給予右美托咪定,首先是負(fù)荷量1 μg/kg ,10 min后以0.5 μg/(kg·h)恒速輸注,Sham組加用同等劑量的生理鹽水,并應(yīng)用硝酸甘油將血壓控制在與Dex組相似的水平上,兩組均于椎體固定完畢后停用。術(shù)中根據(jù)血壓、心率等指標(biāo)調(diào)整藥物劑量。
1.3 觀察指標(biāo)
分別于麻醉誘導(dǎo)前30 min(T1)、氣管導(dǎo)管拔出即刻(T2)、術(shù)畢2 h(T3)、術(shù)畢6 h(T4)、術(shù)畢12 h(T5)、術(shù)畢24 h(T6)時、經(jīng)外周靜脈抽取血樣2 mL,分離血清后置于-20℃冰箱保存待檢。采用酶聯(lián)免疫吸附法,測量各促炎因子,包括血清C反應(yīng)蛋白(CRP)、白細(xì)胞介素-6(IL-6)和腫瘤壞死因子-α(TNF-α)的水平。
1.4 統(tǒng)計(jì)學(xué)處理
應(yīng)用SPSS12.0進(jìn)行分析,計(jì)量資料用均數(shù)±標(biāo)準(zhǔn)差表示,數(shù)據(jù)應(yīng)用單因素方差分析,組間比較采用t檢驗(yàn),P<0.05為差異有統(tǒng)計(jì)學(xué)意義。
2 結(jié)果
2.1 兩組患者的一般情況及術(shù)中情況
各指標(biāo)比較,差異無統(tǒng)計(jì)學(xué)意義(P>0.05),見表1。術(shù)中患者的BP按照需要進(jìn)行控制性降低,但均在正常范圍內(nèi),SpO2維持在99% ~100%。
2.2 兩組患者各炎性因子的比較
組內(nèi)比較,與T1比較,Sham組中CRP從T3時點(diǎn)開始升高, IL-6、TNF-α均從T2時點(diǎn)開始升高,在T4時點(diǎn)升至最高點(diǎn),T5時點(diǎn)開始下降;Dex組CRP從T4時點(diǎn)開始升高,IL-6、TNF-α均從T3時點(diǎn)開始升高,在T4時點(diǎn)升至最高點(diǎn),T5時點(diǎn)開始下降,差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。組間比較,Dex組在T2-6各時點(diǎn)的CRP、IL-6和TNF-α水平均明顯低于Sham組,差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。見表2。
3 討論
CRP、IL-6、TNF-α是機(jī)體內(nèi)重要的促炎因子,三者可以相互作用形成正反饋,導(dǎo)致炎癥進(jìn)一步加重,若機(jī)體內(nèi)濃度過高,可引起全身炎癥反應(yīng)綜合征(svstemic inflammatory response syndrome,SIRS),甚至引發(fā)全身多系統(tǒng)器官衰竭(multiple system organ failure,MSOF)[2]。因此,維持炎癥因子的平衡、減少促炎因子的釋放,是降低SIRS和MSOF發(fā)生率的關(guān)鍵[3]。本研究結(jié)果顯示,Sham組中CRP從T3時點(diǎn)開始升高,IL-6和TNF-ɑ從T2時點(diǎn)開始升高,并在T4時點(diǎn)達(dá)最高值,此后開始不斷降低。此結(jié)果表明,圍術(shù)期間機(jī)體內(nèi)各種促炎因子不斷釋放,IL-6和TNF-ɑ最先產(chǎn)生,通過正反饋使CRP也升高,炎癥反應(yīng)強(qiáng)烈,接著啟動了體內(nèi)的抗炎機(jī)制,因此出現(xiàn)了本實(shí)驗(yàn)中的IL-6和TNF-α于T4時點(diǎn)達(dá)最高值后開始不斷降低的結(jié)果。
Dex是新型的高選擇性α2腎上腺素受體激動劑,具有明顯的鎮(zhèn)靜鎮(zhèn)痛作用[4]及抗交感、抗焦慮、穩(wěn)定圍術(shù)期血流動力學(xué)、抑制圍術(shù)期應(yīng)激反應(yīng)[5]的作用。本研究中輔用右美托咪定可以穩(wěn)定地降低患者圍術(shù)期的血壓,避免了血壓的劇烈波動。同時Takumi Taniguchi等[6]研究指出,Dex能夠降低內(nèi)毒素血癥休克大鼠的死亡率,并通過降低血漿中的IL-6和TNF-α等促炎因子的濃度來減少炎癥反應(yīng)的影響;M.Can等[7]也發(fā)現(xiàn),在脊髓損傷小鼠中應(yīng)用Dex能夠顯著降低IL-6和TNF-α水平;有學(xué)者指出,預(yù)先給予Dex可以降低腹腔鏡膽囊切除患者圍術(shù)期CRP、IL-6和TNF-α水平,提高安全性。本實(shí)驗(yàn)結(jié)果顯示,Dex組CRP從T4時點(diǎn)開始升高,IL-6、TNF-α均從T3時點(diǎn)開始升高,在T4時點(diǎn)升至最高點(diǎn),此后開始不斷下降,但升高幅度比Sham組明顯縮小,此結(jié)果表明 Dex能夠降低炎癥反應(yīng),與上述研究結(jié)果相一致,Dex抗炎癥反應(yīng)可能通過以下兩個機(jī)制發(fā)揮作用:①Dex抑制了交感神經(jīng)的活動,卻相對地激活了膽堿能抗炎通路,從而發(fā)揮抗炎作用[8];②有研究表明,可樂定可以抑制單核細(xì)胞中TNF-α的表達(dá)[9],并且α2腎上腺素受體激動劑可以調(diào)節(jié)巨噬細(xì)胞中脂多糖介導(dǎo)的TNF-α的表達(dá)[10],而可樂定和Dex均屬于α2腎上腺素受體激動劑,其抑制炎癥反應(yīng)的機(jī)制可能都是與直接調(diào)節(jié)單核巨噬細(xì)胞中細(xì)胞因子的表達(dá)有關(guān)。
綜上所述,脊柱手術(shù)患者術(shù)中應(yīng)用右美托咪定不但可以穩(wěn)定的降低血壓,減少圍術(shù)期的應(yīng)激反應(yīng)[11,12],而且可以抑制促炎因子的釋放,減少并發(fā)癥的發(fā)生,提高患者術(shù)后的生存質(zhì)量。
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(收稿日期:2013-08-18)