賈 慧，譚文斐

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喉罩聯(lián)合靶控和手控輸注丙泊酚的臨床觀察

賈 慧，譚文斐*

目的 應(yīng)用喉罩和腦電雙頻指數(shù)(BIS)監(jiān)測(cè)，觀察靶控輸注和手控輸注丙泊酚的臨床效果。方法30例ASA Ⅰ～Ⅱ級(jí)乳腺癌患者擬在全麻下行乳腺改良根治術(shù)，隨機(jī)分為靶控(T組)和手控(M組)組輸注丙泊酚。T組效應(yīng)室靶濃度為6 μg/mL，M組誘導(dǎo)劑量為2.5 mg/kg，初始維持速度5 mg/(kg·h)，復(fù)合靶控輸注效應(yīng)室靶濃度為4 ng/mL瑞芬太尼。維持BIS值在40～60之間，維持平均動(dòng)脈壓(MAP)在基礎(chǔ)值的20%左右。比較兩組用藥量以及入室(T0)、誘導(dǎo)開(kāi)始(T1)、置入喉罩即刻(T2)、置入完畢(T3)、切皮(T4)、停藥(T5)、術(shù)畢(T6)、睜眼(T7)、自主呼吸恢復(fù)(T8)、指令動(dòng)作恢復(fù)(T9)、拔除喉罩(T10)各時(shí)刻MAP、心率(HR)及BIS的變化。結(jié)果T組丙泊酚用量高于M組(P=0.005),瑞芬太尼用量差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05); 術(shù)中異常血壓發(fā)生率差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05);T4時(shí)，T組BIS值低于M組(39.80±9.62 vs.53.07±8.37,P=0.00)；T2、T3時(shí)，T組 MAP均低于M組(P=0.002,P=0.009)；與T1相比，T組在T2～T5時(shí)，MAP明顯降低(P<0.05)，T2～T7時(shí)，HR明顯降低(P<0.05)，T2～T10時(shí)，BIS值明顯降低(P<0.05)；M組在T3和T4時(shí)，MAP明顯降低(P<0.05)，T10時(shí)，HR明顯升高(P<0.05)，T2～T7時(shí)，BIS值明顯降低(P<0.05)。結(jié)論在BIS監(jiān)測(cè)的麻醉深度下，TCI和MCI丙泊酚都能滿足置入喉罩的麻醉需要，具有良好的可控性；與手控輸注相比，喉罩聯(lián)合靶控輸注丙泊酚用量偏大,血流動(dòng)力學(xué)波動(dòng)較大，麻醉深度較確切。

喉罩；丙泊酚；靶控輸注；手控輸注；腦電雙頻指數(shù)

0 引言

靶控輸注(Target controlled infusion，TCI)由Schwildern等設(shè)計(jì)[1-2],麻醉醫(yī)生可以通過(guò)設(shè)置藥物的血漿或效應(yīng)室靶濃度，將劑量效應(yīng)轉(zhuǎn)化成濃度效應(yīng)關(guān)系的理念給藥[2]，獲得期望的臨床效果，增強(qiáng)了麻醉的可控性和準(zhǔn)確性[3-4]，與傳統(tǒng)的手控輸注(Manually controlled infusion，MCI)相比更加方便精確[5-6]。丙泊酚具有分布、代謝和排泄迅速，持續(xù)輸注蓄積少，蘇醒迅速完全等特點(diǎn)[2]。瑞芬太尼是超短效阿片受體μ1激動(dòng)劑，鎮(zhèn)痛效果好，代謝快[7]。因?yàn)楸捶雍腿鸱姨岬乃幚硖匦?，其?lián)合在TCI中得到廣泛應(yīng)用，獲得起效快，麻醉深度確切的效果[8]。乳腺手術(shù)具有范圍相對(duì)表淺、無(wú)內(nèi)臟牽拉、頭部移動(dòng)度小、手術(shù)時(shí)間較短等特點(diǎn)，較適合應(yīng)用喉罩，和氣管導(dǎo)管相比，喉罩具有首次置入率高、血流動(dòng)力學(xué)穩(wěn)定、操作簡(jiǎn)單、術(shù)后氣道損傷并發(fā)癥少等優(yōu)點(diǎn)[9-11]。既往有關(guān)TCI和MCI丙泊酚的對(duì)比多使用氣管導(dǎo)管，尚無(wú)喉罩方面的研究，且缺乏合適的麻醉監(jiān)測(cè)。本研究使用腦電雙頻指數(shù)(Bispectral index，BIS)監(jiān)測(cè)，確保了合適的麻醉深度，聯(lián)合喉罩對(duì)TCI和MCI丙泊酚的臨床效果進(jìn)行觀察。

1 資料與方法

1.1 臨床資料 30例ASAⅠ～Ⅱ級(jí)行乳腺改良根治術(shù)患者，隨機(jī)分為T組(TCI，15例)和M組(MCI，15例)。兩組患者年齡、身高、體重、ASA分級(jí)和氣管插管條件評(píng)價(jià)差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)，見(jiàn)表1。

表1 患者的一般資料(n=15)

1.2 方法 T組使用6 μg/mL的效應(yīng)室靶濃度輸注丙泊酚，M組手控輸注丙泊酚，誘導(dǎo)劑量2.5 mg/kg，起始維持速度5 mg/(kg·h)。復(fù)合靶控輸注效應(yīng)室靶濃度4 ng/mL的瑞芬太尼。待麻醉誘導(dǎo)完成，BIS值降至40時(shí)置入喉罩(如BIS>60，按1.0 mg/kg追加丙泊酚)。術(shù)中如BIS值>60或<40，T組按照0.5 μg/mL的幅度增加或減少丙泊酚，M組幅度為1 mg/(kg·h)；如果平均動(dòng)脈壓(MAP)波動(dòng)超過(guò)基礎(chǔ)值20%但BIS值在40～60之間，按照幅度為0.5 ng/mL增大或減小瑞芬太尼(MAP<60 mmHg采取補(bǔ)液或靜脈注射麻黃堿)。術(shù)畢前10 min停止丙泊酚輸注記為停藥時(shí)間，術(shù)畢停止輸注瑞芬太尼。記錄入室(T0)、誘導(dǎo)開(kāi)始(T1)、置入即刻(T2)、置入完畢(T3)、切皮(T4)、停藥(T5)、術(shù)畢(T6)、睜眼(T7)、自主呼吸恢復(fù)(T8)、指令動(dòng)作恢復(fù)(T9)、拔除喉罩(T10)各時(shí)刻的MAP(mmHg)、心率(HR，次/min)和BIS值。比較異常血壓發(fā)生情況，比較丙泊酚[mg/(kg·min]和瑞芬太尼[μg/(kg·min]用量。

2 結(jié)果

兩組術(shù)中異常血壓發(fā)生率差異無(wú)統(tǒng)計(jì)學(xué)意義；丙泊酚用量T組高于M組(P=0.005)，兩組瑞芬太尼用量差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)。見(jiàn)表2、表3。

表2 術(shù)中異常血壓發(fā)生情況

表3 用藥量對(duì)比

T1時(shí)刻兩組患者M(jìn)AP、HR和BIS比較差異無(wú)統(tǒng)計(jì)學(xué)意義。T4時(shí)刻，T組BIS值低于M組(P=0.00)；T2時(shí)刻T組MAP低于M組(P=0.002)；T3時(shí)刻T組MAP低于M組(P=0.009)。兩組HR在各時(shí)刻差異無(wú)統(tǒng)計(jì)學(xué)意義。

與T1比較，T組在T2～T5時(shí)，MAP降低(P<0.05)；T2～T7時(shí)，HR降低(P<0.05)；T2～T10時(shí)，BIS值降低(P<0.05)；M組在T3和T4時(shí)，MAP降低(P<0.05)；T10時(shí)，HR升高(P<0.05)；T2～T7時(shí)，BIS值降低(P<0.05)，見(jiàn)表4。

表4 兩組各時(shí)點(diǎn)觀察指標(biāo)對(duì)比

組別T6T7T8T9T10MAP(mmHg)T組84．60±10．6298．40±12．6995．67±19．2294．87±11．5897．40±18．38M組81．07±13．5394．80±16．5890．13±15．9397．53±16．81100．33±21．07HR(次/min)T組60．67±8．13#67．60±12．12#72．07±10．4673．60±12．8976．67±12．01M組57．40±7．3971．27±15．4773．00±16．9578．60±15．8484．53±16．46#BIST組69．07±7．79#78．67±3．68#79．07±6．02#79．53±4．85#82．73±4．50#M組70．53±7．72#81．27±5．02#80．80±8．29#82．53±5．04#85．00±6．05#

3 討論

丙泊酚是應(yīng)用最多的麻醉藥物，在全憑靜脈麻醉中，丙泊酚和瑞芬太尼結(jié)合，復(fù)合非去極化肌松藥，是常用的麻醉方法[8]。瑞芬太尼的藥代動(dòng)力學(xué)特性使得其具有良好的可控性，在和丙泊酚聯(lián)合使用時(shí)，可以減少丙泊酚的用量[12]，瑞芬太尼可以減少或消除插管相關(guān)的BIS值增高，降低插管在聽(tīng)覺(jué)誘發(fā)電位的效應(yīng)；而且，瑞芬太尼可以減弱疼痛刺激相關(guān)的心血管效應(yīng)，起效迅速，是抑制短期疼痛刺激(如插管之前應(yīng)用)的理想藥物[13]。

TCI按照目標(biāo)濃度分為血漿藥物濃度和效應(yīng)室藥物濃度。當(dāng)血漿靶濃度設(shè)定后，TCI系統(tǒng)將快速注射丙泊酚達(dá)到設(shè)定水平，隨后效應(yīng)部位濃度逐漸升高，直到和血漿濃度達(dá)到平衡，這依賴于血漿/效應(yīng)室部位的平衡常數(shù)。當(dāng)設(shè)定以效應(yīng)室濃度靶控時(shí)，血漿部位會(huì)出現(xiàn)藥物過(guò)量，使其快速轉(zhuǎn)運(yùn)到效應(yīng)部位[14]。TCI系統(tǒng)使得丙泊酚和瑞芬太尼在短小手術(shù)的誘導(dǎo)和維持中得到應(yīng)用。血漿濃度相比，效應(yīng)室濃度與麻醉深度相關(guān)性更好[15]。

喉罩是按人體喉部解剖形態(tài)制作而成，患者易耐受，異物感小，術(shù)后咽喉痛的發(fā)生率低[9-11]。成功置入喉罩需要合適的麻醉深度，保證患者意識(shí)消失、下頜松弛，上呼吸道反射被抑制等條件。研究表明，置入喉罩的推薦丙泊酚EC50血漿濃度為8.7 μg/mL[16]，推薦誘導(dǎo)劑量為2.5 mg/kg，此劑量可以提供8～10 μg/mL的血漿濃度[17]。TCI方便、精確[3-4]，對(duì)呼吸、循環(huán)抑制較小[18-19]，與MCI相比具有諸多優(yōu)點(diǎn)[5-6]。

單獨(dú)應(yīng)用丙泊酚使50%患者意識(shí)消失的血漿濃度為3.4 μg/mL，在4 μg/mL時(shí)可使90%的患者意識(shí)消失[12]，但抑制插管相關(guān)反應(yīng)的丙泊酚濃度顯著升高[13]。研究顯示，丙泊酚相關(guān)濃度要超過(guò)3.5 μg/mL才能使BIS降到62以下，超過(guò)5.5 μg/mL會(huì)完全抑制插管反應(yīng)，使BIS降到39[20]。當(dāng)丙泊酚血漿濃度降到3.4～1.8 μg/mL時(shí)，意識(shí)開(kāi)始恢復(fù)。因此丙泊酚的血漿濃度需要維持在2 μg/mL以上，瑞芬太尼的效應(yīng)室濃度需要在4 ng/mL以上，丙泊酚和瑞芬太尼聯(lián)合應(yīng)用TCI可以降低丙泊酚使意識(shí)消失的濃度[12]。研究發(fā)現(xiàn)，在不使用肌松藥下，TCI丙泊酚的效應(yīng)室濃度為3.5 μg/mL，瑞芬太尼效應(yīng)室濃度為3.04 μg/mL，可以滿足50%患者置入喉罩的需要，丙泊酚血漿濃度3.4 μg/mL可維持BIS 40～60[21]。

Sintavanuruk等[22]發(fā)現(xiàn)，使用效應(yīng)室靶濃度為6 μg/mL時(shí)，置入喉罩成功率可達(dá)到92.3%，平均誘導(dǎo)時(shí)間為147 s，而以往設(shè)定血漿靶濃度的研究需要10～15 min才能達(dá)到血漿/效應(yīng)室平衡。本研究發(fā)現(xiàn)，從清醒狀態(tài)開(kāi)始誘導(dǎo)直至達(dá)到相同的BIS值40時(shí)，TCI組誘導(dǎo)時(shí)間明顯長(zhǎng)于MCI組。對(duì)于健康年輕患者，想要縮短誘導(dǎo)時(shí)間，可以考慮使用效應(yīng)室靶濃度；而對(duì)于老年人和心功能較差的患者，為了防止血流動(dòng)力學(xué)波動(dòng)過(guò)大，采用血漿靶濃度緩慢誘導(dǎo)較為合適[14]。

有研究發(fā)現(xiàn)，TCI丙泊酚常伴隨著明顯的血壓下降[23]，但一項(xiàng)針對(duì)80歲以上的高齡患者的研究表明，TCI比MCI的血流動(dòng)力學(xué)更加穩(wěn)定[24]。本研究觀察到兩組異常血壓發(fā)生率差異無(wú)統(tǒng)計(jì)學(xué)意義，但誘導(dǎo)后和置入喉罩后，T組的MAP均低于M組，提示TCI在誘導(dǎo)期存在血流動(dòng)力學(xué)偏低的現(xiàn)象，并且在術(shù)中多點(diǎn)時(shí)刻發(fā)生血壓、心率變化，提示和MCI相比，TCI血流動(dòng)力學(xué)波動(dòng)較大。

由于兩種給藥方式不同，本研究預(yù)測(cè)丙泊酚的用量可能有差別，而瑞芬太尼和丙泊酚聯(lián)合使用時(shí)會(huì)減少丙泊酚用量[12]，隨著B(niǎo)IS和血壓不斷調(diào)整，藥物的用量會(huì)有變化，因此本研究對(duì)丙泊酚和瑞芬太尼的用藥量進(jìn)行對(duì)比。觀察發(fā)現(xiàn)兩組瑞芬太尼用量差異無(wú)統(tǒng)計(jì)學(xué)意義，而TCI丙泊酚用量偏大，這與既往部分研究結(jié)果相似[6]，或許與丙泊酚效應(yīng)室濃度估計(jì)不精確有關(guān)。

雖然TCI近年來(lái)得到廣泛認(rèn)可，但也有爭(zhēng)論提出，由于影響TCI系統(tǒng)準(zhǔn)確性因素的存在，如個(gè)體藥代學(xué)差異、合并用藥以體內(nèi)血漿內(nèi)環(huán)境變化，而且TCI是從健康受試志愿者試驗(yàn)得來(lái)，很難代表臨床多變的患者情況，因此TCI的精確度值得懷疑[25]，甚至不建議使用TCI進(jìn)行麻醉，要求對(duì)此提高警惕[26]。因此，使用合適的麻醉檢測(cè)設(shè)備很必要。

BIS對(duì)麻醉深度有很高的敏感性，是麻醉監(jiān)測(cè)的重要手段。既往研究發(fā)現(xiàn)，誘導(dǎo)后，M組BIS顯著低于T組[22]，本研究設(shè)計(jì)在兩組BIS值同降為40時(shí)，再行喉罩置入等操作，目的是觀察操作對(duì)BIS值的影響，對(duì)比兩組的麻醉深度。本研究在切皮時(shí)發(fā)現(xiàn)兩組BIS值出現(xiàn)了顯著差異，T組的BIS值低于M組，因此，推測(cè)TCI有較確切的麻醉深度。有研究發(fā)現(xiàn)，當(dāng)鎮(zhèn)靜藥物與阿片類藥物合用時(shí)，外科手術(shù)刺激可以影響B(tài)IS值的準(zhǔn)確性，所以BIS連續(xù)監(jiān)測(cè)麻醉深度也存在爭(zhēng)議[26]。

近年來(lái)，關(guān)于TCI的研究有了一些新的認(rèn)識(shí)[26]，觀點(diǎn)提出，麻醉管理關(guān)乎患者術(shù)后的生活質(zhì)量和健康狀態(tài)，術(shù)中麻醉深度和術(shù)后認(rèn)知功能障礙以及遠(yuǎn)期致病率和死亡率成為關(guān)注熱點(diǎn)，其中很重要的一點(diǎn)是TCI中常常忽略了藥物對(duì)中樞系統(tǒng)的不良反應(yīng)。TCI模型的數(shù)據(jù)基于健康受試者，在臨床復(fù)雜情況下并不通用，最終可能導(dǎo)致麻醉藥物少量或過(guò)量，發(fā)生不良后果，如麻醉術(shù)中知曉，盡管是少數(shù)，但仍然對(duì)患者術(shù)后生活質(zhì)量和精神狀態(tài)產(chǎn)生巨大的影響，這點(diǎn)在很多回顧研究中得到報(bào)道[27]。由于麻醉藥物的藥代動(dòng)力學(xué)和藥效動(dòng)力學(xué)和丙泊酚的局限性，TCI模型對(duì)于麻醉安全性很關(guān)鍵。而部分研究對(duì)麻醉深度監(jiān)測(cè)設(shè)備的理解還不夠深入，并不能普遍應(yīng)用于不同的麻醉藥物，也并沒(méi)有明確的醫(yī)學(xué)證據(jù)指出常規(guī)應(yīng)用BIS能提供可靠的麻醉深度監(jiān)測(cè)以預(yù)防術(shù)中知曉[28]。由于以上因素，可能導(dǎo)致麻醉過(guò)深或過(guò)淺，從而引發(fā)潛在的并發(fā)癥及遠(yuǎn)期不良后果[29]。

新的TCI方法(啟動(dòng)式輸液，Priming the infusion)[30]可能會(huì)彌補(bǔ)既往TCI的不足之處，有關(guān)此方面的觀察甚少，有待進(jìn)一步研究。

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Clinical observation of target controlled and manually controlled propofol infusions with laryngeal mask airway

JIA Hui, TAN Wen-fei*

(Department of Anesthesiology,The First Affiliated Hospital of China Medical University,Shenyang 110001,China)

Objective To compare the efficacy of laryngeal mask airway (LMA) combined with propofol of target controlled infusion (TCI) and manually controlled infusion (MCI),under the monitoring on depth of anaesthesia by bispectral index (BIS).MethodsThirty patients scheduled for modified radical mastectomy were randomly allocated as target controlled infusion group (group T) and manually controlled infusion group (group M),group T received TCI propofol 6 μg/mL with LMA,while group M received the standard bolus of propofol 2.5 mg/kg and 5 mg/(kg·h) maintained,as well as the TCI remifentanil 4 ng/mL. The BIS was maintained 40～60 and the mean arterial pressure (MAP) was within 20% of baseline. The drug consumption was recorded. The MAP,heart rate (HR),BIS score were compared at the time point of baseline (T0),induction (T1),insertion (T2),completing insertion (T3),incision (T4),withdrawal (T5),end of operation (T6),open eyes (T7),spontaneously breath(T8),instruction (T9),extubation (T10) between the two groups.ResultsThere was no significant difference between the two groups in remifentanil doses. The propofol consumption in group T was more than that of group M (P<0.01). There was no significant difference between the two groups in the incidence of abnormal MAP. The BIS score at T4in group T was lower than that of group M (39.80±9.62 vs. 53.07±8.37,P<0.01). The MAP at T2and T3 in group T (66.33±11.51,67.13±9.16) were significantly lower than those of group M (82.20±14.23,76.00±8.13),there were significant differences (P<0.01).In group T,compared with T1,the MAP was lower at T2～T5(P<0.05),HR was lower at T2～T7(P<0.05),BIS was lower at T2～T10(P<0.05). In group M,compared with T1,the MAP was lower at T3and T4(P<0.05),HR was higher at T10(P<0.05),BIS was lower at T2～T7(P<0.05).ConclusionBoth TCI and MCI propofol administrations are associated with good controllability and could possibly satisfy the LMA insertion during BIS controlled on depth of anaesthesia.TCI cost more propofol than MCI with more variability in haemodynamics but precise depth of anesthesia during the procedure.

Laryngeal mask airway; Propofol; Target controlled infusion; Mannully controlled infusion; Bispectral index

2014-10-19

中國(guó)醫(yī)科大學(xué)附屬第一醫(yī)院麻醉科，沈陽(yáng) 110001

遼寧省自然科學(xué)基金(遼科發(fā)[2014]24號(hào))

10.14053/j.cnki.ppcr.201505010

*通信作者