1、艾司洛爾降心率對(duì)鼻內(nèi)鏡術(shù)降壓患者鼻血流、腦灌注、心輸出量及術(shù)野的影響紀(jì)存良 李天佐 首都醫(yī)科大學(xué)附屬北京同仁醫(yī)院【摘要】目的 評(píng)價(jià)艾司洛爾控制心率對(duì)硝酸甘油降壓時(shí)人鼻粘膜血流、腦灌注、心輸出量和術(shù)野的影響。方法 擇期鼻內(nèi)鏡手術(shù)患者60例ASAI或II級(jí)，體重4985 kg ，BMI30 kg/m2，性別不限，隨機(jī)分為2組(n = 30): 硝酸甘油降壓組(N組)和硝酸甘油降壓復(fù)合艾司洛爾降心率組(E組）。靜脈注射咪達(dá)唑侖、維庫(kù)溴銨、異丙酚和瑞芬太尼麻醉誘導(dǎo)，置入可彎曲喉罩，行機(jī)械通氣，吸入七氟烷復(fù)合笑氣維持麻醉。N組靜脈輸注硝酸甘油1 3 g kg1 min1降壓，E組降壓后給予艾司洛爾50

2、300 g kg1 min1控制心率，術(shù)中維持BIS 40 60，維持MAP為基礎(chǔ)值70%。術(shù)畢待患者清醒拔出可彎曲喉罩。分別于麻醉誘導(dǎo)后降壓開始前(T1)、降壓45min時(shí)(T2)記錄MAP、HR、 SV、CO、鼻粘膜血流BF，同時(shí)采橈動(dòng)脈血和頸內(nèi)靜脈球部血樣，計(jì)算動(dòng)靜脈血氧含量差(Da-jvO2)、腦氧攝取率(CERO2) ，術(shù)畢術(shù)者對(duì)術(shù)野行清晰度評(píng)分（Fromme評(píng)分）。結(jié)果 與N組比較，E組控制心率后CO 、BF和F值降低( p 0.05)，MAP與SV，HR與 BF及F值相關(guān)顯著（p 0.05)。結(jié)論 硝酸甘油降壓時(shí)復(fù)合艾司洛爾降低心率, 可適當(dāng)減少心輸出量,改善鼻粘膜出血，使術(shù)野清

3、晰；不產(chǎn)生嚴(yán)重臟器灌注不足，用于鼻內(nèi)鏡手術(shù)是安全的?！娟P(guān)鍵詞】心輸出量；鼻粘膜血流；術(shù)野清晰度評(píng)分；鼻內(nèi)鏡手術(shù)；腦灌注Effects of heart rate decreased by esmolol on cardiac output，nasal mucosa blood flow , cerebral perfusion and surgical field during endoscopic sinus surgery under controlled hypotension Ji Cun-liang Li Tian-zuo Department of Anesthesiology，B

4、eijing Tongren Hospital, Capital University of Medical Sciences, Beijing 100730, ChinaCorresponding author: Li Tian-zuo , Email: trmzltz126. com1作者單位：100730首都醫(yī)科大學(xué)附屬北京同仁醫(yī)院麻醉科 通信作者:李天佐,Email :trmzltz 126. com【Abstract】 Objective To evaluate the effects of controlled heart rate by esmolol combined with

5、 induced hypotention by nitroglycerin(NTG) on cardiac output ,nasal mucosa blood flow, cerebral perfusion and surgical field in patients undergoing endoscopic sinus surgery. Methods Sixty ASA I or II patients of both sexes, weighing 49-85 kg, body mass index(BMI)30 kg/m2 undergoing endoscopic sinus

6、surgery were randomly divided into 2 groups ( n= 30 each): NTG group (group N) and combined NTG with esmolol group(group E). Anesthesia was induced with midazolam, propofol, remifentanil and vecuronium and maintained with sevoflurane combined with N2O，F(xiàn)LMA was inserted and the patients were mechanic

7、ally ventilated. BIS was maintained at 40-55 and MAP at 70% of the basaeline value with NTG (1-3g kg1 min1 ) infused during operation. Esmolol (50-300g kg1 min1) was infused in Group E to controll HR. MAP , HR ,SV and CO were continuously monitored and recorded.BF was monitored and blood samples of

8、radial artery and jugular blub were drawn before induced hypotention and 45 min after the beginning of induced hypotention and controlled heart rate，Da-jvO2 and CERO2 were calculated and recorded , scores of visibility in surgical field were given by the operator . Results CO,BF and the value of F w

9、as significantly decreased in group E than in group N after the patientsHR was controlled .The patientsHR was correlated significantly with BF and F value. Da-jvO2 and CERO2 of two groups at different times had no statistical significance. Conclusion Esmolol combined with NTG chosed to induce hypote

10、nsion and control HR appropriately in endoscopic sinus surgery can decrease cardiac outputand reduce nasal mucosal bleeding, which makes the surgical field clearer and cerebral oxygen metabolism steady. It is proven to be safe and feasibility.【Key words】 Cardiac output; Nasal mucosa blood flow; Scor

11、es of visibility in surgical field; Endoscopic sinus surgery;Cerebral perfusion前 言鼻內(nèi)鏡手術(shù)( Endoscopic sinus surgery ESS )是治療慢性鼻部疾病的常用手段，術(shù)中常用控制性降壓減少出血1 May M, Levine HL, Mester SJ, et a1. Complications ofendoscopic sinus surgery：: analysis of 2108 patients incidence and prevention. Laryngoscope, 1994,

12、.104: 1080-1083.?；颊咝穆蕼p慢可以增強(qiáng)控制性降壓效果，但有灌注不足產(chǎn)生細(xì)胞損傷的傾向2Siekiewicz A, Drozdowski A, Rogowski M. The assessment of correlation between mean arterial pressure and intraoperative bleeding during endoscopic sinus surgery in patients with low heart rate. Otolaryngol Pol.,2010;, 64(4): 225228.。本研究觀察艾司洛爾控制心率對(duì)硝酸

13、甘油降壓時(shí)人鼻粘膜血流、腦灌注、心輸出量和術(shù)野的影響，并探討其安全性和可控性。資料與方法本研究經(jīng)本院倫理委員會(huì)批準(zhǔn)，患者或家屬簽署知情同意書。擇期擬行鼻內(nèi)鏡手術(shù)患者60例，ASA I或II級(jí)，年齡1845歲，體重4985 kg，BMI30 kg/m2，性別不限，采用LM (Lund- Mackay)評(píng)分判斷病變嚴(yán)重程度，12為輕度病變，12為重度病變3 Rhyoo C, Jung MK, Lee JH. The clinical significance of Lund- Mackay CT staging system in assessing the severity of chronic

14、 rhinosinusitis. Korean J Otolaryngol-Head Neck Surg, 2001;, 44: 837-8 41.。所有患者均無(wú)高血壓病史、哮喘史、明顯心肺疾患、血液病病史及肝腎功能損害，未用任何影響心臟及血管的藥物。隨機(jī)分為2組（n = 30)：硝酸甘油降壓組(N組)和硝酸甘油降壓復(fù)合艾司洛爾降心率組(E組）。所有患者均不用術(shù)前藥。入室后常規(guī)監(jiān)測(cè)ECG、HR和SpO2，開放靜脈通路并行左側(cè)橈動(dòng)脈穿刺置管，連接Flo Trac流量壓力傳感器（Edwards Lifescences公司，美國(guó)），連續(xù)監(jiān)測(cè)MAP、動(dòng)脈壓力波形監(jiān)測(cè)的心排量（APCO)和每搏輸出量（S

15、V）。連接A-2000XP 型BIS監(jiān)測(cè)儀(Aspect公司，美國(guó)）監(jiān)測(cè)BIS。麻醉誘導(dǎo)：靜脈注射咪達(dá)唑侖0.03 mg/kg，3 min后靜脈注射維庫(kù)溴銨0.1 mg/kg、異丙酚1.5 mg/kg和瑞芬太尼2g/kg，根據(jù)患者體重選擇相應(yīng)型號(hào)的可彎曲喉罩（Laryngeal Mask 公司，英國(guó)），確認(rèn)位置無(wú)誤后固定在下頜；連接Fabius麻醉機(jī)(Drager公司，德國(guó)）行機(jī)械通氣，設(shè)定潮氣量6 8 ml/kg，通氣頻率12次/min，吸呼比1:2，氧流量1.5 L/min，氧濃度50%，監(jiān)測(cè)PETCO2。麻醉維持：吸入2 % 3.5%七氟烷復(fù)合50%N2O。術(shù)中維持BIS 40 60。麻

16、醉誘導(dǎo)完成后，術(shù)者用l%丁卡因(含1 : 10000腎上腺素)浸濕棉紗條，填塞鼻腔行表面麻醉，反復(fù)三次后，將鼻粘膜血流監(jiān)測(cè)探頭（9P410彎角不銹鋼探頭）尖端垂直放于一側(cè)下鼻甲前端，調(diào)整探頭位置，將探頭輕觸粘膜，并妥善固定，探頭與PeriFlux 5001激光多普勒血流儀(Perimed公司，瑞典）相連，用于監(jiān)測(cè)鼻粘膜血流量（BF)。同時(shí)，用Getting方法加入?yún)⒖嘉墨I(xiàn)行右頸內(nèi)靜脈穿刺逆行置管，并用肝素水封存以備用，記錄患者誘導(dǎo)后（T1）的MAP、HR、SV和BF，同時(shí)同步采橈動(dòng)脈血和頸內(nèi)靜脈球部血樣，用GEM premier3000血?dú)夥治鰞x行血?dú)夥治?，測(cè)定SaO2、PaO2、SjvO2、

17、PjvO2和Hb，并計(jì)算動(dòng)靜脈血氧含量差(Da-jvO2)、腦氧攝取率(CERO2)。然后對(duì)兩組患者采用硝酸甘油( NTG )1 3 g kg1 min1降壓，維持MAP為基礎(chǔ)值的70%至術(shù)畢填塞前，如發(fā)生血壓較基礎(chǔ)值降低30以上，給予苯腎上腺素4080 g，E組降壓平穩(wěn)后采用艾司洛爾( Esmolol )50 300 g kg1 min1控制心率，使其低于術(shù)前基礎(chǔ)值至降壓結(jié)束，心率低于50 bpm時(shí)給予阿托品0.5 mg。記錄兩組患者降壓45min（T2）時(shí)Da-jvO2、CERO2、MAP、HR、SV和BF；并以BFT1為基礎(chǔ)值，計(jì)算BF的百分比，計(jì)算公式為：BFT2BFT1100。術(shù)中維

18、持輸液量為1520ml/kg，晶體液與膠體液為1:1。術(shù)畢停藥，術(shù)者用Fromme評(píng)分對(duì)術(shù)野行清晰度評(píng)分（Fromme評(píng)分）見附表1，。待患者清醒后拔出可彎曲喉罩，,送入恢復(fù)室。采用SPSS13.0統(tǒng)計(jì)軟件對(duì)數(shù)據(jù)進(jìn)行統(tǒng)計(jì)學(xué)處理。正態(tài)分布的計(jì)量資料以均數(shù)標(biāo)準(zhǔn)差表示( S )，組內(nèi)比較采用重復(fù)測(cè)量設(shè)計(jì)的方差分析，組間比較采用成組t檢驗(yàn)，將各組MAP、HR與CO、BF及F進(jìn)行Spearman相關(guān)分析，P0.05)。見附表2。N組患者應(yīng)用硝酸甘油將MAP降至目標(biāo)值（具體數(shù)值）后，HR 顯著升高（P0.05），SV、和CO表3中CO沒有統(tǒng)計(jì)學(xué)標(biāo)記。較降壓前降低和BF（P0.05），降壓后BF有所降低（P

19、0.05）； E組患者復(fù)合應(yīng)用艾司洛爾進(jìn)一步控制心率后，HR、 降低明顯（P0.05），CO和BF則較N組進(jìn)一步明顯降低（P0.01），SV降低與N組程度相近。術(shù)野評(píng)分，E組F值明顯低于N組（P0.01）； 患者術(shù)中MAP與患者SV呈正相關(guān)，Spearman相關(guān)系數(shù)為0.48（P0.05），患者HR與CO、CO與BF以及F值亦呈正相關(guān)，其Spearman相關(guān)系數(shù)分別為0.56，0.58和0.61（均P0.05）。SaO2在兩組各個(gè)時(shí)刻均為100%，見附表3。討 論鼻腔粘膜血運(yùn)豐富，以靜脈構(gòu)成為主4 柳端今，趙艷玲，周淵等. 鼻粘膜微區(qū)血流量測(cè)定.中華耳鼻咽喉科雜志，1994, 29(6) :3

20、66-367. ，手術(shù)時(shí)極易出血，影響手術(shù)質(zhì)量。鼻內(nèi)鏡手術(shù)并發(fā)癥與模糊術(shù)野密切相關(guān)5 Pavlin JD, Colley PS, Weymuller JrR, van Norman GV, GunnHC, Koerschgen et al. ME. Propofol versus isoflurane for endoscopicsinus surgery. Am J Otolaryngol, 1999;, 20:96-101. 文獻(xiàn)5，可能是間接應(yīng)用，沒有查到原文。臨床上常用全麻復(fù)合控制性降壓減少出血6 Roslfow C. Remifentanil: ：a unique opioid an

21、algesics. Anesthesiology, , 1993, ，79 : 875-876文獻(xiàn)6，沒有上述敘述，請(qǐng)核對(duì)?？刂菩越祲和ǔＭㄟ^降低外周血管阻力和心輸出量或兩者結(jié)合產(chǎn)生文獻(xiàn)7為德文，如果是間接引用，建議刪除。 。7 Larsen R, Kleinschmidt S. Die kontrollierteHypotension (Induced hypotension.) Contrilled Hypotension. Anaesthesist, 1995; 44:291-308., 8 Simpson P. Perioperative blood loss and its redu

22、ction: the role of the anaesthetist. Br J Anaesth, 1992;, 69:498-507.。血管擴(kuò)張藥直接作用于血管平滑肌，降低血管阻力，組織灌注壓降低，血管擴(kuò)張，組織灌流常增加，以異氟烷為例，肌肉組織血流灌注可增加兩到三倍5請(qǐng)核對(duì)文獻(xiàn)內(nèi)容。，硝普鈉等擴(kuò)血管藥物，可使心率反射性增快，增加心輸出量，加重出血，術(shù)野質(zhì)量惡化。因此，低血壓時(shí)出血不一定減少加入文獻(xiàn)。傳統(tǒng)上，認(rèn)為擴(kuò)血管藥用于控制性降壓，可明顯降少出血，作者提出硝普鈉加重出血和低血壓時(shí)出血不一定減少，請(qǐng)附上明確的文獻(xiàn)加以論證。本研究假設(shè)適度降低患者心輸出量實(shí)施控制性降壓，可以減少術(shù)野出血，提

23、高術(shù)野質(zhì)量，術(shù)中采用硝酸甘油和艾司洛爾，控制患者回心血量和心率，通過減少心輸出量達(dá)到降壓目的。假設(shè)部分應(yīng)該放在前言部分。本研究結(jié)果表明，鼻內(nèi)鏡術(shù)中應(yīng)用擴(kuò)張靜脈為主的硝酸甘油降壓，心率雖可反射性增加，但每搏輸出量降低，心輸出量較術(shù)前有所減少?gòu)慕Y(jié)果看心排出量并沒有明顯降低（9.20.68.60.4），與敘述不符合。，鼻粘膜血流降低，；復(fù)合應(yīng)用艾司洛爾，心輸出量和鼻粘膜血流降低更加顯著，術(shù)野質(zhì)量明顯提高。，研究顯示，術(shù)野質(zhì)量與出血呈正比9 Ragab, H. Optimizing the surgical field in pediatric functional endoscopic sinus

24、surgery: A new evidence-based approach OtolaryngologyHead and Neck Surgery. (2010) , 142, 48-54.，而出血與患者合并疾患 (如出血性疾病)，血小板功能及血管分布、局部組織靜脈壓和毛細(xì)血管血流量等因素有關(guān)10 Schindler I，, Andel H，, Leber J，, et a1. Moderate induced hypotensionprovides satisfactory operating conditions in maxillofacial surgery. Acta Anaest

25、hesiol Scand，, 1994, ，38: ：384-387.。鼻內(nèi)鏡手術(shù)出血以小血管滲出為主，受微循環(huán)血管的動(dòng)靜脈血壓差、血管內(nèi)徑及血液粘滯性影響更大。控制性降壓中血壓和血流粘滯度相對(duì)固定，滲血量主要取決于微循環(huán)的血管（尤其是動(dòng)脈血管）內(nèi)徑和血流量。應(yīng)用硝酸甘油合并艾司洛爾降壓即避免了擴(kuò)張動(dòng)脈血管，又使心輸出量降低，微循環(huán)血流減少，局部滲血減少，術(shù)野質(zhì)量提高，。這與Sieskiewicz A等人的研究結(jié)論相同11 Sieskiewicz A;, Drozdowski A, ;Rogowski M. The assessment of correlation between mean

26、arterial pressure and intraoperative bleeding during endoscopic sinus surgery in patients with low heart rate. Otolaryngol Pol, 2010, :64(4): 225-228.與文獻(xiàn)2是一個(gè)文獻(xiàn)?？刂菩越祲河薪M織低氧的趨勢(shì)，心率降低后更加明顯，降壓時(shí)監(jiān)測(cè)組織灌注非常重要12 Gutierrez G, Palizas F, Doglio G, et al. Gastric intramucosal pH as a therapeutic index of dtissue o

27、xygenation in critically ill patients. Lancet, 1992;, 339: 195199.。本研究應(yīng)用Getting方法13 Zomow M, Prough D. ：Fluid management in patients with traumatic brain injury. New Horize, ，1995, ；3: ：488-198間接采集頸內(nèi)靜脈球部的血樣(此處血液為腦組織直接回流的血液)檢測(cè)SjvO2并計(jì)算CERO2和、Da-jv O2。監(jiān)測(cè)對(duì)乏氧敏感的腦組織氧供需平衡。將上述指標(biāo)在血壓和心率降低前后進(jìn)行比較，結(jié)果沒有差異，提示適度降低心

28、輸出量不會(huì)對(duì)組織灌注產(chǎn)生影響。該結(jié)果與Dorothea A加上文獻(xiàn)和Sieskiewicz A 加上文獻(xiàn)的結(jié)論相同。其發(fā)生機(jī)理可能與機(jī)體在應(yīng)激狀態(tài)下神經(jīng)內(nèi)分泌反應(yīng)通過a1受體介導(dǎo)的血管舒縮有關(guān)語(yǔ)言不通順？14 Cauvin M, Bonnet F, Maontembault C, et al. Hepatic plasma flow during sodium nitroprusside-induced hypotension in humans. Anesthesiology, 1985;, 63: 287293.。心輸出量降低后血壓下降，神經(jīng)體液調(diào)節(jié)使血管擴(kuò)張，血流變慢，增加組織交換，防止缺血缺氧，當(dāng)循環(huán)血流量降低與局部血管擴(kuò)張仍然匹配或成比例時(shí)，組織氧供仍可維持正常。Sieskiewicz A認(rèn)為：心率穩(wěn)定在60 bpm/min左右時(shí)，術(shù)野質(zhì)量與MAP呈正比；適度的降壓和降低心率不會(huì)減少組織的灌注15 Blanski L, ;Lutz J, ;Lad