肺保護(hù)性通氣在全身麻醉手術(shù)中的應(yīng)用*

汪海鑫 綜述 徐 懋 審校

(北京大學(xué)第三醫(yī)院麻醉科，北京 100083)

·文獻(xiàn)綜述·

肺保護(hù)性通氣在全身麻醉手術(shù)中的應(yīng)用*

汪海鑫 綜述 徐 懋**審校

(北京大學(xué)第三醫(yī)院麻醉科，北京 100083)

肺保護(hù)性通氣的研究進(jìn)展近年來(lái)逐漸影響著圍手術(shù)期機(jī)械通氣模式的選擇，用以減少術(shù)后肺部并發(fā)癥的發(fā)生率，改善預(yù)后。本文對(duì)肺保護(hù)性通氣在全身麻醉手術(shù)中的應(yīng)用進(jìn)行綜述。

肺保護(hù)性通氣； 術(shù)后肺部并發(fā)癥； 機(jī)械通氣； 全身麻醉

全身麻醉手術(shù)后肺部并發(fā)癥(postoperative pulmonary complications,PPC)可表現(xiàn)為胸膜滲出、肺不張、肺炎和急性肺損傷等，與手術(shù)患者的轉(zhuǎn)歸關(guān)系密切。PPC發(fā)生率為2.6%～5.0%，大手術(shù)后可高達(dá)10%～20%[1～3]。術(shù)后肺部并發(fā)癥不僅延長(zhǎng)住院時(shí)間，增加住院費(fèi)用，嚴(yán)重影響患者術(shù)后康復(fù)，同時(shí)還是患者圍術(shù)期死亡的重要原因[3,4]。全球每年有多達(dá)2.3億外科手術(shù)患者需要進(jìn)行全身麻醉[5]，因此，采取適當(dāng)措施減少術(shù)后肺部并發(fā)癥，對(duì)臨床安全管理具有重要意義。傳統(tǒng)通氣模式應(yīng)用高潮氣量，可能導(dǎo)致與機(jī)械通氣相關(guān)的肺損傷的發(fā)生，使PPC的發(fā)生率增加，近年的研究顯示肺保護(hù)性通氣(protective lung ventilation,PLV)能夠降低PPC的發(fā)生，本文對(duì)肺保護(hù)性通氣在全身麻醉手術(shù)中的應(yīng)用進(jìn)行綜述。

1 術(shù)后肺部并發(fā)癥的機(jī)制

全身麻醉大多需要機(jī)械通氣(mechanical ventilation，MV)。研究表明90%的全身麻醉可導(dǎo)致肺不張[6]，鄰近膈肌的10%～20%肺組織萎陷，并可持續(xù)至術(shù)后數(shù)天，提示全麻機(jī)械通氣可能是術(shù)后肺部并發(fā)癥最重要的因素之一[7,8]。傳統(tǒng)高潮氣量(tidal volumes，VT)機(jī)械通氣導(dǎo)致急性呼吸窘迫綜合征/急性肺損傷(acute respiratory distress syndrome/acute lung injury，ARDS/ALI)患者肺損傷加重，與低潮氣量組相比，高潮氣量組病死率增加(38% vs. 71%，P<0.001)[9]。關(guān)于具有健康肺的患者進(jìn)行機(jī)械通氣的研究[10]也顯示，機(jī)械通氣本身即可導(dǎo)致健康肺損傷。低潮氣量組在入院時(shí)與12小時(shí)機(jī)械通氣后肺泡灌洗液中的IL-8和TNF-α的水平分別為96 vs. 82 pg/ml(P=0.84)和12.3 vs. 6.6 pg/ml(P=0.2)，而高潮氣量組為41 vs. 328 pg/ml(P=0.01)和1.7 vs. 22.0 pg/ml(P=0.06)，說(shuō)明具有健康肺的患者進(jìn)行機(jī)械通氣時(shí)低潮氣量有助于減少肺部炎癥的發(fā)生。

術(shù)后肺部并發(fā)癥是不同因素疊加和相互作用導(dǎo)致的，傳統(tǒng)的高潮氣量通氣可以通過(guò)容積傷、氣壓傷、萎陷傷和生物損傷影響肺功能[11]。高潮氣量導(dǎo)致局部肺泡過(guò)度膨脹造成容積傷。肺泡擴(kuò)張的不均性導(dǎo)致局部肺泡受力增大(氣壓傷)，肺不張產(chǎn)生的萎陷肺泡和正常肺泡交界區(qū)應(yīng)力達(dá)到正常的4～5倍，萎陷肺泡的反復(fù)開(kāi)放和閉陷產(chǎn)生萎陷傷[12]。機(jī)械通氣的機(jī)械刺激，在細(xì)胞水平轉(zhuǎn)導(dǎo)成生物化學(xué)信號(hào)傳入細(xì)胞內(nèi)，生物學(xué)改變可以導(dǎo)致炎性介質(zhì)的大量釋放、氧自由基活化，不同免疫系統(tǒng)活化導(dǎo)致炎癥級(jí)聯(lián)反應(yīng)，造成肺的炎性生物損傷[13]。肺部血管的應(yīng)力損傷是肺損傷機(jī)制之一，內(nèi)皮細(xì)胞多糖包被層作為分子篩，可以增加內(nèi)層的滲透壓，降低白細(xì)胞和血小板吸附，但是炎性細(xì)胞因子導(dǎo)致其損傷[14]。肺內(nèi)的炎性細(xì)胞和炎性介質(zhì)還可通過(guò)受損的肺泡毛細(xì)血管屏障進(jìn)入體循環(huán)，介導(dǎo)全身炎性反應(yīng)，引發(fā)多器官功能障礙[15]。

2 肺保護(hù)性通氣策略

目前，機(jī)械通氣仍以傳統(tǒng)的高潮氣量通氣模式為主。傳統(tǒng)通氣模式產(chǎn)生潛在的機(jī)械通氣相關(guān)肺損傷和遠(yuǎn)隔器官的炎癥反應(yīng)。近年來(lái)的研究提示，以低潮氣量、適當(dāng)呼氣末正壓(positive end-expiratory pressure，PEEP)通氣、肺復(fù)張手法(alveolar recruitment maneuver，ARM)為核心的肺保護(hù)性通氣可降低心肺并發(fā)癥，改善預(yù)后，尤其改善ARDS/ALI患者預(yù)后較為明確。長(zhǎng)時(shí)間機(jī)械通氣的ARDS患者受益于低潮氣量和PEEP通氣，肺保護(hù)性通氣能夠增加生存率，此觀念已為臨床廣泛接受[16]。在Neto等[17]對(duì)7個(gè)研究2184例ARDS患者的數(shù)據(jù)分析中，低潮氣量組(≤7 ml/kg)與高潮氣量組(≥10 ml/kg)相比，PPC持續(xù)的時(shí)間更少[(10.0±10.9)d vs. (13.8±11.6)d，P<0.01]，ICU住院時(shí)間更短[(6.1±8.1)d vs. (8.9±9.4)d，P<0.01]。在ARDS Network[18]的研究中，與高潮氣量(12 ml/kg)組相比，低潮氣量(6 ml/kg)組病死率更低(31.0% vs. 39.8%，P=0.007)，術(shù)后機(jī)械通氣時(shí)間短[(10±11)d vs. (12±11)d，P=0.007]。Hodgson等[19]的研究結(jié)果顯示，與非PEEP組相比，PEEP組氧合指數(shù)[(204±9) vs. (165±9) mm Hg，P=0.005]和肺順應(yīng)性[(49.1±2.9)vs. (33.7±2.7)ml/cm H2O，P<0.001]更高。因此，肺保護(hù)性通氣策略對(duì)于ARDS患者更為有利。

ARDS中機(jī)械通氣研究的進(jìn)展正逐漸影響圍術(shù)期機(jī)械通氣模式的選擇。手術(shù)患者肺功能大多正常，為非ARDS/ALI患者，且機(jī)械通氣時(shí)間較短，但諸多研究顯示術(shù)中肺保護(hù)性通氣更有利于預(yù)防術(shù)后肺部并發(fā)癥[20～22]。12 ml/kg預(yù)計(jì)體重(predicted body weight，PBW)以上的高潮氣量，增加呼氣末肺容積(end expiratory lung volume，EELV)，改善氧合并使萎陷的肺單位重新打開(kāi)，減少肺不張[比值比(OR)=0.36，95%置信區(qū)間(CI)0.22～0.60，P<0.0001]，但也可能因此誘發(fā)和加重術(shù)后肺損傷(OR=0.30，95%CI0.14～0.68，P=0.004)[23]。低潮氣量的應(yīng)用可能會(huì)加劇肺不張的發(fā)生，同時(shí)可能還伴隨著胸腔積液[24]，但在應(yīng)用保護(hù)性低潮氣量的同時(shí)，PEEP和ARM的使用可能有助于在麻醉過(guò)程中防止EELV減少以及小氣道關(guān)閉，減少肺不張[25]。

2.1 低潮氣量的應(yīng)用

對(duì)于非損傷肺而言，在6～9 ml/kg PBW范圍內(nèi)的平均潮氣量已經(jīng)獲得廣泛認(rèn)可[26,27]?？梢员Ｗo(hù)健康肺免于有害影響以及高潮氣量可能造成的傷害。而低潮氣量的有益作用也在不同手術(shù)之中表現(xiàn)出來(lái)。

2.1.1 心臟手術(shù) Sundar等[28]對(duì)擇期心臟手術(shù)患者進(jìn)行的隨機(jī)對(duì)照試驗(yàn)評(píng)價(jià)低潮氣量(6 ml/kg，75例)與高潮氣量(10 ml/kg，74例)帶來(lái)的影響。低潮氣量并沒(méi)有使術(shù)后拔管時(shí)間顯著性降低(中位數(shù)450 vs. 643 min，P=0.10)，但低潮氣量組術(shù)后6～8小時(shí)拔管的比例較高[37.3%(28/75) vs. 20.3%(15/74)，P=0.02]，且再插管率較低[1.3%(1/75) vs. 9.5%(7/74)，P=0.03]。Davoudi等[29]對(duì)低潮氣量通氣體外循環(huán)術(shù)后肺功能影響的研究中，低潮氣量組(VT3 ml/kg，PEEP 5 cm H2O，50例)與對(duì)照組(體外循環(huán)時(shí)不進(jìn)行機(jī)械通氣，50例)相比PaO2較高(85 vs. 75 mm Hg，P<0.05)，并且術(shù)后拔管時(shí)間較短(5 vs. 5.5 h)。因此，在進(jìn)行心臟手術(shù)時(shí)低潮氣量通氣顯示出了優(yōu)勢(shì)。

2.1.2 上腹部手術(shù) Futier等[30]的具有較大影響力的多中心IPROVE研究中，將400例中～高風(fēng)險(xiǎn)肺部并發(fā)癥的非肥胖需大型腹部手術(shù)患者，分為肺保護(hù)性通氣組(VT6～8 ml/kg，PEEP 6～8 cm H2O)與非肺保護(hù)性通氣組(VT10～12 ml/kg，PEEP 0 cm H2O)，肺保護(hù)性通氣組術(shù)后7天內(nèi)術(shù)后肺部并發(fā)癥的發(fā)生率較低[10.5%(21/200)vs. 27.5%(55/200)，相對(duì)危險(xiǎn)度0.40，95%CI0.24～0.68，P=0.001]，同時(shí)住院時(shí)間減少(平均差-2.45 d，95%CI-4.17～-0.72，P=0.006)。在Severgnini等[31]的研究中，與對(duì)照組(27例)相比，肺保護(hù)性通氣組(28例)術(shù)后第1天和第3天動(dòng)脈氧分壓更高[(64.9±11.3)vs. (77.1±13.0)mm Hg，P=0.0006；(69.7±9.3)vs. (80.5±10.1)mm Hg，P=0.0002]。肺保護(hù)性通氣組在術(shù)后氧合方面具有明顯優(yōu)勢(shì)[32]。因此，在上腹部手術(shù)中，肺保護(hù)性通氣的應(yīng)用有助于改善患者的預(yù)后。

2.1.3 開(kāi)胸手術(shù) 開(kāi)胸手術(shù)大多需要單肺通氣(one lung ventilation，OLV)，通常應(yīng)用的潮氣量10 ml/kg的單肺通氣有可能成為過(guò)去。Shen等[33]的臨床研究表明，5～6 ml/kg的潮氣量更適合單肺通氣時(shí)的肺保護(hù)，炎癥因子水平明顯降低[IL-1β(25.42±31.01)vs. (94.96±118.24) pg/ml，IL-6(30.86±75.78)vs.(92.99±72.90)pg/ml，IL-8(258.75±188.24)vs.(403.95±151.44)pg/ml，P均<0.05]，術(shù)后18小時(shí)氧合指數(shù)較好(326.35±34.43 vs. 292.85±28.74，P=0.046)。在Yang等[34]的研究中，在單肺通氣期間，肺保護(hù)性通氣組(VT6 ml/kg，PEEP 5 cm H2O，50例)與傳統(tǒng)通氣組(VT10 ml/kg，PEEP 0 cm H2O，50例)相比，在維持相似的SpO2(>95%)及PaCO2(35～45 mm Hg)的同時(shí)，氣道峰壓在單肺通氣15 min和1 h后均較低[(18±4)vs.(23±3)mm Hg和(18±3) vs.(23±2)mm Hg，P均<0.05]，術(shù)后肺功能障礙的發(fā)生率也較低(4% vs. 22%，P<0.05)。因此，PLV策略對(duì)于需要進(jìn)行單肺通氣的手術(shù)也是適用的。

在臨床麻醉實(shí)施過(guò)程中，需要注意的是，PBW與實(shí)際體重可能存在明顯不同，潮氣量的設(shè)置應(yīng)根據(jù)PBW情況謹(jǐn)慎調(diào)整。

2.2 PEEP的應(yīng)用

PEEP通過(guò)維持呼氣末氣道張力和肺泡開(kāi)放防止肺不張，增加肺泡-毛細(xì)血管氣體交換時(shí)間，改善通氣血流比[35]，PEEP的應(yīng)用效果也在不同手術(shù)中有所體現(xiàn)[36,37]。PEEP對(duì)于腹腔鏡手術(shù)患者更加有利。長(zhǎng)時(shí)間氣腹可以使膈肌向頭側(cè)產(chǎn)生更多的位移，并使氣道閉合容量降低，因此肺損傷和肺不張的幾率增加。Baki等[38]的研究評(píng)價(jià)了腹腔鏡手術(shù)中PEEP對(duì)于動(dòng)脈氧合的作用，分為對(duì)照組(VT10 ml/kg，呼吸頻率12次/min，PEEP 0 cm H2O，30例)和保護(hù)組(VT6 ml/kg，呼吸頻率18次/min，PEEP 5 cm H2O，30例)。結(jié)果氣腹后1小時(shí)對(duì)照組氧分壓下降更明顯[對(duì)照組氣腹前(218.73±50.06)mm Hg，氣腹后1小時(shí)(167.55±42.82)mm Hg，P=0.005；保護(hù)組氣腹前(204.74±26.32)mm Hg，氣腹后1小時(shí)(177.14±46.71)mm Hg，P=0.015]。術(shù)中允許性肺不張(即PEEP最小化并且不結(jié)合ARM)可以限制氧合作用的惡化，但可能需要較高的吸入氧濃度(FiO2)。但在理論上，術(shù)中低水平PEEP甚至零水平PEEP可能會(huì)增加肺不張的發(fā)生率及范圍，甚至在術(shù)后恢復(fù)期導(dǎo)致進(jìn)一步的術(shù)后肺部并發(fā)癥的發(fā)生。

但PEEP設(shè)置的最佳范圍還不明確。Hemmes等[39]主導(dǎo)的一項(xiàng)比較有影響力的隨機(jī)對(duì)照試驗(yàn)PROVHILO是在歐洲和美國(guó)進(jìn)行的國(guó)際性多中心研究，結(jié)果表明，開(kāi)腹手術(shù)期間低潮氣量以及不同PEEP設(shè)置并沒(méi)有導(dǎo)致呼吸系統(tǒng)順應(yīng)性減低和氣體交換進(jìn)行性惡化。研究者在900例非肥胖有較高發(fā)生術(shù)后肺部并發(fā)癥風(fēng)險(xiǎn)需要進(jìn)行開(kāi)腹手術(shù)的患者中，將潮氣量設(shè)為8 ml/kg，對(duì)比12 cm H2O PEEP結(jié)合ARM與2 cm H2O PEEP不結(jié)合ARM的作用，術(shù)后肺部并發(fā)癥無(wú)顯著性差異[高PEEP組39%(174/445)，低PEEP組38%(172/449)，相對(duì)危險(xiǎn)度1.01，95%CI0.86～1.20，P=0.86]。造成差異的原因可能與各項(xiàng)研究之間的手術(shù)時(shí)間長(zhǎng)短、手術(shù)方式(開(kāi)腹vs.腔鏡手術(shù))、手術(shù)部位(上腹vs.全腹部)及麻醉方式(全麻vs.全麻聯(lián)合硬膜外麻醉)有關(guān)。此外，樣本量大小也可能影響最終的研究結(jié)論。

2.3 ARM的應(yīng)用

ARM可以打開(kāi)萎陷的肺泡并使EELV增加，促進(jìn)氣體交換，減輕肺損傷[40]。ARM與PEEP相結(jié)合對(duì)于保護(hù)呼吸功能可能是最有效的。在麻醉過(guò)程中最常用的ARM是氣囊擠壓，即在呼吸機(jī)上進(jìn)行持續(xù)性手動(dòng)膨脹，同時(shí)限制氣道壓力的峰值。其他ARM有逐級(jí)提高的潮氣量及PEEP，或壓力控制機(jī)械通氣及PEEP相結(jié)合。Galas等[41]觀察ARM結(jié)合持續(xù)正壓通氣或ARM結(jié)合PEEP在體外循環(huán)手術(shù)中的表現(xiàn)，結(jié)果顯示麻醉期間氧合指數(shù)(431±124 vs. 229±68，P<0.001)和肺順應(yīng)性[(60±17)vs.(48±13)ml/cm H2O，P<0.001]增加，術(shù)后肺不張、肺部并發(fā)癥和住院時(shí)間減少。單獨(dú)ARM能在麻醉期間改善氧合，結(jié)合PEEP的ARM也能減少術(shù)后肺不張的發(fā)生率，但仍需進(jìn)一步研究評(píng)估ARM的方式對(duì)圍手術(shù)期肺部并發(fā)癥的作用。

2.4 肺保護(hù)性通氣策略的缺點(diǎn)

肺保護(hù)性通氣策略也可能產(chǎn)生不良反應(yīng)，特別是血流動(dòng)力學(xué)方面。肺保護(hù)性通氣的潛在傷害也在PROVHILO研究中有所報(bào)道[39]，患者在接受高水平PEEP和ARM時(shí)低血壓的發(fā)生率更高，需要更多的血管活性藥。這可能是由于高水平PEEP和ARM可能會(huì)減少右心室前負(fù)荷并增加右心系統(tǒng)后負(fù)荷，并因此導(dǎo)致每搏輸出量下降，產(chǎn)生低血壓。

3 展望與小結(jié)

除了比較具有影響力的IPROVE和PROVHILO兩項(xiàng)國(guó)際性多中心大型研究外，2012年開(kāi)始實(shí)施的LASVEGAS(外科手術(shù)全身麻醉期間通氣管理和術(shù)后肺部并發(fā)癥的影響的地區(qū)性評(píng)估)[42]計(jì)劃招募4800例患者，雖然還沒(méi)有最終結(jié)果，但其勢(shì)必會(huì)對(duì)肺保護(hù)性通氣的術(shù)中應(yīng)用產(chǎn)生深遠(yuǎn)影響。

總而言之，術(shù)中肺保護(hù)性通氣策略在降低術(shù)后肺部并發(fā)癥的發(fā)生方面已逐漸為大多數(shù)人所認(rèn)可。低潮氣量(6～8 ml/kg PBW)、適當(dāng)水平PEEP(5～10 cm H2O)以及ARM可以在麻醉期間以及術(shù)后階段為患者提供一定程度的保護(hù)。但這種保護(hù)是多因素的綜合作用，而各因素的最佳設(shè)置，以及每個(gè)獨(dú)立措施的確切作用尚不明確，在不同類型手術(shù)中的保護(hù)作用等還需要進(jìn)一步研究。

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(修回日期：2016-05-07)

(責(zé)任編輯：王惠群)

Application of Protective Lung Ventilation During General Anesthesia

WangHaixin,XuMao.

DepartmentofAnesthesiology,PekingUniversityThirdHospital,Beijing100083,China

XuMao,E-mail:anae@163.com

Protective lung ventilation; Postoperative pulmonary complication; Mechanical ventilation; General anesthesia

北京大學(xué)第三醫(yī)院臨床重點(diǎn)項(xiàng)目青年項(xiàng)目(項(xiàng)目編號(hào)：BYSY2014019)

**通訊作者，E-mail：anae@163.com

A

1009-6604(2016)07-0665-05

10.3969/j.issn.1009-6604.2016.07.023

2016-04-12)

【Summary】 Advances in protective lung ventilation in recent years are gradually affecting the perioperative mechanical ventilation mode selection,which can reduce the incidence of postoperative pulmonary complications and improve patient’s outcomes. This paper reviewed and summarized the application of protective lung ventilation during general anesthesia.