熊旭明， 溫德良， 溫藝超， 劉衛(wèi)江

(廣州醫(yī)學院第二附屬醫(yī)院危重病學科，廣東 廣州 510260)

肺復張對肺內(nèi)、外源性ARDS模型犬氧代謝和血流動力學的影響*

熊旭明△， 溫德良， 溫藝超， 劉衛(wèi)江

(廣州醫(yī)學院第二附屬醫(yī)院危重病學科，廣東 廣州 510260)

目的探討肺復張對肺內(nèi)、外源性急性呼吸窘迫綜合征(ARDS)模型犬氧代謝和血流動力學的影響。方法健康雜種犬12只，隨機分為肺外源性ARDS(ARDSexp)組和肺內(nèi)源性ARDS(ARDSp)組，每組6只。股靜脈注射油酸復制ARDSexp模型，鹽酸灌肺復制ARDSp模型。制模成功后，行機械通氣，采用肺保護通氣策略(LPVS)并給予1次肺復張(RM)。RM采用壓力控制通氣(PCV)，壓力上限為高位轉折點(UIP)， 呼氣末正壓(PEEP)為低位轉折點(LIP)+2 cmH2O， 維持時間60 s，RM后繼續(xù)原方案通氣。觀察不同階段氧代謝指標和血流動力學的變化。結果RM后兩組動脈血氧分壓(PaO2)、靜脈血氧分壓(PvO2) 、混合靜脈血氧飽和度(SvO2)和氧輸送量(DO2)明顯升高，氧攝取率(ERO2) 逐漸降低；ARDSexp組的PaO2、PvO2、SvO2和DO2高于ARDSp組，ERO2則低于ARDSp組。RM時兩組平均肺動脈壓(MPAP)、中心靜脈壓(CVP)、肺動脈嵌壓(PAWP)均顯著增加，ARDSp組與ARDSexp組相比較無顯著性差異，但RM結束后兩組均逐漸恢復至基礎水平。RM時兩組平均動脈壓(MAP)和心臟指數(shù)(CI)下降，但很快恢復至基礎水平，ARDSp組下降幅度更為顯著。結論RM可以提高氧輸送和改善組織缺氧，ARDSexp組的效果優(yōu)于ARDSp組；RM對血液動力學會造成短暫的影響，ARDSp組受到的影響大于ARDSexp組。

急性呼吸窘迫綜合征； 肺復張； 氧代謝； 血流動力學

大量肺泡萎陷、肺容積減少是急性呼吸窘迫綜合征(acute respiratory distress syndrome，ARDS)的主要病理生理特征，肺復張(recruitment maneuver, RM)能有效增加ARDS肺容積，改善肺順應性[1]。但RM過程中胸腔壓力顯著升高，對血流動力學可能產(chǎn)生不利的影響。不同病因所致ARDS的病理表現(xiàn)、呼吸力學不同，對RM的反應也有較大的差異[2]。本研究通過復制犬肺外源性ARDS(extrapulmouary acute respiratory distress syndrom, ARDSexp)和肺內(nèi)源性ARDS(pulmouary acute respiratory distress syndrom, ARDSp)動物模型，實施肺保護通氣策略(lung protective ventilation strategy，LPVS)的同時給予RM，觀察RM后氧代謝和血流動力學的變化，比較其對不同原因ARDS的影響，評價療效和安全性。

材 料 和 方 法

1材料

普通級健康雜種犬12只，體重(17.6±3.1) kg，雌性5只，雄性7只，由廣州醫(yī)學院實驗動物中心提供，隨機分為ARDSexp組和ARDSp組，每組6只。

2模型制備

麻醉成功后行氣管插管, 機械通氣。ARDSexp模型: 20 mL生理鹽水和油酸(0.1 mL/kg)經(jīng)充分混合后，中心靜脈導管緩慢注入，20 min鐘注完。ARDSp模型:pH 1.0的鹽酸2 mL/kg氣管內(nèi)注入, 5 min注完。90 min后進行動脈血氣分析, 氧合指數(shù)(oxygenation index，OI)lt;200 mmHg并穩(wěn)定30 min為ARDS模型復制成功。

3RM實施

基礎通氣條件：容量控制通氣(volume control ventilation,VCV),潮氣量 (tidal volume，VT)8 mL/kg，呼吸頻率(respiratory rate，RR)30 beats/min , 吸氧濃度(fractional oxygen concentration ,FiO2)100%，采用低流速法描繪壓力-容積(pressure-volume curve ,P-V)曲線，采用雙向直線回歸法計算出曲線的低位轉折點(lower inflection point, LIP)和高位轉折點(upper inflection point, UIP)水平，呼氣末正壓(positive end-expiratory pressure ,PEEP)設定為LIP+2 cmH2O。RM實施：壓力控制通氣(pressure controll ventilation ,PCV)，壓力上限為UIP, PEEP為LIP+2 cmH2O，維持時間60 s。RM后繼續(xù)原方案通氣4 h。

4指標檢測

RM前、RM時、RM后10 min、30 min、1 h、2 h、4 h監(jiān)測以下指標 ： (1)抽取動脈血和混合靜脈血檢測動脈血氧分壓(arterial partial pressure of oxygen, PaO2)、靜脈血氧分壓(venous partial pressure of oxygen , PvO2) 、動脈血氧飽和度(arterial oxygen saturation , SaO2)、混合靜脈血氧飽和度(mixed venous oxygen saturation , SvO2)。計算氧運輸量(oxygen delivery , DO2)、氧耗量(oxygen consumption, VO2)、氧攝取率(oxygen extraction ratio, ERO2)。(2)血流動力學指標：心電監(jiān)護心率(heart rate, HR)，左股動脈置管監(jiān)測平均動脈壓(mean arterial pressure, MAP)、右股靜脈置入Swan-Ganz導管監(jiān)測中心靜脈壓(central venous pressure, CVP)、平均肺動脈壓(mean pulmonary arterial pressure, MPAP)、肺動脈嵌壓(pulmonary artery wedge pressure, PAWP)、采用熱稀釋法測心輸出量(cardiac index output, CO)并計算心臟指數(shù) (cardiac index, CI)。CI=CO/BSA; DO2= 13.9×CI×Hb×SaO2；VO2= 13.9×CI×Hb× (SaO2- SvO2); ERO2= VO2/DO2。式中：BSA(body surface area)為體表面積(m2)= 11.2×[體重(g)2/3/10 000]，Hb為血紅蛋白濃度。

5統(tǒng)計學處理

結 果

1模型復制

12只犬分別經(jīng)靜注油酸和氣管內(nèi)滴入稀鹽酸后均達到ARDS 診斷標準，ARDSexp組氧合指數(shù)為(118.3±21.7) mmHg，ARDSp組氧合指數(shù)為(115.1±19.8)mmHg。

2RM對氧代謝的影響

RM后兩組PaO2顯著增加，30 min后逐漸下降，4 h內(nèi)PaO2顯著高于RM前水平(Plt;0.01)；與ARDSp組相比，ARDSexp組PaO2/FiO2改善更為顯著，兩組間比較顯著差異(Plt;0.01)；兩組的PvO2和SvO2在RM后逐漸升高，ARDSp組相比，ARDSexp升高更為顯著(Plt;0.05)；RM后DO2短暫下降后逐漸增加，ERO2逐漸降低，ARDSp組與ARDSexp組相比較，ARDSexp改變更為顯著,見表1。

表1 RM后ARDS犬氧代謝的變化

3RM對血液動力學的影響

實施RM前后HR無明顯變化。在RM過程中，MPAP、CVP和PAWP均顯著增加，但RM結束后逐漸恢復至基礎水平，ARDSp組與ARDSexp組相比較，兩組無顯著差異；MAP和CI在RM過程中顯著下降，RM結束后很快恢復至基礎水平，ARDSp組與ARDSexp組相比較，ARDSp組下降幅度更為顯著(Plt;0.01)。RM后4 h, 兩組的CI均高于基礎值(Plt;0.01),見表2。

表2 RM后ARDS犬血液動力學的變化

討 論

小潮氣量肺保護通氣策略是唯一證實能夠改善ARDS預后的措施，但有明顯的缺陷，容易導致肺膨脹不全而發(fā)生肺泡萎陷，而大量肺泡萎陷、肺容積減少是ARDS的主要病理生理特征，為保證患者氧合，須將萎陷的肺泡再度開放, 并維持其開放狀態(tài)[3]。因此，適當?shù)姆螐蛷埵鞘直匾腫4]。在實施RM時往往需要考慮三方面的問題，一是采用何種方式及壓力水平使更多萎陷肺泡開放，二是復張之后如何設法使已開的肺泡盡量維持于開放狀態(tài)，三是避免在實施RM過程中可能出現(xiàn)的肺損傷和對血流動力學的抑制[5]。我們的研究發(fā)現(xiàn)根據(jù)P-V曲線的特征指導肺復張，即以P-V曲線為導向的肺復張策略能改善肺順應性，減輕肺損傷。但是對于不同原因的ARDS，RM對其氧代謝和血流動力學的影響有何不同，目前研究較少。

糾正低氧血癥和組織缺氧是治療ARDS的根本目標。機體對缺氧的反應首先是通過提高CI增加DO2以維持VO2穩(wěn)定，如通過增加DO2不能滿足代謝需要，機體就通過提高ERO2來增加氧的利用；PvO2和SvO2是全身組織氧合情況的反映，PvO2和SvO2越低，ERO2越高，說明組織氧耗越多，組織越缺氧明顯。我們的研究發(fā)現(xiàn)，RM后各組PaO2顯著增加， PvO2、SvO2和DO2逐漸升高，ERO2逐漸降低，說明RM能改善氧合，糾正組織細胞缺氧。Kanoore等[6]和Grasso等[7]研究發(fā)現(xiàn)ARDS患者行RM后PaO2和DO2較前明顯增加。根據(jù)DO2的計算公式，氧輸送主要受CI、SaO2和血紅蛋白的影響。本研究DO2升高，可能與氧合的改善和心輸出量增加有關。由于ARDSexp組氧合改善更為明顯，且RM對ARDSp組CI影響較ARDSexp組更為顯著，所以ARDSexp組DO2高于ARDSp組。DO2增加并不反映組織細胞水平的氧利用情況，SvO2和ERO2是反映組織缺氧較好的指標。本研究中，RM后PvO2、SvO2逐漸增加，ERO2逐漸降低，提示應用RM后組織缺氧得到改善，而以ARDSexp組的療效更為明顯。

本研究結果提示,在RM過程中，MPAP、CVP、PAWP均顯著增加，但RM結束后很快恢復至基礎水平；在RM過程中MAP和CI顯著下降，RM結束后很快恢復至基礎水平。Park等[8]和Lim等[9]分別對ARDS患者和ARDS動物模型采用RM,發(fā)現(xiàn)RM過程中MAP和CI下降明顯，3-5 min回復正常水平，說明大多數(shù)ARDS患者能夠耐受RM。但是對于血壓低、血容量不足的ARDS患者，RM可導致MAP和CI的顯著下降，甚至引起頑固性休克，所以對于此類患者行RM時必須先補充血容量,保持血流動力學穩(wěn)定，減少RM對血流動力學的影響[10]。我們研究發(fā)現(xiàn)RM后CI逐漸增加，可能與全身血管阻力降低和低氧血癥糾正后心肌收縮力增強有關。我們的研究還發(fā)現(xiàn)，RM對ARDSp組CI和血壓的影響較ARDSexp組更為顯著，可能與ARDSp組的病理特征有關。本組為吸入鹽酸ARDS動物模型，其病理改變主要為局灶性實性變，對肺復張反應不如ARDSexp明顯，RM后肺順應性和復張容積的改變相對不如ARDSexp，導致RM時傳導至胸腔的壓力明顯增加，使靜脈回流減少和右室充盈緩慢，心輸出量明顯減少。另外ARDSp組RM后氧合改善不明顯也可能導致肺血管收縮，肺血管阻力增高，使CI減少。因此，對于ARDSp，尤其是局灶性ARDS，行RM時需密切監(jiān)測血流動力學變化[11]。

綜上所述，RM可以提高氧輸送和改善組織缺氧，ARDSexp組的效果優(yōu)于ARDSp組；對血液動力學會所造成短暫的影響，在ARDSp組更為顯著。

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EffectsofrecruitmentmaneuversonoxygenmetabolismandhemodynamicsincaninemodelsofextrapulmonaryandpulmonaryARDS

XIONG Xu-ming, WEN De-liang, WEN Yi-chao, LIU Wei-jiang

(DepartmentofCriticalCareMedicine,TheSecondAffiliatedHospitalofGuangzhouMedicalCollege,Guangzhou510260,China.E-mail:xiongxuming9@yahoo.com.cn)

AIM: To determine the effects of recruitment maneuver(RM) strategy on oxygen metabolism and hemodynamics in canine models of extrapulmonary acut respiratory distress syndrome(ARDSexp) and pulmonary acute respiratory distress syndrome(ARDSp).METHODSTwelve healthy canines were randomly divided into ARDSexp group and ARDSp group with 6 dogs each. To induce lung injury, the ARDSexp dogs were injected with oleic acid through femoral vein, and hydrochloric acid were administered by lung lavage to the ARDSp dogs. Pressure control ventilation (PCV) with lung protective ventilation strategy (LPVS) was employed to RM. Phighwas set to upper inflection point (UIP), and Plowwas set to lower inflection point (LIP)+2 cmH2O.The duration of RM was 60 s and followed by baseline ventilatory settings. The indexes of oxygen metabolism and hemodynamics were measured before and after RM.RESULTSAfter RM, arterial partial pressure of oxygen (PaO2), venous partial pressure of oxygen (PvO2), mixed venous oxygen saturation (SvO2) and oxygen delivery (DO2) obviously increased, and oxygen extraction ratio (ERO2) gradually decreased in both groups. PaO2, PvO2, SvO2and DO2in ARDSexp group were significantly higher than those in ARDSp group, and ERO2in ARDSexp group were significantly lower than that in ARDSp group. Although mean pulmonary arterial pressure (MPAP), central venous pressure (CVP) and pulmonary artery wedge pressure (PAWP) significantly increased and mean arterial pressure (MAP) and cardiac index (CI) obviously decreased in both groups during RM, they reversed rapidly after RM. During RM, MPAP, CVP and PAWP were significantly higher, and MAP and CI were significantly lower in ARDSp group than those in ARDSexp group.CONCLUSIONRM increases oxygen delivery and improves tissue anoxia, and the better effects are obtained in ARDSexp dogs than those in ARDSp dogs. The effects of RM on hemodynamics are temporary and the ill effects are worse in ARDSp dogs than those in ARDSexp dogs.

Acute respiratory distress syndrome; Pulmonary Recruitment maneuver; Oxygen metabolism; Hemodynamics

1000-4718(2011)04-0759-04

R363

A

10.3969/j.issn.1000-4718.2011.04.026

2010-12-15

2011-03-16

廣東省科技計劃資助項目(No.2007B060401067)

△通訊作者Tel:020-34152225；E-mail：xiongxuming9@yahoo.com.cn