肺复张对肺内、外源性ARDS模型犬氧代谢和血流动力学的影响*

熊旭明， 温德良， 温艺超， 刘卫江

(广州医学院第二附属医院危重病学科，广东 广州 510260)

肺复张对肺内、外源性ARDS模型犬氧代谢和血流动力学的影响*

熊旭明△， 温德良， 温艺超， 刘卫江

(广州医学院第二附属医院危重病学科，广东 广州 510260)

目的探讨肺复张对肺内、外源性急性呼吸窘迫综合征(ARDS)模型犬氧代谢和血流动力学的影响。方法健康杂种犬12只，随机分为肺外源性ARDS(ARDSexp)组和肺内源性ARDS(ARDSp)组，每组6只。股静脉注射油酸复制ARDSexp模型，盐酸灌肺复制ARDSp模型。制模成功后，行机械通气，采用肺保护通气策略(LPVS)并给予1次肺复张(RM)。RM采用压力控制通气(PCV)，压力上限为高位转折点(UIP)， 呼气末正压(PEEP)为低位转折点(LIP)+2 cmH2O， 维持时间60 s，RM后继续原方案通气。观察不同阶段氧代谢指标和血流动力学的变化。结果RM后两组动脉血氧分压(PaO2)、静脉血氧分压(PvO2) 、混合静脉血氧饱和度(SvO2)和氧输送量(DO2)明显升高，氧摄取率(ERO2) 逐渐降低；ARDSexp组的PaO2、PvO2、SvO2和DO2高于ARDSp组，ERO2则低于ARDSp组。RM时两组平均肺动脉压(MPAP)、中心静脉压(CVP)、肺动脉嵌压(PAWP)均显著增加，ARDSp组与ARDSexp组相比较无显著性差异，但RM结束后两组均逐渐恢复至基础水平。RM时两组平均动脉压(MAP)和心脏指数(CI)下降，但很快恢复至基础水平，ARDSp组下降幅度更为显著。结论RM可以提高氧输送和改善组织缺氧，ARDSexp组的效果优于ARDSp组；RM对血液动力学会造成短暂的影响，ARDSp组受到的影响大于ARDSexp组。

急性呼吸窘迫综合征； 肺复张； 氧代谢； 血流动力学

大量肺泡萎陷、肺容积减少是急性呼吸窘迫综合征(acute respiratory distress syndrome，ARDS)的主要病理生理特征，肺复张(recruitment maneuver, RM)能有效增加ARDS肺容积，改善肺顺应性[1]。但RM过程中胸腔压力显著升高，对血流动力学可能产生不利的影响。不同病因所致ARDS的病理表现、呼吸力学不同，对RM的反应也有较大的差异[2]。本研究通过复制犬肺外源性ARDS(extrapulmouary acute respiratory distress syndrom, ARDSexp)和肺内源性ARDS(pulmouary acute respiratory distress syndrom, ARDSp)动物模型，实施肺保护通气策略(lung protective ventilation strategy，LPVS)的同时给予RM，观察RM后氧代谢和血流动力学的变化，比较其对不同原因ARDS的影响，评价疗效和安全性。

材 料 和 方 法

1材料

普通级健康杂种犬12只，体重(17.6±3.1) kg，雌性5只，雄性7只，由广州医学院实验动物中心提供，随机分为ARDSexp组和ARDSp组，每组6只。

2模型制备

麻醉成功后行气管插管, 机械通气。ARDSexp模型: 20 mL生理盐水和油酸(0.1 mL/kg)经充分混合后，中心静脉导管缓慢注入，20 min钟注完。ARDSp模型:pH 1.0的盐酸2 mL/kg气管内注入, 5 min注完。90 min后进行动脉血气分析, 氧合指数(oxygenation index，OI)lt;200 mmHg并稳定30 min为ARDS模型复制成功。

3RM实施

基础通气条件：容量控制通气(volume control ventilation,VCV),潮气量 (tidal volume，VT)8 mL/kg，呼吸频率(respiratory rate，RR)30 beats/min , 吸氧浓度(fractional oxygen concentration ,FiO2)100%，采用低流速法描绘压力-容积(pressure-volume curve ,P-V)曲线，采用双向直线回归法计算出曲线的低位转折点(lower inflection point, LIP)和高位转折点(upper inflection point, UIP)水平，呼气末正压(positive end-expiratory pressure ,PEEP)设定为LIP+2 cmH2O。RM实施：压力控制通气(pressure controll ventilation ,PCV)，压力上限为UIP, PEEP为LIP+2 cmH2O，维持时间60 s。RM后继续原方案通气4 h。

4指标检测

RM前、RM时、RM后10 min、30 min、1 h、2 h、4 h监测以下指标 ： (1)抽取动脉血和混合静脉血检测动脉血氧分压(arterial partial pressure of oxygen, PaO2)、静脉血氧分压(venous partial pressure of oxygen , PvO2) 、动脉血氧饱和度(arterial oxygen saturation , SaO2)、混合静脉血氧饱和度(mixed venous oxygen saturation , SvO2)。计算氧运输量(oxygen delivery , DO2)、氧耗量(oxygen consumption, VO2)、氧摄取率(oxygen extraction ratio, ERO2)。(2)血流动力学指标：心电监护心率(heart rate, HR)，左股动脉置管监测平均动脉压(mean arterial pressure, MAP)、右股静脉置入Swan-Ganz导管监测中心静脉压(central venous pressure, CVP)、平均肺动脉压(mean pulmonary arterial pressure, MPAP)、肺动脉嵌压(pulmonary artery wedge pressure, PAWP)、采用热稀释法测心输出量(cardiac index output, CO)并计算心脏指数 (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)为体表面积(m2)= 11.2×[体重(g)2/3/10 000]，Hb为血红蛋白浓度。

5统计学处理

结 果

1模型复制

12只犬分别经静注油酸和气管内滴入稀盐酸后均达到ARDS 诊断标准，ARDSexp组氧合指数为(118.3±21.7) mmHg，ARDSp组氧合指数为(115.1±19.8)mmHg。

2RM对氧代谢的影响

RM后两组PaO2显著增加，30 min后逐渐下降，4 h内PaO2显著高于RM前水平(Plt;0.01)；与ARDSp组相比，ARDSexp组PaO2/FiO2改善更为显著，两组间比较显著差异(Plt;0.01)；两组的PvO2和SvO2在RM后逐渐升高，ARDSp组相比，ARDSexp升高更为显著(Plt;0.05)；RM后DO2短暂下降后逐渐增加，ERO2逐渐降低，ARDSp组与ARDSexp组相比较，ARDSexp改变更为显著,见表1。

表1 RM后ARDS犬氧代谢的变化

3RM对血液动力学的影响

实施RM前后HR无明显变化。在RM过程中，MPAP、CVP和PAWP均显著增加，但RM结束后逐渐恢复至基础水平，ARDSp组与ARDSexp组相比较，两组无显著差异；MAP和CI在RM过程中显著下降，RM结束后很快恢复至基础水平，ARDSp组与ARDSexp组相比较，ARDSp组下降幅度更为显著(Plt;0.01)。RM后4 h, 两组的CI均高于基础值(Plt;0.01),见表2。

表2 RM后ARDS犬血液动力学的变化

讨 论

小潮气量肺保护通气策略是唯一证实能够改善ARDS预后的措施，但有明显的缺陷，容易导致肺膨胀不全而发生肺泡萎陷，而大量肺泡萎陷、肺容积减少是ARDS的主要病理生理特征，为保证患者氧合，须将萎陷的肺泡再度开放, 并维持其开放状态[3]。因此，适当的肺复张是十分必要的[4]。在实施RM时往往需要考虑三方面的问题，一是采用何种方式及压力水平使更多萎陷肺泡开放，二是复张之后如何设法使已开的肺泡尽量维持于开放状态，三是避免在实施RM过程中可能出现的肺损伤和对血流动力学的抑制[5]。我们的研究发现根据P-V曲线的特征指导肺复张，即以P-V曲线为导向的肺复张策略能改善肺顺应性，减轻肺损伤。但是对于不同原因的ARDS，RM对其氧代谢和血流动力学的影响有何不同，目前研究较少。

纠正低氧血症和组织缺氧是治疗ARDS的根本目标。机体对缺氧的反应首先是通过提高CI增加DO2以维持VO2稳定，如通过增加DO2不能满足代谢需要，机体就通过提高ERO2来增加氧的利用；PvO2和SvO2是全身组织氧合情况的反映，PvO2和SvO2越低，ERO2越高，说明组织氧耗越多，组织越缺氧明显。我们的研究发现，RM后各组PaO2显著增加， PvO2、SvO2和DO2逐渐升高，ERO2逐渐降低，说明RM能改善氧合，纠正组织细胞缺氧。Kanoore等[6]和Grasso等[7]研究发现ARDS患者行RM后PaO2和DO2较前明显增加。根据DO2的计算公式，氧输送主要受CI、SaO2和血红蛋白的影响。本研究DO2升高，可能与氧合的改善和心输出量增加有关。由于ARDSexp组氧合改善更为明显，且RM对ARDSp组CI影响较ARDSexp组更为显著，所以ARDSexp组DO2高于ARDSp组。DO2增加并不反映组织细胞水平的氧利用情况，SvO2和ERO2是反映组织缺氧较好的指标。本研究中，RM后PvO2、SvO2逐渐增加，ERO2逐渐降低，提示应用RM后组织缺氧得到改善，而以ARDSexp组的疗效更为明显。

本研究结果提示,在RM过程中，MPAP、CVP、PAWP均显著增加，但RM结束后很快恢复至基础水平；在RM过程中MAP和CI显著下降，RM结束后很快恢复至基础水平。Park等[8]和Lim等[9]分别对ARDS患者和ARDS动物模型采用RM,发现RM过程中MAP和CI下降明显，3-5 min回复正常水平，说明大多数ARDS患者能够耐受RM。但是对于血压低、血容量不足的ARDS患者，RM可导致MAP和CI的显著下降，甚至引起顽固性休克，所以对于此类患者行RM时必须先补充血容量,保持血流动力学稳定，减少RM对血流动力学的影响[10]。我们研究发现RM后CI逐渐增加，可能与全身血管阻力降低和低氧血症纠正后心肌收缩力增强有关。我们的研究还发现，RM对ARDSp组CI和血压的影响较ARDSexp组更为显著，可能与ARDSp组的病理特征有关。本组为吸入盐酸ARDS动物模型，其病理改变主要为局灶性实性变，对肺复张反应不如ARDSexp明显，RM后肺顺应性和复张容积的改变相对不如ARDSexp，导致RM时传导至胸腔的压力明显增加，使静脉回流减少和右室充盈缓慢，心输出量明显减少。另外ARDSp组RM后氧合改善不明显也可能导致肺血管收缩，肺血管阻力增高，使CI减少。因此，对于ARDSp，尤其是局灶性ARDS，行RM时需密切监测血流动力学变化[11]。

综上所述，RM可以提高氧输送和改善组织缺氧，ARDSexp组的效果优于ARDSp组；对血液动力学会所造成短暂的影响，在ARDSp组更为显著。

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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

广东省科技计划资助项目(No.2007B060401067)

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