跨肺压指导下机械通气对ARDS患者呼吸功能和血流动力学的影响：一项前瞻胜随机对照研究

Effect of different transpulmonary pressures guided mechanical ventilation on respiratory and hemodynamics of patients with ARDS： a prospective randomized controlled trial

目的探讨跨肺压（Ptp）指导下机械通气（MV）对急性呼吸窘迫综合征（ARDS）患者呼吸功能和血流动力学指标的影响，寻找更优化的Ptp。方法采用前瞻性随机对照研究（RCT）方法，选择2013年2月至2016年8月广州医科大学附属深圳沙井医院重症医学科（ICU）和南方医科大学深圳医院急诊重症加强治疗病房（EICU）收治的需MV的ARDS患者，按随机数字表法分为对照组和观察组，观察组再根据Ptp不同设定分为10、15、20cmH2O（1cmH2O=0．098kPa）3个亚组。各组患者均按ARDS国际指南标准进行治疗；对照组MV策略参照ARDS协作网（ARDSNet）意见执行；观察组则采用不同Ptp指导下的MV策略。监测各组患者设定不同Ptp后通气1、24、48h的呼吸功能指标，采用脉搏指示连续心排血量（PiCCO）监测技术检测血流动力学指标；记录各组患者MV时间、ICU住院时间和28d病死率。结果共67例ARDS患者进入研究，其中2例于48h内死亡、1例失访，最终64例纳入分析，其中观察组43例、对照组21例，两组性别构成、年龄、入院4h内氧合指数（PaO2／FiO2）和急性生理学与慢性健康状况评分系统Ⅱ（APACHEⅡ）评分等一般资料均衡，有可比性。对照组患者通气各时间点呼吸功能和血流动力学指标无明显变化；但观察组随通气时间延长，呼吸功能明显改善，并随Ptp升高对血流动力学的影响逐渐增大。与对照组比较，Ptp20cmH2O组设定Ptp后通气48h呼吸功能明显改善，PaO2／FiO2、动脉血二氧化碳分压（PaCO2）、呼气末正压（PEEP）、气道平台压（Pplat）和肺顺应性（Cst）均明显升高[PaO2／FiO2（mmHg，1mmHg=0．133kPa）：220．9±30．8比178．5±42．9，PaCO2（mmHg）：55．1±7．6比38．6±4．8，PEEP（cmH2O）：24．7±4．8比6．6±2．2，Pplat（cmH2O）：34．4±3．7比20．7±3．5，Cst（mL／cmH2O）：23．8±3．6比13．1±4．6；均P〈0．05]，血管外肺水指数（ELWI）则明显降低（mL／kg：6．8±1．7比10．8±2．6，P〈0．05），但平均动脉压（MAP）、心排血指数（CI）和全心舒张期末容积指数（GEDVI）等血流动力学指标也明显下降[MAP（mmHg）：58．8±6．7比69．7±4．7，CI（mL·s^-1·m^-2）：46．7±23.3比73．3±30．0，GEDVI（mL/m^2）：633．2±45．2比702．6±55．7；均p〈0．05]；Ptp10emH2O组PaO2/FiO2、PEEP、Pp]at和Cst均明显升高[PaO2／FiO2（mmHg）：183．4±45．5比178．5±42．9，PEEP（cmH2O）：14．4±3．6比6．6±2．2，Pplat（cmH2O）：25．7±5．6比20．7±3．5，Cst（mL／cmH2O）：16．2±4.3比13．1±4．6；均P〈0．05]，ELWI明显降低（mL／kg：8．7±1．8比10．8±2．6，P〈0．05），但MAP、CI、GEDVI差异无统计学意义[MAP（mmHg）：65．8±4．6比69．7±4．7，CI（mL·s^-1·m^-2）：65．0±35．0比73.3±30．0，GEDVI（mL／m^2）：706．7±54．4比702．6±55．7；均P〉0．05]。说明10cmH2OPtp即可起到与20cmH2O相同的改善氧合和呼吸功能的作用，且对血流动力学无明显影响。与对照组比较，Ptp10cmH2O和15cmH2O组MV时间和ICU住院时间无明显差异，而Ptp20cmH2O组则明显缩短[MV时间（d）：95．5±21．5比130．8±23．6，ICU住院时间（d）：8．1±2．2比12．8±2．8，均P〈0．05]；各组28d病死率差异无统计学意义。结论MV时设定Ptp为10cmH2O可以改善氧合和呼吸力学，且对血流动力学影响小，是心肺保护安全有效的通气策略。

Objective To assess the effect of different transpulmonary pressures （Ptp） guided mechanical ventilation （MV） on respiratory function and hemodynamics parameters of patients with acute respiratory distress syndrome （ARDS）, and to find out a more optimized Ptp. Methods A prospective randomized controlled trial （RCT） was conducted. The ventilated patients with ARDS admitted to Department of Critical Care Medicine （ICU） of Shenzhen Shajing Affiliated Hospital of Guangzhou Medical University and Department of Emergency and Critical Care Medicine （EICU） of Shenzhen Hospital of South Medical University from February 2013 to August 2016 were enrolled. According to random number table method, all patients were divided into control group and observation group. The patients in observation group was subdivided into three subgroups according to the different setting of Ptp, namely Ptp 10, 15, 20 cmH2O （1 cmH2O = 0.098 kPa） subgroups. The patients in all groups received standard treatment in accordance with the international guidelines for ARDS. The patients in control group were ventilated by guidance of ARDSNet, and the patients in observation group were ventilated by guidance of different Ptp. After setting different Ptp at 1, 24, 48 hours in the process of MV, respiratory function parameters of patients in all groups were determined. The hemodynamic parameters were determined by using pulse indicating continuous cardiac output （PiCCO） technology. The duration of MV, length of ICU stay and 28-day mortality were recorded. Results A total of 67 patients with ARDS were enrolled, among whom 2 patients died within 48 hours, and 1 case was lost to follow-up. Finally, 64 patients completed the study, 43 patients in observation group, and 21 in control group. There were no significant differences in gender composition, age, oxygenation index （PaO2/FiO2） within 4 hours after hospital admission and acute physiology and chronic health evaluation Ⅱ （APACHE Ⅱ ） score between the two groups, which showed the baseline was equivalent and comparable. The respiratory function and hemodynamic parameters showed no obvious change in control group at different time points of MV; but with the extension of ventilation, the respiratory function was improved significantly in observation group, and the gradually rising of Ptp had obvious adverse effects on hemodynamics parameters. Compared with control group, at 48 hours of ventilation after setting Ptp, the respiratory function in Ptp 20 cmH2O subgroup was improved significantly, PaO2/FiO2, arterial partial pressure of carbon dioxide （PaCO2）, positive end-expiratory pressure （PEEP）, airway platform pressure （Pplat）, and lung compliance （C50 were significantly increased [PaO2/FiO2 （mmHg, 1 mmHg = 0.133 kPa）： 220.9 ± 30.8 vs. 178.5 ± 42.9, PaCO2 （mmHg）： 55.1 ± 7.6 vs. 38.6 ± 4.8, PEEP （cmH2O）： 24.7 ± 4.8 vs. 6.6 ± 2.2, Pplat （cmH20）： 34.4 ± 3.7 vs. 20.7 ± 3.5, Cst （mL/cmH20）： 23.8 ± 3.6 vs. 13.1 ± 4.6; all P 〈 0.05], and extravascular lung water index （ELWI） was significantly decreased （mL/kg： 6.8 ± 1.7 vs. 10.8 ± 2.6, P 〈 0.05）, but mean artery pressure （MAP）, cardiac index （CI）, global end-diastolic volume index （GEDVI） such as hemodynamics parameters were also significantly reduced [MAP （mmHg）： 58.8±6.7 vs. 69.7±4.7, CI （mL· s^-1 ·m^-2）： 46.7±23.3 vs. 73.3±30.0, GEDVI （mL/m^2）： 633.2±45.2 vs. 702.6±55.7; all P 〈 0.05]; the PaO2/FiO2, PEEP, Pplat, and Cst in Ptp 10 cmH20 subgroup were significantly increased [PaO2/FiO2 （mmHg）： 183.4 ± 45.5 vs. 178.5 ± 42.9, PEEP （cmH2P）： 14.4 ± 3.6 vs. 6.6 ± 2.2, Pplat （cmH2O）： 25.7 ± 5.6 vs. 20.7 ± 3.5, Cst （mL/cmH2O）： 16.2± 4.3 vs. 13.1 ± 4.6; all P 〈 0.05], and ELWI was significantly reduced （mL/kg： 8.7 ± 1.8 vs. 10.8 ± 2.6, P 〈 0.05）, but the MAP, CI and GEDVI showed no significant difference [MAP （mmHg）： 65.8±4.6 vs. 69.7±4.7, CI （mL· s^-1·m^-2）： 65.0±35.0 vs. 73.3±30.0, GEDVI （mL/m2）： 706.7±54.4 vs. 702.6 ± 55.7; all P 〉 0.05]. The above illustrated that 10 cmH2O Ptp could act as the same as 20 cmH2O did to improve oxygenation and respiratory function, but had no obvious effect on hemodynamics. Compared with control group, the duration of MV and the length of ICU stay showed no significant differences in Ptp 10 cmH2O and 15 cmH2O subgroups, but those in 20 cmH2O subgroup were significantly shortened [duration of MV （days）： 95.5 ± 21.5 vs. 130.8 ± 23.6, length of ICU stay （days）： 8.1 ± 2.2 vs. 12.8 ± 2.8, both P 〉 0.05]. There was no significant difference in 28-day mortality among the groups. Conclusions MV guided by Ptp of 10 cmH2O could improve oxygenation and respiratory mechanics, while has less hemodynamic influence. It was a safe and effective cardiopulmonary protection ventilation method.