【作者】 朱传兵；

【导师】 陈荣昌；

【作者基本信息】 广州医学院 ， 内科学， 2011， 硕士

【摘要】 研究背景:呼气流速受限（EFL）是导致动态肺过度充气（DPH）和内源性呼气末正压（PEEPi）的重要机制。DPH和PEEPi可增加吸气阈值负荷、降低吸气肌（尤其是膈肌）功能,导致吸气肌努力增加和中枢-机械-通气失偶联,加重呼吸困难。加用适当水平的外源性呼气末正压（PEEPe）可以减少慢性阻塞性肺疾病（COPD）机械通气患者的吸气肌努力,降低呼吸功耗,改善人机协调性。但PEEPe水平对呼吸力学,尤其是中枢-机械-通气偶联的影响仍有待进一步研究。研究目的:在健康受试者中使用呼气限流器建立EFL模型,模拟COPD的病理生理学变化,探讨不同的持续气道正压（CPAP）水平对EFL时呼气末肺容量（EELV）、中枢-机械-通气偶联和呼吸困难等方面的综合影响。方法:通过深慢呼吸法获得受试者胸壁及肺静态顺应性曲线,构建肺和胸部压力容积曲线（Campbell）图;使用呼气限流器模拟EFL,比较限流前后肺容量/流量、呼吸力学指标及膈肌肌电、中枢-机械-通气偶联的变化;在限流基础上使用CPAP,采集不同压力水平时受试者上述指标的变化,比较不同CPAP水平对上述指标的影响。结果:1.COPD病理生理模型的建立:加用限流器后,受试者出现呼吸困难,并表现与COPD相似的病理生理学变化,如气流受限,动态肺过度充气（深吸气量（IC）减小,P<0.001）,出现静态内源性呼气末正压（PEEPi,stat为4.94±1.33 cmH₂O）,辅助呼吸肌动用增加（潮气呼吸时食道压与跨膈压变化的比值（△Pes/△Pdi）增高,P<0.05）,中枢驱动增加（RMSdi和RMSdi%增高,P<0.01）,中枢-机械-通气偶联恶化（VT/RMS、VT/△Pes下降,P<0.01;△Pdi /RMS,P<0.05）。然而,也存在与COPD患者不一样的变化,表现为潮气量（VT）有增加趋势（从0.74±0.11L增加到1.03±0.27L,P>0.05）,呼吸频率（RR）减慢（P<0.01）。2.CPAP对COPD模型的呼吸力学的影响:在此COPD模型中,随CPAP水平的增加,呼气末肺容量的变化值（ΔEELVx）及其占限流后深吸气量（ICx）的百分比（ΔEELVx /ICx%）呈S型曲线变化,在CPAP小于PEEPi,stat的73.95%时增加较缓,当CPAP超过此界限值后,随CPAP升高明显增加;RMSdi及RMSdi%也有上升;中枢—机械-通气偶联指标--潮气量与膈肌电活动强度比值（VT/RMS）、分钟通气量与膈肌电活动强度比值（VE/RMS）、跨膈压与膈肌电活动强度比值（ΔPdi/RMS）、潮气量与跨膈压比值（VT/ΔPdi）、潮气量与食道吸气负压比值（VT/ΔPes）均有降低趋势,但组间比较均无统计学意义。3.各项评价指标间的相关及回归关系:随着CPAP的逐渐递增,反映呼吸中枢驱动的指标,膈肌肌电活动强度占最大活动强度的百分比（RMSdi%）和平均吸气流速（VT/Ti）的增加,与实验中气促评分（Borg）呈正相关,与IC负相关;而反映中枢-机械-通气偶联的指标,包括VT/ΔPes、ΔPdi/RMS、VT/RMS,与Borg评分呈负相关,与IC正相关。反映流量触发所需要的膈肌活动的指标--RMSdi在吸气开始至流速达40ml/s的积分值与所达到容积的比值（ΣRMS/V）与IC、VT/ΔPes、ΔPdi/RMS、VT/RMS呈负相关,提示吸气起始段膈肌肌电积分值也能很好反映中枢驱动变化。以Borg评分为因变量,对多个自变量进行逐步选择后得5个预测因子:RMSdi%、ΔPdi/RMS、VT/RMS、ΔPes、VT/Ti,其决定系数（R²）为0.614;以ΔEELVx或IC为因变量,逐步选择后得到2个预测因子:CPAP/PEEPi,stat、呼气时间（Te）,其R²分别为0.666和0.718。结论:1.使用限流器能造成呼气流速受限,导致动态肺过度充气和PEEPi形成,成功建立正常受试者COPD模型。此模型可引起呼吸肌努力增加、辅助呼吸肌动用,呼吸中枢驱动增强,中枢-机械-通气偶联恶化,出现呼吸困难。2.在正常受试者COPD模型中,随着CPAP水平递增,呼气末肺容量呈非线性的增加,在CPAP小于PEEPi,stat的73.95%时呼气末肺容量增加较轻微,当CPAP超过此界限值后,CPAP水平的增加导致明显的呼气末肺容量的增加。CPAP并不能改善中枢-机械-通气偶联。此研究结果不支持采用中枢-机械-通气偶联来指导CPAP的合理设置。CPAP（PEEP）水平的设置应该更加重视呼气末肺容量的监控和患者呼吸困难的情况。更多还原

【Abstract】 BACKGROUND: Expiratory flow limitation（EFL） is the main mechanism leading to dynamic pulmonary hyperinflation（DPH）and intrinsic positive end-expiratory pressure（PEEPi）.DPH and PEEPi lead to increased inspiratory threshold load and impaired inspiratory muscle function （especially the diaphragm）, resulting in increased inspiratory muscle efforts and impaired central drive mechanical and ventilation coupling, which is an important mechanism of dyspnea. Appropriate setting of extrinsic PEEP（PEEPe） can decrease inspiratory effort and work of breathing, improve patient-ventilator synchrony in severe COPD patients with PEEPi and treated with mechanical ventilation. The effects of level of PEEPe on respiratory mechanics, especially on central drive mechanical and ventilation coupling, demand further investigation.OBJECTIVE: To investigate the levels of PEEPe on end expiratory lung volume, central drive mechanical and ventilation coupling purpose, dyspnea and other respiratory mechanics parameters on the COPD model of induced with expiratory flow limitation in normal volunteerer.METHODS: The static pressure volume curves of the lung and chest wall （Campbell diagram） were established with slow deep respiratory manoeuvre. Expiratory flow limitator was employed to induce COPD model with expiratory flow limitation and dynanmic hyperinflation. After the model establishment, the changes of end expiratory lung volume, respiratory flow, diaphragm electromyogram, central drive mechanical and ventilation coupling, as well as other respiratory mechanics parameters were evaluated to elucidate the effects of COPD model on respiratory mechanics. Upon this model, incremental CPAP level was applied to investigate the effects of CPAP level on the above mentioned respiratory mechanics parameters.RESULTS:1. The establishment of pathophysiological model of COPD.After the application of flow restrictor, the subjects become dyspnic, and develop the pathophysiological changes similar to COPD, such as flow limitation,dynamic pulmonary hyperinflation （inspiratory capacity（IC） decrease,P<0.001）, static PEEPi（PEEPi,stat were 4.94±1.33 cmH₂O）, increased use of accessory respiratory muscle（elevated ratio of tidal Pes to Pdi swing（△Pes/△Pdi）,P<0.05）. There were also increase of central driver（root mean square of diaphragm electromyogram, RMSdi）、percentage of RMSdi to maximal RMSdi （RMSdi%） （P<0.01）and deterioration of central drive mechanical and ventilation coupling （decreased VT/RMS、VT/△Pes,P<0.01;△Pdi/RMS decrease,P<0.05）. However, there were also some changes different from those in COPD, such as the tendency of elevated tidal volume （VT）（increased from 0.74±0.11L to 1.03±0.27L, P>0.05）, decreased respiratory rate（RR） （P< 0.01）.2. Effects of CPAP on respiratory mechanics in COPD.In this COPD model, as the increment of CPAP level, the change of EELV （ΔEELVx） and its percentage to inspiratory capacity （ΔEELVx/ICx%） increases in a S-shaped curve. In the range of CPAP level less than 73.95% of PEEPi,stat, there is slight impact on EELV. However, when CPAP level is over this critical value, the impact on EELV increased markedly. The parameters representing central drive mechanical and ventilation coupling including VT/RMS, VE/RMS,ΔPdi/RMS, VT/ΔPdi, VT/ΔPes all were shown to have the tendency of decreasing with no significance difference among groups.3. The correlation and relationship between different indexes.As the increase of CPAP level, there were increased in parameters representing respiratory central drive, including RMSdi% and mean inspiratory flow（VT/Ti）, which are positively related to Borg index and negatively related to IC. The parameters representing central drive mechanical and ventilation coupling, including VT/ΔPes、ΔPdi/RMS、VT/RMS were negatively related to Borg index and positively to IC. The parameter representing diaphragmatic muscle activity to achieve inspiratory flow trigger of common ventilators,the integrals of RMS from the beginning to the time of inspiratory flow of 40ml/s normalized by volume（ΣRMS/V）was negatively related to IC,VT/ΔPes,ΔPdi/RMS and VT/RMS and positively related to the RMSdi% and the Borg index, indicating this parameter in the early inspiration can also adequately reflect the changes of respiratory central drive. Let the Borg index as the dependent variable, stepwise multiple factors regression analysis revealed five related factors, including RMSdi%、ΔPdi/RMS、VT/RMS、ΔPes、VT/Ti,with coefficient of determination（R²）of 0.614. Let theΔEELVx or IC as the dependent variables, it was shown that CPAP/PEEPi,stat and Te were related factors with R² of 0.666 and 0.718 respectively.CONCLUSION:1. The COPD model was successfully established with flow restrictor in normal volunterers, with the presentation of dynamic pulmonary hyperinflation and PEEPi. It was observed in this model that there were increased respiratory effort, respiratory central drive, use of accessory respiratory muscle and dyspnea, as well as the deterioration of central drive mechanical and ventilation coupling.2. In this COPD model, as the increment of CPAP level, the change of EELV （ΔEELVx） and its percentage to inspiratory capacity （ΔEELVx/ICx%） increases in a S-shaped curve. In the range of CPAP level less than 73.95% of PEEPi,stat, there is slight impact on EELV. However, when CPAP level is over this critical value, the impact on EELV increased markedly. CPAP can not improve the central drive mechanical ventilation coupling. These results did not support the use of central drive mechanical and ventilation coupling to guide the rational setting CPAP level.More attention should be paid to the monitoring EELV and the patients’dyspnea in the titration of CPAP （PEEP） level in COPD.更多还原