【作者】 左姗姗；

【导师】 胡振杰； 张玉想；

【作者基本信息】 河北医科大学 ， 急诊医学， 2010， 硕士

【摘要】 目的:ALI/ARDS(Acute Lung Injury/Acute Respiratory Distress Syndrome)是ICU(Intensive Care Unit)危重病患者的常见病,病死率高。渗透性肺水肿是ALI/ARDS的重要特征,应用脉波指示剂连续心排血量(Pulse Indicator Contious Cadiac Output, PICCO)技术测得的肺血管通透性(Pulmonary Vascular Permeability Index, PVPI)、血管外肺水指数(Extra Vascular Lung Water Index, EVLWI)是判断肺水肿类型和评价肺水肿程度的指标,动态监测EVLW可了解肺水肿的病情变化,为临床防止和治疗肺水肿提供直观依据。ALI/ARDS患者肺毛细血管内皮细胞与肺泡上皮细胞屏障的通透性增高,肺泡与肺间质内积聚大量的水肿液,其中富含蛋白如中性粒细胞弹性蛋白酶(Neutrophil Elastase,NE)及以中性粒细胞为主的多种炎症细胞。此外,肺泡上皮细胞以及成纤维细胞也能产生多种细胞因子如血管内皮生长因子(Vascular Endothel- ial Growth Factor,VEGF),进而加剧炎症反应过程。NE和VEGF具有强效的促炎作用,被认为是全身炎症反应的关键介质,可导致肺上皮和肺毛细血管内皮通透性增高从而引起不同程度的肺水肿。随着对ARDS的发病机制和连续性血液净化(Continuous Bood Purification, CBP)的作用机制的研究,20世纪80年代开始人们把血液净化引入ARDS的治疗,特别是持续高容量血液滤过(High volume Hemofiltration, HVHF)通过增加置换液输入量进一步提高对大中分子溶质的对流清除。本实验15例ALI/ARDS患者通过HVHF治疗前后应用PICCO技术观察EVLWI变化及氧合状态改善情况,同时检测HVHF治疗前后患者血浆NE和VEGF的变化,探讨血浆NE和VEGF在ALI/ARDS患者的作用机制及HVHF的清除作用对血管外肺水的影响。方法:按1994年欧美联合会议(American-European Consensus Coference, AECC)定义的诊断标准选择ALI/ARDS患者15例,且这些患者具有应用HVHF治疗指征,给予HVHF治疗,并应用PiCCO监测仪(单指示剂经肺热稀释技术)记录患者入选时(T0)和HVHF治疗后24h(T1)、48h(T2)、72h(T3)的血管外肺水指数(EVLWI)、肺血管通透性指数(Pulmonary Vascular Permeability Index, PVPI)、胸腔内血容积指数(Intrathoracic Blood Volume Index,ITBVI)及氧合指数(Oxygenation ratio, PaO2/FiO2 ratio),中心静脉压(Central Venous Pressure, CVP),急性肺损伤评分(Lung Injury Score, LIS)和急性生理和慢性健康( Acute Physiology and Chronic Health Evaluation ,APACHEⅡ)评分,同时抽静脉血用酶联免疫吸附法(Enzyme Linked Immunosorbent Assay, ELISA)的方法测定患者血浆中性粒细胞弹性蛋白酶(NE)和血管内皮生长因子(VEGF)。根据患者预后分为存活组及死亡组,以及20名健康体检的志愿者作为血浆NE和VEGF水平的健康对照。结果:1 HVHF治疗后ALI/ARDS患者PICCO监测指标及PaO2/FiO2的变化:所有患者HVHF治疗过程后CVP,T3与T0时间点相比有统计学意义(P<0.05)。ITBVI各时间点没有统计学差异。EVLWI呈下降趋势,T2和T3与T0时间点相比均有统计学意义(P<0.05),比较PVPI发现T2与T0时间点差异有统计学意义(P<0.05),T3与T0时间点比较有显著统计学意义(P<0.01)。PaO2/FiO2升高,T1、T2与T0时间点比较均有统计学意义(P<0.05),且T3与T0比较有显著统计学意义(P<0.01)。2 HVHF治疗前后ALI/ARDS患者APACHEⅡ评分、LIS评分的变化: HVHF治疗后APACHEⅡ评分逐渐降低,具有统计学意义(P<0.05)。LIS评分亦呈降低趋势,具有统计学意义(P<0.05或P<0.01)。3 ALI/ARDS患者与健康志愿者比较:与健康志愿者比较,ALI/ARDS患者HVHF治疗前血浆NE和VEGF水平较健康志愿者均显著升高(P<0.01)。4 HVHF治疗前后ALI/ARDS患者血浆NE和VEGF水平变化: HVHF治疗后所有患者血浆NE和VEGF水平均显著降低,与T0比较,各时间点差异均有统计学意义(P<0.05或P<0.01)。存活组患者血浆NE和VEGF水平呈下降趋势,T3与T0时间点相比差异有统计学意义(P<0.05);VEGF经HVHF干预后T3较T0时间点相比有显著统计学意义(P<0.01)。死亡组患者血浆NE和VEGF经治疗后48小时内有统计学意义(P<0.05),但72小时后均无统计学意义。超滤液中均检出NE和VEGF。结论:1 ALI/ARDS患者经过HVHF治疗后降低了肺血管通透性,减少了血管外肺水,改善了氧合状态。2 ALI/ARDS患者血浆NE和VEGF水平增高,肺血管通透性增高,引起肺水肿,且持续高水平NE和VEGF的ALI/ARDS患者预后差。3 HVHF治疗可通过清除ALI/ARDS患者血浆部分NE和VEGF,减轻炎症反应,改善肺血管通透性,减少血管外肺水,减轻肺水肿,从而改善氧合状态。4 HVHF治疗可降低ALI/ARDS患者死亡率,改善预后,可作为治疗ALI/ARDS的重要手段之一。更多还原

【Abstract】 Objective: ALI/ARDS (acute lung injury/acute respiratory distress syndrome) is the common diseases of critically ill patients in ICU (Intensive Care Unit), which with a high fatality rate. Permeability pulmonary edema was an important feature of the ALI/ARDS patients. Pulse indicator contious cadiac output (PICCO) technology can measured Pulmonary Vascular Permeability Index (PVPI) and Extravascular Lung Water Index (EVLWI) which are to determine the type of pulmonary edema and evaluation indicators. Dynamic monitoring of EVIWI can be helped to identify pulmonary edema, and to beneficial for clinical prevention and treatment of pulmonary edema. There are pulmonary capillary endothelial cells and alveolar epithelial cells barrier permeability, alveolar and interstitial pulmonary edema in ALI/ARDS patients. The accumulation of a large number of fluid, which is rich in protein such as Neutrophil Elastase (NE) and with a variety of neutrophil-based inflammatory cells is also found. In addition, the alveolar epithelial cells and fibroblasts can produce much inflammatory cytokines cytokines such as Vascular Endothelial Growth Factor (VEGF), and thus exacerbate inflammatory reactions. NE and VEGF which has a potent pro-inflammatory role of systemic inflammatory response are considered to lead to lung epithelial and pulmonary capillary endothelial permeability and contribute to pulmonary edema. With the development of the pathogenesis of ARDS and the mechanism of Continuous Blood Purification (CBP), people began to treat ARDS with CBP in 20th century. High Volume Hemofiltration (HVHF) is considered to increase the replacement fluid input and to improve the large and medium sized solutes removal. In this study, 15 patients with ALI/ARDS, were choosed before and after treatment with HVHF. PICCO technique was used to observe state of oxygen and the changes of EVLWI., while the changes of NE and VEGF were also detected before and after treatment with HVHF. The purpose of this study was to explore the role of plasma NE and VEGF in the pathophysiology of ALI/ARDS, the effects of extravascular lung water after treatment with HVHF.Methods:Fifteen patients,which were diagnosed as ALI/ARDS according to American-European Consensus Conference (AECC) criteria in 1994, were selected in this study. All the patients treated with HVHF and apply the PiCCO monitor (single-instruction agent through the lung-heat dilution technique). Records were enrolled at the following time points: pre-HVHF (T0) and after treatment with HVHF 24h (T1), 48h (T2), 72h (T3). The parameters included extravascular lung water index (EVLWI), pulmonary vascular permeability permeability index (PVPI), Oxygenation ratio (PaO2/FiO2 ratio), Intra-thoracic Blood Volume Index (ITBVI) ,central venous pressure (CVP), acute lung injury score (LIS) and acute physiology and chronic Health (APACHEⅡ) score. At the same time, venous blood samples were measured in plasma neutrophil elastase (NE) and vascular endothelial growth factor (VEGF) by enzyme linked immunosorbent assay (ELISA). According to the prognosis, the patients were divided into the survival group and death group. Twenty healthy volunteers were as a control for VEGF and NE levels.Results:1 The hemodynamic indexes and PaO2/FiO2 changes after HVHF treatment:In 15 patients, compared with T3 and T0 point, CVP changes in pre-HVHF and pro-HVHF, were statistically significant difference (P<0.05). As for ITBVI, there were no statistically significant differences among all time points. EVLEI had downward trend, and T2 and T3 compared with T0 point were statistically significant difference (P<0.05). For PVPI, there are significant differences betewen T2 and T0 point (P<0.01). So did in T3 compared with T0 point (P<0.05). PaO2/FiO2 were increased, and T1, T2 compared with T0 time point were statistically significant difference (P<0.05), but the difference of T3 compared with T0 was significantly (P<0.01).2 The APACHEⅡscore, LIS score changes before and after HVHF treatment :APACHEⅡscore after treatment HVHF gradually reduced, with statistical significance (P<0.05). LIS score was also trend lower, with statistically significant (P<0.05 or P<0.01).3 The comparison between ALI / ARDS patients and healthy volunteers: Compared with the healthy volunteers, the plasma NE, and VEGF in ALI /ARDS patients were significantly higher before HVHF treatment (P<0.01).4 The VEGF and NE levels before and after HVHF treatment : After HVHF treatment, the NE and VEGF levels of all patients were significantly lower. Compared with the T0 point, each time point differences were statistically significant (P<0.05 or P<0.01). In survival group, the VEGF and NE levels showed a downward trend. Compared with T3 and T0 time Points, the difference was statistically significant (P<0.05). Compared with T0 point, The VEGF levels after HVHF treatment time point in T3 had significantly statistically difference (P<0.01). In death cases, treated within 48 hours, the NE, and VEGF had statistically significant difference (P<0.05), but there was no statistical difference after 72 hours. Ultrafiltrate were detected in both the NE and VEGF.Conclusion:1 For all the ALI/ARDS patients after HVHF treatment, pulmonary vascular permeability were reduced, and extravascular lung water decreased, and oxygen were improved.2 For all the ALI/ARDS patients, neutrophil elastase and vascular endothelial growth factor levels were significantly higher compared with healthy people, and continuing high levels of NE and VEGF had poor prognosis.3 HVHF treatment had the effects of clearing part of the NE and VEGF, reducing their concentrations, reducing inflammation and improving blood vessel permeability, and reducing extravascular lung water, and then reducing pulmonary edema, thereby improving the oxygen and status.4 HVHF treatment can reduce the mortality of ALI/ARDS patients, improve the prognosis, which may be a useful treatment for ALI/ARDS.更多还原