血管外肺水与脓毒症相关性ALI/ARDS预后关系的Meta分析

目的 研究血管外肺水(EVLW)在预测脓毒症相关性急性肺损伤/急性呼吸窘迫综合征预后中的价值.方法 检索1991年到2011年国内外公开发表的关于血管外肺水与脓毒症相关性ALI/ARDS预后关系的中英文文献,通过Stata软件进行Meta分析.结果 根据纳入和剔除标准筛选出7篇文献,Meta分析表明脓毒症相关性急性肺损伤/急性呼吸窘迫综合征患者中死亡组3d内的EVLW均维持在较高水平,而存活组有明显下降趋势,两组EVLW差距日趋扩大(SMDd1＜SMDd2＜SMD.d3),首日:SMD d1=0.29,95％CI:0.047～0.532;次日:SMDd2=1.64,95％ CI:0.14-3.13;第3天:SMDd3 =1.83,95％ CI:0.56～3.10.结论 脓毒症相关性急性肺损伤/急性呼吸窘迫综合征发病早期EVLW水平及其动态变化可作为预后评估指标,持续高水平的EVLW将增加死亡风险.     

Lung recruitment maneuver effects on respiratory mechanics and extravascular lung water index in patients with acute respiratory distress syndrome

BACKGROUND:

Animal experiments showed that recruitment maneuver (RM) and protective ventilation strategy of the lung could improve oxygenation and reduce extravascular lung water. This study was to investigate the effects of RM on respiratory mechanics and extravascular lung water index (EVLWI) in patients with acute respiratory distress syndrome (ARDS).

METHODS:

Thirty patients with ARDS were randomized into a RM group and a non-RM group. In the RM group, after basic mechanical ventilation stabilized for 30 minutes, RM was performed and repeated once every 12 hours for 3 days. In the non-RM group, lung protective strategy was conducted without RM. Oxygenation index (PaO₂/FiO₂), peak inspiratory pressure (PIP), Plateau pressure (Pplat), static pulmonary compliance (Cst) and EVLWI of patients before treatment and at 12, 24, 48, 72 hours after the treatment were measured and compared between the groups. Hemodynamic changes were observed before and after RM. One-way ANOVA, Student''s t test and Fisher''s exact test were used to process the data.

RESULTS:

The levels of PaO₂/FiO₂ and Cst increased after treatment in the two groups, but they were higher in the RM group than in the non-RM group (P<0.05). The PIP and Pplat decreased after treatment in the two groups, but they were lower in the RM group than in the non-RM group (P<0.05). The EVLWI in the two groups showed downward trend after treatment (P<0.05), and the differences were signifcant at all time points (P<0.01); the EVLWI in the RM group was lower than that in the non-RM group at 12, 24, 48 and 72 hours (P<0.05 or P<0.01). Compared with pre-RM, hemodynamics changes during RM were significantly different (P<0.01); compared with pre-RM, the changes were not significantly different at 120 seconds after the end of RM (P>0.05).

CONCLUSIONS:

RM could reduce EVLWI, increase oxygenation and lung compliance. The effect of RM on hemodynamics was transient.KEY WORDS: Lung recruitment maneuver, Acute respiratory distress syndrome, Respiratory mechanics, Extravascular lung water index, Hemodynamics, Lung protective ventilation, Oxygenation index     

不同液体管理策略对急性呼吸窘迫综合征患者血管外肺水指数的影响

目的 通过观察不同液体管理策略对急性呼吸窘迫综合征(ARDS)患者血管外肺水指数(EVLWI)、氧合指数(PaO2/FiO2)、24 h液体平衡量、机械通气时间、住ICU时间的影响,探寻ARDS患者的最佳液体管理策略.方法 选取符合入选标准的ARDS患者为研究对象,随机分为保守性液体管理策略组(保守组)和开放性液体管理策略组(开放组),动态监测中心静脉压(CVP)、平均动脉压(MAP)、心脏指数(CI)、PaO2/FiO2、尿量及EVLWI等,记录24 h液体平衡量、机械通气时间及住ICU时间.结果 保守组除第1天外每日液体均处于负平衡,而开放组每日液体均处于正平衡.保守组EVLWI下降程度、PaO2/FiO2改善程度明显好于开放组,机械通气时间、住ICU时间明显短于开放组(P均<0.05).结论 保守性液体管理策略可以明显降低ARDS患者血管外肺水,改善肺功能,缩短ARDS患者机械通气时间和住ICU时间.保守性液体管理策略是降低血管外肺水的有效治疗手段.     

An attempt to validate the modification of the American-European consensus definition of acute lung injury/acute respiratory distress syndrome by the Berlin definition in a university hospital

Purpose

The Berlin definition for acute respiratory distress syndrome (ARDS) is a new proposal for changing the American-European consensus definition but has not been assessed prospectively as yet. In the present study, we aimed to determine (1) the prevalence and incidence of ARDS with both definitions, and (2) the initial characteristics of patients with ARDS and 28-day mortality with the Berlin definition.

Methods

We performed a 6-month prospective observational study in the ten adult ICUs affiliated to the Public University Hospital in Lyon, France, from March to September 2012. Patients under invasive or noninvasive mechanical ventilation, with PaO₂/FiO₂ <300 mmHg regardless of the positive end-expiratory pressure (PEEP) level, and acute onset of new or increased bilateral infiltrates or opacities on chest X-ray were screened from ICU admission up to discharge. Patients with cardiogenic pulmonary edema were excluded. Patients were further classified into specific categories by using the American-European Consensus Conference and the Berlin definition criteria. The complete data set was measured at the time of inclusion. Patient outcome was measured at day 28 after inclusion.

Results

During the study period 3,504 patients were admitted and 278 fulfilled the American-European Consensus Conference criteria. Among them, 18 (6.5 %) did not comply with the Berlin criterion PEEP ≥ 5 cmH₂O and 20 (7.2 %) had PaO₂/FiO₂ ratio ≤200 while on noninvasive ventilation. By using the Berlin definition in the remaining 240 patients (n = 42 mild, n = 123 moderate, n = 75 severe), the overall prevalence was 6.85 % and it was 1.20, 3.51, and 2.14 % for mild, moderate, and severe ARDS, respectively (P > 0.05 between the three groups). The incidence of ARDS amounted to 32 per 100,000 population per year, with values for mild, moderate, and severe ARDS of 5.6, 16.3, and 10 per 100,000 population per year, respectively (P < 0.05 between the three groups). The 28-day mortality was 35.0 %. It amounted to 30.9 % in mild, 27.9 % in moderate, and 49.3 % in severe categories (P < 0.01 between mild or moderate and severe, P = 0.70 between mild and moderate). In the Cox proportional hazard regression analysis ARDS stage was not significantly associated with patient death at day 28.

Conclusions

The present study did not validate the Berlin definition of ARDS. Neither the stratification by severity nor the PaO₂/FiO₂ at study entry was independently associated with mortality.     

急性呼吸窘迫综合征患者血管外肺水指数动态变化与预后的关系

目的分析急性呼吸窘迫综合征(ARDS)患者血管外肺水指数(EVLWI)的变化特点,探讨其在ARDS患者液体管理中的指导意义以及对预后评估的价值。方法采用回顾性研究的方法 ,将2011年1月至12月收住湖州市第一人民医院重症监护室(ICU)的24例ARDS患者根据临床转归分为存活组(16例)与死亡组(8例),观察两组患者的临床特点,运用脉搏指示持续心输出量监护仪进行血流动力学监测。结果两组患者入住ICU第1天的一般情况、平均动脉压、中心静脉压(CVP)、氧合指数、血乳酸水平、心排指数和EVLWI差异均无统计学意义(P均>0.05)。从第1天到第3天,存活组氧合指数逐天上升,EVLWI、血乳酸值逐天降低,而死亡组三个指标均逐天降低,三个指标在两组间有统计学意义(P均<0.05)。另EVLWI与氧合指数呈明显负相关(r=-0.46,P<0.01),而EVLWI与CVP无明显相关性(r=-0.11,P=0.146)。第3天的EVLWI与预后的接受者操作特性曲线下面积为0.738±0.069,当EVLWI>8.5ml/kg时,预后评价的敏感度为85.3%,特异度为56.8%。结论 EVLWI的动态变化可用于评估治疗效果和患者预后,EVLWI可能是客观评价肺毛细血管渗漏的指标之一。     

肺复张对急性呼吸窘迫综合征患者血管外肺水的影响

目的 探讨肺复张(RM)策略对急性呼吸窘迫综合征(ARDS)患者血管外肺水(EVLW)的影响.方法 采用随机对照病例研究方法,将20例ARDS患者随机分为RM组和对照组.按肺保护性通气策略的原则给患者进行机械通气;用双水平气道正压(BIPAP)通气模式进行RM,每8 h重复1次,连续7 d或至脱机前;除RM外,其余治疗两组相同.记录患者的基线资料和每日RM结束后的EVLW、血管外肺水指数(EVLWI)、呼吸力学参数、氧合指数(PaO2/FiO2)、中心静脉压(CVP)、血浆胶体渗透压(COP)以及糖皮质激素、肾上腺素能药物用量和24 h液体出入量平衡等影响EVLW各因素的数值.结果 RM组和对照组EVLW、EVLWI随时间延长呈逐渐降低趋势,但两组间比较差异无统计学意义(P均>0.05).两组间CVP、COP和去甲肾上腺素、氢化可的松用量比较差异均无统计学意义(P均>0.05);RM组多巴胺用量在4 d时明显少于对照组(P<0.05);液体出入量平衡RM组7 d时为负平衡,对照组则为正平衡(P<0.05).RM组平均气道压(Pmean)的均值[(18.8±3.2)cm H2O(1 cm H2O=0.098 kPa)]和肺准静态顺应性(Cstat)的均值[(36.5±14.5)ml/cm H2O]均明显高于对照组[(16.6±3.9)cm H2O和(29.3±12.0)ml/cm H2O,P均<0.05];其中RM组5 d时Cstat大于2 d和3 d时(P均<0.05).两组间PaO2/FiO2比较则未见明显差异(P均>0.05).结论 针对ARDS患者实施的RM治疗并没有明显影响EVLW,而仅起到了改善肺呼吸力学特征的作用.本研究中所涉及的影响肺水的因素并未影响肺水的形成和清除.     

Acute respiratory distress syndrome mimickers lacking common risk factors of the Berlin definition

Purpose

Some patients presenting with acute respiratory failure and meeting the Berlin criteria for acute respiratory distress syndrome (ARDS) lack exposure to common risk factors (CRF). These so-called ARDS mimickers often lack histological diffuse alveolar damage. We aimed to describe such ARDS mimickers lacking CRF (ARDS_CRF?) in comparison with others (ARDS_CRF+).

Methods

Retrospective study including all patients receiving invasive mechanical ventilation for ARDS admitted to the intensive care units (ICUs) of two tertiary care centers from January 2003 to December 2012.

Results

The prevalence of ARDS_CRF? was 7.5 % (95 % CI [5.5–9.5]; n = 50/665). On the basis of medical history, bronchoalveolar lavage fluid cytology, and chest CT scan patterns, four etiological categories were identified: immune (n = 18; 36 %), drug-induced (n = 13; 26 %), malignant (n = 7; 14 %), and idiopathic (n = 12; 24 %). Although the ARDS_CRF? patients had a lower logistic organ dysfunction score (4 [3–8] vs. 10 [6–13]; p < 0.0001) and less often shock upon ICU admission (44 vs. 80 %; p < 0.0001) than their counterparts, their overall ICU mortality rate was very high (66 % [46–74]), and the absence of CRF remained associated with ICU mortality by multivariable logistic regression analysis (adjusted OR = 2.06; 95 % CI [1.02–4.18]; p = 0.044). Among ARDS_CRF? patients, the presence of potentially reversible lung lesions with corticosteroids (aOR = 0.14; 95 % CI [0.03–0.62]) was associated with ICU survival.

Conclusions

The absence of CRF among patients with ARDS is common and associated with a higher risk of mortality. For such atypical ARDS, a complete diagnostic workup, including bronchoalveolar lavage fluid cytology and chest CT scan patterns, should be performed to identify those patients who might benefit from specific therapies, including corticosteroids.

     

改良肺超声评分用于评估急性呼吸窘迫综合征严重程度

目的 提出改良肺超声评分(LUS),观察其用于评估急性呼吸窘迫综合征(ARDS)严重程度的价值。方法 回顾性分析33例突发ARDS患者肺超声及X线胸片等资料,根据氧合指数(OI)将患者归入中-重度组(n=16)及轻度组(n=17);比较组间LUS、改良LUS及肺水肿放射学(RALE)评分;绘制受试者工作特征(ROC)曲线,计算曲线下面积(AUC),分析影像学评分评估ARDS严重程度的效能;以Pearson相关分析观察ARDS患者影像学评分与OI的相关性,以及RALE评分与LUS及改良LUS的相关性。结果 中-重度组LUS及改良LUS均高于轻度组(P均＜0.05);RALE评分组间差异无统计学意义(P＞0.05)。以LUS、改良LUS及RALE评分评估ARDS严重程度的AUC分别为0.809、0.853及0.640。ARDS患者LUS及改良LUS均与OI呈中度负相关(r=－0.570,P=0.001;r=－0.708,P＜0.001),而RALE评分与OI无明显相关(r=－0.229,P=0.201)。ARDS患者 RALE评分与LUS及改良LUS均呈中度正相关(r=0.588,P＜0.001;r=0.502,P=0.003)。结论 本研究提出的改良LUS可有效评估ARDS严重程度,且其效能优于LUS及RALE评分。     

Relationship between ventilatory settings and barotrauma in the acute respiratory distress syndrome

OBJECTIVE: High pressures or volumes may increase the risk of barotrauma in the acute respiratory distress syndrome (ARDS). METHODS: The first part of the study analyzed data from a prospective trial of two ventilation strategies in 116 patients with ARDS retrospectively, and ventilatory pressures and volumes were compared in patients with or without pneumothorax. The second part consisted of a literature analysis of prospective trials (14 clinical studies, 2270 patients) describing incidence and risk factors for barotrauma in ARDS patients, and mean values of ventilatory parameters were plotted against incidence of barotrauma. RESULTS: In our clinical trial comparing two tidal volumes, 15 patients (12.3%) developed pneumothorax. There was no significant difference in any pressure or volume between these patients and the rest of the population, including end-inspiratory plateau pressure (P(plat)), driving pressure (P(plat)-PEEP), respiratory rate and compliance. Multiple trauma was more frequent among patients with pneumothorax (27%) than in those without (7%). Duration of mechanical ventilation tended to be longer with pneumothorax. In the literature review, the incidence of barotrauma varied between 0% and 49%, and correlated strongly with P(plat), with a high incidence above 35 cmH(2)O, and with compliance, with a high incidence below 30 ml/cmH(2)O. CONCLUSION: Clinical studies maintaining P(plat) lower than 35 cmH(2)O found no apparent relationship between ventilatory parameters and pneumothorax. Analysis of the literature suggests a correlation when patients receive mechanical ventilation with P(plat) levels exceeding 35 cmH(2)O.     

血管内皮生长因子与急性呼吸窘迫综合征关系的研究

目的探讨血管内皮生长因子(VEGF)在急性呼吸窘迫综合征(ARDS)肺毛细血管通透性改变中的作用。方法测定30例ARDS患者、18例具有发生ARDS高危因素但未发生ARDS的患者、12例单纯机械通气患者以及11例正常对照者血浆VEGF、IL-6、sVEGFR-1、sVEGFR-2水平。结果ARDS患者血浆VEGF水平与未发生ARDS高危因素组和单纯机械通气组比较明显升高[(181.25±57.60)pg/mLvs(122.03±54.02)pg/mL和(82.33±36.38)pg/mL,P均<0.001];ARDS患者存活组VEGF水平与死亡组比较差异无统计学意义(P>0.05)。ARDS组血浆sVEGFR-1水平分别与未发生ARDS的高危因素组、单纯机械通气组及正常对照组比较差异无统计学意义(P>0.05),sVEGFR-2水平有低于正常对照组趋势,但无统计学意义。ARDS患者血浆IL-6水平较未发生ARDS的高危因素患者明显升高(P<0.001),且与IL-6水平呈正相关(r's=0.587,P<0.001)。结论升高的VEGF可能在ARDS早期发生中发挥了作用,IL-6可能参与此调节机制中。     

Acute lung injury and the acute respiratory distress syndrome

Although ALI/ARDS mortality rates have improved over the last several decades, they remain high, particularly in the geriatric patient population. Although considerable progress has been made in understanding the pathogenesis of the disease, a large number of promising treatments have proven unsuccessful. One exception has been in the area of ventilator management, where a strategy of protective ventilation with low tidal volumes has demonstrated a significant mortality benefit. Basic research continues to help advance our understanding of this complex syndrome and identify interesting new directions of investigation. The results of several large, randomized trials of new ventilatory and pharmacologic strategies currently underway may help identify successful methods of treating this important disease.     

肺部超声在急性呼吸窘迫综合征严重程度评估中的应用

目的探讨肺部超声在急性呼吸窘迫综合征(ARDS)严重程度评估中的应用。方法选取我院诊治的ARDS患者119例,均行胸部CT、肺部超声检查,并制定肺部超声评分(LUS),依据病情分为轻中度组67例和重度组52例,依据预后分为生存组72例和死亡组47例,比较其LUS评分、急性生理学与慢性健康状况评分系统Ⅱ(APACHEⅡ)评分、动脉血氧分压与吸入氧浓度比值(PaO_2/FiO_2)及呼气末正压(PEEP)。Pearson相关性分析法分析LUS与APACHEⅡ评分、PEEP及PaO_2/FiO_2的相关性。绘制LUS评估ARDS严重程度的受试者工作特征(ROC)曲线,并计算其效能。Logistic回归性分析ARDS患者死亡的独立影响因素。结果在LUS、APACHEⅡ评分及PEEP方面比较,重度组明显高于轻中度组,死亡组明显高于生存组(均P0.05);在PaO_2/FiO_2比较,重度组明显低于轻中度组,死亡组明显低于生存组(均P0.05)。相关性分析显示,LUS与APACHEⅡ评分、PEEP均呈正相关(r=0.763、0.593,均P0.05),与PaO_2/FiO_2呈负相关(r=-0.637,P0.05)。ROC曲线分析显示,以LUS 18.00分为截断值,其评估ARDS严重程度的敏感性、特异性及准确率分别为96.15%、94.03%及94.96%。Logistic回归性分析显示,LUS、APACHEⅡ评分、PEEP及PaO_2/FiO_2是ARDS患者死亡的独立影响因素(均P0.05)。结论 LUS与ARDS患者APACHEⅡ评分、PaO_2/FiO_2及PEEP密切相关,可作为评估ARDS严重程度的重要指标,且上述指标是患者死亡的独立影响因素。     

Pharmacotherapy of acute lung injury and the acute respiratory distress syndrome

Acute lung injury and the acute respiratory distress syndrome are common syndromes with a high mortality rate that affect both medical and surgical patients. Better understanding of the pathophysiology of acute lung injury and the acute respiratory distress syndrome and advances in supportive care and mechanical ventilation have led to improved clinical outcomes since the syndrome was first described in 1967. Although several promising pharmacological therapies, including surfactant, nitric oxide, glucocorticoids and lysofylline, have been studied in patients with acute lung injury and the acute respiratory distress syndrome, none of these pharmacological treatments reduced mortality. This article provides an overview of pharmacological therapies of acute lung injury and the acute respiratory distress syndrome tested in clinical trials and current recommendations for their use as well as a discussion of potential future pharmacological therapies including beta(2)-adrenergic agonist therapy, keratinocyte growth factor, and activated protein C.     

急性肺损伤/急性呼吸窘迫综合征的药物治疗

急性肺损伤(acute lung injury,ALI)/急性呼吸窘迫综合征(acute respiratory dysfunction syndrome,ARDS)是危重病医学的重要课题,死亡率很高.尽管一些药物治疗包括肺表面活性物质、一氧化氮、糖皮质激素以及利索茶碱已经在ALI/ARDS 患者中应用,但是没有一种药物可降低死亡率.本文综述了ALI/ARDS治疗药物的临床试验结果及其目前推荐应用的等级,同时也就一些有望在未来临床应用的药物,如β2-受体激动剂、角质化细胞生长因子以及活化蛋白-C 进行讨论.     

Epidemiology of acute lung injury and acute respiratory distress syndrome

PURPOSE OF REVIEW: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are diseases with a significant influence in the public health. A better knowledge of their epidemiology could help to improve the outcome of these diseases. RECENT FINDINGS: Although the clinical criteria of the American-European Consensus Conference definitions for ALI and ARDS are simple, there is a risk of misclassification due to a poor reliability. Except for new emerging infectious diseases, such as severe acute respiratory syndrome, the etiology of ALI/ARDS has remained the same for several years. The only recent innovation is the hypothesis that pulmonary ARDS and extrapulmonary ARDS could be different clinical entities. In recent years, there has been a special interest in the study of genetic predisposition to development ALI/ARDS. Recent studies have estimated the incidence of these diseases to be between 15 and 34 cases per 100,000 inhabitants per year. This wide range could stem from differences in the methodology used to calculate the incidence or could be a true variation due to regional differences. Mortality rate of ALI/ARDS have remained steady for several years. Respiratory failure is the cause of the death in less than 20% of the patients. SUMMARY: The epidemiology of ALI and ARDS has some issues to improve, such as the accuracy of the clinical criteria of ALI/ARDS. Future research must to include study of genetic polymorphisms of the mediators involve in the development of ALI/ARDS. Studies to define better the population at risk are necessary to estimate better their true incidence.     

Act fast and ventilate soft: The Düsseldorf hands-on translation of the acute respiratory distress syndrome Berlin definition

Early identification of acute respiratory distress syndrome (ARDS) and forceful implementation of standardized therapy algorithms are the mandatory basis of an effective therapy to improve patient outcome. Recently, a new definition of ARDS was implemented, which simplified the diagnostic criteria for ARDS. Evidence-based therapies are rare, but some cornerstone interventions can be recommended. Lung-protective ventilation with high positive end-expiratory pressure and low tidal volume and early prone positioning in severe cases improve survival rate. We here present an integrated “Düsseldorf hands-on translation” in the form of a “one-page” standard operating procedure in order to fasten and standardize both diagnosis and therapeutic algorithms on an intensive care unit.