血管外肺水的研究进展

血管外肺水（EVLW）是指肺血管腔以外的肺组织含水，包括肺间质含水、肺各种细胞含水以及肺泡腔内表面膜含水。狭义的EVLw仅指肺间质含水。EVLW是研究肺水肿的定量监测指标，可以早期、灵敏、直观地提供肺水肿发生发展及演变的病理过程，有助于指导治疗及预后评估，现将其研究综述如下。     

肺部超声评估血管外肺水研究进展

正常情况下,肺内充满空气,而超声波对空气有强烈的反射作用,因而长期以来肺部是超声检查的盲区。然而病理情况下,如心源性肺水肿时流体静压增高,以及急性呼吸窘迫综合征（acute respiratory distress syndrome,ARDS）时内皮细胞和上皮细胞渗透性增加时,血管外肺水（extravascular lung water,EVLW）增多。此时超声影像可观察到特征性变化。     

血管外肺水:重症临床应用进展

血管外肺水即肺血管外的液体,能够反映肺水肿的严重程度,指导ICU的危重患者液体管理,可以用来评估患者的治疗及预后。为加深对(extravascular lung water,EVLW)的理解及应用,本文着重介绍EVLW在危重症疾病中的监测、临床应用、进展及局限性。     

血管外肺水监测的方法及其临床意义

呼吸困难、咳嗽、咳血性痰、双肺湿性啰音是肺水肿的主要临床症状和体征,但这些临床特征的出现往往提示肺水肿已发展到严重阶段。血管外肺水(extravascular lung water,EVLW)概念的提出可利于     

血管外肺水在鉴别心源性和非心源性呼吸困难的临床价值

目的 通过对心源性和非心源性呼吸困难患者血管外肺水的比较，探讨血管外肺水在鉴别心源性和非心源性呼吸困难时的临床价值。方法对21例呼吸困难的患者根据临床症状及中心静脉压（CVP）值将患者分为二组：心源性呼吸困难组（Ⅰ）和非心源性呼吸困难组（Ⅱ）。入住ICU24h内行PiCCO监测，获取心输出量（CO）、心脏指数（Cl）、中心静脉压（CVP）、血管外肺水（EVLW）、胸腔内血容量（ITBV）、全心舒张末期容量（GEDV）等参数。比较二组间EVLW的差异。结果 1．二组患者年龄、性别、APACHE Ⅱ评分、血白蛋白浓度无显著差异；2．CO、CI，1组显著低于Ⅱ组；3．CVP、EVLW、ITBV、GEDV，1组显著高于Ⅱ组；4．1组EVLW增加与CVP升高呈正相关，与年龄、APACHEⅡ评分、血白蛋白浓度、CO、CI、GEDV均无关。结论心源性呼吸困难患者EVLW增加与CVP升高呈正相关，与血浆白蛋白（Alb）浓度无显著相关性，表明心源性肺水肿是一种高压性水肿；EVLW可以用于鉴别肺水肿类型，用于鉴别心源性呼吸困难和非心源性呼吸困难。     

血管外肺水和胸腔内血容量参数的监测及临床意义

血流动力学监测是重症监护病房(ICU)危重症患者病情评估及抢救治疗中的重要监测手段,其中需要监测的常见指征是肺水肿和心脏前负荷. 相当比例的危重患者治疗过程中,首要目的是维持和改善重要器官的灌注,为了达到这个目的,就需要保证有一定的前负荷,这样就有发生肺水肿的危险[1].肺水肿的危害较大,可能因延误治疗引起呼吸功能不良、心律失常、心力衰竭,甚至引起多器官功能障碍,导致严重后果.因此,及早发现并治疗肺水肿是很必要的.血管外肺水(EVLW)能直观反映肺水肿的存在及严重程度,为及时、准确地发现肺水肿提供依据.心脏前负荷亦称容量负荷,指心肌收缩之前遇到的负荷,即心室舒张期末容积,用传统监测指标中心静脉压(CVP)和肺动脉楔压(PAWP)代替容量监测存在一定局限性,易受心血管顺应性、胸腔内压、瓣膜反流等因素影响,不能准确反映心脏前负荷的变化.因此胸腔内血容量(ITBV)作为心脏前负荷监测指标更敏感,可准确反映容量信息,且可应用于小儿患者[2].     

肺部超声B线征与肺水肿病理的相关性研究

目的探讨肺部超声B线征与肺水肿病理严重程度的相关性。方法20只新西兰兔随机分为对照组5只和实验组15只,实验组经耳缘静脉注射油酸0.12ml/kg,制备肺水肿模型后打开胸腔根据肉眼观察将肺组织分为无病变区、轻度病变区、中度病变区和重度病变区,并于相应区域行直视下肺部超声检查,再分别留取相应的肺组织行病理组织学检查,分析肉眼观病变严重程度、B线数量与肺病理严重程度的相关性。结果随着肉眼观病变严重程度增加,直视下肺部超声B线评分增加(P<0.05),肺病理组织学评分增加(P<0.05);直视下肺部超声B线评分与肉眼观不同病变程度、病理组织学评分相关性高(r值分别为0.893、0.897,P<0.001),肉眼观不同病变程度与病理组织学评分相关性较高(r=0.735,P<0.001)。结论肺部超声B线征可反映肺水肿病理组织学严重程度,可用于半定量评估肺水肿。     

感染性休克患者血管外肺水动态变化与预后的关系

目的 分析感染性休克患者血管外肺水(extravascular lung water,EVLW)的变化特点,试图阐明其与感染性休克预后的关系,并寻找客观评价毛细血管渗漏的指标.方法 采用前瞻没计,同顾性分析的方法,将2007年8月至10月期间,收入法旧路易·巴斯德大学附属民众医院内科ICU并经脉搏指数连续心输出量(PICCO)监护仪测定,其血流动力学特征符合高排低阻型的感染性休克患者,根据患者临床转归分为存活组与死亡组进行对照研究.连续3 d利用PICCO监护仪测定入选患者EVLW的动态变化,并分析其与患者预后的关系.结果 共有20例患者进入本研究,男13例,女7例.年龄48～84岁,平均69.1岁.12例存活患者,8例死亡.人院时两组病例出血乳酸水平外,其他临床资料差异均无统计学意义.两组患者入ICU时EVLW均明显增加[均数分别(19.9±8.0)mL/kg与(18.7±8.1)mL/kg,P＞0.05],目无明显差异.但是,在强化治疗的第2天,存活组患者EVLW开始明显下降,死亡组患者的EVLW仅轻度下降;在两组间EVLW 出现明显差异[均数分别为(13.8±4.5)ML/kg与(18.6±6.3)mL/kg,P＜0.05].治疗后第3大两组患者EVLW 间的差别更加明显[(10.1±2.7)mL/kg与(16.6±6.3)mL/kg,P＜0.05].结论 EVLW的动态变化可用于评估治疗效果和患者预后,同时,也提示EVLW可能是客观评价肺毛细血管渗漏的指标之一.     

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.     

床旁肺超声B线特征在评价急性心源性肺水肿程度及治疗疗效中的作用

目的应用床旁肺超声观察急性心源性肺水肿患者肺超声B线特征及其变化,探讨B线在判断临床病变程度及评估治疗效果中的价值。方法选取19例确诊为急性心源性肺水肿的患者,于治疗前和治疗后2周行床旁肺部12区超声检查(左肺6区和右肺6区),比较治疗前后肺超声评分;应用Pearson相关分析法分析B线出现频率(出现B线的肺扫描区个数)与动脉血氧分压(Pa O2)和血浆脑利钠肽(BNP)水平的相关性。结果所有患者均可观察到两肺弥漫性B线,治疗前后肺超声评分比较差异有统计学意义(7.3±2.4 vs.2.1±1.1,P0.01)。B线出现频率与血浆BNP水平呈正相关(r=0.65),与Pa O2呈负相关(r=-0.73)。结论床旁肺超声B线可有效评估急性心源性肺水肿病变程度和治疗效果。     

Effect of high-dose prednisolone on lung fluid in patients with non-cardiogenic lung edema

The influence of high-dose prednisolone on extravascular lung water (EVLW) was studied in a randomized trial in patients with noncardiac pulmonary edema. The patients were treated every 6 hours for 48 hours with 2 g of prednisolone-hemisuccinate or placebo. In the prednisolone-group (n = 7) EVLW decreased from 16.4 +/- 6.2 before to 11.8 +/- 5.1 ml/kg after treatment (p less than 0.05). Additionally alveolar-arterial oxygen gradient (AaDO2/FiO2), pulmonary vascular resistance and heart rate decreased, while arterial oxygen tension (PaO2/FiO2) and mean arterial pressure increased (p less than 0.05). In the placebo-group (n = 7) EVLW increased slightly from 17.5 +/- 3.1 before to 19.3 +/- 10.3 ml/kg after treatment. Additionally all other parameters did not change significantly in this group. Although no statistical significant difference was found between the two groups of treatment, a decrease in EVLW was observed in all prednisolone-treated patients, whereas a pronounced increase in EVLW was found in 3 placebo-treated patients. Probably, those patients would have benefited from high-dose prednisolone treatment. High-dose prednisolone reduced EVLW and improved hemodynamics and gas exchange in patients with noncardiac pulmonary edema, whereas placebo did not achieve comparable effects. Therefore, high-dose prednisolone appears beneficial in noncardiac pulmonary edema in respect of EVLW, hemodynamics, and gas exchange.     

基于B线的肺部超声评分定量评估肺部疾病研究进展

肺部疾病常伴不同程度肺含水量增加,可致肺水肿及肺实变等。肺部超声(LUS)有助于诊断肺部疾病,B线为其重要征象。LUS评分可根据B线的数目及分布定量评估肺部疾病,有助于监测病情及指导治疗。本文就基于B线的LUS评分定量评估肺部疾病的研究进展进行综述。     

不同液体对急性呼吸窘迫综合征绵羊血流动力学和血管外肺水的影响

目的:探讨贺斯(HES)和林格液对急性呼吸窘迫综合征(ARDS)绵羊血流动力学和血管外肺水(EVLW)变化的影响.方法:利用内毒素静脉注射复制绵羊ARDS模型,补充贺斯(A组)10 mL/kg和林格液(B组)20 mL/kg,分别记录模型时(0 h)、补液后1、2、3 h的心率(HR)、心输出量(CO)、胸腔内血容量(ITBV)、心脏舒张末期容积(GEDV)以及EVLW的变化,并观察不同液体对上述指标的影响.结果:两组HR在模型成功0 min明显升高,补液后下降,两组间无明显差异;补液后A组CO、ITBV升高明显大于B组;两组间各时点平均动脉压(MAP)、中心静脉压(CVP)、肺动脉楔压(PAWP)均无显著差异.两组EVLW成模后均明显升高,补液后2、3 h B组EVLW明显高于A组.结论:HES对血流动力学的影响优于林格液,且不明显增加EVLW和肺水肿程度.     

Acute lung injury, overhydration or both?

Acute lung injury or acute respiratory distress syndrome (ALI/ARDS) in the course of sepsis is thought to result from increased pulmonary capillary permeability and resultant edema. However, when the edema is assessed at the bedside by measuring the extravascular thermal volume by transpulmonary dilution, some ALI/ARDS patients with sepsis may have normal extravascular lung water (EVLW). Conversely, a raised EVLW may be present even when criteria for ALI/ARDS are not met, according to GS Martin and colleagues in this issue of Critical Care. This commentary puts the findings into a broader perspective and focuses on the difficulty, at the bedside, in recognizing and separating various types of pulmonary edema. Some of these forms of edema, classically differentiated on the basis of increased permeability and cardiogenic/hydrostatic factors, may overlap, whereas the criteria for ALI/ARDS may be loose, poorly reproducible, relatively insensitive and nonspecific, and highly therapy-dependent. Overhydration is particularly difficult to recognize. Additional diagnostics may be required to improve the delineation of pulmonary edema so as to redirect or redefine treatment and improve patient morbidity and, perhaps, mortality. Monitoring EVLW by single transpulmonary thermal dilution, for instance, might have a future role in this process.     

床边肺超声B线评价急性心源性肺水肿及治疗疗效

目的：肺间质性病变患者肺超声出现特征性的垂直于胸膜强回声线的“彗星尾”伪像,称为B线。本研究应用床边肺超声观察急性心源性肺水肿患者肺超声B线特征及其变化,探讨B线在临床病变程度判断及治疗效果评价中的价值。方法：19例急诊入院确诊为急性心源性肺水肿患者,均行床边肺部12区超声检查(左肺6区,右肺6区),B线出现频率(出现B线的肺扫描区个数)分别与动脉血氧分压(PaO2),血中脑利钠肽(BNP)水平行相关分析。治疗两周后重复肺超声检查,比较治疗前后B线出现频率。结果：所有患者均可观察到两肺弥漫性B线,出现频率与血浆BNP水平呈正相关(r＝0.65),和PaO2呈负相关(r＝-0.73)。治疗两周后B线出现频率较治疗前明显减低(2.1±1.1 vs 7.3±2.4,p<0.01)。结论：床边肺超声B线可作为有效评估急性心源性肺水肿病变程度及随访治疗效果的简便手段。     

Bedside assessment of extravascular lung water by dilution methods: temptations and pitfalls

OBJECTIVES: To review the advantages and limitations of dilution methods to assess extravascular lung water (EVLW) at the bedside and to discuss the clinical value of EVLW measurements. DATA SOURCE: Experimental and clinical studies were searched in PUBMED by using "extravascular lung water" and "dilution method" as keywords and further selected as studies investigating either the reliability or the clinical usefulness of dilution methods to assess EVLW. Related articles and the reference lists of selected studies were scanned for additional relevant references. CONCLUSIONS: Both the double-indicator (thermo-dye) dilution and the single-indicator (cold saline) dilution methods showed close agreement with gravimetric measurement of EVLW (the reference ex vivo method) and have the advantage of being available at the bedside. Most limitations of dilution methods have been described in experimental conditions and lead to an underestimation of EVLW. These limitations include large pulmonary vascular obstruction, focal lung injury, and lung resection. Dilution methods provide an easy and clinically acceptable estimation of EVLW in most critically ill patients, including those with acute respiratory distress syndrome (ARDS). Assessing EVLW may be useful to predict outcome, to diagnose pulmonary edema, to better characterize patients with ARDS, to guide fluid therapy, and to assess the value of new treatments or ventilatory strategies in patients with pulmonary edema.     

Influence of fluid replacement on extravascular lung water (EVLW) in patients with diabetic ketoacidosis

Fluid replacement is a major issue in the treatment of patients with diabetic ketoacidosis. During this therapy, development of pulmonary edema has been reported and attributed to an increase in pulmonary microvascular pressure and a decrease in colloid-osmotic pressure (COP). Because clinically apparent pulmonary edema is associated with an increase in extravascular lung water (EVLW) and impairment of pulmonary gas exchange, we studied the effect of fluid replacement on EVLW, COP, pulmonary hemodynamics and gas exchange parameters in 8 patients with diabetic ketoacidosis (blood glucose>300 mg/dl, pH<7.1). EVLW was estimated by the thermal-dye technique. All variables were successively determined upon adminssion (A), after initial fluid replacement (IFR), when glucose had fallen below 180 mg/dl, after 8 h of intravenous glucose treatment (G), and after 24 h of total parenteral nutrition (TPN). Despite a total net fluid intake of 6.0±1.61, a significant decrease (p<0.001) in COP from 29.6±5.5 at A to 18.8±2.2 mmHg after TPE and a significant increase (p<0.001) in PCWP from 4±2 at A to 10±3 mmHg after TPE, EVLW remained almost unchanged. EVLW was 5.1±2.8 at A, 5.3±2.1 after IFR, 4.8±1.4 after G, and 5.3±1.7 ml/kg after TPN. However, PaO₂ decreased from 137±17 at A to 87±10 mmHg after TPE (p<0.001), while Q_s/Q_t increased significantly (p<0.05). The alterations in gas exchange may be indicative of pulmonary dysfunction but as they were not associated with accumulation of EVLW, they may as well reflect the compensation of metabolic derangements in diabetic ketoacidosis.     

Correlation of oxygenation with vascular permeability-surface area but not with lung water in humans with acute respiratory failure and pulmonary edema.

We used a single-pass multiple tracer technique to measure cardiac output, extravascular lung water (EVLW) and lung vascular [14C]urea permeability-surface area (PSu) in 14 patients with acute respiratory failure and pulmonary edema. All patients had increased EVLW, but EVLW in the 10 surviving patients (0.26 +/- 0.06 SE ml/ml total lung capacity [TLC]) was not significantly different from that in the five patients who died (0.22 +/- 0.05). EVLW did not correlate with intravascular pressures or with alveolar-arterial oxygen pressure difference (A-aDO2). PSu was lower in surviving patients (0.50 +/- 0.16 SE ml/s X liter TLC) than in patients who died (3.44 +/- 0.36; P less than 0.05) and also lower than in previously reported data in patients with normal PSu. PSu correlated significantly with A-aDO2. Serial studies showed that PSu returned from a low value toward normal in a patient who survived but remained high in a patient who died. We conclude that the amount of edema in the lungs measured by indicator methods was not the principal determinant of either the magnitude of oxygenation defect or survival in the patients studied. We interpret the low PSu in surviving patients as decreased surface area and infer that the ability of the lung circulation to reduce perfusion of damaged and edematous areas was important in preserving oxygenation. A high PSu, presumably reflecting perfusion of areas with increased permeability, was a sign of especially poor prognosis. Multiple tracer techniques for measuring lung vascular PSu may help to define the pathogenesis and to evaluate therapies of acute lung injury in humans. Such measurements may be a more useful clinical tool than measurements of lung water in patients with acute respiratory failure and pulmonary edema.     

Factors associated with increased extravascular lung water in cardiac tamponade and myocardial ischemia.

OBJECTIVE: To evaluate and compare the factors associated with pulmonary edema in cardiac tamponade and myocardial ischemia. DESIGN: Prospective, controlled laboratory study. SETTING: Animal research laboratory of a university hospital. SUBJECTS: Fourteen anesthetized dogs. INTERVENTION: Extravascular lung water (EVLW) was measured with thermal indocyanine green dye double-indicator dilution method and hemodynamic indices were determined by the pulmonary artery flotation catheter. Seven dogs were used in the tamponade model, and seven other dogs were used in the myocardial ischemia model. Furthermore, ten dogs were dedicated to measure plasma colloid osmotic pressure (COP) and blood gas analysis during cardiac tamponade and myocardial ischemia. MEASUREMENTS AND MAIN RESULTS: Mean right atrial pressure (MRAP) (7-->10 mm Hg), pulmonary capillary wedge pressure (PCWP) (10-->13 mm Hg), and EVLW (5.4-->10.1 mL/kg) increased during tamponade, but all of these indices returned to the control level after release of tamponade (MRAP, 7 mm Hg; mean PCWP, 11 mm Hg; mean EVLW, 5.2 mL/kg). Myocardial ischemia caused increases in PCWP (10-->14 mm Hg) and EVLW (5.6-->9.6 mL/kg). Although PCWP returned to the control level, EVLW remained elevated (9.2 mL/kg) after reperfusion. EVLW had good correlations with MRAP (r2 = .64, p < .05) and PCWP (r2 = .62, p < .05) during cardiac tamponade. Despite a fair correlation between EVLW and PCWP during ischemia (r2 = .73, p < .05), EVLW was not related to PCWP after reperfusion. COP decreased during myocardial ischemia and at the reperfusion period, but there was no significant change in COP in the cardiac tamponade model. CONCLUSIONS: In contrast to a close relation between hydrostatic pressure and EVLW in cardiac tamponade, hydrostatic pressure was not a determinant of pulmonary edema during the reperfusion period after myocardial ischemia.