肺血管通透性指数对急性肺损伤患者的预后价值

目的探讨肺血管通透性指数（PVPI）对急性肺损伤（ALI）患者的预后判断价值。方法收集2010年10月至2013年10月入住重症医学科（ICU）,需要机械通气的64例ALI患者,根据预后分为急性呼吸窘迫综合征（ARDS）组（30例）和非ARDS组（34例）。比较两组患者入组时的心指数、平均中心静脉压（CVPm）、全心舒张末容积指数（GEDVI）、PVPI、血管外肺水指数（EVLWI）、氧合指数和肺损伤评分（LIS）等指标。绘制ROC曲线,根据曲线下面积（AUC）评价PVPI对ARDS的预测价值,最佳诊断临界值评估其敏感性和特异性。结果非ARDS组入组时的PVPI、EVLWI和LIS均显著低于ARDS组（P均〈0.05）,而两组间心指数、CVPm、GEDVI和氧合指数等指标比较差异均无统计学意义（P均〉0.05）。PVPI预测ALI患者发生ARDS的AUC为0.886;最佳诊断临界值为3.10时,敏感度为93.3%,特异度为82.4%。结论 PVPI能早期评估ALI的严重程度,可作为预测ALI患者是否会进展为ARDS的参考指标之一。     

Extravascular lung water determined with single transpulmonary thermodilution correlates with the severity of sepsis-induced acute lung injury

OBJECTIVE: To find out if the extravascular lung water index (EVLWI) and the derived permeability indexes determined by the single transpulmonary thermodilution technique are associated with markers of acute lung injury in human septic shock. DESIGN: Prospective, observational study. SETTING: Mixed intensive care unit of a 900-bed university hospital. PATIENTS: Thirty-eight consecutive adult patients with septic shock and acute lung injury. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The variables were assessed over a 72-hr period and included hemodynamics, EVLWI, and pulmonary vascular permeability indexes determined with the single indicator transpulmonary thermodilution technique, lung compliance, oxygenation ratio (Pao2/Fio2), lung injury score, cell counts, and the plasma concentration of endothelin-1. At day 1, EVLWI was elevated (>or=7 mL/kg) in 28 (74%) patients and correlated with lung compliance (r=-.48, p=.002), Pao2/Fio2 (r=-.50, p=.001), lung injury score (r=.46, p=.004), roentgenogram quadrants (r=.39, p=.02), and platelet count (r=-.43, p=.007). At day 3, EVLWI correlated with compliance (r=-.51, p=.002), Pao2/Fio2 (r=-.49, p = .006), and lung injury score (r=.53, p=.003). At day 3, EVLWI and pulmonary vascular permeability indexes were higher in nonsurvivors (p<.05). The plasma concentration of endothelin-1 (mean+/-sd) was significantly higher in patients with elevated EVLWI (>or=7 mL/kg) (3.85+/-1.40 vs. 2.07+/-0.38 pg/mL, respectively). Twenty-two (59%) patients died before day 28. CONCLUSIONS: In human septic shock, EVLWI demonstrated moderate correlation with markers of acute lung injury, such as lung compliance, oxygenation ratio, roentgenogram quadrants, and lung injury score. In nonsurvivors, EVLWI and permeability indexes were significantly increased at day 3. Thus, EVLWI might be of value as an indicator of prognosis and severity of sepsis-induced acute lung injury.     

Transpulmonary lactate gradient after hypothermic cardiopulmonary bypass

Objective Several studies demonstrated that the lungs could produce lactate in patients with acute lung injury (ALI). Because after cardiopulmonary bypass (CPB) some patients develop ALI, the effect of CPB on pulmonary lactate release was investigated.Design Prospective observational clinical study.Setting Twenty-beds, surgical ICU at a university hospital.Patients Sixteen deeply sedated, ventilated and post-cardiac surgery patients, all equipped with a pulmonary artery catheter.Measurements and results Lactate concentration was measured using a lactate analyser in simultaneously drawn arterial (A) and mixed venous (V) blood samples. Three measurements per patients were taken at 30-min interval, after body temperature reached 37°C. Concomitantly, measurements of cardiac output were also obtained. Pulmonary lactate release was calculated as the product of transpulmonary A-V lactate and cardiac index. The mean cardiopulmonary bypass duration was 100±44 min (SD), and the aortic cross-clamping time was 71±33 min. After CPB, lactate release was 0.136±0.210 mmol/min m^–2. These values were not correlated with cardiopulmonary bypass duration.Conclusion The present study shows that in patients receiving mechanical ventilation after CPB, the lung is a source of lactate production. This pulmonary release was not dependent on cardiopulmonary bypass duration.     

Surfactant therapy for acute lung injury and acute respiratory distress syndrome

This article examines exogenous lung surfactant replacement therapy and its usefulness in mitigating clinical acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). Surfactant therapy is beneficial in term infants with pneumonia and meconium aspiration lung injury, and in children up to age 21 years with direct pulmonary forms of ALI/ARDS. However, extension of exogenous surfactant therapy to adults with respiratory failure and clinical ALI/ARDS remains a challenge. This article reviews clinical studies of surfactant therapy in pediatric and adult patients with ALI/ARDS, focusing on its potential advantages in patients with direct pulmonary forms of these syndromes.     

The impact of clinical risk factors in the conversion from acute lung injury to acute respiratory distress syndrome in severe multiple trauma patients

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are different stages of the same disease, the aggravated stage of ALI leading to ARDS. Patients with ARDS have higher hospital mortality rates and reduced long-term pulmonary function and quality of life. It is, therefore, important to prevent ALI converting to ARDS. This study evaluated 17 risk factors potentially associated with the conversion from ALI to ARDS in severe multiple trauma. The results indicate that the impact of pulmonary contusion, APACHE II score, gastrointestinal haemorrhage and disseminated intravascular coagulation may help to predict conversion from ALI to ARDS in the early phase after multiple-trauma injury. Trauma duration, in particular, strongly impacted the short- and long-term development of ALI. Being elderly (aged > or = 65 years) and undergoing multiple blood transfusions in the early phase were independent risk factors correlated with secondary sepsis, deterioration of pulmonary function and transfusion-related acute lung injury due to early multiple fluid resuscitation.     

Pulmonary coagulopathy as a new target in therapeutic studies of acute lung injury or pneumonia--a review

OBJECTIVES: To review the involvement of coagulation and fibrinolysis in the pathogenesis of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), pulmonary infection, and ventilator-induced lung injury (VILI). DATA SOURCE: Published articles on experimental and clinical studies of coagulation and fibrinolysis in ALI/ARDS, pneumonia, and mechanical ventilation. CONCLUSIONS: Alveolar fibrin deposition is an important feature of ALI/ARDS and pulmonary infection. The mechanisms that contribute to disturbed alveolar fibrin turnover are localized tissue factor-mediated thrombin generation and depression of bronchoalveolar urokinase plasminogen activator-mediated fibrinolysis, caused by the increase of plasminogen activator inhibitors. These effects on pulmonary coagulation and fibrinolysis are regulated by various proinflammatory cytokines and are similar to those found in the intravascular spaces during severe systemic inflammation. Some studies also suggest that pulmonary coagulopathy is a feature of VILI. Recent studies have demonstrated the beneficial effect of anticoagulant therapy in sepsis. Theoretical considerations suggest that this anticoagulant therapy will benefit patients with primary lung pathology including VILI, but clinical studies are needed to examine this hypothesis before such therapy is to be advocated as a standard of care in critically ill patients.     

Airway pressure release ventilation in acute respiratory distress syndrome

Airway pressure release ventilation (APRV) is an alternative mode of ventilation that is increasingly used in patients with acute respiratory failure, acute lung injury (ALI), and acute respiratory distress syndrome (ARDS). Animal and clinical studies have demonstrated that, compared with conventional ventilation, APRV has beneficial effects on lung recruitment, oxygenation, end-organ blood flow, pulmonary vasoconstriction, and sedation requirements. Further studies, however, are required to directly compare APRV to ARDSnet protocol ventilation, specifically in patients with ALI/ARDS, and to determine whether managing ALI/ARDS with APRV will also achieve mortality reduction.     

急性肺损伤病人中性粒细胞凋亡变化的研究

目的　观察急性肺损伤 (ALI)病人中性粒细胞 (PMN)凋亡的发生以及与肺损伤的关系 ,并探讨其临床意义。方法　对 37例符合ALI诊断标准的病人 ,分离纯化肺灌洗液中的PMN ,应用流式细胞术测定PMN凋亡、坏死、存活细胞比例及呼吸瀑发功能的变化 ,设健康对照组 ,并观察与乳酸脱氢酶 (LDH)和胞浆游离Ca2 变化之间的关系。结果　ALI病人肺灌洗液中PMN凋亡比例显著降低 ,2 4h持续在低水平 (P <0 0 5 ,P <0 0 1) ;各检测点活细胞增多 (P <0 0 5 ,P <0 0 1) ;而灌洗液PMN的呼吸瀑发明显升高 ,8h达峰值 ,并持续升高 (P <0 0 1)。灌洗液中LDH水平 2～ 2 4h明显高于正常对照组 (P <0 0 5 ,P<0 0 1) ;PMN胞浆游离Ca2 各检测点显著增高 (P <0 0 5 ,P <0 0 1)。PMN凋亡与LDH水平呈显著相关性 (r =- 0 715 1,P <0 0 1) ;PMN凋亡与胞浆游离Ca2 的浓度有显著的相关性 ( r=- 0 6 0 39,P <0 0 1)。结论　ALI时PMN在肺组织中大量扣押 ,且正常的凋亡途径发生障碍 ,造成PMN持续处于激活状态及毒性内容物的持续释放 ,与肺组织的损伤有密切关系 ,并且PMN凋亡延迟可能与LDH、胞浆游离Ca2 的升高有关     

Extravascular lung water to blood volume ratios as measures of pulmonary capillary permeability in nonseptic critically ill patients

Purpose

The aim of this study is to evaluate the value of extravascular lung water (EVLW) to intrathoracic blood volume, global end-diastolic volume, or pulmonary blood volume ratios as a reflection of pulmonary permeability in nonseptic critically ill patients with or at risk for acute lung injury/acute respiratory distress syndrome (ALI/ARDS).

Methods

Pulmonary permeability was measured by the pulmonary leak index (PLI) for ⁶⁷gallium-labeled transferrin and EVLW and blood volumes by the transpulmonary indicator dilution technique in 20 mechanically ventilated patients, before and after fluid loading, guided by changes in central venous pressure.

Results

Nine (45%) patients had ALI/ARDS according to current criteria. The PLI was high (≥30.0 × 10⁻³/min) in 25% before and 30% after fluid loading. The EVLW was high (≥10 mL/kg) in 10% before and in none after fluid loading and did not increase with fluid loading, whereas blood volumes increased. Before fluid loading, PLI related to EVLW/blood volume ratios (minimum r = 0.48, P = .032). After fluid loading, PLI related to EVLW to pulmonary blood volume or intrathoracic blood volume ratios (minimum r = 0.46, P = .041). The relations were unaffected by fluid loading and pressure forces.

Conclusions

The EVLW/blood volume ratios are determined, at least in part, by moderately increased pulmonary permeability in nonseptic critically ill patients with or at risk for ALI/ARDS, independent of fluid status and pressure forces. Normal ratios may help to exclude high permeability.     

Daily changes of the area of density in the dependent lung region – evaluation using transesophageal echocardiography

OBJECTIVE: To evaluate the daily changes of the area of density using transesophageal echocardiography (TEE) in acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) patients. DESIGN: Retrospective observational study. SETTING: General ICU in a university hospital. PATIENTS: Fifteen patients with ARDS or ALI who underwent TEE examination for more than 5 days. MEASUREMENTS: Densities in the lower left lung region were observed through the descending aorta by TEE. Daily changes of the area of density were evaluated. The areas of density estimated by TEE were compared with those obtained by computed tomography (CT). The relation between the area of density and PaO(2)/FIO(2)was calculated. RESULTS: The area of density in the dependent lung region measured by TEE was 11.1+/-5.7 cm(2) (mean +/- SD) at the mid-esophageal position. The area of density in ARDS patients changed daily from 12.0+/-2.8 cm(2) to 8.5+/-6.7 cm(2).The areas of density evaluated using TEE in the left lung correlated significantly with those estimated using CT ( r=0.72, p<0.01). In addition, we found a significant correlation between PaO(2)/FIO(2) and the area of density estimated by TEE ( r=-0.53, p<0.05). CONCLUSION: Using TEE, we could evaluate daily changes of the area of density in the dependent lung region in the intensive care situation. The areas of density in ARDS patients changed from day to day following the changes of oxygenation.     

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.     

急性肺损伤治疗措施的研究进展

急性肺损伤(acute lung injury,ALI)及其严重形式急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)是临床常见的急危重症,此类患者住院时间长、病死率高,其标志性病理特征为肺部炎症和肺组织结构破坏,主要临床表现为低氧合和低肺顺应性。ALI的发病机制并不是很明确,目前已知氧化应激及炎症反应失控是其发生发展的重要机制。临床上ALI常用治疗手段包括药物和机械通气等综合疗法,但其病死率仍居高不下。新兴的治疗方式如干细胞、分子靶向疗法等已取得一定研究成果,有望成为ALI潜在的可靠治疗方法。     

急性肺损伤患者血清肺表面活性物质蛋白A的变化及其意义

目的；动态观测急性肺损伤虱血清肺表面活性物质蛋白Ａ（ＳＰ－Ａ）的变化，并探讨其临床意义。方法：选择符合ＡＬＩ诊断标准并已给予机械通气治疗的患者２０例，于入组时和出组时抽取静脉血，多数患者在观察期间病情有明显变化时重复抽血，共收集静脉血标本７１例次；并同时记录动脉血气测值和呼吸机参数，计算动脉血氧分压与吸入气氧浓度比值和静态总呼吸顺应性。     

Monitoring of extravascular lung water in patients with severe sepsis

The key objective of the case study was the possibility to monitor the extravascular lung water (EVLW) in severe cases. Twelve mechanically ventilated patients with severe sepsis complicated by septic shock and by an acute lung injury (ALI) were involved in the prospective study. The measurements, performed on days 1 and 3 after the onset of sepsis, comprised hemodynamics, EVLW as assessed by Pulsion PiCCO method, blood gases and severity scores. The EVLW correlated significantly with lung injury score (r = 0.46), oxygenation (r = -0.46) and with pulmonary compliance (r = -0.58) versus the central venous pressure. The EVLW and lung injury scores were found to be essentially higher in non-survivors on day 3. The clinical situations, described in the present article, are indicative of a potential EVLW value applicable to sepsis treatment. Finally, the monitoring of EVLW is a useful tool in the purpose-oriented therapy of sepsis-induced ALI; moreover, the method has an important prognostic value.     

The clinical usefulness of extravascular lung water and pulmonary vascular permeability index to diagnose and characterize pulmonary edema: a prospective multicenter study on the quantitative differential diagnostic definition for acute lung injury/acute respiratory distress syndrome

Introduction

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by features other than increased pulmonary vascular permeability. Pulmonary vascular permeability combined with increased extravascular lung water content has been considered a quantitative diagnostic criterion of ALI/ARDS. This prospective, multi-institutional, observational study aimed to clarify the clinical pathophysiological features of ALI/ARDS and establish its quantitative diagnostic criteria.

Methods

The extravascular lung water index (EVLWI) and the pulmonary vascular permeability index (PVPI) were measured using the transpulmonary thermodilution method in 266 patients with PaO₂/FiO₂ ratio ≤ 300 mmHg and bilateral infiltration on chest radiography, in 23 ICUs of academic tertiary referral hospitals. Pulmonary edema was defined as EVLWI ≥ 10 ml/kg. Three experts retrospectively determined the pathophysiological features of respiratory insufficiency by considering the patients'' history, clinical presentation, chest computed tomography and radiography, echocardiography, EVLWI and brain natriuretic peptide level, and the time course of all preceding findings under systemic and respiratory therapy.

Results

Patients were divided into the following three categories on the basis of the pathophysiological diagnostic differentiation of respiratory insufficiency: ALI/ARDS, cardiogenic edema, and pleural effusion with atelectasis, which were noted in 207 patients, 26 patients, and 33 patients, respectively. EVLWI was greater in ALI/ARDS and cardiogenic edema patients than in patients with pleural effusion with atelectasis (18.5 ± 6.8, 14.4 ± 4.0, and 8.3 ± 2.1, respectively; P < 0.01). PVPI was higher in ALI/ARDS patients than in cardiogenic edema or pleural effusion with atelectasis patients (3.2 ± 1.4, 2.0 ± 0.8, and 1.6 ± 0.5; P < 0.01). In ALI/ARDS patients, EVLWI increased with increasing pulmonary vascular permeability (r = 0.729, P < 0.01) and was weakly correlated with intrathoracic blood volume (r = 0.236, P < 0.01). EVLWI was weakly correlated with the PaO₂/FiO₂ ratio in the ALI/ARDS and cardiogenic edema patients. A PVPI value of 2.6 to 2.85 provided a definitive diagnosis of ALI/ARDS (specificity, 0.90 to 0.95), and a value < 1.7 ruled out an ALI/ARDS diagnosis (specificity, 0.95).

Conclusion

PVPI may be a useful quantitative diagnostic tool for ARDS in patients with hypoxemic respiratory failure and radiographic infiltrates.

Trial registration

UMIN-CTR ID UMIN000003627     

Computed tomography assessment of exogenous surfactant-induced lung reaeration in patients with acute lung injury

Introduction  

Previous randomized trials failed to demonstrate a decrease in mortality of patients with acute lung injury treated by exogenous surfactant. The aim of this prospective randomized study was to evaluate the effects of exogenous porcine-derived surfactant on pulmonary reaeration and lung tissue in patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS).     

Pulmonary endothelium in acute lung injury: from basic science to the critically ill

Background Pulmonary endothelium is an active organ possessing numerous physiological, immunological, and metabolic functions. These functions may be altered early in acute lung injury (ALI) and further contribute to the development of acute respiratory distress syndrome (ARDS). Pulmonary endothelium is strategically located to filter the entire blood before it enters the systemic circulation; consequently its integrity is essential for the maintenance of adequate homeostasis in both the pulmonary and systemic circulations. Noxious agents that affect pulmonary endothelium induce alterations in hemodynamics and hemofluidity, promote interactions with circulating blood cells, and lead to increased vascular permeability and pulmonary edema formation.Objective We highlight pathogenic mechanisms of pulmonary endothelial injury and their clinical implications in ALI/ARDS patients.     

Acute lung injury and the coagulation pathway: potential role of gene polymorphisms in the protein C and fibrinolytic pathways

There is evidence that dysregulation of coagulation and fibrinolysis may participate in the pathogenesis of acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). Altered concentrations of several proteins of the coagulation and fibrinolytic pathways in plasma and pulmonary edema fluid from patients with acute lung injury have been related to the severity of lung injury and clinical outcomes. Polymorphisms in the genes encoding for proteins of the protein C and fibrinolysis pathways are known to regulate the production of the respective proteins. It is plausible that these polymorphisms may be associated with the susceptibility to and severity of illness in ALI and ARDS. Well-designed studies that examine the association of these polymorphisms with susceptibility and severity of ALI and ARDS are needed to test the influence of both genetic and environmental factors on the clinical outcomes in patients with ALI and ARDS. There are several important considerations in the design of these genetic association studies, including selection of candidate genes with the most biological plausibility, definition of the phenotype, selection of appropriate controls, determination of the appropriate sample size and assessment of Hardy–Weinberg equilibrium among controls as a measure of internal validity.