乌司他丁对急性肺损伤/急性呼吸窘迫综合征的治疗研究

目的研究大剂量乌司他丁在急性肺损伤/急性呼吸窘迫综合征中的治疗效果。方法回顾性分析2006年1月至2010年1月广西医科大学第一附属医院ICU收治的154例ALI/ARDS患者的临床资料,根据治疗方案分为乌司他丁组(UTI组)(n=80),对照组(n=74)。记录两组患者开始治疗、治疗第3天、治疗第7天的生命体征、动脉血气分析、血生化检查结果;记录患者在ICU治疗的转归。应用SPSS 13.0软件对结果进行统计学分析。结果经治疗3天UTI组呼吸频率低于对照组;动脉血气分析提示两组患者PaO2、PaO2/Fi O2、SaO2均有上升,UTI组PaO2/Fi O2略低于对照组(P0.01),而两组患者PaO2、SaO2比较无统计学差异。UTI组与对照组的死亡率比较(UTI组52.5%,对照组52.7%,P=0.980)无统计学差异,机械通气时间UTI组低于对照组[UTI组(14.8±3.9)天,对照组(16.7±4.2)天,P=0.020]。根据ALI/ARDS发生的病因分为肺内源性及肺外源性进行亚组分析(A组:肺内源性ALI/ARDS,使用UTI治疗;B组:肺内源性ALI/ARDS,不使用UTI治疗;C组:肺外源性ALI/ARDS,使用UTI治疗;D组:肺外源性ALI/ARDS,不使用UTI治疗),发现乌司他丁对肺外源性ALI/ARDS患者(C组)的ICU时间、ICU内死亡率及机械通气时间均低于不使用UTI的患者(D组)。结论大剂量乌司他丁用于ALI/ARDS的临床治疗可有效改善患者氧合指数,减少机械通气时间,且高血糖的发生率低,尤其是乌司他丁治疗肺外源性ALI/ARDS患者的预后优于肺内源性的ALI/ARDS。     

肺损伤的干细胞治疗

急性肺损伤(acute lung injury,ALI)是一种起病迅速的非心源性、双肺炎症浸润综合征,晚期进展至高致死性急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS),是重症患者死亡的第一杀手。ALI/ARDS病理特征:肺泡-毛细血管受损,炎性、嗜中性粒细胞积累,释放炎性细胞因子致弥漫性肺损害,剧烈炎症反应导致肺结构畸形,通气受限、阻碍气体交换、限制患者运动、降低生活质量及住院病人转归。ALI/ARDS病死率50%,成年人病死率高达22%,目前尚无有效纠正难治性低氧血症、持续性呼吸衰竭的治疗方法。ALI/ARDS患者需终生依赖机械通气,住院病人对机械通气的敏感性多器官功能最终发生障碍,提高政府医疗财务成本。治疗潜力强大的间充质干细胞(mesenchymal stem cells,MSC),可从胎儿的肺、脂肪、脐索和成人骨髓获得。MSC治疗ALI/ARDS的关键在于旁分泌可溶性细胞因子:调节免疫应答同时改变上皮、内皮对损伤的反应。此文就干细胞治疗肺损伤的核心机制及其突出特点进行综述。     

急性肺损伤中IL-6/GP130/STAT3信号通路的研究进展

正急性肺损伤(ALI)/急性呼吸窘迫综合征(ARDS)是由多种效应细胞、炎性介质共同参与,并呈现出级联放大的继发性弥漫性肺实质损伤和瀑布样炎症继发性损伤。据统计[1],ALI/ARDS的病死率在26%~35%,其致病环节众多、发病机制复杂、病因多元化,已成为临床危重病学研究的难点和热点问题。近年来,IL-6/GP130/STAT3信号通路靶向治疗急性肺损伤已成为了研究热点,为急性肺损伤患者提供了一种新的治疗方式,也为急性肺损伤患者带来新的希望。本文就IL-6/GP130/STAT3信号通路在急性肺损伤治     

肺泡表面活性物质(PS)对盐酸吸人性肺损伤的治疗进展

急性肺损伤/急性呼吸窘迫综合征(Au/ARDS)是临床上常见的危重症,治疗措施包括机械通气及药物综合治疗.肺泡表面活性物质(PS)在维持正常的肺功能起着重要作用,业已证明,PS异常与ALI/ARDS的发病有关,给予外源性PS亦可治疗ALI/ARDS.本文就外源性PS在盐酸吸入性AU/ARDS的第二时相中的疗效及其可能的作用机制做一综述.     

肺泡表面活性物质（PS）对盐酸吸入性肺损伤的治疗进展

急性肺损伤／急性呼吸窘迫综合征（ALI/ARDS）是临床上常见的危重症,治疗措施包括机械通气及药物综合治疗。肺泡表面活性物质（PS）在维持正常的肺功能起着重要作用,业已证明,PS异常与ALI／ARDS的发病有关,给予外源性PS亦可治疗ALI／ARDS。本文就外源性PS在盐酸吸入性ALI／ARDS的第二时相中的疗效及其可能的作用机制做一综述。     

间充质干细胞通过旁分泌治疗急性肺损伤的机制

近年来急性肺损伤(acute lung injury,ALI)/急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS),病死率高达40%,越来越得到临床及科研工作者的重视。ALI/ARDS发病终末阶段,患者临床表现持续性难治性呼吸困难,依赖机械通气从而并发敏感性多器官功能障碍,最终死于呼吸衰竭。而降低肺损伤严重程度的药物疗法,至今尚未转化为临床治疗的可选择手段,因此仍需进行大量实验研究,开发安全、高效的治疗药物及诊疗方法。面对这一亟待解决、威胁全人类的健康问题,中外研究者在动物实验中发现干细胞可以根据需要,选择性修复身体受伤部位,来源广泛的间充质干细胞将有望成为人体损伤器官修复的最新"工具箱"。尽管面对ALI/ARDS持续升高的病死率,我们仍然有信心寄希望于干细胞组织修复的治疗技术。     

严重多发伤合并ARDS患者的呼吸机治疗

目的探讨严重多发伤合并急性呼吸窘迫综合征(ARDS)患者的呼吸机治疗效果。方法回顾性分析我院EICU 30例严重多发伤合并ARDS患者应用呼吸机治疗前后的血气分析。结果 30例严重多发伤患者EICU住院时间3~28天,其中死亡5例,死亡原因为脑疝形成3例、失血性休克并弥漫性血管内凝血1例、多器官功能障碍综合征(MODS)1例。多数患者在加强治疗原发伤的基础上,采用肺保护性较低潮气量机械通气、限制性液体复苏、控制系统性炎症反应等综合治疗的效果较好。结论严重多发伤合并ARDS患者早期、及时气管插管或气管切开通畅气道,采取肺保护性通气策略是提高治愈率和减少并发症的关键,可有效降低严重多发伤合并ARDS的致死率,提高生存率和治愈率。     

肺表面活性物质的临床应用研究进展

国内外研究表明,肺表面活性物质(pulmonary surfactant,PS)异常与急性肺损伤/急性呼吸窘迫综合征(ALI/ARDS)的发生、发展关系密切。因此,临床上对外源性肺表面活性物质制剂的替代疗法也日益重视。本文就肺表面活性物质的功能、急性肺损伤后的变化及其治疗急性肺损伤的相关研究作一综述。     

肠道菌群与急性肺损伤/急性呼吸窘迫综合征的关系

肠道和肺部具备相似的黏膜结构、生理功能和免疫功能。胃肠道和呼吸道黏膜菌群紊乱影响肠道疾病和急性肺损伤/急性呼吸窘迫综合征(acute lung injury/acute respiratory distress syndrome,ALI/ARDS)发展和预后。当肠道微生物群失调时会导致肠道炎症的发生,诱发肠道免疫反应并增加肠黏膜上皮的通透性,细菌及炎症因子经肠-肺轴或其他路径引发肺部疾病,致使组织器官缺血缺氧,造成肺部疾病预后不良。本文将重点关注肠道菌群失调与ALI/ARDS的关系,阐述肠道菌群失调引发的肠道和肺部慢性炎症,为肠道菌群失调引发肺部疾病的原因及其内在机制的研究提供新思路,为后续治疗提供新的线索。     

中性粒细胞胞外诱捕网与急性肺损伤

中性粒细胞胞外诱捕网(NET)有助机体抵抗病原体入侵。研究表明NET与许多疾病的病理过程有关,包括肺部疾病。急性肺损伤(ALI)或急性呼吸窘迫综合征(ARDS),以及肺部的细菌、病毒、真菌感染都发现了NET。病原体和宿主因素刺激NET形成。NET的某些组分具有免疫原性,且能损伤宿主组织。形成与清除NET之间的平衡是有效杀灭病原体而损伤最小化所必需的,发现与开发调节NET形成与清除的物质有助于设计ALI/ARDS治疗方案。     

乌司他丁与沐舒坦治疗严重烧伤伴吸入性损伤的疗效分析

目的:探讨严重烧伤伴中重度吸入性损伤患者早期联合使用大剂量乌司他丁与沐舒坦的临床疗效。方法:选择2003年5月~2013年5月在我院接受治疗的185例严重烧伤伴中重度吸入性损伤患者,随机分为两组,治疗组93例,对照组92例。两组患者在确诊为中重度吸入性损伤后,立即给予传统常规治疗:吸氧、视情尽早预防性气管切开、湿化气道及气道灌洗、翻身拍背吸痰、呼吸机辅助呼吸等。治疗组在常规治疗的基础上给予乌司他丁40万单位,每隔8h静脉滴注,沐舒坦450 mg,每隔12h微泵静推;对照组给予乌司他丁10万单位,每隔8h静滴,沐舒坦30 mg,每隔8h静滴,疗程为10天,比较两组患者急性肺损伤(ALI)的发生率、急性呼吸窘迫综合征(ARDS)的发生率、呼吸机使用时间、死亡率。结果:治疗组93例患者,治愈92例,死亡1例,死亡率为1.08%(1/93),治疗过程中发生ALI34例,ARDS12例,呼吸机使用时间为(4.2±2.1)d。对照组92例患者治愈88例,死亡4例,死亡率率为4.35%(4/92),治疗过程中发生ALI43例,ARDS17例,呼吸机使用时间为(8.2±2.7)d。两组患者ALI发生率、ARDS发生率、呼吸机使用时间、治愈率差异均有统计学意义(P0.05)。结论:对于严重烧伤伴中重度吸入性损伤的患者,在气管切开的前提下,给予常规传统治疗的同时,采用大剂量乌司他丁与沐舒坦早期联合使用给药,能够明显的提高治愈率,降低并发症,值得在临床上广泛推广应用。     

Biomarkers for oxidative stress in acute lung injury induced in rabbits submitted to different strategies of mechanical ventilation

Oxidative damage has been said to play an important role in pulmonary injury, which is associated with the development and progression of acute respiratory distress syndrome (ARDS). We aimed to identify biomarkers to determine the oxidative stress in an animal model of acute lung injury (ALI) using two different strategies of mechanical ventilation. Rabbits were ventilated using either conventional mechanical ventilation (CMV) or high-frequency oscillatory ventilation (HFOV). Lung injury was induced by tracheal saline infusion (30 ml/kg, 38°C). In addition, five healthy rabbits were studied for oxidative stress. Isolated lymphocytes from peripheral blood and lung tissue samples were analyzed by alkaline single cell gel electrophoresis (comet assay) to determine DNA damage. Total antioxidant performance (TAP) assay was applied to measure overall antioxidant performance in plasma and lung tissue. HFOV rabbits had similar results to healthy animals, showing significantly higher antioxidant performance and lower DNA damage compared with CMV in lung tissue and plasma. Total antioxidant performance showed a significant positive correlation (r = 0.58; P = 0.0006) in plasma and lung tissue. In addition, comet assay presented a significant positive correlation (r = 0.66; P = 0.007) between cells recovered from target tissue and peripheral blood. Moreover, antioxidant performance was significantly and negatively correlated with DNA damage (r = -0.50; P = 0.002) in lung tissue. This study indicates that both TAP and comet assay identify increased oxidative stress in CMV rabbits compared with HFOV. Antioxidant performance analyzed by TAP and oxidative DNA damage by comet assay, both in plasma, reflects oxidative stress in the target tissue, which warrants further studies in humans.     

Pressure and volume limited ventilation for the ventilatory management of patients with acute lung injury: a systematic review and meta-analysis

Background

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life threatening clinical conditions seen in critically ill patients with diverse underlying illnesses. Lung injury may be perpetuated by ventilation strategies that do not limit lung volumes and airway pressures. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing pressure and volume-limited (PVL) ventilation strategies with more traditional mechanical ventilation in adults with ALI and ARDS.

Methods and Findings

We searched Medline, EMBASE, HEALTHSTAR and CENTRAL, related articles on PubMed™, conference proceedings and bibliographies of identified articles for randomized trials comparing PVL ventilation with traditional approaches to ventilation in critically ill adults with ALI and ARDS. Two reviewers independently selected trials, assessed trial quality, and abstracted data. We identified ten trials (n = 1,749) meeting study inclusion criteria. Tidal volumes achieved in control groups were at the lower end of the traditional range of 10–15 mL/kg. We found a clinically important but borderline statistically significant reduction in hospital mortality with PVL [relative risk (RR) 0.84; 95% CI 0.70, 1.00; p = 0.05]. This reduction in risk was attenuated (RR 0.90; 95% CI 0.74, 1.09, p = 0.27) in a sensitivity analysis which excluded 2 trials that combined PVL with open-lung strategies and stopped early for benefit. We found no effect of PVL on barotrauma; however, use of paralytic agents increased significantly with PVL (RR 1.37; 95% CI, 1.04, 1.82; p = 0.03).

Conclusions

This systematic review suggests that PVL strategies for mechanical ventilation in ALI and ARDS reduce mortality and are associated with increased use of paralytic agents.     

乌司他丁与沭舒坦治疗严重烧伤伴吸人性损伤的疗效分析

目的：探讨严重烧伤伴中重度吸入性损伤患者早期联合使用大剂量乌司他丁与沐舒坦的临床疗效。方法：选择2003年5月-2013年5月在我院接受治疗的185例严重烧伤伴中重度吸入性损伤患者,随机分为两组,治疗组93例,对照组92例。两组患者在确诊为中重度吸入性损伤后,立即给予传统常规治疗：吸氧、视情尽早预防性气管切开、湿化气道及气道灌洗、翻身拍背吸痰、呼吸机辅助呼吸等。治疗组在常规治疗的基础上给予乌司他丁40万单位,每隔8h静脉滴注,沐舒坦450mg,每隔12h微泵静推;对照组给予乌司他丁10万单位,每隔8h静滴,沐舒坦30mg,每隔8h静滴,疗程为10天,比较两组患者急性肺损伤（Au）的发生率、急性呼吸窘迫综合征（ARDS）的发生率、呼吸机使用时间、死亡率。结果：治疗组93例患者,治愈92例,死亡1例,死亡率为1．08％（1／93）,治疗过程中发生AL134例,ARDS12例,呼吸机使用时间为（4．2±2．1）d。对照组92例患者治愈88例,死亡4例,死亡率率为4．35％（4／92）,治疗过程中发生AL143例,ARDS17例,呼吸机使用时间为（8．2±2．7）d。两组患者ALI发生率、ARDS发生率、呼吸机使用时间、治愈率差异均有统计学意义（P〈0．05）。结论：对于严重烧伤伴中重度吸入性损伤的患者,在气管切开的前提下,给予常规传统治疗的同时,采用大剂量乌司他丁与沐舒坦早期联合使用给药,能够明显的提高治愈率,降低并发症,值得在临床上广泛推广应用。     

Acute effects of caffeine and cigarette smoking on ventricular long-axis function in healthy subjects

Background

Differential diagnosis between acute cardiogenic pulmonary edema (APE) and acute lung injury/acute respiratory distress syndrome (ALI/ARDS) may often be difficult. We evaluated the ability of chest sonography in the identification of characteristic pleuropulmonary signs useful in the diagnosis of ALI/ARDS and APE.

Methods

Chest sonography was performed on admission to the intensive care unit in 58 consecutive patients affected by ALI/ARDS or by acute pulmonary edema (APE).

Results

Ultrasound examination was focalised on finding in the two groups the presence of: 1) alveolar-interstitial syndrome (AIS) 2) pleural lines abnormalities 3) absence or reduction of "gliding" sign 4) "spared areas" 5) consolidations 6) pleural effusion 7) "lung pulse". AIS was found in 100% of patients with ALI/ARDS and in 100% of patients with APE (p = ns). Pleural line abnormalities were observed in 100% of patients with ALI/ARDS and in 25% of patients with APE (p < 0.0001). Absence or reduction of the 'gliding sign' was observed in 100% of patients with ALI/ARDS and in 0% of patients with APE. 'Spared areas' were observed in 100% of patients with ALI/ARDS and in 0% of patients with APE (p < 0.0001). Consolidations were present in 83.3% of patients with ALI/ARDS in 0% of patients with APE (p < 0.0001). A pleural effusion was present in 66.6% of patients with ALI/ARDS and in 95% of patients with APE (p < 0.004). 'Lung pulse' was observed in 50% of patients with ALI/ARDS and in 0% of patients with APE (p < 0.0001). All signs, except the presence of AIS, presented a statistically significant difference in presentation between the two syndromes resulting specific for the ultrasonographic characterization of ALI/ARDS.

Conclusion

Pleuroparenchimal patterns in ALI/ARDS do find a characterization through ultrasonographic lung scan. In the critically ill the ultrasound demonstration of a dyshomogeneous AIS with spared areas, pleural line modifications and lung consolidations is strongly predictive, in an early phase, of non-cardiogenic pulmonary edema.     

Elevation of KL-6, a lung epithelial cell marker,in plasma and epithelial lining fluid in acute respiratory distress syndrome

KL-6 is a pulmonary epithelial mucin more prominently expressed on the surface membrane of alveolar type II cells when these cells are proliferating, stimulated, and/or injured. We hypothesized that high levels of KL-6 in epithelial lining fluid and plasma would reflect the severity of lung injury in patients with acute lung injury (ALI). Epithelial lining fluid was obtained at onset (day 0) and day 1 of acute respiratory distress syndrome (ARDS)/ALI by bronchoscopic microsampling procedure in 35 patients. On day 0, KL-6 and albumin concentrations in epithelial lining fluid were significantly higher than in normal controls (P < 0.001), and the concentrations of KL-6 in epithelial lining fluid (P < 0.002) and in plasma (P < 0.0001) were higher in nonsurvivors than in survivors of ALI/ARDS. These observations were corroborated by the immunohistochemical localization of KL-6 protein expression in the lungs of nonsurvivors with ALI and KL-6 secretion from cultured human alveolar type II cells stimulated by proinflammatory cytokines. Because injury to distal lung epithelial cells, including alveolar type II cells, is important in the pathogenesis of ALI, the elevation of KL-6 concentrations in plasma and epithelial lining fluid could be valuable indicators for poor prognosis in clinical ALI.     

Posttraumatische Belastungsstörung nach ARDS und septischem Schock

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) define medical conditions of acute respiratory insufficiency deriving from direct and indirect damage of the alveolar parenchyma and often associated with multiorgan dysfunction (MODS). As a rule, intensive care is based on mechanical ventilation often requiring high doses of sedatives and narcotics. Despite major progress in intensive care medicine the rate of mortality is still very high. Whereas in the past the level of medical progress has been rated based on the mortality rate alone, the many negative somatic and psychological sequelae in long-term-survivors of ARDS are only now being appreciated. From a perspective of C/L psychiatry persisting cognitive dysfunctions, anxiety and mood disorders, posttraumatic stress disorders (PTSD) in their negative impact on health-related quality of life are intensively investigated. In the etiopathogenesis of PTSD associated with ALI/ARDS, many influences have to be discussed, e.g., increases in CO₂ triggering panic affects, a mismatch of norepinephric overstimulation and cortisol insufficiency, negative effects of high doses of benzodiazepines resulting in oversedation, prolonged phases of weaning and more frequent states of delirium. Consolidation and retrieval of traumatic memories of the ICU stay are influenced by complex factors. From a clinical point of view prophylactic stress doses of hydrocortisone may reduce the major risk of PTSD associated with ALI / ARDS.     

Protective effect of purinergic agonist ATPgammaS against acute lung injury

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are major causes of acute respiratory failure associated with high morbidity and mortality. Although ALI/ARDS pathogenesis is only partly understood, pulmonary endothelium plays a major role by regulating lung fluid balance and pulmonary edema formation. Consequently, endothelium-targeted therapies may have beneficial effects in ALI/ARDS. Recently, attention has been given to the therapeutic potential of purinergic agonists and antagonists for the treatment of cardiovascular and pulmonary diseases. Extracellular purines (adenosine, ADP, and ATP) and pyrimidines (UDP and UTP) are important signaling molecules that mediate diverse biological effects via cell-surface P2Y receptors. We previously described ATP-induced endothelial cell (EC) barrier enhancement via a complex cell signaling and hypothesized endothelial purinoreceptors activation to exert anti-inflammatory barrier-protective effects. To test this hypothesis, we used a murine model of ALI induced by intratracheal administration of endotoxin/lipopolysaccharide (LPS) and cultured pulmonary EC. The nonhydrolyzed ATP analog ATPgammaS (50-100 muM final blood concentration) attenuated inflammatory response with decreased accumulation of cells (48%, P < 0.01) and proteins (57%, P < 0.01) in bronchoalveolar lavage and reduced neutrophil infiltration and extravasation of Evans blue albumin dye into lung tissue. In cell culture model, ATPgammaS inhibited junctional permeability induced by LPS. These findings suggest that purinergic receptor stimulation exerts a protective role against ALI by preserving integrity of endothelial cell-cell junctions.