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.     

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.     

Evidence-based management of acute lung injury and acute respiratory distress syndrome

This report explores the efficacy of existing therapies for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), primarily in terms of clinically important outcomes such as the duration of mechanical ventilation and hospital mortality. Of the 15 therapies reviewed, the strongest evidence suggests that ALI/ARDS should be managed with a low-tidal-volume, pressure-limited approach, with either low or moderately high positive end-expiratory pressure. To date there have been few large, sufficiently powered, randomized controlled clinical trials of ALI/ARDS therapies that addressed patient outcomes. However, there is relatively strong evidence to support conservative fluid management and high-fat, anti-oxidant nutritional formulations. Although most pharmacologic ALI/ARDS therapies have been ineffective, high-dose methylprednisolone is indicated in the subgroups of ALI/ARDS patients who have pneumonia or are at risk of ARDS due to fat embolization.     

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.     

Lung ultrasound in acute respiratory distress syndrome and acute lung injury

PURPOSE OF REVIEW: Lung ultrasound at the bedside can provide accurate information on lung status in critically ill patients with acute respiratory distress syndrome. RECENT FINDINGS: Lung ultrasound can replace bedside chest radiography and lung computed tomography for assessment of pleural effusion, pneumothorax, alveolar-interstitial syndrome, lung consolidation, pulmonary abscess and lung recruitment/de-recruitment. It can also accurately determine the type of lung morphology at the bedside (focal or diffuse aeration loss), and therefore it is useful for optimizing positive end-expiratory pressure. The learning curve is brief, so most intensive care physicians will be able to use it after a few weeks of training. SUMMARY: Lung ultrasound is noninvasive, easily repeatable and allows assessment of changes in lung aeration induced by the various therapies. It is among the most promising bedside techniques for monitoring patients with acute respiratory distress syndrome.     

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.     

Peripheral airways injury in acute lung injury/acute respiratory distress syndrome

PURPOSE OF REVIEW: Peripheral airways are less than 2 mm in diameter and comprise a relatively large cross-sectional area, which allows for slower, laminar airflow. They include both membranous bronchioles and gas exchange ducts, and have been referred to in the past as the 'quiet zone', partly because these structures were felt to contribute little to lung mechanics, and partly because they are difficult to study directly. RECENT FINDINGS: Recent studies suggest that peripheral airway dysfunction plays a significant role in acute respiratory distress syndrome, which may be exacerbated by injurious mechanical ventilation strategies. The presence of elevated airways resistance, intrinsic positive end-expiratory pressure or a lower inflection point on a pressure-volume curve of the respiratory system may indicate presence of impaired peripheral airway function. In-vitro animal and human studies have begun to elucidate the signaling mechanisms responsible for stretch and shear mediated cellular injury. SUMMARY: Understanding the pathophysiology of peripheral airway dysfunction in acute respiratory distress syndrome and mechanical ventilation continues to evolve. Greater insight into the signaling mechanisms involved in cellular injury and repair will lead to further alterations in mechanical ventilation strategies, and may lead to specific treatment options.     

Bronchoalveolar hemostasis in lung injury and acute respiratory distress syndrome

Summary. Enhanced intrapulmonary fibrin deposition as a result of abnormal broncho‐alveolar fibrin turnover is a hallmark of acute respiratory distress syndrome (ARDS), pneumonia and ventilator‐induced lung injury (VILI), and is important to the pathogenesis of these conditions. The mechanisms that contribute to alveolar coagulopathy are localized tissue factor‐mediated thrombin generation, impaired activity of natural coagulation inhibitors and depression of bronchoalveolar urokinase plasminogen activator‐mediated fibrinolysis, caused by the increase of plasminogen activator inhibitors. There is an intense and bidirectional interaction between coagulation and inflammatory pathways in the bronchoalveolar compartment. Systemic or local administration of anticoagulant agents (including activated protein C, antithrombin and heparin) and profibrinolytic agents (such as plasminogen activators) attenuate pulmonary coagulopathy. Several preclinical studies show additional anti‐inflammatory effects of these therapies in ARDS and pneumonia.     

Acute lung injury and acute respiratory distress syndrome in pregnancy

Acute respiratory failure can be the result of a variety of clinical conditions, such as congestive heart failure, pneumonia, pulmonary embolism, exacerbation of obstructive lung diseases, and acute respiratory distress syndrome (ARDS). This article focuses on developments related to acute lung injury and ARDS and reviews epidemiology, pathogenesis and therapeutic advances with an emphasis on the obstetric population. A brief discussion of tocolytic-induced pulmonary edema, preeclampsia, venous air embolism, and aspiration-related ARDS is included. Management of pregnant women with ARDS is outlined.     

急性肺损伤/急性呼吸窘迫综合征的困惑与思考

急性肺损伤/急性呼吸窘迫综合征(ALI/ARDS)的认识和治疗虽然已经取得长足的进展,但目前对ALI/ARDS的诊断及治疗仍有较多的困惑,值得思考.诊断方面虽有诊断标准,但仍待改进.治疗方面也存在争议: ①保护性通气策略中潮气量与平台压,哪项更为重要?②最佳呼气末正压(PEEP)的选择,争论已久,尚无定论?③肺复张是否真正有效?④肺水管理:限制性液体策略还是开放性液体策略?     

The epithelium in acute lung injury/acute respiratory distress syndrome

PURPOSE OF REVIEW: The mechanisms of epithelial injury in acute lung injury/acute respiratory distress syndrome have been of interest since the syndrome was first described. Cell therapies to replace injured epithelium are a futuristic dream; however, there is ongoing research to achieve this goal. We review research regarding the function of the epithelium in acute lung injury/acute respiratory distress syndrome, including potential novel therapies. RELEVANT FINDINGS: Altered fluid clearance from the injured lungs in acute lung injury/acute respiratory distress syndrome patients has been consistently found and is an important prognostic finding. New research suggests that neutrophils that enter the lung late and which are enticed into the lung through a specific chemokine system may be important for causing lung injury. If this is the case, then blockers of this system could be a possible therapy. The role of fibrinolysis and coagulation abnormalities in lung injury due to infection and other perturbations is examined. These abnormal findings may be useful diagnostic tools for prognostication as well as targets for future therapies. SUMMARY: Epithelial damage is a hallmark of acute lung injury/acute respiratory distress syndrome. An increased understanding of the function of these cells and of the abnormalities that occur when these lung cells are injured should allow the development of novel therapies and, perhaps, lead to replacement therapies.     

The endothelium in acute lung injury/acute respiratory distress syndrome

PURPOSE OF REVIEW: Since pulmonary edema from increased endothelial permeability is the hallmark of acute lung injury, a frequently encountered entity in critical care medicine, the study of endothelial responses in this setting is crucial to the development of effective endothelial-targeted treatments. RECENT FINDINGS: From the enormous amount of research in the field of endothelial pathophysiology, we have focused on work delineating endothelial alterations elicited by noxious stimuli implicated in acute lung injury. The bulk of the material covered deals with molecular and cellular aspects of the pathogenesis, reflecting current trends in the published literature. We initially discuss pathways of endothelial dysfunction in acute lung injury and then cover the mechanisms of endothelial protection. Several experimental treatments in animal models are presented, which aid in the understanding of the disease pathogenesis and provide evidence for potentially useful therapies. SUMMARY: Mechanistic studies have delivered several interventions, which are effective in preventing and treating experimental acute lung injury and have thus provided objectives for translational studies. Some of these modalities may evolve into clinically useful tools in the treatment of this devastating illness.     

Surfactant therapy for acute lung injury/acute respiratory distress syndrome

PURPOSE OF REVIEW: Currently, three phase III surfactant replacement trials for acute lung injury (ALI)/acute respiratory distress syndromes (ARDS) patients are underway. Although the efficacy of surfactant replacement therapy will first have to be proved in these phase III trials, recent reports indicate some enticing possibilities for the future of surfactant therapy. RECENT FINDINGS: Patients requiring mechanical ventilation show alterations in their endogenous surfactant composition. Depending on the type of lung injury or the elapsed time, modifications to surfactant preparations could enhance the efficacy of these preparations. Surfactants that closely resemble natural surfactant, especially those containing surfactant proteins (SP-B/C) and nonphospholipids (cholesterol), are able to restore normal surfactant physiology. Furthermore, lipids that are able to withstand degradation by lipases could further enhance surfactant therapy. SUMMARY: If surfactant therapy fulfills the promises expected from the ongoing phase III trials, future surfactant preparations may even enhance therapy efficacy and restore the altered endogenous surfactant pool as soon as possible.     

Dynamic versus static respiratory mechanics in acute lung injury and acute respiratory distress syndrome

OBJECTIVES: It is not clear whether the mechanical properties of the respiratory system assessed under the dynamic condition of mechanical ventilation are equivalent to those assessed under static conditions. We hypothesized that the analyses of dynamic and static respiratory mechanics provide different information in acute respiratory failure. DESIGN: Prospective multiple-center study. SETTING: Intensive care units of eight German university hospitals. PATIENTS: A total of 28 patients with acute lung injury and acute respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS: Dynamic respiratory mechanics were determined during ongoing mechanical ventilation with an incremental positive end-expiratory pressure (PEEP) protocol with PEEP steps of 2 cm H2O every ten breaths. Static respiratory mechanics were determined using a low-flow inflation. MAIN RESULTS: The dynamic compliance was lower than the static compliance. The difference between dynamic and static compliance was dependent on alveolar pressure. At an alveolar pressure of 25 cm H2O, dynamic compliance was 29.8 (17.1) mL/cm H2O and static compliance was 59.6 (39.8) mL/cm H2O (median [interquartile range], p < .05). End-inspiratory volumes during the incremental PEEP trial coincided with the static pressure-volume curve, whereas end-expiratory volumes significantly exceeded the static pressure-volume curve. The differences could be attributed to PEEP-related recruitment, accounting for 40.8% (10.3%) of the total volume gain of 1964 (1449) mL during the incremental PEEP trial. Recruited volume per PEEP step increased from 6.4 (46) mL at zero end-expiratory pressure to 145 (91) mL at a PEEP of 20 cm H2O (p < .001). Dynamic compliance decreased at low alveolar pressure while recruitment simultaneously increased. Static mechanics did not allow this differentiation. The decrease in static compliance occurred at higher alveolar pressures compared with the dynamic analysis. CONCLUSIONS: Exploiting dynamic respiratory mechanics during incremental PEEP, both compliance and recruitment can be assessed simultaneously. Based on these findings, application of dynamic respiratory mechanics as a diagnostic tool in ventilated patients should be more appropriate than using static pressure-volume curves.     

Elastic pressure-volume curves in acute lung injury and acute respiratory distress syndrome

Background The principal features of elastic pressure-volume curves of lungs or the respiratory system (P_el/V curves) recorded during reexpansion of collapsed lungs and subsequent deflation have been known since the 1950s. In acute respiratory failure and acute respiratory distress syndrome such curves have recently attracted increasing interest because new knowledge can be acquired from them, and because such curves may be useful as guidelines in setting the ventilator so as to avoid ventilator-induced lung injury.Discussion This article reviews recording methods, underlying physiology and utility of P_el/V curves in research and clinical work.This work was supported by the Swedish Medical Research Council (02872) and by the Swedish Heart Lung Foundation