High-frequency oscillatory ventilation with tracheal gas insufflation: the rescue strategy for brain-lung interaction

The occurrence of moderate to severe acute respiratory distress syndrome due to traumatic brain injury is not uncommon and is associated with an extremely high incidence of morbidity and mortality. Owing to the complex interaction between the lung and brain, protective ventilation for the lung with lower tidal volume and higher positive end-expiratory pressure with or without mild hypercapnia might be harmful for the brain, and maintaining normocapnia or mild hypocapnia by increasing tidal volume or respiratory rate (or both) with lower positive end-expiratory pressure levels for protecting the brain might lead to ventilator-induced lung injury. Balancing the end-point between lungs and brain becomes a challenging issue, and non-conventional modes of mechanical ventilation might play a role in the more difficult clinical cases. In this commentary, the authors discuss the rationale, based on the physiologic principle of targeting both vital organs, of applying high-frequency oscillation and tracheal gas insufflation in acute respiratory distress syndrome patients with traumatic brain injury.     

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.     

Bench-to-bedside review: Ventilator strategies to reduce lung injury – lessons from pediatric and neonatal intensive care

As in the adult with acute lung injury and acute respiratory distress syndrome, the use of lung-protective ventilation has improved outcomes for neonatal lung diseases. Animal models of neonatal respiratory distress syndrome and congenital diaphragmatic hernia have provided evidence that 'gentle ventilation' with low tidal volumes and 'open-lung' strategies of using positive end-expiratory pressure or high-frequency oscillatory ventilation result in less lung injury than do the traditional modes of mechanical ventilation with high inflating pressures and volumes. Although findings of retrospective studies in infants with respiratory distress syndrome, congenital diaphragmatic hernia, and persistent pulmonary hypertension of the newborn have been similar to those of the animal studies, prospective, randomized, controlled trials have yielded conflicting results. Successful clinical trial design in these infants and in children with acute lung injury/acute respiratory distress syndrome will require an appreciation of the data supporting the modern ventilator management strategies for infants with lung disease.     

Bench-to-bedside review: Ventilator strategies to reduce lung injury -- lessons from pediatric and neonatal intensive care

As in the adult with acute lung injury and acute respiratory distress syndrome, the use of lung-protective ventilation has improved outcomes for neonatal lung diseases. Animal models of neonatal respiratory distress syndrome and congenital diaphragmatic hernia have provided evidence that 'gentle ventilation' with low tidal volumes and 'open-lung' strategies of using positive end-expiratory pressure or high-frequency oscillatory ventilation result in less lung injury than do the traditional modes of mechanical ventilation with high inflating pressures and volumes. Although findings of retrospective studies in infants with respiratory distress syndrome, congenital diaphragmatic hernia, and persistent pulmonary hypertension of the newborn have been similar to those of the animal studies, prospective, randomized, controlled trials have yielded conflicting results. Successful clinical trial design in these infants and in children with acute lung injury/acute respiratory distress syndrome will require an appreciation of the data supporting the modern ventilator management strategies for infants with lung disease.     

Uneven distribution of ventilation in acute respiratory distress syndrome

As in the adult with acute lung injury and acute respiratory distress syndrome, the use of lung-protective ventilation has improved outcomes for neonatal lung diseases. Animal models of neonatal respiratory distress syndrome and congenital diaphragmatic hernia have provided evidence that 'gentle ventilation' with low tidal volumes and 'open-lung' strategies of using positive end-expiratory pressure or high-frequency oscillatory ventilation result in less lung injury than do the traditional modes of mechanical ventilation with high inflating pressures and volumes. Although findings of retrospective studies in infants with respiratory distress syndrome, congenital diaphragmatic hernia, and persistent pulmonary hypertension of the newborn have been similar to those of the animal studies, prospective, randomized, controlled trials have yielded conflicting results. Successful clinical trial design in these infants and in children with acute lung injury/acute respiratory distress syndrome will require an appreciation of the data supporting the modern ventilator management strategies for infants with lung disease.     

Epidemiology of acute lung injury

PURPOSE OF REVIEW: Acute lung injury and its extreme manifestation, acute respiratory distress syndrome, complicate a wide variety of serious medical and surgical conditions, only some of which affect the lung directly. Despite recent evidence-based advances in clinical management, acute lung injury and acute respiratory distress syndrome are associated with significant mortality. Detailed epidemiology is essential in guiding the recruitment of patients into trials of new therapeutic interventions, thereby improving outcome and allowing directed allocation of scarce resources. RECENT FINDINGS: The incidence of acute lung injury in the United States overall (17-64 per 100,000 person-years) seems to be higher than in Europe, Australia, and other developed countries (17-34 per 100, 000 person-years). The mortality rates for patients with acute respiratory distress syndrome range from 34 to 58%. The hypothesis that pulmonary and extrapulmonary acute respiratory distress syndromes are different disease entities continues to gain momentum. A genetic predisposition to acute respiratory distress syndrome may contribute to its pathogenesis and outcome. SUMMARY: Recent epidemiologic studies of the incidence of acute lung injury and acute respiratory distress syndrome have indicated a similar incidence in developed societies, and they confirm that mortality is falling in comparison with a decade ago. The awaited publication of new consensus guidelines for the definition of acute lung injury and acute respiratory distress syndrome may render new studies necessary.     

Bench-to-bedside review: High-frequency oscillatory ventilation in adults with acute respiratory distress syndrome

Mechanical ventilation is the cornerstone of therapy for patients with acute respiratory distress syndrome (ARDS). Paradoxically, mechanical ventilation can exacerbate lung damage – a phenomenon known as ventilator-induced lung injury. While new ventilation strategies have reduced the mortality rate in patients with ARDS, this mortality rate still remains high. High-frequency oscillatory ventilation (HFOV) is an unconventional form of ventilation that may improve oxygenation in patients with ARDS, while limiting further lung injury associated with high ventilatory pressures and volumes delivered during conventional ventilation. HFOV has been used for almost two decades in the neonatal population, but there is more limited experience with HFOV in the adult population. In adults, the majority of the published literature is in the form of small observational studies in which HFOV was used as 'rescue' therapy for patients with very severe ARDS who were failing conventional ventilation. Two prospective randomized controlled trials, however, while showing no mortality benefit, have suggested that HFOV, compared with conventional ventilation, is a safe and effective ventilation strategy for adults with ARDS. Several studies suggest that HFOV may improve outcomes if used early in the course of ARDS, or if used in certain populations. This review will summarize the evidence supporting the use of HFOV in adults with ARDS.     

Acute respiratory distress syndrome: diagnosis and management

Acute respiratory distress syndrome manifests as rapidly progressive dyspnea, tachypnea, and hypoxemia. Diagnostic criteria include acute onset, profound hypoxemia, bilateral pulmonary infiltrates, and the absence of left atrial hypertension. Acute respiratory distress syndrome is believed to occur when a pulmonary or extrapulmonary insult causes the release of inflammatory mediators, promoting neutrophil accumulation in the microcirculation of the lung. Neutrophils damage the vascular endothelium and alveolar epithelium, leading to pulmonary edema, hyaline membrane formation, decreased lung compliance, and difficult air exchange. Most cases of acute respiratory distress syndrome are associated with pneumonia or sepsis. It is estimated that 7.1 percent of all patients admitted to an intensive care unit and 16.1 percent of all patients on mechanical ventilation develop acute lung injury or acute respiratory distress syndrome. In-hospital mortality related to these conditions is between 34 and 55 percent, and most deaths are due to multiorgan failure. Acute respiratory distress syndrome often has to be differentiated from congestive heart failure, which usually has signs of fluid overload, and from pneumonia. Treatment of acute respiratory distress syndrome is supportive and includes mechanical ventilation, prophylaxis for stress ulcers and venous thromboembolism, nutritional support, and treatment of the underlying injury. Low tidal volume, high positive end-expiratory pressure, and conservative fluid therapy may improve outcomes. A spontaneous breathing trial is indicated as the patient improves and the underlying illness resolves. Patients who survive acute respiratory distress syndrome are at risk of diminished functional capacity, mental illness, and decreased quality of life; ongoing care by a primary care physician is beneficial for these patients.     

Clinical implementation of the ARDS network protocol is associated with reduced hospital mortality compared with historical controls

OBJECTIVE: To assess the impact of implementing a low tidal volume ventilation strategy on hospital mortality for patients with acute lung injury or acute respiratory distress syndrome. DESIGN: Retrospective, uncontrolled study. SETTING: Adult medical-surgical and trauma intensive care units at a major inner city, university-affiliated hospital. PATIENTS: A total of 292 patients with acute lung injury or acute respiratory distress syndrome. INTERVENTIONS: Between the years 2000 and 2003, 200 prospectively identified patients with acute lung injury/acute respiratory distress syndrome were managed by the ARDS Network low tidal volume protocol. A historical control group of 92 acute respiratory distress syndrome patients managed by routine practice from 1998 to 1999 was used for comparison. MEASUREMENTS AND MAIN RESULTS: Patients managed with the ARDS Network protocol had a lower hospital mortality compared with historical controls (32% vs. 51%, respectively; p = .004). Multivariate logistic regression estimated an odds ratio of 0.32 (95% CI, 0.17-0.59; p = .0003) for mortality risk with use of the ARDS Network protocol. Protocol-managed patients had a lower tidal volume (6.2 +/- 1.1 vs. 9.8 +/- 1.5 mL/kg; p < .0001) and plateau pressure (27.5 +/- 6.4 vs. 33.8 +/- 8.9 cm H2O; p < .0001) than historical controls. CONCLUSION: Adoption of the ARDS Network protocol for routine ventilator management of acute lung injury/acute respiratory distress syndrome patients was associated with a lower mortality compared with recent historical controls.     

Nonventilatory interventions in the acute respiratory distress syndrome

Acute respiratory distress syndrome was first described in 1967. Acute respiratory distress syndrome and acute lung injury are diseases the busy intensivist treats almost daily. The etiologies of acute respiratory distress syndrome are many. A significant distinction is based on whether the insult to the lung was direct, such as in pneumonia, or indirect, such as trauma or sepsis. Strategies for managing patients with acute respiratory distress syndrome/acute lung injury can be subdivided into 2 large groups, those based in manipulation of mechanical ventilation and those based in nonventilatory modalities. This review focuses on the nonventlilatory strategies and includes fluid restriction, exogenous surfactant, inhaled nitric oxide, manipulation of production, or administration of eicosanoids, neuromuscular blocking agents, prone position ventilation, glucocorticoids, extracorporeal membrane oxygenation, and administration of beta-agonists. Most of these therapies either have not been studied in large trials or have failed to show a benefit in terms of long-term patient mortality. Many of these therapies have shown promise in terms of improved oxygenation and may therefore be beneficial as rescue therapy for severely hypoxic patients. Recommendations regarding the use of each of these strategies are made, and an algorithm for implementing these strategies is suggested.     

Systematic review of determinants of mortality in high frequency oscillatory ventilation in acute respiratory distress syndrome

Introduction  

Mechanical ventilation has been shown to cause lung injury and to have a significant impact on mortality in acute respiratory distress syndrome. Theoretically, high frequency oscillatory ventilation seems an ideal lung protective ventilation mode. This review evaluates determinants of mortality during use of high frequency oscillatory ventilation.     

Acute respiratory distress syndrome: a clinical update.

BACKGROUND: Because of recent advances in the treatment and improved outcome of acute respiratory distress syndrome (ARDS), we present an overview of ARDS to update general practitioners on the management of this condition. METHODS AND RESULTS: We searched MEDLINE for original articles, editorials, and reviews on ARDS, acute lung injury, and mechanical ventilation. A large amount of data is available on this subject. We reviewed relevant articles that address definition, pathogenesis, clinical presentation, and management of ARDS, giving special emphasis to ventilatory support of patients with ARDS. CONCLUSION: Acute respiratory distress syndrome is a severe form of acute lung injury associated with significant mortality and morbidity. In recent years, significant progress has been made in the understanding of this condition, but the management of ARDS remains complex and requires multidisciplinary and specialized care.     

Surfactant therapy in adults with acute lung injury/acute respiratory distress syndrome

PURPOSE OF REVIEW: Several phase II and phase III studies have been performed to investigate safety, efficacy and the improvement of survival due to exogenous surfactant instillation in patients with acute lung injury or acute respiratory distress syndrome. In this review we will discuss the most recent of these studies, paying particular attention to differences in the composition of the exogenous surfactant used, the diverse modes of delivery and dose of therapy and the influence of mechanical ventilation. RECENT FINDINGS: Several phase II studies performed on patients with acute lung injury or acute respiratory distress syndrome and a phase III study performed on a pediatric population have shown beneficial effects of surfactant on oxygenation and survival. No effect of exogenous surfactant has been shown on survival in phase III studies in adult patients. SUMMARY: The changes in the surfactant system of patients with acute lung injury and acute respiratory distress syndrome form the rationale for the instillation of exogenous surfactant. There is enough evidence to use surfactant instillation for pediatric patients with acute lung injury. Due to the results of the randomized controlled trials performed so far, however, exogenous surfactant is not recommended for routine use in patients with acute lung injury or acute respiratory distress syndrome. In the future, other surfactants with different compositions may show beneficial effects.     

Ventilator strategies for posttraumatic acute respiratory distress syndrome: airway pressure release ventilation and the role of spontaneous breathing in critically ill patients

PURPOSE OF REVIEW: Patients who experience severe trauma are at increased risk for the development of acute lung injury and acute respiratory distress syndrome. The management strategies used to treat respiratory failure in this patient population should be comprehensive. Current trends in the management of acute lung injury and acute respiratory distress syndrome consist of maintaining acceptable gas exchange while limiting ventilator-associated lung injury. RECENT FINDINGS: Currently, two distinct forms of ventilator-associated lung injury are recognized to produce alveolar stress failure and have been termed low-volume lung injury (intratidal alveolar recruitment and derecruitment) and high-volume lung injury (alveolar stretch and overdistension). Pathologically, alveolar stress failure from low- and high-volume ventilation can produce lung injury in animal models and is termed ventilator-induced lung injury. The management goal in acute lung injury and acute respiratory distress syndrome challenges clinicians to achieve the optimal balance that both limits the forms of alveolar stress failure and maintains effective gas exchange. The integration of new ventilator modes that include the augmentation of spontaneous breathing during mechanical ventilation may be beneficial and may improve the ability to attain these goals. SUMMARY: Airway pressure release ventilation is a mode of mechanical ventilation that maintains lung volume to limit intra tidal recruitment /derecruitment and improves gas exchange while limiting over distension. Clinical and experimental data demonstrate improvements in arterial oxygenation, ventilation-perfusion matching (less shunt and dead space ventilation), cardiac output, oxygen delivery, and lower airway pressures during airway pressure release ventilation. Mechanical ventilation with airway pressure release ventilation permits spontaneous breathing throughout the entire respiratory cycle, improves patient comfort, reduces the use of sedation, and may reduce ventilator days.     

Hyperoxic acute lung injury and ventilator-induced/associated lung injury: new insights into intracellular signaling pathways

In patients with acute respiratory distress syndrome (ARDS), supportive therapy with mechanical ventilation and oxygen is often life saving. Further acute lung injury however, is an unfortunate consequence of oxygen therapy as well as mechanical injury secondary to ventilator induced/associated lung injury (VI/ALI). In this issue of Critical Care, Li et al. expand on the intra-cellular signaling pathways regulating interactions between injury cascades resulting from hyperoxia and high tidal volume ventilation. The findings, suggest that interference or cooperation of different signals may have critical consequences as evidenced by indices of increased lung inflammation, microvascular permeability, and lung epithelial apoptotic cell death.     

氯氮平中毒继发急性肺损伤/急性呼吸窘迫综合征的抢救体会

目的:探讨氯氮平中毒继发急性肺损伤/急性呼吸窘迫综合征(ALI/ARDS)有效的治疗方法。方法:总结分析16例氯氮平中毒继发ALI/ARDS患者的临床表现和治疗方法。患者在中毒后6～144h出现ALI/ARDS表现,予气管插管、机械通气,抗胆碱药物治疗及血液灌流等综合治疗。结果:本组患者均治愈,平均住院时间(14±1.6)d;机械通气时间平均(134±12)h,中毒后(48～96)h意识转清。结论:氯氮平中毒继发的急性肺损伤/急性呼吸窘迫综合征主要与肺水肿、吸入性肺炎及氯氮平对肺组织的直接损伤作用有关。早期进行机械通气联合血液灌流和合理抗胆碱药物的,是治疗重度氯氮平重度并发急性肺损伤/急性呼吸窘迫综合征(ALI/ARDS)的有效方法。     

急性呼吸窘迫综合征机械通气中的自主呼吸：兴利除弊

急性呼吸窘迫综合征（ARDS）是重症医学科（ICU）常见危重症。尽管人们不断地探索其诊疗方法,但病死率仍高达40%。肺保护性通气策略指导的机械通气仍是ARDS治疗的基石。ARDS患者接受机械通气时保留适度的自主呼吸有助于塌陷肺泡的复张、改善氧合、预防膈肌功能障碍等。联合有效的监测技术,设置恰当的机械通气模式及参数等措施使患者保持耐受性良好的自主呼吸状态,预防患者自身诱发性肺损伤（P-SILI）,可能是肺保护性通气策略的又一重要组成部分。     

Static pressure-volume curves of the respiratory system: were they just a passing fad?

PURPOSE OF REVIEW: The aim of this article is to describe the physiologic utility, correlation with lung morphology, difficulties in interpretation and current clinical applications of static respiratory system pressure-volume curves at the bedside in patients with acute lung injury or acute respiratory distress syndrome. RECENT FINDINGS: Complex interpretation of pressure-volume curves indicates that alveolar reopening continues past the lower inflection point on the linear part of the curve and suggests the presence of homogeneous lung disease in which recruitment is still possible by positive end-expiratory pressure application. Setting positive end-expiratory pressure above the lower inflection point and tidal ventilation (approximately 6 ml/kg) in the linear portion of the respiratory system pressure-volume curve improved mortality and ameliorated lung and plasma inflammatory mediators compared with ventilation with the lowest positive end-expiratory pressure at traditional tidal volumes. Recent studies have found that regular use of pressure-volume curves provides useful physiological data that help to optimize mechanical ventilation at the bedside. SUMMARY: The physiologic data obtained by measuring the static pressure-volume curves have helped clinicians to better understand the behavior of the respiratory system when positive-pressure ventilation is applied. The advanced technology incorporated into modern ventilators allows routine measurement of pressure-volume curves under sedation without paralysis, with acceptable variability and no serious adverse effects.     

How to set positive end-expiratory pressure

Application of positive end-expiratory pressure (PEEP) in acute lung injury patients under mechanical ventilation improves oxygenation and increases lung volume. The effect of PEEP is to recruit lung tissue in patients with diffuse lung edema. This effect is particularly important in patients ventilated with low tidal volumes. Measurement of respiratory system mechanics in patients with acute respiratory distress syndrome is important to assess the status of the disease and to choose appropriate ventilator settings that provide maximum alveolar recruitment while avoiding overdistention. In patients with acute respiratory distress syndrome in whom the lungs have been near-optimally recruited by PEEP and tidal volume, the use of recruitment maneuvers as adjuncts to mechanical ventilation remains controversial. The application of PEEP in patients with unilateral lung disease may be detrimental if PEEP hyperinflates normal lung regions, thus directing blood flow to diseased lung regions. In patients with air flow limitation and lung hyperinflation, the application of additional external PEEP to compensate for intrinsic PEEP and flow limitation frequently decreases the inspiratory effort to initiate an assisted breath, thus decreasing breathing work load.     

Science review: mechanisms of ventilator-induced injury

Acute respiratory distress syndrome (ARDS) and acute lung injury are among the most frequent reasons for intensive care unit admission, accounting for approximately one-third of admissions. Mortality from ARDS has been estimated as high as 70% in some studies. Until recently, however, no targeted therapy had been found to improve patient outcome, including mortality. With the completion of the National Institutes of Health-sponsored Acute Respiratory Distress Syndrome Network low tidal volume study, clinicians now have convincing evidence that ventilation with tidal volumes lower than those conventionally used in this patient population reduces the relative risk of mortality by 21%. These data confirm the long-held suspicion that the role of mechanical ventilation for acute hypoxemic respiratory failure is more than supportive, in that mechanical ventilation can also actively contribute to lung injury. The mechanisms of the protective effects of low tidal volume ventilation in conjunction with positive end expiratory pressure are incompletely understood and are the focus of ongoing studies. The objective of the present article is to review the potential cellular mechanisms of lung injury attributable to mechanical ventilation in patients with ARDS and acute lung injury.