Respiratory failure

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common causes of hypoxemic respiratory failure. Multiple etiologies lead to direct and indirect pulmonary injury that progresses through an acute exudative phase, fibroproliferative phase, and recovery phase. Inflammatory mechanisms are thought to play a predominant role in the pathophysiology of ALI/ARDS. Mechanical ventilation with a lower tidal volume and an inspiratory plateau pressure of < or = 30 cm H2O is one intervention that has demonstrated a reduction in mortality. A clinical trial to determine the role of restrictive versus liberal fluid management is underway. Inhaled nitric oxide has been used to improve oxygenation but has not resulted in any outcome benefit. Glucocorticoids may be beneficial in the fibroproliferative phase of lung injury by suppressing chronic inflammation. Rigorous clinical trials of new and established interventions are required to determine optimum therapy and reduce mortality in ALI/ARDS.     

Surfactant Treatment for Congenital Heart Disease Patients with Acute Respiratory Distress Syndrome

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) can be a significant source of morbidity for pediatric cardiac patients in the intensive care unit. Children with unrepaired or palliated congenital heart disease are at increased risk for lower respiratory tract infections, while postoperatively they are at risk for ALI/ARDS precipitated by cardiopulmonary bypass. Surfactant dysfunction and inactivation are key contributors to the pathophysiology of ALI/ARDS, and there is growing evidence that exogenous intratracheal surfactant administration in noncardiac patients may ameliorate the lung injury seen in children with ALI/ARDS, leading to improved outcomes and survival. Evidence for a beneficial effect of exogenous surfactant treatment in congenital heart disease patients with ALI/ARDS is lacking. We present three consecutive children with congenital heart disease and ARDS who had significant and sustained improvement in lung function and oxygenation after treatment with exogenous surfactant, hastening their recovery from life-threatening hypoxemia.     

Conventional mechanical ventilation in acute lung injury and acute respiratory distress syndrome

Acute lung injury and acute respiratory distress syndrome are inflammatory conditions involving a broad spectrum of lung injury from mild respiratory abnormality to severe respiratory derangement. Regardless of cause (direct or indirect lung injury), pulmonary physiology and mechanics are altered, leading to hypoxemic respiratory failure. the use of positive pressure ventilation itself may cause lung injury (ventilator-induced lung injury, or VILI). VILI may amplify preexisting injury, delay lung recovery, and result in adverse outcomes. This article examines the evidence supporting lung-protective ventilation strategies and addresses the methods, outcomes, and potential obstacles to implementation of such approaches.     

High-frequency oscillatory ventilation in pediatric patients

HFOV is a mode of ventilation that can achieve oxygenation and ventilation while maintaining maximal lung recruitment on the deflation limb of its pressure-volume curve. The primary theoretical advantages of HFOV over CMV in the management of acute lung injury are that HFOV allows adequate alveolar ventilation with minimal peak-trough pressure changes, provides lung recruitment, and avoids end-inspiratory overdistension of the relatively compliant nondependent lung. Taken together, the results of studies in animals, preterm and term neonates, and older pediatric patients reveal that an "open-lung" strategy, with the goal of a high end-expiratory lung volume, is safe and superior to CMV in both the short-term (rapidly improved oxygenation and/or ventilation) and longer-term (lower incidence of chronic lung disease). The improved longer-term clinical outcomes on HFOV are presumably because of less ventilator-induced lung injury. As experience with HFOV in older patients grows, ventilator technology matures, and understanding of the pathophysiology of acute respiratory distress syndrome (RDS) deepens, it is likely that HFOV will find widespread use for the management of respiratory failure caused by acute lung injury in patients from preterm neonates to adults.     

Therapy for late-phase acute respiratory distress syndrome

Prolonged hypoxemic respiratory failure and evidence of lung organization and fibrosis are features of an ARDS subgroup that is variably identified as "late," "persistent," or "fibroproliferative" ARDS. Early reports suggested that patients with late ARDS had a high mortality unless treated with corticosteroids. A large recent study with improved methodology has demonstrated that despite improvements of pulmonary physiology, corticosteroids do not change mortality of patients who continue to meet ARDS criteria 7 to 28 days after onset of acute lung injury. Additionally, there is no compelling evidence that persistent ARDS confers a higher mortality than that of ALI/ARDS. Observational and interventional studies are needed to increase understanding of the incidence, best management, and outcomes of patients with persistent ARDS.     

Intensive care management of life-threatening avian influenza A (H5N1)

A large proportion of patients with avian influenza A (H5N1) develop life-threatening manifestations, often including ARDS, acute renal failure and multiple organ failure that requires aggressive intensive care management. The pace of development of respiratory failure is often rapid and can occur in previously healthy hosts, mandating close observation and timely intervention of infected individuals. Use of standard, contact, droplet and airborne isolation precautions is recommended to protect healthcare workers. Key components of ARDS management encompass appropriate mechanical ventilation including limiting tidal volume to ≤6 mL/kg of predicted body weight, maintaining transpulmonary pressures ≤30 cm H₂O, and utilizing positive end–expiratory pressure to limit alveolar deflation and to improve oxygenation. Additional strategies include conservative fluid management and using nutrition supplemented with antioxidants. Use of corticosteroids is controversial for both early and late ARDS and although often used for avian influenza, beneficial effects on outcomes have not been demonstrated for corticosteroids. Prone positioning can improve oxygenation temporarily and might be useful as rescue therapy for severe hypoxemia. Administration of inhaled nitric oxide and high frequency oscillatory ventilation can improve oxygenation but have not been demonstrated to improve survival in ARDS—their role in avian influenza is uncertain and availability limited. Management of multiple organ failure may include vasopressor support for septic shock and renal replacement therapy for acute renal failure.     

Akute respiratorische Insuffizienz

Acute respiratory distress syndrome (ARDS) is the clinical manifestation of an acute lung injury caused by a variety of direct and indirect injuries to the lung. The cardinal clinical feature of ARDS, refractory arterial hypoxemia, is the result of protein-rich alveolar edema with impaired surfactant function, due to vascular leakage and dysfunction with consequently impaired matching of ventilation to perfusion. Better understanding of the pathophysiology of ARDS has led to the development of novel therapies, pharmacological strategies, and advances in mechanical ventilation. However, protective ventilation is the only confirmed option in ARDS management improving survival, and few other therapies have translated into improved oxygenation or reduced ventilation time. The development of innovative therapy options, such as extracorporeal membrane oxygenation, have the potential to further improve survival of this devastating disease.     

Acute respiratory distress syndrome caused by respiratory syncytial virus

Acute respiratory distress syndrome (ARDS) complicating severe respiratory syncytial virus (RSV) infection has been described in only a few infants. In contrast to the low mortality rates usually associated with RSV infections (<5%), mortality rates in the range of 40–70% have been reported in pediatric patients with ARDS. However, studies on patients with ARDS are usually lumped with respect to causation, and the disease course of RSV-induced ARDS has not been previously studied. We examined the pulmonary function abnormalities of 37 infants with RSV-induced respiratory failure who were admitted to our pediatric intensive care unit for assisted ventilation. Measurements included respiratory mechanics, maximum expiratory flow-volume curves, and lung volumes. These allowed the calculation of a Murray lung injury score (modified for pediatric use) in which radiographic findings, ventilator settings, lung compliance, and blood gas results were considered. We identified ten infants with severe restrictive lung disease who fulfilled the clinical criteria for classification as ARDS. All had lung injury scores above 2.5, compatible with a diagnosis of ARDS. Twenty-seven infants had obstructive patterns of lung function consistent with a clinical diagnosis of RSV bronchiolitis. The patients with RSV-induced ARDS were significantly younger, and had a longer time on assisted ventilation (P < 0.05) and a higher proportion of predisposing illnesses (P < 0.05, odds ratio = 6.67, two-tailed Fisher's exact test) when compared with the patients who had obstructive disease. Only one patient (who had immunodeficiency) died, and all others were successfully managed on conventional mechanical ventilation. We conclude that RSV-induced respiratory failure represents a relatively benign cause of ARDS in pediatric patients. Our observations support the notion of differentiating ARDS with respect to causation, especially when novel and experimental therapy is considered and mortality rates are analyzed. Pediatr. Pulmonol. 1997; 23:176–183 © 1997 Wiley-Liss, Inc.     

无创机械通气在ARDS治疗中的应用

目的探讨无创机械通气治疗急性呼吸窘迫综合征(ARDS)患者的临床疗效。方法对20例ARDS患者采用无创机械通气,根据治疗效果分为成功组和失败组。记录两组病人治疗前后心率(HR)、呼吸频率(RR)、氧合指数(PaO2/FiO2)、氧分压(PaO2)、二氧化碳分压(PaCO2)、血氧饱和度(SaO2)。结果无创机械通气成功组11例均为ARDS早期患者,治疗2h后PaO2/FiO2、HR、PaO2、SaO2、RR都有明显好转。无创机械通气治疗失败组全为呼吸窘迫较严重的ARDS患者,治疗2h后PaO2/FiO2、HR、PaO2、PaCO2、SaO2、RR无明显变化。结论无创机械通气对部分ARDS患者有良好的通气支持作用,尤其是ARDS的早期阶段。     

Prone positioning in patients with acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) is a severe form of respiratory failure that is characterized by marked hypoxemia, bilateral infiltrates on chest radiograph, and no clinical evidence of left ventricular failure. Mechanical ventilation with positive end-expiratory pressure (PEEP) is a cornerstone therapy for ARDS patients. Because the fundamental aim of supportive treatment is to improve arterial oxygenation, several alternatives to mechanical ventilation with PEEP have been used. One of these alternative therapies is prone positioning, which has been used safely to improve oxygenation in many patients with ARDS. Despite encouraging results, however, the use of prone positioning is not widely accepted as an adjunct to therapy in hypoxemic patients because, aside from temporarily improving gas exchange, it does not seem to affect the outcome of these patients. This article reviews the rationale for using prone positioning in ARDS patients who require intubation and mechanical ventilation.     

Tidal volume reduction in patients with acute lung injury when plateau pressures are not high

Use of a volume- and pressure-limited mechanical ventilation strategy improves clinical outcomes of patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS). However, the extent to which tidal volumes and inspiratory airway pressures should be reduced to optimize clinical outcomes is a controversial topic. This article addresses the question, "Is there a safe upper limit to inspiratory plateau pressure in patients with ALI/ARDS?" We reviewed data from animal models with and without preexisting lung injury, studies of normal human respiratory system mechanics, and the results of five clinical trials of lung-protective mechanical ventilation strategies. We also present an original analysis of data from the largest of the five clinical trials. The available data from each of these assessments do not support the commonly held view that inspiratory plateau pressures of 30 to 35 cm H2O are safe. We could not identify a safe upper limit for plateau pressures in patients with ALI/ARDS.     

不同病因导致急性呼吸窘迫综合征应用体外膜式氧合治疗体会

目的:观察不同病因引起急性呼吸窘迫综合征(ARDS)的患者,应用体外膜式氧合(ECMO)的治疗效果。方法:回顾性分析2007年6月至2008年8月我院3例ARDS应用ECMO病例。发生原因分别是重症肺炎、胸腹联合创伤后合并呼吸机相关性肺炎(VAP)、以及肺栓塞肺动脉内膜血栓剥脱术后灌注肺;观察应用ECMO前基础状态(Base)、用后8 h、24 h、48 h及72 h动脉血气分析、血压、脉搏和呼吸机调整参数。结果:应用ECMO后,例1重症肺炎患者8 h、24 h、48 h及72 h血压、脉搏及氧合等项指标平稳,但ECMO参数下调时,缺氧状态无缓解,最终ECMO辅助14 d后死亡;例2胸腹联合创伤后VAP合并ARDS患者和例3肺栓塞术后灌注肺患者,ECMO辅助8 h、24 h、48 h、72 h血压、脉搏、氧合等项指标明显改善,分别于ECMO辅助4 d后和24 h后停机。结论:不同病因导致的ARDS应用ECMO后可能结果有所不同。ECMO能改善ARDS患者氧合和气体交换,减轻肺部病理损伤,减轻机体因低氧血症带来的多器官损伤,为治疗原发病赢得时间。     

心脏病体外循环术后急性呼吸窘迫综合征的诊断与治疗

目的：探讨心脏病体外循环术后急性呼吸窘迫综合征（ARDS）的诊断,发病机理和治疗原则,方法：对86例体外循环后急性进行性呼吸窘迫综合征和难以纠正的低氧血症及时作出诊断,给予呼吸机辅助机械通气,降低肺毛细血管楔压,血管外肺水含量和维护心功能等治疗措施,结果：2例合并严重肾功能衰竭,3例术后ARDS导致多器官功能衰竭死亡,其余均痊愈出院,且远期随访均无肺损伤后遗症,结论：早期及时的诊断和积极有效的治疗是降低ARDS死亡率和提高治愈率的关键。     

Pathophysiology of acute lung injury

The acute respiratory distress syndrome (ARDS) is a life-threatening syndrome that may occur in any patient without any predisposition and that is mostly triggered by underlying processes such as sepsis, pneumonia, trauma, multiple transfusions, and pancreatitis. ARDS is defined by (1) acute onset, (2) bilateral infiltrates in chest x-rays, (3) absence of left ventricular failure, and (4) severe arterial hypoxemia with a PaO2/FiO2 ratio less than 200 mmHg. Still, ARDS is feared (mortality 30-40%) and relatively frequent (incidence between 13.5 per 100,000 to 75 per 100,000). Acute lung injury (ALI) describes a similar, but less severe, clinical condition, with PaO2/FiO2 values between 200 and 300 mmHg. Despite ongoing and intensive scientific research in this area, the mechanisms underlying ALI/ARDS are still not completely understood, and until recently, there were no studies demonstrating any beneficial effect of a single treatment modality in ARDS. The recent report that a specific approach to ventilatory support can significantly reduce mortality in ARDS underscores the need for better understanding of the pathophysiological events occurring in this syndrome. This review therefore summarizes the current pathophysiological concepts underlying the evolution of acute hypoxemic respiratory failure and focuses on: (1) possible reasons for the development of ALI/ARDS; (2) cellular and humoral mediator responses leading to a sustained and self-perpetuating inflammation of the lung; (3) consequences with regard to fluid balance, pulmonary perfusion, ventilation, and efficiency of gas exchange; and (4) mechanisms underlying the aggravating complications commonly seen in ARDS, especially ventilator-associated lung injury, ventilator-associated pneumonia, and lung fibrosis.     

Ventilator-associated lung injury: a search for better therapeutic targets.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) represent a continuum of injury that may arise from a number of primary insults. Localised injury may progress due to trauma from mechanical ventilation, a finding that has led to intense debate in the clinical and experimental literature over optimal ventilator management. The implementation of low tidal volume strategies has led to an improvement in outcomes; however, mortality remains unacceptably high. In the current review, ventilator-associated lung injury is examined, as it relates to the pathophysiological changes beyond direct airway trauma in ALI and ARDS, and an attempt is made to provide a historical perspective to outline potential current and future pitfalls in the use of surrogate end-points and the discovery of potential biomarkers. The systemic responses that lead to multi-organ dysfunction, the leading causes of morbidity and mortality in ALI and ARDS, are caused by pro-inflammatory signalling cascades and the activation of such diverse mediators as reactive oxygen species, immune response elements, apoptotic constituents and coagulation proteins. These areas are examined, including key mediators, and possible future areas of interest are discussed, including the potential of an "acute lung injury chip" to integrate measured surrogate biomarkers with real-time clinical information to improve patient outcomes.     

Pediatric acute lung injury: prospective evaluation of risk factors associated with mortality

RATIONALE: The 1994 American European Consensus Committee definitions of acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) have not been applied systematically in the pediatric population. OBJECTIVES: The purpose of this study was to evaluate prospectively the epidemiology and clinical risk factors associated with death and prolonged mechanical ventilation in all pediatric patients admitted to two large, pediatric intensive care units with ALI/ARDS using Consensus criteria. METHODS: All pediatric patients meeting Consensus Committee definitions for ALI were prospectively identified and included in a relational database. MEASUREMENTS AND MAIN RESULTS: There were 328 admissions for ALI/ARDS with a mortality of 22%. Multivariate logistic regression analyses revealed (1) the initial severity of oxygenation defect, as measured by the Pa(O2)/FI(O2) ratio; (2) the presence of nonpulmonary and non-central nervous system (CNS) organ dysfunction; and (3) the presence of CNS dysfunction were independently associated with mortality and prolonged mechanical ventilation. A substantial fraction of patients (28%) did not require mechanical ventilation at the onset of ALI; 46% of these patients eventually required intubation for worsening ALI. CONCLUSIONS: Mortality in pediatric ALI/ARDS is high and several risk factors have major prognostic value. In contrast to ALI/ARDS in adults, the initial severity of arterial hypoxemia in children correlates well with mortality. A significant fraction of patients with pediatric ALI/ARDS can be identified before endotracheal intubation is required. These patients provide a valuable group in whom new therapies can be tested.     

Prone position in acute respiratory distress syndrome.

In the last few years prone positioning has been used increasingly in the treatment of patients with acute respiratory distress syndrome (ARDS) and this manoeuvre is now considered a simple and safe method to improve oxygenation. However, the physiological mechanisms causing respiratory function improvement as well as the real clinical benefit are not yet fully understood. The aim of this review is to discuss the physiological and clinical effects of prone positioning in patients with ARDS. The main physiological aims of prone positioning are: 1) to improve oxygenation; 2) to improve respiratory mechanics; 3) to homogenise the pleural pressure gradient, the alveolar inflation and the ventilation distribution; 4) to increase lung volume and reduce the amount of atelectatic regions; 5) to facilitate the drainage of secretions; and 6) to reduce ventilator-associated lung injury. According to the available data, the authors conclude that: 1) oxygenation improves in approximately 70-80% of patients with early acute respiratory distress syndrome; 2) the beneficial effects of oxygenation reduce after 1 week of mechanical ventilation; 3) the aetiology of acute respiratory distress syndrome may markedly affect the response to prone positioning; 4) extreme care is necessary when the manoeuvre is performed; 5) pressure sores are frequent and related to the number of pronations; 6) the supports used to prone and during positioning are different and nonstandardised among centres; and 7) intensive care unit and hospital stay and mortality still remain high despite prone positioning.     

Hemodynamic effects of high-frequency oscillatory ventilation in children

The purpose of this study was to evaluate the acute hemodynamic effects of transitioning a patient from conventional mechanical ventilation (CMV) to high-frequency oscillatory ventilation (HFOV). Our hypothesis was that hemodynamic status would not be adversely affected by such a change. Ten pediatric patients with acute hypoxemic respiratory failure and a thermodilution pulmonary arterial catheter in place were prospectively evaluated on the transition from CMV to HFOV. Hemodynamic and respiratory data were obtained before and within 1 hour of transition to HFOV with a “high-volume” ventilation strategy. On CMV, the mean oxygenation index of the patients was 18 ± 4. Despite increases in mean airway pressure and decreases in mean arterial pressure and systemic vascular resistance on HFOV, there was no change in pulmonary circulation variables, cardiac index, or oxygen delivery. We concluded that in pediatric patients with acute respiratory failure and unstable cardiovascular status, the transition from CMV to HFOV was not accompanied by a decrease in cardiac function or oxygen delivery. Pediatr Pulmonol. 1998; 25:371–374. © 1998 Wiley-Liss, Inc.     

高频震荡通气治疗先天性心脏病术后重症ARDS32例效果观察

目的探讨高频震荡通气(HFOV)对小儿心脏手术后重症ARDS的治疗效果。方法对32例心脏手术后常频通气(CMV)治疗无效的重症ARDS患儿行HFOV治疗,设置相应的参数并行氧合、通气管理,每次吸痰后行肺复张。观察治疗前后血气指标变化、HFOV治疗时间、肺复张期间循环指标变化、整体治疗期间并发症发生情况及患儿存活情况。结果 HFOV治疗后通气及气体交换在较短的时间内改善,12～48 h血气相关指标PaO2、PaCO2、吸入氧浓度(FiO2)、氧合指数(PaO2/FiO2)均明显改善且稳定。HFOV治疗时间43～238(128.5±67.49)h,肺复张期间循环指标未出现异常变化,末梢血氧饱和度快速恢复至吸痰前水平,呼吸机的吸氧浓度快速降低。整体治疗期间出现气胸9例,均安置胸腔闭式引流。本组患儿存活21例(65.6%),死亡11例。结论 HFOV对CMV治疗无效的重症ARDS能在较短时间内改善通气及气体交换,可作为小儿心脏术后重症ARDS的重要抢救措施。