Definition Of Acute Lung Injury Research Articles

Assessment of Acute Respiratory Failure

Acute respiratory failure (ARF) is fundamentally a dysfunction of gas exchange and can be due to either inadequate carbon dioxide elimination causing hypercapnia or poor oxygen exchange and delivery causing hypoxemia. A variety of etiologies exist that cause ARF in the surgical patient, including previous lung disease, such as chronic obstructive pulmonary disease or asthma, neurologic compromise of respiratory drive, nutritional and metabolic derangements that can alter respiratory metabolism and mechanics, direct lung injury, and infection. The type of surgery and the time since surgery are other key factors that influence medical decision making and that will influence priorities in the assessment and management of ARF. This review explores the full spectrum of ARF in the surgical patient, focusing particularly on its assessment and initial management. Figures illustrate algorithms in the approach to the surgical patient with ARF and show example radiographic images of acute respiratory distress syndrome (ARDS), a common complication. Tables summarize indications for emergent intubation, key etiologies of ARF, and the evolving definitions of acute lung injury and ARDS. Key words: acute respiratory distress syndrome, acute respiratory failure, hypercapnia, hypoxemia, mechanical ventilation

Infection site is predictive of outcome in acute lung injury associated with severe sepsis and septic shock.

Sepsis is a leading cause of acute lung injury (ALI); however, the characteristics and outcome of sepsis-associated ALI are poorly understood. We aimed to elucidate factors that predict patient outcome in sepsis-associated ALI. Secondary analysis of a multicenter, prospective, observational study was performed. Among 624 patients with severe sepsis and septic shock, 251 (40.2%) fulfilled the definition of American-European Consensus Conference definition of ALI. All-cause 28-day and in-hospital mortalities were 30.7% and 38.6%, respectively. More than 40% of ALI patients had neurological, cardiovascular and haematological dysfunctions or disseminated intravascular coagulation, all of which were associated with higher mortality. We report a significant correlation between infection site and mortality in patients with ALI, but not in those without ALI. The proportion of ALI was significantly higher in pulmonary sepsis; further, a complication of ALI was associated with higher mortality in sepsis from pulmonary and other sources, but not in abdominal sepsis. Among the other sepsis sites, urinary tract, central nervous system, catheter-related and undetermined foci of infection had worse outcomes when associated with ALI. None of the individual severe sepsis bundles, including fluid resuscitation and early antibiotic administration, correlated with mortality. Compliance with a set of sepsis management bundles was associated with better outcomes. In severe sepsis and septic shock, the proportion and effect on outcome was not uniform among infection sites. The infection site was predictive of outcome in patients with ALI but not in those without ALI.

Impact of Distinct Definitions of Acute Lung Injury on Its Incidence and Outcomes in Brazilian ICUs

Evaluation of prevalence and outcomes of acute lung injury in a large cohort of critically ill patients in Brazil and comparison of predictive receiver operating characteristic curve mortality of American European Consensus conference definition with new Berlin definition of acute respiratory distress syndrome. A 15-month prospective, multicenter, observational study. Fourteen medical ICUs in Espirito Santo, a state of Brazil. Mechanically ventilated patients who fulfilled American European Consensus conference criteria of acute lung injury or Berlin definition of acute respiratory distress syndrome. Clinical and respiratory data were collected for 7 consecutive days and on the 14 and 28 days. Twenty-eight day mortality, hospital mortality, and predictive receiver operating characteristic curve mortality were calculated. Of 7,133 patients, 130 patients (1.8%) fulfilled criteria for acute lung injury (American European Consensus conference) or acute respiratory distress syndrome (Berlin definition). Median time for diagnosis was 2 days (interquartile range, 0-3 d). Main risk factors were pneumonia (35.3%) and nonpulmonary sepsis (31.5%). Mean age was 44.2 ± 15.9 years, and 61.5% were men. Mean Acute Physiology and Chronic Health Evaluation II score was 20.7 ± 7.9. Mean PaO2/FIO2 was 206 ± 61.5, significantly lower in nonsurvivors on day 7 (p = 0.003). Mean mechanical ventilation time was 21 ± 15 days. Length of ICU stay was 26.4 ± 18.7 days. Twenty-eight-day mortality was 38.5% (95% CI, 30.1-46.8); hospital mortality was 49.2% (95% CI, 40.6-57.8). Predictive 28-day mortality area under the receiver operating characteristic curve for American European Consensus conference definition was 0.5625 (95% CI, 0.4783-0.6467) and for the Berlin definition 0.5664 (95% CI, 0.4759-0.6568; p = 0.9510). In our population, prevalence of acute lung injury was low, most cases were diagnosed 2 days after ICU admission, and Berlin definition was not different from American European Consensus conference definition in predicting mortality. There are still several problems with the global epidemiology, definition, and mortality predictive indices that should be added to the classification of this still lethal syndrome to improve its predictive mortality power in the future.

Recent concept and new definition of acute lung injury and acute respiratory distress syndrome

Recent concept and new definition of acute lung injury and acute respiratory distress syndrome

Prevalence of Acute Lung Injury Among Medical Patients in the Emergency Department

Acute lung injury (ALI) affects an estimated 190,000 persons per year in U.S. intensive care units (ICUs), but little is known about its prevalence in the emergency department (ED). The objective was to describe the prevalence of ALI among mechanically ventilated adult nontrauma patients in the ED. The hypothesis was that the prevalence of ALI in adult ED patients would be low. This was a retrospective cohort study of admitted nontrauma patients presenting to an academic ED. Two trained investigators abstracted data from patient records using a standardized form. The use of mechanical ventilation in the ED was identified in two phases. First, all ED patients were screened for the current procedural terminology (CPT) code for endotracheal intubation (CPT 31500) from January 1, 2003, to December 31, 2006. Second, each patient record was reviewed to verify the use of mechanical ventilation. ALI was defined in accordance with a modified version of the American-European Consensus Conference criteria as: 1) hypoxemia defined as PaO(2) /FiO(2) ratio ≤300 mm Hg on all arterial blood gases (ABGs) in the ED and the first 24 hours of admission, 2) the presence of bilateral infiltrates on chest radiograph, and 3) the absence of left atrial hypertension. Data are presented in absolute numbers and percentages. Interobserver agreement was evaluated using the kappa statistic. Of the 552 patients who received mechanical ventilation in the ED and were subsequently admitted, a total of 134 (24.3%, 95% confidence interval [CI] = 20.8% to 28.0%) met hypoxemia criteria. Of these, 34 had evidence of left atrial hypertension, 52 did not have chest radiograph findings consistent with ALI, and two did not have a chest radiograph performed; the remaining 46 met ALI criteria. An additional two patients who died in the ED had clinical evidence of ALI. Thus, 48 of 552, or 8.7% (95% CI = 6.6% to 11.3%), met criteria for ALI. The kappa value for determination of ALI was 0.84 (95% CI = 0.54 to 1.0). The prevalence of ALI was nearly 9% in adult nontrauma patients receiving mechanical ventilation in the ED. Further study is required to determine which types of patients present to the ED with ALI, the extent to which lung protective ventilation is used, and the need for ED ventilator management algorithms.

Embracing Physical and Neuropsychological Dysfunction in Acute Lung Injury Survivors: The Time Has Come

Embracing Physical and Neuropsychological Dysfunction in Acute Lung Injury Survivors: The Time Has Come

Claudin-4 Levels Are Associated with Intact Alveolar Fluid Clearance in Human Lungs

The removal of edema from the air spaces is a critical function of the alveolar barrier requiring intact tight junctions. Alveolar fluid clearance contributes to graft function after transplantation and is associated with survival in patients with acute lung injury. Claudin-4 concentrations are known to increase during lung injury and the loss of claudin-4 decreases alveolar fluid clearance in mice. This study was therefore undertaken to evaluate whether differences in lung expression of the tight junction protein claudin-4 are associated with alveolar fluid clearance or clinical measures of lung function. Alveolar fluid clearance rates were measured in ex vivo perfused human lungs not used for transplantation and were compared with histological lung injury and clinical measures of lung injury in the donors. Claudin-4 staining demonstrated a positive correlation with alveolar fluid clearance (Spearman rank correlation [r(s)] = 0.71; P < 0.003); however, claudin-4 staining was not strongly associated with histological measures of lung injury. The expression of other tight junction proteins (including ZO-1) was not associated with alveolar fluid clearance or claudin-4 levels. Claudin-4 staining was lower in lungs from donors with greater impairment in respiratory physiology. These data suggest that claudin-4 may promote alveolar fluid clearance and demonstrate that the amount of claudin-4 expressed may provide specific information regarding alveolar epithelial barrier function that strengthens the link between histological changes and physiological impairment.

1. The Concept and Definitions of Acute Lung Injury and Acute Respiratory Distress Syndrome.

1. The Concept and Definitions of Acute Lung Injury and Acute Respiratory Distress Syndrome.

The Design of Future Pediatric Mechanical Ventilation Trials for Acute Lung Injury

Pediatric practitioners face unique challenges when attempting to translate or adapt adult-derived evidence regarding ventilation practices for acute lung injury or acute respiratory distress syndrome into pediatric practice. Fortunately or unfortunately, there appears to be selective adoption of adult practices for pediatric mechanical ventilation, many of which pose considerable challenges or uncertainty when translated to pediatrics. These differences, combined with heterogeneous management strategies within pediatric critical care, can complicate clinical practice and make designing robust clinical trials in pediatric acute respiratory failure particularly difficult. These issues surround the lack of explicit ventilator protocols in pediatrics, either computer or paper based; differences in modes of conventional ventilation and perceived marked differences in the approach to high-frequency oscillatory ventilation; challenges with patient recruitment; the shortcomings of the definition of acute lung injury and acute respiratory distress syndrome; the more reliable yet still somewhat unpredictable relationship between lung injury severity and outcome; and the reliance on potentially biased surrogate outcome measures, such as ventilator-free days, for all pediatric trials. The purpose of this review is to highlight these challenges, discuss pertinent work that has begun to address them, and propose potential solutions or future investigations that may help facilitate comprehensive trials on pediatric mechanical ventilation and define clinical practice standards.

Defining acute lung disease in children with the oxygenation saturation index*

To evaluate whether a formula could be derived using oxygen saturation (Spo2) to replace Pao2 that would allow identification of children with acute lung injury and acute respiratory distress syndrome. Definitions of acute lung injury and acute respiratory distress syndrome require arterial blood gases to determine the Pao2/Fio2 ratio of 300 (acute lung injury) and 200 (acute respiratory distress syndrome). Post hoc data analysis of measurements abstracted from two prospective databases of randomized controlled trials. Academic pediatric intensive care units. A total of 255 children enrolled in two large prospective trials of therapeutic intervention for acute lung disease: calfactant and prone positioning. Data were abstracted including Pao2, Paco2, pH, Fio2, and mean airway pressure. Repeated-measures analyses, using linear mixed-effects models, were used to build separate prediction equations for the Spo2/Fio2 ratio, oxygenation index [(Fio2 x Mean Airway Pressure)/Pao2], and oxygen saturation index [(Fio2 x Mean Airway Pressure)/Spo2 ]. A generalization of R was used to measure goodness-of-fit. Generalized estimating equations with a logit link were used to calculate the sensitivity and specificity for the cutoffs of Pao2/Fio2 ratio of 200 and 300 and equivalent values of Spo2/Fio2 ratio, oxygenation index, and oxygen saturation index. An Spo2/Fio2 ratio of 253 and 212 would equal criteria for acute lung injury and acute respiratory distress syndrome, respectively. An oxygenation index of 5.3 would equal acute lung injury criteria, and an oxygenation index of 8.1 would qualify for acute respiratory distress syndrome. An oxygen saturation index, which includes the mean airway pressure and the noninvasive measure of oxygenation, of 6.5 would be equivalent to the acute lung injury criteria, and an oxygen saturation index of 7.8 would equal acute respiratory distress syndrome criteria. Noninvasive methods of assessing oxygenation may be utilized with reasonable sensitivity and specificity to define acute lung injury and acute respiratory distress syndrome, and, with prospective validation, have the potential to increase the number of children enrolled into clinical trials.

The Importance of Fluid Management in Acute Lung Injury Secondary to Septic Shock

Recent studies have suggested that early goal-directed resuscitation of patients with septic shock and conservative fluid management of patients with acute lung injury (ALI) can improve outcomes. Because these may be seen as potentially conflicting practices, we set out to determine the influence of fluid management on the outcomes of patients with septic shock complicated by ALI. A retrospective analysis was performed at Barnes-Jewish Hospital (St. Louis, MO) and in the medical ICU of Mayo Medical Center (Rochester, MN). Patients hospitalized with septic shock were enrolled into the study if they met the American-European Consensus definition of ALI within 72 h of septic shock onset. Adequate initial fluid resuscitation (AIFR) was defined as the administration of an initial fluid bolus of >or= 20 mL/kg prior to and achievement of a central venous pressure of >or= 8 mm Hg within 6 h after the onset of therapy with vasopressors. Conservative late fluid management (CLFM) was defined as even-to-negative fluid balance measured on at least 2 consecutive days during the first 7 days after septic shock onset. The study cohort was made up of 212 patients with ALI complicating septic shock. Hospital mortality was statistically lowest for those achieving both AIFR and CLFM and higher for those achieving only CLFM, those achieving only AIFR, and those achieving neither (17 of 93 patients [18.3%] vs 13 of 31 patients [41.9%] vs 30 of 53 patients [56.6%] vs 27 of 35 [77.1%], respectively; p < 0.001). Both early and late fluid management of septic shock complicated by ALI can influence patient outcomes.

Blood product transfusions and clinical outcomes in pediatric patients with acute lung injury*

There are data suggesting that blood product transfusions increase the risk of developing acute lung injury (ALI) in adults, and may be associated with increased mortality in adults with ALI. A possible association between transfusions and adverse outcomes of pediatric patients with ALI has not been studied previously. We tested the hypothesis that blood product transfusions to pediatric patients with ALI within the first 72 hours of the diagnosis would be associated with increased mortality and prolonged mechanical ventilation. An epidemiologic database of pediatric ALI prospectively gathered from July 1996 to May 2000 was analyzed. Children were enrolled from both a tertiary referral hospital and a major community children's hospital. Three hundred fifteen patients who met the 1994 American European Consensus Committee definition of ALI between the ages of 36 weeks corrected gestational age and 18 years. Mortality in the pediatric intensive care unit. Multivariate analyses indicated that the transfusion of fresh-frozen plasma (FFP) was associated with increased mortality, independent of the severity of hypoxemia (Pao2/Fio2), presence of multiple organ system failure or disseminated intravascular coagulation (odds ratio = 1.08, 95% confidence interval = 1.00-1.17, p = 0.04). FFP transfusion was analyzed as a continuous variable, so that for each milliliter of FFP transfused per kilogram patient body weight per day, the odds of death increased by 1.08. There was a trend toward an association of the transfusion of FFP with a fewer number of days of unassisted ventilation (regression coefficient = -0.21, 95% confidence interval = -0.42-0.01, p = 0.06). The transfusion of FFP is associated with an increased risk of mortality in children with ALI. The association between FFP and mortality in children with ALI should be investigated further.

Noninvasive positive pressure ventilation for patients with acute hypoxemic respiratory failure?

The re-emergence of noninvasive positive pressure ventilation (NIV) represents perhaps the single greatest advance in mechanical ventilation over the last 20 years. Clear benefit has been demonstrated for patients with respiratory failure in the setting of acute exacerbations of chronic obstructive pulmonary disease and cardiogenic pulmonary edema. While there are advocates for the use of NIV in patients presenting with acute hypoxemic respiratory failure not due to cardiogenic pulmonary edema, benefit for these patients is less clear. This article reviews briefly the heterogeneity of hypoxemic respiratory failure and looks at the current evidence to support NIV in this setting in some depth. Presently, there is little evidence to support the use of NIV for patients presenting with hypoxemic respiratory failure who fulfill the American and European Consensus Conference definition of acute lung injury or acute respiratory distress syndrome, other than in patients with high risk for death if endotracheally intubated (immunocompromised patients, postlung resection acute respiratory distress syndrome). As there are reasonable rationales for both benefit and harm, there is a need for a large, multicenter, randomized, controlled trial to clarify whether NIV offers benefit in terms of a reduced need for endotracheal intubation, length of stay and hospital mortality.

Toward a more accurate definition of acute lung injury and the acute respiratory distress syndrome in pediatric patients*

Department of Pediatric Critical Care, Children’s Hospital and Research Center at Oakland, Oakland, CA *See also p. 335. The author has not disclosed any potential conflicts of interest.

Epidemiology of acute lung injury

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. 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. 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.

Pediatric Acute Lung Injury

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. 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. All pediatric patients meeting Consensus Committee definitions for ALI were prospectively identified and included in a relational database. 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. 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.

Clinical Epidemiology of Acute Lung Injury

Acute lung injury (ALI) remains a serious threat to critically ill patients and continues to pose challenges to clinicians and investigators as they strive to better identify and treat these patients. Over 30 years of clinical and basic science investigations have led to a better understanding of the pathophysiology, risk factors, and prognosis of this entity but we still lack a "gold standard'' for its identification. The American-European Consensus Conference definition has helped in the effort to standardize the definition of ALI but is still fraught with difficulties in the application of criteria for the chest radiograph, hypoxemia, and left atrial hypertension. As further efforts are undertaken to better define ALI and to more accurately describe its incidence, it is critical that methodology to assess the accuracy and reliability of such definitions be utilized. This union of clinical epidemiology, clinical research, and basic science will not only better describe the population burden of ALI but will also better track the effect of current and future therapeutic interventions.

Current definitions of acute lung injury and the acute respiratory distress syndrome do not reflect their true severity and outcome.

Despite intensive research, there are no universally accepted clinical definitions for acute lung injury (ALI) or the acute respiratory distress syndrome (ARDS). A recent joint American-European Consensus Conference on ARDS formally defined the difference between ALI and ARDS based on the degree of oxygenation impairment. However, this definition may not reflect the true prevalence, severity and prognosis of these syndromes. During a 22-month period, 56 consecutive mechanically ventilated patients who met the American-European Consensus definition for ARDS [arterial oxygen tension/fractional inspired oxygen (PaO(2)/FIO(2) </= 200 mmHg regardless of the level of positive end-expiratory pressure (PEEP), bilateral pulmonary infiltrates, and no evidence of left heart failure] were admitted into the intensive care units (ICU) of the Hospital del Pino, Las Palmas, Spain, and prospectively studied. The diagnosis of ALI and ARDS was made by a PEEP-FIO(2) trial, 24 h after patients met the Consensus inclusion criteria. Patients were classified as having ALI(-24 h) if the PaO(2)/FIO(2) was > 150 mmHg with PEEP = 5 cmH(2)O, and ARDS(-24 h) if the PaO(2) /FIO(2) was </= 150 mmHg with PEEP >/= 5 cmH(2)O. Overall mortality was 43 % (24 of 56). However, 24 h after inclusion, PaO(2) response to PEEP 5 cmH(2)O allowed the separation of our patients into two different groups: 31 patients met our ALI(-24 h) criteria (PaO(2)/FIO(2) > 150 mmHg) and their mortality was 22.6 %; 25 patients met our ARDS(-24 h) criteria (PaO(2)/FIO(2) </= 150 mmHg) and their mortality was 68 % (p = 0.0016). The differences in the respiratory severity index during the first 24 h of inclusion, PaO(2)/FIO(2) ratio at baseline and at 24 h, maximum plateau airway pressure, maximum level of PEEP, and number of organ system failures during the ICU stay were statistically significant. Since the use of PEEP in the American-European Consensus criteria for ARDS is not mandatory, that definition does not reflect the true severity of lung damage and outcome. Our data support the need for guidelines based on a specific method of evaluating oxygenation status before the American-European Consensus definition is adopted.

New approaches to acute lung injury

The lung responds to acute injury of diverse aetiology via a series of common pathways. The pathological changes caused by a variety of toxic and infectious agents evolve over time from endothelial and epithelial injury to alveolar consolidation and finally to fibroblast proliferation and collagen deposition. Widespread acute injury to the lung produces diffuse alveolar damage [33], a well characterized anatomical entity that forms the basis of the protean clinical picture of acute respiratory failure. This clinical picture has been identified in the past by a host of terms, creating some confusion. Recently, a panel of experts clarified the definition of acute lung injury [4]. The terms acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are proposed to describe the continuum of a syndrome of primary respiratory failure, characterized by the acute onset of dyspnoea, hypoxaemia and bilateral consolidation on the chest radiograph (table 1). ALI is considered to be the early stage of ARDS, with milder abnormalities of respiratory function, and it may subsequently evolve into the more severe and more easily diagnosed syndrome of ARDS. The major reason to define ALI is to facilitate experimental and clinical investigation of the early stages of ARDS, in order to improve the early recognition and treatment of this syndrome [4].

Acute respiratory distress syndrome: diagnosis and management.

This review will attempt to put together the voluminous studies and concepts that have been published during the past 25 years following the description of the acute respiratory distress syndrome (ARDS) regarding diagnosis and management. The initial discussion will focus on how to clinically diagnose ARDS based recommendations. This also gives the current definition of acute lung injury and when to call it ARDS. The radiographic and hemodynamic characteristics are discussed including oxygenation parameters. The management outlines the conventional as well as new therapies intended to improve survival of this devastating disease.