Evaluation of the classifications of severity in acute respiratory distress syndrome in childhood by the Berlin Consensus and the Pediatric Acute Lung Injury Consensus Conference.

OBJECTIVE: To compare two methods for defining and classifying the severity of pediatric acute respiratory distress syndrome: the Berlin classification, which uses the relationship between the partial pressure of oxygen and the fraction of inspired oxygen, and the classification of the Pediatric Acute Lung Injury Consensus Conference, which uses the oxygenation index. METHODS: This was a prospective study of patients aged 0 - 18 years with a diagnosis of acute respiratory distress syndrome who were invasively mechanically ventilated and provided one to three arterial blood gas samples, totaling 140 valid measurements. These measures were evaluated for correlation using the Spearman test and agreement using the kappa coefficient between the two classifications, initially using the general population of the study and then subdividing it into patients with and without bronchospasm and those with and without the use of neuromuscular blockers. The effect of these two factors (bronchospasm and neuromuscular blocking agent) separately and together on both classifications was also assessed using two-way analysis of variance. RESULTS: In the general population, who were 54 patients aged 0 - 18 years a strong negative correlation was found by Spearman's test (ρ -0.91; p < 0.001), and strong agreement was found by the kappa coefficient (0.62; p < 0.001) in the comparison between Berlin and Pediatric Acute Lung Injury Consensus Conference. In the populations with and without bronchospasm and who did and did not use neuromuscular blockers, the correlation coefficients were similar to those of the general population, though among patients not using neuromuscular blockers, there was greater agreement between the classifications than for patients using neuromuscular blockers (kappa 0.67 versus 0.56, p < 0.001 for both). Neuromuscular blockers had a significant effect on the relationship between the partial pressure of oxygen and the fraction of inspired oxygen (analysis of variance; F: 12.9; p < 0.001) and the oxygenation index (analysis of variance; F: 8.3; p = 0.004). CONCLUSION: There was a strong correlation and agreement between the two classifications in the general population and in the subgroups studied. Use of neuromuscular blockers had a significant effect on the severity of acute respiratory distress syndrome.

Proposed revised nomenclature for transfusion-related acute lung injury.

A decade ago, definitions of "transfusionߚrelated acute lung injury (TRALI)" and "possible TRALI" were standardized for research and clinical diagnosis. Since then, evidence has confirmed that TRALI is often due to transfusion of white blood cell antibodies to at-risk patients, and the term "TRALI, antibody mediated" is appropriate for such cases. Other TRALI cases are non-antibody mediated. Because specific, nonantibody transfusion factors have not yet been confirmed to cause TRALI in humans, the general term "TRALI, non-antibody mediated" is appropriate for such cases. In contrast, evidence is against possible TRALI being due to transfusion with the more likely cause of the acute respiratory distress syndrome (ARDS) being the alternative ARDS risk factor present in these patients. We propose to drop the misleading term "possible TRALI" and to rename this category of cases as "transfused ARDS." These nomenclature updates will more accurately categorize ARDS cases that develop after transfusion.

Pepper spray injury severity: ten-year case experience of a poison control system.

BACKGROUND: Pepper spray is a common lacrimator used by law enforcement and the public to subdue individuals and for self-defense. The risk factors for severe injury due to pepper spray exposure are not well documented and there is a lack of guidelines to identify patients that require transport and medical evaluation in an emergency department. OBJECTIVE: The aim of this study was to determine the prevalence of and circumstances associated with symptoms suggestive of tissue injury beyond transient irritation in persons exposed to pepper spray. METHODS: We reviewed all human exposures to pepper spray reported to a poison control system between 2002 and 2011. Cases were differentiated into 2 outcome groups: minor or self-limiting symptoms versus those with more severe symptoms suggestive of tissue injury that warranted a medical evaluation. A comparison of the variables between the outcome groups was performed using odds ratios (ORs), 95% confidence intervals (CIs), and associated P values. RESULTS: A total of 4,544 cases were identified and 3,671 met the inclusion criteria. Of these, 249 cases (6.8%) were found to have more severe symptoms that warranted a medical evaluation. There were no reported deaths. The cases with more severe symptoms most commonly involved the ocular (53.8%), respiratory (31.7%), and dermal (17.7%) organ systems. Factors with largest independent associations with more severe outcomes were use for law enforcement training (OR, 7.39; 95% CI, 2.98-18.28), direct intentional exposure for purposeful use to incapacitate (OR, 3.02; 95% CI, 1.80-5.06), and for law enforcement on individual target suspects or crowd control (OR, 2.45; 95% CI, 1.42-4.23). CONCLUSIONS: There was a low 1 in 15 potential risk for more severe adverse health effects in persons exposed to pepper spray that warranted a medical evaluation. The risk was highest when used for training of law enforcement personnel and involved severe ocular symptoms. This suggests that routine use of pepper spray for training of law enforcement or military personnel be reconsidered. Protective goggles may be an option when direct spraying into the face of trainees. Transport for medical evaluation should be considered for exposed persons that manifest persistent ocular or respiratory symptoms.

An attempt to validate the modification of the American-European consensus definition of acute lung injury/acute respiratory distress syndrome by the Berlin definition in a university hospital.

PURPOSE: The Berlin definition for acute respiratory distress syndrome (ARDS) is a new proposal for changing the American-European consensus definition but has not been assessed prospectively as yet. In the present study, we aimed to determine (1) the prevalence and incidence of ARDS with both definitions, and (2) the initial characteristics of patients with ARDS and 28-day mortality with the Berlin definition. METHODS: We performed a 6-month prospective observational study in the ten adult ICUs affiliated to the Public University Hospital in Lyon, France, from March to September 2012. Patients under invasive or noninvasive mechanical ventilation, with PaO2/FiO2 <300 mmHg regardless of the positive end-expiratory pressure (PEEP) level, and acute onset of new or increased bilateral infiltrates or opacities on chest X-ray were screened from ICU admission up to discharge. Patients with cardiogenic pulmonary edema were excluded. Patients were further classified into specific categories by using the American-European Consensus Conference and the Berlin definition criteria. The complete data set was measured at the time of inclusion. Patient outcome was measured at day 28 after inclusion. RESULTS: During the study period 3,504 patients were admitted and 278 fulfilled the American-European Consensus Conference criteria. Among them, 18 (6.5 %) did not comply with the Berlin criterion PEEP ≥ 5 cmH2O and 20 (7.2 %) had PaO2/FiO2 ratio ≤200 while on noninvasive ventilation. By using the Berlin definition in the remaining 240 patients (n = 42 mild, n = 123 moderate, n = 75 severe), the overall prevalence was 6.85 % and it was 1.20, 3.51, and 2.14 % for mild, moderate, and severe ARDS, respectively (P > 0.05 between the three groups). The incidence of ARDS amounted to 32 per 100,000 population per year, with values for mild, moderate, and severe ARDS of 5.6, 16.3, and 10 per 100,000 population per year, respectively (P < 0.05 between the three groups). The 28-day mortality was 35.0 %. It amounted to 30.9 % in mild, 27.9 % in moderate, and 49.3 % in severe categories (P < 0.01 between mild or moderate and severe, P = 0.70 between mild and moderate). In the Cox proportional hazard regression analysis ARDS stage was not significantly associated with patient death at day 28. CONCLUSIONS: The present study did not validate the Berlin definition of ARDS. Neither the stratification by severity nor the PaO2/FiO2 at study entry was independently associated with mortality.

Acute pulmonary injury: high-resolution CT and histopathological spectrum.

Acute lung injury usually causes hypoxaemic respiratory failure and acute respiratory distress syndrome (ARDS). Although diffuse alveolar damage is the hallmark of ARDS, other histopathological patterns of injury, such as acute and fibrinoid organising pneumonia, can be associated with acute respiratory failure. Acute eosinophilic pneumonia can also cause acute hypoxaemic respiratory failure and mimic ARDS. This pictorial essay reviews the high-resolution CT findings of acute lung injury and the correlative histopathological findings.

Antiplatelet therapy is associated with decreased transfusion-associated risk of lung dysfunction, multiple organ failure, and mortality in trauma patients.

OBJECTIVE: To determine whether prehospital antiplatelet therapy was associated with reduced incidence of acute lung dysfunction, multiple organ failure, and mortality in blunt trauma patients. DESIGN: Secondary analysis of a cohort enrolled in the National Institute of General Medical Sciences Trauma Glue Grant database. SETTING: Multicenter study including nine U.S. level-1 trauma centers. PATIENTS: A total of 839 severely injured blunt trauma patients at risk for multiple organ failure (age > 45 yr, base deficit > 6 mEq/L or systolic blood pressure < 90 mm Hg, who received a blood transfusion). Severe/isolated head injuries were excluded. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were lung dysfunction (defined as grades 2-3 by the Denver multiple organ failure score), multiple organ failure (Denver multiple organ failure score >3), and mortality. Patients were documented as on antiplatelet therapy if taking acetylsalicylic acid, clopidogrel, and/or ticlopidine. Fifteen percent were taking antiplatelet therapy prior to injury. Median injury severity score was 30 (interquartile range 22-51), mean age 61 + 0.4 yr and median RBCs volume transfused was 1700 mL (interquartile range 800-3150 mL). Overall, 63% developed lung dysfunction, 19% had multiple organ failure, and 21% died. After adjustment for age, gender, comorbidities, blood products, crystalloid/12 hrs, presence of any head injury, injury severity score, and 12 hrs base deficit > 8 mEq/L, 12 hrs RBC transfusion was associated with a significantly smaller risk of lung dysfunction and multiple organ failure among the group receiving antiplatelet therapy compared with those not receiving it (lung dysfunction p = 0.0116, multiple organ failure p = 0.0291). In addition, antiplatelet therapy had a smaller risk (albeit not significant, p = 0.06) of death for patients receiving RBC compared to those not on antiplatelet therapy after adjustment for confounders, CONCLUSIONS: Pre-injury antiplatelet therapy is associated with a decreased risk of lung dysfunction, multiple organ failure, and possibly mortality in high-risk blunt trauma patients who received blood transfusions. These findings suggest platelets have a role in organ dysfunction development and have potential therapeutic implications.

The new definition for acute lung injury and acute respiratory distress syndrome: is there room for improvement?

PURPOSE OF REVIEW: To review the new (Berlin) definition of the acute respiratory distress syndrome (ARDS) and to propose potential improvements. RECENT FINDINGS: The Berlin definition resulted in the following modifications: a criterion of less than 7 days was used to define acute onset; the requirement of pulmonary artery wedge pressure was removed. Clinical judgment for characterizing hydrostatic pulmonary edema suffices, unless there is no apparent ARDS risk factor, in which case an objective evaluation is required; the category of acute lung injury was removed, and ARDS was divided into three categories of severity based on the P/F ratio - mild (from 201 to 300), moderate (from 101 to 200), and severe (≤100  mmHg). A positive end-expiratory pressure value of at least 5  cm H(2)O became required for the diagnosis of ARDS. In this review, we propose that both the use of P/F ratio after some stabilization (first 24  h) and the use of compliance stratified at 0.4  ml/cm H(2)O/kg ideal body weight might improve the stratification of patients. SUMMARY: The Berlin definition brought improvement and simplification over the previous definitions. The use of data over the first 24  h to reclassify the severity of the disease and the use of compliance to stratify each oxygenation category might further improve the definition.

Circulating leukotriene B4 identifies respiratory complications after trauma.

BACKGROUND: Leukotriene B4 (LTB4), a proinflammatory lipid mediator correlates well with the acute phase of Acute Respiratory Distress Syndrome (ARDS). Therefore, LTB4-levels were investigated to determine whether they might be a useful clinical marker in predicting pulmonary complications (PC) in multiply traumatized patients. METHODS: Plasma levels of LTB4 were determined in 100 patients on admission (ED) and for five consecutive days (daily). Twenty healthy volunteers served as control. LTB4-levels were measured by ELISA. Thirty patients developed PC (pneumonia, respiratory failure, acute lung injury (ALI), ARDS, pulmonary embolism) and 70 had no PC (ØPC). RESULTS: LTB4-levels in the PC-group [127.8 pg/mL, IQR: 104-200pg/ml] were significantly higher compared to the ØPC-group on admission [95.6 pg/mL, IQR: 55-143 pg/mL] or control-group [58.4 pg/mL, IQR: 36-108 pg/mL]. LTB4 continuously declined to basal levels from day 1 to 5 without differences between the groups. The cutoff to predict PC was calculated at 109.6 pg/mL (72% specificity, 67% sensitivity). LTB4 was not influenced by overall or chest injury severity, age, gender or massive transfusion. Patients with PC received mechanical ventilation for a significantly longer period of time, and had prolonged intensive care unit and overall hospital stay. CONCLUSION: High LTB4-levels indicate risk for PC development in multiply traumatized patients.

Inhibition of neutrophil apoptosis by PAI-1.

Increased circulating and tissue levels of plasminogen activator inhibitor 1 (PAI-1) are often present in severe inflammatory states associated with neutrophil activation and accumulation and correlate with poor clinical outcome from many of these conditions. The mechanisms by which PAI-1 contributes to inflammation have not been fully delineated. In the present experiments, we found that addition of PAI-1 to neutrophil cultures diminished the rate of spontaneous and TNF-related apoptosis-inducing ligand-induced apoptotic cell death. The effects of PAI-1 on cell viability were associated with activation of antiapoptotic signaling pathways, including upregulation of PKB/Akt, Mcl-1, and Bcl-x(L). Although urokinase-plasminogen activator receptor, lipoprotein receptor-related protein, and vitronectin are primary ligands for PAI-1, these molecules were not involved in mediating its antiapoptotic properties. In contrast, blocking pertussis toxin-sensitive G protein-coupled receptors and selective inhibition of phosphatidylinositide 3-kinase reversed the ability of PAI-1 to extend neutrophil viability. The antiapoptotic effects of PAI-1 were also evident under in vivo conditions during LPS-induced acute lung injury, where enhanced apoptosis was present among neutrophils accumulating in the lungs of PAI-1(-/-) compared with PAI-1(+/+) mice. These results demonstrate a novel antiapoptotic role for PAI-1 that may contribute to its participation in neutrophil-associated inflammatory responses.

[Post-transfusion pulmonary oedema: the French hemovigilance network classification method]. / Œdèmes pulmonaires transfusionnels: classification des cas notifiés en hémovigilance.

Pulmonary oedema after transfusion of blood products may be hydrostatic (transfusion-associated circulatory overload [taco]) or exsudative (transfusion-related acute lung injury [trali]). Both conditions have been recognized as major hazards to transfusion recipients. Risk characterization is necessary to improve safety and to monitor trends in the national blood transfusion system. A collaborative multidisciplinary working group of the French National Hemovigilance Committee has proposed an analysis framework for case definitions and classification. The method relies on internationally used definitions and is adapted to the codification procedures used in the french transfusion incident reports electronic data management.

Degree of endothelium injury promotes fibroelastogenesis in experimental acute lung injury.

We tested the hypothesis that at the early phase of acute lung injury (ALI) the degree of endothelium injury may predict lung parenchyma remodelling. For this purpose, two models of extrapulmonary ALI induced by Escherichia coli lipopolysaccharide (ALI-LPS) or cecal ligation and puncture (ALI-CLP) were developed in mice. At day 1, these models had similar degrees of lung mechanical compromise, epithelial damage, and intraperitoneal inflammation, but endothelial lesion was greater in ALI-CLP. A time course analysis revealed, at day 7: ALI-CLP had higher degrees of epithelial lesion, denudation of basement membrane, endothelial damage, elastic and collagen fibre content, neutrophils in bronchoalveolar lavage fluid (BALF), peritoneal fluid and blood, levels of interleukin-6, KC (murine analogue of IL-8), and transforming growth factor-ß in BALF. Conversely, the number of lung apoptotic cells was similar in both groups. In conclusion, the intensity of fibroelastogenesis was affected by endothelium injury in addition to the maintenance of epithelial damage and intraperitoneal inflammation.

An alternative method of acute lung injury classification for use in observational studies.

BACKGROUND: In observational studies using acute lung injury (ALI) as an outcome, a spectrum of lung injury and difficult-to-interpret chest radiographs (CXRs) may hamper efforts to uncover risk factor associations. We assessed the impact of excluding patients with difficult-to-classify or equivocal ALI diagnosis on clinical and genetic risk factor associations for ALI after trauma. METHODS: This study was of a prospective cohort of 280 critically ill trauma patients. The primary outcome was the development of ALI. Patients were classified into one of three groups: (1) definite ALI (patients who fulfilled the American-European Consensus Conference [AECC] criteria for ALI), (2)equivocal ALI (patients who had difficult-to-interpret CXRs), and (3) definite non-ALI. We compared clinical and genetic ALI risk factor associations between two classification schemes: AECC classification (definite ALI vs rest) and alternative classification (definite ALI vs definite non-ALI, excluding equivocal ALI). RESULTS: Ninety-three (35%) patients were classified as definite ALI, 67 (25%) as equivocal, and 104 (39%) as definite non-ALI. Estimates of clinical and genetic ALI risk factor associations were farther from the null using the alternative classification. In a multivariable risk factor model, the C statistic of the alternative classification was significantly higher than that derived from the AECC classification (0.82 vs 0.74; P < .01). CONCLUSIONS: The ability to detect ALI risk factors may be improved by excluding patients with equivocal or difficult-to-classify ALI. Such analyses may provide improved ability to detect clinical and genetic risk factor associations in future epidemiologic studies of ALI.