An aqueous pomegranate peel extract (Punica granatum) protect against Elastase-induced pulmonary emphysema in Sprague Dawley rats model

We investigated the effect of Punica granatum peel aqueous extract (PGE), on pulmonary inflammation and alveolar degradation induced by intratracheal administration of Elastase in Sprague Dawley rats. Lung inflammation was induced in rats by intratracheal instillation of Elastase. On day 1 and 2, animals received an intraperitoneal injection of PGE (200 mg/mL), three hours later, they were intratracheally instilled with 25U/kg pancreatic porcine Elastase. Animals were sacrificed 7 days later. Bronchoalveolar lavage (BAL) were collected and cellularity, histology and mRNA expression of Monocyte chemotactic protein 1(MCP-1), Tumor Necrosis Factor-Alpha (TNF-α), Interleukin 6 (IL-6), and Matrix Metalloproteinase-2 (MMP-2) were studied. In addition, activity of TNF- α, IL-6 and MCP-1 on BAL were also analyzed by ELISA Kit. Elastase administration increased: BAL cellularity, neutrophils recruitment and BAL MCP1, IL-6 expressions. It also increased lung TNF-α, MCP-1, MMP-2 expressions, platelets recruitment, histological parameters at 7th day of elastase treatment. Intraperitoneal injection of 200 mg/kg of PGE reduced, significantly, BAL cellularity, and neutrophils recruitment. However, in animal treated with PGE, MCP-1, MMP-2 and IL-6 on day 7, were similar to the Sham group. Treatment with PGE (200 mg/ kg) also significantly reduced lung TNF-α, and MCP-1 expression. This study reveals that PGE Punica granatum protects against elastase lung inflammation and alveolar degradation induced in rats

A consensus redefinition of transfusion-related acute lung injury.

BACKGROUND: Transfusion-related acute lung injury (TRALI) is a serious complication of blood transfusion and is among the leading causes of transfusion-related morbidity and mortality in most developed countries. In the past decade, the pathophysiology of this potentially life-threatening syndrome has been increasingly elucidated, large cohort studies have identified associated patient conditions and transfusion risk factors, and preventive strategies have been successfully implemented. These new insights provide a rationale for updating the 2004 consensus definition of TRALI. STUDY DESIGN AND METHODS: An international expert panel used the Delphi methodology to develop a redefinition of TRALI by modifying and updating the 2004 definition. Additionally, the panel reviewed issues related to TRALI nomenclature, patient conditions associated with acute respiratory distress syndrome (ARDS) and TRALI, TRALI pathophysiology, and standardization of reporting of TRALI cases. RESULTS: In the redefinition, the term "possible TRALI" has been dropped. The terminology of TRALI Type I (without an ARDS risk factor) and TRALI Type II (with an ARDS risk factor or with mild existing ARDS) is proposed. Cases with an ARDS risk factor that meet ARDS diagnostic criteria and where respiratory deterioration over the 12 hours before transfusion implicates the risk factor as causative should be classified as ARDS. TRALI remains a clinical diagnosis and does not require detection of cognate white blood cell antibodies. CONCLUSIONS: Clinicians should report all cases of posttransfusion pulmonary edema to the transfusion service so that further investigation can allow for classification of such cases as TRALI (Type I or Type II), ARDS, transfusion-associated circulatory overload (TACO), or TRALI or TACO cannot distinguish or an alternate diagnosis.

Lung ultrasound for monitoring cardiogenic pulmonary edema.

Several studies address the accuracy of lung ultrasound (LUS) in the diagnosis of cardiogenic pulmonary edema (CPE) evaluating the interstitial syndrome, which is characterized by multiple and diffuse vertical artifacts (B-lines), and correlates with extravascular lung water. We studied the potential role of LUS in monitoring CPE response to therapy, by evaluating the clearance of interstitial syndrome within the first 24 h after Emergency Department (ED) admission. LUS was performed at arrival (T0), after 3 (T3) and 24 (T24) hours. Eleven regions were evaluated in the antero-lateral chest; the B-lines burden was estimated in each region (0 = no B-lines, 1 = multiple B-lines, 2 = confluent B-lines/white lung) and a mean score (B-Score, range 0-2) was calculated. Patients received conventional CPE treatment. Blood chemistry, vital signs, blood gas analysis, diuresis at T0, T3, T24 were also recorded. A complete echocardiography was obtained during hospitalization. Forty-one patients were enrolled. Respiratory and hemodynamic parameters improved in all patients between T0 and T3 and between T3 and T24. Mean B-score significantly decreased at T3 (from 1.59 ± 0.40 to 0.73 ± 0.44, P < 0.001) and between T3 and T 24 (from 0.73 ± 0.44 to 0.38 ± 0.33, P < 0.001). B-score was higher in the lower pulmonary regions at any time. At final evaluation (T24) 75 % of apical and only 38 % of basal regions were cleared. LUS allows one to assess the clearance of interstitial syndrome and its distribution in the early hours of treatment of CPE, thus representing a possible tool to guide therapy titration.

Cytokines and clinical predictors in distinguishing pulmonary transfusion reactions.

BACKGROUND: Pulmonary transfusion reactions are important complications of blood transfusion, yet differentiating these clinical syndromes is diagnostically challenging. We hypothesized that biologic markers of inflammation could be used in conjunction with clinical predictors to distinguish transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO), and possible TRALI. STUDY DESIGN AND METHODS: In a nested case-control study performed at the University of California at San Francisco and Mayo Clinic, Rochester, we evaluated clinical data and blood samples drawn before and after transfusion in patients with TRALI (n = 70), possible TRALI (n = 48), TACO (n = 29), and controls (n = 147). Cytokines measured included granulocyte-macrophage-colony-stimulating factor, interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor-α. Logistic regression and receiver operating characteristics curve analyses were used to determine the accuracy of clinical predictors and laboratory markers in differentiating TACO, TRALI, and possible TRALI. RESULTS: Before and after transfusion, IL-6 and IL-8 were elevated in patients with TRALI and possible TRALI relative to controls, and IL-10 was elevated in patients with TACO and possible TRALI relative to that of TRALI and controls. For all pulmonary transfusion reactions, the combination of clinical variables and cytokine measurements displayed optimal diagnostic performance, and the model comparing TACO and TRALI correctly classified 92% of cases relative to expert panel diagnoses. CONCLUSIONS: Before transfusion, there is evidence of systemic inflammation in patients who develop TRALI and possible TRALI but not TACO. A predictive model incorporating readily available clinical and cytokine data effectively differentiated transfusion-related respiratory complications such as TRALI and TACO.

Clinical characteristics and outcome of children stung by scorpion.

UNLABELLED: Scorpion envenomation is a health problem in children in tropical and subtropical regions. The aim of this study was to evaluate demographic and clinical characteristics as well as outcomes in referred children to Assiut University Children Hospital during the year 2012 with a history of scorpion sting. The medical files of these patients were reviewed retrospectively for demographic data, time and site of biting, and clinical manifestations. Laboratory investigations of the patients were reviewed for complete blood count (CBC), liver function tests, creatinine phosphokinase (CPK), lactate dehydrogenase (LDH), arterial blood gases, and serum electrolytes. Results showed 111 children with a history of scorpion sting; 69 males and 42 females with a median age of 5 years. Out of the studied patients, 53.2 % were classified as class III of clinical severity with recorded pulmonary edema in 33.3 %, cardiogenic shock in 46.8 %, and severe neurological manifestations in 22.8 %. Twelve patients (10.8 %) were classified as class II with mild systemic manifestations, and 36 % of the patients were classified as class I with only local reaction. Outcomes of these patients were discharge without sequelae in 55.8 %, discharge with sequelae in 26.1 %, and death in 18.1 %. CONCLUSION: more than half of stung children had a severe clinical presentation and about one fifth died. Aggressive treatment regimens are recommended for such patients to improve the outcome.

[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.

New classification and clinical characteristics of reexpansion pulmonary edema after treatment of spontaneous pneumothorax.

OBJECTIVE: Reexpansion pulmonary edema (REPE) is a rare yet sometimes fatal complication associated with the treatment of lung diseases such as pleural effusion, pneumothorax, and hemothorax. The current study summarizes our experience with REPE for a 3-year period. METHODS: We prospectively collected demographic and clinical data on consecutive patients presenting to an academic university-based emergency department with spontaneous pneumothorax that was treated with closed thoracostomy for a 3-year period. RESULTS: Eighty-four study patients were enrolled between December 2002 and September 2005. Reexpansion pulmonary edema developed in 25 of 84 (29.8% [95% confidence interval, 21.0-40.2]) patients. Many cases of REPE were small and asymptomatic and only diagnosed on computed tomography of the chest. There was only one death (1.2% [95% confidence interval, A to B]). Reexpansion pulmonary edema was associated with patients with larger pneumothoraces without fibrotic changes and with patients with hypoxia and fibrotic changes. Classic REPE as seen on chest radiograph was 16 (19.0%) in 84 patients. Diffuse REPE as seen only on computed tomography and involved more than 1 lobe was 1 (1.2%) in 84 patients. Isolated REPE as seen only on computed tomography and limited to lesser than 1 lobe was 8 (9.5%) in 84 patients. CONCLUSIONS: The rate of REPE after tube thoracostomy of spontaneous pneumothorax is greater than previously reported and often asymptomatic. The risk of developing REPE is greater with larger pneumothorax, especially in patients without fibrotic lung changes, and with hypoxia in patients with fibrotic changes.

Uso da ventilação não-invasiva na terapêutica do edema pulmonar cardiogênico / Use of noninvasive mechanical ventilation in the treatment of cardiogenic pulmonary edema

Em pacientes com edema agudo de pulmão, a redução na complacência pulmonar correlaciona-se à congestão pulmonar. Clinicamente importante é o fato de que o desconforto respiratório não está diretamente relacionado à hipoxemia e não pode ser revertido apenas com administração de O2. A terapia médica usual inclui diuréticos, vasodilatadores e inotrópicos. Embora muitos pacientes respondam rapidamente ao tratamento de rotina, um número significante progride para insuficiência respiratória severa, com intubação endotraqueal e suas complicações associadas. O uso de pressão positiva não-invasiva por máscara reduz a necessidade de intubação endotraqueal. A análise da literatura atual comprova que a ventilação não-invasiva é segura e efetiva em reduzir a necessidade de intubação endotraqueal em pacientes com desconforto respiratório de origem cardíaca. Os resultados reforçam o conceito que a pressão positiva não-invasiva deve ser considerada uma forma não farmacológica de tratamento do edema agudo de pulmão cardiogênico e não simplesmente uma medida de suporte.

In patients with cardiogenic pulmonary edema, the reduction in lung compliance correlates with pulmonary congestion. Of clinical relevance is the fact that respiratory distress is not related directly to hypoxemia and cannot be reversed with O2 administration alone. Standard medical therapy includes diuretics, vasodilators and inotropics. Although many patients respond rapidly to standard treatment, a significant number progress to severe respiratory distress leading to endotracheal intubation with its associated complications. Noninvasive use of positive pressure delivered through a mask reduces the need for endotracheal intubation. The analysis of the current literature shows that noninvasive ventilation is safe and is effective in preventing the need for endotracheal intubation in patients with respiratory distress of cardiac origin. The results support the concept that noninvasive positive pressure ventilation must be seen as a non pharmacological form of treatment of acute pulmonary edema, rather than only as a supportive measure.

[Current concepts of pathophysiology, monitoring and resolution of pulmonary edema]. / Conceptos actuales en la fisiopatología, monitorización y resolución del edema pulmonar*

Pulmonary edema, both in its lesional as well as hydrostatic version, is a frequent cause of acute respiratory failure. From the pathophysiological point of view, the most important advance is undoubtedly the knowledge that the reabsorption process of pulmonary edema is an active process with energy consumption. This concept has revolutionized this field due to the possibility of finding substances or factors that stimulate or inhibit this reabsorption. Furthermore, in the monitoring field, significant advances have also been experimented due to the possibility of quantifying the edema in a simple and reliable way with transpulmonary thermodilution.

Accuracy of transpulmonary thermodilution versus gravimetric measurement of extravascular lung water.

OBJECTIVE: Pulmonary edema is a severe and often life-threatening condition. The diagnosis of pulmonary edema and its quantification have great clinical significance and yet can be difficult. A new technique based on thermodilution measurement using a single indicator has recently been developed (PiCCO, Pulsion Medical Systems, AG Germany). This method allows the measurement of extravascular lung water and thus can quantify degree of pulmonary edema. The technique has not been compared with a gold standard, gravimetric measurement of extravascular lung water. Therefore, the objective of this study was to determine the ability of extravascular lung water measurement with the PiCCO to reflect the extravascular lung water as measured with a gravimetric technique in a dog model of pulmonary edema. DESIGN: Prospective, randomized animal study. SETTING: A university animal research laboratory. SUBJECTS: Fifteen mongrel dogs (n = 5/group) weighing 20-30 kg. INTERVENTIONS: The dogs were anesthetized and mechanically ventilated. Five dogs served as controls; in five dogs hydrostatic pulmonary edema was induced using inflation of a left atrial balloon combined with fluid administration to maintain a high pulmonary artery occlusion pressure; and in five dogs pulmonary edema was induced by intravenous injection of oleic acid. After a period of stabilization in a state of pulmonary edema, extravascular lung water was measured with the PiCCO monitor. The animals were then killed, and extravascular lung water was measured using a gravimetric technique. MEASUREMENTS AND MAIN RESULTS: There was a very close (r =.967, p <.001) relationship between transpulmonary thermodilution and gravimetric measurements. The measurement with the PiCCO was consistently higher, by 3.01 +/- 1.34 mL/kg, than the gravimetric measurement. CONCLUSIONS: Measurement of extravascular lung water using transpulmonary thermodilution with a single indicator is very closely correlated with gravimetric measurement of lung water in both increased permeability and hydrostatic pulmonary edema.

Clinical relevance of time of onset, duration, and type of pulmonary edema after liver transplantation.

We investigated the clinical significance of time of onset, duration, and type of pulmonary edema after orthotopic liver transplantation by retrospectively reviewing 93 consecutive recipients. Pulmonary edema was diagnosed by means of radiographic criteria and Pao(2)/Fio(2) ratio <300. Type was identified by pulmonary artery wedge pressure (hydrostatic, >18 mm Hg; permeability, < or =18 mm Hg). Of 91 evaluable patients, 44 (48%) had no pulmonary edema, 23 (25%) had immediate pulmonary edema resolving within 24 hours, 8 (9%) had late pulmonary edema (developing de novo in the first 16 to 24 hours), and 16 (18%) had persistent pulmonary edema (developing immediately and persisting for at least 16 hours). At 16 to 24 hours, mean arterial pressure was lower with persistent permeability-type edema than without pulmonary edema (75 versus 87 mm Hg, P <.01). Patients with persistent permeability-type edema had higher mean pulmonary arterial pressure (23 versus 16 mm Hg, P <.01) and higher pulmonary vascular resistance (103 versus 53 dyn. second. m(-5), P <.05), consistent with a resistance-dependent mechanism. Patients with persistent hydrostatic-type edema did not differ from those without edema in mean arterial pressure (84 versus 87 mm Hg, P >.05) or pulmonary vascular resistance (67 versus 53 dyn. second. m(-5), P >.05), but had increased mean pulmonary arterial pressure (27 versus 16, P <.01), suggesting a flow volume-dependent mechanism. Duration of mechanical ventilation, intensive care, and hospital stay were prolonged in patients with late or persistent permeability-type edema but not in patients with immediate pulmonary edema of any type. In conclusion, immediate pulmonary edema resolving within 24 hours after liver transplantation had little clinical consequence; persistent permeability-type pulmonary edema portended a worse outcome.

Significance of the changes in the respiratory system pressure-volume curve during acute lung injury in rats.

UNLABELLED: The hypothesis that the changes in the respiratory system pressure- volume (PV) curve during pulmonary edema mainly reflect distal airway obstruction was investigated in rats. Normal rats had a well-defined upper inflection point (UIP) at low airway pressure. Airway occlusion by liquid instillation decreased compliance (Crs) and the volume (Vuip) of the UIP, and increased end-inspiratory pressure. The same changes were observed during the progression of edema produced by high volume ventilation (HV). Changes in Vuip and in Crs produced by HV were correlated with edema severity in normal rats or rats with lungs preinjured with alpha-naphthylthiourea. Vuip and Crs changes were proportional, reflecting compression of the PV curve on the volume axis and suggesting reduction of the amount of ventilatable lung at low airway pressure. In keeping with this explanation, the lower Vuip and Crs were before HV, the more severe HV-induced edema was in alpha-naphthylthiourea-injected rats. When edema was profuse, PV curves displayed a marked lower inflection point (LIP), the UIP at low pressure disappeared but another was seen at high volume above the LIP, and the correlation between Vuip changes and edema severity was lost. These observations may have clinical relevance in the context of the "open lung" strategy. KEYWORDS: ventilator-induced lung injury; respiratory mechanics; acute respiratory distress syndrome

Clinical and radiologic features of pulmonary edema.

Pulmonary edema may be classified as increased hydrostatic pressure edema, permeability edema with diffuse alveolar damage (DAD), permeability edema without DAD, or mixed edema. Pulmonary edema has variable manifestations. Postobstructive pulmonary edema typically manifests radiologically as septal lines, peribronchial cuffing, and, in more severe cases, central alveolar edema. Pulmonary edema with chronic pulmonary embolism manifests as sharply demarcated areas of increased ground-glass attenuation. Pulmonary edema with veno-occlusive disease manifests as large pulmonary arteries, diffuse interstitial edema with numerous Kerley lines, peribronchial cuffing, and a dilated right ventricle. Stage 1 near drowning pulmonary edema manifests as Kerley lines, peribronchial cuffing, and patchy, perihilar alveolar areas of airspace consolidation; stage 2 and 3 lesions are radiologically nonspecific. Pulmonary edema following administration of cytokines demonstrates bilateral, symmetric interstitial edema with thickened septal lines. High-altitude pulmonary edema usually manifests as central interstitial edema associated with peribronchial cuffing, ill-defined vessels, and patchy airspace consolidation. Neurogenic pulmonary edema manifests as bilateral, rather homogeneous airspace consolidations that predominate at the apices in about 50% of cases. Reperfusion pulmonary edema usually demonstrates heterogeneous airspace consolidations that predominate in the areas distal to the recanalized vessels. Postreduction pulmonary edema manifests as mild airspace consolidation involving the ipsilateral lung, whereas pulmonary edema due to air embolism initially demonstrates interstitial edema followed by bilateral, peripheral alveolar areas of increased opacity that predominate at the lung bases. Familiarity with the spectrum of radiologic findings in pulmonary edema from various causes will often help narrow the differential diagnosis.

Edema agudo de pulmao / Acute pulmonare edema

O edema agudo de pulmao pode ter causa cardiogenica)por pressao capilar pulmonar elevada)ou nao cardiogenica(com baixa pressao capilar).O edema pulmonar cardiogenico e associado com um aumento da pressao hidrostatica capilar ventricular esquerda(disfuncao sistolica)ou insuficiencia cardiaca diastolica secundaria,por exemplo,a estenose mitral,hypertensao arterial e cardiomiopatia hipertrofica.A historia medica e exame fisico em geral sao suficientes para iniciar o tratamento

Near-drowning and drowning classification: a proposal to stratify mortality based on the analysis of 1,831 cases.

STUDY OBJECTIVE: To establish an updated classification for near-drowning and drowning (ND/D) according to severity, based on mortality rate of the subgroups. MATERIALS AND METHODS: We reviewed 41,279 cases of predominantly sea water rescues from the coastal area of Rio de Janeiro City, Brazil, from 1972 to 1991. Of this total, 2,304 cases (5.5%) were referred to the Near-Drowning Recuperation Center, and this group was used as the study database. At the accident site, the following clinical parameters were recorded: presence of breathing, arterial pulse, pulmonary auscultation, and arterial BP. Cases lacking records of clinical parameters were not studied. The ND/D were classified in six subgroups: grade 1--normal pulmonary auscultation with coughing; grade 2--abnormal pulmonary auscultation with rales in some pulmonary fields; grade 3--pulmonary auscultation of acute pulmonary edema without arterial hypotension; grade 4--pulmonary auscultation of acute pulmonary edema with arterial hypotension; grade 5--isolated respiratory arrest; and grade 6--cardiopulmonary arrest. RESULTS: From 2,304 cases in the database, 1,831 cases presented all clinical parameters recorded and were selected for classification. From these 1,831 cases, 1,189 (65%) were classified as grade 1 (mortality=0%); 338 (18.4%) as grade 2 (mortality=0.6%); 58 (3.2%) as grade 3 (mortality=5.2%); 36 (2%) as grade 4 (mortality=19.4%); 25 (1.4%) as grade 5 (mortality=44%); and 185 (10%) as grade 6 (mortality=93%) (p<0.000001). CONCLUSION: The study revealed that it is possible to establish six subgroups based on mortality rate by applying clinical criteria obtained from first-aid observations. These subgroups constitute the basis of a new classification.