Estudo da permeabilidade vascular pulmonar e das junções interendoteliais na malária experimental / Study of pulmonary vascular permeability and interendothelial junctions in experimental malaria

Infecções por Plasmodium spp. podem acarretar em complicações pulmonares (1 a 40% dos casos), que podem resultar no desenvolvimento da síndrome do desconforto respiratório agudo (SDRA). Esta síndrome é caracterizada por inflamação aguda, lesão do endotélio alveolar e do parênquima pulmonar, disfunção e aumento da permeabilidade da barreira alvéolo-capilar pulmonar e, consequente, formação de efusão pleural. Neste sentido, os mecanismos de regulação da permeabilidade das células endoteliais e as junções interendoteliais têm papel crítico na manutenção do endotélio pulmonar. O objetivo do estudo foi determinar precocemente o desenvolvimento da SDRA associada à malária por tomografia computadorizada por emissão de fóton único (SPECT/CT), além de identificar alterações nas junções interendoteliais das células endoteliais pulmonares primárias de camundongos DBA/2 (CEPP-DBA/2), após contato com os eritrócitos parasitados de Plasmodium berghei ANKA (EP-PbA). Os nossos resultados demonstraram que é possível identificar alterações na aeração pulmonar no 5° e 7° dia após a infecção e, consequentemente, diferenciar os animais que desenvolveriam SDRA daqueles que evoluiriam para hiperparasitemia (HP). Além disso, observamos em CEPP-DBA/2 que o contato direto com EP-PbA aumenta da abertura das junções interendoteliais e da permeabilidade vascular. Assim, avaliamos a diminuição da expressão das proteínas das junções interendoteliais que contribuem para o aumento da permeabilidade vascular, por imunofluorescência e Western Blot. Apesar da SDRA ter sido identificada há mais de 50 anos, ainda não se conhece formas de diagnóstico precoce e os mecanimos efetivos de desenvolvimento desta enfermidade, que permitam um tratamento efetivo e que evite a morte do paciente. Portanto, sugere-se que a técnica de SPECT/CT seja uma importante ferramenta de diagnóstico para identificação precoce de SDRA associado a malária

Infections by Plasmodium spp. can lead to pulmonary complications (1 to 40% of the cases), that can result in the development of acute respiratory distress syndrome (ARDS). This syndrome is characterized by the acute inflammation, injury of the alveolar endothelium and pulmonary parenchyma, dysfunction and increased permeability of the pulmonary alveolar-capillary barrier and, consequently, formation of pleural effusion. In this aspect, mechanisms of regulation of endothelial cell permeability and interendothelial junctions play a critical role in the maintenance of the pulmonary endothelium. The present study aimed to determine the early development of single-photon emission computed tomography (SPECT/CT) associated malaria ARDS in addition to identifying changes in the interendothelial junctions of the primary pulmonary endothelial cells of DBA/2 mice (CEPP-DBA/2) after contact with erythrocytes infected with Plasmodium berghei ANKA (EP-PbA). Our results demonstrated that is possible to identify changes in lung aeration on the 5th and 7th day after infection and, consequently, differentiate the animals that should develop ARDS from those that would evolve to hyperparasitemia (HP). In addition, we observed in CEPP-DBA/2 that direct contact with EP-PbA increases the opening of the interendothelial junctions and vascular permeability. Thus, we evaluated that decrease the expression of interendothelial junction proteins contribute to the increase of vascular permeability, by immunofluorescence and Western Blot. Although ARDS was identified more than 50 years ago, it is not yet known what forms of early diagnosis, and the effective mechanisms of development of this disease, that allow an effective treatment and that prevent the death of the patient. Therefore, it is suggested that the SPECT/CT technique is a valuable tool to promote the early identification of ARDS associated with malaria

Effect of rhubarb on extravascular lung water in patients with acute respiratory distress syndrome

Summary Objective: The aim of this study was to evaluate the effect of rhubarb on extravascular lung water (EVLW) in patients with acute respiratory distress syndrome (ARDS). Method: A total of 80 patients with ARDS were randomly divided into a treatment group (40 cases) and control group (40 cases). Patients in the treatment group received rhubarb (30.0 g/d) and patients in the control group received conventional therapy for seven consecutive days. Extravascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI) were determined using pulse contour cardiac output (PiCCO) technology, and the oxygenation index was measured by blood gas analysis at baseline and on days 3, 5 and 7 after treatment. Results: The oxygenation index was higher and the levels of EVLWI and PVPI were lower after treatment in the two groups; however, these indexes showed significant differences on the 5th and 7th days after rhubarb treatment compared with the results in the control group (p<0.05). Conclusion: Rhubarb can decrease EVLWI and PVPI, and improve oxygenation in patients with ARDS.

Edema pulmonar por presión negativa / Negative pressure pulmonary edema

El edema pulmonar por presión negativa representa el 0.1% de las complicaciones pulmonares de los pacientes post ­ quirúrgicos, y la condicionante del incremento de dicha incidencia es la existencia de algún tipo de obstrucción de la vía aérea llegando hasta un 11% de casos. Su incidencia y prevalencia no son claras ya que es una entidad con infradiagnóstico. En los reportes de casos se coincide que la mayoría de pacientes son jóvenes con evaluaciones de riesgo quirúrgico bajos previamente sanos y que desarrollan en forma súbita un cuadro de edema agudo de pulmón, casi siempre posterior a la anesthesia, encontrándose ya no orointubados...(AU)

Predictors of Response to Corticosteroid Treatment in Patients with Early Acute Respiratory Distress Syndrome: Results of a Pilot Study

Prospective observational cohort study was performed to evaluate predictors for responsiveness to corticosteroid treatment in patients with acute respiratory distress syndrome (ARDS). Over the study period, a total of 20 patients (male 70%, median age 69) with ARDS were treated with corticosteroid within 72 h after intubation. The median lung injury score (LIS) and partial pressure of arterial oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratios (PF ratios) were 3.0 (interquartile range, 2.7-3.0) and 146.6 (119.9-179.4), respectively. The median levels of triggering receptor expressed on myeloid cells (TREM-1) and procollagen peptide type III in bronchoalveolar lavage (BAL) fluid were 349.3 (225.6-634.9) pg/mL and 19.6 (11.7-39.7) pg/mL, respectively. After 7 days of corticosteroid treatment, 10 (50%) patients showed response to the treatment (successful extubation in 7 and 1-point or more reduction in LIS in 3). Compared to non-responders, responders had higher initial PF ratios (170.5 vs. 127.2, p=0.023), lower level of TREM-1 in BAL fluid (313.6 pg/mL vs. 520.5 pg/mL, p=0.029), and greater reduction in LIS at 3 days (-1 vs. 0, p<0.001). In conclusion, PF ratios and TREM-1 level in BAL fluid at baseline, and reduction in LIS at day 3 after the treatment were associated with the response to prolonged corticosteroid treatment (ClinicalTrials.gov Identifier: NCT01093287).

Preventive Effect of Korean Red Ginseng for Acute Respiratory Illness: A Randomized and Double-Blind Clinical Trial

Korean Red Ginseng (KRG) is a functional food and has been well known for keeping good health due to its anti-fatigue and immunomodulating activities. However, there is no data on Korean red ginseng for its preventive activity against acute respiratory illness (ARI). The study was conducted in a randomized, double-blinded, placebo-controlled trial in healthy volunteers (Clinical Trial Number: NCT01478009). Our primary efficacy end point was the number of ARI reported and secondary efficacy end point was severity of symptoms, number of symptoms, and duration of ARI. A total of 100 volunteers were enrolled in the study. Fewer subjects in the KRG group reported contracting at least 1 ARI than in the placebo group (12 [24.5%] vs 22 [44.9%], P = 0.034), the difference was statistically significant between the two groups. The symptom duration of the subjects who experienced the ARI, was similar between the two groups (KRG vs placebo; 5.2 +/- 2.3 vs 6.3 +/- 5.0, P = 0.475). The symptom scores were low tendency in KRG group (KRG vs placebo; 9.5 +/- 4.5 vs 17.6 +/- 23.1, P = 0.241). The study suggests that KRG may be effective in protecting subjects from contracting ARI, and may have the tendency to decrease the duration and scores of ARI symptoms.

Revisiting steroid treatment for septic shock: molecular actions and clinical effects - a review

Corticosteroids are widely used to treat a diversity of pathological conditions including allergic, autoimmune and some infectious diseases. These drugs have complex mechanisms of action involving both genomic and non-genomic mechanisms and interfere with different signal transduction pathways in the cell. The use of corticosteroids to treat critically ill patients with acute respiratory distress syndrome and severe infections, such as sepsis and pneumonia, is still a matter of intense debate in the scientific and medical community with evidence both for and against its use in these patients. Here, we review the basic molecular mechanisms important for corticosteroid action as well as current evidence for their use, or not, in septic patients. We also present an analysis of the reasons why this is still such a controversial point in the literature.

Intoxicación por Paraquat: descripción de un caso clínico / Paraquat poisoning: a case report

El paraquat es el herbicida más vendido en todo el mundo. Se absorbe por las vías digestiva e inhalatoria. Si llega a los pulmones, produce congestión, edema alveolar con aumento de macrófagos que progresa a fibrosis y edema pulmonar, los cuales se presentan hasta 14 días después de la exposición si el afectado no recibió tratamiento oportuno y correcto. El paraquat se dirige fundamentalmente a los pulmones y genera allí radicales libres oxidantes; por eso, en los casos de intoxicación aguda está totalmente contraindicado usar oxígeno excepto cuando la presión parcial de oxigeno en sangre arterial sea inferior a 50 mmHg. Se presenta un caso clínico de un paciente quien desarrolló un síndrome de distress respiratorio del adulto (SDRA) secundario a ingesta intencional de paraquat. El manejo inicial se realizó con lavado gástrico y tierra de Fuller en solución acuosa al 30%. Posteriormente, el paciente desarrolló compromiso pulmonar y renal, los cuales fueron manejados con pulso de ciclofosfamida a 15 mg/kg/día por 2 días, metilprednisolona 1g/día por 3 días y posteriormente dexametasona 5 mg IV cada 6 horas por 5 días con una evolución clínica satisfactoria.

Paraquat is the best-selling herbicide throughout the world. It is absorbed by the digestive and inhalatory routes. If it reaches the lungs, congestion with swelling is developed, increased alveolar macrophages that progresses to fibrosis and pulmonary edema, which occur until 14 days after exposure if not treated timely and correct. Paraquat is directed primarily to the lungs and therefore generates free radicals oxidants, which is why, in cases of acute poisoning is absolutely forbidden to use oxygen except where arterial blood partial pressure of oxygen in is less than 50 mm Hg. A patient who developed an adult respiratory distress syndrome (ARDS) secondary to deliberate ingestion of paraquat is presented. Initial patient management was performed with gastric lavage and land Fuller in aqueous solution at 30%. Subsequently developing pulmonary and renal failure were handled with cyclophosphamide pulse of 15 mg/kg/day for 2 days, methylprednisolone 1g/día for 3 days, then dexamethasone 5 mg IV every 6 hours for 5 days, with favourable outcome.

Methylprednisolone therapy in a child with unresolving ARDS.

We report successful use of methyl-prednisolone in a 21-month old child with ARDS that did not improve with conventional therapy. The child improved and could be extubated after 10 days of methylprednisolone therapy. Subsequently, the child was weaned off supplementary oxygen. Methylprednisolone appeared to be safe and effective in a child with unresolving ARDS.

Influencia del reclutamiento alveolar sobre los efectos del surfactante exogeno / Influence of pulmonary recruitment on exogenous surfactant effects

Se investigaron los efectos producidos por una maniobra de insuflación sostenida previa a la administraciónde surfactante exógeno y los producidos por diferentes patrones ventilatorios sobre la respuesta al mismo. Se estudiaron 20 ratas albinas adultas a las que se les produjo una injuria pulmonar por repetidos lavados con solución fisiológica. Se evaluó el pH, PaO2, PaCO2, la presión arterial sistólica, la compliance toracopulmonar y la histología. Los animales se dividieron en 2 grupos según se les hubiera aplicado o no insuflación sostenida para evaluar el efecto inmediato de la misma. Posteriormente los grupos citados fueron subdivididos en función de la capacidad residual funcional (CRF) aplicada, quedando conformados 4 grupos experimentales. El grupo 1 recibió previo al surfactante una insuflación sostenida de 30 cm H2O durante 15 segundos y se ventiló posteriormente con presión al final de la espiración (PEEP) de10 cm H2O. El grupo 2, no recibió insuflación sostenida y se ventiló con PEEP 10 cm H2O. El grupo 3, recibió insuflación sostenida y se ventiló con PEEP 4 cm H2O y el grupo 4, sin insuflación sostenida se ventiló con PEEP 4 cm H2O. Los efectos inmediatos del surfactante no fueron modificados por la aplicación previa de insuflación sostenida. Se verificó durante el transcurso de la experiencia un aumento de la PaO2 asociada al aumento de la capacidad residual funcional (Grupo1 p=0.0001; Grupo2 p= 0.0001), e independiente de la insuflación sostenida. El uso de insuflación sostenida previo a la administración de surfactante sumado a la ventilación con capacidad residual funcional alta se asoció con infiltración de polimorfonucleares debajo del epitelio bronquiolar (p = 0.008). Nuestros resultados no avalan el uso de insuflación sostenida previo a la administración de surfactante exógeno.

Corticosteroids in acute respiratory distress syndrome

Improving the course and outcome of patients with acute respiratory distress syndrome presents a challenge. By understanding the immune status of a patient, physicians can consider manipulating proinflammatory systems more rationally. In this context, corticosteroids could be a therapeutic tool in the armamentarium against acute respiratory distress syndrome. Corticosteroid therapy has been studied in three situations: prevention in high-risk patients, early treatment with high-dose, short-course therapy, and prolonged therapy in unresolving cases. There are differences between the corticosteroid trials of the past and recent trials: today, treatment starts 2-10 days after disease onset in patients that failed to improve; in the past, the corticosteroid doses employed were 5-140 times higher than those used now. Additionally, in the past treatment consisted of administering one to four doses every 6 h (methylprednisolone, 30 mg/kg) versus prolonging treatment as long as necessary in the new trials (2 mg kg-1 day-1 every 6 h). The variable response to corticosteroid treatment could be attributed to the heterogeneous biochemical and molecular mechanisms activated in response to different initial insults. Numerous factors need to be taken into account when corticosteroids are used to treat acute respiratory distress syndrome: the specificity of inhibition, the duration and degree of inhibition, and the timing of inhibition. The major continuing problem is when to administer corticosteroids and how to monitor their use. The inflammatory mechanisms are continuous and cyclic, sometimes causing deterioration or improvement of lung function. This article reviews the mechanisms of action of corticosteroids and the results of experimental and clinical studies regarding the use of corticosteroids in acute respiratory distress syndrome.

Sindrome de distres respiratorio agudo utilidad de los costicoides / Acute respiratory distress syndrome: role of steroids

En Argentina, el síndrome de distrés respiratorio agudo (SDRA) representa el 7.7% de las admisiones en terapia intensiva y está asociado con una alta morbilidad y mortalidad (58%). Con frecuencia la muerte puede ser atribuida a más de una causa. La hipoxemia refractaria es una causa de muerte poco frecuente (15%) y en muchos casos puede coexistir con disfunción multiorgánica, sepsis o shock séptico. La utilidad de los esteroides como parte del tratamiento es aún motivo de debate a pesar de las múltiples series de casos y estudios clínicos publicados. En el artículo se evalúa la utilidad de los esteroides en el SDRA a través de la revisión de la bibliografía disponible. Se concluye que los esteroides estarían indicados en un pequeño subgrupo de pacientes con SDRA no resuelto o tardío, después de descartar o controlar una infección activa.

Pentoxifylline decreases tumor necrosis factor and interleukin-1 during high tidal volume

Tumor necrosis factor-alpha (TNF-alpha) is one of the most important proinflammatory cytokines which plays a central role in host defense and in the acute inflammatory response related to tissue injury. The major source of TNF-alpha are immune cells such as neutrophils and macrophages. We tested the hypothesis that pentoxifylline, a methylxanthine derivative, down-regulates proinflammatory cytokine expression during acute lung injury in rats. Male Wistar rats weighing 250 to 450 g were anesthetized ip with 50 mg/kg sodium thiopental and randomly divided into three groups: group 1 (N = 7): tidal volume (V T) = 7 ml/kg, respiratory rate (RR) = 50 breaths/min and normal saline infusion; group 2 (N = 7): V T = 42 ml/kg, RR = 9 breaths/min and normal saline infusion; group 3 (N = 7): V T = 42 ml/kg, RR = 9 breaths/min and pentoxifylline infusion. The animals were ventilated with an inspired oxygen fraction of 1.0, a positive end-expiratory pressure of 3 cmH2O, and normal saline or pentoxifylline injected into the left femoral vein. The mRNA of TNF-alpha rapidly increased in the lung tissue within 180 min of ventilation with a higher V T with normal saline infusion. The concentrations of inflammatory mediators were decreased in plasma and bronchoalveolar lavage (BAL) in the presence of higher V T with pentoxifylline infusion (TNF-alpha: plasma, 102.2 ± 90.9 and BAL, 118.2 ± 82.1; IL-1ß: plasma, 45.2 ± 42.7 and BAL, 50.2 ± 34.9, P < 0.05). We conclude that TNF-alpha produced by neutrophil influx may function as an alert signal in host defense to induce production of other inflammatory mediators

protective effects of early treatment with propofol on endotoxin-induced acute lung injury in rats

To investigate the effects of treatment with propofol administration at different time point in acute lung injury of endotoxin-induced shock in rats. 76 male wistar rats were randomly assigned to five groups: A] control group; B] endotoxemic group, receiving intravenous lipopolysaccharide [LPS] 8mgkg -1; C] pretreatment group, treated identically to endotoxemic group with the additional administration of propofol [5mgkg -1 bolus, followed by infusion at 10 mgkg -1h -1] of lhr prior to the injection of LPS; D] simultaneously treatment group, treated identically to endotoxemic group with the additional administration of propofol simultaneously with the injection of LPS; E] post-treatment group, which was treated identically to endotoxemic group except for administration of propofol lhr after the injection of LPS. PaO 2, pH, MAP and survival rate were recorded and plasma NO, TNF-alpha were measured during 5-hr after the injection of LPS. After the rats were killed, lung tissue was sampled to measured expression of inducible nitric oxide synthase [iNOS], nitrotyrosine [NT], myeloperoxidase [MPO] activity, malondialdehyde [MDA], wet-to-dry lung weight ratio [W/D], and pulmonary permeability index [PPI]. Compared with the endotoxemic group, both the pretreatment and simultaneously treatment groups, significantly improved PaO 2, pH, MAP and 5th hour survival rate of rats, and attenuated endotoxin-induced increased iNOSmRNA, NT expression, MPO activity and MDA level in lung tissue, and decreased pulmonary microvascular permeability, TNF alpha, NO in plasma. But these beneficial efficacies were blunted in the post-treatment group. These findings showed that propofol administration may provide protective effects on acute lung injury in endotoxin-induced shock

Atypical fulminant Rickettsia rickettsii infection (Brazilian spotted fever) presenting as septic shock and adult respiratory distress syndrome

Brazilian spotted fever, caused by Rickettsia rickettsii, has been increasingly reported in Brazil especially in the southeastern states. The severe and fulminant forms of the disease are not unusual but most of the reported fatal cases have shown some typical clinical clue, which leads the attending physician to a correct diagnosis. We report a probable case of atypical fulminant Brazilian spotted fever that presented full-blown septic shock associated with Adult Respiratory Distress Syndrome (ARDS) and delayed uncharacteristic rash with an over four-fold increase in reciprocal IgM, but not IgG titer against Rickettsia rickettsii. Brazilian practitioners should be aware of the possibility of Brazilian spotted fever as a cause of fulminant primary sepsis with ARDS; improved laboratory methods are necessary for the rapid diagnosis of such cases.

Profilaxia e tratamento da síndrome do desconforto respiratório com diferentes surfactantes / Prophylaxis and treatment of respiratory distress syndrome with different surfactants

O tratamento etiológico da síndrome do desconforto respiratório (SDR) por imaturidade pulmonar com surfactante exógeno é uma estratégia de eficácia comprovada. Entretanto, a eficácia relativa dos diversos preparados tensoativos, de origem natural ou sintética, pode näo ser semelhante. O objetivo é avaliar se há evidencias de que um ou mais preparados tensoativos podem ser considerados mais eficazes no tratamento e profilaxia da síndroome do desconforto respiratório. Foi realizada uma pesquisa bibliográfica intensa em várias bases de dados, para identificar os estudos comparativos dos diferentes compostos tensoativos. Existem casos que corroboram que os surfactantes de origem natural produzem uma melhora mais rápida da oxigenaçäo, em comparaçäo com os de origem sintética. Também foram observadas as taxas de complicaçöes e as de mortalidade mais baixas com o emprego de surfactantes naturais. Dos dois surfactantes naturais comercializados na Espanha, o produto de origem porcina(poractant alfa) parece apresentar vantagens sobre o produto de origem bovina (beractant), como uma açäo mais rápida, expressa por uma razäo de PaO2/PaO2 mais favorável dentro das primeiras 24 horas de tratamento. Também existe uma tendência a que os pacientes tratados com surfactante porcino apresentem uma taxa de mortalidade global mais baixa, em comparaçäo com os pacientes tratados com surfactante bovino. Näo existe nenhuma razäo científica que corrobore o uso dos surfactantes sintéticos comercializados atualmente. O surfactante natural de origem porcina poderia ser considerado de primeira escolha, embora seja conveniente dispor de estudos adicionais que confirmem esse achado.(au)