RESUMO
Previously, we demonstrated that supplementation of resuscitation fluids with the Kv7 voltage-activated potassium channel inhibitor linopirdine reduces fluid resuscitation requirements and stabilizes hemodynamics in various rat models of hemorrhagic shock. To further evaluate the therapeutic potential of linopirdine, we tested the effects of linopirdine-supplemented resuscitation fluids in a rat model of ischemia-reperfusion injury-induced acute respiratory distress syndrome (ARDS). Ventilated rats underwent unilateral lung ischemia from t=0-75 min, followed by lung reperfusion and fluid resuscitation to a mean arterial blood pressure of 60 mmHg with normal saline (NS, n=9) or NS supplemented with 50 µg/ml linopridine (NS-L), n=7) until t=360 min. As compared with NS, fluid resuscitation with NS-L stabilized blood pressure and reduced fluid requirements by 40% (p<0.05 vs. NS at t=240-360 min). While NS-L did not affect ARDS development, it reduced mortality from 66% with NS to 14% with NS-L (p=0.03, hazard ratio 0.14; 95% confidence interval of the hazard ratio: 0.03-0.65). Median survival time was 240 min with NS and >360 min with NS-L. As compared with NS treated animals that survived the observation period (n=3), however, plasma lactate and creatinine concentrations at t=360 min were higher with NS-L (n=6; p<0.05). Our findings extend therapeutic potential of NS-L from hypovolemic/hemorrhagic shock to hemodynamic instability under normovolemic conditions during organ ischemia-reperfusion injury. Possible adverse effects of NS-L, such as impairment of renal function and/or organ hypoperfusion, require further evaluation in long-term pre-clinical models.
Assuntos
Hidratação , Indóis/administração & dosagem , Bloqueadores dos Canais de Potássio/administração & dosagem , Piridinas/administração & dosagem , Traumatismo por Reperfusão/complicações , Síndrome do Desconforto Respiratório/terapia , Ressuscitação , Solução Salina/administração & dosagem , Animais , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Infusões Intravenosas , Masculino , Ratos Sprague-Dawley , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/fisiopatologia , Fatores de TempoRESUMO
Infection with Leptospira spp. is common in Réunion, a tropical island in the Indian Ocean. However, respiratory coinfections between strains of Leptospira spp. and other microorganisms are rarely described. Here, we describe the first reported case of coinfection between Leptospira spp. and Chlamydia pneumoniae, responsible for refractory acute respiratory distress syndrome requiring extracorporeal membrane oxygenation with a favorable outcome. In a case of leptospirosis with severe respiratory illness, testing for respiratory coinfection, especially with atypical pathogens, could explain the seriousness of the clinical condition and lead to specific treatment.
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Antibacterianos/uso terapêutico , Infecções por Chlamydophila/complicações , Coinfecção , Leptospirose/complicações , Síndrome do Desconforto Respiratório/tratamento farmacológico , Síndrome do Desconforto Respiratório/terapia , Adulto , Chlamydophila pneumoniae/isolamento & purificação , Oxigenação por Membrana Extracorpórea , Humanos , Leptospira/isolamento & purificação , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/fisiopatologia , Reunião , Resultado do TratamentoRESUMO
INTRODUCTION: Hyperoxic lung injury is a condition that can occur in patients in need of supplemental oxygen, such as premature infants with bronchopulmonary dysplasia or adults with acute respiratory distress syndrome. Cytochrome P450 (CYP) enzymes play critical roles in the metabolism of endogenous and exogenous compounds. AREAS COVERED: Through their complex pathways, some subfamilies of these enzymes may contribute to or protect against hyperoxic lung injury. Oxidative stress from reactive oxygen species (ROS) production is most likely a major contributor of hyperoxic lung injury. CYP1A enzymes have been shown to protect against hyperoxic lung injury while CYP1B enzymes seem to contribute to it. CYP2J2 enzymes help protect against hyperoxic lung injury by triggering EET production, thereby, increasing antioxidant enzymes. The metabolism of arachidonic acid to ω-terminal hydroxyeicosatetraenoic acid (20-HETEs) by CYP4A and CYP4F enzymes could impact hyperoxic lung injury via the vasodilating effects of 20-HETE. CYP2E1 and CYP2A enzymes may contribute to the oxidative stress in the lungs caused by ethanol- and nicotine-metabolism, respectively. EXPERT OPINION: Overall, the CYP enzymes, depending upon the isoform, play a contributory or protective role in hyperoxic lung injury, and are, therefore, ideal candidates for developing drugs that can treat oxygen-mediated lung injury.
Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Hiperóxia/complicações , Lesão Pulmonar/etiologia , Adulto , Animais , Displasia Broncopulmonar/enzimologia , Displasia Broncopulmonar/fisiopatologia , Humanos , Hiperóxia/enzimologia , Recém-Nascido , Recém-Nascido Prematuro , Lesão Pulmonar/enzimologia , Lesão Pulmonar/fisiopatologia , Estresse Oxidativo/fisiologia , Síndrome do Desconforto Respiratório/enzimologia , Síndrome do Desconforto Respiratório/fisiopatologiaRESUMO
INTRODUCTION: Sepsis is the most common etiology of acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Capillary leakage caused by lung endothelial injury is the central cause of ARDS. The results of research in modern medicine in reducing endothelial damage and restoring endothelial functions are limited. In the previous clinical observations, we found that the Fusu mixture not only improves the clinical symptoms but also reduces the leakage of pulmonary capillaries. Therefore, the purpose of this study is to determine the clinical efficacy of the Fusu mixture combined with Western medicine in the treatment of ARDS caused by sepsis and to explore the mechanism of traditional Chinese medicine. METHODS: This is a prospective, single-center, randomized, single-blind, and controlled clinical study involving 620 eligible patients. The patients will be randomly divided into 2 groups: the Western medicine treatment group and the combination of Chinese and Western medicine treatment group. After 14 days of intervention, the clinical efficacy and safety of the Fusu mixture on sepsis-induced ARDS patients will be observed. The primary outcome will be measured as 28-day mortality. The secondary outcome indices include inflammatory markers (CRP, PCT, IL-6, TNF - α), APACHE II score, SOFA score, days without a ventilator, blood gas analysis (Lac, PaO2â/ FiO2), intensive care unit hospital stay time, intensive care unit mortality. Simultaneously, the analysis of the exploratory results will be carried out to analyze the possible mechanism of Fusu mixture in the treatment of sepsis-induced ARDS by the high-throughput sequencing and bioinformatics. DISCUSSION: The purpose of this study is to evaluate the clinical efficacy of Fusu mixture in the treatment of sepsis-induced ARDS and explore its possible mechanism of action. If successful, it will provide evidence-based adjuvant therapy for the clinical treatment of ARDS.
Assuntos
Síndrome do Desconforto Respiratório/tratamento farmacológico , Síndrome do Desconforto Respiratório/etiologia , Sepse/complicações , Adulto , Gasometria , Síndrome de Vazamento Capilar/complicações , Síndrome de Vazamento Capilar/etiologia , Feminino , Humanos , Masculino , Medicina Tradicional Chinesa/métodos , Medicina Tradicional Chinesa/normas , Pessoa de Meia-Idade , Estudos Prospectivos , Síndrome do Desconforto Respiratório/fisiopatologia , Sepse/tratamento farmacológico , Sepse/fisiopatologia , Método Simples-Cego , Resultado do TratamentoRESUMO
BACKGROUND: This study investigated the potential therapeutic effects of acupoint catgut embedding (ACE) at ST36 and BL13 on lipopolysaccharide- (LPS-) induced acute respiratory distress syndrome (ARDS) in rats. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomized into the normal saline (NS group with a sham procedure), lipopolysaccharide (LPS group with a sham procedure), and LPS plus ACE (LPS+ACE with ACE at bilateral BL13 and ST36 acupoints one day before LPS injection) groups. After intratracheal instillation of normal saline or LPS (0.5 mg/kg), all rats were subjected to mechanical ventilation for 4 h. Their blood gas was analyzed before and after lung injury, and their lung pressure-volumes were measured longitudinally. The levels of TNF-α, IL-6, IL-10, and phosphatidylcholine (PC) and total proteins (TP) in bronchial alveolar lavage fluid (BALF) were assessed. Their wet to dry lung weight ratios, histology, myeloperoxidase (MPO), superoxide dismutase (SOD) activity, and malondialdehyde (MDA) levels were measured. Their lung aquaporin 1 (AQP1) and Occludin protein levels were analyzed. RESULTS: LPS administration significantly decreased the ratios of PaO2/FiO2 and pressure-volumes and induced lung inflammation and injury by increased concentrations of TNF-α, IL-6, IL-10, and TP in BALF and MPO and MDA in the lung but decreased PC in BALF and SOD activity in the lungs. LPS also reduced AQP1 and Occludin protein levels in the lung of rats. In contrast, ACE significantly mitigated the LPS-induced lung injury, inflammation, and oxidative stress and preserved the AQP1 and Occludin contents in the lung of rats. CONCLUSIONS: ACE significantly improved respiratory function by mitigating inflammation and oxidative stress and preserving AQP1 and Occludin expression in the lung in a rat model of LPS-induced ARDS.
Assuntos
Pontos de Acupuntura , Categute , Síndrome do Desconforto Respiratório , Animais , Materiais Biocompatíveis/farmacologia , Líquido da Lavagem Broncoalveolar/química , Citocinas/metabolismo , Lipopolissacarídeos/efeitos adversos , Pulmão/química , Pulmão/fisiologia , Complacência Pulmonar/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Síndrome do Desconforto Respiratório/induzido quimicamente , Síndrome do Desconforto Respiratório/metabolismo , Síndrome do Desconforto Respiratório/fisiopatologiaRESUMO
CASE PRESENTATION: A 55-year-old man presented to the ED with a 3-week history of worsening cough and shortness of breath. He had blood-tinged sputum, fever, night sweats, and a 2.7 kg weight loss within the same period. For the past few days, he had taken amoxicillin-clavulanate for presumed sinusitis. Despite this, his symptoms persisted, prompting him to seek further evaluation. His medical history was significant for ulcerative colitis and he had some bloody diarrhea for the past few weeks. Medications included aspirin, mesalamine, multivitamins, folic acid, and herbal supplements including gingko biloba, ginseng, and turmeric-ginger. He never smoked and drank alcohol occasionally. Family history was notable for stroke and myocardial infarction.
Assuntos
Obstrução das Vias Respiratórias , Broncoscopia/métodos , Colite Ulcerativa , Criocirurgia/métodos , Glucocorticoides/administração & dosagem , Infliximab/administração & dosagem , Úlcera , Obstrução das Vias Respiratórias/diagnóstico por imagem , Obstrução das Vias Respiratórias/etiologia , Obstrução das Vias Respiratórias/patologia , Obstrução das Vias Respiratórias/terapia , Antirreumáticos/administração & dosagem , Colite Ulcerativa/complicações , Colite Ulcerativa/fisiopatologia , Colite Ulcerativa/terapia , Tosse/diagnóstico , Tosse/etiologia , Diagnóstico Diferencial , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Necrose/complicações , Necrose/patologia , Necrose/terapia , Respiração Artificial/métodos , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/fisiopatologia , Síndrome do Desconforto Respiratório/terapia , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Úlcera/etiologia , Úlcera/patologiaRESUMO
This review summarizes current understanding of mitochondrial bioenergetic dysfunction applicable to mechanisms of lung diseases and outlines challenges and future directions in this rapidly emerging field. Although the role of mitochondria extends beyond the term of cellular "powerhouse", energy generation remains the most fundamental function of these organelles. It is not counterintuitive to propose that intact energy supply is important for favorable cellular fate following pulmonary insult. In this review, the discussion of mitochondrial dysfunction focuses on those molecular mechanisms that alter cellular bioenergetics in the lungs: (a) inhibition of mitochondrial respiratory chain, (b) mitochondrial leak and uncoupling, (c) alteration of mitochondrial Ca2+ handling, (d) mitochondrial production of reactive oxygen species and self-oxidation. The discussed lung diseases were selected according to their pathological nature and relevance to pediatrics: Acute lung injury (ALI), defined as acute parenchymal lung disease associated with cellular demise and inflammation (Acute Respiratory Distress Syndrome, ARDS, Pneumonia), alveolar developmental failure (Bronchopulmonary Dysplasia, BPD or chronic lung disease in premature infants), obstructive airway diseases (Bronchial asthma) and vascular remodeling affecting pulmonary circulation (Pulmonary Hypertension, PH). The analysis highlights primary mechanisms of mitochondrial bioenergetic dysfunction contributing to the disease-specific pulmonary insufficiency and proposes potential therapeutic targets.
Assuntos
Metabolismo Energético , Pneumopatias/metabolismo , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/fisiopatologia , Asma/metabolismo , Asma/fisiopatologia , Displasia Broncopulmonar/metabolismo , Displasia Broncopulmonar/fisiopatologia , Cálcio/metabolismo , Respiração Celular , Transporte de Elétrons , Humanos , Hiperóxia/metabolismo , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/fisiopatologia , Pneumopatias/fisiopatologia , Pneumonia/metabolismo , Pneumonia/fisiopatologia , Síndrome do Desconforto Respiratório/metabolismo , Síndrome do Desconforto Respiratório/fisiopatologia , Remodelação VascularRESUMO
INTRODUCTION: The acute respiratory distress syndrome (ARDS) is a common and catastrophic condition, with a high mortality rate and economic burden on society. Despite 50 years of study, there is no specific pharmacological therapy for ARDS. Areas covered: This review outlines the definitions, epidemiology, risk factors and pathophysiology of ARDS. The priority of developing a clinically-relevant model for ARDS to test pre-clinical candidates is discussed, together with the limitations of current models. The scientific rationale of emerging therapeutic candidates is outlined in the setting of the biological mechanisms implicated in the complex pathogenesis of ARDS. Emerging therapies, currently in clinical trials, are discussed, including the pre-clinical basis for their use and the expected timeline to trial completion. Expert opinion: We highlight the necessity of improving pre-clinical models of ARDS and the design of clinical trials for the development of novel pharmacological therapies. We reflect on the most promising emerging strategies and their potential role in ARDS management.
Assuntos
Desenvolvimento de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Síndrome do Desconforto Respiratório/tratamento farmacológico , Animais , Ensaios Clínicos como Assunto/métodos , Efeitos Psicossociais da Doença , Humanos , Projetos de Pesquisa , Síndrome do Desconforto Respiratório/mortalidade , Síndrome do Desconforto Respiratório/fisiopatologia , Fatores de RiscoRESUMO
PURPOSE: To assess the role of high-flow nasal therapy (HFNT) compared to standard oxygen (SO) as complementary therapy to non-invasive ventilation (NIV). METHODS: Multicenter trial including patients (nâ¯=â¯54) anticipated to receive NIV for ≥24â¯h due to acute or acute-on-chronic respiratory failure. Subjects were randomized (1:1) to SO or HFNT during breaks off NIV. Primary outcome was total time on and off NIV. Secondary outcomes were comfort and dyspnea, respiratory rate (RR), oxygen saturation (SpO2), tolerance and side effects. RESULTS: Total time per patient on NIV (1315 vs 1441â¯min) and breaks (1362 vs 1196â¯min), and mean duration of each break (520 vs 370â¯min) were similar in the HFNT and SO arms (pâ¯>â¯.05). Comfort score was higher on HFNT than on SO (8.3⯱â¯2.7 vs 6.9⯱â¯2.3, pâ¯=â¯.001). Dyspnea, RR and SpO2 were similar in the two arms, but the increase in RR and dyspnea seen with SO during breaks did not occur with HFNT. CONCLUSION: Compared to SO, HFNT did not reduce time on NIV. However, it was more comfortable and the increase in RR and dyspnea seen with SO did not occur with HFNT. Therefore, HFNT could be a suitable alternative to SO during breaks off NIV.
Assuntos
Ventilação não Invasiva/métodos , Oxigenoterapia/métodos , Oxigênio/administração & dosagem , Síndrome do Desconforto Respiratório/terapia , Insuficiência Respiratória/terapia , Idoso , Idoso de 80 Anos ou mais , Dispneia/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxigênio/análise , Projetos Piloto , Síndrome do Desconforto Respiratório/fisiopatologia , Insuficiência Respiratória/fisiopatologia , Taxa Respiratória/fisiologiaRESUMO
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.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Água Extravascular Pulmonar/efeitos dos fármacos , Síndrome do Desconforto Respiratório/tratamento farmacológico , Rheum/química , Adulto , Idoso , Análise de Variância , Gasometria , Permeabilidade Capilar/efeitos dos fármacos , Permeabilidade Capilar/fisiologia , Débito Cardíaco/efeitos dos fármacos , Débito Cardíaco/fisiologia , Água Extravascular Pulmonar/fisiologia , Feminino , Humanos , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Oxigênio/fisiologia , Edema Pulmonar/tratamento farmacológico , Reprodutibilidade dos Testes , Síndrome do Desconforto Respiratório/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Critically ill patients require regular body position changes to minimize the adverse effects of bed rest, inactivity and immobilization. However, uncertainty surrounds the effectiveness of lateral positioning for improving pulmonary gas exchange, aiding drainage of tracheobronchial secretions and preventing morbidity. In addition, it is unclear whether the perceived risk levied by respiratory and haemodynamic instability upon turning critically ill patients outweighs the respiratory benefits of side-to-side rotation. Thus, lack of certainty may contribute to variation in positioning practice and equivocal patient outcomes. OBJECTIVES: To evaluate effects of the lateral position compared with other body positions on patient outcomes (mortality, morbidity and clinical adverse events) in critically ill adult patients. (Clinical adverse events include hypoxaemia, hypotension, low oxygen delivery and global indicators of impaired tissue oxygenation.) We examined single use of the lateral position (i.e. on the right or left side) and repeat use of the lateral position (i.e. lateral positioning) within a positioning schedule. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 5), MEDLINE (1950 to 23 May 2015), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1937 to 23 May 2015), the Allied and Complementary Medicine Database (AMED) (1984 to 23 May 2015), Latin American Caribbean Health Sciences Literature (LILACS) (1901 to 23 May 2015), Web of Science (1945 to 23 May 2015), Index to Theses in Great Britain and Ireland (1950 to 23 May 2015), Trove (2009 to 23 May 2015; previously Australasian Digital Theses Program (1997 to December 2008)) and Proquest Dissertations and Theses (2009 to 23 May 2015; previously Proquest Digital Dissertations (1980 to 23 May 2015)). We handsearched the reference lists of potentially relevant reports and two nursing journals. SELECTION CRITERIA: We included randomized and quasi-randomized trials examining effects of lateral positioning in critically ill adults. We included manual or automated turns but limited eligibility to studies that included duration of body position of 10 minutes or longer. We examined each lateral position versus at least one comparator (opposite lateral position and/or another body position) for single therapy effects, and the lateral positioning schedule (repeated lateral turning) versus other positioning schedules for repetitive therapy effects. DATA COLLECTION AND ANALYSIS: We pre-specified methods to be used for data collection, risk of bias assessment and analysis. Two independent review authors carried out each stage of selection and data extraction and settled differences in opinion by consensus, or by third party adjudication when disagreements remained unresolved. We planned analysis of pair-wise comparisons under composite time intervals with the aim of considering recommendations based on meta-analyses of studies with low risk of bias. MAIN RESULTS: We included 24 studies of critically ill adults. No study reported mortality as an outcome of interest. Two randomized controlled trials (RCTs) examined lateral positioning for pulmonary morbidity outcomes but provided insufficient information for meta-analysis. A total of 22 randomized trials examined effects of lateral positioning (four parallel-group and 18 cross-over designs) by measuring various continuous data outcomes commonly used to detect adverse cardiopulmonary events within critical care areas. However, parallel-group studies were not comparable, and cross-over studies provided limited data as the result of unit of analysis errors. Eight studies provided some data; most of these were single studies with small effects that were imprecise. We pooled partial pressure of arterial oxygen (PaO2) as a measure to detect hypoxaemia from two small studies of participants with unilateral lung disease (n = 19). The mean difference (MD) between lateral positions (bad lung down versus good lung down) was approximately 50 mmHg (MD -49.26 mmHg, 95% confidence interval (CI) -67.33 to -31.18; P value < 0.00001). Despite a lower mean PaO2 for bad lung down, hypoxaemia (mean PaO2 < 60 mmHg) was not consistently reported. Furthermore, pooled data had methodological shortcomings with unclear risk of bias. We had similar doubts regarding internal validity for other studies included in the review. AUTHORS' CONCLUSIONS: Review authors could provide no clinical practice recommendations based on the findings of included studies. Available research could not eliminate the uncertainty surrounding benefits and/or risks associated with lateral positioning of critically ill adult patients. Research gaps include the effectiveness of lateral positioning compared with semi recumbent positioning for mechanically ventilated patients, lateral positioning compared with prone positioning for acute respiratory distress syndrome (ARDS) and less frequent changes in body position. We recommend that future research be undertaken to address whether the routine practice of repositioning patients on their side benefits all, some or few critically ill patients.
Assuntos
Estado Terminal , Posicionamento do Paciente/métodos , Postura , Adulto , Humanos , Hipóxia/diagnóstico , Pneumopatias/fisiopatologia , Pessoa de Meia-Idade , Oxigênio/sangue , Pressão Parcial , Posicionamento do Paciente/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Síndrome do Desconforto Respiratório/fisiopatologia , IncertezaRESUMO
OBJECTIVE: To observe the effects of Xuanbai Chengqi decoction on lung compliance for patients with exogenous pulmonary acute respiratory distress syndrome. SUBJECTS AND METHODS: A total of 53 patients with exogenous pulmonary acute respiratory distress syndrome, who were admitted to the intensive care unit of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine from March 2009 to February 2013, were selected. They were randomly divided into the treatment group (25 cases) and the control group (28 cases). Both the groups were treated with conventional treatment and lung-protective ventilation strategy; apart from these, enema therapy with Xuanbai Chengqi decoction was given to the treatment group. Meanwhile, static lung compliance, dynamic lung compliance, peak airway pressure, plateau pressure, and positive end-expiratory pressure (PEEP) for patients in both the groups were observed and recorded at 24, 48, and 72 hours after the drug was used. Moreover, variations in the duration of parenteral nutrition, incidence rate of complications, and case fatality rate in patients after treatment were recorded. RESULTS: For patients in the treatment group, at 48 and 72 hours after treatment, the static lung compliance and dynamic lung compliance were significantly higher than those in the control group, while plateau pressure, peak airway pressure, and PEEP were significantly lower than those before treatment. At the same time, PEEP for patients in the treatment group at 72 hours after treatment was remarkably lower than that in the control group, showing significant difference (P<0.05). The duration of parenteral nutrition in the treatment group was significantly shorter than that in the control group (P<0.05). Both the incidence rate and the fatality rate of complications, such as abdominal distension and ventilator-associated pneumonia, for patients in the treatment group were distinctly smaller than those in the control group (P<0.05). CONCLUSION: Xuanbai Chengqi decoction not only can improve the static lung compliance and dynamic compliance of patients with exogenous pulmonary distress syndrome but also can shorten the parenteral nutrition duration, as well as reducing the complication incidence rate and fatality rate.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Síndrome do Desconforto Respiratório/tratamento farmacológico , Síndrome do Desconforto Respiratório/fisiopatologia , Adulto , Idoso , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/química , Feminino , Humanos , Complacência Pulmonar/efeitos dos fármacos , Masculino , Medicina Tradicional Chinesa , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Interleukin-17A is a proinflammatory cytokine known to play a role in host defense and pathologic inflammation in murine models of lung injury. The relationship between interleukin-17A and inflammation in human lung injury is unknown. Our primary objective was to determine whether interleukin-17A levels are associated with alveolar measures of inflammation and injury in patients with acute respiratory distress syndrome. Our secondary objective was to test whether interleukin-17A levels are associated with acute respiratory distress syndrome-related outcomes. DESIGN: Observational study. SETTING: Six North American medical centers. PATIENTS: We studied two groups of patients with acute respiratory distress syndrome: 1) patients previously enrolled in a placebo-controlled clinical trial of omega-3 fatty acids performed at five North American medical centers (n = 86, acute respiratory distress syndrome 1), and 2) patients with systemic inflammatory response syndrome admitted to an ICU who developed acute respiratory distress syndrome (n = 140, acute respiratory distress syndrome 2). In acute respiratory distress syndrome 1, we used paired serum and bronchoalveolar lavage fluid samples obtained within 48 hours of acute respiratory distress syndrome onset, whereas in acute respiratory distress syndrome 2, we used plasma obtained within the first 24 hours of ICU admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We measured circulating interleukin-17A in acute respiratory distress syndrome 1 and acute respiratory distress syndrome 2. We also measured interleukin-17A, neutrophil counts, and total protein in bronchoalveolar lavage fluid from acute respiratory distress syndrome 1. We found that bronchoalveolar lavage interleukin-17A was strongly associated with higher bronchoalveolar lavage percent neutrophils (p < 0.001) and bronchoalveolar lavage total protein (p < 0.01) in acute respiratory distress syndrome1. In both acute respiratory distress syndrome 1 and acute respiratory distress syndrome 2, elevated interleukin-17A was associated with higher Sequential Organ Failure Assessment scores (p < 0.05). CONCLUSIONS: Elevated circulating and alveolar levels of interleukin-17A are associated with increased percentage of alveolar neutrophils, alveolar permeability, and organ dysfunction in acute respiratory distress syndrome.
Assuntos
Inflamação/imunologia , Interleucina-17/sangue , Alvéolos Pulmonares/fisiopatologia , Síndrome do Desconforto Respiratório/imunologia , Lesão Pulmonar Aguda/imunologia , Idoso , Líquido da Lavagem Broncoalveolar/química , Citocinas/metabolismo , Feminino , Humanos , Unidades de Terapia Intensiva , Interleucina-17/análise , Interleucina-8/sangue , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Escores de Disfunção Orgânica , Síndrome do Desconforto Respiratório/fisiopatologia , Sepse , Resultado do TratamentoRESUMO
Acute lung injury (ALI) and its most severe manifestation, acute respiratory distress syndrome (ARDS), is a clinical syndrome defined by acute hypoxemic respiratory failure and bilateral pulmonary infiltrates consistent with edema. In-hospital mortality is 38.5% for AL, and 41.1% for ARDS. Activation of alveolar macrophages in the donor lung causes the release of pro-inflammatory chemokines and cytokines, such as TNF-α. To determine the relevance of TNF-α in disrupting bronchial endothelial cell function, we stimulated human THP-1 macrophages with lipopolysaccharide (LPS) and used the resulting cytokine-supplemented media to disrupt normal endothelial cell functions. Endothelial tube formation was disrupted in the presence of LPS-activated THP- 1 conditioned media, with reversal of the effect occurring in the presence of 0.1µg/ml Enbrel, indicating that TNF-α was the major serum component inhibiting endothelial tube formation. To facilitate lung conditioning, we tested liposomal and porous silicon (pSi) delivery systems for their ability to selectively silence TNFR1 using siRNA technology. Of the three types of liposomes tested, only cationic liposomes had substantial endothelial uptake, with human cells taking up 10-fold more liposomes than their pig counterparts; however, non-specific cellular activation prohibited their use as immunosuppressive agents. On the other hand, pSi microparticles enabled the accumulation of large amounts of siRNA in endothelial cells compared to standard transfection with Lipofectamine(®) LTX, in the absence of non-specific activation of endothelia. Silencing of TNFR1 decreased TNF-α mediated inhibition of endothelial tube formation, as well as TNF-α-induced upregulation of ICAM-1, VCAM, and E-selection in human lung microvascular endothelial cells.
Assuntos
Lesão Pulmonar Aguda/fisiopatologia , RNA Interferente Pequeno/administração & dosagem , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Síndrome do Desconforto Respiratório/fisiopatologia , Animais , Cátions/metabolismo , Citocinas/metabolismo , Selectina E/genética , Células Endoteliais/metabolismo , Inativação Gênica , Humanos , Molécula 1 de Adesão Intercelular/genética , Lipopolissacarídeos/farmacologia , Lipossomos , Macrófagos/metabolismo , Microvasos/citologia , Microvasos/metabolismo , Especificidade da Espécie , Suínos , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima/genética , Molécula 1 de Adesão de Célula Vascular/genéticaRESUMO
PURPOSE OF REVIEW: Despite recent advances in the management of patients with acute respiratory distress syndrome (ARDS) by using protective ventilator strategies, the mortality rate of ARDS remains high. The complexity of the pathogenesis and the heterogeneity of coexisting diseases in patients with ARDS require critical care physicians and researchers to search for multiple therapeutic approaches in order to further improve patient outcome. This review article therefore focuses on the recent studies in the field of pharmacological intervention in ARDS. RECENT FINDINGS: A number of approaches for pharmacological intervention have been evaluated in patients with ARDS, but most of them failed to reduce mortality or improve outcomes despite some promising observations seen in preclinical studies. Prior methods such as nitric oxide inhalation, neuromuscular blocking agents and corticosteroids may still have a place in the treatment, while novel therapeutic approaches including the use of angiotensin-converting enzyme inhibitors, statins and stem cells are currently under investigation. SUMMARY: Overall, there is no proven pharmacological therapy in ARDS, but some pharmacological interventions were associated with beneficial effects in certain subgroups of patients depending on the cause, underlying diseases, the concurrent supportive therapies and timing. Further clinical trials are warranted to assess multiple outcome measurement of the promising pharmacological interventions in selected patients with ARDS.
Assuntos
Síndrome do Desconforto Respiratório/tratamento farmacológico , Administração por Inalação , Corticosteroides/uso terapêutico , Adulto , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anticoagulantes/uso terapêutico , Estado Terminal , Feminino , Hidratação , Terapia Genética , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipnóticos e Sedativos/uso terapêutico , Masculino , Bloqueadores Neuromusculares/uso terapêutico , Terapia Nutricional , Surfactantes Pulmonares/uso terapêutico , Síndrome do Desconforto Respiratório/fisiopatologia , Transplante de Células-Tronco , Resultado do TratamentoAssuntos
Síndrome do Desconforto Respiratório/terapia , Lesão Pulmonar Aguda/terapia , Albuterol/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Broncodilatadores/uso terapêutico , Suplementos Nutricionais , Nutrição Enteral/métodos , Hidratação/métodos , Glucocorticoides/uso terapêutico , Humanos , Pentoxifilina/análogos & derivados , Pentoxifilina/uso terapêutico , Respiração Artificial/métodos , Síndrome do Desconforto Respiratório/fisiopatologia , Volume de Ventilação Pulmonar/fisiologia , Resultado do TratamentoRESUMO
OBJECTIVE: To observe the clinical significance of changes of nitric oxide (NO) and vascular endothelial growth factor A (VEGF-A) in exhaled breath condensate (EBC) of patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) after they were treated by Xuebijing (XBJ), and to evaluate the effect of the EBC detection technology. METHODS: Totally 32 ALI/ARDS patients receiving mechanical ventilation at intensive care unit (ICU) were randomly assigned to the treatment group and the control group, 16 cases in each group. Patients in the control group were treated by routine therapy, while those in the treatment group were treated by routine therapy + XBJ. The therapeutic course for all was 5 days. The EBC sample was collected by improved EcoScreen condenser within 24 h after confirmed diagnosis of ALI/ARDS and on the fifth day of medication. The levels of NO and VEGF-A were measured by EIA in EBC and serum. The changes of NO and VEGF-A in EBC were observed before and after treatment. RESULTS: Compared with before treatment, the level of NO in EBC and serum decreased and VEGF-A increased after treatment, showing statistical difference (P < 0.05, P < 0.01). After treatment the level of NO in EBC and serum was lower in the treatment group than in the control group (P < 0.05). The VEGF-A in EBC was higher in the treatment group than in the control group (P < 0.05). There was no statistical difference in the serum VEGF-A level between the two groups (P > 0.05). CONCLUSIONS: XBJ was an effective therapeutic drug capable to control the in vivo inflammation reaction in patients with ALI/ARDS. The detection of changes of VEGF-A and NO levels by EBC could judge the inflammatory reaction degree in ALI/ARDS patients, and help evaluating the therapeutic effect.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Óxido Nítrico/metabolismo , Síndrome do Desconforto Respiratório/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Testes Respiratórios , Expiração , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/sangue , Síndrome do Desconforto Respiratório/fisiopatologia , Fator A de Crescimento do Endotélio Vascular/sangueRESUMO
Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) are serious complications of acute illness and injury, associated with an inpatient mortality of up to 40%. Despite considerable basic science and clinical research, therapeutic options for established ALI are limited. Survivors of ARDS are often faced with poor health-related quality of life, depressive-anxiety disorders, cognitive deficits, and financial strain. An attractive approach toward managing ALI lies in its prevention and early treatment. In addition to improving recognition of at-risk patients, it is necessary to identify novel treatments targeting the pathways that may prevent or ameliorate lung injury. The rationale and animal and clinical evidence for aspirin, systemic and inhaled steroids, ß-agonists, renin-angiotensin axis blockers, statins, peroxisome proliferator agonist receptor ligands, curcumin, and inhaled heparin are included in this narrative review. Randomized, controlled trials are currently being designed and implemented to address their efficacy in populations at risk for ALI.
Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Terapia de Alvo Molecular , Síndrome do Desconforto Respiratório/tratamento farmacológico , Lesão Pulmonar Aguda/fisiopatologia , Lesão Pulmonar Aguda/prevenção & controle , Animais , Desenho de Fármacos , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Síndrome do Desconforto Respiratório/fisiopatologia , Síndrome do Desconforto Respiratório/prevenção & controle , Fatores de Risco , Fatores de TempoRESUMO
Acute respiratory distress syndrome (ARDS) is characterized by the formation of a protein-rich alveolar edema caused by increased permeability of the alveolocapillary membrane. The key clinical feature is refractory arterial hypoxemia, which in severe cases necessitates the application of extracorporeal membrane oxygenation. Besides lung-protective ventilation as a confirmed therapeutic option, supportive therapy is an integral part of ARDS management. In this context, modern and individualized nutritional regimens are of special importance; however, their prognostic impact, especially of immunonutrition, for ARDS patients is controversial. In this review, basic features of nutrition in intensive care medicine and ARDS-specific aspects (e.g., immunonutrition) are presented and discussed.
Assuntos
Cuidados Críticos/métodos , Apoio Nutricional/métodos , Síndrome do Desconforto Respiratório/terapia , Nutrição Enteral/métodos , Medicina Baseada em Evidências/métodos , Emulsões Gordurosas Intravenosas/administração & dosagem , Ácidos Graxos Ômega-3/fisiologia , Humanos , Pulmão/fisiopatologia , Necessidades Nutricionais/fisiologia , Oxigênio/sangue , Nutrição Parenteral Total/métodos , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/fisiopatologiaRESUMO
PURPOSE: The purpose of this study is to evaluate the effects of an enteral diet enriched with ginger extract on inflammatory factors, respiratory profile, and outcome of patients with acute respiratory distress syndrome (ARDS). MATERIALS AND METHODS: Thirty-two patients with ARDS were randomized to receive a high-protein enteral diet enriched with ginger or placebo. Serum levels of interleukin (IL) 1, IL-6, tumor necrosis factor α, and leukotriene B4; red blood cell glutathione; oxygenation; and static compliance were measured on days 0, 5, and 10. RESULTS: Patients fed enteral diet enriched with ginger had significantly lower serum levels of IL-1, IL-6, and tumor necrosis factor α and higher level of RBC glutathione on days 5 and 10 compared with control group (P < .05). Significant improvement in oxygenation was observed on day 5 (P = .02) and 10 (P = .003) in ginger group compared with control group. Static compliance was increased on day 5 (P = .01) in ginger group compared with control group. A significant difference was found in duration of mechanical ventilation (P = .02) and length of intensive care unit stay (P = .04) in favor of ginger group. We did not find any difference in barotraumas, organ failure, and mortality between the study groups. CONCLUSIONS: An enteral diet supplemented with ginger in patients with ARDS may be beneficial for gas exchange and could decrease duration of mechanical ventilation and length of stay in intensive care unit.