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1.
Crit Care Resusc ; 22(1): 63-71, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32102644

RESUMO

BACKGROUND: The best sedative medication to reduce delirium, mortality and long term brain dysfunction in mechanically ventilated septic patients is unclear. This multicentre, double-blind, randomised trial investigates the short term and long term effects of dexmedetomidine versus propofol for sedation in mechanically ventilated severely septic patients. OBJECTIVES: To describe the statistical analysis plan for this randomised clinical trial comprehensively and place it in the public domain before unblinding. METHODS: To ensure that analyses are not selectively reported, we developed a comprehensive statistical analysis plan before unblinding. This trial has an enrolment target of 420 severely septic and mechanically ventilated adult patients, randomly assigned to dexmedetomidine or propofol in a 1:1 ratio. Enrolment was completed in January 2019, and the study was estimated to be completed in September 2019. The primary endpoint is days alive without delirium or coma during first 14 study days. Secondary outcomes include 28-day ventilator-free days, 90-day all-cause mortality and cognitive function at 180 days. Time frames all begin on the day of randomisation. All analyses will be conducted on an intention-to-treat basis. CONCLUSION: This study will compare the effects of two sedatives in mechanically ventilated severely septic patients. In keeping with the guidance on statistical principles for clinical trials, we have developed a comprehensive statistical analysis plan by which we will adhere, as this will avoid bias and support transparency and reproducibility. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01739933).


Assuntos
Delírio/induzido quimicamente , Respiração Artificial/estatística & dados numéricos , Insuficiência Respiratória/complicações , Sepse/complicações , Adulto , Estado Terminal , Delírio/diagnóstico , Delírio/prevenção & controle , Método Duplo-Cego , Mortalidade Hospitalar , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Unidades de Terapia Intensiva , Reprodutibilidade dos Testes , Respiração Artificial/efeitos adversos , Insuficiência Respiratória/terapia , Sepse/mortalidade
2.
Life Sci ; 242: 117240, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31891722

RESUMO

Lycium barbarum polysaccharides (LBP) are derived from Wolfberry and have antioxidant activities. This study aimed to evaluate the efficacy of LBP for kidney injury in a rat model of sepsis. Male rats were divided randomly to control group (Con), LPS group (LPS), ulinastatin group (ULI), low dose LBP group (LBP-1), middle dose LBP group (LBP-2) and high dose LBP group (LBP-3). After intraperitoneal injection of LPS (5 mg/kg) to make sepsis model (LPS group), 10,000 U/kg ulinastatin were given in ULI group, and 200, 400 and 800 mg/kg LBP was given in LBP-1, -2, -3 group, respectively. Serum IL-1ß, IL-6, IL-8, TNF-α and NF-κB levels were measured by ELISA. Nrf2, Keap1, NF-κB, HO-1 and NQO1 expression levels were detected by PCR and Western blot analysis. We found that LBP decreased the levels of NF-κB and pro-inflammatory cytokines while attenuated kidney injury. In addition, LBP regulated Keap1-Nrf2/ARE signaling pathway in the kidney. In conclusion, LBP attenuates inflammation injury in the kidney via possible regulation of Keap1-Nrf2/ARE signaling.


Assuntos
Lesão Renal Aguda/prevenção & controle , Elementos de Resposta Antioxidante/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Sepse/complicações , Transdução de Sinais/efeitos dos fármacos , Animais , Western Blotting , Citocinas/metabolismo , Modelos Animais de Doenças , Masculino , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real
3.
Medicine (Baltimore) ; 99(4): e18788, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31977869

RESUMO

BACKGROUND: This systematic review and meta-analysis were performed to evaluate kidney function in patients with sepsis-associated acute kidney injury (SA-AKI) on alkaline phosphatase (AP) therapy. METHODS: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched electronically from inception until May 4, 2019 and randomized controlled studies assessing AP treatment in patients with SA-AKI were included. Pool analyses with fixed effects or random effects models calculated pooled mean, standard deviation, and odds ratio (OR) with 95% confidence interval (CI). RESULTS: Four randomized controlled trials involving AP therapy for 392 patients with SA-AKI were included. AP had a positive effect on endogenous creatinine clearance (ECC) in patients with SA-AKI at day 14 (random effects: mean difference = 10.56, 95% CI = 2.27-18.84, P = .01) and day 28 (random effects: mean difference = 14.30, 95% CI = 6.27-22.33, P = .0005). All-cause mortality at day 28 (fixed effects: OR = 0.62, 95% CI = 0.40-0.97, P = .04) and day 90 (fixed effects: OR = 0.61, 95% CI = 0.39-0.96, P = .03) improved. Plasma creatinine level (fixed effects: mean difference = -76.83, 95% CI = -146.92 to -6.74, P = .03) and biomarkers level (random effects: mean difference = -6.57, 95% CI = -10.74 to -2.40, P < .00001) also improved in the therapy group compared with placebo. CONCLUSION: In patients with SA-AKI, AP showed a relatively late protective effect by improving ECC at days 7, 14, and 28. ECC level improved when patients received AP dose of 0.212 mg/kg. Mortality improved at days 28 and 90, respectively, when patients received AP dose of 1.6 mg/kg. Levels of overall AKI biomarkers were improved in short term.


Assuntos
Lesão Renal Aguda/tratamento farmacológico , Fosfatase Alcalina/administração & dosagem , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/metabolismo , Fosfatase Alcalina/farmacologia , Creatinina/sangue , Relação Dose-Resposta a Droga , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sepse/complicações
4.
J Korean Med Sci ; 35(4): e24, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-31997614

RESUMO

BACKGROUND: The impact of myocardial damage on the prognosis of patients with septic shock is not clearly elucidated because complex hemodynamic changes in sepsis obscure the direct relationship. We evaluated left ventricular (LV) conditions that reflect myocardial damage independently from hemodynamic changes in septic shock and their influence on the prognosis of patients. METHODS: We retrospectively enrolled 208 adult patients who were admitted to the intensive care unit and underwent echocardiography within 7 days from the diagnosis of septic shock. Patients who were previously diagnosed with structural heart disease or coronary artery disease were excluded. Left ventricular ejection fraction (LVEF) was divided into four categories: normal, ≥ 50%; mild, ≥ 40%; moderate, ≥ 30%; and severe dysfunction, < 30%. Wall motion impairment was categorized into the following patterns: normal, diffuse, ballooning, and focal. RESULTS: There were 141 patients with normal LVEF. Among patients with impaired LV wall motion, the diffuse pattern was the most common (34 patients), followed by the ballooning pattern (26 patients). Finally, 102 patients died, and in-hospital mortality was significantly higher in patients with severe LV systolic dysfunction (hazard ratio [HR], 1.97; 95% confidence interval [CI], 1.04-3.75; P = 0.039) and in patients with diffuse pattern of LV wall motion impairment (HR, 2.28; 95% CI, 1.19-4.36; P = 0.013) than in those with a normal LV systolic function. CONCLUSION: Severe LV systolic dysfunction and diffuse pattern of LV wall motion impairment significantly affected in-hospital mortality in patients with septic shock. Conventional echocardiographic evaluation provides adequate information on the development of myocardial damage and accurately predicts the prognosis of patients with septic shock.


Assuntos
Sepse , Choque Séptico , Disfunção Ventricular Esquerda , Idoso , Ecocardiografia , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Prognóstico , Sepse/complicações , Sepse/mortalidade , Choque Séptico/complicações , Choque Séptico/mortalidade , Disfunção Ventricular Esquerda/complicações , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/mortalidade , Função Ventricular Esquerda
5.
Life Sci ; 240: 117081, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31756342

RESUMO

BACKGROUND AND GOAL OF THE STUDY: Pulmonary inflammation, increased vascular permeability, and pulmonary edema, occur in response to primary pulmonary infections like pneumonia but are also evident in endotoxemia or sepsis. Mechanical ventilation augments pre-existing lung injury and inflammation resulting from exposure to microbial products. The objective of this study was to test the hypothesis that low-tidal-volume prevent ventilation induced lung injury in sepsis. MATERIALS AND METHODS: 10-12-week-old male C57BL/6N-mice received an intraperitoneal (i.p.) injection with equipotent dosages of LPS, 1668-thioate, 1612-thioate, or PBS. 120 min after injection, mice were randomized to low- (LV, 7 ± 1 ml/kg) or high-tidal-volume (HV, 25 ± 1 ml/kg) ventilation. Hemodynamic and ventilatory parameters were recorded and inflammatory markers were analyzed form BAL that was generated after 90 minute ventilation. RESULTS AND DISCUSSION: Arterial blood pressures declined during mechanical ventilation in all groups. pO2 decreased in LPS injected and CO2 increased in sham, LPS, and 1612-thioate administered mice at 45 min and in 1668-thioate injected mice after 90 minute LV ventilation compared to respective HV groups. BAL protein concentrations increased in HV ventilated and 1668- or 1612-thioat pre-treated mice. BAL TNF-α protein concentrations increased in both LPS- and 1668-thioate-injected and IL-1ß protein concentrations only in LPS-injected and HV ventilated mice. Most notably, no increased protein concentrations were observed in any of the LV ventilated groups. CONCLUSION: We conclude that low-tidal-volume ventilation may be a potential strategy for the prevention of ventilator induced lung injury in a murine model of systemic TLR agonist induced lung injury.


Assuntos
Inflamação/terapia , Sepse/terapia , Volume de Ventilação Pulmonar , Lesão Pulmonar Induzida por Ventilação Mecânica/prevenção & controle , Animais , Pressão Arterial , Líquido da Lavagem Broncoalveolar , Dióxido de Carbono/sangue , Hemodinâmica , Inflamação/complicações , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Oxigênio/sangue , Mecânica Respiratória , Sepse/complicações , Sepse/patologia , Lesão Pulmonar Induzida por Ventilação Mecânica/patologia
6.
An Acad Bras Cienc ; 91(4): e20190434, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31800708

RESUMO

Sepsis is a life-threatening organ dysfunction induced by a disrupted host response to infecting pathogens. Inflammation and oxidative stress are intrinsically related to sepsis progression and organ failure. Vitamin B6 is an important cellular cofactor for metabolic processes and has anti-inflammatory and antioxidant properties. We aimed at evaluating the effect of vit B6 on inflammation and oxidative stress markers in the liver and lung of rats subjected to a relevant animal model of polymicrobial sepsis. Adult male Wistar rats were submitted to cecal ligation and perforation model and immediately after sepsis induction, vit B6 was administered as a single dose (600 mg/kg, subcutaneous). Twenty-four hours later, the lung and liver were harvest for neutrophil infiltration, oxidative markers to lipids and protein and antioxidant activity of endogenous enzyme. Vitamin B6 diminished neutrophil infiltration in both organs, oxidative markers in the liver and restored catalase activity levels in the lung of septic animals. Vitamin B6 exerts anti-inflammatory and antioxidant effects in peripheral organs after polymicrobial sepsis.


Assuntos
Antioxidantes/farmacologia , Inflamação/prevenção & controle , Fígado/patologia , Pulmão/patologia , Estresse Oxidativo/efeitos dos fármacos , Sepse/complicações , Vitamina B 6/farmacologia , Animais , Biomarcadores/metabolismo , Modelos Animais de Doenças , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Ratos , Ratos Wistar , Sepse/patologia
7.
BMC Infect Dis ; 19(1): 1020, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791247

RESUMO

BACKGROUND: Vitamin D deficiency, determined by blood levels of 25-hydroxyvitamin D [25(OH) D, i.e. the major vitamin D form in blood], has been shown to associate with all-cause mortalities. We recently demonstrated that blood levels of 1,25-dihydroxyvitamin D [1,25(OH)2D, i.e. the active vitamin D] were significantly lower in non-survivors compared to survivors among sepsis patients. Unexpectedly, despite the well documented roles of 1,25(OH)2D in multiple biological functions such as regulation of immune responses, stimulation of antimicrobials, and maintenance of barrier function, 1,25(OH)2D supplementation failed to improve disease outcomes. These previous findings suggest that, in addition to 1,25(OH)2D deficiency, disorders leading to the 1,25(OH)2D deficiency also contribute to mortality among sepsis patients. Therefore, this study investigated the mechanisms leading to sepsis-associated 1,25(OH)2D deficiency. METHODS: We studied mechanisms known to regulate kidney 25-hydroxylvitamin D 1α-hydroxylase which physiologically catalyzes the conversion of 25(OH) D into 1,25(OH)2D. Such mechanisms included parathyroid hormone (PTH), insulin-like growth factor 1 (IGF-1), fibroblast growth factor 23 (FGF-23), and kidney function. RESULTS: We demonstrated in both human subjects and mice that sepsis-associated 1,25(OH)2D deficiency could not be overcome by increased production of PTH which stimulates 1α-hydroxylase. Further studies showed that this failure of PTH to maintain blood 1,25(OH)2D levels was associated with decreased blood levels of IGF-1, increased blood levels of FGF-23, and kidney failure. Since the increase in blood levels of FGF-23 is known to associate with kidney failure, we further investigated the mechanisms leading to sepsis-induced decrease in blood levels of IGF-1. Our data showed that blood levels of growth hormone, which stimulates IGF-1 production in liver, were increased but could not overcome the IGF-1 deficiency. Additionally, we found that the inability of growth hormone to restore the IGF-1 deficiency was associated with suppressed expression and signaling of growth hormone receptor in liver. CONCLUSIONS: Because FGF-23 and IGF-1 have multiple biological functions besides their role in regulating kidney 1α-hydroxylase, our data suggest that FGF-23 and IGF-1 are warranted for further investigation as potential agents for the correction of 1,25(OH)2D deficiency and for the improvement of survival among sepsis patients.


Assuntos
Sepse/sangue , Sepse/complicações , Deficiência de Vitamina D/etiologia , Vitamina D/análogos & derivados , Animais , Estudos de Casos e Controles , Modelos Animais de Doenças , Regulação para Baixo , Feminino , Fatores de Crescimento de Fibroblastos/sangue , Humanos , Fator de Crescimento Insulin-Like I , Rim/efeitos dos fármacos , Testes de Função Renal , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hormônio Paratireóideo/sangue , Sepse/fisiopatologia , Transdução de Sinais , Vitamina D/sangue , Vitamina D/metabolismo , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/fisiopatologia
8.
Folia Histochem Cytobiol ; 57(4): 168-178, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31825519

RESUMO

INTRODUCTION: Sepsis-induced acute lung injury (ALI) is an inflammatory process involved with simultaneous production of inflammatory cytokines and chemokines. In this study, we investigated the regulatory role of miR-539-5p in sepsis-induced ALI using a mouse model of cecal ligation puncture (CLP) and an in vitro model of primary murine pulmonary microvascular endothelial cells (MPVECs). MATERIAL AND METHODS: Adult male C57BL/6 mice were intravenously injected with or without miR-539-5p agomir or scrambled control one week before CLP operation. MPVECs were transfected with miR-539-5p mimics or control mimics, followed by lipopolysaccharide (LPS) stimulation. ROCK1 was predicted and confirmed as a direct target of miR-539-5p using dual-luciferase reporter assay. In rescue experiment, MPVECs were co-transfected with lentiviral vector expressing ROCK1 (or empty vector) and miR-539-5p mimics 24 h before LPS treatment. The transcriptional activity of caspase-3, the apoptosis ratio, the levels of miR-539-5p, interleukin-1b (IL-1b), interleukin-6 (IL-6), and ROCK1 were assessed. RESULTS: Compared to sham group, mice following CLP showed pulmonary morphological abnormalities, elevated production of IL-1b and IL-6, and increased caspase-3 activity and apoptosis ratio in the lung. In MPVECs, LPS stimulation resulted in a significant induction of inflammatory cytokine levels and apoptosis compared to untreated cells. The overexpression of miR-539-5p in septic mice alleviated sepsis-induced pulmonary injury, apoptosis, and inflammation. MiR-539-5p also demonstrated anti-apoptotic and anti-inflammatory effect in LPS-treated MPVECs. The upregulation of ROCK1 in MPVECs recovered miR-539-5p-suppressed caspase-3 activity and proinflammatory cytokine production. CONCLUSION: In conclusion, miR-539-5p alleviated sepsis-induced ALI via suppressing its downstream target ROCK1, suggesting a therapeutic potential of miR-539-5p for the management of sepsis-induced ALI.


Assuntos
Lesão Pulmonar Aguda/terapia , MicroRNAs/uso terapêutico , Quinases Associadas a rho/metabolismo , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/metabolismo , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular , Regulação para Baixo , Inflamação/terapia , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos , Pulmão/patologia , Masculino , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/metabolismo , Sepse/induzido quimicamente , Sepse/complicações , Transfecção
11.
Lancet ; 394(10212): 1949-1964, 2019 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-31777389

RESUMO

Acute kidney injury (AKI) is defined by a rapid increase in serum creatinine, decrease in urine output, or both. AKI occurs in approximately 10-15% of patients admitted to hospital, while its incidence in intensive care has been reported in more than 50% of patients. Kidney dysfunction or damage can occur over a longer period or follow AKI in a continuum with acute and chronic kidney disease. Biomarkers of kidney injury or stress are new tools for risk assessment and could possibly guide therapy. AKI is not a single disease but rather a loose collection of syndromes as diverse as sepsis, cardiorenal syndrome, and urinary tract obstruction. The approach to a patient with AKI depends on the clinical context and can also vary by resource availability. Although the effectiveness of several widely applied treatments is still controversial, evidence for several interventions, especially when used together, has increased over the past decade.


Assuntos
Lesão Renal Aguda , Lesão Renal Aguda/diagnóstico , Lesão Renal Aguda/epidemiologia , Lesão Renal Aguda/fisiopatologia , Lesão Renal Aguda/terapia , Biomarcadores/sangue , Creatinina/sangue , Humanos , Incidência , Medição de Risco , Sepse/complicações
13.
Med. intensiva (Madr., Ed. impr.) ; 43(8): 464-473, nov. 2019. graf, tab
Artigo em Inglês | IBECS | ID: ibc-185883

RESUMO

Purpose: To determine the differences in short- and long-term mortality in elderly septic patients with multiorgan dysfunction syndrome and establish the factors related to non-survival. Materials and methods: A retrospective cohort study was made of 206 patients over 65 years of age with septic and septic shock criteria admitted to the ICU of Rio Hortega Hospital between January 2011 and February 2017. Study variables were obtained from electronic database records. Results: A total of 206 patients were included, divided into three groups of age (65-74, 75-85, >85 years). There were no significant differences in mortality according to age group after 28 days, 90 days or one year (28.6%, 32.1% and 45.2% in the 65-74 years age group; 32.5%, 38.6% and 45.8% in the 75-85 years age group, 41%, 48.7% and 56.4% in the >85 years age group). The factors related to mortality were: chronic heart failure, non-haematological cancer, liver dysfunction and central nervous system dysfunction. Conclusions: The results indicate that there is no significant difference in mortality among the different age groups. About 50% of the elderly patients survive a septic process. There is a close relationship between the number of affected organs and days of dysfunction, the use of interventional techniques and long-term mortality


Objetivo: Determinar las diferencias en la mortalidad a corto y largo plazo en pacientes sépticos ancianos con síndrome de disfunción multiorgánica, y cuáles son los factores de riesgo determinantes de esta. Materiales y métodos: Estudio retrospectivo de cohortes de 206 pacientes mayores de 65 años con criterios de shock séptico y sepsis admitidos en la UCI del Hospital Río Hortega entre enero de 2011 y febrero de 2017. Los datos analizados se obtuvieron a través de los registros de bases de datos electrónicas de la unidad. Resultados: Se incluyeron 206 pacientes divididos en 3 grupos de edad (65-74; 75-85; >85). No encontramos diferencias estadísticas en la mortalidad por grupo de edad al cabo de 28 días, 90 días y un año (28,6, 32,1 y 45,2% en el grupo de 65-74 años; 32,5, 38,6 y 45,8% en el grupo de 75-85 años; 41, 48,7 y 56,4% en el grupo de edad >85) Los factores relacionados con la mortalidad fueron: insuficiencia cardíaca crónica, cáncer no hematológico, disfunción hepática y disfunción del sistema nervioso central. Conclusión: Los resultados indican que no hay una diferencia significativa en la mortalidad entre los diferentes grupos de edad. Alrededor del 50% de los pacientes ancianos sobreviven ante un proceso séptico. Existe una estrecha relación entre el número de órganos disfuncionantes, los días de disfunción, el uso de técnicas de intervención y la mortalidad a largo plazo


Assuntos
Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Insuficiência de Múltiplos Órgãos/mortalidade , Fatores de Risco , Estudos de Coortes , Insuficiência de Múltiplos Órgãos/epidemiologia , Estudos Retrospectivos , Choque Séptico/diagnóstico , Sepse/complicações , Unidades de Terapia Intensiva , Registros de Mortalidade , Registros Eletrônicos de Saúde
15.
Praxis (Bern 1994) ; 108(13): 877-882, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31571546

RESUMO

Death within Hours Abstract. The clinical picture of invasive meningococcal disease is broad, it mostly manifests as meningitis and/or sepsis. The severity ranges from a simple bacteremia associated with mild, unspecific symptoms to fulminant sepsis with multiorgan failure and death, which happens in 10-15 % of cases. Sometimes purely local infections (e.g. septic arthritis or conjunctivitis) or rarely a chronic course (prolonged, intermittent fever, rash, arthritis and headache) are the only clinical manifestation - which can also lead to a disseminated fulminant disease. Our case illustrates the tragic progression of a fulminant meningococcal sepsis with rapid death.


Assuntos
Artrite Infecciosa , Bacteriemia , Infecções Meningocócicas , Sepse , Bacteriemia/complicações , Humanos , Infecções Meningocócicas/complicações , Insuficiência de Múltiplos Órgãos , Sepse/complicações
16.
JAMA ; 322(13): 1261-1270, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31573637

RESUMO

Importance: Experimental data suggest that intravenous vitamin C may attenuate inflammation and vascular injury associated with sepsis and acute respiratory distress syndrome (ARDS). Objective: To determine the effect of intravenous vitamin C infusion on organ failure scores and biological markers of inflammation and vascular injury in patients with sepsis and ARDS. Design, Setting, and Participants: The CITRIS-ALI trial was a randomized, double-blind, placebo-controlled, multicenter trial conducted in 7 medical intensive care units in the United States, enrolling patients (N = 167) with sepsis and ARDS present for less than 24 hours. The study was conducted from September 2014 to November 2017, and final follow-up was January 2018. Interventions: Patients were randomly assigned to receive intravenous infusion of vitamin C (50 mg/kg in dextrose 5% in water, n = 84) or placebo (dextrose 5% in water only, n = 83) every 6 hours for 96 hours. Main Outcomes and Measures: The primary outcomes were change in organ failure as assessed by a modified Sequential Organ Failure Assessment score (range, 0-20, with higher scores indicating more dysfunction) from baseline to 96 hours, and plasma biomarkers of inflammation (C-reactive protein levels) and vascular injury (thrombomodulin levels) measured at 0, 48, 96, and 168 hours. Results: Among 167 randomized patients (mean [SD] age, 54.8 years [16.7]; 90 men [54%]), 103 (62%) completed the study to day 60. There were no significant differences between the vitamin C and placebo groups in the primary end points of change in mean modified Sequential Organ Failure Assessment score from baseline to 96 hours (from 9.8 to 6.8 in the vitamin C group [3 points] and from 10.3 to 6.8 in the placebo group [3.5 points]; difference, -0.10; 95% CI, -1.23 to 1.03; P = .86) or in C-reactive protein levels (54.1 vs 46.1 µg/mL; difference, 7.94 µg/mL; 95% CI, -8.2 to 24.11; P = .33) and thrombomodulin levels (14.5 vs 13.8 ng/mL; difference, 0.69 ng/mL; 95% CI, -2.8 to 4.2; P = .70) at 168 hours. Conclusions and Relevance: In this preliminary study of patients with sepsis and ARDS, a 96-hour infusion of vitamin C compared with placebo did not significantly improve organ dysfunction scores or alter markers of inflammation and vascular injury. Further research is needed to evaluate the potential role of vitamin C for other outcomes in sepsis and ARDS. Trial Registration: ClinicalTrials.gov Identifier: NCT02106975.


Assuntos
Ácido Ascórbico/administração & dosagem , Insuficiência de Múltiplos Órgãos/prevenção & controle , Síndrome do Desconforto Respiratório do Adulto/tratamento farmacológico , Sepse/tratamento farmacológico , Vitaminas/administração & dosagem , Adulto , Idoso , Ácido Ascórbico/uso terapêutico , Biomarcadores/sangue , Proteína C-Reativa/análise , Método Duplo-Cego , Feminino , Humanos , Infusões Intravenosas , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Escores de Disfunção Orgânica , Síndrome do Desconforto Respiratório do Adulto/complicações , Síndrome do Desconforto Respiratório do Adulto/mortalidade , Sepse/complicações , Sepse/mortalidade , Trombomodulina/sangue , Vitaminas/uso terapêutico
17.
Medicine (Baltimore) ; 98(42): e17512, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626109

RESUMO

BACKGROUND: Retinopathy of prematurity (ROP) is a retinal vasoproliferative disease affected by multiple factors such as infection and preterm birth. The role of sepsis in the development of ROP remains controversial. This systematic review and meta-analysis aimed to identify the impact of sepsis on ROP. METHODS: The PubMed, Embase, and Cochrane Library databases were searched using terms related to sepsis and ROP. Cohort or case-control studies that reported the association of sepsis and ROP were eligible. The odds ratios (ORs) together with the 95% confidence interval (CI) were extracted from the studies or computed by authors if not provided. RESULTS: Thirty-four studies were ultimately included in this meta-analysis. The pooled results showed that sepsis increased the risk for the development of any stage ROP (OR = 2.16; 95% CI: 1.65-2.82). Both early onset (OR = 2.50; 95% CI: 1.97-3.18) and late-onset (OR = 1.37; 95% CI: 1.22-1.55) sepsis were associated with severe ROP. Furthermore, both bacterial sepsis (OR = 1.74; 95% CI: 1.21-2.50) and fungal sepsis (OR = 2.96; 95% CI: 2.05-4.28) were also found to be associated with severe ROP. CONCLUSION: Sepsis increased the risk of any stage ROP, especially for the severe ROP. Further high-quality clinical studies are needed to eliminate heterogeneity and publication bias to validate these findings.


Assuntos
Doenças do Prematuro/etiologia , Retinopatia da Prematuridade/etiologia , Sepse/complicações , Feminino , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Razão de Chances
18.
Emergencias (Sant Vicenç dels Horts) ; 31(5): 311-317, oct. 2019. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-184120

RESUMO

Objetivos. El diagnóstico correcto de la sepsis en urgencias es clave para iniciar el tratamiento de forma adecuada. Para ello, se han estudiado múltiples biomarcadores que podrían ser de utilidad. El objetivo principal de este estudio fue evaluar la capacidad diagnóstica de presepsina en sangre, en comparación con procalcitonina (PCT), proteína C reactiva (PCR) y lactato, para predecir sepsis o shock séptico según la definición de Sepsis-3. El objetivo secundario fue valorar la capacidad de estos biomarcadores para predecir bacteriemia, independientemente del diagnóstico final de sepsis o shock séptico. Método. Estudio prospectivo de cohorte observacional, realizado en un único servicio de urgencias (SU) de un hospital universitario. Se incluyeron pacientes con sospecha clínica de infección y al menos dos criterios de síndrome de respuesta inflamatoria sistémica. En todos los pacientes se determinó en sangre presepsina, PCT, PCR y lactato en el momento de la visita en el SU. Resultados. Se analizaron 359 pacientes, de los que 228 (63,5%) presentaban criterios de sepsis y 20 (5,6%) de shock séptico. PCT y presepsina fueron los mejores biomarcadores para predecir la sepsis/shock séptico con un área bajo la curva (ABC) de la capacidad operativa del receptor (ROC) de 0,711 (IC 95% 0,660-0,758; p < 0,001) y 0,709 (IC 95% 0,658-0,756; p < 0,001). La PCR obtuvo una ABC de 0,635 (IC 95% 0,582-0,686; p < 0,05), y el lactato una ABC de 0,61 (IC 95% 0,556-0,661; p < 0,05). Se utilizó un punto de decisión de 0,25 ng/ml para PCT y de 500 pg/ml para presepsina. La odds ratio de presepsina para predecir sepsis fue de 3,19 (IC 95% 1,91-5,31) y para PCT de 2,51 (IC 95% 1,53-4,12). El diagnóstico de sepsis/shock séptico no mejoró al combinar presepsina y PCT (el ABC-ROC fue de 0,714, IC 95% 0,66-0,76; p < 0,001) en comparación con PCT aislada. La PCT fue el predictor más preciso de bacteriemia en pacientes con infección con un ABC-ROC de 0,835 (IC 95% 0,79-0,87; p < 0,001). Conclusión. La presepsina y la PCT son los biomarcadores con mejor rendimiento para el diagnóstico de sepsis y shock séptico en el SU


Objectives. An accurate diagnosis of sepsis in the emergency department must be made before appropriate treatment can be started. Many biomarkers that are potentially useful have been studied. The main aim of this study was to compare the diagnostic accuracy of blood levels of presepsin, lactate, C-reactive protein (CRP), and procalcitonin (PCT) for predicting sepsis as defined by the Sepsis-3 criteria. The secondary aim was to evaluate the diagnostic accuracy of these biomarkers for predicting bacteremia whether or not sepsis or septic shock was present. Methods. Single-center, prospective, observational cohort study in the emergency department of a university hospital. Consecutive patients suspected of having infection were enrolled prospectively if they had at least 2 criteria for systemic inflammatory response syndrome. We measured presepsin, PCT, CRP, and lactate in blood extracted on admission. Results. Blood samples from 359 patients were analyzed; 228 (63.5%) met the criteria for sepsis and 20 (5.6%) met the criteria for septic shock. PCT and presepsin levels were the best predictors of sepsis and septic shock with areas under the receiver operating characteristic curve (AUC) of 0.711 (95% CI, 0.660-0.758) and 0.709 (95% CI, 0.658-0.756), respectively (P<.001, both comparisons). The AUCs for CRP and lactate concentrations were, respectively, 0.63 (95% CI, 0.58-0.69) and 0.61 (95% CI, 0.56-0.66) (P<.05, both comparisons). On applying the diagnostic cut points of 0.25 ng/mL for PCT and 500 pg/mL for presepsin, the odds ratios were 2.51 (95% CI, 1.53-4.12) for PCT and 3.19 (95% CI, 1.91-5.31) for presepsin. The diagnostic accuracy of the combination of presepsin and PCT results (AUC, 0.71; 95% CI 0.66-0.76; P<.001) was no better than the accuracy of PCT alone. The most accurate predictor of bacteremia was PCT (AUC, 0.835; 95% CI, 0.79-0.87; P<.001). Conclusion. Presepsin and PCT seem to be the best predictors of a diagnosis of sepsis or septic shock in emergency department patients


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Sepse/complicações , Sepse/diagnóstico , Choque Séptico/diagnóstico , Biomarcadores , Bacteriemia/diagnóstico , Pró-Calcitonina/administração & dosagem , Estudos Prospectivos , Hospitais Universitários , Curva ROC
19.
Mol Med Rep ; 20(3): 2511-2518, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31524263

RESUMO

Sepsis­induced myocardial injury is one of the manifestations of multiple organ dysfunction in sepsis. The aim of the present study was to determine the mechanism of alleviation of lipopolysaccharide (LPS)­induced injury on cardiomyocytes by Sestrin2. A sepsis model using LPS injection was constructed in Sprague­Dawley (SD) rats, and after 6, 12 and 24 h, rat blood was collected and cardiac troponin T (CTnT) levels were determined using ELISA. Heart specimens were excised, tumor necrosis factor­α (TNF­α) and interleukin 6 (IL­6) levels were detected by ELISA, malondialdehyde (MDA) levels were estimated using colorimetric analysis, and phosphorylated (p)­S6K and p­AMP­activated protein kinase (AMPK) levels were determined by western blot analysis. In the septic rats, phenomenon of myocardial fiber rupture, interstitial edema and inflammatory cell infiltration were observed under light microscope. Following LPS injection, CTnT in serum and MDA in myocardial homogenate were increased time­dependently. TNF­α and IL­6 levels were significantly increased, with a peak at 6 h. p­S6K levels were adaptively downregulated, and levels of p­AMPK and Sestrin2 were adaptively upregulated by LPS. In LPS­injured H9c2 cells, Sestrin2 overexpression attenuated the LPS­mediated inhibitory effects on cell viability, suppressed LPS­mediated increase in CTnT, TNF­α, IL­6 and MDA levels, as well as attenuated p­S6K levels and elevated p­AMPK and Sestrin2 levels. Sestrin2 interference showed the opposite effect. Sestrin2 promoted cell viability and inhibited the inflammatory responses of LPS­injured myocardial cells. The phenomena may be associated with inhibition of p­S6K and activation of the p­AMPK pathway.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Cardiopatias/etiologia , Cardiopatias/metabolismo , Proteínas Nucleares/genética , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Sepse/complicações , Animais , Sobrevivência Celular/efeitos dos fármacos , Feminino , Expressão Gênica , Cardiopatias/fisiopatologia , Lipopolissacarídeos/farmacologia , Miocárdio/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Ratos , Transdução de Sinais/efeitos dos fármacos
20.
Niger J Clin Pract ; 22(9): 1229-1235, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31489859

RESUMO

Background: Knowledge of ICU clinicians about Intensive Care Unit Acquired Weakness (ICU-AW) is a vital step in implementing prevention strategies. Aim of Study: The purpose of this study was to investigate the level of knowledge of ICU clinicians in teaching hospitals in Southwest Nigeria about ICU-AW. Methods: ICU clinicians were surveyed using a self-administered questionnaire to obtain data on knowledge about ICUAW. Data were summarized as frequency and percentages, mean and standard deviation using SPSS version 20. Results: Total of 134 ICU clinicians (56 anesthetists, 35 physiotherapists, and 43 nurses) responded to the questionnaire, of which 100 were aware of ICUAW. Three of the 100 correctly identified ICU-AW as a neuromuscular disease. Totally, 40% correctly indicated Medical Research Council Scoring Scale as a diagnostic tool for ICU-AW. Severe sepsis and prolonged mechanical ventilation were the two highest identified risk factors for ICU-AW. However, only 35% of respondents were able to identify either use of aminoglycosides, and prolonged use of vasopressors as risk factors for ICUAW. Almost half (49%) reported having methods of managing ICUAW at their institution. Conclusion: Though awareness about Intensive care unit-acquired weakness (ICUAW) among clinicians in teaching hospitals in the Southwestern Nigeria is high, but knowledge about diagnosis and classification is low. This highlights the need for specialized training of ICU clinicians about ICUAW to enhance prevention and early detection.


Assuntos
Pessoal de Saúde/psicologia , Unidades de Terapia Intensiva , Debilidade Muscular/etiologia , Sepse/complicações , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde/estatística & dados numéricos , Humanos , Masculino , Nigéria , Respiração Artificial/efeitos adversos , Fatores de Risco , Inquéritos e Questionários
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