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1.
Crit Care Resusc ; 22(3): 191-199, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32900325

RESUMO

OBJECTIVE: To determine whether hydrocortisone is a cost-effective treatment for patients with septic shock. DESIGN: Data linkage-based cost-effectiveness analysis. SETTING: New South Wales and Queensland intensive care units. PARTICIPANTS AND INTERVENTION: Patients with septic shock randomly assigned to treatment with hydrocortisone or placebo in the Adjunctive Glucocorticoid Therapy in Patients with Septic Shock (ADRENAL) trial. MAIN OUTCOME MEASURES: Health-related quality of life at 6 months using the EuroQoL 5-dimension 5-level questionnaire. Data on hospital resource use and costs were obtained by linking the ADRENAL dataset to government administrative health databases. Clinical outcomes included mortality, health-related quality of life, and quality-adjusted life-years gained; economic outcomes included hospital resource use, costs and cost-effectiveness from the health care payer perspective. We also assessed cost-effectiveness by sex. To increase the precision of cost-effectiveness estimates, we conducted unrestricted bootstrapping. RESULTS: Of 3800 patients in the ADRENAL trial, 1772 (46.6%) were eligible and 1513 (85.4% of those eligible) were included. There was no difference between hydrocortisone or placebo groups in regards to mortality (218/742 [29.4%] v 227/759 [29.9%]; HR, 0.93; 95% CI, 0.78-1.12; P = 0.47), mean number of QALYs gained (0.10 ± 0.09 v 0.10 ± 0.09; P = 0.52), or total hospital costs (A$73 515 ± 61 376 v A$69 748 ± 61 793; mean difference, A$3767; 95% CI, -A$2891 to A$10 425; P = 0.27). The incremental cost of hydrocortisone was A$1 254 078 per quality-adjusted life-year gained. In females, hydrocortisone was cost-effective in 46.2% of bootstrapped replications and in males it was cost-effective in 2.7% of bootstrapped replications. CONCLUSIONS: Adjunctive hydrocortisone did not significantly affect longer term mortality, health-related quality of life, health care resource use or costs, and is unlikely to be cost-effective.


Assuntos
Anti-Inflamatórios/economia , Anti-Inflamatórios/uso terapêutico , Hidrocortisona/economia , Hidrocortisona/uso terapêutico , Choque Séptico/tratamento farmacológico , Análise Custo-Benefício , Feminino , Humanos , Masculino , New South Wales , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Choque Séptico/mortalidade
2.
BMC Infect Dis ; 20(1): 665, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32907533

RESUMO

BACKGROUND: Pseudomonas aeruginosa (P. aeruginosa) is a major Gram-negative pathogen, which has been reported to result in high mortality. We aim to investigate the prognostic value and optimum cut-off point of time-to-positivity (TTP) of blood culture in children with P. aeruginosa bacteremia. METHODS: From August 2014 to November 2018, we enrolled the inpatients with P. aeruginosa bacteremia in a 1500-bed tertiary teaching hospital in Chongqing, China retrospectively. Receiver operating characteristic (ROC) analysis was used to determine the optimum cut-off point of TTP, and logistic regression were employed to explore the risk factors for in-hospital mortality and septic shock. RESULTS: Totally, 52 children with P. aeruginosa bacteremia were enrolled. The standard cut-off point of TTP was18 h. Early TTP (≤18 h) group patients had remarkably higher in-hospital mortality (42.9% vs 9.7%, P = 0.014), higher incidence of septic shock (52.4% vs12.9%, P = 0.06), higher Pitt bacteremia scores [3.00 (1.00-5.00) vs 1.00 (1.00-4.00), P = 0.046] and more intensive care unit admission (61.9% vs 22.6%, P = 0.008) when compared with late TTP (> 18 h) groups. Multivariate analysis indicated TTP ≤18 h, Pitt bacteremia scores ≥4 were the independent risk factors for in-hospital mortality (OR 5.88, 95%CI 1.21-21.96, P = 0.035; OR 4.95, 95%CI 1.26-27.50, P = 0.024; respectively). The independent risk factors for septic shock were as follows: TTP ≤18 h, Pitt bacteremia scores ≥4 and hypoalbuminemia (OR 6.30, 95%CI 1.18-33.77, P = 0.032; OR 8.15, 95%CI 1.15-42.43, P = 0.014; OR 6.46, 95% CI 1.19-33.19 P = 0.031; respectively). CONCLUSIONS: Early TTP (≤18 hours) appeared to be associated with worse outcomes for P. aeruginosa bacteremia children.


Assuntos
Bacteriemia/diagnóstico , Hemocultura , Infecções por Pseudomonas/diagnóstico , Pseudomonas aeruginosa/isolamento & purificação , Bacteriemia/mortalidade , Criança , Pré-Escolar , China , Feminino , Mortalidade Hospitalar , Hospitalização , Humanos , Lactente , Unidades de Terapia Intensiva , Modelos Logísticos , Masculino , Prognóstico , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/mortalidade , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Choque Séptico/mortalidade , Centros de Atenção Terciária , Fatores de Tempo
3.
Cell Mol Immunol ; 17(9): 992-994, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32620787
4.
Medicine (Baltimore) ; 99(26): e20914, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590802

RESUMO

RATIONALE: Methicillin-resistant Staphylococcus aureus (MRSA) has been established as an important cause of severe community-acquired pneumonia (CAP) with very high mortality. Panton-Valentine leukocidin (PVL) producing MRSA has been reported to be associated with necrotizing pneumonia and worse outcome. The incidence of community-acquired MRSA (CA-MRSA) pneumonia is very low, as only a few CA-MRSA pneumonia cases were reported in the last few years. We present a case of severe CAP caused by PVL-positive MRSA with ensuing septic shock. PATIENT CONCERNS: A 68-year-old male with no concerning medical history had developed a fever that reached 39.0°C, a productive cough that was sustained for 5 days, and hypodynamia. He was treated with azithromycin and alexipyretic in a nearby clinic for 2 days in which the symptoms were alleviated. However, 1 day later, the symptoms worsened, and he was taken to a local Chinese medicine hospital for traditional medicine treatment. However, his clinical condition deteriorated rapidly, and he then developed dyspnea and hemoptysis. DIAGNOSIS: CA-MRSA pneumonia and septic shock. The sputum culture showed MRSA. Polymerase chain reaction of MRSA isolates was positive for PVL genes. INTERVENTIONS: Mechanical ventilation, fluid resuscitation, and antibiotic therapy were performed. Antibiotic therapy included mezlocillin sodium/sulbactam sodium, linezolid, and oseltamivir. OUTCOMES: He died after 12 hours of treatment. LESSONS: This is a report of severe pneumonia due to PVL-positive CA-MRSA in a healthy adult. CA-MRSA should be considered a pathogen of severe CAP, especially when combined with septic shock in previously healthy individuals.


Assuntos
Pneumonia Associada a Assistência à Saúde/etiologia , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Infecções Estafilocócicas/complicações , Idoso , Antibacterianos/uso terapêutico , Tosse/etiologia , Pneumonia Associada a Assistência à Saúde/tratamento farmacológico , Pneumonia Associada a Assistência à Saúde/microbiologia , Humanos , Hipocinesia/etiologia , Linezolida/uso terapêutico , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Mezlocilina/uso terapêutico , Oseltamivir/uso terapêutico , Choque Séptico/etiologia , Choque Séptico/mortalidade , Choque Séptico/fisiopatologia
5.
Medicine (Baltimore) ; 99(22): e20495, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481464

RESUMO

Biomarkers are valuable tools for the prediction of mortality in patients with sepsis. However, the use of a single biomarker to predict patient outcomes is challenging owing to the complexity and redundancy of the immune response to infections.We aimed to conduct a prospective observational analysis to investigate the prognostic value of pentraxin 3, interleukin 6, procalcitonin, and lactate combined in predicting the 28-day mortality rate in patients with sepsis or septic shock (n = 160; sepsis, 78; sepsis shock, 82). Two methods (the frequency sum of values above the cutoff, and the multivariate logistic regression model) were used to assess the prognostic value of the biomarker combination.In the receiver operating characteristic curve analyses, the combination of the 4 biomarkers was better than the Sequential Organ Failure Assessment (SOFA) score in predicting the 28-day mortality rate, regardless of whether the frequency sum of values above the cutoff or the multivariate logistic model was used for the analysis. The addition of the SOFA score to the biomarker combination did not result in a better performance for the prediction of mortality.The combined biomarker approach showed good performance in predicting 28-day all-cause mortality among patients diagnosed with either sepsis or septic shock according to the Sepsis-3 definitions. Furthermore, it was superior to the SOFA score in predicting mortality.


Assuntos
Biomarcadores/sangue , Escores de Disfunção Orgânica , Sepse/mortalidade , Choque Séptico/mortalidade , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/metabolismo , Feminino , Humanos , Interleucina-6/sangue , Lactatos/sangue , Masculino , Valor Preditivo dos Testes , Pró-Calcitonina/sangue , Prognóstico , Estudos Prospectivos , Componente Amiloide P Sérico/metabolismo
6.
Zhonghua Nei Ke Za Zhi ; 59(6): 451-459, 2020 Jun 01.
Artigo em Chinês | MEDLINE | ID: mdl-32486586

RESUMO

Objective: To evaluate the effect of corticosteroids on the prognosis of patients with septic shock. Method: In order to compare administration of corticosteroids with placebo or standard supportive care in adults with septic shock, clinical randomized controlled trials (RCT) were searched and selected, according to inclusion and exclusion criteria. A systemic assessment and meta-analysis was performed using RevMan 5.3. Result: A total of 16 RCTs enrolling 6 896 patients were finally included in present analysis. The corticosteroids group included 3 448 patients, and the control group included 3 448 patients. The 28-day mortality in corticosteroids group and control group were 28.6% and 31.2%, respectively (P=0.16). The 90-day mortality, the mortality in intensive care unit (ICU) and the mortality in the hospital between corticosteroids group and control group were 31.7% vs. 34.0% (P=0.16), 37.5% vs. 37.5% (P=0.87), and 41.0% vs. 43.9% (P=0.35) respectively, which indicated that corticosteroids could not improve the mortality of patients with septic shock. Subgroup analyses showed that hydrocortisone combined with hydrocortisone could reduce the 28-day mortality, and the 28-day mortality in corticosteroids group and control group were 37.7% and 43.3%, respectively (P=0.02). However, other types of corticosteroids had no influence on 28-day mortality. The incidence of gastrointestinal hemorrhage and super-infections showed no statistical difference in corticosteroids group and control group. However, incidence of hyperglycemia was significantly increased in corticosteroids group, 27.1% vs. 25% (P<0.000 1). Conclusion: Corticosteroids could not improve the mortality of patients with septic shock, and simultaneously, significantly increase incidence of hyperglycemia. Corticosteroids have no influence on the incidence of gastrointestinal hemorrhage and super-infections. Subgroup analyses showed that hydrocortisone combined with hydrocortisone could reduce the 28-day mortality.


Assuntos
Corticosteroides/uso terapêutico , Hidrocortisona/uso terapêutico , Choque Séptico/tratamento farmacológico , Corticosteroides/administração & dosagem , Adulto , China/epidemiologia , Hemorragia Gastrointestinal , Humanos , Hidrocortisona/administração & dosagem , Hiperglicemia/epidemiologia , Incidência , Unidades de Terapia Intensiva , Prognóstico , Choque Séptico/mortalidade
7.
Medicine (Baltimore) ; 99(19): e19906, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32384433

RESUMO

Septic shock is associated with a strong inflammatory response that induces vasodilation and vascular hyporeactivity. We investigated the role for tryptophan-pathway catabolites of proinflammatory cytokines in septic shock.We prospectively included 30 patients with very recent-onset septic shock and 30 healthy volunteers. The following were assayed once in the controls and on days 1, 2, 3, 7, and 14 in each patient: plasma free and total tryptophan, platelet and plasma serotonin, total blood serotonin, urinary serotonin, plasma and urinary 5-hydroxyindolacetic acid, plasma kynurenine, monoamine oxidase activity, and total indole amine 2,3-dioxygenase activity. Organ-system failure and mortality were recorded.Compared with the healthy controls, the patients with septic shock had 2-fold to 3-fold lower total tryptophan levels throughout the 14-day study period. Platelet serotonin was substantially lower, while monoamine oxidase activity and 5-hydroxyindolacetic acid were markedly higher in the patients than in the controls, consistent with the known conversion of tryptophan to serotonin, which is then promptly and largely degraded to 5-hydroxyindolacetic acid. Plasma kynurenine was moderately increased and indole amine 2,3-dioxygenase activity markedly increased in the patients versus the volunteers, reflecting conversion of tryptophan to kynurenine. Changes over time in tryptophan metabolites were not associated with survival in the patients but were associated with the Sequential Organ Failure Assessment score and hemodynamic variables including hypotension and norepinephrine requirements.Our results demonstrate major tryptophan pathway alterations in septic shock. Marked alterations were found compared with healthy volunteers, and tryptophan metabolite levels were associated with organ failure and hemodynamic alterations. Tryptophan metabolite levels were not associated with surviving septic shock, although this result might be ascribable to the small sample size.Trial registration: ClinicalTrials.gov; No: NCT00684736; URL: www.clinicaltrials.gov.


Assuntos
Choque Séptico/sangue , Choque Séptico/mortalidade , Triptofano/sangue , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Ácido Hidroxi-Indolacético/sangue , Indolamina-Pirrol 2,3,-Dioxigenase/sangue , Cinurenina/sangue , Masculino , Pessoa de Meia-Idade , Monoaminoxidase/sangue , Escores de Disfunção Orgânica , Estudos Prospectivos , Serotonina/sangue , Taxa de Sobrevida
8.
PLoS One ; 15(5): e0233317, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32437390

RESUMO

BACKGROUND: No African countries were included in the development of the Simplified Acute Physiology Score 3 (SAPS 3). This study aimed to assess the performance of the SAPS 3 as a predictor of hospital mortality in patients admitted to a multi-disciplinary tertiary intensive care unit (ICU) in South Africa. METHODS: A prospective cohort study was undertaken in a tertiary single-centre closed multidisciplinary ICU with 16 beds over 12 months in 2017. First time admissions 12 years and over were included. Exclusions were patients who died within six hours of admission, incomplete data sets and unknown outcome after ICU discharge. Demographic data, clinical admission data and co-morbidities were recorded. The SAPS 3 score was calculated within the first hour of ICU admission. The highest Sequential Organ Failure Assessment score, vasopressor use, mechanical ventilation requirements and details of acute kidney injury, if present, were recorded. Discrimination of the model was evaluated using an area under the receiver operating characteristic curve (AUROC) and calibration by the Hosmer-Lemeshow (HL) Goodness of Fit Test (C and H statistic). The observed versus the SAPS 3 model predicted mortality ratios were compared and the standardized mortality ratio (SMR) was calculated. RESULTS: A total of 829 admissions with a mean SAPS 3 (SD) of 48.1 (16) were included. Of patients with a known human immunodeficiency virus (HIV) status, 32,4% were positive. The ICU and hospital mortality rates were 13.3% and 21.4% respectively. The SAPS 3 model had a AUROC of 0.796 and HL C and H statistics were 12.1 and 11.8 (p-values 0.15 and 0.16). The SMR for the model was 1.002 (95%CI: 0.91-1.10). The mortality of 41% for the subgroup with sepsis/septic shock was higher than predicted with a SMR of 1.24 (95% CI 1.11-1.37). CONCLUSIONS: The SAPS 3 model showed good calibration and fair discrimination when applied to the cohort. The SAPS 3 model can be used to describe the case mix in this African ICU with a high incidence of HIV. Ongoing efforts should be made to improve outcomes of septic patients.


Assuntos
Mortalidade Hospitalar , Unidades de Terapia Intensiva/estatística & dados numéricos , Escala Psicológica Aguda Simplificada , Centros de Atenção Terciária/estatística & dados numéricos , Lesão Renal Aguda/mortalidade , Adulto , Área Sob a Curva , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Prognóstico , Estudos Prospectivos , Curva ROC , Síndrome do Desconforto Respiratório do Adulto/mortalidade , Choque Séptico/mortalidade , África do Sul/epidemiologia
9.
Nat Commun ; 11(1): 2607, 2020 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-32451375

RESUMO

Quantification of pathogen and host biomarkers is essential for the diagnosis, monitoring, and treatment of infectious diseases. Here, we demonstrate sensitive and rapid quantification of bacterial load and cytokines from human biological samples to generate actionable hypotheses. Our digital assay measures IL-6 and TNF-α proteins, gram-negative (GN) and gram-positive (GP) bacterial DNA, and the antibiotic-resistance gene blaTEM with femtomolar sensitivity. We use our method to characterize bronchoalveolar lavage fluid from patients with asthma, and find elevated GN bacteria and IL-6 levels compared to healthy subjects. We then analyze plasma from patients with septic shock and find that increasing levels of IL-6 and blaTEM are associated with mortality, while decreasing IL-6 levels are associated with recovery. Surprisingly, lower GN bacteria levels are associated with higher probability of death. Applying decision-tree analysis to our measurements, we are able to predict mortality and rate of recovery from septic shock with over 90% accuracy.


Assuntos
Citocinas/sangue , DNA Bacteriano/sangue , Choque Séptico/imunologia , Choque Séptico/microbiologia , Asma/imunologia , Asma/microbiologia , Carga Bacteriana , Biomarcadores/análise , Biomarcadores/sangue , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/imunologia , Líquido da Lavagem Broncoalveolar/microbiologia , Estudos de Casos e Controles , Citocinas/análise , DNA Bacteriano/genética , Árvores de Decisões , Genes Bacterianos , Bactérias Gram-Negativas/genética , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/genética , Bactérias Gram-Positivas/isolamento & purificação , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Interleucina-6/análise , Interleucina-6/sangue , Reação em Cadeia da Polimerase Multiplex/métodos , Reação em Cadeia da Polimerase Multiplex/estatística & dados numéricos , Prognóstico , Sensibilidade e Especificidade , Choque Séptico/mortalidade , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/sangue , Resistência beta-Lactâmica/genética
10.
Med. intensiva (Madr., Ed. impr.) ; 44(4): 226-232, mayo 2020. graf, tab
Artigo em Inglês | IBECS | ID: ibc-190574

RESUMO

OBJECTIVE: A comparison is made of the accuracy between severity models, based on different sepsis definitions (systemic inflammatory response syndrome (SIRS), predisposition, insult, response, organ dysfunction (PIRO), and sequential organ failure assessment (SOFA) concepts), in predicting outcomes among sepsis PATIENTS: DESIGN: A retrospective study was carried out. SETTING: The study was conducted in the Intensive Care Unit (ICU) of a university teaching hospital. PATIENTS: Septic patients admitted to the ICU during 2007-2016. Main variables of interest: The primary outcome was in-hospital mortality, with ICU mortality being the secondary outcome. RESULTS: A total of 2152 septic patient were identified, with ICU and in-hospital mortality rates of 33.3% and 45.9%, respectively. The Moreno PIRO (AUC, 95%CI) (0.835; 0.818-0.852) showed the highest discriminating capacity, followed by SOFA (0.828; 0.811-0.846), qSOFA (0.792; 0.775-0.809), Rubulotta PIRO (0.708; 0.687-0.730), Howell PIRO (0.706; 0.685-0.728) and SIRS (0.578; 0.556-0.600). The AUC of the SOFA score was comparable to that of the Moreno PIRO (p = 0.43), though the AUCs of both of these scores were significantly higher than those of the other scores (p < 0.001 for all other comparisons). However, the SOFA score showed the best discriminating capacity in predicting ICU mortality (0.838; 0.820-0.855), followed by Moreno PIRO (0.804; 0.785-0.823) and qSOFA (0.787; 0.770-0.805). The accuracy of the qSOFA in predicting ICU mortality was comparable to that of the Moreno PIRO score (p = 0.15). CONCLUSIÓN: The SOFA score and Moreno PIRO score showed the best accuracy in predicting in-hospital mortality among septic patients admitted to the ICU


OBJETIVO: Comparar la precisión entre varios modelos de intensidad, basándose en diferentes definiciones de la sepsis (síndrome de respuesta inflamatoria sistémica [SIRS, por sus siglas en inglés], predisposición, infección, respuesta, disfunción orgánica [PIRO por sus siglas en inglés] y puntuación de la evaluación del fallo orgánico secuencial [SOFA por sus siglas en inglés]) para predecir los desenlaces en los pacientes con sepsis. DISEÑO: Estudio retrospectivo. Ámbito: El estudio se llevó a cabo en la unidad de cuidados intensivos (UCI) de un hospital universitario. PACIENTES: Enfermos con sepsis ingresados en la UCI durante 2007-2016. Variables de interés principales: El desenlace principal fue la mortalidad hospitalaria, mientras que la mortalidad en la UCI fue el desenlace secundario. RESULTADOS: Se identificó un total de 2.152 pacientes con sepsis, con unas tasas de mortalidad en la UCI e intrahospitalaria del 33,3 y del 45,9%, respectivamente. El modelo Moreno-PIRO (AUC, IC del 95%) (0,835; 0,818-0,852) fue el que presentó una mayor capacidad de discriminación, seguido del modelo SOFA (0,828; 0,811-0,846), modelo qSOFA (0,792; 0,775-0,809), modelo Rubulotta-PIRO (0,708; 0,687-0,730), modelo Howell-PIRO (0,706; 0,685-0,728) y modelo SIRS (0,578; 0,556-0,600). El AUC de la puntuación SOFA fue comparable al de Moreno-PIRO (p = 0,43), si bien el AUC de ambas puntuaciones fue significativamente superior al de otras puntuaciones (p < 0,001 para todas las demás comparaciones). Sin embargo, la puntuación SOFA es la que presenta la mayor capacidad de discriminación para predecir la mortalidad en la UCI (0,838; 0,820-0,855), seguida de Moreno-PIRO (0,804; 0,785-0,823) y qSOFA (0,787; 0,770-0,805). La precisión de la puntuación qSOFA en cuanto a la predicción de la mortalidad en la UCI fue comparable a la de la puntuación Moreno-PIRO (p = 0,15). CONCLUSIÓN: La puntuación SOFA y la puntuación Moreno-PIRO mostraron la mejor precisión en la predicción Mortalidad intrahospitalaria entre pacientes sépticos ingresados en la UCI


Assuntos
Humanos , Escores de Disfunção Orgânica , Previsões , Mortalidade Hospitalar , Síndrome de Resposta Inflamatória Sistêmica/mortalidade , Unidades de Terapia Intensiva , Estudos Retrospectivos , Síndrome de Resposta Inflamatória Sistêmica/epidemiologia , Choque Séptico/mortalidade
12.
Epidemiol Infect ; 148: e87, 2020 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-32238212

RESUMO

There has been no study exploring the prognostic values of neutrophil percentage-to-albumin ratio (NPAR). We hypothesised that NPAR is a novel marker of inflammation and is associated with all-cause mortality in patients with severe sepsis or septic shock. Patient data were extracted from the MIMIC-III V1.4 database. Only the data for the first intensive care unit (ICU) admission of each patient were used and baseline data were extracted within 24 h after ICU admission. The clinical endpoints were 30-, 90- and 365-day all-cause mortality in critically ill patients with severe sepsis or septic shock. Cox proportional hazards models and subgroup analyses were used to determine the relationship between NPAR and these clinical endpoints. A total of 2166 patients were eligible for this analysis. In multivariate analysis, after adjustments for age, ethnicity and gender, higher NPAR was associated with increased risk of 30-, 90- and 365-day all-cause mortality in critically ill patients with severe sepsis or septic shock. Furthermore, after adjusting for more confounding factors, higher NPAR remained a significant predictor of all-cause mortality (tertile 3 vs. tertile 1: HR, 95% CI: 1.29, 1.04-1.61; 1.41, 1.16-1.72; 1.44, 1.21-1.71). A similar trend was observed in NPAR levels stratified by quartiles. Higher NPAR was associated with increased risk of all-cause mortality in critically ill patients with severe sepsis or septic shock.


Assuntos
Albuminas , Neutrófilos , Sepse/mortalidade , Choque Séptico/mortalidade , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
PLoS One ; 15(4): e0231555, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32315321

RESUMO

The proline-specific enzymes dipeptidyl peptidase 4 (DPP4), prolylcarboxypeptidase (PRCP), fibroblast activation protein α (FAP) and prolyl oligopeptidase (PREP) are known for their involvement in the immune system and blood pressure regulation. Only very limited information is currently available on their enzymatic activity and possible involvement in patients with sepsis and septic-shock. The activity of the enzymes was measured in EDTA-plasma of patients admitted to the intensive care unit (ICU): 40 septic shock patients (sepsis-2) and 22 ICU control patients after major intracranial surgery. These data were used to generate receiver operating characteristic (ROC) curves. A survival analysis (at 90 days) and an association study with other parameters was performed. PRCP (day 1) and PREP (all days) enzymatic activities were higher in septic shock patients compared to controls. In contrast, FAP and DPP4 were lower in these patients on all studied time points. Since large differences were found, ROC curves were generated and these yielded area under the curve (AUC) values for PREP, FAP and DPP4 of 0.88 (CI: 0.80-0.96), 0.94 (CI: 0.89-0.99) and 0.86 (CI: 0.77-0.95), respectively. PRCP had a lower predicting value with an AUC of 0.71 (CI: 0.58-0.83). A nominally significant association was observed between survival and the DPP4 enzymatic activity at day 1 (p<0.05), with a higher DPP4 activity being associated with an increase in survival. All four enzymes were dysregulated in septic shock patients. DPP4, FAP and PREP are good in discriminating between septic shock patients and ICU controls and should be further explored to see whether they are already dysregulated in earlier stages, opening perspectives for their further investigation as biomarkers in sepsis. DPP4 also shows potential as a prognostic biomarker. Additionally, the associations found warrant further research.


Assuntos
Carboxipeptidases/sangue , Dipeptidil Peptidase 4/sangue , Gelatinases/sangue , Proteínas de Membrana/sangue , Serina Endopeptidases/sangue , Choque Séptico/sangue , Choque Séptico/enzimologia , Área Sob a Curva , Biomarcadores/sangue , Cuidados Críticos , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prolina/metabolismo , Estudos Prospectivos , Curva ROC , Choque Séptico/mortalidade , Choque Séptico/terapia , Análise de Sobrevida
14.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(1): 39-43, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-32148229

RESUMO

OBJECTIVE: To evaluate the prognostic value of arterial lactate (Lac) combined with central venous-to-arterial carbon dioxide difference to arterial-to-central venous oxygen content difference ratio (Pcv-aCO2/Ca-cvO2) in patients with septic shock following early fluid resuscitation. METHODS: A total of 97 patients with septic shock admitted to intensive care unit (ICU) of Lanzhou University Second Hospital from January 2017 to December 2019 were enrolled. The Pcv-aCO2/Ca-cvO2 ratio was calculated from blood gas analysis of radial artery and superior vena cava which was performed before resuscitation and at 6 hours of resuscitation at the same time. The patients were divided into death group and survival group according to the 28-day prognosis. The baseline data, acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure score (SOFA), clinical therapy, lactate clearance rate (LCR) at 6 hours, the length of ICU stay, hemodynamics and oxygen metabolism parameters before and after resuscitation were compared between the two groups. Risk factors were analyzed by multivariate Cox regression for 28-day mortality of patients with septic shock. The receiver operating characteristic (ROC) curve was plotted to assess the prognostic values of these factors for 28-day mortality. RESULTS: (1) Compared with the survival group, the patients in the death group showed significantly higher levels of APACHE II score (23.96±4.31 vs. 17.70±3.92) and SOFA score (12.74±2.80 vs. 9.23±2.43, both P < 0.01), significantly higher proportions of mechanical ventilation [85.2% (23/27) vs. 50.0% (35/70)] and continuous renal replacement therapy [CRRT; 51.9% (14/27) vs. 25.7% (18/70), both P < 0.05], a significantly more fluid replacement at 6 hours (L: 2.92±0.24 vs. 2.63±0.25, P < 0.01), a significantly lower level of LCR at 6 hours [(11.61±7.76)% vs. (27.67±13.71)%, P < 0.01], and a shorter length of ICU stay (days: 6.37±2.70 vs. 7.67±2.31, P < 0.05). (2) Compared with the survival group, the patients before resuscitation in the death group showed a significantly lower level of mean arterial pressure [MAP (mmHg, 1 mmHg = 0.133 kPa): 52.63±4.35 vs. 55.74±3.01, P < 0.01], significantly higher levels of Lac and Pcv-aCO2/Ca-cvO2 ratio [Lac (mmol/L): 7.13±1.75 vs. 5.22±1.36, Pcv-aCO2/Ca-cvO2 ratio: 1.67±0.29 vs. 1.48±0.22, both P < 0.01]; and the patients at 6 hours of resuscitation in the death group showed a significantly lower level of MAP (mmHg: 62.59±4.80 vs. 66.71±3.91, P < 0.01), significantly higher levels of central venous pressure (CVP), Lac, Pcv-aCO2 and Pcv-aCO2/Ca-cvO2 ratio [CVP (mmHg): 10.74±1.40 vs. 8.80±0.75, Lac (mmol/L): 6.36±1.86 vs. 3.90±1.95, Pcv-aCO2 (mmHg): 7.59±2.02 vs. 4.34±1.37, Pcv-aCO2/Ca-cvO2 ratio: 1.87±0.51 vs. 1.03±0.27, all P < 0.01]. (3) Multivariate Cox regression analysis showed that the independent risk factors for 28-day mortality in patients with septic shock were Lac and Pcv-aCO2/Ca-cvO2 ratio whether before or at 6 hours of resuscitation [Lac before resuscitation: relative risk (RR) = 1.434, 95% confidence interval (95%CI) was 1.070-1.922, P = 0.016; Lac at 6 hours of resuscitation: RR = 1.564, 95%CI was 1.202-2.035, P = 0.001; Pcv-aCO2/Ca-cvO2 ratio before resuscitation: RR = 2.828, 95%CI was 1.108-4.207, P = 0.038; Pcv-aCO2/Ca-cvO2 ratio at 6 hours of resuscitation: RR = 4.386, 95%CI was 2.842-5.730, P = 0.000]. (4) ROC curve analysis showed that Lac and Pcv-aCO2/Ca-cvO2 ratio at 6 hours of resuscitation had predictive value for the prognosis of patients with septic shock, the area under ROC curve (AUC) was 0.849 (95%CI was 0.762-0.914) and 0.905 (95%CI was 0.828-0.955), respectively. However, the predictive value of Lac combined with Pcv-aCO2/Ca-cvO2 ratio in patients with septic shock was significantly higher than Lac [AUC (95%CI): 0.976 (0.923-0.996) vs. 0.849 (0.762-0.914), Z = 3.354, P = 0.001], the sensitivity was 97.14%, and the specificity was 88.89%. CONCLUSIONS: Lac and Pcv-aCO2/Ca-cvO2 ratio are independent risk factors for predicting 28-day mortality in patients with septic shock. Lac combined with Pcv-aCO2/Ca-cvO2 ratio can assess the prognosis of patients with septic shock more accurately.


Assuntos
Gasometria , Dióxido de Carbono/sangue , Ácido Láctico/sangue , Oxigênio/sangue , Choque Séptico/diagnóstico , Hidratação , Humanos , Prognóstico , Fatores de Risco , Choque Séptico/mortalidade
15.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(1): 44-49, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-32148230

RESUMO

OBJECTIVE: To investigate the relationship between serum cholinesterase (SChE) level and the prognosis of patients with septic shock (SS). METHODS: A total of 594 patients with SS admitted to the First Affiliated Hospital of Zhengzhou University from June 2013 to June 2017 were enrolled. General data such as gender, age, acute physiology and chronic health evaluation II (APACHE II) score were recorded as well as routine blood test, procalcitonin (PCT), hepatic function, renal function, coagulation function and blood gas analysis parameters within 48 hours of SS diagnosis. The patients were followed by telephone from September to October in 2019, and the outcome was recorded. The primary outcome was all-cause death 28 days after discharge. The secondary outcomes were all-cause death in intensive care unit (ICU) and 2 years after discharge, and the length of ICU stay. The patients were divided into two groups according to prognosis of 28 days: the survival group and the death group. The clinical data of the two groups were compared. Multivariate Cox regression analysis was used to screen prognostic risk factors of 28 days in patients with SS. The receiver operating characteristic (ROC) curve was used to explore predictive value of liver function parameter SChE for 28-day prognosis of patients with SS. The patients were divided into two groups according to the levels of SChE: the low SChE group (SChE ≤ 4 000 U/L) and the normal SChE group (SChE > 4 000 U/L). Kaplan-Meier survival curves were used to compare the cumulative survival rates without endpoint event of patients with different SChE levels. RESULTS: A total of 385 patients with SS were enrolled according to the inclusion and exclusion criteria, and a total of 356 patients were followed up successfully, with a follow-up rate of 92.5% (356/385). There were 142 survival patients and 214 death patients at 28 days, with a 28-day mortality rate of 60.1% (214/356). There were 116 survival patients and 240 death patients at 2 years, with a 2-year mortality rate of 67.4% (240/356). Compared with the 28-day survival group, the patients in the death group were older and had higher APACHE II score, partial hepatic and renal function parameters, higher level of blood lactate (Lac) and lower levels of white blood cell count (WBC), platelet count (PLT) and SChE with statistically significant differences. Multivariate Cox regression analysis showed that the age [relative risk (RR) = 1.444, 95% confidence interval (95%CI) was 1.090-1.914, P = 0.010], APACHE II score (RR = 2.249, 95%CI was 1.688-2.997, P = 0.000), SChE (RR = 1.469, 95%CI was 1.057-2.043, P = 0.022), and Lac (RR = 2.190, 95%CI was 1.636-2.931, P = 0.000) were independent risk factors for 28-day mortality of patients with SS. The ROC curve analysis showed that SChE had a weak prognostic value for 28-day prognosis of patients with SS [the area under ROC curve (AUC) was 0.574]. However, the combined predictive value of SChE, APACHE II score and Lac was greater than APACHE II score or Lac alone for prediction (AUC: 0.807 vs. 0.785, 0.697), with a sensitivity of 79.9% and a specificity of 68.5%. Compared with the normal SChE group (n = 88), the 28-day mortality of patients in the low SChE group (n = 268) was significantly increased [63.1% (169/268) vs. 51.1% (45/88), P < 0.05], but ICU mortality [59.7% (160/268) vs. 48.9% (43/88)], 2-year mortality [69.8% (187/268) vs. 60.2% (53/88)] or the length of ICU stay [days: 4 (2, 7) vs. 5 (2, 9)] between the two groups showed no statistical significance (all P > 0.05). Kaplan-Meier survival curve analysis showed that the cumulative survival rate without endpoint event of patients in the low SChE group was significantly lower than that in the normal SChE group (Log-Rank test: χ2 = 5.852, P = 0.016). CONCLUSIONS: Increased risk of 28-day mortality in patients with SS whose SChE is below normal. The level of SChE is an independent risk factor for 28-day death in SS patients, and it is one of the indicators to evaluate the short-term prognosis of patients with SS.


Assuntos
Colinesterases/sangue , Choque Séptico/diagnóstico , APACHE , Humanos , Unidades de Terapia Intensiva , Prognóstico , Curva ROC , Estudos Retrospectivos , Choque Séptico/enzimologia , Choque Séptico/mortalidade
16.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(1): 56-61, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-32148232

RESUMO

OBJECTIVE: To systematically review the efficacy of ultrasound-guided fluid resuscitation and early goal-directed therapy (EGDT) in patients with septic shock. METHODS: Multiple databases including Wanfang, CNKI, SinoMed, VIP, PubMed, Embase, Cochrane Library and Web of Science were searched from initial to August 2019 for randomized controlled trial (RCT) studies about the comparison of ultrasound-guided fluid resuscitation and EGDT on resuscitation effect in patients with septic shock. Language, country and region were unlimited. Data extraction and quality evaluation were carried out by means of independent review and cross check results by two researchers. RESULTS: Finally, only two English RCT studies were enrolled. In the two RCT studies, the ultrasound groups used inferior vena cava collapse index (VCCI) and ultrasound score to guide fluid resuscitation, which resulted in clinical heterogeneity. Because the results could not be pooled, only systematic review, not meta-analysis, could be done. There were measurement bias and selection bias in the two RCT studies, and the literature quality level was B and C respectively. System review results showed that using ultrasound would reduce 7-day mortality (15.0% vs. 35.0%, P = 0.039) and prescribe less of 24-hour intravenous fluids (mL: 900 vs. 1 850, P < 0.01) for patients with septic shock as compared with EGDT. Ultrasound was easy to assess the reactive capacity and cardiac function of patients with septic shock, so as to decrease the incidence of pulmonary edema, which was significantly lower than EGDT (15.0% vs. 37.5%, P = 0.022). However, there was no statistically significant difference in 28-day mortality, duration of mechanical ventilation or length of intensive care unit (ICU) stay between the two groups. CONCLUSIONS: The ultrasound-guided fluid resuscitation may be useful and practical for septic shock patients within 7 days after admission as compared with EGDT, but it cannot reduce the 28-day mortality, duration of mechanical ventilation or length of ICU stay.


Assuntos
Terapia Precoce Guiada por Metas , Hidratação , Choque Séptico/terapia , Ultrassonografia , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Ensaios Clínicos Controlados Aleatórios como Assunto , Choque Séptico/mortalidade
17.
Crit Care ; 24(1): 117, 2020 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-32216822

RESUMO

BACKGROUND: Almost one third of the patients with candidemia develop septic shock. The understanding why some patients do and others do not develop septic shock is very limited. The objective of this study was to identify variables associated with septic shock development in a large population of patients with candidemia. METHODS: A post hoc analysis was performed on two prospective, multicenter cohort of patients with candidemia from 12 hospitals in Spain and Italy. All episodes occurring from September 2016 to February 2018 were analyzed to assess variables associated with septic shock development defined according to The Third International Consensus Definition for Sepsis and Septic Shock (Sepsis-3). RESULTS: Of 317 candidemic patients, 99 (31.2%) presented septic shock attributable to candidemia. Multivariate logistic regression analysis identifies the following factors associated with septic shock development: age > 50 years (OR 2.57, 95% CI 1.03-6.41, p = 0.04), abdominal source of the infection (OR 2.18, 95% CI 1.04-4.55, p = 0.04), and admission to a general ward at the time of candidemia onset (OR 0.21, 95% CI, 0.12-0.44, p = 0.001). Septic shock development was independently associated with a greater risk of 30-day mortality (OR 2.14, 95% CI 1.08-4.24, p = 0.02). CONCLUSIONS: Age and abdominal source of the infection are the most important factors significantly associated with the development of septic shock in patients with candidemia. Our findings suggest that host factors and source of the infection may be more important for development of septic shock than intrinsic virulence factors of organisms.


Assuntos
Candidemia/complicações , Candidemia/mortalidade , Hospitalização/estatística & dados numéricos , Choque Séptico/microbiologia , Choque Séptico/mortalidade , Abdome , Fatores Etários , Idoso , Candidemia/tratamento farmacológico , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Choque Séptico/tratamento farmacológico , Espanha/epidemiologia , Taxa de Sobrevida , Resultado do Tratamento
18.
BMC Infect Dis ; 20(1): 221, 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32171247

RESUMO

BACKGROUND: The goal of the study was to evaluate a potential role for tumor necrosis factor alpha (TNF-α) genetic variability as biomarker in sepsis. In particular, we aimed to determine if single nucleotide polymorphisms (SNPs) of TNF-α gene are associated with sepsis in terms of risk, severity and outcome. METHODS: We performed a prospective study on 163 adult critically ill septic patients (septic shock 65, sepsis 98, further divided in 40 survivors and 123 deceased) and 232 healthy controls. Genotyping of TNF-α SNPs (-308G/A, -238G/A, -376G/A and +489G/A) was performed for all patients and controls and plasma cytokine levels were measured during the first 24 h after sepsis onset. RESULTS: TNF-α +489G/A A-allele carriage was associated with significantly lower risk of developing sepsis and sepsis shock (AA+AG vs GG: OR = 0.53; p = 0.004; 95% CI = 0.34-0.82 and OR = 0.39; p = 0.003; 95% CI = 0.21-0.74, respectively) but not with sepsis-related outcomes. There was no significant association between any of the other TNF-α promoter SNPs, or their haplotype frequencies and sepsis or septic shock risk. Circulating TNF-α levels were higher in septic shock; they were not correlated with SNP genotype distribution; GG homozygosity for each polymorphism was correlated with higher TNF-α levels in septic shock. CONCLUSIONS: TNF-α +489G/A SNP A-allele carriage may confer protection against sepsis and septic shock development but apparently does not influence sepsis-related mortality. Promoter TNF-α SNPs did not affect transcription and were not associated with distinct sepsis, septic shock risk or outcomes.


Assuntos
Progressão da Doença , Polimorfismo de Nucleotídeo Único , Choque Séptico/genética , Choque Séptico/mortalidade , Fator de Necrose Tumoral alfa/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Biomarcadores , Estado Terminal , Suscetibilidade a Doenças , Feminino , Haplótipos/genética , Homozigoto , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Regiões Promotoras Genéticas , Estudos Prospectivos
19.
Crit Care ; 24(1): 110, 2020 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-32192532

RESUMO

BACKGROUND: Decreased monocytic (m)HLA-DR expression is the most studied biomarker of sepsis-induced immunosuppression. To date, little is known about the relationship between sepsis characteristics, such as the site of infection, causative pathogen, or severity of disease, and mHLA-DR expression kinetics. METHODS: We evaluated mHLA-DR expression kinetics in 241 septic shock patients with different primary sites of infection and pathogens. Furthermore, we used unsupervised clustering analysis to identify mHLA-DR trajectories and evaluated their association with outcome parameters. RESULTS: No differences in mHLA-DR expression kinetics were found between groups of patients with different sites of infection (abdominal vs. respiratory, p = 0.13; abdominal vs. urinary tract, p = 0.53) and between pathogen categories (Gram-positive vs. Gram-negative, p = 0.54; Gram-positive vs. negative cultures, p = 0.84). The mHLA-DR expression kinetics differed between survivors and non-survivors (p < 0.001), with an increase over time in survivors only. Furthermore, we identified three mHLA-DR trajectories ('early improvers', 'delayed or non-improvers' and 'decliners'). The probability for adverse outcome (secondary infection or death) was higher in the delayed or non-improvers and decliners vs. the early improvers (delayed or non-improvers log-rank p = 0.03, adjusted hazard ratio 2.0 [95% CI 1.0-4.0], p = 0.057 and decliners log-rank p = 0.01, adjusted hazard ratio 2.8 [95% CI 1.1-7.1], p = 0.03). CONCLUSION: Sites of primary infection or causative pathogens are not associated with mHLA-DR expression kinetics in septic shock patients. However, patients showing delayed or no improvement in or a declining mHLA-DR expression have a higher risk for adverse outcome compared with patients exhibiting a swift increase in mHLA-DR expression. Our study signifies that changes in mHLA-DR expression over time, and not absolute values or static measurements, are of clinical importance in septic shock patients.


Assuntos
Antígenos HLA-DR/metabolismo , Choque Séptico/imunologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Infecção Hospitalar , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Prognóstico , Fatores de Risco , Choque Séptico/mortalidade
20.
PLoS One ; 15(3): e0229919, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32160234

RESUMO

BACKGROUND: Dysglycemia is frequently observed in patients with sepsis. However, the relationship between dysglycemia and outcome is inconsistent. We evaluate the clinical characteristics, glycemic abnormalities, and the relationship between the initial glucose level and mortality in patients with sepsis. METHODS: This is a retrospective sub-analysis of a multicenter, prospective cohort study. Adult patients with severe sepsis (Sepsis-2) were divided into groups based on blood glucose categories (<70 (hypoglycemia), 70-139, 140-179, and ≥180 mg/dL), according to the admission values. In-hospital mortality and the relationship between pre-existing diabetes and septic shock were evaluated. RESULTS: Of 1158 patients, 69, 543, 233, and 313 patients were categorized as glucose levels <70, 70-139, 140-179, ≥180 mg/dL, respectively. Both the Acute Physiological and Chronic Health Evaluation II and Sequential Organ Failure Assessment (SOFA) scores on the day of enrollment were higher in the hypoglycemic patients than in those with 70-179 mg/dL. The hepatic SOFA scores were also higher in hypoglycemic patients. In-hospital mortality rates were higher in hypoglycemic patients than in those with 70-139 mg/dL (26/68, 38.2% vs 43/221, 19.5%). A significant relationship between mortality and hypoglycemia was demonstrated only in patients without known diabetes. Mortality in patients with both hypoglycemia and septic shock was 2.5-times higher than that in patients without hypoglycemia and septic shock. CONCLUSIONS: Hypoglycemia may be related to increased severity and high mortality in patients with severe sepsis. These relationships were evident only in patients without known diabetes. Patients with both hypoglycemia and septic shock had an associated increased mortality rate.


Assuntos
Diabetes Mellitus/fisiopatologia , Hipoglicemia/fisiopatologia , Sepse/fisiopatologia , Choque Séptico/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Glicemia , Diabetes Mellitus/sangue , Diabetes Mellitus/mortalidade , Feminino , Glucose/metabolismo , Humanos , Hipoglicemia/sangue , Hipoglicemia/complicações , Hipoglicemia/mortalidade , Hipoglicemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Mortalidade , Estudos Prospectivos , Sepse/sangue , Sepse/complicações , Sepse/mortalidade , Índice de Gravidade de Doença , Choque Séptico/sangue , Choque Séptico/mortalidade
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