Xuebijing injection, a Chinese patent medicine, against severe pneumonia: Current research progress and future perspectives / 中西医结合学报

Severe pneumonia is one of the most common infectious diseases and the leading cause of sepsis and septic shock. Preventing infection, balancing the patient's immune status, and anti-coagulation therapy are all important elements in the treatment of severe pneumonia. As multi-target agents, Xuebijing injection (XBJ) has shown unique advantages in targeting complex conditions and saving the lives of patients with severe pneumonia. This review outlines progress in the understanding of XBJ's anti-inflammatory, endotoxin antagonism, and anticoagulation effects. From the hundreds of publications released over the past few years, the key results from representative clinical studies of XBJ in the treatment of severe pneumonia were selected and summarized. XBJ was observed to effectively suppress the release of pro-inflammatory cytokines, counter the effects of endotoxin, and assert an anticoagulation effect in most clinical trials, which are consistent with experimental studies. Collectively, this evidence suggests that XBJ could play an important and expanding role in clinical medicine, especially for sepsis, septic shock and severe pneumonia. Please cite this article as: Zhang M, Zheng R, Liu WJ, Hou JL, Yang YL, Shang HC. Xuebijing injection, a Chinese patent medicine, against severe pneumonia: Current research progress and future perspectives. J Integr Med. 2023; 21(5): 413-422.

The value of maximal rate of left ventricular pressure in evaluating cardiac function in patients with sepsis-induced cardiomyopathy / 中华危重病急救医学

OBJECTIVE@#To investigate the value of maximal rate of left ventricular pressure (dp/dtmax) in evaluating the changes of cardiac function before and after heart rate reduction in patients with sepsis-induced cardiomyopathy (SIC).@*METHODS@#A single-center, prospective randomized controlled study was conducted. Adult patients with sepsis/septic shock admitted to the department of intensive care unit (ICU) of Tianjin Third Central Hospital from April 1, 2020 to February 28, 2022 were enrolled. Speckle tracking echocardiography (STE) and pulse indication continuous cardiac output (PiCCO) monitoring were performed immediately after the completion of the 1 h-Bundle therapy. The patients with heart rate over 100 beats/minutes were selected and randomly divided into esmolol group and regular treatment group, 55 cases in each group. All patients underwent STE and PiCCO monitoring at 6, 24 and 48 hours after admission in ICU and calculated acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA). Primary outcome measure: change in dp/dtmax after reducing heart rate by esmolol. Secondary outcome measures: correlation between dp/dtmax and global longitudinal strain (GLS); changes of vasoactive drug dosage, oxygen delivery (DO2), oxygen consumption (VO2) and stroke volume (SV) after the administration of esmolol; proportion of heart rate reaching the target after the administration of esmolol; 28-day and 90-day mortality in two groups.@*RESULTS@#Baseline data on age, gender, body mass index, SOFA score, APACHE II score, heart rate, mean arterial pressure, lactic acid, 24-hour fluid balance, sepsis etiology and prior comorbidities were similar between esmolol group and regular treatment group, there were no significant differences between the two groups. All SIC patients achieved the target heart rate after 24 hours of esmolol treatment. Compared with regular treatment group, parameters reflecting myocardial contraction such as GLS, global ejection fraction (GEF) and dp/dtmax were significantly increased in esmolol group [GLS: (-12.55±4.61)% vs. (-10.73±4.82)%, GEF: (27.33±4.62)% vs. (24.18±5.35)%, dp/dtmax (mmHg/s): 1 312.1±312.4 vs. 1 140.9±301.0, all P < 0.05], and N-terminal pro-brain natriuretic peptide (NT-proBNP) significantly decreased [μg/L: 1 364.52 (754.18, 2 389.17) vs. 3 508.85 (1 433.21, 6 988.12), P < 0.05], DO2 and SV were significantly increased [DO2 (mL×min-1×m-2): 647.69±100.89 vs. 610.31±78.56, SV (mL): 49.97±14.71 vs. 42.79±15.77, both P < 0.05]. The system vascular resistance index (SVRI) in esmolol group was significantly higher than that in regular treatment group (kPa×s×L-1: 287.71±66.32 vs. 251.17±78.21, P < 0.05), even when the dosage of norepinephrine was similar between the two groups. Pearson correlation analysis showed that dp/dtmax was negatively correlated with GLS in SIC patients at 24 hours and 48 hours after ICU admission (r values were -0.916 and -0.935, respectively, both P < 0.05). Although there was no significant difference in 28-day mortality between esmolol group and regular treatment group [30.9% (17/55) vs. 49.1% (27/55), χ2 = 3.788, P = 0.052], the rate of esmolol use in patients who died within 28 days was lower than that in patients who survived [38.6% (17/44) vs. 57.6% (38/66), χ2 = 3.788, P = 0.040]. In addition, esmolol has no effect on the 90-day mortality of patients. Logistic regression analysis showed that after adjusting for SOFA score and DO2 factors, patients who used esmolol had a significantly lower risk of 28-day mortality compared with patients who did not use esmolol [odds ratio (OR) = 2.700, 95% confidence interval (95%CI) was 1.038-7.023, P = 0.042].@*CONCLUSIONS@#dp/dtmax in PiCCO parameter can be used as a bedside indicator to evaluate cardiac function in SIC patients due to its simplicity and ease of operation. Esmolol control of heart rate in SIC patients can improve cardiac function and reduce short-term mortality.

Effects of dexmedetomidine on hemodynamic, oxygenation, microcirculation, and inflammatory markers in a porcine model of sepsis

Purpose: To determine whether dexmedetomidine aggravates hemodynamic, metabolic variables, inflammatory markers, and microcirculation in experimental septic shock. Methods: Twenty-four pigs randomized into: Sham group (n = 8), received saline; Shock group (n = 8), received an intravenous infusion of Escherichia coli O55 (3 × 109 cells/mL, 0.75 mL/kg, 1 hour); Dex-Shock group (n = 8), received bacteria and intravenous dexmedetomidine (bolus 0.5 mcg/kg followed by 0.7 mcg/kg/h). Fluid therapy and/ornorepinephrine were administered to maintain a mean arterial pressure > 65 mmHg. Hemodynamic, metabolic, oxygenation, inflammatory markers, and microcirculation were assessed at baseline, at the end of bacterial infusion, and after 60, 120, 180, and 240 minutes. Results: Compared to Shock group, Dex-Shock group presented a significantly increased oxygen extraction ratio at T180 (23.1 ± 9.7 vs. 32.5 ± 9.2%, P = 0.0220), decreased central venous pressure at T120 (11.6 ± 1 vs. 9.61 ± 1.2 mmHg, P = 0.0214), mixed-venous oxygen saturation at T180 (72.9 ± 9.6 vs. 63.5 ± 9.2%, P = 0.026), and increased plasma lactate (3.7 ± 0.5 vs. 5.5 ± 1 mmol/L, P = 0.003). Despite the Dex-Shock group having a better sublingual vessel density at T240 (12.5 ± 0.4 vs. 14.4 ± 0.3 mL/m2; P = 0.0003), sublingual blood flow was not different from that in the Shock group (2.4 ± 0.2 vs. 2.4 ± 0.1 mL/kg, P = 0.4418). Conclusions: Dexmedetomidine did not worsen the hemodynamic, metabolic, inflammatory, or sublingual blood flow disorders resulting from septic shock. Despite inducing a better sublingual vessel density, dexmedetomidine initially and transitorily increased the mismatch between oxygen supply and demand.

Immunomodulator use in paediatric severe sepsis and septic shock

INTRODUCTION@#The use of drugs that modulate the immune system during paediatric severe sepsis and septic shock may alter the course of disease and is poorly studied. This study aims to characterise these children who received immunomodulators and describe their clinical outcomes.@*METHODS@#This is a retrospective chart review of patients with severe sepsis and septic shock admitted into the paediatric intensive care unit (PICU). Clinical, haematological and outcome characteristics of patients with or without exposure to immune-modulating drugs were compared. Primary outcome was PICU mortality; secondary outcomes were 28-day ventilator-free days (VFD) and intensive care unit-free days (IFD). Univariate and multivariable analyses were performed for these outcomes.@*RESULTS@#A total of 109 patients with paediatric severe sepsis or septic shock were identified. Of this number, 47 (43.1%), 16 (14.7%) and 3 (2.8%) patients received systemic corticosteroids, intravenous immunoglobulins and granulocyte colony stimulating factor, respectively. Patients who received immune-modulating drugs were more likely to require invasive ventilation (38/54 [70.4%] versus 26/55 [47.3%], @*CONCLUSION@#Immune-modulating drugs were frequently used in paediatric severe sepsis and septic shock. Patients who received these drugs seemed to require more PICU support. Further studies are required to examine this association thoroughly.

Evolución clínica de niños con shock séptico refractario a fluidos tratados con dopamina o adrenalina. Estudio retrospectivo en un servicio de emergencias pediátrico de Argentina / Clinical outcome of children with fluid-refractory septic shock treated with dopamine or epinephrine. A retrospective study at a pediatric emergency department in Argentina

RESUMEN Objetivo: Analizar la evolución clínica de niños con shock séptico refractario a volumen tratados inicialmente con dopamina o adrenalina. Métodos: Estudio de cohorte retrospectivo con ámbito en un servicio de urgencias pediátrico de un hospital de tercer nivel. Población: niños ingresados con shock séptico refractario a volumen. Se comparó la evolución clínica entre 2 grupos: Grupo Dopamina y Grupo Adrenalina. Las variables de interés fueron: uso de ventilación mecánica invasiva, días de inotrópicos, estancia hospitalaria, estancia en cuidados intensivos y mortalidad. Para variables numéricas y categóricas utilizamos medidas de tendencia central y para comparación las pruebas de U Mann Whitney y χ2 test. Resultados: Incluimos 118 pacientes. El 58,5% recibió dopamina y 41,5% adrenalina. El uso de ventilación mecánica invasiva fue 38,8% para adrenalina versus 40,6% para dopamina (p = 0,84) con una mediana de 4 días para adrenalina y 5,5 para dopamina (p = 0,104). La mediana para días de inotrópicos fue de 2 días para ambos grupos (p = 0,714). La mediana de estancia hospitalaria fue de 11 para adrenalina y 13 para dopamina (p = 0,554) y de estancia en cuidados intensivos se registró una mediana de 4 días (0 - 81 días) siendo igual en ambos grupos (p = 0,748). La mortalidad fue de 5% para el Grupo Adrenalina versus 9% para el Grupo Dopamina (p = 0,64). Conclusiones: En nuestro centro, no observamos diferencias en uso de ventilación mecánica invasiva y tiempo de inotrópicos, estancia hospitalaria y cuidados intensivos y mortalidad entre niños ingresados al servicio de urgencias pediátrico con diagnóstico de shock séptico refractario a volumen tratados inicialmente con dopamina o adrenalina.

Abstract Objective: To analyze the clinical outcome of children with fluid-refractory septic shock initially treated with dopamine or epinephrine. Methods: A retrospective cohort study was conducted at a pediatric emergency department of a tertiary hospital. Population: children admitted because of fluid-refractory septic shock. Clinical outcome was compared between two groups: Dopamine and Epinephrine. Variables evaluated were use of invasive mechanical ventilation, days of inotropic therapy, length of hospital stay, intensive care stay, and mortality. For numerical and categorical variables, we used measures of central tendency. They were compared by the Mann-Whitney U-test and the (2 test. Results: We included 118 patients. A total of 58.5% received dopamine and 41.5% received epinephrine. The rate of invasive mechanical ventilation was 38.8% for epinephrine versus 40.6% for dopamine (p = 0.84), with a median of 4 days for the Epinephrine Group and 5.5 for the Dopamine Group (p = 0.104). Median time of inotropic therapy was 2 days for both groups (p = 0.714). Median hospital stay was 11 and 13 days for the Epinephrine and Dopamine groups, respectively (p = 0.554), and median stay in intensive care was 4 days (0 - 81 days) in both groups (p = 0.748). Mortality was 5% for the Epinephrine Group versus 9% for the Dopamine Group (p = 0.64). Conclusions: At our center, no differences in use of invasive mechanical ventilation, time of inotropic therapy, length of hospital stay, length of intensive care unit stay, or mortality were observed in children admitted to the pediatric emergency department with a diagnosis of fluid-refractory septic shock initially treated with dopamine versus epinephrine.

Experiencia en shock séptico en emergencias. Factores asociados a falta de respuesta a fluídos / Experience in septic shock in Emergencies. Factors associated with lack of response to fluid resuscitation

Introducción: La sepsis es una de las principales causas de muerte infantil a nivel mundial. Las guías de tratamiento utilizadas en nuestro servicio se basan en parámetros clínicos para un soporte hemodinámico temprano con énfasis en el uso de fluidos e inotrópicos guiados por metas clínicas. Objetivos: Describir las características epidemiológicas y clínicas en una cohorte de niños con diagnóstico de shock séptico (SS) en el área de emergencias, controlando tasa de respuesta a fluidos, mortalidad y su relación con las características de los pacientes. Materiales y métodos: Estudio observacional de cohorte prospectivo entre Julio del 2009 y Julio del 2010. Se incluyeron 83 pacientes entre 0 a 18 años que cumplieron con los criterios diagnósticos de SS. La respuesta a volumen se definió como: respondedores (RE) a los pacientes que solo requirieron expansión con volumen y no respondedores (nRE) a aquellos que requirieron inotrópicos luego de llegar a 60 ml/kg o aparición de signos de sobrecarga cardíaca. Resultados: 64% fueron varones con mediana de edad de 5,8 años (RIC 2-12). 71% presentaban alguna enfermedad crónica preexistente, siendo 40% pacientes oncológicos. El 25 % requirió asistencia respiratoria mecánica y 65% inotrópicos. La mediana de estadía hospitalaria fue 10 días (RIC 7-16 días). Un 35% fue RE. Solo la hipotensión al ingreso resultó ser factor de riesgo para nRE (p0,035), pero en el modelo multivariado no resultó estadísticamente significativo. El 8% de los pacientes fallecieron. Conclusiones: En nuestra población, los pacientes con enfermedades oncológicas representan un número importante de los casos de SS y posiblemente tengan una mayor mortalidad. La tasa de respuesta a volumen ocurrió en 35% de los casos. La hipotensión inicial constituye un probable factor de riesgo para nRE (AU)

Introduction: Sepsis is one of the main causes of childhood death worldwide. Treatment guidelines used at our department are based on clinical parameters for early hemodynamic support with emphasis on fluid resuscitation and inotropics use guided by clinical goals. Objectives: To describe the epidemiologic and clinical features of a cohort of children with septic shock (SS) seen at the emergency department evaluating response rate to fluid resuscitation and mortality related to patient characteristics. Materials and methods: A prospective, observational cohort study was conducted between July 2009 and July 2010. Overall, 83 patients between 0 and 18 years of age that met the diagnostic criteria of SS were included. Response to fluid resuscitation was defined as: responders (RE), those patients that only required volume expansion, and non-responders (nRE), those that required inotropes after having reached 60 ml/kg or appearance of signs of fluid overload. Results: 64% were boys; median age was 5.8 years (IQR 2-12); 71% had some type of preexisting chronic disease, consisting of cancer in 40%. Overall, 25% required mechanical ventilation and 65% inotropes. Median length of hospital stay was 10 days (IQR 7-16 days). 35% of the patients were RE. Only hypotension on admission was found to be a risk factor for nRE (p 0.035); however, in a multivariate model, this finding did not show to be statistically significant. Eight percent of the patients died. Conclusions: In our cohort, patients with cancer accounted for a large number of those who developed SS; in these patients mortality may be increased. Response rate to fluid resuscitation was 35%. Initial hypotension may be a risk factor for nRE.

Successful multiple-exchange peritoneal dialysis in a patient with severe hematological toxicity by methotrexate: case report and literature review / Diálise peritoneal com múltiplas trocas bem-sucedida em paciente com grave toxicidade hematológica por metotrexato: relato de caso e revisão de literatura

Abstract Methotrexate is an effective medication to control several diseases; however, it can be very toxic, being myelosuppression one of its main adverse effects, which increases in severity and frequency in patients with renal failure. We present the case of a 68-year-old man with chronic, end-stage renal disease associated with ANCA vasculitis, under treatment with peritoneal dialysis, who received the medication at a low dose, indicated by disease activity, which presented as a complication with severe pancytopenia with mucositis that improved with support measures and multiple-exchange peritoneal dialysis. We reviewed 20 cases published to date of pancytopenia associated with methotrexate in patients on dialysis and found high morbidity and mortality, which is why its use in this type of patient is not recommended. However, when this complication occurs, a therapeutic option could be the use of multiple-exchange peritoneal dialysis in addition to supportive therapy for drug-related toxicity, although it is recognized that studies are required to show the role of multiple-exchange peritoneal dialysis in the removal of this medication.

Resumo Apesar de sua toxicidade, o metotrexato é um medicamento eficaz no controle de várias doenças. A mielossupressão, um de seus principais efeitos adversos, aumenta em gravidade e frequência nos pacientes com insuficiência renal. Apresentamos o caso de um homem de 68 anos de idade com doença renal terminal relacionada à vasculite associada ao ANCA em diálise peritoneal, que recebeu a medicação em dose baixa em função da atividade da doença e que teve como complicação pancitopenia grave com mucosite, tratada com medidas de suporte e diálise peritoneal com múltiplas trocas. Revisamos 20 casos publicados até o presente momento sobre pancitopenia associada a metotrexato em pacientes em diálise. Foi identificada alta morbidade e mortalidade, razão pela qual seu uso nesse tipo de paciente não é recomendado. No entanto, quando esta complicação ocorre, uma opção terapêutica pode ser o uso de diálise peritoneal com múltiplas trocas, além da terapia de suporte para toxicidade medicamentosa. Maiores estudos são necessários para demonstrar o papel da diálise peritoneal com múltiplas trocas na remoção desse medicamento.

Análisis clínico y microbiológico de la sepsis grave y el choque séptico por Escherichia coli en Medellín, Colombia / Severe sepsis and septic shock by Escherichia coli, clinical and microbiological analysis in Medellin, Colombia

Resumen Introducción: Escherichia coli es causa frecuente de un amplio espectro de infecciones, desde una infeccion urinaria no complicada hasta la sepsis grave y el choque septico, asociadas con desenlaces de alto impacto como ingreso a UCI y mortalidad. Objetivos: Determinar las diferencias en mortalidad. ingreso a UCI/UCE, presencia de cepas BLEE y tratamiento antimicrobiano en pacientes con sepsis grave y choque séptico por E. coli, con o sin bacteriemia, asi como su variabilidad dependiendo del foco infeccioso. Material y Métodos: Análisis secundario de estudio de cohorte prospective multicéntrico. Resultados: De 458 pacientes que tenian infeccion por E. coli, 123 tenian aislamiento solo en hemocultivo, 222 solo en urocultivo y 113 en ambas muestras. El aislamiento solo en hemocultivo se asocio mayor frecuencia de ingreso a UCI (n = 63; 5,2%). mayor necesidad de ventilacion mecánica (n = 19; 15,5%), mayor mortalidad y estancia hospitalaria (n = 22; 18%; mediana de 12 dias, RIQ= 7-17, respectivamente), pero con menor presencia de cepas productoras de BLEE en comparacion con urocultivos y hemocultivo, urocultivo (n = 20; 17,7% y n = 46; 20,7%, respectivamente). Recibieron tratamiento antimicrobiano en las primeras 24 h 424 pacientes (92,6%), con mas frecuencia piperacilina/ tazobactam (n = 256,60,3%). La proporcion de pacientes tratados empiricamente con carbapenemicos vs no carbapenemicos fue similar en los tres grupos. Discusión: El foco infeccioso. sumado a factores de nesgo para cepas productoras de BLEE, son herramientas utiles para definir pronostico y tratamiento en esta población, debido a la variabilidad clínica y microbiologica en los distintos aislados. Conclusión: Los pacientes con aislamiento de E. coli solo en hemocultivo presentan con mayor frecuencia desenlaces desfavorables en comparación con los pacientes con E. coli en urocultivo, con o sin bacteriemia. Llama la atencion en nuestro medio la menor cantidad de cepas productoras de BLEE en los pacientes con solo hemocultivo positivo.

Background: Escherichia coli is a common cause of a broad spectrum of infections, from non-complicated urinary tract infection, to severe sepsis and septic shock, that are associated to high impact outcomes, such as ICU admission and mortality. Aims: To establish differences in mortality, ICU admission, ESBL positive strains and antibiotic treatment, between patients with E. coli related severe sepsis and septic shock, with or without bacteremia and its variability based on the source of infection. Method: Secondary data analysis of a multicentric prospective cohort study. Results: From 458 patients with E. coli isolation, 123 had E. coli exclusively in blood culture, 222 solely in urine culture, and 113 in both samples. Escherichia coli isolation exclusively in blood culture was associated with higher frequency of ICU admission (n = 63; 51.2%), higher rate of mechanical ventilation requirement (n = 19; 15.5%), higher mortality and longer hospital stay (n = 22; 18%; median of 12 days, IQR= 7 - 17, respectively); but with a lower occurrence of ESBL strains, compared to patients with positive urine culture and positive blood/urine cultures (n = 20; 17.7% and n = 46; 20.7%, respectively). 424 patients (92.6%) received antibiotic treatment in the first 24 hours. The most commonly prescribed was piperacilin/tazobactam (n = 256;60.3%). The proportion of patients empirically treated with carbapenems vs non-carbapenems was similar in the three groups. Discussion: The source of infection, associated with ESBL strains risk factors, are useful tools to define prognosis and treatment in this population, because of their clinical and microbiological variability. Conclusion: Patients with E. coli isolation exclusively in the blood culture had higher frequency of non-favorable outcomes in comparison to patients with E. coli in urine culture with or without bacteremia. Additionally, in our population patients with E. coli solely in blood culture have lower prevalence of ESBL positive strains.

Perfil epidemiológico e análise da efetividade para prevenção de óbitos de pacientes inseridos em protocolo de sepse / Epidemiological profile and effectiveness analysis for the prevention of deaths of patients enrolled in a sepsis protocol

Objetivo: Avaliar casos de sepse e choque séptico verificando perfil epidemiológico, tratamento, adesão às recomendações internacionais e grau de efetividade das intervenções, para analisar sua efetividade na redução da mortalidade. Métodos: Trata-se de estudo observacional transversal com revisão dos atendimentos de sepse e choque séptico entre abril de 2013 e dezembro de 2015. Quanto à efetividade na prevenção de óbitos, o período foi de 2014 a 2015. Resultados: Foram incluídos 412 pacientes (55,3 anos), sendo 58% do sexo masculino. Dentre os pacientes, 80,1% foram inseridos no protocolo no tempo preconizado, 79,9% tiveram coleta de lactato e 91,7% de hemocultura no prazo (p<0,05). Iniciaram antibioticoterapia no prazo 87,4% da amostra. Ocorreram 68 óbitos no pronto-socorro, sendo 80,9% relacionados à sepse. Para a efetividade de prevenção de óbitos, foram incluídos 351 pacientes. O total de prevenção de óbitos foi de 325 pacientes, sendo 52,9% em 2014. O índice de prevenção de óbitos foi crescente (92,6%), indicando alta efetividade. Conclusão: Evidenciou- se alta letalidade nos quadros sépticos. A análise de dados epidemiológicos aponta possíveis melhorias para uniformizar e garantir o melhor atendimento dos pacientes. A adesão e a efetividade do protocolo têm sido crescentes, alcançando índice de prevenção de óbitos muito próximo do ideal. (AU)

Objective: To evaluate cases of sepsis and septic shock checking epidemiological profile, treatment, adherence to the international recommendations, and effectiveness degree of interventions, to analyze the effectiveness in mortality reduction. Methods: This is a cross-sectional observational study with review of sepsis and septic shock between april of 2013 and December of 2015. Regarding effectiveness in preventing deaths, the period was from 2014 to 2015. Results: A total of 412 patients (55.3 years) were included, with 58% male individuals. Of these patients, 80.1% were inserted in the protocol at the recommended time, 79.9% underwent lactate collection, and 91.7% underwent blood culture within the term (p<0.05). Antibiotic therapy was initiated in 87.4% within the term. There were 68 deaths in the emergency room, 80.9% of which were related to sepsis. For the effectiveness of death prevention, 351 patients were included. The total number of prevented deaths was 325 patients, 52.9% in 2014. The death prevention index was increasing (92.6%), indicating high effectiveness. Conclusion: High lethality was observed in septic patients. Epidemiological data analysis points to possible improvement to standardize and guarantee the best care for patients. Protocol compliance and effectiveness have been increasing, reaching an index of deaths prevention very close to the optimal one. (AU)

Construção e validação de cenários simulados em casos clínicos de sepse: identificação e manejo precoce para graduandos e equipe multiprofissional / Construction and validation of simulated scenarios in clinical cases of sepsis: early identification and management for undergraduates and multiprofessional staff

Esta pesquisa descritiva e metodológica tem como objetivo geral a construção e validação de cenários simulados na identificação precoce e manejo da sepse para graduandos e equipe multiprofissional. Após aprovação do Comitê de ética em Pesquisa da Escola de Enfermagem de Ribeirão Preto da USP, o estudo foi desenvolvido em etapas. Na 1ª etapa foi realizado um levantamento bibliográfico para subsidiar a construção de cenário simulado na detecção precoce, triagem e manejo do paciente em sepse. Na 2ª etapa os cenários clínicos foram construídos com o apoio de um grupo multiprofissional em oficinas realizadas em uma Universidade Pública, localizada em uma cidade do interior de São Paulo. O estudo desta etapa foi baseado em casos clínicos reais de pacientes com sepse e choque séptico em unidades de pronto atendimento, enfermarias e unidades intensivas, que foram distribuídos nos principais focos de sepse. Participaram deste grupo enfermeiros e médicos com experiência profissional assistencial. Os cenários foram estruturados através de um roteiro norteador da construção de campos clínicos simulados que tem como base a utilização da opinião de peritos. A confecção dos cenários teve como alicerce os critérios de FABRI (2017), por meio de sete subunidades de significância, além das unidades contextuais do preparo dos mesmos. Na 3ª etapa ocorreu a validação do cenário em aparência e conteúdo. Estes campos foram validados por juízes (experts, peritos, especialistas, convidados para contribuir na veracidade e validade de casos clínicos), utilizando o método de Delphi que consiste na realização de consultas a um grupo de experts a respeito de eventos futuros, com o propósito de se obter um consenso de opiniões através de questionários estruturados que circula entre eles repetidas vezes até que se chegue a um consenso. O método de Delphi consiste nas seguintes etapas: na primeira etapa os experts individualmente recebem o material e respondem de maneira quantitativa, podendo conter justificativas ou informações qualitativas. A cada nova rodada o material é apresentado e os experts devem analisar -se nas colaborações anteriores dadas pelos demais respondentes na fase anterior há possibilidade de realizarem novas contribuições. Esse processo é repetido por várias vezes, até que a divergência das opiniões se reduza e que seja considerada como a previsão do grupo, resultando em um consenso. Na 4ª Etapa ocorre a adequação do cenário a partir das recomendações da validação de conteúdo e de aparência, considerando concordância de 80%, para aferir a concordância dos juízes em cada item. Após codificação, comparação e análise dos dados, a discussão dos resultados da pesquisa foi realizada com fundamentação na revisão da literatura, pertinentes aos objetivos propostos e apresentados na forma de relatório discursivo

This descriptive and methodological research aims to build and validate simulated scenarios in the early identification and management of sepsis for undergraduates and multiprofessional staff. After approval by the Research Ethics Committee of the Ribeirão Preto College of Nursing at USP, the study was developed in stages.In the first stage, a bibliographic survey was conducted to support the construction of a simulated scenario in the early detection, screening and management of the sepsis patient. In the 2nd stage, the clinical scenarios were built with the support of a multiprofessional group in workshops held at a Public University, located in a city in the interior of São Paulo. The study of this stage was based on actual clinical cases of sepsis and septic shock patients in emergency units, wards and intensive care units, which were distributed in the main sepsis foci. Nurses and doctors with professional care experience participated in this group. The scenarios were structured through a guiding roadmap for the construction of simulated clinical fields based on the use of expert opinion. The preparation of the scenarios was based on the criteria of FABRI (2017), through seven subunits of significance, in addition to the contextual units of their preparation. In the 3rd stage, the scenario was validated in appearance and content. These fields were validated by judges (experts, experts, experts, invited to contribute to the veracity and validity of clinical cases), using the Delphi method, which consists of consultations with a group of experts regarding future events, with the purpose of to reach a consensus of opinion through structured questionnaires that circulate among them over and over until a consensus is reached. The Delphi method consists of the following steps: In the first step the experts individually receive the material and respond in a quantitative manner, which may contain justifications or qualitative information. With each new round the material is presented and the experts should analyze in the previous collaborations given by the other respondents in the previous phase there is possibility of making new contributions. This process is repeated several times, until the divergence of opinions is reduced and is considered as the group's prediction, resulting in a consensus. In the 4th Stage, the scenario is adjusted based on the content validation and appearance recommendations, considering a content of 80%, to assess the judges' agreement on each item. After coding, comparing and analyzing the data, the discussion of the research results was based on the literature review, relevant to the proposed objectives and presented as a discursive report

Utilização da vasopressina no tratamento de choque séptico refratário / Use of vasopressin in the treatment of refractory septic shock

RESUMO Objetivo: Avaliar a evolução em curto prazo de pacientes com choque séptico refratário à norepinefrina tratados com vasopressina em uma unidade de terapia intensiva de um hospital universitário. Métodos: Foi realizado estudo retrospectivo não comparado (série de casos). Foram coletados dados clínicos, laboratoriais e antropométricos de pacientes que receberam infusão de vasopressina para tratamento de choque refratário a catecolaminas no período de dezembro de 2014 a junho de 2016. Para a avaliação de gravidade, foram utilizados o APACHE II e o SOFA. O desfecho principal foi mortalidade em 3 e em 30 dias. Resultados: Foram incluídos 80 pacientes, sendo 60% do sexo masculino. Em 86,3% dos casos, verificou-se APACHE II nas faixas mais altas (> 20). A mortalidade em 30 dias foi de 86,2%, sendo que 75% dos pacientes foram a óbito dentro de 72 horas após início do uso da vasopressina. Conclusão: A série avaliada apresentou alta mortalidade nas primeiras 72 horas de tratamento com vasopressina. O uso de vasopressina em pacientes refratários à norepinefrina teve pouco ou nenhum impacto na mortalidade. Não é possível excluir que a alta mortalidade no presente estudo esteja vinculada ao início relativamente tardio (após estabelecida refratariedade à norepinefrina) da vasopressina, devendo essa hipótese ser melhor avaliada por estudo randomizado.

ABSTRACT Objective: To evaluate the short-term evolution of patients with septic shock refractory to norepinephrine treated with vasopressin in an intensive care unit of a university hospital. Methods: An unmatched retrospective study (case series) was performed. Clinical, laboratory, and anthropometric data were collected from patients who received vasopressin infusion for treatment of catecholamine-refractory shock from December 2014 to June 2016. For the assessment of severity, APACHE II and SOFA scores were used. The main outcome was mortality at 3 and 30 days. Results: A total of 80 patients were included, of which 60% were male. In 86.3% of the cases, APACHE II was observed in the highest ranges (> 20). The 30-day mortality was 86.2%, and 75% of the patients died within 72 hours after starting vasopressin. Conclusion: The series evaluated had high mortality in the first 72 hours of treatment with vasopressin. The use of vasopressin in patients who are refractory to norepinephrine had little or no impact on mortality. It was not possible to exclude the possibility that the high mortality in the present study was linked to the relatively late onset (after established refractoriness of norepinephrine) of vasopressin; this hypothesis should be further evaluated in a randomized study.

Espectro dos efeitos cardiovasculares da dobutamina - de voluntários saudáveis a pacientes em choque séptico / The spectrum of cardiovascular effects of dobutamine - from healthy subjects to septic shock patients

RESUMO A dobutamina é o inotrópico mais comumente utilizado em pacientes com choque séptico, com o objetivo de aumentar o débito cardíaco e corrigir a hipoperfusão. Embora alguns ensaios clínicos tenham demonstrado que a dobutamina pode melhorar a hemodinâmica sistêmica e regional, outras pesquisas identificaram que seus efeitos são heterogêneos e imprevisíveis. Nesta revisão, analisamos as propriedades farmacodinâmicas da dobutamina e seus efeitos fisiológicos. Nosso objetivo foi demonstrar que os efeitos da dobutamina podem diferir entre voluntários saudáveis, estudos experimentais e insuficiência cardíaca clínica, em modelos de estudo em animais e em pacientes com choque séptico. Discutimos as evidências que suportam a afirmativa de que a dobutamina utilizada no tratamento do choque séptico frequentemente se comporta como fármaco cronotrópico e vasodilatador, sem evidências de ação inotrópica. Como seus efeitos colaterais são muito comuns e os benefícios terapêuticos não são claros, sugerimos que ela deve ser utilizada com cautela no choque séptico. Antes de uma decisão terapêutica definitiva, a eficácia e a tolerabilidade da dobutamina devem ser avaliadas por um tempo curto com monitoramento estrito de seus efeitos positivos e efeitos colaterais negativos.

ABSTRACT Dobutamine is the inotrope most commonly used in septic shock patients to increase cardiac output and correct hypoperfusion. Although some experimental and clinical studies have shown that dobutamine can improve systemic and regional hemodynamics, other research has found that its effects are heterogenous and unpredictable. In this review, we analyze the pharmacodynamic properties of dobutamine and its physiologic effects. Our goal is to show that the effects of dobutamine might differ between healthy subjects, in experimental and clinical cardiac failure, in animal models and in patients with septic shock. We discuss evidence supporting the claim that dobutamine, in septic shock, frequently behaves as a chronotropic and vasodilatory drug, without evidence of inotropic action. Since the side effects are very common, and the therapeutic benefits are unclear, we suggest that dobutamine should be used cautiously in septic shock. Before a definitive therapeutic decision, the efficacy and tolerance of dobutamine should be assessed during a brief time with close monitoring of its positive and negative side effects.

Microcirculation improvement after short-term infusion of vasopressin in septic shock is dependent on noradrenaline

OBJECTIVES: To assess the impact of vasopressin on the microcirculation and to develop a predictive model to estimate the probability of microcirculatory recruitment in patients with septic shock. METHODS: This prospective interventional study included patients with septic shock receiving noradrenaline for less than 48 hours. We infused vasopressin at 0.04 U/min for one hour. Hemodynamic measurements, including sidestream dark-field imaging, were obtained immediately before vasopressin infusion, 1 hour after vasopressin infusion and 1 hour after vasopressin withdrawal. We defined patients with more than a 10% increase in total vascular density and perfused vascular density as responders. ClinicalTrials.gov: NCT02053675. RESULTS: Eighteen patients were included, and nine (50%) showed improved microcirculation after infusion of vasopressin. The noradrenaline dose was significantly reduced after vasopressin (p=0.001) and was higher both at baseline and during vasopressin infusion in the responders than in the non-responders. The strongest predictor for a favorable microcirculatory response was the dose of noradrenaline at baseline (OR=4.5; 95% CI: 1.2-17.0; p=0.027). For patients using a noradrenaline dose higher than 0.38 mcg/kg/min, the probability that microcirculatory perfusion would be improved with vasopressin was 53% (sensitivity 78%, specificity 77%). CONCLUSIONS: In patients with septic shock for no longer than 48 h, administration of vasopressin is likely to result in an improvement in microcirculation when the baseline noradrenaline dose is higher than 0.38 mcg/kg/min.

Descalonamento, adequação antimicrobiana e positividade de culturas em pacientes sépticos: estudo observacional / De-escalation, adequacy of antibiotic therapy and culture positivity in septic patients: an observational study

RESUMO Objetivo: Avaliar a prevalência de descalonamento antibiótico em pacientes com diagnóstico de sepse grave ou choque séptico em hospital acadêmico, público e terciário, além da adequação antibiótica e da positividade de culturas. Métodos: Foram analisadas prevalência de descalonamento, adequação antibiótica e positividade de culturas entre portadores de sepse grave e choque séptico, entre abril e dezembro de 2013, em uma unidade de terapia intensiva de um hospital universitário terciário. Resultados: Entre os 224 pacientes incluídos, o descalonamento era possível em 29,4% dos casos (66 pacientes), mas foi implementado em 19,6% deles (44 pacientes). Entre os pacientes que receberam descalonamento, metade foi por estreitamento de espectro antimicrobiano. A mortalidade foi de 56,3%, não havendo diferença entre pacientes com ou sem descalonamento (56,8% versus 56,1%; p = 0,999), assim como no tempo de internação. Terapia antimicrobiana empírica foi adequada em 89% dos casos. Houve isolamento de germe em 30% de todas as culturas e em 26,3% das hemoculturas. Conclusão: A taxa de adequação antibiótica empírica foi alta, refletindo ativa política institucional de monitorização do perfil epidemiológico e protocolos institucionais de uso de antimicrobianos. No entanto, o descalonamento antimicrobiano poderia ter sido maior do que o registrado. O descalonamento não impactou mortalidade.

ABSTRACT Objective: To evaluate the prevalence of antibiotic de-escalation in patients diagnosed with severe sepsis or septic shock at a public academic tertiary hospital and to evaluate antibiotic adequacy and culture positivity. Methods: The prevalence of antibiotic de-escalation, the adequacy of antibiotic treatment and the rates of culture positivity were analyzed in patients with severe sepsis and septic shock between April and December 2013 at an intensive care unit in a tertiary university hospital. Results: Among the 224 patients included in the study, de-escalation was appropriate in 66 patients (29.4%) but was implemented in 44 patients (19.6%). Among the patients who underwent de-escalation, half experienced narrowing of the antimicrobial spectrum. The mortality rate was 56.3%, with no differences between the patients with or without de-escalation (56.8% versus 56.1%; p = 0.999) nor in the length of hospital stay. Empirical antibiotic therapy was appropriate in 89% of cases. Microorganisms were isolated from total cultures in 30% of cases and from blood cultures in 26.3% of cases. Conclusion: The adequacy rate of empirical antibiotic therapy was high, reflecting an active institutional policy of monitoring epidemiological profiles and institutional protocols on antimicrobial use. However, antibiotic de-escalation could have been implemented in a greater number of patients. De-escalation did not affect mortality rates.

Megalocytic Interstitial Nephritis Following Acute Pyelonephritis with Escherichia coli Bacteremia: A Case Report

Megalocytic interstitial nephritis is a rare form of kidney disease caused by chronic inflammation. We report a case of megalocytic interstitial nephritis occurring in a 45-yrold woman who presented with oliguric acute kidney injury and acute pyelonephritis accompanied by Escherichia coli bacteremia. Her renal function was not recovered despite adequate duration of susceptible antibiotic treatment, accompanied by negative conversion of bacteremia and bacteriuria. Kidney biopsy revealed an infiltration of numerous histiocytes without Michaelis-Gutmann bodies. The patient's renal function was markedly improved after short-term treatment with high-dose steroid.

La microcirculación en el paciente crítico: parte II: evaluación y microcirculación como objetivo terapéutico / Microcirculation in the critically ill patient: part II: evaluation and microcirculation as a therapeutic target

La sepsis grave y shock séptico involucran una compleja red de alteraciones circulatorias, inflamatorias y metabólicas que llevan finalmente a una disrupción energética celular. Las alteraciones microcirculatorias son frecuentes en el paciente séptico. Su observación directa mediante el uso de vídeomicroscopia como sides-tream dark field (SDF) ha permitido la construcción de falla microcirculatoria como concepto clínico en el paciente crítico. Diversas intervenciones terapéuticas empleadas rutinariamente en el tratamiento del paciente crítico parecen estar asociadas con cambios limitados en la perfusión de la microcirculación, con independencia de la hemodinamia sistémica, debido a la naturaleza heterogénea de estas alteraciones y los mecanismos potencialmente involucrados.

Severe sepsis and septic shock involve circulatory, inflammatory and metabolic disorders eventually resulting in a disruption of cellular energy. Microcirculatory disturbances are common in septic patients. Direct observation using sidestream dark field (SDF) videomicroscopy has enabled the construction of microcirculatory failure as a clinical concept in the critically ill patients. Many therapeutic interventions routinely used in the treatment of critically ill patients seem to be associated with limited changes in microcirculatory perfusion, irrespective of systemic hemodynamics, given the heterogeneous nature of these changes and the mechanisms potentially involved.

Severe sepsis in the emergency department: an observational cohort study from the university hospital of the West Indies / Sepsis severa en la sala de emergencias: un estudio observacional de cohorte en el hospital universitario de West Indies

OBJECTIVE: To describe the incidence, treatment and outcomes of patients with severe sepsis and septic shock in a setting where early goal directed therapy (EGDT) is not routinely performed. METHOD: An observational study of all adult patients admitted from the emergency department (ED) of the University Hospital of the West Indies (UHWI) with a diagnosis of severe sepsis and septic shock from July 5, 2007 to September 1, 2008 was conducted. Baseline parameters, treatment patterns and inhospital outcomes were evaluated. RESULTS: A total of 58 011 patients were seen and 762 (1.3%) had sepsis, 117 (15.4%) of whom were classified as severe sepsis or septic shock. Mean (SD) age was 59.2 (23.3) years and 49% were female. Medical history included hypertension (29%), diabetes mellitus (26%), stroke (8%), heart failure (6%) and HIV (6%). The most common sources of sepsis were pneumonia (67%) and urinary tract infection (46%). Median, interquartile range (IQR) time from triage to antibiotic administration was 126 (88, 220) minutes and antibiotics were given to 65.7% within three hours. Overall, organisms were sensitive to empirical antibiotics in 69%. Median (IQR) lactate was 5.3 (4.5, 7.5) mmol/L. Most patients (95%) were admitted to the ward; 1% went to the intensive care unit (ICU) and 2% died in the ED. Mean (SD) length of hospital stay was 9.5 (10.3) days. Inhospital mortality was 25% and survival correlated inversely with age (r pb = 0.25; p = 0.006). CONCLUSION: Despite a lack of EGDT, sepsis treatment patterns were consistent with "bestpractice" and mortality was lower than international comparators.

OBJETIVO: Describir la incidencia, el tratamiento y los resultados para pacientes con sepsis severa y shock séptico en un entorno donde la terapia dirigida por metas tempranas (TDMT) no se realiza de modo rutinario. MÉTODO: Se realizó un estudio observacional de todos los pacientes adultos con diagnóstico de sepsis severa y shock séptico, ingresados en la Sala de Emergencias del Hospital Universitario de West Indies (HUWI) desde el 5 de julio de 2007 al 1ero. de septiembre de 2008. Se evaluaron los parámetros iniciales de referencia, los patrones de tratamiento, y la evolución intrahospitalaria. RESULTADOS: Un total de 58 011 pacientes fueron vistos, 762 (1.3%) de ellos con sepsis. De estos casos con sepsis, 117 (15.4%) fueron clasificados como sepsis severa o shock séptico. La edad media (SD) fue 59.2 (23.3) años y 49% eran mujeres. Historia clínica incluía hipertensión (29%), diabetes (26%), accidente cerebrovascular (8%), insuficiencia cardíaca (6%) y VIH (6%). Las fuentes más comunes de la sepsis fueron neumonía (67%) e infección del tracto urinario (46%). La mediana del tiempo (IQR) transcurrido desde la selección (triaje) hasta la administración de antibióticos fue 126 (88, 220) minutos, y los antibióticos fueron entregados al 65.7% dentro de las tres horas. En general, los organismos fueron sensibles a los antibióticos empíricos en 69%. La mediana del lactato (IQR) fue 5.3 (4.5, 7.5) mmol/L. La mayoría de los pacientes (95%) fueron ingresados a la sala; 1% se destinó a la unidad de cuidados intensivos (UCI), y el 2% murió en la Sala de Emergencias. El promedio (SD) de la estancia hospitalaria fue de 9.5 (10.3) días. La mortalidad intrahospitalaria fue de 25%, y la supervivencia se halló en correlación inversa con la edad (rpb = .25; p = 0.006). CONCLUSIÓN: A pesar de la falta de TDMT, los patrones del tratamiento de sepsis fueron consistentes con las "mejores prácticas", y la mortalidad fue menor comparada con los datos de comparación a nivel internacional.

A case of staphylococcus toxic shock syndrome presenting with multiple pneumatocoeles in the chest.

Staphylococcus toxic shock syndrome is a severe illness caused by infection with toxin producing Staphylococcus aureus and is associated with a poor outcome. We report a case of Staphylococcus TSS presenting with cough and expectoration along with multiple pneumatoceles visible on the chest radiograph that progressed to acute respiratory distress syndrome with eventual foci in brain. The patient was aggressively managed and recovered completely.