ABSTRACT
OBJECTIVE@#To investigate the functional pathways enriched and differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMCs) of patients with gram-positive and gram-negative sepsis.@*METHODS@#Dataset GSE9960 obtained from NCBI GEO database containing PBMC samples from 16 non-infectious systematic inflammatory response syndrome (SIRS) patients, 17 gram-positive septic patients and 18 gram-negative septic patients were included in the study. Functional pathway annotations were conducted by gene set enrichment analysis and weighted gene co-expression network analysis. DEGs were filtered and master DEGs were then validated in PBMCs of gram-positive septic, gram-negative septic and non-infectious SIRS patients.@*RESULTS@#The enriched gene sets in gram-positive sepsis and gram-negative sepsis were significantly different. The results indicated the opposite co-expression networks in SIRS and gram-negative sepsis, and the entirely different co-expression networks in gram-positive and gram-negative sepsis. Furthermore, we validated that @*CONCLUSIONS@#The results indicate that there are differences in the mechanism and pathogenesis of gram-positive and gram-negative sepsis, which may provide potential markers for sepsis diagnosis and empirical antimicrobial therapy.
Subject(s)
Humans , Biomarkers/analysis , Gene Expression Profiling , Gram-Negative Bacterial Infections/physiopathology , Gram-Positive Bacterial Infections/physiopathology , Leukocytes, Mononuclear/pathology , Sepsis/physiopathologyABSTRACT
Abstract Background: Sepsis is a life-threatening organ dysfunction with non-specific clinical features that can mimic other clinical conditions with hyper metabolic state such as malignant hyperthermia. Perioperatively anesthesia providers come across such scenarios, which are extremely challenging with the need for urgent intervention. Objective: To illustrate the need for early intervention and consultation for added assistance to approach and rule out malignant hyperthermia and other possible causes during such a scenario. Case report: A 63-year-old male underwent an uneventful elective flexible cystoscopy and transrectal ultrasound-guided prostate biopsy. Postoperatively he developed symptoms raising suspicion for malignant hyperthermia. Immediately malignant hyperthermia protocol was initiated that included administration of dantrolene and consultation of malignant hyperthermia association hotline along with other diagnostic and interventional management aimed at patient optimization. While early administration of dantrolene helped in hemodynamically stabilizing the patient, the consultation with other providers and malignant hyperthermia association hotline along with repeated examinations and lab works helped in ruling out malignant hyperthermia as the possible diagnosis. The patient later recovered in the intensive care unit where he was treated for the bacteremia that grew in his blood cultures. Conclusions: Sepsis shares clinical symptoms that mimic malignant hyperthermia. While sepsis rapidly progresses to secondary injuries, malignant hyperthermia is life threatening. Providing ideal care requires good clinical judgment and a high level of suspicion where timely and appropriate care such as early administration of dantrolene and consultation of malignant hyperthermia association hotline for added assistance can influence positive outcomes.
Resumo Justificativa: A sepse é uma disfunção orgânica fatal com características clínicas inespecíficas que podem imitar outras condições clínicas com quadro hipermetabólico, como a hipertermia maligna. Os cenários são extremamente desafiadores para a anestesia perioperatória e requerem intervenção urgente. Objetivo: Ilustrar a necessidade de intervenção e consulta precoces para uma assistência adicional na abordagem e exclusão de hipertermia maligna e outras possíveis causas durante tal cenário. Relato de caso: Paciente do sexo masculino, 63 anos, submetido à cistoscopia eletiva com cistoscópio flexível e biópsia transretal da próstata guiada por ultrassom sem intercorrências. No pós-operatório, o paciente desenvolveu sintomas que levantaram a suspeita de hipertermia maligna. O protocolo de hipertermia maligna foi imediatamente iniciado, inclusive a administração de dantrolene e uma consulta pela linha direta da associação de hipertermia maligna, juntamente com outros diagnósticos e manejos intervencionistas com vistas ao aprimoramento do paciente. Enquanto a administração precoce de dantrolene ajudou na estabilização hemodinâmica do paciente, a consulta com outros anestesistas e com a Associação de Hipertermia Maligna, juntamente com repetidos exames físicos e laboratoriais, ajudou a excluir a hipertermia maligna como o possível diagnóstico. O paciente recuperou-se mais tarde na unidade de terapia intensiva, onde recebeu tratamento para a bacteremia detectada em suas hemoculturas. Conclusões: A sepse compartilha sintomas clínicos que mimetizam a hipertermia maligna. Enquanto a sepse progride rapidamente para lesões secundárias, a hipertermia maligna é uma ameaça à vida. Proporcionar o tratamento ideal requer um bom julgamento clínico e um alto nível de suspeita quanto aos cuidados oportunos e apropriados, como a administração precoce de dantrolene e a consulta pela linha direta da Associação de Hipertermia Maligna para assistência adicional, que podem resultar em desfechos positivos.
Subject(s)
Humans , Male , Postoperative Complications/diagnosis , Sepsis/diagnosis , Malignant Hyperthermia/diagnosis , Postoperative Complications/physiopathology , Postoperative Complications/therapy , Time Factors , Acute Disease , Sepsis/physiopathology , Sepsis/therapy , Cystoscopy/methods , Dantrolene/administration & dosage , Image-Guided Biopsy/methods , Malignant Hyperthermia/physiopathology , Middle AgedABSTRACT
Abstract Although increasing evidence supports the monitoring of peripheral perfusion in septic patients, no systematic review has been undertaken to explore the strength of association between poor perfusion assessed in microcirculation of peripheral tissues and mortality. A search of the most important databases was carried out to find articles published until February 2018 that met the criteria of this study using different keywords: sepsis, mortality, prognosis, microcirculation and peripheral perfusion. The inclusion criteria were studies that assessed association between peripheral perfusion/microcirculation and mortality in sepsis. The exclusion criteria adopted were: review articles, animal/pre-clinical studies, meta-analyzes, abstracts, annals of congress, editorials, letters, case-reports, duplicate and articles that did not present abstracts and/or had no text. In the 26 articles were chosen in which 2465 patients with sepsis were evaluated using at least one recognized method for monitoring peripheral perfusion. The review demonstrated a heterogeneous critically ill group with a mortality-rate between 3% and 71% (median = 37% [28%-43%]). The most commonly used methods for measurement were Near-Infrared Spectroscopy (NIRS) (7 articles) and Sidestream Dark-Field (SDF) imaging (5 articles). The vascular bed most studied was the sublingual/buccal microcirculation (8 articles), followed by fingertip (4 articles). The majority of the studies (23 articles) demonstrated a clear relationship between poor peripheral perfusion and mortality. In conclusion, the diagnosis of hypoperfusion/microcirculatory abnormalities in peripheral non-vital organs was associated with increased mortality. However, additional studies must be undertaken to verify if this association can be considered a marker of the gravity or a trigger factor for organ failure in sepsis.
Resumo Embora evidências crescentes apoiem a monitoração da perfusão periférica em pacientes sépticos, nenhuma revisão sistemática foi feita para explorar a força da associação entre a má perfusão avaliada na microcirculação dos tecidos periféricos e a mortalidade. Uma busca nas bases de dados mais importantes foi feita para encontrar artigos publicados até fevereiro de 2018 que correspondessem aos critérios deste estudo, com diferentes palavras-chave: sepse, mortalidade, prognóstico, microcirculação e perfusão periférica. Os critérios de inclusão foram estudos que avaliaram a associação entre perfusão/microcirculação periférica e mortalidade em sepse. Os critérios de exclusão adotados foram os seguintes: artigos de revisão, estudos com animais/pré-clínicos, metanálises, resumos, anais de congressos, editoriais, cartas, relatos de casos, artigos duplicados e artigos que não continham resumos e/ou texto. Foram selecionados 26 artigos nos quais 2465 pacientes com sepse foram avaliados com pelo menos um método reconhecido para monitorar a perfusão periférica. A revisão demonstrou um grupo heterogêneo de pacientes gravemente enfermos com uma taxa de mortalidade entre 3% e 71% (mediana = 37% [28%-43%]). Os métodos de avaliação mais comumente usados foram a espectroscopia na região do infravermelho próximo (Near-Infrared Spectroscopy - NIRS) (7 artigos) e a análise de imagens em campo escuro (Sidestream Dark-Field - SDF) (5 artigos). O leito vascular mais avaliado foi a microcirculação sublingual/bucal (8 artigos), seguida pela ponta do dedo (4 artigos). A maioria dos estudos (23 artigos) demonstrou uma clara relação entre má perfusão periférica e mortalidade. Em conclusão, o diagnóstico de hipoperfusão/anormalidades microcirculatórias em órgãos não vitais periféricos foi associado ao aumento da mortalidade. No entanto, estudos adicionais devem ser feitos para verificar se essa associação pode ser considerada um marcador da gravidade ou um fator desencadeante da falência de órgãos na sepse.
Subject(s)
Humans , Critical Illness/mortality , Sepsis/physiopathology , Microcirculation/physiology , Prognosis , Sepsis/mortality , Perfusion IndexABSTRACT
Em 1992, a Organização Mundial da Saúde (OMS) propôs a seguinte definição: Sepse puerperal é uma infecção do trato genital ocorrendo, em qualquer momento, entre a ruptura das membranas ou o trabalho e o 42º dia após o parto, no qual estão presentes dois ou mais dos seguintes eventos: ⢠Dor pélvica; ⢠Febre (temperatura oral de 38,5 °C ou superior em qualquer ocasião); ⢠Corrimento vaginal anormal, por exemplo, presença de pus; ⢠Cheiro anormal/mau cheiro do corrimento vaginal; ⢠Atraso na redução do tamanho do útero (<2 cm/dia durante os primeiros oito dias). 1. O conceito de infecção puerperal deve ser complementado com o de morbidade febril puerperal, pela dificuldade de caracterizar a infecção que ocorre logo após o parto. 2. Outras definições que se fazem necessárias são: ⢠Bacteremia: presença de bactérias na corrente sanguínea; ⢠Sepse: síndrome clínica caracterizada pela resposta da hospedeira a um processo infeccioso, acompanhada de uma resposta inflamatória sistêmica; ⢠Sepse grave: sepse associada à disfunção de um ou mais órgãos (sistema nervoso central, renal, pulmonar, hepática, cardíaca, coagulopatia, acidose metabólica); ⢠Choque séptico: sepse com hipotensão refratária à ressuscitação volêmica. 3. A OMS incluiu o termo "infecção puerperal", pois hoje estão morrendo mulheres com infecções de outros locais do corpo.
Subject(s)
Humans , Female , Pregnancy , Pregnancy Complications/epidemiology , Puerperal Infection/prevention & control , Pneumonia , Shock, Septic , Skin/physiopathology , Urologic Diseases , Risk Factors , Bacteremia , Pelvic Pain , Soft Tissue Infections/physiopathology , Sepsis/physiopathology , Mastitis/physiopathologyABSTRACT
RESUMO Objetivo: Comparar as características clínicas e os desfechos de pacientes com sepse adquirida na comunidade ou no hospital. Métodos: Trata-se de estudo retrospectivo de coorte, que incluiu todos os pacientes com diagnóstico de sepse detectada entre janeiro de 2010 e dezembro de 2015 em um hospital privado localizado na Região Sul do Brasil. Os desfechos (mortalidade, tempo de permanência na unidade de terapia intensiva e no hospital) foram avaliados por meio da análise dos registros eletrônicos. Resultados: Foram hospitalizados, no total, 543 pacientes com diagnóstico de sepse, com frequência de 90,5 (85 a 105) casos por ano. Destes, 319 (58%) casos foram classificados como sepse adquirida no hospital. Este grupo apresentava doença mais grave e tinha um maior número de disfunções de órgãos, assim como teve um tempo maior de permanência no hospital [8 (8 - 10) versus 23 (20 - 27) dias; p < 0,001] e na unidade de terapia intensiva [5 (4 - 7) versus 8,5 (7 - 10); p < 0,001] do aqueles que apresentavam sepse adquirida na comunidade. Após ajustar quanto à idade, escore APACHE II e disfunção hemodinâmica e respiratória, a sepse adquirida no hospital persistiu associada com maior mortalidade (OR 1,96; IC95% 1,15 - 3,32, p = 0,013). Conclusão: Nossos resultados contribuem para a definição do perfil epidemiológico da sepse na amostra estudada, na qual a sepse adquirida no hospital foi mais grave e associada com mortalidade mais alta.
ABSTRACT Objective: To compare the clinical characteristics and outcomes of patients with community-acquired and hospital-acquired sepsis. Methods: This is a retrospective cohort study that included all patients with a diagnosis of sepsis detected between January 2010 and December 2015 at a private hospital in southern Brazil. Outcomes (mortality, intensive care unit and hospital lengths of stay) were measured by analyzing electronic records. Results: There were 543 hospitalized patients with a diagnosis of sepsis, with a frequency of 90.5 (85 to 105) cases/year. Of these, 319 (58%) cases were classified as hospital-acquired sepsis. This group exhibited more severe disease and had a larger number of organ dysfunctions, with higher hospital [8 (8 - 10) versus 23 (20 - 27) days; p < 0.001] and intensive care unit [5 (4 - 7) versus 8.5 (7 - 10); p < 0.001] lengths of stay and higher in-hospital mortality (30.7% versus 15.6%; p < 0.001) than those with community-acquired sepsis. After adjusting for age, APACHE II scores, and hemodynamic and respiratory dysfunction, hospital-acquired sepsis remained associated with increased mortality (OR 1.96; 95%CI 1.15 - 3.32, p = 0.013). Conclusion: The present results contribute to the definition of the epidemiological profile of sepsis in the sample studied, in which hospital-acquired sepsis was more severe and was associated with higher mortality.
Subject(s)
Humans , Male , Female , Aged , Cross Infection/physiopathology , Hospital Mortality , Sepsis/physiopathology , Intensive Care Units/statistics & numerical data , Brazil , Cross Infection/mortality , Retrospective Studies , Cohort Studies , Hospitals, Private , Sepsis/mortality , APACHE , Length of Stay , Middle AgedABSTRACT
ABSTRACT Objective: To determine the sensitivity and specificity of peripheral and respiratory muscle strength tests in diagnosing critical illness polyneuromyopathy (CIPNM), compared with an electrophysiological examination. Methods: Fifty septic patients who required mechanical ventilation for at least five days, and without a previous history of muscle weakness, were included. Peripheral muscle strength was assessed using the Medical Research Council (MRC) score, handgrip strength by dynamometry, and respiratory muscle strength with maximum respiratory pressures. Diagnosis of CIPNM was either confirmed or rejected by an electrophysiological examination. Receiver operating characteristic curve analysis was performed to determine the cut-off values with the best sensitivity (SN) and specificity (SP) of the studied variables in the presence or absence of CIPNM. Results: Patients with CIPNM were older, more critical (APACHE IV/SAPS 3), had a longer hospitalization, required mechanical ventilation for longer, and had a higher rate of intensive care unit readmission. Cutoff values identified CIPNM patients using MRC scores, dynamometry according to sex, maximal expiratory and inspiratory pressures, as well as being confirmed by the electrophysiological examination, with good sensitivity and specificity: < 40 (SN: 0.893; SP: 0.955); < 7 kg (SN: 1; SP: 0.909) for men, < 4 kg (SN: 0.882; SP: 1) for women; < 34 cmH2O (SN: 0.808; SP: 0.909) and > −40 cmH2O (SN: 0.846; SP: 0.909), respectively. Conclusion: The MRC score, dynamometry or maximum respiratory pressures can be used to identify patients with CIPNM at the intensive care bedside assessment. The healthcare professional can choose any of the methods studied to evaluate the patient, based on his experience and the resource available.
RESUMO Objetivo: Determinar a sensibilidade (SN) e especificidade (SP) dos testes de força muscular periférica e respiratória no diagnóstico da Polineuromiopatia do Doente Crítico (PNDC) em comparação com o estudo eletrofisiológico. Métodos: Foram incluídos 50 pacientes sépticos, em ventilação mecânica (VM) durante pelo menos cinco dias e sem história prévia de fraqueza muscular. A força muscular foi avaliada utilizando o escore Medical Research Council (MRC), a força de preensão palmar e as pressões respiratórias máximas. O diagnóstico de PNDC foi confirmado ou excluído pelo estudo eletrofisiológico. A análise da curva ROC foi realizada para determinar os valores de corte com a melhor SN e SP. Resultados: Os pacientes com PNDC eram mais velhos, mais graves, tiveram hospitalização mais longa, necessitaram de VM por mais tempo e apresentaram maior taxa de readmissão na Unidade de Terapia Intensiva. Os valores de corte identificaram os pacientes com PNDC usando o MRC, a dinamometria de acordo com o sexo, as pressões expiratórias e inspiratórias máximas, também confirmado pelo estudo eletrofisiológico, com boa sensibilidade e especificidade: < 40 (SN: 0.893; SP: 0.955), < 7 kg (SN: 1; SP: 0,909) para homens, < 4 kg (SN: 0,882; SP: 1) para mulheres, <34 cmH2O (SN: 0,808; SP: 0,909) e > −40 cmH2O (SN: 0,846; SP: 0,909), respectivamente. Conclusão: Tanto o MRC, a dinamometria quanto as pressões respiratórias máximas podem ser usadas para identificar pacientes com PNDC na avaliação à beira do leito, podendo o profissional de saúde escolher qualquer um dos métodos baseado em sua experiência e no recurso disponível.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Polyneuropathies/diagnosis , Polyneuropathies/physiopathology , Critical Illness , Sepsis/physiopathology , Reference Values , Respiratory Muscles/physiopathology , Prospective Studies , Reproducibility of Results , Sensitivity and Specificity , Statistics, Nonparametric , APACHE , Electromyography/methods , Muscle Strength/physiology , Muscle Strength Dynamometer , Point-of-Care Testing , Maximal Respiratory Pressures , Intensive Care UnitsABSTRACT
INTRODUCTION: Sepsis corresponds to a dysregulated host response to infection that occurs with some degree of organic dysfunction. OBJECTIVE: To conduct a narrative review of the literature about the anesthetic management of the septic patient. METHODS: A structured search of the literature was carried out in the following databases: EBSCO, Pubmed, Embase, SciELO and Cochrane Library, with the terms: Anesthesia AND sepsis; anesthesia AND sepsis AND management; sepsis AND treatment; both English and Spanish. RESULTS: About 45 articles were found with important information for the development of the present review. CONCLUSIONS: The type of anesthesia, as well as the inducers and medications involved in the maintenance of general anesthesia should be chosen according to the particular condition of each patient and the experience of the anesthesiologist. Resuscitation goals, as well as protective ventilation maneuvers, should be continued or implemented during the surgery.
ANTECEDENTES: La sepsis corresponde a una respuesta disregulada del huésped a la infección que cursa con algún grado de disfunción orgánica. Frecuentemente, el paciente séptico requiere anestesia general para control del foco. OBJETIVO: Realizar una revisión narrativa de la literatura acerca del manejo anestésico del paciente séptico. MÉTODOS: Se realizó una búsqueda estructurada de la literatura en las siguientes las bases de datos: EBSCO, Pubmed, Embase, SciELO y Cochrane Library, con los términos: Anesthesia AND sepsis; anesthesia AND sepsis AND management; sepsis AND treatment; en inglés y con sus equivalentes DeCS en español. RESULTADOS: Se encontraron alrededor de 45 artículos con información importante para el desarrollo de la presente revisión. CONCLUSIONES: El tipo de anestesia, así como los inductores y medicamentos involucrados en el mantenimiento de la anestesia general deben escogerse de acuerdo a la condición particular de cada paciente y a la experiencia del anestesiólogo. Las metas de reanimación, así como las maniobras de ventilación protectora deben continuarse o implementarse en el transoperatorio
Subject(s)
Humans , Sepsis/therapy , Anesthesia, General/methods , Oxygen Inhalation Therapy , Shock, Septic/therapy , Vasoconstrictor Agents/administration & dosage , Blood Transfusion , Cardiotonic Agents/administration & dosage , Monitoring, Intraoperative , Cardiopulmonary Resuscitation , Adrenal Cortex Hormones/administration & dosage , Sepsis/physiopathology , Perioperative CareABSTRACT
Sepsis remains a major cause of morbidity and mortality worldwide, with increased burden in low- and middle-resource settings. The role of the inflammatory response in the pathogenesis of the syndrome has supported the modern concept of sepsis. Nevertheless, a definition of sepsis and the criteria for its recognition is a continuous process, which reflects the growing knowledge of its mechanisms and the success and failure of diagnostic and therapeutic interventions. Here we review the evolving concepts of sepsis, from the "systemic inflammatory response syndrome triggered by infection" (Sepsis-1) to "a severe, potentially fatal, organic dysfunction caused by an inadequate or dysregulated host response to infection" (Sepsis-3). We focused in the pathophysiology behind the concept and the criteria for recognition and diagnosis of sepsis. A major challenge in evaluating the host response in sepsis is to characterize what is protective and what is harmful, and we discuss that, at least in part, the apparent dysregulated host response may be an effort to adapt to a hostile environment. The new criteria for recognition and diagnosis of sepsis were derived from robust databases, restricted, however, to developed countries. Since then, the criteria have been supported in different clinical settings and in different economic and epidemiological contexts, but still raise discussion regarding their use for the identification versus the prognostication of the septic patient. Clinicians should not be restricted to definition criteria when evaluating patients with infection and should wisely use the broad array of information obtained by rigorous clinical observation.
Subject(s)
Humans , Sepsis/physiopathology , Sepsis/immunology , Sepsis/diagnosis , Sepsis/metabolism , Lactic Acid/blood , Organ Dysfunction Scores , Medical IllustrationABSTRACT
A sepse é manifestada por um conjunto de reações fisiológicas do organismo que ocorrem de maneira desregulada em resposta à uma infecção. A mortalidade por essa síndrome é de aproximadamente 60%, a depender da gravidade das manifestações clínicas. Nas Unidades de Terapia Intensiva (UTI), pelo menos 30% dos leitos são ocupados por pacientes com sepse e estima-se que após esse agravo, há um aumento da morbidade e do risco de óbito. O diabetes mellitus do tipo 2 (DM2) é uma comorbidade presente em 20% dos pacientes com sepse. O diabetes acomete 415 milhões de pessoas no mundo, com expectativas de aumento da prevalência nos próximos anos. Acredita-se que diabéticos são mais susceptíveis às infecções e apresentam diferenças nas defesas do organismo como a redução da fagocitose dos leucócitos, elevação dos níveis séricos de fator de necrose tumoral alfa, que associados podem acarretar a inflamação mais persistente, especialmente em face à sepse. O objetivo deste estudo foi analisar a influência da resposta inflamatória em cultura de sangue total e a evolução clínica de diabéticos e não diabéticos com sepse. A resposta inflamatória foi analisada por delineamento experimental, em culturas de sangue total ex vivo. Foram exploradas variáveis relativas ao perfil antropométrico, glicêmico, lipídico e inflamatório basal. Após as culturas de sangue serem estimuladas com lipopolissacarídeo, foram dosadas as concentrações de nitrato, atividade da enzima catalase e IL-10. A evolução clínica foi estudada por desenvolvimento não experimental do tipo coorte, em que foram avaliadas as características sociodemográficas, clínicas, laboratoriais e relativas à internação em uma UTI. Ambos os delineamentos incluíram grupos de pacientes: não diabéticos e diabéticos. No delineamento experimental 25 pacientes compuseram cada grupo. Observou-se diferenças estatísticas significantes em relação a idade, a presença e o número de comorbidades e os níveis de LDL, glicemia, Hb1Ac, concentrações de nitrato e nitrito basal. Nas culturas não se obsersou diferenças entre os grupos. No estudo de coorte, cada grupo foi composto por 102 pacientes. Os números de óbitos e de comorbidades, a gravidade/prognóstico na admissão e os índices glicêmicos foram mais elevados em pacientes diabéticos quando comparados com pacientes não diabéticos com sepse. O perfil inflamatório e metabólico basal difere em pacientes diabéticos e não diabéticos, mas a hipótese de que o DM2 influencia na resposta inflamatória não foi comprovada, entretanto, a evolução clínica foi diferente entre os grupos, com piores resultados para aqueles com DM2
Sepsis is manifested by a set of physiological reactions of the body that occur in an unregulated manner in response to an infection. Mortality from this syndrome is approximately 60%, depending on the severity of clinical manifestations. In Intensive Care Units (ICU), at least 30% of beds are occupied by patients with sepsis and it is estimated that after this worsening, there is an increase in morbidity and risk of death. Diabetes mellitus type 2 (T2DM) is a comorbidity present in 20% of patients with sepsis. Diabetes affects 415 million people worldwide, with expectations of increased prevalence in the coming years. It is believed that diabetics are more susceptible to infections and present differences in the body's defenses, such as reduction of leukocyte phagocytosis, increase in serum levels of alpha tumor necrosis factor, which may lead to more persistent inflammation, especially in the face of sepsis. The objective of this study was to analyze the influence of the inflammatory response in whole blood culture and the clinical evolution of diabetics and non-diabetics patients with sepsis. The inflammatory response was analyzed by experimental design, in ex vivo cultures of whole blood. Variables related to anthropometric, glycemic, lipidic and basal inflammatory profile were explored. After blood cultures were stimulated with lipopolysaccharide, nitrate concentrations, catalase enzyme activity and IL-10 were measured. The clinical evolution was studied by non-experimental cohort development, in which sociodemographic, clinical, laboratory and ICU-related characteristics were evaluated. Both designs included groups of patients: non-diabetic and diabetic. In the experimental design, 25 patients composed each group. Significant statistical differences were observed regarding age, presence and number of comorbidities and levels of LDL, glycemia, Hb1Ac, nitrate and basal nitrite concentrations. No differences between the groups were observed in the cultures. In the cohort study, each group was composed of 102 patients. The number of deaths and comorbidities, the severity/prognosis at admission and the glycemic indexes were higher in diabetic patients when compared to non-diabetic patients with sepsis. The basal inflammatory and metabolic profile differs in diabetic and non diabetic patients, but the hypothesis that DM2 influences the inflammatory response was not proven, however, clinical evolution was different between the groups, with worse results for those with T2DM
Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Blood Glucose , Mortality , Sepsis/physiopathology , Diabetes Mellitus , Inflammation/diagnosisABSTRACT
RESUMO Objetivo: Avaliar a acurácia dos níveis de interleucina 3 para predizer prognóstico em pacientes sépticos. Métodos: Conduzimos uma coorte prospectiva que incluiu pacientes adultos internados em unidade de terapia intensiva, que apresentassem sepse ou choque séptico iniciados há até 48 horas. Mediram-se os níveis séricos de interleucina 3 quando da inclusão (dia 1) e nos dias 3 e 7. O desfecho primário analisado foi a mortalidade hospitalar por qualquer causa. Resultados: Foram incluídos 120 pacientes. Os níveis séricos de interleucina 3 dosados à inclusão foram significativamente mais elevados em pacientes que faleceram em comparação aos que sobreviveram à internação hospitalar (91,2pg/mL versus 36pg/mL; p = 0,024). Em modelo de sobrevivência de Cox com inclusão de idade e valores sequenciais de SOFA, os níveis de interleucina 3 mensurados na inclusão mantiveram-se independentemente associados à mortalidade hospitalar (HR 1,032; IC95% 1,010 - 1,055; p = 0,005). Em curva Característica de Operação do Receptor construída para investigação adicional da acurácia da interleucina 3 na predição do prognóstico, encontrou-se área sob a curva de 0,62 (IC95% 0,51 - 0,73; p = 0,024) para mortalidade hospitalar. Valores iniciais de interleucina 3 acima de 127,5pg/mL mostraram-se significativamente associados à mortalidade hospitalar (p = 0,019; OR = 2,97; IC95% 1,27 - 6,97; p = 0,019), entretanto com baixo desempenho (especificidade de 82%, sensibilidade de 39%, valor preditivo positivo de 53%, valor preditivo negativo de 72%, razão de verossimilhança negativa de 0,73 e razão de verossimilhança positiva de 2,16). Conclusão: Níveis elevados de interleucina 3 mostraram-se independentemente associados à mortalidade hospitalar em pacientes sépticos, entretanto com baixo desempenho clínico.
ABSTRACT Objective: To evaluate the accuracy of IL-3 to predict the outcome of septic patients. Methods: Prospective cohort study with adult patients in an intensive care unit with sepsis or septic shock diagnosed within the previous 48 hours. Circulating IL-3 levels were measured upon inclusion (day 1) and on days 3 and 7. The primary outcome was hospital mortality. Results: One hundred and twenty patients were included. Serum levels of IL-3 on day 1 were significantly higher among patients who died than among patients who survived the hospital stay (91.2pg/mL versus 36pg/mL, p = 0.024). In a Cox survival model considering the IL-3 levels at inclusion, age and sequential SOFA, IL-3 values remained independently associated with mortality (HR 1.032; 95%CI 1.010 - 1.055; p = 0.005). An receiver operating characteristic curve was built to further investigate the accuracy of IL-3, with an area under the curve of 0.62 (95%CI 0.51 - 0.73; p = 0.024) for hospital mortality. A cutoff initial IL-3 value above 127.5pg/mL was associated with hospital mortality (OR 2.97; 95%CI: 1.27 - 6.97; p = 0.0019) but with a low performance (82% for specificity, 39% for sensibility, 53% for the positive predictive value, 72% for the negative predictive value, 0.73 for the negative likelihood and 2.16 for the positive likelihood ratio). Conclusion: Higher levels of IL-3 are shown to be independently associated with hospital mortality in septic patients but with poor clinical performance.
Subject(s)
Humans , Male , Female , Adult , Aged , Shock, Septic/physiopathology , Interleukin-3/blood , Hospital Mortality , Sepsis/physiopathology , Prognosis , Shock, Septic/mortality , Shock, Septic/blood , Predictive Value of Tests , Prospective Studies , Reproducibility of Results , Cohort Studies , Sensitivity and Specificity , Sepsis/mortality , Sepsis/blood , Intensive Care Units , Middle AgedABSTRACT
Resumen La fiebre es un signo frecuente en el niño críticamente enfermo durante su estadía en la unidad de cuidados intensivos, y debe ser entendida como una respuesta biológica evolutiva, de carácter adaptativo normal del huésped al estrés fisiológico. Es el resultado de una compleja respuesta a estímulos pirogénicos, resultando en la generación de citocinas y prostaglandinas. Los mecanismos moleculares implicados en el inicio de la fiebre aún no están totalmente precisados, originando dificultades en el conocimiento de los procesos fisiopatológicos exactos involucrados y, por ende, necesarios para elaborar una adecuada y específica estrategia terapéutica. Estudios experimentales concluyen que la fiebre y la inflamación son benéficas para el huésped; no obstante, la terapia antipirética es comúnmente empleada y estudios en humanos sobre la presencia de fiebre y su tratamiento para el pronóstico del paciente crítico con sepsis no son concluyentes. Para el médico intensivista es esencial disponer de información actualizada referente a la fisiología de la termorregulación humana, el efecto de la temperatura en rango febril sobre múltiples procesos biológicos involucrados en la defensa del huésped y las intervenciones termorreguladoras en el paciente con sepsis.
Abstract Fever is a very common sign to observe in critically ill children during their intensive care unit stay. This should be understood as an evolutionary biological response, of normal adaptive character, from the host to the physiological stress. It is the result of a complex response to pyrogenic stimuli, resulting in the generation of cytokines and prostaglandins. The molecular mechanisms involved in the onset of fever are not yet fully specified, thus creating difficulties in the knowledge of the exact pathophysiological processes involved and, therefore, necessary to elaborate an adequate and specific therapeutic strategy. Experimental studies conclude that fever and inflammation are beneficial to the host. However, antipyretic therapy is commonly employed and human studies on the presence of fever and its treatment for the prognosis of critically ill septic patients are inconclusive. Up-to-date information on the physiology of human thermoregulation, the effect of temperature on febrile range over multiple biological processes involved in host defense, and thermoregulatory interventions in the septic patient are essential to know by the critical care physician.
Subject(s)
Child , Humans , Sepsis/drug therapy , Antipyretics/therapeutic use , Fever/drug therapy , Critical Illness , Sepsis/physiopathology , Critical Care , Fever/etiology , Intensive Care UnitsABSTRACT
Resumen Introducción: La sepsis en pediatría es la principal causa de muerte hospitalaria. Se han intentado crear herramientas que faciliten su identificación, como el índice de choque (IC), definido como el cociente entre frecuencia cardíaca y tensión arterial sistólica. El objetivo de este trabajo fue identificar el mejor momento del IC para predecir la mortalidad en pacientes pediátricos con sepsis grave y choque séptico. Métodos: Cohorte retrospectiva con 165 pacientes pediátricos que desarrollaron sepsis grave y choque séptico en la Unidad de Terapia Intensiva Pediatrica. Se calculó el IC al diagnóstico (IC0), a las dos, cuatro y seis horas posteriores al mismo (IC2, IC4 e IC6). Se crearon dos grupos según el desenlace (sobrevivientes/muertos). La comparación estadística se realizó con prueba U-Mann Whitney y χ2. Se compararon los factores de riesgo entre los sobrevivientes y muertos, calculando la razón de momios (RM). Resultados: Se comparó el valor del IC entre grupos; en el grupo de choque séptico, el IC se encontró más elevado en IC4 e IC6 (p = 0.010 y p = 0.005). Se encontró que, en los pacientes muertos, el IC incrementó progresivamente su valor en IC4 e IC6 (p < 0.05). Los valores de IC4 e IC6 elevados incrementaron el riesgo de muerte en los pacientes (IC4, RM: 442.1; IC 95% [intervalo de confianza al 95%]: 54.2-3,601.7; p < 0.001; e IC6, RM: 81,951.3; IC 95%: 427.1-15,700,000; p < 0.001). Conclusiones: La elevación del valor del IC se asocia con mayor mortalidad de la sepsis. El valor de IC6 es el más útil para predecir mortalidad.
Abstract Background: Pediatric sepsis is considered the main cause of hospital death around the world. Many groups have tried to create tools that facilitate its early identification, as the shock index (SI) defined as the ratio between cardiac frequency and systolic blood pressure. The objective of this study was to determine the utility of SI to predict mortality in pediatric patients with severe sepsis and septic shock. Methods: Retrospective cohort with 165 pediatric patients with severe sepsis or septic shock in the Pediatric Intensive Care Unit. SI was calculated at diagnosis, 2, 4 and 6 hours after (SI2, SI4 and SI6). We divided the population in two groups depending their outcome: survivors and non-survivors. The statistical analysis was performed with U Mann-Whitney and chi squared tests. The risk factors were compared between the survivors and the dead, and we calculated the odds ratio (OR). Results: The median value of SI was compared between groups; in the group of septic shock, SI showed a tendency to remain high in SI4 and SI6 (p = 0.010 and p = 0.005, respectively). Among the survivors and the non-survivors, we found that in the latter, SI was progressively increased in SI4 and SI6 (p < 0.05). High values of SI4 and SI6 increased the risk of death in patients (SI4: OR: 442.1; CI 95% [confidence interval 95%]: 54.2-3,601.7; p < 0.001 and SI6: OR: 81,951.3; CI 95%: 427.1-15,700,000]; p < 0.001). Conclusions: High values of SI are associated with increased mortality. The IS6 value is the most useful to predict mortality.
Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Shock, Septic/mortality , Severity of Illness Index , Blood Pressure/physiology , Sepsis/mortality , Shock, Septic/physiopathology , Time Factors , Retrospective Studies , Risk Factors , Cohort Studies , Survivors , Sepsis/physiopathologyABSTRACT
Stress hyperglycemia is frequently diagnosed in septic patients in critical care units (ICU) and it is associated with greater illness severity and higher morbimortality rates. In response to an acute injury, high levels of counterregulatory hormones such as glucocorticoids and catecholamines are released causing increased hepatic gluconeogenesis and insulin resistance. Furthermore, during sepsis, proinflammatory cytokines also participate in the pathogenesis of this phenomenon. Septic patients represent a subtype of the critical ill patients in the ICU: this metabolic disarrangement management strategies and insulin therapy recommendations had been inconsistent. In this article, we describe the pathophysiological mechanisms of stress hyperglycemia in critical patients including the action of hormones, inflammatory cytokines and tissue resistance to insulin. In addition, we analyzed the main published studies for the treatment of acute hyperglycemia in critical patients.
Subject(s)
Humans , Sepsis/complications , Hyperglycemia/etiology , Stress, Physiological , Sepsis/physiopathology , Sepsis/metabolism , Glucose Transport Proteins, Facilitative/metabolism , Glucose/metabolism , Hyperglycemia/physiopathology , Hyperglycemia/metabolism , Hyperglycemia/therapy , Intensive Care UnitsABSTRACT
Abstract Objective: The aim of this study was to verify the association of echocardiogram, ferritin, C-reactive protein, and leukocyte count with unfavorable outcomes in pediatric sepsis. Methods: A prospective cohort study was carried out from March to December 2014, with pediatric critical care patients aged between 28 days and 18 years. Inclusion criteria were diagnosis of sepsis, need for mechanical ventilation for more than 48 h, and vasoactive drugs. Serum levels of C-reactive protein, ferritin, and leukocyte count were collected on the first day (D0), 24 h (D1), and 72 h (D3) after recruitment. Patients underwent transthoracic echocardiography to determine the ejection fraction of the left ventricle on D1 and D3. The outcomes measured were length of hospital stay and in the pediatric intensive care unit, mechanical ventilation duration, free hours of VM, duration of use of inotropic agents, maximum inotropic score, and mortality. Results: Twenty patients completed the study. Patients with elevated ferritin levels on D0 had also fewer ventilator-free hours (p = 0.046) and higher maximum inotropic score (p = 0.009). Patients with cardiac dysfunction by echocardiogram on D1 had longer hospital stay (p = 0.047), pediatric intensive care unit stay (p = 0.020), duration of mechanical ventilation (p = 0.011), maximum inotropic score (p = 0.001), and fewer ventilator-free hours (p = 0.020). Conclusion: Cardiac dysfunction by echocardiography and serum ferritin value was significantly associated with unfavorable outcomes in pediatric patients with sepsis.
Resumo Objetivo: Verificar a associação do ecocardiograma, da ferritina, da proteína C reativa (PCR) e da contagem de leucócitos com desfechos desfavoráveis na sepse pediátrica. Métodos: Estudo de coorte prospectivo, de março a dezembro de 2014, com pacientes críticos pediátricos entre 28 dias e 18 anos. Critérios de inclusão foram diagnóstico de sepse, necessidade de ventilação mecânica (VM) por mais de 48 horas e uso de drogas vasoativas. Avaliaram‐se os níveis séricos PCR, ferritina, contagem de leucócitos, no recrutamento (D0), 24 horas (D1) e 72 horas (D3) após o recrutamento. No D1 e no D3 todos os pacientes foram submetidos a ecocardiograma transtorácico para determinação da Fração de Ejeção (FE) do ventrículo esquerdo. Os desfechos avaliados foram tempo de internação hospitalar e na Unidade de Terapia Intensiva Pediátrica (UTIP); duração da VM; horas livres de VM; duração do uso de inotrópicos; escore de inotrópicos máximo e mortalidade. Resultados: Vinte pacientes completaram o estudo. Ferritina elevada no D0 associou‐se com menor tempo livre de ventilação (p = 0,046) e maior escore de inotrópicos máximo (p = 0,009). A disfunção cardíaca pelo ecocardiograma no D1 relacionou‐se com maior tempo de internação hospitalar (p = 0,047), de UTIP (p = 0,020), VM total (p = 0,011), escore de inotrópicos máximo (p = 0,001) e menor tempo livre de VM (p = 0,020). Conclusão: A disfunção cardíaca pelo ecocardiograma e o valor de ferritina sérica associaram‐se significativamente com desfechos desfavoráveis nos pacientes pediátricos com sepse.
Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , C-Reactive Protein/analysis , Echocardiography, Doppler , Sepsis/diagnosis , Ferritins/metabolism , Ferritins/blood , Heart/physiopathology , Echocardiography , Biomarkers/blood , Intensive Care Units, Pediatric , Prospective Studies , Sepsis/complications , Sepsis/physiopathology , Sepsis/blood , Length of Stay , Leukocyte CountSubject(s)
Humans , Shock, Septic/diagnosis , Sepsis/diagnosis , Organ Dysfunction Scores , Sepsis/physiopathologySubject(s)
Humans , Female , Paraneoplastic Syndromes/diagnosis , Adenocarcinoma/diagnosis , Sepsis/diagnosis , Carcinoma, Ovarian Epithelial/diagnosis , Muscular Diseases/diagnosis , Necrosis/pathology , Paraneoplastic Syndromes/physiopathology , Paraneoplastic Syndromes/therapy , Weight Loss , Adenocarcinoma/physiopathology , Adenocarcinoma/therapy , Deglutition Disorders , Fatal Outcome , Sepsis/physiopathology , Lower Extremity , Edema , Dysphonia , Carcinoma, Ovarian Epithelial/physiopathology , Carcinoma, Ovarian Epithelial/therapy , Middle Aged , Muscular Diseases/pathologyABSTRACT
La sepsis es un síndrome de respuesta inflamatoria sistémica (SRIS) que se activa por infección. Por su parte, el síndrome de disfunción orgánica múltiple (SDOM) es el fallo de la función de órganos y sistemas críticos en pacientes que han desarrollado una SRIS. Debido a que SRIS y SDOM son consecuencias de una excesiva activación inflamatoria. El objetivo de este artículo es ofrecer una revisión sobre algunos aspectos fisiopatológicos del constructo SRIS / SDOM de origen infeccioso, utilizando a la colangitis aguda como un ejemplo de esta cadena de eventos.
Sepsis is a systemic inflammatory response syndrome (SIRS) that is triggered by infection. On the other hand, multiple organ dysfunction syndrome (MODS) is the failure of critical organ function in patients suffering from SIRS.Because SIRS and SDOM are consequences of excessive inflammatory activation. The aim of this article is to provide a review of some pathophysiological aspects of the SRIS / SDOM construct of infectious origin, using the acute cholangitis as an example of this chain of events.
Subject(s)
Humans , Cholangitis/physiopathology , Systemic Inflammatory Response Syndrome/physiopathology , Sepsis/physiopathology , Multiple Organ Failure/physiopathologyABSTRACT
RESUMO A despeito dos avanços nos últimos anos, a sepse ainda é uma das principais causas de internação e mortalidade em lactentes e crianças. A presença de biomarcadores na resposta a um insulto infeccioso resulta em seu uso na triagem, no diagnóstico, no prognóstico (estratificação de risco), na monitorização da resposta terapêutica e no uso racional de antibióticos (duração adequada, por exemplo). Os estudos sobre biomarcadores na sepse em crianças são ainda relativamente escassos. Esta revisão aborda o uso de biomarcadores na sepse em pacientes pediátricos, com ênfase em proteína C-reativa, procalcitonina, interleucinas 6, 8 e 18, gelatinase dos neutrófilos humanos e proadrenomedulina, que podem ser úteis na abordagem da sepse pediátrica.
ABSTRACT Despite advances in recent years, sepsis is still a leading cause of hospitalization and mortality in infants and children. The presence of biomarkers during the response to an infectious insult makes it possible to use such biomarkers in screening, diagnosis, prognosis (risk stratification), monitoring of therapeutic response, and rational use of antibiotics (for example, the determination of adequate treatment length). Studies of biomarkers in sepsis in children are still relatively scarce. This review addresses the use of biomarkers in sepsis in pediatric patients with emphasis on C-reactive protein, procalcitonin, interleukins 6, 8, and 18, human neutrophil gelatinase, and proadrenomedullin. Assessment of these biomarkers may be useful in the management of pediatric sepsis.
Subject(s)
Humans , Infant , Child , Biomarkers/metabolism , Sepsis/diagnosis , Anti-Bacterial Agents/administration & dosage , Prognosis , Age Factors , Sepsis/physiopathology , Sepsis/drug therapyABSTRACT
Abstract Experimental models of human pathology are useful guides to new approaches towards improving clinical and surgical treatments. A systematic search through PubMed using the syntax (shock) AND (trauma) AND (animal model) AND (cardiovascular) AND ("2010/01/01"[PDat]: "2015/12/31"[PDat]) found 88 articles, which were reduced by manual inspection to 43 entries. These were divided into themes and each theme is subsequently narrated and discussed conjointly. Taken together, these articles indicate that valuable information has been developed over the past 5 years concerning endothelial stability, mesenteric lymph, vascular reactivity, traumatic injuries, burn and sepsis. A surviving interest in hypertonic saline resuscitation still exists.