Platelet-derived exosomes from septic shock patients induce myocardial dysfunction

Abstract\ud \ud \ud \ud Introduction\ud \ud Mechanisms underlying inotropic failure in septic shock are incompletely understood. We previously identified the presence of exosomes in the plasma of septic shock patients. These exosomes are released mainly by platelets, produce superoxide, and induce apoptosis in vascular cells by a redox-dependent pathway. We hypothesized that circulating platelet-derived exosomes could contribute to inotropic dysfunction of sepsis.\ud \ud \ud \ud Methods\ud \ud We collected blood samples from 55 patients with septic shock and 12 healthy volunteers for exosome separation. Exosomes from septic patients and healthy individuals were investigated concerning their myocardial depressant effect in isolated heart and papillary muscle preparations.\ud \ud \ud \ud Results\ud \ud Exosomes from the plasma of septic patients significantly decreased positive and negative derivatives of left ventricular pressure in isolated rabbit hearts or developed tension and its first positive derivative in papillary muscles. Exosomes from healthy individuals decreased these variables non-significantly. In hearts from rabbits previously exposed to endotoxin, septic exosomes decreased positive and negative derivatives of ventricular pressure. This negative inotropic effect was fully reversible upon withdrawal of exosomes. Nitric oxide (NO) production from exosomes derived from septic shock patients was demonstrated by fluorescence. Also, there was an increase in myocardial nitrate content after exposure to septic exosomes.\ud \ud \ud \ud Conclusion\ud \ud Circulating platelet-derived exosomes from septic patients induced myocardial dysfunction in isolated heart and papillary muscle preparations, a phenomenon enhanced by previous in vivo exposure to lipopolysaccharide. The generation of NO by septic exosomes and the increased myocardial nitrate content after incubation with exosomes from septic patients suggest an NO-dependent mechanism that may contribute to myocardial dysfunction of sepsis.This work received financial support from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP).This work received financial support from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Hemodynamic and respiratory support using venoarterial extracorporeal membrane oxygenation (ECMO) in a polytrauma patient

Existem poucos relatos na literatura sobre o uso de oxigenação extracorpórea por membrana venoarterial por dupla disfunção decorrente de contusão cardíaca e pulmonar no paciente politraumatizado. Relatamos o caso de um paciente de 48 anos, vítima de acidente de motocicleta e automóvel, que evoluiu rapidamente com choque refratário com baixo débito cardíaco por contusão miocárdica e hipoxemia refratária decorrente de contusão pulmonar, tórax instável e pneumotórax bilateral. O suporte extracorpóreo foi uma medida efetiva de resgate para esse caso dramático, e o seu uso pôde ser interrompido com sucesso no 4º dia após o trauma. O paciente evoluiu com extenso infarto cerebral, morrendo no 7º dia de internaçãoThere are few reports in the literature regarding the use of venoarterial extracorporeal membrane oxygenation (ECMO) for double-dysfunction from both heart and lung contusions in polytrauma patients. This article reports a 48-year-old patient admitted after a traffic accident. He rapidly progressed to shock with low cardiac output due to myocardial contusion and refractory hypoxemia due to pulmonary contusion, an unstable chest wall and bilateral pneumothorax. ECMO was an effective rescue procedure in this dramatic situation and was successfully discontinued on the fourth day after the trauma. The patient also developed an extensive brain infarction and eventually died on the seventh day after admissio

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Observational study on the association between timing of antibiotic therapy and worsening organ dysfunctions in non-septic surgical patients with suspected nosocomial infection

INTRODUÇÃO: Na presença de sepse, choque séptico ou foco infeccioso evidente, antimicrobianos devem ser administrados imediatamente. Entretanto, poucos estudos avaliaram essa conduta na suspeita de infecção sem foco infeccioso evidente e sem sepse. O objetivo do presente estudo foi avaliar se há associação entre postergar a administração de antibioticoterapia empírica precoce em pacientes críticos cirúrgicos com suspeita de infecção nosocomial, porém sem disfunções orgânicas agudas e sem foco óbvio de infecção, com progressão de disfunções orgânicas. MÉTODOS: Estudo retrospectivo observacional, incluindo pacientes que tiveram culturas coletadas devido a hipótese diagnóstica de infecção nosocomial. Grupo Terapia Antimicrobiana Empírica Precoce (GTEP): indivíduos que receberam antibióticos com espectro de ação ativo para tratamento de infecções nosocomiais em até 24 horas após coleta de culturas. Grupo Conservador (GC): pacientes que receberam antibióticos somente após 24 horas de coleta de culturas, ou que não receberam antimicrobianos. Os principais critérios de exclusão foram: sepse, choque séptico ou foco de infecção evidente. O desfecho primário foi composto por: aumento da escala SOFA acima de um ponto (sepse); hipotensão, hiperlactatemia e uso de vasopressores (choque séptico); ou morte em até 14 dias após a inclusão. Análise Multivariada foi prevista devido aos desbalanços entre os grupos. RESULTADOS: De 2007 admissões na UTI no período, 751 apresentaram suspeita de infecção nosocomial e 340 pacientes foram elegíveis para inclusão (74% vítimas de trauma). A maior parte das exclusões ocorreu devido a sepse (221 pacientes), choque séptico (81 pacientes) ou foco óbvio de infecção (51 pacientes). Idade, sexo, motivo de admissão hospitalar, escala Simplified Acute Physiology Score (SAPS3), escala Sequential Organ Failure Assessment (SOFA), uso de vasopressor ou de ventilação mecânica não foram diferentes entre os grupos. No GC, 57% dos pacientes receberam antibióticos em até 14 dias da inclusão (vs. 100% no GTEP). O desfecho composto ocorreu em 40% dos indivíduos no GC e 56% no GTEP (p<0,01). Análise multivariada evidenciou que a principal variável associada ao desfecho primário foi a infecção presumida com foco diagnosticado após inclusão (Odds Ratio 2,57; IC95:1,48-4,56; p<0,01). Não houve associação entre desfecho primário e o grupo alocado (GC ou GTEP). Na subanálise incluindo apenas pacientes com infecção confirmada por culturas, o atraso na instituição da antibioticoterapia apropriada teve associação independente com o desfecho primário (Odds Ratio 1,16 por dia de atraso; IC95:1,02-1,33; p=0,03). CONCLUSÕES: A ausência de antibioticoterapia empírica precoce em pacientes críticos cirúrgicos não sépticos com suspeita de infecção nosocomial sem foco infeccioso evidente não se associa com aumento da incidência de sepse, choque séptico ou óbito em 14 dias. Na subanálise realizada apenas em pacientes com infecções confirmadas por cultura, o atraso na administração do antibiótico efetivo contra o patógeno isolado esteve associado a piores desfechosINTRODUCTION: In patients with sepsis, septic shock or in the presence of an obvious source of infection, antibiotics should be promptly administered. However, few studies evaluated this approach in suspected infection without an obvious source of infection or sepsis. The objective of this study was to evaluate if withholding early empiric antibiotic administration in critically ill surgical patients with suspected nosocomial infection, but without an obvious source of infection or acute organ dysfunctions, is associated with detrimental outcomes. METHODS: Retrospective observational study including patients who have cultures collected for suspected nosocomial infection. Early Empiric Antimicrobial Therapy Group (EEAG): individuals who received active antibiotics for nosocomial infection within 24 hours after cultures harvesting. Conservative Group (CG): patients who received these antibiotics only after 24 hours from culture harvesting or did not receive antibiotics at all. Sepsis, septic shock or an obvious source of infection were the main exclusion criteria. The primary outcome was composite of an increase in SOFA score one point (sepsis); hypotension, hyperlactatemia and use of vasopressor (septic shock); or death within fourteen days after inclusion. Multivariate analysis was foreseen due to imbalances between groups. RESULTS: From 2007 ICU admissions on databank, 751 had suspected nosocomial infection and 340 patients were eligible for inclusion (74% trauma patients). Most exclusions were due to sepsis (221 patients), septic shock (81 patients) or an obvious source of infection (51 patients). Age, gender, the reason for hospital admission, Simplified Acute Physiology Score (SAPS 3), Sequential Organ Failure Assessment (SOFA) score and use of vasopressors or mechanical ventilation were not different between groups. In CG, 57% of patients received antibiotics within 14 days of inclusion (vs. 100% on EEAG). The composite primary outcome occurred in 40% of patients in the CG and 56% in the EEAG, (p<0.01). Presumed infection with a source of infection diagnosed after inclusion was the main variable associated with the primary outcome in multivariate analysis (Odds Ratio 2.57; IC95:1.48-4.56; p<0.01). There was no association between primary outcome and group allocation (CG or EEAG). In the subanalysis including only patients with confirmed infection (by cultures) delay in initiation of adequate antimicrobial therapy had an independent association with the primary outcome (Odds Ratio 1.16 per day of delay; IC95: IC95:1.02-1.33; p=0.03). CONCLUSIONS: In critically ill non-septic surgical patients with suspected nosocomial infection without an obvious source, withholding early empiric antibiotic therapy was not associated with an increase in the incidence of sepsis, septic shock or death within 14 days. In the subanalysis including only confirmed infection patients, delay in the administration of active therapy against the isolated pathogens was associated with worse outcome

Therapeutic Strategies for High-Dose Vasopressor-Dependent Shock

There is no consensual definition of refractory shock. The use of more than 0.5 mcg/kg/min of norepinephrine or epinephrine to maintain target blood pressure is often used in clinical trials as a threshold. Nearly 6% of critically ill patients will develop refractory shock, which accounts for 18% of deaths in intensive care unit. Mortality rates are usually greater than 50%. The assessment of fluid responsiveness and cardiac function can help to guide therapy, and inotropes may be used if hypoperfusion signs persist after initial resuscitation. Arginine vasopressin is frequently used in refractory shock, although definite evidence to support this practice is still missing. Its associations with corticosteroids improved outcome in observational studies and are therefore promising alternatives. Other rescue therapies such as terlipressin, methylene blue, and high-volume isovolemic hemofiltration await more evidence before use in routine practice

Association of antimicrobial use and incidence of hospital-acquired pneumonia in critically ill trauma patients with pulmonary contusion: an observational study

Background: Pneumonia occurs in about 20% of trauma patients with pulmonary contusions. This study aims to evaluate the association between empirical antibiotic therapy and nosocomial pneumonia in this population. Methods: Retrospective cohort of adult patients admitted to a trauma-surgical ICU. The Antibiotic Therapy Group (ATG) was defined by intravenous antibiotic use for more than 48 h starting on hospital admission, while the Conservative Group (CG) was determined by antibiotic use no longer than 48 h. Primary outcome was microbiologically documented nosocomial pneumonia within 14 days after hospital admission. Logistic regression was used to estimate the association between group allocation and primary outcome. Exploratory analyses evaluating the association between resistant strains in pneumonia and antibiotic use were performed. Results: The study included 177 patients with chest trauma and pulmonary contusion on CT scan. ATG were more severely ill than CG, as shown by higher Injury Severity Score, SAPS3, SOFA score, higher rates, and longer duration of mechanical ventilation. In the multivariate analysis, ATG was associated with a lower incidence of primary outcome (OR = 0.25, 95% CI 0.09–0.64; p < 0.01). Similar results were found in the sensitivity analysis with another set of variables. However, each day of antibiotic use was associated with an increased risk of pneumonia by resistant bacteria (OR = 1.18 per day, 95% CI 1.05–1.36; p < 0.01). Conclusions: Empiric antibiotic therapy was independently associated with lower incidence of nosocomial pneumonia in critically ill patients with pulmonary contusion. However, each day of antibiotic use was associated with increased resistant strains in infected patients