RESUMO
Sepsis is defined as a dysregulated host response to infection that leads to life-threatening acute organ dysfunction. It afflicts approximately 50 million people worldwide annually and is often deadly, even when evidence-based guidelines are applied promptly. Many randomized trials tested therapies for sepsis over the past 2 decades, but most have not proven beneficial. This may be because sepsis is a heterogeneous syndrome, characterized by a vast set of clinical and biologic features. Combinations of these features, however, may identify previously unrecognized groups, or "subclasses" with different risks of outcome and response to a given treatment. As efforts to identify sepsis subclasses become more common, many unanswered questions and challenges arise. These include: 1) the semantic underpinning of sepsis subclasses, 2) the conceptual goal of subclasses, 3) considerations about study design, data sources, and statistical methods, 4) the role of emerging data types, and 5) how to determine whether subclasses represent "truth." We discuss these challenges and present a framework for the broader study of sepsis subclasses. This framework is intended to aid in the understanding and interpretation of sepsis subclasses, provide a mechanism for explaining subclasses generated by different methodologic approaches, and guide clinicians in how to consider subclasses in bedside care.
Assuntos
Unidades de Terapia Intensiva , Sepse/classificação , Sepse/terapia , Diagnóstico Precoce , Medicina Baseada em Evidências , Humanos , Choque Séptico/classificação , Choque Séptico/terapiaRESUMO
Zika virus (ZIKAV) is classically described as causing minor symptoms in adult patients, however neurologic complications have been recognized. The recent outbreak in Central and South America has resulted in serious illness in some adult patients. We report adult patients in Latin America diagnosed with ZIKAV infection admitted to Intensive Care Units (ICUs). METHODS: Multicenter, prospective case series of adult patients with laboratory diagnosis of ZIKAV in 16 ICUs in 8 countries. RESULTS: Between December 1st 2015 and April 2nd 2016, 16 ICUs in 8 countries enrolled 49 critically ill patients with diagnosis of ZIKAV infection. We included 10 critically ill patients with ZIKAV infection, as diagnosed with RT-PCR, admitted to the ICU. Neurologic manifestations concordant with Guillain-Barre Syndrome (GBS) were present in all patients, although 2 evolved into an encephalitis-like picture. 2 cases died, one due to encephalitis, the other septic shock. CONCLUSIONS: Differing from what was usually reported, ZIKAV infection can result in life-threatening neurologic illness in adults, including GBS and encephalitis. Collaborative reporting to identify severe illness from an emerging pathogen can provide valuable insights into disease epidemiology and clinical presentation, and inform public health authorities about acute care priorities.
Assuntos
Surtos de Doenças , Encefalite Viral/complicações , Síndrome de Guillain-Barré/complicações , Infecção por Zika virus/epidemiologia , APACHE , Adulto , Idoso , Cuidados Críticos , Estado Terminal/epidemiologia , Encefalite Viral/virologia , Feminino , Síndrome de Guillain-Barré/virologia , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , América do Sul/epidemiologia , Adulto Jovem , Zika virus , Infecção por Zika virus/complicaçõesRESUMO
BACKGROUND: Venous thromboembolism (VTE) is a common complication of critical illness with important clinical consequences. The Prophylaxis for ThromboEmbolism in Critical Care Trial (PROTECT) is a multicenter, blinded, randomized controlled trial comparing the effectiveness of the two most common pharmocoprevention strategies, unfractionated heparin (UFH) and low molecular weight heparin (LMWH) dalteparin, in medical-surgical patients in the intensive care unit (ICU). E-PROTECT is a prospective and concurrent economic evaluation of the PROTECT trial. METHODS/DESIGN: The primary objective of E-PROTECT is to identify and quantify the total (direct and indirect, variable and fixed) costs associated with the management of critically ill patients participating in the PROTECT trial, and, to combine costs and outcome results to determine the incremental cost-effectiveness of LMWH versus UFH, from the acute healthcare system perspective, over a data-rich time horizon of ICU admission and hospital admission. We derive baseline characteristics and probabilities of in-ICU and in-hospital events from all enrolled patients. Total costs are derived from centers, proportional to the numbers of patients enrolled in each country. Direct costs include medication, physician and other personnel costs, diagnostic radiology and laboratory testing, operative and non-operative procedures, costs associated with bleeding, transfusions and treatment-related complications. Indirect costs include ICU and hospital ward overhead costs. Outcomes are the ratio of incremental costs per incremental effects of LMWH versus UFH during hospitalization; incremental cost to prevent a thrombosis at any site (primary outcome); incremental cost to prevent a pulmonary embolism, deep vein thrombosis, major bleeding event or episode of heparin-induced thrombocytopenia (secondary outcomes) and incremental cost per life-year gained (tertiary outcome). Pre-specified subgroups and sensitivity analyses will be performed and confidence intervals for the estimates of incremental cost-effectiveness will be obtained using bootstrapping. DISCUSSION: This economic evaluation employs a prospective costing methodology concurrent with a randomized controlled blinded clinical trial, with a pre-specified analytic plan, outcome measures, subgroup and sensitivity analyses. This economic evaluation has received only peer-reviewed funding and funders will not play a role in the generation, analysis or decision to submit the manuscripts for publication. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00182143 . Date of registration: 10 September 2005.
Assuntos
Anticoagulantes/administração & dosagem , Anticoagulantes/economia , Dalteparina/administração & dosagem , Dalteparina/economia , Custos de Medicamentos , Fibrinolíticos/administração & dosagem , Fibrinolíticos/economia , Heparina/administração & dosagem , Heparina/economia , Custos Hospitalares , Tromboembolia Venosa/economia , Tromboembolia Venosa/prevenção & controle , Anticoagulantes/efeitos adversos , Austrália , Brasil , Protocolos Clínicos , Redução de Custos , Análise Custo-Benefício , Cuidados Críticos , Dalteparina/efeitos adversos , Fibrinolíticos/efeitos adversos , Heparina/efeitos adversos , Humanos , Modelos Econômicos , América do Norte , Estudos Prospectivos , Anos de Vida Ajustados por Qualidade de Vida , Projetos de Pesquisa , Arábia Saudita , Fatores de Tempo , Resultado do Tratamento , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/etiologiaRESUMO
BACKGROUND: Swine origin influenza A/H1N1 infection (H1N1) emerged in early 2009 and rapidly spread to humans. For most infected individuals, symptoms were mild and self-limited; however, a small number developed a more severe clinical syndrome characterized by profound respiratory failure with hospital mortality ranging from 10 to 30%. While supportive care and neuraminidase inhibitors are the main treatment for influenza, data from observational and interventional studies suggest that the course of influenza can be favorably influenced by agents not classically considered as influenza treatments. Multiple observational studies have suggested that HMGCoA reductase inhibitors (statins) can exert a class effect in attenuating inflammation. The Collaborative H1N1 Adjuvant Treatment (CHAT) Pilot Trial sought to investigate the feasibility of conducting a trial during a global pandemic in critically ill patients with H1N1 with the goal of informing the design of a larger trial powered to determine impact of statins on important outcomes. METHODS/DESIGN: A multi-national, pilot randomized controlled trial (RCT) of once daily enteral rosuvastatin versus matched placebo administered for 14 days for the treatment of critically ill patients with suspected, probable or confirmed H1N1 infection. We propose to randomize 80 critically ill adults with a moderate to high index of suspicion for H1N1 infection who require mechanical ventilation and have received antiviral therapy for ≤ 72 hours. Site investigators, research coordinators and clinical pharmacists will be blinded to treatment assignment. Only research pharmacy staff will be aware of treatment assignment. We propose several approaches to informed consent including a priori consent from the substitute decision maker (SDM), waived and deferred consent. The primary outcome of the CHAT trial is the proportion of eligible patients enrolled in the study. Secondary outcomes will evaluate adherence to medication administration regimens, the proportion of primary and secondary endpoints collected, the number of patients receiving open-label statins, consent withdrawals and the effect of approved consent models on recruitment rates. DISCUSSION: Several aspects of study design including the need to include central randomization, preserve allocation concealment, ensure study blinding compare to a matched placebo and the use novel consent models pose challenges to investigators conducting pandemic research. Moreover, study implementation requires that trial design be pragmatic and initiated in a short time period amidst uncertainty regarding the scope and duration of the pandemic. TRIAL REGISTRATION NUMBER: ISRCTN45190901.
Assuntos
Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , Fluorbenzenos/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Vírus da Influenza A Subtipo H1N1/patogenicidade , Influenza Humana/tratamento farmacológico , Pirimidinas/uso terapêutico , Projetos de Pesquisa , Sulfonamidas/uso terapêutico , Doença Aguda , Argentina , Austrália , Canadá , Comportamento Cooperativo , Cuidados Críticos , Estado Terminal , Quimioterapia Combinada , Estudos de Viabilidade , Humanos , Influenza Humana/diagnóstico , Influenza Humana/virologia , Consentimento Livre e Esclarecido , México , Nova Zelândia , Seleção de Pacientes , Projetos Piloto , Respiração Artificial , Rosuvastatina Cálcica , Arábia Saudita , Resultado do TratamentoRESUMO
BACKGROUND: The Surviving Sepsis Campaign (SSC) was launched in 2002 as a collaborative initiative of the European Society of Intensive Care Medicine (ESICM), the International Sepsis Forum (ISF), and the Society of Critical Care Medicine (SCCM). Its objective was, through the development and promulgation of evidence-based guidelines that facilitated the application of knowledge derived from clinical trials to bedside practice, to effect a 25% reduction in the relative risk of death from severe sepsis and septic shock. METHODS: The evolution and content of the SSC is summarized and the scientific basis of the conclusions is reviewed from the literature. RESULTS: The SSC developed evidence-based management guidelines and undertook a broad educational program to implement them by integrating their recommendations into resuscitation and management bundles. The process engaged practitioners in North America, Europe, and South America and was supported by professional societies around the world. It also engendered controversy based on accusations of undue industry influence and some dissatisfaction among individuals who were antagonistic toward protocolization of care. By its conclusion, more than 22,000 patients with sepsis had been entered in the SSC database, and analysis of the results showed that participation in the SSC was associated with a 5.4% absolute survival benefit. CONCLUSIONS: The SSC has impacted the care of septic patients and catalyzed changes that are likely to persist and evolve.
Assuntos
Sepse/mortalidade , Sepse/terapia , Choque Séptico/mortalidade , Choque Séptico/terapia , Bases de Dados Factuais , Europa (Continente) , Humanos , América do Norte , Guias de Prática Clínica como Assunto , América do SulRESUMO
A solução salina hipertônica (SSH) vem demonstrando uma série de ações imunomoduladoras em leucócitos humanos. Neste trabalho, leucócitos polimorfonucleares humanos (PMN) foram submetidos, "in vitro", à SSH na concentração de 500mOsm e a lipopolissacarídeo (LPS) com o objetivo de estudar: a) a influência da SSH nas taxas apoptose dos PMN e b) o efeito da interação da SSH com o LPS nas referidas taxas. Após o isolamento de PMN humanos de voluntários sadios, foram realizados os experimentos: a) as soluções com PMN foram expostas à SSH na osmolaridade final de 500mOsm por períodos de tempo de 20, 40, 60 e 120 minutos; b) as soluções com PMN foram expostas ao LPS e em seguida à SSH, por 60 minutos a cada solução. Em outra amostra, os PMN foram submetidos previamente à SSH e em seguida a LPS, por 60 minutos a cada solução. Após os experimentos, todas as soluções foram centrifudagas e ressuspensas em meio isotônico por 16h, sendo submetidas à quantificação da apoptose por citometria de fluxo (citômetro Coulter EPICS XL-MCL), através da análise do DNA hipodiplóide corado com "propidium iodidae". Na análise estatística foi utilizado o programa STATISTICA for Windows (Copyright), em pregando-se o método do T-pareado. Conclui-se que as taxas de apoptose em PMN, "in vitro": I) elevam-se de forma estatisticamente significativa com a a exposição à SSH, ocorrendo aumento das taxas com o tempo de exposição; II) são alteradas de forma estatisticamente significativa conforme a ordem de exposição à LPS e SSH ou vice-versa: a) PMN ativadas por LPS não sofrem influência da exposição subseqüente à SSH, demonstrando taxas similares à exposição isolada ao LPS; b) a exposição prévia de PMN à SSH, anula o efeito inibidor da apoptose do LPS, produzindo taxas sem diferença estatisticamente significativa do controle