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1.
Crit Care ; 28(1): 46, 2024 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365828

RESUMO

Septic shock typically requires the administration of vasopressors. Adrenergic agents remain the first choice, namely norepinephrine. However, their use to counteract life-threatening hypotension comes with potential adverse effects, so that non-adrenergic vasopressors may also be considered. The use of agents that act through different mechanisms may also provide an advantage. Nitric oxide (NO) is the main driver of the vasodilation that leads to hypotension in septic shock, so several agents have been tested to counteract its effects. The use of non-selective NO synthase inhibitors has been of questionable benefit. Methylene blue, an inhibitor of soluble guanylate cyclase, an important enzyme involved in the NO signaling pathway in the vascular smooth muscle cell, has also been proposed. However, more than 25 years since the first clinical evaluation of MB administration in septic shock, the safety and benefits of its use are still not fully established, and it should not be used routinely in clinical practice until further evidence of its efficacy is available.


Assuntos
Hipotensão , Choque Séptico , Humanos , Azul de Metileno/efeitos adversos , Choque Séptico/tratamento farmacológico , Choque Séptico/metabolismo , Hipotensão/tratamento farmacológico , Guanilil Ciclase Solúvel , Norepinefrina , Vasoconstritores/efeitos adversos
2.
Curr Opin Crit Care ; 29(3): 231-235, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37078636

RESUMO

PURPOSE OF REVIEW: To review recently published data on pulmonary artery catheter (PAC) use in critically ill patients and consider optimal use of the PAC in personalized clinical practice. RECENT FINDINGS: Although PAC use has decreased considerably since the mid-1990s, PAC-derived variables can still have an important role in elucidating hemodynamic status and directing management in complex patients. Recent studies have suggested benefit, notably in patients having cardiac surgery. SUMMARY: Only a small number of acutely ill patients require a PAC and insertion should be individualized based on clinical context, availability of trained staff, and the possibility that measured variables will be able to help guide therapy.


Assuntos
Cateterismo de Swan-Ganz , Artéria Pulmonar , Humanos , Artéria Pulmonar/cirurgia , Cuidados Críticos , Hemodinâmica , Catéteres
3.
Crit Care Med ; 49(4): e360-e368, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33566467

RESUMO

OBJECTIVES: Although early recognition of sepsis is vital to improving outcomes, the diagnosis may be missed or delayed in many patients. Acute kidney injury is one of the most common organ failures in patients with sepsis but may not be apparent on presentation. Novel biomarkers for acute kidney injury might improve organ failure recognition and facilitate earlier sepsis care. DESIGN: Retrospective, international, Sapphire study. SETTING: Academic Medical Center. PATIENTS: Adults admitted to the ICU without evidence of acute kidney injury at time of enrollment. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We stratified patients enrolled in the Sapphire study into three groups-those with a clinical diagnosis of sepsis (n = 216), those with infection without sepsis (n = 120), and those without infection (n = 387) at enrollment. We then examined 30-day mortality stratified by acute kidney injury within each group. Finally, we determined the operating characteristics for kidney stress markers (tissue inhibitor of metalloproteinases-2) × (insulin-like growth factor binding protein 7) for prediction of acute kidney injury as a sepsis-defining organ failure in patients with infection without a clinical diagnosis of sepsis at enrollment. Combining all groups, 30-day mortality was 23% for patients who developed stage 2-3 acute kidney injury within the first 3 days compared with 14% without stage 2-3 acute kidney injury. However, this difference was greatest in the infection without sepsis group (34% vs 11%; odds ratio, 4.09; 95% CI, 1.53-11.12; p = 0.005). Using a (tissue inhibitor of metalloproteinases-2) × (insulin-like growth factor binding protein 7) cutoff of 2.0 units, 14 patients (11.7%), in the infection/no sepsis group, tested positive of which 10 (71.4%) developed stage 2-3 acute kidney injury. The positive test result occurred a median of 19 hours (interquartile range, 0.8-34.0 hr) before acute kidney injury manifested by serum creatinine or urine output. Similar results were obtained using a cutoff of 1.0 for any stage of acute kidney injury. CONCLUSIONS: Use of the urinary (tissue inhibitor of metalloproteinases-2) × (insulin-like growth factor binding protein 7) test could identify acute kidney injury in patients with infection, possibly helping to detect sepsis, nearly a day before acute kidney injury is apparent by clinical criteria.


Assuntos
Injúria Renal Aguda/sangue , Injúria Renal Aguda/diagnóstico , Infecções/diagnóstico , Sepse/diagnóstico , Índice de Gravidade de Doença , Idoso , Biomarcadores/sangue , Creatinina/sangue , Estado Terminal , Feminino , Humanos , Infecções/complicações , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sepse/complicações , Inibidor Tecidual de Metaloproteinase-2/sangue
6.
Crit Care Med ; 47(12): 1680-1691, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31567349

RESUMO

OBJECTIVES: To determine which multicenter randomized controlled trials in critically ill patients have shown that the study intervention was associated with a statistically significant reduction in mortality. Our analysis provides an update to a report published 10 years ago. DATA SOURCES: MEDLINE database and PubMed interface from inception until April 30, 2019. STUDY SELECTION: All adult multicenter randomized controlled trials that evaluated the effects of any intervention or monitoring system in critically ill patients and reported mortality as a primary or secondary outcome were included. DATA EXTRACTION: Numbers of centers and patients, type of intervention, reported mortality outcome, and rate and level of significance were extracted into predefined tables. Included randomized controlled trials were classified as reporting reduced, increased, or no effect of the intervention on mortality. Methodologic quality of trials was evaluated using the updated Consolidated Standards of Reporting Trials statement. DATA SYNTHESIS: A total of 212 trials met the inclusion criteria: 27 (13%) reported a significant reduction in mortality, 16 (7%) an increase in mortality, and 170 (80%) no difference in mortality (one study was reported in 2 groups). Of the 27 trials reporting reduced mortality, six had assessed interventions likely to decrease ventilator-induced lung injury, including low tidal volume, prone position, and neuromuscular blockers, demonstrating the negative effects of mechanical ventilation strategies or improved process of care rather than positive effects of new therapies. Seven of the 27 trials reported beneficial effects of noninvasive ventilation. Results from some positive randomized controlled trials, for example, studies of recombinant activated protein C, talactoferrin, interleukin-1 receptor antagonist in sepsis, and muscle relaxants in severe acute respiratory distress syndrome were not replicated in subsequent randomized controlled trials. Other interventions, for example, gastric tonometry, have been abandoned. CONCLUSIONS: A systematic literature search provided no conclusive evidence of any pharmacologic intervention that has consistently reduced mortality in critically ill patients. Strategies associated with improved or noninvasive mechanical ventilation were associated with reduced mortality.


Assuntos
Cuidados Críticos , Estado Terminal/mortalidade , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos
7.
BMC Anesthesiol ; 18(1): 49, 2018 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-29743022

RESUMO

BACKGROUND: Patients undergoing abdominal surgery for solid tumours frequently develop major postoperative complications, which negatively affect quality of life, costs of care and survival. Few studies have identified the determinants of perioperative complications in this group. METHODS: We performed a prospective observational study including all patients (age > 18) undergoing abdominal surgery for cancer at a single institution between June 2011 and August 2013. Patients undergoing emergency surgery, palliative procedures, or participating in other studies were excluded. Primary outcome was a composite of 30-day all-cause mortality and infectious, cardiovascular, respiratory, neurologic, renal and surgical complications. Univariate and multiple logistic regression analyses were performed to identify predictive factors for major perioperative adverse events. RESULTS: Of a total 308 included patients, 106 (34.4%) developed a major complication during the 30-day follow-up period. Independent predictors of postoperative major complications were: age (odds ratio [OR] 1.03 [95% CI 1.01-1.06], p = 0.012 per year), ASA (American Society of Anesthesiologists) physical status greater than or equal to 3 (OR 2.61 [95% CI 1.33-5.17], p = 0.003), a preoperative haemoglobin level lower than 12 g/dL (OR 2.13 [95% CI 1.21-4.07], p = 0.014), intraoperative use of colloids (OR 1.89, [95% CI 1.03-4.07], p = 0.047), total amount of intravenous fluids (OR 1.22 [95% CI 0.98-1.59], p = 0.106 per litre), intraoperative blood losses greater than 500 mL (2.07 [95% CI 1.00-4.31], p = 0.043), and hypotension needing vasopressor support (OR 4.68 [95% CI 1.55-27.72], p = 0.004). The model had good discrimination with the area under the ROC curve being 0.80 (95% CI 0.75-0.84, p < 0.001). CONCLUSIONS: Our findings suggest that a perioperative strategy aimed at reducing perioperative complications in cancer surgery should include treatment of preoperative anaemia and an optimal fluid strategy, avoiding fluid overload and intraoperative use of colloids.


Assuntos
Abdome/cirurgia , Procedimentos Cirúrgicos Eletivos/estatística & dados numéricos , Neoplasias/epidemiologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Anemia/epidemiologia , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Brasil/epidemiologia , Coloides/uso terapêutico , Comorbidade , Feminino , Hidratação/estatística & dados numéricos , Seguimentos , Nível de Saúde , Hemoglobinas , Humanos , Hipotensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
8.
Crit Care Med ; 46(8): e742-e750, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29727370

RESUMO

OBJECTIVES: The aim of this study was to evaluate the efficacy of perioperative intra-aortic balloon pump use in high-risk cardiac surgery patients. DESIGN: A single-center randomized controlled trial and a meta-analysis of randomized controlled trials. SETTING: Heart Institute of São Paulo University. PATIENTS: High-risk patients undergoing elective coronary artery bypass surgery. INTERVENTION: Patients were randomized to receive preskin incision intra-aortic balloon pump insertion after anesthesia induction versus no intra-aortic balloon pump use. MEASUREMENTS AND MAIN RESULTS: The primary outcome was a composite endpoint of 30-day mortality and major morbidity (cardiogenic shock, stroke, acute renal failure, mediastinitis, prolonged mechanical ventilation, and a need for reoperation). A total of 181 patients (mean [SD] age 65.4 [9.4] yr; 32% female) were randomized. The primary outcome was observed in 43 patients (47.8%) in the intra-aortic balloon pump group and 42 patients (46.2%) in the control group (p = 0.46). The median duration of inotrope use (51 hr [interquartile range, 32-94 hr] vs 39 hr [interquartile range, 25-66 hr]; p = 0.007) and the ICU length of stay (5 d [interquartile range, 3-8 d] vs 4 d [interquartile range, 3-6 d]; p = 0.035) were longer in the intra-aortic balloon pump group than in the control group. A meta-analysis of 11 randomized controlled trials confirmed a lack of survival improvement in high-risk cardiac surgery patients with perioperative intra-aortic balloon pump use. CONCLUSIONS: In high-risk patients undergoing cardiac surgery, the perioperative use of an intra-aortic balloon pump did not reduce the occurrence of a composite outcome of 30-day mortality and major complications compared with usual care alone.


Assuntos
Procedimentos Cirúrgicos Cardíacos/mortalidade , Procedimentos Cirúrgicos Cardíacos/métodos , Balão Intra-Aórtico/métodos , Complicações Pós-Operatórias/epidemiologia , Idoso , Cardiotônicos/administração & dosagem , Feminino , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Fatores de Risco , Método Simples-Cego
9.
Chest ; 152(2): 321-329, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28483610

RESUMO

BACKGROUND: Many critically ill patients who die will do so after a decision has been made to withhold/withdraw life-sustaining therapy. The objective of this study was to document the characteristics of ICU patients with a decision to withhold/withdraw life-sustaining treatment, including the types of supportive treatments used, patterns of organ dysfunction, and international differences, including gross national income (GNI). METHODS: In this observational cohort study conducted in 730 ICUs in 84 countries, all adult patients admitted between May 8, 2012, and May 18, 2012 (except admissions for routine postoperative surveillance), were included. RESULTS: The analysis included 9,524 patients, with a hospital mortality of 24%. A decision to withhold/withdraw life-sustaining treatment was reported during the ICU stay in 1,259 patients (13%), including 820 (40%) nonsurvivors and 439 (5%) survivors. Hospital mortality in patients with a decision to withhold/withdraw life-sustaining treatment was 69%. The proportion of deaths in patients with a decision to withhold/withdraw life-sustaining treatment ranged from 10% in South Asia to 67% in Oceania. Decisions to withhold/withdraw life-sustaining treatment were less frequent in low/lower-middle GNI countries than in high GNI countries (6% vs 14%; P < .001). Greater disease severity, presence of ≥ 2 organ failures, severe comorbidities, medical and trauma admissions, and admission from the ED or hospital floor were independent predictors of a decision to withhold/withdraw life-sustaining treatment. CONCLUSIONS: There is considerable worldwide variability in decisions to withhold/withdraw life-sustaining treatments. Interestingly, almost one-third of patients with a decision to withhold/withdraw life-sustaining treatment left the hospital alive.


Assuntos
Cuidados Críticos/estatística & dados numéricos , Cuidados para Prolongar a Vida/estatística & dados numéricos , Assistência Terminal/estatística & dados numéricos , Suspensão de Tratamento/estatística & dados numéricos , Tomada de Decisão Clínica/ética , Estudos de Coortes , Cuidados Críticos/ética , Feminino , Saúde Global , Humanos , Unidades de Terapia Intensiva/ética , Unidades de Terapia Intensiva/estatística & dados numéricos , Cuidados para Prolongar a Vida/ética , Masculino , Pessoa de Meia-Idade , Prognóstico , Respiração Artificial/ética , Respiração Artificial/estatística & dados numéricos , Assistência Terminal/ética , Suspensão de Tratamento/ética
10.
Anesthesiology ; 126(1): 85-93, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27841822

RESUMO

BACKGROUND: Vasoplegic syndrome is a common complication after cardiac surgery and impacts negatively on patient outcomes. The objective of this study was to evaluate whether vasopressin is superior to norepinephrine in reducing postoperative complications in patients with vasoplegic syndrome. METHODS: This prospective, randomized, double-blind trial was conducted at the Heart Institute, University of Sao Paulo, Sao Paulo, Brazil, between January 2012 and March 2014. Patients with vasoplegic shock (defined as mean arterial pressure less than 65 mmHg resistant to fluid challenge and cardiac index greater than 2.2 l · min · m) after cardiac surgery were randomized to receive vasopressin (0.01 to 0.06 U/min) or norepinephrine (10 to 60 µg/min) to maintain arterial pressure. The primary endpoint was a composite of mortality or severe complications (stroke, requirement for mechanical ventilation for longer than 48 h, deep sternal wound infection, reoperation, or acute renal failure) within 30 days. RESULTS: A total of 330 patients were randomized, and 300 were infused with one of the study drugs (vasopressin, 149; norepinephrine, 151). The primary outcome occurred in 32% of the vasopressin patients and in 49% of the norepinephrine patients (unadjusted hazard ratio, 0.55; 95% CI, 0.38 to 0.80; P = 0.0014). Regarding adverse events, the authors found a lower occurrence of atrial fibrillation in the vasopressin group (63.8% vs. 82.1%; P = 0.0004) and no difference between groups in the rates of digital ischemia, mesenteric ischemia, hyponatremia, and myocardial infarction. CONCLUSIONS: The authors' results suggest that vasopressin can be used as a first-line vasopressor agent in postcardiac surgery vasoplegic shock and improves clinical outcomes.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Norepinefrina/farmacologia , Complicações Pós-Operatórias/tratamento farmacológico , Choque/tratamento farmacológico , Vasoplegia/tratamento farmacológico , Vasopressinas/farmacologia , Brasil , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Choque/complicações , Resultado do Tratamento , Vasoconstritores/farmacologia , Vasoplegia/complicações
11.
J Thorac Cardiovasc Surg ; 150(5): 1314-20, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26318355

RESUMO

OBJECTIVE: The aim of this study was to compare outcomes in patients undergoing cardiac surgery who are aged 60 years or more or less than 60 years after implementation of a restrictive or a liberal transfusion strategy. METHODS: This is a substudy of the Transfusion Requirements After Cardiac Surgery (TRACS) randomized controlled trial. In this subgroup analysis, we separated patients into those aged 60 years or more (elderly) and those aged less than 60 years randomized to a restrictive or a liberal strategy of red blood cell transfusion. The primary outcome was a composite defined as a combination of 30-day all-cause mortality and severe morbidity. RESULTS: Of the 502 patients included in the Transfusion Requirements After Cardiac Surgery study, 260 (51.8%) were aged 60 years or more and 242 (48.2%) were aged less than 60 years and were included in this study. The primary end point occurred in 11.9% of patients in the liberal strategy group and 16.8% of patients in the restrictive strategy group (P = .254) for those aged 60 years or more and in 6.8% of patients in the liberal strategy group and 5.6% of patients in the restrictive strategy group for those aged less than 60 years (P = .714). However, in the older patients, cardiogenic shock was more frequent in patients in the restrictive transfusion group (12.8% vs 5.2%, P = .031). Thirty-day mortality, acute respiratory distress syndrome, and acute renal injury were similar in the restrictive and liberal transfusion groups in both age groups. CONCLUSIONS: Although there was no difference between groups regarding the primary outcome, a restrictive transfusion strategy may result in an increased rate of cardiogenic shock in elderly patients undergoing cardiac surgery compared with a more liberal strategy. Cardiovascular risk of anemia may be more harmful than the risk of blood transfusion in older patients.


Assuntos
Anemia/terapia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Transfusão de Eritrócitos/métodos , Choque Cardiogênico/prevenção & controle , Adulto , Fatores Etários , Idoso , Anemia/sangue , Anemia/diagnóstico , Anemia/mortalidade , Biomarcadores/sangue , Brasil , Procedimentos Cirúrgicos Cardíacos/mortalidade , Transfusão de Eritrócitos/efeitos adversos , Transfusão de Eritrócitos/mortalidade , Hematócrito , Hemoglobinas/metabolismo , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Choque Cardiogênico/diagnóstico , Choque Cardiogênico/etiologia , Choque Cardiogênico/mortalidade , Fatores de Tempo , Resultado do Tratamento
12.
Anesthesiology ; 122(1): 29-38, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25401417

RESUMO

BACKGROUND: Several studies have indicated that a restrictive erythrocyte transfusion strategy is as safe as a liberal one in critically ill patients, but there is no clear evidence to support the superiority of any perioperative transfusion strategy in patients with cancer. METHODS: In a randomized, controlled, parallel-group, double-blind (patients and outcome assessors) superiority trial in the intensive care unit of a tertiary oncology hospital, the authors evaluated whether a restrictive strategy of erythrocyte transfusion (transfusion when hemoglobin concentration <7 g/dl) was superior to a liberal one (transfusion when hemoglobin concentration <9 g/dl) for reducing mortality and severe clinical complications among patients having major cancer surgery. All adult patients with cancer having major abdominal surgery who required postoperative intensive care were included and randomly allocated to treatment with the liberal or the restrictive erythrocyte transfusion strategy. The primary outcome was a composite endpoint of mortality and morbidity. RESULTS: A total of 198 patients were included as follows: 101 in the restrictive group and 97 in the liberal group. The primary composite endpoint occurred in 19.6% (95% CI, 12.9 to 28.6%) of patients in the liberal-strategy group and in 35.6% (27.0 to 45.4%) of patients in the restrictive-strategy group (P = 0.012). Compared with the restrictive strategy, the liberal transfusion strategy was associated with an absolute risk reduction for the composite outcome of 16% (3.8 to 28.2%) and a number needed to treat of 6.2 (3.5 to 26.5). CONCLUSION: A liberal erythrocyte transfusion strategy with a hemoglobin trigger of 9 g/dl was associated with fewer major postoperative complications in patients having major cancer surgery compared with a restrictive strategy.


Assuntos
Neoplasias Abdominais/cirurgia , Transfusão de Eritrócitos/métodos , Transfusão de Eritrócitos/estatística & dados numéricos , Brasil/epidemiologia , Método Duplo-Cego , Feminino , Seguimentos , Hemoglobinas/análise , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Risco
14.
J Thorac Cardiovasc Surg ; 148(4): 1647-55, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24951020

RESUMO

OBJECTIVES: Acute acquired hypofibrinogenemia in children undergoing cardiac surgery is a major concern because it often results in perioperative bleeding and high rates of allogeneic blood transfusion. Fibrinogen concentrate has been proposed as an alternative to cryoprecipitate (the gold standard therapy), with minimal infectious and immunologic risks. Our objective was to investigate the efficacy and safety of fibrinogen concentrate in children undergoing cardiac surgery. METHODS: In this randomized pilot study, patients were allocated to receive fibrinogen concentrate (60 mg/kg) or cryoprecipitate (10 mL/kg) if bleeding was associated with fibrinogen levels<1 g/dL after cardiopulmonary bypass weaning. The primary outcome was postoperative blood losses during the 48 hours after surgery. RESULTS: A total of 63 patients were included in the study, 30 in the fibrinogen concentrate group and 33 in the cryoprecipitate group. The median 48-hour blood loss was not significantly different between the 2 groups (320 mL [interquartile range, 157-750] vs 410 mL [interquartile range, 215-510], respectively; P=.672). After treatment, plasma fibrinogen concentration increased similarly following administration of both products. There were no differences in allogeneic blood transfusion after intervention treatment. CONCLUSIONS: A large trial comparing fibrinogen concentrate and cryoprecipitate in the management of children with acute acquired hypofibrinogenemia during heart surgery is feasible. The preliminary results of our study showed that the use of fibrinogen concentrate was as efficient and safe as cryoprecipitate in the management of bleeding children undergoing cardiac surgery.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Fator VIII/uso terapêutico , Fibrinogênio/uso terapêutico , Testes de Coagulação Sanguínea , Perda Sanguínea Cirúrgica , Brasil , Ponte Cardiopulmonar , Criança , Pré-Escolar , Transfusão de Eritrócitos/estatística & dados numéricos , Feminino , Humanos , Lactente , Masculino , Projetos Piloto , Estudos Prospectivos , Resultado do Tratamento
15.
Crit Care Med ; 42(7): 1714-21, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24717456

RESUMO

OBJECTIVE: The developmental pipeline for novel therapeutics to treat sepsis has diminished to a trickle compared to previous years of sepsis research. While enormous strides have been made in understanding the basic molecular mechanisms that underlie the pathophysiology of sepsis, a long list of novel agents have now been tested in clinical trials without a single immunomodulating therapy showing consistent benefit. The only antisepsis agent to successfully complete a phase III clinical trial was human recumbent activated protein C. This drug was taken off the market after a follow-up placebo-controlled trial (human recombinant activated Protein C Worldwide Evaluation of Severe Sepsis and septic Shock [PROWESS SHOCK]) failed to replicate the favorable results of the initial registration trial performed ten years earlier. We must critically reevaluate our basic approach to the preclinical and clinical evaluation of new sepsis therapies. DATA SOURCES: We selected the major clinical studies that investigated interventional trials with novel therapies to treat sepsis over the last 30 years. STUDY SELECTION: Phase II and phase III trials investigating new treatments for sepsis and editorials and critiques of these studies. DATA EXTRACTION: Selected manuscripts and clinical study reports were analyzed from sepsis trials. Specific shortcomings and potential pit falls in preclinical evaluation and clinical study design and analysis were reviewed and synthesized. DATA SYNTHESIS: After review and discussion, a series of 12 recommendations were generated with suggestions to guide future studies with new treatments for sepsis. CONCLUSIONS: We need to improve our ability to define appropriate molecular targets for preclinical development and develop better methods to determine the clinical value of novel sepsis agents. Clinical trials must have realistic sample sizes and meaningful endpoints. Biomarker-driven studies should be considered to categorize specific "at risk" populations most likely to benefit from a new treatment. Innovations in clinical trial design such as parallel crossover design, alternative endpoints, or adaptive trials should be pursued to improve the outlook for future interventional trials in sepsis.


Assuntos
Ensaios Clínicos Fase II como Assunto/métodos , Ensaios Clínicos Fase III como Assunto/métodos , Fibrinolíticos/uso terapêutico , Proteína C/uso terapêutico , Sepse/tratamento farmacológico , Biomarcadores , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Proteínas Recombinantes/uso terapêutico , Projetos de Pesquisa
16.
Rev. bras. ter. intensiva ; 25(4): 345-347, Oct-Dec/2013. graf
Artigo em Português | LILACS | ID: lil-701404

RESUMO

Descrevemos o caso de um paciente com hematoma intramural e trombo flutuante após ressuscitação cardiopulmonar. Esse homem, de 92 anos de idade, teve uma parada cardíaca causada por fibrilação atrial e testemunhas iniciaram imediatamente manobras manuais de ressuscitação cardiopulmonar. Ao ser admitido no hospital, o paciente apresentava-se em choque cardiogênico, sendo, então, imediatamente submetido a ecocardiografia transesofágica. Além de uma parede anterior acinética, o exame da aorta torácica descendente mostrou um hematoma intramural e um trombo intra-aórtico flutuante a uma distância de 40cm do arco dental. Não havia dissecção da aorta. O trombo foi atribuído à compressão aórtica durante a ressuscitação cardiopulmonar. Embora o trombo aórtico e o hematoma intramural não tenham se associado a qualquer complicação nesse paciente, a inserção de um balão intra-aórtico poderia ter levado a uma ruptura da aorta ou a eventos embólicos. Recomenda-se a realização de ecocardiografia transesofágica, quando disponível, antes da inserção de um balão intra-aórtico de contrapulsação em pacientes submetidos à ressuscitação cardiopulmonar.


We describe the case of a patient with an intramural hematoma and floating thrombus after cardiopulmonary resuscitation. The 92-year old man had a cardiac arrest due to ventricular fibrillation and witnesses immediately initiated manual cardiopulmonary resuscitation. Transesophageal echocardiography was performed immediately on hospital admission because the patient was in cardiogenic shock. In addition to an akinetic anterior wall, examination of the descending thoracic aorta demonstrated an intramural hematoma and a floating intra-aortic thrombus at a distance of 40cm from the dental arch. There was no aortic dissection. The thrombus was attributed to aortic compression during cardiopulmonary resuscitation. Although the aortic thrombus and intramural hematoma were not associated with any complications in this patient, insertion of an intra-aortic balloon may have led to aortic rupture or embolic events. Transesophageal echocardiography should be performed, when available, prior to insertion of an intra-aortic balloon for counterpulsation in patients who have undergone cardiopulmonary resuscitation.


Assuntos
Idoso de 80 Anos ou mais , Humanos , Masculino , Doenças da Aorta/etiologia , Reanimação Cardiopulmonar/efeitos adversos , Hematoma/etiologia , Trombose/etiologia , Aorta Torácica/patologia , Doenças da Aorta/patologia , Reanimação Cardiopulmonar/métodos , Ecocardiografia Transesofagiana/métodos , Parada Cardíaca/etiologia , Parada Cardíaca/terapia , Hematoma/patologia , Trombose/patologia , Fibrilação Ventricular/complicações
17.
J Thorac Cardiovasc Surg ; 146(2): 455-60, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23507124

RESUMO

OBJECTIVE: Although hyperlactatemia after cardiac surgery is common, the implications of raised levels remain controversial. The aim of this study was to evaluate whether high lactate levels after cardiac surgery are predictors of major complications including mortality. PATIENTS AND METHODS: This was a substudy of TRACS (Transfusion Requirements After Cardiac Surgery), which was designed as a prospective, randomized, controlled trial evaluating the effects of a transfusion strategy on morbidity and mortality. RESULTS: Of the 502 patients enrolled, 52 (10%) had at least 1 major complication. Patients with complications were older, had a higher EuroSCORE, lower left ventricular ejection fraction, lower preoperative hemoglobin, a higher prevalence of renal disease, and received more blood transfusions than the group without complications. Lactate levels were higher in the group with complications at the end of surgery (3.6 mmol/L [2.8-5.1] vs 3.3 mmol/L [2.2-4.8]; P = .018), immediately after intensive care unit (ICU) admission (0 hour) (4.4 mmol/L [3.1-8.4] vs 4 mmol/L [2.6-6.4]; P = .048); 6 hours (4 mmol/L [2.7-5.8] vs 2.6 mmol/L [2-3.6], P < .001), and 12 hours after admission (2.3 mmol/L [1.8-3.2] vs 1.7 mmol/L [1.3-2]; P < .001). In a multivariate model, higher age (odds ratio [OR], 1.048, 95% confidence interval [CI], 1.011-1.086; P = .010), left ventricular ejection fraction (LVEF) lower than 40% (OR, 3.03; 95% CI, 1.200-7.510; P = .019 compared with LVEF of 40%-59%; OR, 3.571; 95% CI, 1.503-8.196; P = .004 compared with LVEF higher than 60%), higher EuroSCORE (OR, 1.138; 95% CI; 1.007-1.285; P = .038), red blood cell transfusion (OR, 1.230; 95% CI, 1.086-1.393; P = .001), and lactate levels 6 hours after ICU admission (OR, 3.28, 95% CI; 1.61-6.69; P = .001) are predictors of major complications. CONCLUSIONS: Hyperlactatemia 6 hours after ICU admission is an independent risk factor for worse outcomes in adult patients after cardiac surgery.


Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Ácido Láctico/sangue , Injúria Renal Aguda/sangue , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/terapia , Fatores Etários , Idoso , Biomarcadores/sangue , Brasil , Procedimentos Cirúrgicos Cardíacos/mortalidade , Distribuição de Qui-Quadrado , Transfusão de Eritrócitos/efeitos adversos , Transfusão de Eritrócitos/mortalidade , Feminino , Humanos , Unidades de Terapia Intensiva , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Estudos Prospectivos , Terapia de Substituição Renal , Síndrome do Desconforto Respiratório/sangue , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/mortalidade , Medição de Risco , Fatores de Risco , Choque Cardiogênico/sangue , Choque Cardiogênico/etiologia , Choque Cardiogênico/mortalidade , Volume Sistólico , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima , Função Ventricular Esquerda
18.
Rev Bras Ter Intensiva ; 25(4): 345-7, 2013.
Artigo em Inglês, Português | MEDLINE | ID: mdl-24553517

RESUMO

We describe the case of a patient with an intramural hematoma and floating thrombus after cardiopulmonary resuscitation. The 92-year old man had a cardiac arrest due to ventricular fibrillation and witnesses immediately initiated manual cardiopulmonary resuscitation. Transesophageal echocardiography was performed immediately on hospital admission because the patient was in cardiogenic shock. In addition to an akinetic anterior wall, examination of the descending thoracic aorta demonstrated an intramural hematoma and a floating intra-aortic thrombus at a distance of 40cm from the dental arch. There was no aortic dissection. The thrombus was attributed to aortic compression during cardiopulmonary resuscitation. Although the aortic thrombus and intramural hematoma were not associated with any complications in this patient, insertion of an intra-aortic balloon may have led to aortic rupture or embolic events. Transesophageal echocardiography should be performed, when available, prior to insertion of an intra-aortic balloon for counterpulsation in patients who have undergone cardiopulmonary resuscitation.


Assuntos
Doenças da Aorta/etiologia , Reanimação Cardiopulmonar/efeitos adversos , Hematoma/etiologia , Trombose/etiologia , Idoso de 80 Anos ou mais , Aorta Torácica/patologia , Doenças da Aorta/patologia , Reanimação Cardiopulmonar/métodos , Ecocardiografia Transesofagiana/métodos , Parada Cardíaca/etiologia , Parada Cardíaca/terapia , Hematoma/patologia , Humanos , Masculino , Trombose/patologia , Fibrilação Ventricular/complicações
19.
Rev. bras. ter. intensiva ; 24(2): 143-150, abr.-jun. 2012. tab
Artigo em Português | LILACS | ID: lil-644644

RESUMO

OBJETIVO: Demonstrar as taxas de prevalência de infecção em unidades de terapia intensiva brasileiras e mortalidade atribuída pela análise dos dados ­obtidos pelo estudo Extended Prevalence of Infection in Intensive Care (EPIC II). MÉTODOS: O EPIC II é um estudo multicêntrico, internacional, prospectivo, de prevalência de infecção em UTIs, realizado em apenas um dia. Ele descreve as características demográficas, fisiológicas, bacteriológicas, terapêuticas, acompanhamento até o 60º dia, a prevalência de infecção, a taxa de mortalidade de todos os pacientes internados nas unidades de terapia intensiva participantes entre zero hora e meia noite do dia 8 de maio de 2007. Um total de 14.414 pacientes foram inlcuídos no estudo original, sendo que destes, 1.235 eram brasileiros provenientes de 90 unidades de terapia intensiva do país, que representaram o foco do estudo. RESULTADOS: Dos 1.235 pacientes, 61,6% apresentavam infecção no dia do estudo, sendo que o pulmão era o principal sítio de infecção (71,2%). Metade dos pacientes apresentava cultura positiva, sendo que o predomínio foi de bacilos Gram-negativos (72%). No dia do estudo, o Sequential Organ Failure Assessment (SOFA) mediano foi 5 (3-8) e o Simplified Acute Physiology Score II (SAPS II) mediano 36 (26-47). Os doentes infectados apresentaram escore SOFA significativamente maior do que os não infectados, 6 (4-9) e 3 (2-6), respectivamente. A taxa de mortalidade global na unidade de terapia intensiva foi 28,4%, sendo de 37,6% em infectados e 13,2% em não infectados (p<0,001). Da mesma forma, a taxa de mortalidade hospitalar foi maior em pacientes infectados (44,2% versus 17,7%), tendo como taxa global 34,2% (p<0,001). Na análise multivariada, os principais fatores relacioanados ao desenvolvimento de infecção foram cirurgia de emergência (OR: 2,89, IC95%=1,72-4,86; p<0,001), ventilação mecânica (OR=2,06, IC95%=1,5-2,82; p<0,001), SAPS II - por ponto obtido (OR=1,04, IC95%=1,03-1,06; p<0,001) e para mortalidade foram insuficiência cardíaca congestiva (ICC) Classe Funcional III/IV (OR=3,0, IC95%=1,51-5,98; p<0,01), diabetes mellitus (OR=0,48, IC95%=0,25-0,95; p<0,03), cirrose (OR=4,62, IC95%=1,47-14,5; p<0,01), gênero masculino (OR=0,68, IC95%=0,46-1,0; p<0,05), ventilação mecânica (OR=1,87, IC95%=1,19-2,95; p<0,01), hemodiálise (OR 1,98, IC95%=1,05-3,75; p<0,03), SAPS II - por ponto obtido (OR=1,08, IC95%=1,06-1,10; p<0,001). CONCLUSÃO: Taxas de prevalência de infecção e de mortalidade mais elevadas que outros relatos foram observadas na presente amostra. Há clara relação entre infecção e mortalidade.


OBJECTIVE: To determine the prevalence of infections in Brazilian intensive care units and the associated mortality by analyzing the data obtained in the Extended Prevalence of Infection in Intensive Care (EPIC II) study. METHODS: EPIC II was a multicenter, international, cross-sectional prospective study of infection prevalence. It described the demographic, physiological, bacteriological, and therapeutic characteristics, outcome up to the 60th day, prevalence of infection, and mortality of all the patients admitted to the participating ICUs between zero hour and midnight on May 8, 2007. A total of 14,414 patients were included in the original study. Of these 14,414 patients, 1,235 were Brazilian and were hospitalized in 90 Brazilian ICUs. They represent the focus of this study. RESULTS: Among these 1,235 Brazilian patients, 61,6% had an infection on the day of the trial, and the lungs were the main site of infection (71.2%). Half of the patients had positive cultures, predominantly gram-negative bacilli (72%). On the day of the study, the median SOFA score was 5 (3-8) and the median SAPS II score was 36 (26-47). The infected patients had SOFA scores significantly higher than those of the non-infected patients 6 (4-9) and 3 (2-6), respectively). The overall ICU mortality rate was 28.4%: 37.6% in the infected patients, and 13.2% in the non-infected patients (p<0.001). Similarly, the in-hospital mortality rate was 34.2%, with a higher rate in the infected than in the non-infected patients (44.2% vs. 17.7%) (p<0.001). In the multivariate analysis, the main factors associated with infection incidence were emergency surgery (OR 2.89, 95%CI [1.72-4.86], p<0.001), mechanical ventilation (OR 2.06, 95% CI [1.5-2.82], p<0.001), and the SAPS II score (OR 1.04, 95% CI [1.03-1.06], p<0.001). The main factors related to mortality were ICC functional class III/ IV (OR 3.0, 95% CI [1.51-5.98], p<0.01), diabetes mellitus (OR 0.48, 95% CI [0.25-0.95], p<0.03), cirrhosis (OR 4.62, 95% CI [1.47-14,5], p<0.01), male gender (OR 0.68, 95% CI [0.46-1.0], p<0.05), mechanical ventilation (OR 1.87, 95% CI [1.19-2.95], p<0.01), hemodialysis (OR 1.98, 95% CI [1.05-3.75], p<0.03), and the SAPS II score (OR 1.08, 95% CI [1.06-1.10], p<0.001). CONCLUSION: The present study revealed a higher prevalence of infections in Brazilian ICUs than has been previously reported. There was a clear association between infection and mortality.

20.
Intensive Care Med ; 38(3): 404-12, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22222566

RESUMO

PURPOSE: This study investigated the association between physician education in EOL and variability in EOL practice, as well as the differences between beliefs and practices regarding EOL in the ICU. METHODS: Physicians from 11 ICUs at a university hospital completed a survey presenting a patient in a vegetative state with no family or advance directives. Questions addressed approaches to EOL care, as well physicians' personal, professional and EOL educational characteristics. RESULTS: The response rate was 89%, with 105 questionnaires analyzed. Mean age was 38 ± 8 years, with a mean of 14 ± 7 years since graduation. Physicians who did not apply do-not-resuscitate (DNR) orders were less likely to have attended EOL classes than those who applied written DNR orders [0/7 vs. 31/47, OR = 0.549 (0.356-0.848), P = 0.001]. Physicians who involved nurses in the decision-making process were more likely to be ICU specialists [17/22 vs. 46/83, OR = 4.1959 (1.271-13.845), P = 0.013] than physicians who made such decisions among themselves or referred to ethical or judicial committees. Physicians who would apply "full code" had less often read about EOL [3/22 vs. 11/20, OR = 0.0939 (0.012-0.710), P = 0.012] and had less interest in discussing EOL [17/22 vs. 20/20, OR = 0.210 (0.122-0.361), P < 0.001], than physicians who would withdraw life-sustaining therapies. Forty-four percent of respondents would not do what they believed was best for their patient, with 98% of them believing a less aggressive attitude preferable. Legal concerns were the leading cause for this dichotomy. CONCLUSIONS: Physician education about EOL is associated with variability in EOL decisions in the ICU. Moreover, actual practice may differ from what physicians believe is best for the patient.


Assuntos
Atitude do Pessoal de Saúde , Cuidados Críticos/normas , Unidades de Terapia Intensiva/normas , Assistência Terminal/normas , Adulto , Análise de Variância , Brasil , Cuidados Críticos/ética , Cuidados Críticos/métodos , Tomada de Decisões , Educação Médica/normas , Educação Médica/estatística & dados numéricos , Comitês de Ética Clínica , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Relações Médico-Enfermeiro , Padrões de Prática Médica , Ordens quanto à Conduta (Ética Médica)/ética , Assistência Terminal/ética , Assistência Terminal/métodos , Recursos Humanos
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