RESUMO
OBJECTIVES: To investigate the safety of percutaneous dilatational tracheostomy in severe respiratory failure patients during veno-venous extracorporeal membrane oxygenation support. DESIGN: A single-center, retrospective, observational cohort study. SETTING: Tertiary referral severe respiratory failure center, university teaching hospital. PATIENTS: Severe respiratory failure patients consecutively admitted and supported with veno-venous extracorporeal membrane oxygenation between January 2010 and December 2015. INTERVENTION: A bronchoscopy-guided percutaneous dilatational tracheostomy was performed in all cases. MEASUREMENTS AND MAIN RESULTS: Sixty-five veno-venous extracorporeal membrane oxygenation patients (median [interquartile range] age, 47 yr [interquartile range, 35-59 yr]; 39 males; Acute Physiology and Chronic Health Evaluation-II score, 18 [interquartile range, 17-22] Sequential Organ Failure Assessment score, 10 [interquartile range, 7-16]) underwent percutaneous dilatational tracheostomy. Ten patients (15%) developed one or more major complications. Of these, seven (11%) had major bleeding, and three of these also required circuit change due to extracorporeal membrane oxygenation circuit dysfunction. Two more patients (3.1%) presented with isolated extracorporeal membrane oxygenation circuit dysfunction requiring circuit change, and one developed bilateral pneumothoraces (1.5%) requiring intercostal drain insertion. Patients who developed complications had significantly lower extracorporeal membrane oxygenation postoxygenator PO2 prior to percutaneous dilatational tracheostomy (45.8 kPa [interquartile range, 36.9-56.5 kPa] vs 57.9 kPa [interquartile range, 45.1-64.2 kPa]; p = 0.019]. On multivariate analysis, including demographic, clinical, biochemical, hematologic variables, and extracorporeal membrane oxygenation circuit functional variables, extracorporeal membrane oxygenation postoxygenator PO2 was the only independent variable associated with major complications following percutaneous dilatational tracheostomy (beta = -0.09; odds ratio, 0.9; 95% CI, 0.84-0.99; p = 0.03). CONCLUSIONS: Percutaneous dilatational tracheostomy is associated with a considerable complication rate in veno-venous extracorporeal membrane oxygenation patients. Preprocedure circuit performance as indicated by extracorporeal membrane oxygenation postoxygenator PO2 is an independent predictor of major complications following percutaneous dilatational tracheostomy.
Assuntos
Oxigenação por Membrana Extracorpórea/métodos , Insuficiência Respiratória/terapia , Traqueostomia , Doença Aguda , Adulto , Oxigenação por Membrana Extracorpórea/efeitos adversos , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Traqueostomia/efeitos adversos , Traqueostomia/métodosRESUMO
Middle East Respiratory Syndrome (MERS) is a highly lethal pulmonary infection caused by a previously unidentified coronavirus (CoV), likely transmitted to humans by infected camels. There is no licensed vaccine or antiviral for MERS, therefore new prophylactic and therapeutic strategies to combat human infections are needed. In this study, we describe, for the first time, to our knowledge, the isolation of a potent MERS-CoV-neutralizing antibody from memory B cells of an infected individual. The antibody, named LCA60, binds to a novel site on the spike protein and potently neutralizes infection of multiple MERS-CoV isolates by interfering with the binding to the cellular receptor CD26. Importantly, using mice transduced with adenovirus expressing human CD26 and infected with MERS-CoV, we show that LCA60 can effectively protect in both prophylactic and postexposure settings. This antibody can be used for prophylaxis, for postexposure prophylaxis of individuals at risk, or for the treatment of human cases of MERS-CoV infection. The fact that it took only 4 mo from the initial screening of B cells derived from a convalescent patient for the development of a stable chinese hamster ovary (CHO) cell line producing neutralizing antibodies at more than 5 g/L provides an example of a rapid pathway toward the generation of effective antiviral therapies against emerging viruses.
Assuntos
Anticorpos Monoclonais/imunologia , Memória Imunológica , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Sequência de Aminoácidos , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Linfócitos B/imunologia , Sítios de Ligação , Células CHO , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Cricetinae , Cricetulus , Dipeptidil Peptidase 4/química , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Conformação Molecular , Dados de Sequência Molecular , Mutação , Ligação Proteica , Homologia de Sequência de Aminoácidos , Glicoproteína da Espícula de Coronavírus/química , Vacinas ViraisRESUMO
OBJECTIVES: For patients supported with veno-venous extracorporeal membrane oxygenation, the occurrence of intracranial hemorrhage is associated with a high mortality. It is unclear whether intracranial hemorrhage is a consequence of the extracorporeal intervention or of the underlying severe respiratory pathology. In a cohort of patients transferred to a regional severe respiratory failure center that routinely employs admission brain imaging, we sought 1) the prevalence of intracranial hemorrhage; 2) survival and neurologic outcomes; and 3) factors associated with intracranial hemorrhage. DESIGN: A single-center, retrospective, observational cohort study. SETTING: Tertiary referral severe respiratory failure center, university teaching hospital. PATIENTS: Patients admitted between December 2011 and February 2016. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Three hundred forty-two patients were identified: 250 managed with extracorporeal support and 92 managed using conventional ventilation. The prevalence of intracranial hemorrhage was 16.4% in extracorporeal membrane oxygenation patients and 7.6% in conventionally managed patients (p = 0.04). Multivariate analysis revealed factors independently associated with intracranial hemorrhage to be duration of ventilation (d) (odds ratio, 1.13 [95% CI, 1.03-1.23]; p = 0.011) and admission fibrinogen (g/L) (odds ratio, 0.73 [0.57-0.91]; p = 0.009); extracorporeal membrane oxygenation was not an independent risk factor (odds ratio, 3.29 [0.96-15.99]; p = 0.088). In patients who received veno-venous extracorporeal membrane oxygenation, there was no significant difference in 6-month survival between patients with and without intracranial hemorrhage (68.3% vs 76.0%; p = 0.350). Good neurologic function was observed in 92%. CONCLUSIONS: We report a higher prevalence of intracranial hemorrhage than has previously been described with high level of neurologically intact survival. Duration of mechanical ventilation and admission fibrinogen, but not exposure to extracorporeal support, are independently associated with intracranial hemorrhage.