Asunto(s)
Transcriptoma/genética , Heridas no Penetrantes/genética , Heridas no Penetrantes/mortalidad , Biomarcadores/sangre , Femenino , Mortalidad Hospitalaria , Humanos , Puntaje de Gravedad del Traumatismo , Interleucina-6/sangre , Leucocitos/fisiología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Medición de Riesgo , Análisis de Supervivencia , Centros Traumatológicos , Heridas no Penetrantes/sangreRESUMEN
OBJECTIVE: To determine the incidence and risk factors of chronic critical illness after severe blunt trauma. DESIGN: Prospective observational cohort study (NCT01810328). SETTING: Two level-one trauma centers in the United States. PATIENTS: One hundred thirty-five adult blunt trauma patients with hemorrhagic shock who survived beyond 48 hours after injury. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Chronic critical illness was defined as an ICU stay lasting 14 days or more with evidence of persistent organ dysfunction. Three subjects (2%) died within the first 7 days, 107 (79%) exhibited rapid recovery and 25 (19%) progressed to chronic critical illness. Patients who developed chronic critical illness were older (55 vs 44-year-old; p = 0.01), had more severe shock (base deficit, -9.2 vs -5.5; p = 0.005), greater organ failure severity (Denver multiple organ failure score, 3.5 ± 2.4 vs 0.8 ± 1.1; p < 0.0001) and developed more infectious complications (84% vs 35%; p < 0.0001). Chronic critical illness patients were more likely to be discharged to a long-term care setting (56% vs 34%; p = 0.008) than to a rehabilitation facility/home. At 4 months, chronic critical illness patients had higher mortality (16.0% vs 1.9%; p < 0.05), with survivors scoring lower in general health measures (p < 0.005). Multivariate analysis revealed age greater than or equal to 55 years, systolic hypotension less than or equal to 70 mm Hg, transfusion greater than or equal to 5 units packed red blood cells within 24 hours, and Denver multiple organ failure score at 72 hours as independent predictors of chronic critical illness (area under the receiver operating curve, 0.87; 95% CI, 0.75-0.95). CONCLUSIONS: Although early mortality is low after severe trauma, chronic critical illness is a common trajectory in survivors and is associated with poor long-term outcomes. Advancing age, shock severity, and persistent organ dysfunction are predictive of chronic critical illness. Early identification may facilitate targeted interventions to change the trajectory of this morbid phenotype.
Asunto(s)
Enfermedad Crónica/epidemiología , Enfermedad Crítica/epidemiología , Unidades de Cuidados Intensivos/estadística & datos numéricos , Centros Traumatológicos/estadística & datos numéricos , Heridas no Penetrantes/epidemiología , Adulto , Factores de Edad , Anciano , Transfusión Sanguínea/estadística & datos numéricos , Enfermedad Crónica/mortalidad , Enfermedad Crítica/mortalidad , Infección Hospitalaria/epidemiología , Femenino , Humanos , Hipotensión/epidemiología , Puntaje de Gravedad del Traumatismo , Tiempo de Internación , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/epidemiología , Alta del Paciente , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Choque Hemorrágico/epidemiología , Heridas no Penetrantes/mortalidadRESUMEN
Gene expression analysis can be a powerful tool in predicting patient outcomes and identifying patients who may benefit from targeted therapies. However, isolating human blood polymorphonuclear cells (PMNs) for genomic analysis has been challenging. We used a novel microfluidic technique that isolates PMNs by capturing CD66b(+) cells and compared it with dextran-Ficoll gradient isolation. We also used microfluidic isolation techniques for blood and bronchoalveolar lavage (BAL) samples of patients with acute respiratory distress syndrome (ARDS) to evaluate PMN genomic alterations secondary to pulmonary sequestration. PMNs obtained from ex vivo lipopolysaccharide (LPS)-stimulated or -unstimulated whole blood from five healthy volunteers were isolated by either dextran-Ficoll gradient, microfluidics capture, or a combination of the two techniques. Blood and BAL fluid PMNs were also isolated using microfluidics from seven hospitalized patients with ARDS. Gene expression was inferred from extracted RNA using Affymetrix U133 Plus 2.0 GeneChips. All methods of PMN isolation produced similar quantities of high-quality RNA, when adjusted for recovered cell number. Unsupervised analysis and hierarchical clustering indicated that LPS stimulation was the primary factor affecting gene expression patterns among all ex vivo samples. Patterns of gene expression from blood and BAL PMNs differed significantly from each other in the patients with ARDS. Isolation of PMNs by microfluidics can be applied to both blood and BAL specimens from critically ill, hospitalized patients. Unique genomic expression patterns are obtained from the blood and BAL fluid of critically ill patients with ARDS, and these differ significantly from genomic patterns seen after ex vivo LPS stimulation.