RESUMEN
BACKGROUND: No consensus exists regarding the definition of ventilator-associated pneumonia (VAP). Even within a single institution, inconsistent diagnostic criteria result in conflicting rates of VAP. As a Level 1 trauma center participating in the Trauma Quality Improvement Project (TQIP) and the National Healthcare Safety Network (NHSN), our institution showed inconsistencies in VAP rates depending on which criteria was applied. The purpose of this study was to compare VAP definitions, defined by culture-based criteria, National Trauma Data Bank (NTDB) and NHSN, using incidence in trauma patients. METHODS: A retrospective chart review of consecutive trauma patients who were diagnosed with VAP and met pre-determined inclusion and exclusion criteria admitted to our rural, 861-bed, Level 1 trauma and tertiary care center between January 2008 and December 2011 was performed. These patients were identified from the National Trauma Registry of the American College of Surgeons (NTRACS) database and an in-house infection control database. Ventilator-associated pneumonia diagnosis criteria defined by the U.S. Center for Disease Control and Prevention (used by the NHSN), the NTDB, and our institutional, culture-based criteria gold standard were compared among patients. RESULTS: Two hundred seventy-nine patients were diagnosed with VAP (25.4% met NHSN criteria, 88.2% met NTDB, and 76.3% met culture-based criteria). Only 58 (20.1%) patients met all three criteria. When NHSN criteria were compared with culture-based criteria, NHSN showed a high specificity (92.5%) and low sensitivity (28.2%). The positive predictive value (PPV) was 84.5%, but the negative predictive value (NPV) was 47.1%. The agreement between the NHSN and the culture-based criteria was poor (κ = 0.18). Conversely, the NTDB showed a lower specificity (57.8%), but greater sensitivity (86.4%) compared with culture-based criteria. The PPV and NPV were both 74% and the two criteria showed fair agreement (κ = 0.41). CONCLUSIONS: The lack of standard diagnostic criteria for VAP resulted in variable reporting to different agencies. Emphasis on establishing a consensus VAP definition should be undertaken.
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Neumonía Asociada al Ventilador/diagnóstico , Heridas y Lesiones/complicaciones , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bases de Datos Factuales , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Neumonía Asociada al Ventilador/epidemiología , Neumonía Asociada al Ventilador/etiología , Sistema de Registros , Estudios Retrospectivos , Sensibilidad y Especificidad , Centros Traumatológicos , Estados Unidos , Adulto JovenRESUMEN
BACKGROUND: Concomitant lung/brain traumatic injury results in significant morbidity and mortality. Lung protective ventilation (Acute Respiratory Distress Syndrome Network [ARDSNet]) has become the standard for managing adult respiratory distress syndrome; however, the resulting permissive hypercapnea may compound traumatic brain injury. Airway pressure release ventilation (APRV) offers an alternative strategy for the management of this patient population. APRV was hypothesized to retard the progression of acute lung/brain injury to a degree greater than ARDSNet in a swine model. METHODS: Yorkshire swine were randomized to ARDSNet, APRV, or sham. Ventilatory settings and pulmonary parameters, vitals, blood gases, quantitative histopathology, and cerebral microdialysis were compared between groups using χ2, Fisher's exact, Student's t test, Wilcoxon rank-sum, and mixed-effects repeated-measures modeling. RESULTS: Twenty-two swine (17 male, 5 female), weighing a mean (SD) of 25 (6.0) kg, were randomized to APRV (n = 9), ARDSNet (n = 12), or sham (n = 1). PaO2/FIO2 ratio dropped significantly, while intracranial pressure increased significantly for all three groups immediately following lung and brain injury. Over time, peak inspiratory pressure, mean airway pressure, and PaO2/FIO2 ratio significantly increased, while total respiratory rate significantly decreased within the APRV group compared with the ARDSNet group. Histopathology did not show significant differences between groups in overall brain or lung tissue injury; however, cerebral microdialysis trends suggested increased ischemia within the APRV group compared with ARDSNet over time. CONCLUSION: Previous studies have not evaluated the effects of APRV in this population. While our macroscopic parameters and histopathology did not observe a significant difference between groups, microdialysis data suggest a trend toward increased cerebral ischemia associated with APRV over time. Additional and future studies should focus on extending the time interval for observation to further delineate differences between groups.
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Lesión Pulmonar Aguda/prevención & control , Lesiones Encefálicas/prevención & control , Presión de las Vías Aéreas Positiva Contínua/métodos , Lesión Pulmonar Aguda/complicaciones , Lesión Pulmonar Aguda/patología , Lesión Pulmonar Aguda/fisiopatología , Animales , Lesiones Encefálicas/complicaciones , Lesiones Encefálicas/patología , Lesiones Encefálicas/fisiopatología , Hemodinámica/fisiología , Rendimiento Pulmonar/fisiología , Microdiálisis , Proyectos Piloto , Distribución Aleatoria , Pruebas de Función Respiratoria , PorcinosRESUMEN
BACKGROUND: Helicopter emergency medical service (HEMS) transport of trauma patients is costly and of unproven benefit. Recent retrospective studies fail to control for crew expertise and therefore compare highly trained advance life support with less-trained basic life support crews. The purpose of our study was to compare HEMS with ground, interfacility transport while controlling for crew training. We hypothesized that patients transported by HEMS would experience shorter interhospital transport time and reduced mortality. METHODS: Our National Trauma Registry of the American College of Surgeons database was retrospectively queried to identify consecutive interfacility, hospital transfers (January 1, 2008, to November 1, 2012) to our Level I trauma center. Transfers were stratified by transportation vehicle (i.e., HEMS vs. ground transport). Cohorts were compared across standard demographic and clinical variables using univariate analysis. Multivariate logistic regression was performed to determine the association of these variables with mortality. RESULTS: The HEMS (n = 2,190) and ground (n = 223) cohorts were well matched overall, with no significant differences for demographics, injury severity, physiology, hospital length of stay, or complications. Median (interquartile range) time to definitive care was significantly lower for HEMS (150 [114] minutes vs. 255 [157] minutes, p < 0.001), without change in mortality (9.0% vs. 8.1%, p = 0.71). Multivariate logistic regression did not identify an association between transport mode and mortality. CONCLUSION: Despite faster interfacility transport times, HEMS offered no mortality benefit compared with ground when crew expertise was controlled for, contradicting recent large, retrospective National Trauma Data Bank studies. Our study may represent the best approximation of a prospective study by focusing on patients deemed worthy of HEMS by referring providers. Although HEMS may seem intuitively beneficial for time-dependent injuries, larger studies with a similar methodology are warranted to justify the cost and risk of HEMS and identify subsets of patients who may benefit. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III.
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Ambulancias , Cuidados para Prolongación de la Vida/métodos , Transferencia de Pacientes/métodos , Adulto , Ambulancias Aéreas/normas , Femenino , Mortalidad Hospitalaria , Humanos , Cuidados para Prolongación de la Vida/normas , Modelos Logísticos , Masculino , Transferencia de Pacientes/normas , Estudios Retrospectivos , Centros Traumatológicos , Heridas y Lesiones/mortalidad , Heridas y Lesiones/terapiaRESUMEN
In glaucoma, retinal ganglion cells (RGCs) die by apoptosis, generally attributed to an elevated intraocular pressure (IOP). We now describe the impact of elevated IOP in the rat on expression of caspase 8 and caspase 9, initiators of the extrinsic and intrinsic caspase cascades, respectively. Activation of both caspases was demonstrated by the presence of cleaved forms of the caspases and the detection of cleaved Bid and PARP, downstream consequences of caspase activation. Surprisingly, the absolute level of procaspase 9 was also elevated after 10 days of increased IOP. To examine the cause of increased levels of the procaspase, we used laser capture microdissection to capture Fluorogold back-labeled RGCs and real-time polymerase chain reaction to measure mRNA changes of initiating caspases. The mRNA levels of both caspase 8 and caspase 9 were increased specifically in RGCs. These data suggest that elevated IOP activates a transcriptional up-regulation and activation of initiating caspases in RGCs and triggers apoptosis through both extrinsic and intrinsic caspase cascades.
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Caspasas/genética , Caspasas/metabolismo , Glaucoma/enzimología , Transcripción Genética , Animales , Caspasa 8 , Caspasa 9 , Recuento de Células , Activación Enzimática , Glaucoma/patología , Glaucoma/fisiopatología , Presión Intraocular , Poli(ADP-Ribosa) Polimerasas/metabolismo , ARN Mensajero/metabolismo , Ratas , Ratas Endogámicas BN , Retina/enzimología , Células Ganglionares de la Retina/patología , Regulación hacia ArribaRESUMEN
Retinal ganglion cells die by apoptosis after optic nerve crush. FK506 has been shown to be neuroprotective in this model but the mechanism(s) by which it exerts these actions remains unknown. We and others have shown that caspase 9 is cleaved in the retina in other injury models and we hypothesized that the neuroprotection observed with FK506 was mediated by interference with caspase 9 activation. The present study examined the cellular localization of caspase 9 cleavage after intraorbital optic nerve crush in rats, the time course of caspase 9 cleavage after optic nerve crush and the ability of orally administered FK506 to block caspase 9 cleavage after optic nerve crush. We show by immunohistochemistry that cleaved caspase 9 is present in retinal ganglion cells (identified by prior backlabelling) after optic nerve crush. Immunoblot analysis showed that caspase 9 cleavage is significantly elevated 5 and 8 days after optic nerve crush. We show that orally administered FK506 reaches the retina and is pharmacologically active in retinal tissue. Furthermore, the oral administration of FK506 5 mg kg(-1) day(-1) blocks the cleavage of caspase 9 at both time points. These data suggest that caspase 9 activation may play an important role in retinal ganglion cell death following optic nerve crush and that the neuroprotection seen with FK506 may be mediated by interfering with the activation of caspase 9.
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Inhibidores de Caspasas , Inmunosupresores/uso terapéutico , Traumatismos del Nervio Óptico/tratamiento farmacológico , Células Ganglionares de la Retina/enzimología , Tacrolimus/uso terapéutico , Animales , Western Blotting/métodos , Calcineurina/metabolismo , Caspasa 9 , Caspasas/análisis , Caspasas/metabolismo , Depresión Química , Activación Enzimática/efectos de los fármacos , Inmunohistoquímica/métodos , Masculino , Compresión Nerviosa , Traumatismos del Nervio Óptico/enzimología , Traumatismos del Nervio Óptico/metabolismo , Ratas , Ratas Endogámicas BN , Retina/metabolismo , Factores de TiempoRESUMEN
PURPOSE: We investigated retinal ganglion cell (RGC) death and activation of caspase 9 in rats with experimental glaucoma. METHODS: Elevated intraocular pressure (IOP) was induced in rats using the Morrison model. Surviving backlabeled RGC were counted and TUNEL staining detected apoptosis. Procaspase 9 expression and activated caspase 9 were studied by immunoblot and immunohistochemistry. RESULTS: IOP correlated with surviving RGC. TUNEL-positive RGC were observed in animals with elevated IOP. Procaspase 9 levels increased with IOP intensity. Cleaved caspase 9 was detected by immunoblot only in rats with peak IOP above 35 mm Hg for > or =6 days. Cleaved caspase 9 staining was seen only in the ganglion cell layer of retinas from rats with peak IOP > or =32 mm Hg. CONCLUSIONS: RGC loss is correlated with IOP in experimental glaucoma. These results support activation of caspase 9, the intrinsic caspase cascade, in RGC death in experimental glaucoma.