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Namas R.A.,McGowan Institute for Regenerative Medicine | Namas R.,Michigan State University | Mi Q.,McGowan Institute for Regenerative Medicine | Mi Q.,Michigan State University | And 11 more authors.
Molecular Medicine | Year: 2012

Improper compartmentalization of the inflammatory response leads to systemic inflammation in sepsis. Hemoadsorption (HA) is an emerging approach to modulate sepsis-induced inflammation. We sought to define the effects of HA on inflammatory compartmentalization in Escherichia coli-induced fibrin peritonitis in rats. Hypothesis: HA both reprograms and recompartmentalizes inflammation in sepsis. Sprague Dawley male rats were subjected to E. coli peritonitis and, after 24 h, were randomized to HA or sham treatment (sepsis alone). Venous blood samples collected at 0, 1, 3 and 6 h (that is, 24-30 h of total experimental sepsis), and peritoneal samples collected at 0 and 6 h, were assayed for 14 cytokines along with NO2-/NO3-. Bacterial counts were assessed in the peritoneal fluid at 0 and 6 h. Plasma tumor necrosis factor (TNF)-α, interleukin (IL)-6, CXCL-1, and CCL2 were significantly reduced in HA versus sham. Principal component analysis (PCA) suggested that inflammation in sham was driven by IL-6 and TNF-α, whereas HA-associated inflammation was driven primarily by TNF-α, CXCL-1, IL-10 and CCL2. Whereas peritoneal bacterial counts, plasma aspartate transaminase levels and peritoneal IL-5, IL-6, IL-18, interferon (IFN)-γ and NO2-/NO3- were significantly lower, both CXCL-1 and CCL2 as well as the peritoneal-to-plasma ratios of TNF-α, CXCL-1 and CCL2 were significantly higher in HA versus sham, suggesting that HA-induced inflammatory recompartmentalization leads to the different inflammatory drivers discerned in part by PCA. In conclusion, this study demonstrates the utility of combined in vivo/in silico methods and suggests that HA exerts differential effects on mediator gradients between local and systemic compartments that ultimately benefit the host.

Nguyen Y.-L.,University Paris - Sud | Wunsch H.,Columbia University | Angus D.C.,CRISMA Clinical Research | Angus D.C.,University of Pittsburgh
Current Opinion in Critical Care | Year: 2010

Purpose of review The organization and management of ICUs are key components that can affect delivery and outcome of critical care. Recent findings At the healthcare system level, the provision of critical care services and the presence of a regionalized system of critical care delivery may improve optimal matching of patient severity with level of care and is associated with improved patient outcomes. In hospitals, rapid response teams and step-down beds affect admission and discharge criteria to and from the ICU, although the influence on outcome is unclear. And within the ICU, the presence of intensivists, physically or via telemedicine, and multidisciplinary teams may promote better use of therapeutic and preventive measures with improved patient outcomes. Recent findings also emphasize that strategies that promote teamwork and communication, standardize processes of care, emphasize engagement in quality improvement, and provide a positive safety culture are associated with improved patient outcomes and staff morale. Summary Evidence suggests the implementation of some ICU organizational and managerial patterns are associated with improved patient and staff outcomes. Broader adoption of some of these strategies could, therefore, improve overall critical care delivery. Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

Seymour C.W.,CRISMA Clinical Research | Seymour C.W.,University of Pittsburgh | Pandharipande P.P.,Anesthesia Service | Koestner T.,University of Memphis | And 7 more authors.
Critical Care Medicine | Year: 2012

OBJECTIVE: To determine whether benzodiazepine and propofol doses are increased at night and whether daytime and nighttime sedative doses are associated with delirium, coma, and delayed liberation from mechanical ventilation. DESIGN: Single-center, prospective cohort study nested within the Awakening and Breathing Controlled randomized trial. SETTING: Saint Thomas Hospital in Nashville, TN, from 2004 to 2006. PATIENTS: Adult patients receiving mechanical ventilation for >12 hrs with continuous recording of hourly sedation dosing. INTERVENTIONS: We measured hourly doses of benzodiazepine and propofol exposure during the daytime (7 AM to 11 PM) and nighttime (11 PM to 7 AM) for 5 days. We quantified nighttime dose increases by subtracting the average hourly daytime dose on the preceding day from subsequent average hourly nighttime dose. We used multivariable logistic regression to determine whether daytime and nighttime dose increases were independently associated with delirium, coma, and delayed liberation from mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Among 140 patients, the median Acute Physiology and Chronic Health Evaluation II score was 27 (interquartile range 22-33). Among those receiving the sedatives, benzodiazepine and propofol doses were increased at night on 40% and 41% of patient-days, respectively. Of 485 patient-days, delirium was present on 160 (33%) and coma on 206 (42%). In adjusted models, greater daytime benzodiazepine dose was independently associated with failed spontaneous breathing trial and extubation, and subsequent delirium (p <.02 for all). Nighttime increase in benzodiazepine dose was associated with failed spontaneous breathing trial (p <.01) and delirium (p =.05). Daytime propofol dose was marginally associated with subsequent delirium (p =.06). CONCLUSIONS: Nearly half of mechanically ventilated intensive care unit patients received greater doses of sedation at night, a practice associated with failed spontaneous breathing trials, coma, and delirium. Over the first 5 days in our study, patients spent 75% of their time in coma or delirium, outcomes that may be reduced by efforts to decrease sedative exposure during both daytime and nighttime hours in the intensive care unit. Copyright © 2012 by the Society of Critical Care Medicine and Lippincott Williams and Wilkins.

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