12 research outputs found

    Protocol for a prospective, observational cohort study of awareness in mechanically ventilated patients admitted from the emergency department: The ED-AWARENESS study

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    INTRODUCTION: Awareness with paralysis is a complication with potentially devastating psychological consequences for mechanically ventilated patients. While rigorous investigation into awareness has occurred for operating room patients, little attention has been paid outside of this domain. Mechanically ventilated patients in the emergency department (ED) have been historically managed in a way that predisposes them to awareness events: high incidence of neuromuscular blockade use, underdosing of analgesia and sedation, delayed administration of analgesia and sedation after intubation, and a lack of monitoring of sedation targets and depth. These practice patterns are discordant to recommendations for reducing the incidence of awareness, suggesting there is significant rationale to examine awareness in the ED population. METHODS AND ANALYSIS: This is a single centre, prospective cohort study examining the incidence of awareness in mechanically ventilated ED patients. A cohort of 383 mechanically ventilated ED patients will be included. The primary outcome is awareness with paralysis. Qualitative reports of all awareness events will be provided. Recognising the potential problem with conventional multivariable analysis arising from a small number of events (expected less than 10-phenomenon of separation), Firth penalised method, exact logistic regression model or penalised maximum likelihood estimation shrinkage (Ridge, LASSO) will be used to assess for predictors of awareness. ETHICS AND DISSEMINATION: Approval of the study by the Human Research Protection Office has been obtained. This work will be disseminated by publication of peer-reviewed manuscripts, presentation in abstract form at scientific meetings and data sharing with other investigators through academically established means

    Clinical effectiveness of a sedation protocol minimizing benzodiazepine infusions and favoring early dexmedetomidine: A before-after study

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    INTRODUCTION: Randomized controlled trials suggest clinical outcomes may be improved with dexmedetomidine as compared to benzodiazepines, however further study and validation is needed. The objective of this study was to determine the clinical effectiveness of a sedation protocol minimizing benzodiazepine use in favor of early dexmedetomidine. METHODS: This was a before-after study including adult surgical and medical ICU patients requiring mechanical ventilation and continuous sedation for at least 24 hours. The before phase included consecutive patients admitted between April 1 and August 31, 2011. Subsequently, the protocol was modified to minimize use of benzodiazepines in favor of early dexmedetomidine through a multidisciplinary approach and staff education was provided. The after phase included consecutive eligible patients between May 1 and October 31, 2012. RESULTS: 199 patients were included, with 97 patients in the before and 102 in the after phase. Baseline characteristics were well balanced between groups. Use of midazolam as initial sedation (58% vs. 27%, p \u3c 0.0001) or at any point during the ICU stay (76% vs. 48%, p \u3c 0.0001) was significantly reduced in the after phase. Dexmedetomidine use as initial sedation (2% vs. 39%, p \u3c 0.0001) or at any point during the ICU stay (39% vs. 82%, p \u3c 0.0001) significantly increased. Both the prevalence (81% vs. 93%, p =0.013) and median percent of days with delirium (55% (IQR 18-83) vs. 71% (IQR 45-100), p = 0.001) were increased in the after phase. The median duration of mechanical ventilation was significantly reduced in the after phase (110 (IQR 59-192) vs. 74.5 (IQR 42-148) hrs, p = 0.029) and significantly fewer patients required tracheostomy (20% vs. 9%, p = 0.040). The median ICU length of stay was 8 (IQR 4-12) days in the before phase and 6 (IQR 3-11) days in the after phase (p = 0.252). CONCLUSIONS: Implementing a sedation protocol that targeted light sedation and reduced benzodiazepine use led to significant improvements in the duration of mechanical ventilation and requirement for tracheostomy despite increases in the prevalence and duration of ICU delirium

    Dysregulation of specialized delay/interference-dependent working memory following loss of dysbindin-1A in schizophrenia-related phenotypes

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    Dysbindin-1, a protein that regulates aspects of early and late brain development, has been implicated in the pathobiology of schizophrenia. As the functional roles of the three major isoforms of dysbindin-1, (A, B, and C) remain unknown, we generated a novel mutant mouse, dys-1A -/-, with selective loss of dysbindin-1A and investigated schizophrenia-related phenotypes in both males and females. Loss of dysbindin-1A resulted in heightened initial exploration and disruption in subsequent habituation to a novel environment, together with heightened anxiety-related behavior in a stressful environment. Loss of dysbindin-1A was not associated with disruption of either long-term (olfactory) memory or spontaneous alternation behavior. However, dys-1A -/-showed enhancement in delay-dependent working memory under high levels of interference relative to controls, ie, impairment in sensitivity to the disruptive effect of such interference. These findings in dys-1A -/-provide the first evidence for differential functional roles for dysbindin-1A vs dysbindin-1C isoforms among phenotypes relevant to the pathobiology of schizophrenia. Future studies should investigate putative sex differences in these phenotypic effects

    The use of dexmedetomidine in the emergency department: A cohort study

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    INTRODUCTION: Management of sedation, analgesia, and anxiolysis are cornerstone therapies in the emergency department (ED). Dexmedetomidine (DEX), a central alpha-2 agonist, is increasingly being used, and intensive care unit (ICU) data demonstrate improved outcomes in patients with respiratory failure. However, there is a lack of ED-based data. We therefore sought to: 1) characterize ED DEX use; 2) describe the incidence of adverse events; and 3) explore factors associated with adverse events among patients receiving DEX in the ED. METHODS: This was a single-center, retrospective, cohort study of consecutive ED patients administered DEX (January 1, 2017-July 1, 2019) at an academic, tertiary care ED with an annual census of ~90,000 patient visits. All included patients (n= 103) were analyzed for characterization of DEX use in the ED. The primary outcome was a composite of adverse events, bradycardia and hypotension. Secondary clinical outcomes included ventilator-, ICU-, and hospital-free days, and hospital mortality. To examine for variables associated with adverse events, we used a multivariable logistic regression model. RESULTS: We report on 103 patients. Dexmedetomidine was most commonly given for acute respiratory failure, including sedation for mechanical ventilation (28.9%) and facilitation of non-invasive ventilation (17.4%). Fifty-four (52.4%) patients experienced the composite adverse event, with hypotension occurring in 41 patients (39.8%) and bradycardia occurring in 18 patients (17.5%). Dexmedetomidine was stopped secondary to an adverse event in eight patients (7.8%). Duration of DEX use in the ED was associated with an increase adverse event risk (adjusted odds ratio, 1.004; 95% confidence interval, 1.001, 1.008). CONCLUSION: Dexmedetomidine is most commonly administered in the ED for patients with acute respiratory failure. Adverse events are relatively common, yet DEX is discontinued comparatively infrequently due to adverse events. Our results suggest that DEX could be a viable option for analgesia, anxiolysis, and sedation in ED patients
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