Objective The debilitating and persistent effects of intensive care unit (ICU)-acquired delirium and weakness warrant testing of prevention strategies. The purpose of this study was to evaluate the effectiveness and safety of implementing the Awakening and Breathing Coordination, Delirium monitoring/management, and Early exercise/mobility (ABCDE) bundle into everyday practice. Design Eighteen-month, prospective, cohort, before-after study conducted between November 2010 and May 2012. Setting Five adult ICUs, one step-down unit, and one oncology/hematology special care unit located in a 624-bed tertiary medical center. Patients Two hundred ninety-six patients (146 pre- and 150 post-bundle implementation), age ≥ 19 years, managed by the institutions’ medical or surgical critical care service. Interventions ABCDE bundle. Measurements For mechanically ventilated patients (n = 187), we examined the association between bundle implementation and ventilator-free days. For all patients, we used regression models to quantify the relationship between ABCDE bundle implementation and the prevalence/duration of delirium and coma, early mobilization, mortality, time to discharge, and change in residence. Safety outcomes and bundle adherence were monitored. Main Results Patients in the post-implementation period spent three more days breathing without mechanical assistance than did those in the pre-implementation period (median [IQR], 24 [7 to 26] vs. 21 [0 to 25]; p = 0.04). After adjusting for age, sex, severity of illness, comorbidity, and mechanical ventilation status, patients managed with the ABCDE bundle experienced a near halving of the odds of delirium (odds ratio [OR], 0.55; 95% confidence interval [CI], 0.33–0.93; p = 0.03) and increased odds of mobilizing out of bed at least once during an ICU stay (OR, 2.11; 95% CI, 1.29–3.45; p = 0.003). No significant differences were noted in self-extubation or reintubation rates. Conclusions Critically ill patients managed with the ABCDE bundle spent three more days breathing without assistance, experienced less delirium, and were more likely to be mobilized during their ICU stay than patients treated with usual care.

Objective The Awakening and Breathing Coordination, Delirium monitoring/management and Early exercise/mobility (ABCDE) bundle is an evidence-based, interprofessional, multicomponent strategy for minimizing sedative exposure, reducing duration of mechanical ventilation and managing intensive care unit (ICU) acquired delirium and weakness. The purpose of this study was to identify facilitators and barriers to ABCDE bundle adoption and to evaluate the extent to which bundle implementation was effective, sustainable, and conducive to dissemination. Design Prospective, before-after, mixed-methods study. Setting Five adult ICUs, 1 step-down unit, and a special care unit located in a 624 bed, academic medical center Subjects Interprofessional ICU team members at participating institution. Interventions and Measurements In collaboration with the participating institution, we developed, implemented, and refined an ABCDE bundle policy. Over the course of an 18 month period, all ICU team members were offered the opportunity to participate in numerous, multimodal educational efforts. Three focus group sessions, 3 online surveys, and 1 educational evaluation were administered in an attempt to identify facilitators and barriers to bundle adoption. Main Results Factors believed to facilitate bundle implementation included: 1) the performance of daily, interdisciplinary, rounds, 2) engagement of key implementation leaders, 3) sustained and diverse educational efforts, and 4) the bundle's quality and strength. Barriers identified included: 1) intervention related issues (e.g. timing of trials, fear of adverse events), 2) communication and care coordination challenges, 3) knowledge deficits, 4) workload concerns, and 5) documentation burden. Despite these challenges, participants believed implementation ultimately benefited patients, improved interdisciplinary communication, and empowered nurses and other ICU team members. Conclusions In this study of the implementation of the ABCDE bundle in a tertiary care setting, clear factors were identified that both advanced and impeded adoption of this complex intervention that requires interprofessional education, coordination, and cooperation. Focusing on these factors preemptively should enable a more effective and lasting implementation of the bundle and better care for critically ill patients. Lessons learned from this study will also help healthcare providers optimize implementation of the recent ICU Pain, Agitation and Delirium (PAD) Guidelines, which has many similarities but also some important differences as compared to the ABCDE bundle

Activated neutrophils cause conversion of xanthine dehydrogenase to its oxidase form (xanthine oxidase) in endothelial cells, the mechanism of which may be related to the cytotoxic effect of activated neutrophils. The elastase inhibitors, elastatinal, alpha 1-antitrypsin, and MeO-Suc-(Ala)2-Pro-Val-CH2Cl, significantly inhibited xanthine dehydrogenase to oxidase conversion by phorbol myristate acetate-stimulated neutrophils without inhibition of neutrophil adherence to the endothelial cell monolayer. The role of elastase in this enzyme conversion process was confirmed by the ability of purified elastase to cause conversion of xanthine dehydrogenase to xanthine oxidase in intact endothelial cells (or cell extracts) without causing cytotoxicity. In contrast, cathepsin G failed to cause conversion. The kinetics of conversion induced by elastase was relatively rapid, being essentially completed by 30 min. Upon removal of elastase, the effect was slowly (greater than 12 h) reversible and could be inhibited by cycloheximide treatment. Exposure of endothelial cells to hypoxia failed to enhance the elastase-induced conversion. Treatment of endothelial cells with Ca2+ ionophores failed to cause conversion of xanthine dehydrogenase to oxidase, suggesting that intracellular Ca(2+)-activated proteases are not sufficient to induce this process. Neutrophil-induced xanthine dehydrogenase to oxidase conversion was inhibited by concomitant treatment with antibodies to CD11b. The results suggest that activated neutrophils induce conversion of xanthine dehydrogenase to oxidase by secretion of elastase in close proximity to the endothelial cells and that this intimate contact between the two cell types enables high local concentrations of elastase to be attained, which are sufficient to cause xanthine dehydrogenase to xanthine oxidase conversion.

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-First reported in 1898, post-dural puncture headache (PDPH) remains a significant clinical issue. Here, we present a brief case history and a summary of the current evidence for methods to reduce PDPH rates, along with the experience in our department of implementing these methods in clinical practice. The key points to note are that needle design, gauge and orientation, as well as stylet reinsertion, are factors known to affect the incidence of PDPH, and that there is no evidence to support the use of hydration and bed rest to reduce headache following dural puncture.

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