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ICUs are experiencing an epidemic of patients with acute brain dysfunction (delirium) and weakness, both associated with increased mortality and long-term disability. These conditions are commonly acquired in the ICU and are often initiated or exacerbated by sedation and ventilation decisions and management. Despite > 10 years of evidence revealing the hazards of delirium, the quality chasm between current and ideal processes of care continues to exist. Monitoring of delirium and sedation levels remains inconsistent. In addition, sedation, ventilation, and physical therapy practices proven successful at reducing the frequency and severity of adverse outcomes are not routinely practiced. In this article, we advocate for the adoption and implementation of a standard bundle of ICU measures with great potential to reduce the burden of ICU-acquired delirium and weakness. Individual components of this bundle are evidence based and can help standardize communication, improve interdisciplinary care, reduce mortality, and improve cognitive and functional outcomes. We refer to this as the "ABCDE bundle," for awakening and breathing coordination, delirium monitoring, and exercise/early mobility. This evidence-based bundle of practices will build a bridge across the current quality chasm from the "front end" to the "back end" of critical care and toward improved cognitive and functional outcomes for ICU survivors. [ABSTRACT FROM AUTHOR]

Rationale: Studies have shown that reducing sedation of critically ill patients shortens time on the ventilator and in the intensive care unit (ICU). Little is known, however, of how such strategies affect long-term cognitive, psychological, and functional outcomes.Objectives: To determine the long-term effects of a wake up and breathe protocol that interrupts and reduces sedative exposure in the ICU.Methods: In this a priori planned substudy conducted at one tertiary care hospital during the Awakening and Breathing Controlled Trial, a multicenter randomized controlled trial, we assessed cognitive, psychological, and functional/quality-of-life outcomes 3 and 12 months postdischarge among 180 medical ICU patients randomized to paired daily spontaneous awakening trials with spontaneous breathing trials (SBTs) or to sedation per usual care plus daily SBTs.Measurements and Main Results: Cognitive impairment was less common in the intervention group at 3-month follow-up (absolute risk reduction, 20.2%; 95% confidence interval, 1.5-36.1%; P = 0.03) but not at 12-month follow-up (absolute risk reduction, -1.9%; 95% CI, -21.3 to 27.1%; P = 0.89). Composite cognitive scores, alternatively, were similar in the two groups at 3-month and 12-month follow-up (P = 0.80 and 0.61, respectively), as were symptoms of depression (P = 0.59 and 0.82) and posttraumatic stress disorder (P = 0.59 and 0.97). Activities of daily living, functional status, and mental and physical quality of life were similar between groups throughout follow-up.Conclusions: In this trial, management of mechanically ventilated medical ICU patients with a wake up and breathe protocol resulted in similar cognitive, psychological, and functional outcomes among patients tested 3 and 12 months post-ICU. The proven benefits of this protocol, including improved 1-year survival, were not offset by adverse long-term outcomes. Clinical trial registered with www.clinicaltrials.gov (NCT 00097630). [ABSTRACT FROM AUTHOR]

The prevention and treatment of pain, anxiety, and delirium in the ICU are important goals. But achieving a balance between sedation and analgesia, especially in critically ill patients on mechanical ventilation, can be challenging. Both under- and oversedation carry grave risks. Without having an agreed-upon end point for sedation, different providers will likely have disparate treatment goals, increasing the risk of iatrogenic complications and possibly impeding recovery. In 2002 the Society of Critical Care Medicine, along with the American Society of Health-System Pharmacists, updated recommendations in its clinical practice guidelines for the sustained use of sedatives and analgesics in adults. This two-part series examines those recommendations concerning sedation assessment and management, as well as the current literature. Last month, Part 1 reviewed pertinent recommendations concerning pain and delirium and discussed tools for assessing pain, delirium, and sedation. This month, Part 2 explores pharmacologic and nonpharmacologic management of anxiety and agitation in the ICU.The second in a two-part series focuses on the pharmacologic and nonpharmacologic management of anxiety and agitation in the ICU. [ABSTRACT FROM AUTHOR]

Objective: To implement sedation and delirium monitoring via a process-improvement project in accordance with Society of Critical Care Medicine guidelines and to evaluate the challenges of modifying intensive care unit (ICU) organizational practice styles.Design: Prospective observational cohort study.Setting: The medical ICUs at two institutions: the Vanderbilt University Medical Center (VUMC) and a community Veterans Affairs hospital (York-VA).Subjects: Seven hundred eleven patients admitted to the medical ICUs for >24 hrs and followed over 4,163 days during a 21-month study period.Interventions: Unit-wide nursing documentation was changed to accommodate a sedation scale (Richmond Agitation-Sedation Scale) and delirium instrument (Confusion Assessment Method for the ICU). A 20-min introductory in-service was performed for all ICU nurses, followed by graded, staged educational interventions at regular intervals. Data were collected daily for compliance, and randomly 40% of nurses each day were chosen for accuracy spot-checks by reference raters. An implementation survey questionnaire was distributed at 6 months.Measurements and Main Results: The implementation project involved 64 nurses (40 at VUMC and 24 at York-VA). Sedation and delirium monitoring data were recorded for 711 patients (614 at VUMC and 97 at York-VA). Compliance with the Richmond Agitation-Sedation Scale was 94.4% (21,931 of 23,220) at VUMC and 99.7% (5,387 of 5,403) at York-VA. Compliance with the Confusion Assessment Method for the ICU was 90% (7,323 of 8,166) at VUMC and 84% (1,571 of 1,871) at York-VA. The Confusion Assessment Method for the ICU was performed more often than requested on 63% of shifts (5,146 of 8,166) at VUMC and on 8% (151 of 1871) of shifts at York-VA. Overall weighted-kappa between bedside nurses and references raters for the Richmond Agitation-Sedation Scale were 0.89 (95% confidence interval, 0.88 to 0.92) at VUMC and 0.77 (95% confidence interval, 0.72 to 0.83) at York-VA. Overall agreement (kappa) between bedside nurses and reference raters using the Confusion Assessment Method for the ICU was 0.92 (95% confidence interval, 0.90-0.94) at VUMC and 0.75 (95% confidence interval, 0.68-0.81) at York-VA. The two most-often-cited barriers to implementation were physician buy-in and time.Conclusions: With minimal training, the compliance of bedside nurses using sedation and delirium instruments was excellent. Agreement of data from bedside nurses and a reference-standard rater was very high for both the sedation scale and the delirium assessment over the duration of this process-improvement project. [ABSTRACT FROM AUTHOR]

During the coronavirus disease 2019 pandemic, crisis changes in clinical care increased rates of delirium in the intensive care unit (ICU). Deep sedation, unfamiliar environments with visitor restrictions, and such factors due to high workload and health system strain contributed to the occurrence of delirium doubling in the ICU. As the pandemic wanes, health care systems and ICU leadership must emphasize post-pandemic recovery, integrating lessons learned about delirium management, evidence-based care, and family involvement. Strategies to empower clinicians, creatively deliver care, and integrate families pave the way forward for a more holistic approach to patient care in the post-pandemic era., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

Background: Adoption of early mobility interventions into intensive care unit (ICU) practice has been slow and varied., Objectives: To examine factors associated with early mobility performance in critically ill adults and evaluate factors' effects on predicting next-day early mobility performance., Methods: A secondary analysis of 66 ICUs' data from patients admitted for at least 24 hours. Mixed-effects logistic regression modeling was done, with area under the receiver operating characteristic curve (AUC) calculated., Results: In 12 489 patients, factors independently associated with higher odds of next-day mobility included significant pain (adjusted odds ratio [AOR], 1.16; 95% CI, 1.09-1.23), documented sedation target (AOR, 1.09; 95% CI, 1.01-1.18), performance of spontaneous awakening trials (AOR, 1.77; 95% CI, 1.59-1.96), spontaneous breathing trials (AOR, 2.35; 95% CI, 2.14-2.58), mobility safety screening (AOR, 2.26; 95% CI, 2.04-2.49), and prior-day physical/occupational therapy (AOR, 1.44; 95% CI, 1.30-1.59). Factors independently associated with lower odds of next-day mobility included deep sedation (AOR, 0.44; 95% CI, 0.39-0.49), delirium (AOR, 0.63; 95% CI, 0.59-0.69), benzodiazepine administration (AOR, 0.85; 95% CI, 0.79-0.92), physical restraints (AOR, 0.74; 95% CI, 0.68-0.80), and mechanical ventilation (AOR, 0.73; 95% CI, 0.68-0.78). Black and Hispanic patients had lower odds of next-day mobility than other patients. Models incorporating patient, practice, and between-unit variations displayed high discriminant accuracy (AUC, 0.853) in predicting next-day early mobility performance., Conclusions: Collectively, several modifiable and nonmodifiable factors provide excellent prediction of next-day early mobility performance., (©2024 American Association of Critical-Care Nurses.)

Background: Delirium is common during critical illness and is associated with long-term cognitive impairment and disability. Antipsychotics are frequently used to treat delirium, but their effects on long-term outcomes are unknown. We aimed to investigate the effects of antipsychotic treatment of delirious, critically ill patients on long-term cognitive, functional, psychological, and quality-of-life outcomes., Methods: This prespecified, long-term follow-up to the randomised, double-blind, placebo-controlled phase 3 MIND-USA Study was conducted in 16 hospitals throughout the USA. Adults (aged ≥18 years) who had been admitted to an intensive care unit with respiratory failure or septic or cardiogenic shock were eligible for inclusion in the study if they had delirium. Participants were randomly assigned-using a computer-generated, permuted-block randomisation scheme with stratification by trial site and age-in a 1:1:1 ratio to receive intravenous placebo, haloperidol, or ziprasidone for up to 14 days. Investigators and participants were masked to treatment group assignment. 3 months and 12 months after randomisation, we assessed survivors' cognitive, functional, psychological, quality-of-life, and employment outcomes using validated telephone-administered tests and questionnaires. This trial was registered with ClinicalTrials.gov, NCT01211522, and is complete., Findings: Between Dec 7, 2011, and Aug 12, 2017, we screened 20 914 individuals, of whom 566 were eligible and consented or had consent provided to participate. Of these 566 patients, 184 were assigned to the placebo group, 192 to the haloperidol group, and 190 to the ziprasidone group. 1-year survival and follow-up rates were similar between groups. Cognitive impairment was common in all three treatment groups, with a third of survivors impaired at both 3-month and 12-month follow-up in all groups. More than half of the surveyed survivors in each group had cognitive or physical limitations (or both) that precluded employment at both 3-month and 12-month follow-up. At both 3 months and 12 months, neither haloperidol (adjusted odds ratio 1·22 [95% CI 0·73-2.04] at 3 months and 1·12 [0·60-2·11] at 12 months) nor ziprasidone (1·07 [0·59-1·96] at 3 months and 0·94 [0·62-1·44] at 12 months) significantly altered cognitive outcomes, as measured by the Telephone Interview for Cognitive Status T score, compared with placebo. We also found no evidence that functional, psychological, quality-of-life, or employment outcomes improved with haloperidol or ziprasidone compared with placebo., Interpretation: In delirious, critically ill patients, neither haloperidol nor ziprasidone had a significant effect on cognitive, functional, psychological, or quality-of-life outcomes among survivors. Our findings, along with insufficient evidence of short-term benefit and frequent inappropriate continuation of antipsychotics at hospital discharge, indicate that antipsychotics should not be used routinely to treat delirium in critically ill adults., Funding: National Institutes of Health and the US Department of Veterans Affairs., Competing Interests: Declaration of interests The following declarations of interest are reported outside of the submitted work. MFM reports grants from the National Institutes of Health (NIH) and the US Department of Veterans Affairs. LMB reports grants from the NIH and the American Association of Critical Care Nurses. MNG reports grants from the NIH, the Agency for Healthcare Research and Quality, and the US Centers for Disease Control and Prevention; consulting fees for a role as scientific advisor for Endpoint Health; honoraria for grand rounds presentation at Yale University (New Haven, CT, USA); travel support from the American Thoracic Society executive committee; and participation on the data safety monitoring board for a trial on monoclonal antibodies for COVID-19, funded by Regeneron (NCT04452318). AM reports consulting fees from Zoll, Eli Lilly, LivaNova, and Jazz Pharmaceuticals; and a philanthropic contribution from ResMed to the University of California San Diego (La Jolla, CA, USA). BAK reports grants from the NIH, payment for expert testimony for a medicolegal case in the state of Indiana (USA), payment for participation on a data safety monitoring board for the PANDORA trial, and a leadership role as president of the American Delirium Society. SSC reports grants from the NIH and direct payments for participation on the data safety monitoring board of an NIH-funded study unrelated to delirium. CLH reports grants from the NIH. PR reports grants from the NIH and the US Department of Defense, payment and travel support for a continuing medical education event at the Johns Hopkins School of Medicine, and previous leadership of the Association of Academic Anesthesiology Chairs and Society of Academic Associations of Anesthesiology and Perioperative Medicine. BTP reports leadership as co-chair of the Society of Critical Care Medicine ICU Liberation Committee. PPP reports grants from the NIH. NEB reports grants from the NIH and travel support for the Society of Intensive Care Medicine Singapore annual meeting. CGH reports consulting fees for Sedana Medical. MBP reports grants from CSL Behring, the NIH, and the US Department of Defense; royalties for serving as an associate editor with Elsevier on a surgical textbook; travel support for continuing medical education events with the Eastern Association for the Surgery of Trauma, Society of University Surgeons, and American College of Surgeons; a patent for image-derived prognostic models unrelated to this work; participation on a data safety monitoring board for Liberate Medical; and leadership as treasurer for the Eastern Association for the Surgery of Trauma. JLS reports honoria for presentations for the Society of Critical Care Medicine, American College of Chest Physicians, the Chilean Society of Critical Care Medicine, and the Spanish Society of Hospital Pharmacy; travel support for meetings with the Society of Critical Care Medicine, the Saudi Society of Clinical Pharmacy, and the Chilean Society of Critical Care Medicine; and leadership on committees with the Society of Critical Care Medicine. EWE reports grant support from the NIH and the US Department of Veterans Affairs, honoraria for continuing medical education lectures sponsored by Pfizer, and study support (investigational drug provision, no direct payments) from Eli Lilly. TDG reports grants from the NIH, research funding from Ceribell, and personal fees from Haisco Pharmaceutical and Lungpacer Medical. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

The goals of this exploratory study were to engage professionals from the Society for Critical Care Medicine ICU Liberation Collaborative ICUs to: 1) conceptualize strategies to enhance daily implementation of the Assess, prevent, and manage pain; Both spontaneous awakening and breathing trials; Choice of analgesia and sedation; Delirium assess, prevent, and manage; Early mobility and exercise; and Family engagement and empowerment (ABCDEF) bundle from different perspectives and 2) identify strategies to prioritize for implementation., Design: Mixed-methods group concept mapping over 8 months using an online method. Participants provided strategies in response to a prompt about what was needed for successful daily ABCDEF bundle implementation. Responses were summarized into a set of unique statements and then rated on a 5-point scale on degree of necessity (essential) and degree to which currently used., Setting: Sixty-eight academic, community, and federal ICUs., Participants: A total of 121 ICU professionals consisting of frontline and leadership professionals., Interventions: None., Measurements and Main Results: A final set of 76 strategies (reduced from 188 responses) were suggested: education (16 strategies), collaboration (15 strategies), processes and protocols (13 strategies), feedback (10 strategies), sedation/pain practices (nine strategies), education (eight strategies), and family (five strategies). Nine strategies were rated as very essential but infrequently used: adequate staffing, adequate mobility equipment, attention to (patient's) sleep, open discussion and collaborative problem solving, nonsedation methods to address ventilator dyssynchrony, specific expectations for night and day shifts, education of whole team on interdependent nature of the bundle, and effective sleep protocol., Conclusions: In this concept mapping study, ICU professionals provided strategies that spanned a number of conceptual implementation clusters. Results can be used by ICU leaders for implementation planning to address context-specific interdisciplinary approaches to improve ABCDEF bundle implementation., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: Safe, reliable, high-quality critical care delivery depends upon interprofessional teamwork., Objective: To describe perceptions of intensive care unit (ICU) teamwork and healthy work environments and evaluate whether perceptions vary by profession., Methods: In August 2015, Assessment of Interprofessional Team Collaboration Scale (AITCS) and the American Association of Critical-Care Nurses Healthy Work Environment Assessment Tool (HWEAT) surveys were distributed to all interprofessional members at the 68 ICUs participating in the ICU Liberation Collaborative. Overall scores range from 1 (needs improvement) to 5 (excellent)., Results: Most of the 3586 surveys completed were from registered nurses (51.2%), followed by respiratory therapists (17.8%), attending physicians (10.5%), rehabilitation therapists (8.3%), pharmacists (4.9%), nursing assistants (3.1%), and physician trainees (4.1%). Overall, respondents rated teamwork and work environment health favorably (mean [SD] scores: AITCS, 3.92 [0.64]; HWEAT, 3.45 [0.79]). The highest-rated AITCS domain was "partnership/shared decision-making" (mean [SD], 4.00 [0.63); lowest, "coordination" (3.67 [0.80]). The highest-scoring HWEAT standard was "effective decision-making" (mean [SD], 3.60 [0.79]); lowest, "meaningful recognition" (3.30 [0.92]). Compared with attending physicians (mean [SD] scores: AITCS, 3.99 [0.54]; HWEAT, 3.48 [0.70]), AITCS scores were lower for registered nurses (3.91 [0.62]), respiratory therapists (3.86 [0.76]), rehabilitation therapists (3.84 [0.65]), and pharmacists (3.83 [0.55]), and HWEAT scores were lower for respiratory therapists (3.38 [0.86]) (all P ≤ .05)., Conclusions: Teamwork and work environment health were rated by ICU team members as good but not excellent. Care coordination and meaningful recognition can be improved., (©2022 American Association of Critical-Care Nurses.)

Objective: Many intensive care unit (ICU) survivors suffer disabling long-term cognitive impairment (LTCI) after critical illness. We compared EEG characteristics during critical illness with patients' 1-year neuropsychological outcomes., Methods: We performed a post hoc analysis of patients in the BRAIN-ICU study who had undergone EEG for clinical purposes during admission (n = 10). All survivors underwent formal cognitive assessments at 12-month follow-up. We evaluated EEGs by conventional visual inspection and computed 10 quantitative features. We explored associations between EEG and patterns of LTCI using Wilcoxon rank-sum tests and Spearman's rank correlations., Results: Of 521 Vanderbilt patients enrolled in the parent study, 24 had EEG recordings during admission. Ten survivors had EEG tracings available and completed follow-up cognitive testing. All but one inpatient EEG showed generalized background slowing. All patients demonstrated cognitive impairment in at least one domain at follow-up. The most common deficits occurred in delayed memory (DM-median index 62) and visuospatial/constructional (VC-median index 69) domains. Relative alpha power correlated with VC score (ρ = 0.78, P = .008). Peak interhemispheric coherence correlated negatively with DM (ρ = -0.81, P = .018)., Conclusions: Quantitative EEG features during critical illness correlated with domain-specific cognitive performance in our small cohort of ICU survivors. Further study in larger prospective cohorts is required to determine whether these relationships hold., Significance: EEG may serve as a prognostic biomarker predicting patterns of long-term cognitive impairment.

Background: The ABCDEF bundle (Assess, prevent, and manage pain and Delirium; Both spontaneous awakening and breathing trials; Choice of analgesia/sedation; Early mobility; and Family engagement) improves intensive care unit outcomes, but adoption into practice is poor., Objective: To assess the effect of quality improvement collaborative participation on ABCDEF bundle performance., Methods: This interrupted time series analysis included 20 months of bundle performance data from 15 226 adults admitted to 68 US intensive care units. Segmented regression models were used to quantify complete and individual bundle element performance changes over time and compare performance patterns before (6 months) and after (14 months) collaborative initiation., Results: Complete bundle performance rates were very low at baseline (<4%) but increased to 12% by the end. Complete bundle performance increased by 2 percentage points (SE, 0.9; P = .06) immediately after collaborative initiation. Each subsequent month was associated with an increase of 0.6 percentage points (SE, 0.2; P = .04). Performance rates increased significantly immediately after initiation for pain assessment (7.6% [SE, 2.0%], P = .002), sedation assessment (9.1% [SE, 3.7%], P = .02), and family engagement (7.8% [SE, 3%], P = .02) and then increased monthly at the same speed as the trend in the baseline period. Performance rates were lowest for spontaneous awakening/breathing trials and early mobility., Conclusions: Quality improvement collaborative participation resulted in clinically meaningful, but small and variable, improvements in bundle performance. Opportunities remain to improve adoption of sedation, mechanical ventilation, and early mobility practices., (©2022 American Association of Critical-Care Nurses.)

Delirium is the most common manifestation of brain dysfunction in critically ill patients. In the intensive care unit (ICU), duration of delirium is independently predictive of excess death, length of stay, cost of care, and acquired dementia. There are numerous neurotransmitter/functional and/or injury-causing hypotheses rather than a unifying mechanism for delirium. Without using a validated delirium instrument, delirium can be misdiagnosed (under, but also overdiagnosed and trivialized), supporting the recommendation to use a monitoring instrument routinely. The best-validated ICU bedside instruments are CAM-ICU and ICDSC, both of which also detect subsyndromal delirium. Both tools have some inherent limitations in the neurologically injured patients, yet still provide valuable information about delirium once the sequelae of the primary injury settle into a new post-injury baseline. Now it is known that antipsychotics and other psychoactive medications do not reliably improve brain function in critically ill delirious patients. ICU teams should systematically screen for predisposing and precipitating factors. These include exacerbations of cardiac/respiratory failure or sepsis, metabolic disturbances (hypoglycemia, dysnatremia, uremia and ammonemia) receipt of psychoactive medications, and sensory deprivation through prolonged immobilization, uncorrected vision and hearing deficits, poor sleep hygiene, and isolation from loved ones so common during COVID-19 pandemic. The ABCDEF (A2F) bundle is a means to facilitate implementation of the 2018 Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU (PADIS) Guidelines. In over 25,000 patients across nearly 100 institutions, the A2F bundle has been shown in a dose-response fashion (i.e., greater bundle compliance) to yield improved survival, length of stay, coma and delirium duration, cost, and less ICU bounce-backs and discharge to nursing homes., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

The advent of modern critical care medicine has revolutionized care of the critically ill patient in the last 50 years. The Society of Critical Care Medicine (was formed in recognition of the challenges and need for specialized treatment for these fragile patients. As the specialty has grown, it has achieved impressive scientific advances that have reduced mortality and saved lives. With those advances, however, came growing recognition that the burden of critical illness did not end at the doorstep of the hospital. Delirium, once thought to be a mere by-product of critical illness, was found to be an independent predictor of mortality, prolonged mechanical ventilation, and long-lasting cognitive impairment. Similarly, deep sedation and immobility, so often used to keep patients "comfortable" and to facilitate mechanical ventilation and recovery, worsen mortality and lead to the development of ICU-acquired weakness. The realization that these outcomes are inextricably linked to one another and how we manage our patients has helped us recognize the need for culture change. We, as a specialty, now understand that although celebrating the successes of survival, we now also have a duty to focus on those who survive their diseases. Led by initiatives such as the ICU Liberation Campaign of the Society of Critical Care Medicine, the natural progression of the field is now focused on getting patients back to their homes and lives unencumbered by disability and impairment. Much work remains to be done, but the futures of our most critically ill patients will continue to benefit if we leverage and build on the history of our first 50 years., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: Guidelines currently recommend targeting light sedation with dexmedetomidine or propofol for adults receiving mechanical ventilation. Differences exist between these sedatives in arousability, immunity, and inflammation. Whether they affect outcomes differentially in mechanically ventilated adults with sepsis undergoing light sedation is unknown., Methods: In a multicenter, double-blind trial, we randomly assigned mechanically ventilated adults with sepsis to receive dexmedetomidine (0.2 to 1.5 μg per kilogram of body weight per hour) or propofol (5 to 50 μg per kilogram per minute), with doses adjusted by bedside nurses to achieve target sedation goals set by clinicians according to the Richmond Agitation-Sedation Scale (RASS, on which scores range from -5 [unresponsive] to +4 [combative]). The primary end point was days alive without delirium or coma during the 14-day intervention period. Secondary end points were ventilator-free days at 28 days, death at 90 days, and age-adjusted total score on the Telephone Interview for Cognitive Status questionnaire (TICS-T; scores range from 0 to 100, with a mean of 50±10 and lower scores indicating worse cognition) at 6 months., Results: Of 432 patients who underwent randomization, 422 were assigned to receive a trial drug and were included in the analyses - 214 patients received dexmedetomidine at a median dose of 0.27 μg per kilogram per hour, and 208 received propofol at a median dose of 10.21 μg per kilogram per minute. The median duration of receipt of the trial drugs was 3.0 days (interquartile range, 2.0 to 6.0), and the median RASS score was -2.0 (interquartile range, -3.0 to -1.0). We found no difference between dexmedetomidine and propofol in the number of days alive without delirium or coma (adjusted median, 10.7 vs. 10.8 days; odds ratio, 0.96; 95% confidence interval [CI], 0.74 to 1.26), ventilator-free days (adjusted median, 23.7 vs. 24.0 days; odds ratio, 0.98; 95% CI, 0.63 to 1.51), death at 90 days (38% vs. 39%; hazard ratio, 1.06; 95% CI, 0.74 to 1.52), or TICS-T score at 6 months (adjusted median score, 40.9 vs. 41.4; odds ratio, 0.94; 95% CI, 0.66 to 1.33). Safety end points were similar in the two groups., Conclusions: Among mechanically ventilated adults with sepsis who were being treated with recommended light-sedation approaches, outcomes in patients who received dexmedetomidine did not differ from outcomes in those who received propofol. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01739933.)., (Copyright © 2021 Massachusetts Medical Society.)

Background: To date, 750 000 patients with COVID-19 worldwide have required mechanical ventilation and thus are at high risk of acute brain dysfunction (coma and delirium). We aimed to investigate the prevalence of delirium and coma, and risk factors for delirium in critically ill patients with COVID-19, to aid the development of strategies to mitigate delirium and associated sequelae., Methods: This multicentre cohort study included 69 adult intensive care units (ICUs), across 14 countries. We included all patients (aged ≥18 years) admitted to participating ICUs with severe acute respiratory syndrome coronavirus 2 infection before April 28, 2020. Patients who were moribund or had life-support measures withdrawn within 24 h of ICU admission, prisoners, patients with pre-existing mental illness, neurodegenerative disorders, congenital or acquired brain damage, hepatic coma, drug overdose, suicide attempt, or those who were blind or deaf were excluded. We collected de-identified data from electronic health records on patient demographics, delirium and coma assessments, and management strategies for a 21-day period. Additional data on ventilator support, ICU length of stay, and vital status was collected for a 28-day period. The primary outcome was to determine the prevalence of delirium and coma and to investigate any associated risk factors associated with development of delirium the next day. We also investigated predictors of number of days alive without delirium or coma. These outcomes were investigated using multivariable regression., Findings: Between Jan 20 and April 28, 2020, 4530 patients with COVID-19 were admitted to 69 ICUs, of whom 2088 patients were included in the study cohort. The median age of patients was 64 years (IQR 54 to 71) with a median Simplified Acute Physiology Score (SAPS) II of 40·0 (30·0 to 53·0). 1397 (66·9%) of 2088 patients were invasively mechanically ventilated on the day of ICU admission and 1827 (87·5%) were invasively mechanical ventilated at some point during hospitalisation. Infusion with sedatives while on mechanical ventilation was common: 1337 (64·0%) of 2088 patients were given benzodiazepines for a median of 7·0 days (4·0 to 12·0) and 1481 (70·9%) were given propofol for a median of 7·0 days (4·0 to 11·0). Median Richmond Agitation-Sedation Scale score while on invasive mechanical ventilation was -4 (-5 to -3). 1704 (81·6%) of 2088 patients were comatose for a median of 10·0 days (6·0 to 15·0) and 1147 (54·9%) were delirious for a median of 3·0 days (2·0 to 6·0). Mechanical ventilation, use of restraints, and benzodiazepine, opioid, and vasopressor infusions, and antipsychotics were each associated with a higher risk of delirium the next day (all p≤0·04), whereas family visitation (in person or virtual) was associated with a lower risk of delirium (p<0·0001). During the 21-day study period, patients were alive without delirium or coma for a median of 5·0 days (0·0 to 14·0). At baseline, older age, higher SAPS II scores, male sex, smoking or alcohol abuse, use of vasopressors on day 1, and invasive mechanical ventilation on day 1 were independently associated with fewer days alive and free of delirium and coma (all p<0·01). 601 (28·8%) of 2088 patients died within 28 days of admission, with most of those deaths occurring in the ICU., Interpretation: Acute brain dysfunction was highly prevalent and prolonged in critically ill patients with COVID-19. Benzodiazepine use and lack of family visitation were identified as modifiable risk factors for delirium, and thus these data present an opportunity to reduce acute brain dysfunction in patients with COVID-19., Funding: None., Translations: For the French and Spanish translations of the abstract see Supplementary Materials section., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: ABCDEF bundle implementation in the Intensive Care Unit (ICU) is associated with dose dependent improvements in patient outcomes. The objective was to compare nurse attitudes about the ABCDEF bundle to self-reported adherence to bundle components., Research Methodology/design: Cross-sectional study., Setting: Nurses providing direct patient care in 28 ICUs within 18 hospitals across the United States., Main Outcome Measures: 53-item survey of attitudes and practice of the ABCDEF bundle components was administered between November 2011 and August 2015 (n = 1661)., Results: We did not find clinically significant correlations between nurse attitudes and adherence to Awakening trials, Breathing trials, and sedation protocol adherence (r s  = 0.05-0.28) or sedation plan discussion during rounds and Awakening and Breathing trial Coordination (r s  = 0.19). Delirium is more likely to be discussed during rounds when ICU physicians and nurse managers facilitate delirium reduction (r s  = 0.27-0.36). Early mobilization is more likely to occur when ICU physicians, nurse managers, staffing, equipment, and the ICU environment facilitate early mobility (r s  = 0.36-0.47). Physician leadership had the strongest correlation with reporting an ICU environment that facilitates ABCDEF bundle implementation (r s  = 0.63-0.74)., Conclusions: Nurse attitudes about bundle implementation did not predict bundle adherence. Nurse manager and physician leadership played a large role in creating a supportive ICU environment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The ICU Liberation (ABCDEF) Bundle can help to improve care and outcomes for ICU patients, but bundle implementation is far from universal. Understanding how ICU organizational characteristics influence bundle implementation could inform quality improvement efforts. We surveyed all hospitals in Michigan with adult ICUs to determine whether organizational characteristics were associated with bundle implementation and to determine the level of agreement between ICU physician and nurse leaders around ICU organizational characteristics and bundle implementation., Design: We surveyed ICU physician and nurse leaders, assessing their safety culture, ICU team collaboration, and work environment. Using logistic and linear regression models, we compared these organizational characteristics to bundle element implementation, and also compared physician and nurse leaders' perceptions about organizational characteristics and bundle implementation., Setting: All ( n = 72) acute care hospitals with adult ICUs in Michigan., Subjects: ICU physician and nurse leader pairs from each hospital's main ICU., Interventions: We developed, pilot-tested, and deployed an electronic survey to all subjects over a 3 month period in 2016., Results: Results from 73 surveys (28 physicians, 45 nurses, 60% hospital response rate) demonstrated significant variation in hospital and ICU size and type, organizational characteristics, and physician/nurse perceptions of ICU organization and bundle implementation. We found that a robust safety culture and collaborative work environment that uses checklists to facilitate team communication are strongly associated with bundle implementation. There is also a significant dose-response effect between safety culture, a collaborative work environment, and overall bundle implementation., Conclusions: We identified several specific ICU practices that can facilitate ABCDEF Bundle implementation. Our results can be used to develop effective bundle implementation strategies that leverage safety culture, interprofessional collaboration, and routine checklist use in ICUs to improve bundle implementation and performance., Competing Interests: Dr. Barr has received speaking honoraria from the Society of Critical Care Medicine and the Ohio Hospital Association and is a Scientific Advisor for Medasense Biometrics and Masimo. The remaining authors have disclosed that they do not have any potential conflicts of interest.

The novel coronavirus, SARS-CoV-2-causing Coronavirus Disease 19 (COVID-19), emerged as a public health threat in December 2019 and was declared a pandemic by the World Health Organization in March 2020. Delirium, a dangerous untoward prognostic development, serves as a barometer of systemic injury in critical illness. The early reports of 25% encephalopathy from China are likely a gross underestimation, which we know occurs whenever delirium is not monitored with a valid tool. Indeed, patients with COVID-19 are at accelerated risk for delirium due to at least seven factors including (1) direct central nervous system (CNS) invasion, (2) induction of CNS inflammatory mediators, (3) secondary effect of other organ system failure, (4) effect of sedative strategies, (5) prolonged mechanical ventilation time, (6) immobilization, and (7) other needed but unfortunate environmental factors including social isolation and quarantine without family. Given early insights into the pathobiology of the virus, as well as the emerging interventions utilized to treat the critically ill patients, delirium prevention and management will prove exceedingly challenging, especially in the intensive care unit (ICU). The main focus during the COVID-19 pandemic lies within organizational issues, i.e., lack of ventilators, shortage of personal protection equipment, resource allocation, prioritization of limited mechanical ventilation options, and end-of-life care. However, the standard of care for ICU patients, including delirium management, must remain the highest quality possible with an eye towards long-term survival and minimization of issues related to post-intensive care syndrome (PICS). This article discusses how ICU professionals (e.g., physicians, nurses, physiotherapists, pharmacologists) can use our knowledge and resources to limit the burden of delirium on patients by reducing modifiable risk factors despite the imposed heavy workload and difficult clinical challenges posed by the pandemic.

Objectives: Daily ICU interprofessional team rounds, which incorporate the ICU Liberation ("A" for Assessment, Prevention, and Manage Pain; "B" for Both Spontaneous Awakening Trials and Spontaneous Breathing Trials; "C" for Choice of Analgesia and Sedation; "D" for Delirium Assess, Prevent, and Manage; "E" for Early Mobility and Exercise; "F" for Family Engagement and Empowerment [ABCDEF]) Bundle, support both the care coordination and regular provider communication necessary for Bundle execution. This article describes evidence-based practices for conducting effective interprofessional team rounds in the ICU to improve Bundle performance., Design: Best practice synthesis., Methods: The authors, each extensively involved in the Society of Critical Care Medicine's ICU Liberation Campaign, reviewed the pertinent literature to identify how ICU interprofessional team rounds can be optimized to increase ICU Liberation adherence., Results: Daily ICU interprofessional team rounds that foster ICU Liberation Bundle use support both care coordination and regular provider communication within and between teams. Evidence-based best practices for conducting effective interprofessional team rounds in the ICU include the optimal structure for ICU interprofessional team rounds; the importance of conducting rounds at patients' bedside; essential participants in rounds; the inclusion of ICU patients and their families in rounds-based discussions; and incorporation of the Bundle into the Electronic Health Record. Interprofessional team rounds in the ICU ideally employ communication strategies to foster inclusive and supportive behaviors consistent with interprofessional collaboration in the ICU. Patient care discussions during interprofessional team rounds benefit from being patient-centered and goal-oriented. Documentation of ICU Liberation Bundle elements in the Electronic Health Record may help facilitate team communication and decision-making., Conclusions: Conducting high-quality interprofessional team rounds in the ICU is a key strategy to support ICU Liberation Bundle use.

Background: The best sedative medication to reduce delirium, mortality and long term brain dysfunction in mechanically ventilated septic patients is unclear. This multicentre, double-blind, randomised trial investigates the short term and long term effects of dexmedetomidine versus propofol for sedation in mechanically ventilated severely septic patients., Objectives: To describe the statistical analysis plan for this randomised clinical trial comprehensively and place it in the public domain before unblinding., Methods: To ensure that analyses are not selectively reported, we developed a comprehensive statistical analysis plan before unblinding. This trial has an enrolment target of 420 severely septic and mechanically ventilated adult patients, randomly assigned to dexmedetomidine or propofol in a 1:1 ratio. Enrolment was completed in January 2019, and the study was estimated to be completed in September 2019. The primary endpoint is days alive without delirium or coma during first 14 study days. Secondary outcomes include 28-day ventilator-free days, 90-day all-cause mortality and cognitive function at 180 days. Time frames all begin on the day of randomisation. All analyses will be conducted on an intention-to-treat basis., Conclusion: This study will compare the effects of two sedatives in mechanically ventilated severely septic patients. In keeping with the guidance on statistical principles for clinical trials, we have developed a comprehensive statistical analysis plan by which we will adhere, as this will avoid bias and support transparency and reproducibility., Trial Registration: ClinicalTrials.gov (NCT01739933).

Importance: Overall, 1 of 5 decedents in the United States is admitted to an intensive care unit (ICU) before death., Objective: To describe structures, processes, and variability of end-of-life care delivered in ICUs in the United States., Design, Setting, and Participants: This nationwide cohort study used data on 16 945 adults who were cared for in ICUs that participated in the 68-unit ICU Liberation Collaborative quality improvement project from January 2015 through April 2017. Data were analyzed between August 2018 and June 2019., Main Outcomes and Measures: Published quality measures and end-of-life events, organized by key domains of end-of-life care in the ICU., Results: Of 16 945 eligible patients in the collaborative, 1536 (9.1%) died during their initial ICU stay. Of decedents, 654 (42.6%) were women, 1037 (67.5%) were 60 years or older, and 1088 (70.8%) were identified as white individuals. Wide unit-level variation in end-of-life care delivery was found. For example, the median unit-stratified rate of cardiopulmonary resuscitation avoidance in the last hour of life was 89.5% (interquartile range, 83.3%-96.1%; range, 50.0%-100%). Median rates of patients who were pain free and delirium free in last 24 hours of life were 75.1% (interquartile range, 66.0%-85.7%; range, 0-100%) and 60.0% (interquartile range, 43.7%-85.2%; range, 9.1%-100%), respectively. Ascertainment of an advance directive was associated with lower odds of cardiopulmonary resuscitation in the last hour of life (odds ratio, 0.70; 95% CI, 0.49-0.99; P = .04), and a documented offer or delivery of spiritual support was associated with higher odds of family presence at the time of death (odds ratio, 1.95; 95% CI, 1.37-2.77; P < .001). Death in a unit with an open visitation policy was associated with higher odds of pain in the last 24 hours of life (odds ratio, 2.21; 95% CI, 1.15-4.27; P = .02). Unsupervised cluster analysis revealed 3 mutually exclusive unit-level patterns of end-of-life care delivery among 63 ICUs with complete data. Cluster 1 units (14 units [22.2%]) had the lowest rate of cardiopulmonary resuscitation avoidance but achieved the highest pain-free rate. Cluster 2 (25 units [39.7%]) had the lowest delirium-free rate but achieved high rates of all other end-of-life events. Cluster 3 (24 units [38.1%]) achieved high rates across all favorable end-of-life events., Conclusions and Relevance: In this study, end-of-life care delivery varied substantially among ICUs in the United States, and the patterns of care observed suggest that units can be characterized as higher and lower performing. To achieve optimal care for patients who die in an ICU, future research should target unit-level variation and disseminate the successes of higher-performing units.

Delirium, one of the most common manifestations of acute brain dysfunction, is a serious complication in patients receiving care throughout the hospital and a strong predictor of worse outcome. Although delirium monitoring is advocated in numerous evidence-based guidelines as part of routine clinical care, it is still not widely and consistently performed at the bedside in different patient care settings. In a debate on delirium monitoring in hospitalized patients at the 7th American Delirium Society meeting in Nashville, Tennessee, June 2017, areas related to the feasibility, acceptability, and effectiveness of routine delirium monitoring of hospitalized patients were identified, and arguments both for (pro) and against (con) the practice were presented. These arguments and others arising in the discussion were subsequently expanded. The goals were to present a conversation among clinicians and researchers from different settings and to identify the evidence-practice gaps for delirium monitoring for future research and organizational quality improvement programs. Further research is needed to determine whether or not delirium monitoring should become routine clinical care for every patient in every hospital setting.

The ABCDEF bundle (A, assess, prevent, and manage pain; B, both spontaneous awakening and spontaneous breathing trials; C, choice of analgesic and sedation; D, delirium: assess, prevent, and manage; E, early mobility and exercise; and F, family engagement and empowerment) improves intensive care unit patient-centered outcomes and promotes interprofessional teamwork and collaboration. The Society of Critical Care Medicine recently completed the ICU Liberation ABCDEF Bundle Improvement Collaborative, a 20-month, multicenter, national quality improvement initiative that formalized dissemination and implementation strategies to promote effective adoption of the ABCDEF bundle. The purpose of this article is to describe 8 of the most frequently asked questions during the Collaborative and to provide practical advice from leading experts to other institutions implementing the ABCDEF bundle., (©2019 American Association of Critical-Care Nurses.)

Although growing evidence supports the safety and effectiveness of the ABCDEF bundle (A, assess, prevent, and manage pain; B, both spontaneous awakening and spontaneous breathing trials; C, choice of analgesic and sedation; D, delirium: assess, prevent, and manage; E, early mobility and exercise; and F, family engagement and empowerment), intensive care unit providers often struggle with how to reliably and consistently incorporate this interprofessional, evidence-based intervention into everyday clinical practice. Recently, the Society of Critical Care Medicine completed the ICU Liberation ABCDEF Bundle Improvement Collaborative, a 20-month, nationwide, multicenter quality improvement initiative that formalized dissemination and implementation strategies and tracked key performance metrics to overcome barriers to ABCDEF bundle adoption. The purpose of this article is to discuss some of the most challenging implementation issues that Collaborative teams experienced, and to provide some practical advice from leading experts on ways to overcome these barriers., (©2019 American Association of Critical-Care Nurses.)

Objective: Decades-old, common ICU practices including deep sedation, immobilization, and limited family access are being challenged. We endeavoured to evaluate the relationship between ABCDEF bundle performance and patient-centered outcomes in critical care., Design: Prospective, multicenter, cohort study from a national quality improvement collaborative., Setting: 68 academic, community, and federal ICUs collected data during a 20-month period., Patients: 15,226 adults with at least one ICU day., Interventions: We defined ABCDEF bundle performance (our main exposure) in two ways: 1) complete performance (patient received every eligible bundle element on any given day) and 2) proportional performance (percentage of eligible bundle elements performed on any given day). We explored the association between complete and proportional ABCDEF bundle performance and three sets of outcomes: patient-related (mortality, ICU and hospital discharge), symptom-related (mechanical ventilation, coma, delirium, pain, restraint use), and system-related (ICU readmission, discharge destination). All models were adjusted for a minimum of 18 a priori determined potential confounders., Measurements and Results: Complete ABCDEF bundle performance was associated with lower likelihood of seven outcomes: hospital death within 7 days (adjusted hazard ratio, 0.32; CI, 0.17-0.62), next-day mechanical ventilation (adjusted odds ratio [AOR], 0.28; CI, 0.22-0.36), coma (AOR, 0.35; CI, 0.22-0.56), delirium (AOR, 0.60; CI, 0.49-0.72), physical restraint use (AOR, 0.37; CI, 0.30-0.46), ICU readmission (AOR, 0.54; CI, 0.37-0.79), and discharge to a facility other than home (AOR, 0.64; CI, 0.51-0.80). There was a consistent dose-response relationship between higher proportional bundle performance and improvements in each of the above-mentioned clinical outcomes (all p < 0.002). Significant pain was more frequently reported as bundle performance proportionally increased (p = 0.0001)., Conclusions: ABCDEF bundle performance showed significant and clinically meaningful improvements in outcomes including survival, mechanical ventilation use, coma, delirium, restraint-free care, ICU readmissions, and post-ICU discharge disposition.

Background: There are conflicting data on the effects of antipsychotic medications on delirium in patients in the intensive care unit (ICU)., Methods: In a randomized, double-blind, placebo-controlled trial, we assigned patients with acute respiratory failure or shock and hypoactive or hyperactive delirium to receive intravenous boluses of haloperidol (maximum dose, 20 mg daily), ziprasidone (maximum dose, 40 mg daily), or placebo. The volume and dose of a trial drug or placebo was halved or doubled at 12-hour intervals on the basis of the presence or absence of delirium, as detected with the use of the Confusion Assessment Method for the ICU, and of side effects of the intervention. The primary end point was the number of days alive without delirium or coma during the 14-day intervention period. Secondary end points included 30-day and 90-day survival, time to freedom from mechanical ventilation, and time to ICU and hospital discharge. Safety end points included extrapyramidal symptoms and excessive sedation., Results: Written informed consent was obtained from 1183 patients or their authorized representatives. Delirium developed in 566 patients (48%), of whom 89% had hypoactive delirium and 11% had hyperactive delirium. Of the 566 patients, 184 were randomly assigned to receive placebo, 192 to receive haloperidol, and 190 to receive ziprasidone. The median duration of exposure to a trial drug or placebo was 4 days (interquartile range, 3 to 7). The median number of days alive without delirium or coma was 8.5 (95% confidence interval [CI], 5.6 to 9.9) in the placebo group, 7.9 (95% CI, 4.4 to 9.6) in the haloperidol group, and 8.7 (95% CI, 5.9 to 10.0) in the ziprasidone group (P=0.26 for overall effect across trial groups). The use of haloperidol or ziprasidone, as compared with placebo, had no significant effect on the primary end point (odds ratios, 0.88 [95% CI, 0.64 to 1.21] and 1.04 [95% CI, 0.73 to 1.48], respectively). There were no significant between-group differences with respect to the secondary end points or the frequency of extrapyramidal symptoms., Conclusions: The use of haloperidol or ziprasidone, as compared with placebo, in patients with acute respiratory failure or shock and hypoactive or hyperactive delirium in the ICU did not significantly alter the duration of delirium. (Funded by the National Institutes of Health and the VA Geriatric Research Education and Clinical Center; MIND-USA ClinicalTrials.gov number, NCT01211522 .).

Objectives: The Society of Critical Care Medicine recommends routine delirium monitoring, based on data in critically ill patients without primary neurologic injury. We sought to answer whether there are valid and reliable tools to monitor delirium in neurocritically ill patients and whether delirium is associated with relevant clinical outcomes (e.g., survival, length of stay, functional independence, cognition) in this population., Data Sources: We systematically reviewed Cumulative Index to Nursing and Allied Health Literature, Web of Science, and PubMed., Study Selection and Data Extraction: Inclusion criteria allowed any study design investigating delirium monitoring in neurocritically ill patients (e.g., neurotrauma, ischemic, and/or hemorrhagic stroke) of any age. We extracted data relevant to delirium tool sensitivity, specificity, negative predictive value, positive predictive value, interrater reliability, and associated clinical outcomes., Data Synthesis: Among seven prospective cohort studies and a total of 1,173 patients, delirium was assessed in neurocritically patients using validated delirium tools after considering primary neurologic diagnoses and associated complications, finding a pooled prevalence rate of 12-43%. When able to compare against a common reference standard, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, the test characteristics showed a sensitivity of 62-76%, specificity of 74-98%, positive predictive value of 63-91%, negative predictive value of 70-94%, and reliability kappa of 0.64-0.94. Among four studies reporting multivariable analyses, delirium in neurocritically patients was associated with increased hospital length of stay (n = 3) and ICU length of stay (n = 1), as well as worse functional independence (n = 1) and cognition (n = 2), but not survival., Conclusions: These data from studies of neurocritically ill patients demonstrate that patients with primary neurologic diagnoses can meet diagnostic criteria for delirium and that delirious features may predict relevant untoward clinical outcomes. There is a need for ongoing investigations regarding delirium in these complicated neurocritically ill patients.

Objective: To update and expand the 2013 Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the ICU., Design: Thirty-two international experts, four methodologists, and four critical illness survivors met virtually at least monthly. All section groups gathered face-to-face at annual Society of Critical Care Medicine congresses; virtual connections included those unable to attend. A formal conflict of interest policy was developed a priori and enforced throughout the process. Teleconferences and electronic discussions among subgroups and whole panel were part of the guidelines' development. A general content review was completed face-to-face by all panel members in January 2017., Methods: Content experts, methodologists, and ICU survivors were represented in each of the five sections of the guidelines: Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption). Each section created Population, Intervention, Comparison, and Outcome, and nonactionable, descriptive questions based on perceived clinical relevance. The guideline group then voted their ranking, and patients prioritized their importance. For each Population, Intervention, Comparison, and Outcome question, sections searched the best available evidence, determined its quality, and formulated recommendations as "strong," "conditional," or "good" practice statements based on Grading of Recommendations Assessment, Development and Evaluation principles. In addition, evidence gaps and clinical caveats were explicitly identified., Results: The Pain, Agitation/Sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) panel issued 37 recommendations (three strong and 34 conditional), two good practice statements, and 32 ungraded, nonactionable statements. Three questions from the patient-centered prioritized question list remained without recommendation., Conclusions: We found substantial agreement among a large, interdisciplinary cohort of international experts regarding evidence supporting recommendations, and the remaining literature gaps in the assessment, prevention, and treatment of Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) in critically ill adults. Highlighting this evidence and the research needs will improve Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) management and provide the foundation for improved outcomes and science in this vulnerable population.

Background: Patients admitted to intensive care units (ICUs) often experience pain, oversedation, prolonged mechanical ventilation, delirium, and weakness. These conditions are important in that they often lead to protracted physical, neurocognitive, and mental health sequelae now termed postintensive care syndrome. Changing current ICU practice will not only require the adoption of evidence-based interventions but the development of effective and reliable teams to support these new practices., Objectives: To build on the success of bundled care and bridge an ongoing evidence-practice gap, the Society of Critical Care Medicine (SCCM) recently launched the ICU Liberation ABCDEF Bundle Improvement Collaborative. The Collaborative aimed to foster the bedside application of the SCCM's Pain, Agitation, and Delirium Guidelines via the ABCDEF bundle. The purpose of this paper is to describe the history of the Collaborative, the evidence-based implementation strategies used to foster change and teamwork, and the performance and outcome metrics used to monitor progress., Methods: Collaborative participants were required to attend four in-person meetings, monthly colearning calls, database training sessions, an e-Community listserv, and select in-person site visits. Teams submitted patient-level data and completed pre- and postimplementation questionnaires focused on the assessment of teamwork and collaboration, work environment, and overall ICU care. Faculty shared the evidence used to derive each bundle element as well as team-based implementation strategies for improvement and sustainment., Results: Retention in the Collaborative was high, with 67 of 69 adult and eight of nine pediatric ICUs fully completing the program. Baseline and prospective data were collected on over 17,000 critically ill patients. A variety of evidence-based professional behavioral change interventions and novel implementation techniques were utilized and shared among Collaborative members., Linking Evidence to Action: Hospitals and health systems can use the Collaborative structure, strategies, and tools described in this paper to help successfully implement the ABCDEF bundle in their ICUs., (© 2018 Sigma Theta Tau International.)

Background: Delirium during critical illness results from numerous insults, which might be interconnected and yet individually contribute to long-term cognitive impairment. We sought to describe the prevalence and duration of clinical phenotypes of delirium (ie, phenotypes defined by clinical risk factors) and to understand associations between these clinical phenotypes and severity of subsequent long-term cognitive impairment., Methods: In this multicentre, prospective cohort study, we included adult (≥18 years) medical or surgical ICU patients with respiratory failure, shock, or both as part of two parallel studies: the Bringing to Light the Risk Factors and Incidence of Neuropsychological Dysfunction in ICU Survivors (BRAIN-ICU) study, and the Delirium and Dementia in Veterans Surviving ICU Care (MIND-ICU) study. We assessed patients at least once a day for delirium using the Confusion Assessment Method-ICU and identified a priori-defined, non-mutually exclusive phenotypes of delirium per the presence of hypoxia, sepsis, sedative exposure, or metabolic (eg, renal or hepatic) dysfunction. We considered delirium in the absence of hypoxia, sepsis, sedation, and metabolic dysfunction to be unclassified. 3 and 12 months after discharge, we assessed cognition with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). We used multiple linear regression to separately analyse associations between the duration of each phenotype of delirium and RBANS global cognition scores at 3-month and 12-month follow-up, adjusting for potential confounders., Findings: Between March 14, 2007, and May 27, 2010, 1048 participants were enrolled, eight of whom could not be analysed. Of 1040 participants, 708 survived to 3 months of follow-up and 628 to 12 months. Delirium was common, affecting 740 (71%) of 1040 participants at some point during the study and occurring on 4187 (31%) of all 13 434 participant-days. A single delirium phenotype was present on only 1355 (32%) of all 4187 participant-delirium days, whereas two or more phenotypes were present during 2832 (68%) delirium days. Sedative-associated delirium was most common (present during 2634 [63%] delirium days), and a longer duration of sedative-associated delirium predicted a worse RBANS global cognition score 12 months later, after adjusting for covariates (difference in score comparing 3 days vs 0 days: -4·03, 95% CI -7·80 to -0·26). Similarly, longer durations of hypoxic delirium (-3·76, 95% CI -7·16 to -0·37), septic delirium (-3·67, -7·13 to -0·22), and unclassified delirium (-4·70, -7·16 to -2·25) also predicted worse cognitive function at 12 months, whereas duration of metabolic delirium did not (1·14, -0·12 to 3·01)., Interpretation: Our findings suggest that clinicians should consider sedative-associated, hypoxic, and septic delirium, which often co-occur, as distinct indicators of acute brain injury and seek to identify all potential risk factors that may impact on long-term cognitive impairment, especially those that are iatrogenic and potentially modifiable such as sedation., Funding: National Institutes of Health and the Department of Veterans Affairs., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Delirium is highly prevalent in critically ill patients. Its detection with valid tools is crucial., Objective: To analyze the development and psychometric properties of delirium assessment tools for critically ill adults., Methods: Databases were searched to identify relevant studies. Inclusion criteria were English language, publication before January 2015, 30 or more patients, and patient population of critically ill adults (>18 years old). Search terms were delirium, scales, critically ill patients, adult, validity, and reliability. Thirty-six manuscripts were identified, encompassing 5 delirium assessment tools (Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), Cognitive Test for Delirium, Delirium Detection Score, Intensive Care Delirium Screening Checklist (ICDSC), and Nursing Delirium Screening Scale). Two independent reviewers analyzed the psychometric properties of these tools by using a standardized scoring system (range, 0-20) to assess the tool development process, reliability, validity, feasibility, and implementation of each tool., Results: Psychometric properties were very good for the CAM-ICU (19.6) and the ICDSC (19.2), moderate for the Nursing Delirium Screening Scale (13.6), low for the Delirium Detection Score (11.2), and very low for the Cognitive Test for Delirium (8.2)., Conclusions: The results indicate that the CAM-ICU and the ICDSC are the most valid and reliable delirium assessment tools for critically ill adults. Additional studies are needed to further validate these tools in critically ill patients with neurological disorders and those at various levels of sedation or consciousness., (©2018 American Association of Critical-Care Nurses.)

Background: Critical illness is associated with cognitive impairment, but mental health and functional disabilities in survivors of intensive care are inadequately characterised. We aimed to assess associations of age and duration of delirium with mental health and functional disabilities in this group., Methods: In this prospective, multicentre cohort study, we enrolled patients with respiratory failure or shock who were undergoing treatment in medical or surgical ICUs in Nashville, TN, USA. We obtained data for baseline demographics and in-hospital variables, and assessed survivors at 3 months and 12 months with measures of depression (Beck Depression Inventory II), post-traumatic stress disorder (PTSD, Post-Traumatic Stress Disorder Checklist-Event Specific Version), and functional disability (activities of daily living scales, Pfeffer Functional Activities Questionnaire, and Katz Activities of Daily Living Scale). We used linear and proportional odds logistic regression to assess the independent associations between age and duration of delirium with mental health and functional disabilities. This study is registered with ClinicalTrials.gov, number NCT00392795., Findings: We enrolled 821 patients with a median age of 61 years (IQR 51-71), assessing 448 patients at 3 months and 382 patients at 12 months after discharge. At 3 months, 149 (37%) of 406 patients with available data reported at least mild depression, as did 116 (33%) of 347 patients at 12 months; this depression was mainly due to somatic rather than cognitive-affective symptoms. Depressive symptoms were common even among individuals without a history of depression (as reported by a proxy), occurring in 76 (30%) of 255 patients with data at 3 months and 62 (29%) of 217 individuals at 12 months. Only 7% of patients (27 of 415 at 3 months and 24 of 361 at 12 months) had symptoms consistent with post-traumatic distress disorder. Disabilities in basic activities of daily living (ADL) were present in 139 (32%) of 428 patients at 3 months and 102 (27%) of 374 at 12 months, as were disabilities in instrumental ADL in 108 (26%) of 422 individuals at 3 months and 87 (23%) of 372 at 12 months. Mental health and functional difficulties were prevalent in patients of all ages. Although old age was frequently associated with mental health problems and functional disabilities, we observed no consistent association between the presence of delirium and these outcomes., Interpretation: Poor mental health and functional disability is common in patients treated in intensive-care units. Depression is five times more common than is post-traumatic distress disorder after critical illness and is driven by somatic symptoms, suggesting approaches targeting physical rather than cognitive causes could benefit patients leaving critical care., Funding: National Institutes of Health AG027472 and the Geriatric Research, Education and Clinical Center (GRECC), Department of Veterans Affairs Medical Center, Tennessee Valley Healthcare System., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Arsenic (As) is a metalloid that occurs in different inorganic and organic forms, which are found in the environment from both natural occurrence and anthropogenic activity. The inorganic forms of As (iAs) are more toxic as compared with the organic As, but so far most of the occurrence data in food collected in the framework of official food control are still reported as total As without differentiating the various As species. In this paper, total As and iAs contents of 600 total diet study (TDS) samples, subdivided into 15 different food groups, were quantified by high-resolution inductively coupled plasma mass spectrometry (HR-ICP/MS) and hydride generation (HG) ICP/MS respectively. The method detection limits for both total As and iAs were 3 μg As kg(-1). As the samples were prepared for TDS, food items were purchased directly from the market or prepared as for normal consumption, i.e. table ready, in the manner most representative of and consistent with cultural habits in Hong Kong as far as practicable. The highest total As and iAs content were found in 'fish, seafood and their products' and 'vegetables and their products' respectively. Besides, this paper also presents the ratios of iAs and total As content in different ready-to-eat food items. The highest ratio of iAs to total As was found in 'vegetables and their products'. It is likely that iAs in vegetables maintained its status even after cooking.

Purpose: Cognitive impairment after critical illness is common and debilitating. We developed a cognitive therapy program for critically ill patients and assessed the feasibility and safety of administering combined cognitive and physical therapy early during a critical illness., Methods: We randomized 87 medical and surgical ICU patients with respiratory failure and/or shock in a 1:1:2 manner to three groups: usual care, early once-daily physical therapy, or early once-daily physical therapy plus a novel, progressive, twice-daily cognitive therapy protocol. Cognitive therapy included orientation, memory, attention, and problem-solving exercises, and other activities. We assessed feasibility outcomes of the early cognitive plus physical therapy intervention. At 3 months, we also assessed cognitive, functional, and health-related quality of life outcomes. Data are presented as median (interquartile range) or frequency (%)., Results: Early cognitive therapy was a delivered to 41/43 (95%) of cognitive plus physical therapy patients on 100% (92-100%) of study days beginning 1.0 (1.0-1.0) day following enrollment. Physical therapy was received by 17/22 (77%) of usual care patients, by 21/22 (95%) of physical therapy only patients, and 42/43 (98%) of cognitive plus physical therapy patients on 17% (10-26%), 67% (46-87%), and 75% (59-88%) of study days, respectively. Cognitive, functional, and health-related quality of life outcomes did not differ between groups at 3-month follow-up., Conclusions: This pilot study demonstrates that early rehabilitation can be extended beyond physical therapy to include cognitive therapy. Future work to determine optimal patient selection, intensity of treatment, and benefits of cognitive therapy in the critically ill is needed.

Background: Survivors of critical illness often have a prolonged and disabling form of cognitive impairment that remains inadequately characterized., Methods: We enrolled adults with respiratory failure or shock in the medical or surgical intensive care unit (ICU), evaluated them for in-hospital delirium, and assessed global cognition and executive function 3 and 12 months after discharge with the use of the Repeatable Battery for the Assessment of Neuropsychological Status (population age-adjusted mean [±SD] score, 100±15, with lower values indicating worse global cognition) and the Trail Making Test, Part B (population age-, sex-, and education-adjusted mean score, 50±10, with lower scores indicating worse executive function). Associations of the duration of delirium and the use of sedative or analgesic agents with the outcomes were assessed with the use of linear regression, with adjustment for potential confounders., Results: Of the 821 patients enrolled, 6% had cognitive impairment at baseline, and delirium developed in 74% during the hospital stay. At 3 months, 40% of the patients had global cognition scores that were 1.5 SD below the population means (similar to scores for patients with moderate traumatic brain injury), and 26% had scores 2 SD below the population means (similar to scores for patients with mild Alzheimer's disease). Deficits occurred in both older and younger patients and persisted, with 34% and 24% of all patients with assessments at 12 months that were similar to scores for patients with moderate traumatic brain injury and scores for patients with mild Alzheimer's disease, respectively. A longer duration of delirium was independently associated with worse global cognition at 3 and 12 months (P=0.001 and P=0.04, respectively) and worse executive function at 3 and 12 months (P=0.004 and P=0.007, respectively). Use of sedative or analgesic medications was not consistently associated with cognitive impairment at 3 and 12 months., Conclusions: Patients in medical and surgical ICUs are at high risk for long-term cognitive impairment. A longer duration of delirium in the hospital was associated with worse global cognition and executive function scores at 3 and 12 months. (Funded by the National Institutes of Health and others; BRAIN-ICU ClinicalTrials.gov number, NCT00392795.).

Objective: To review delirium screening tools available for use in the adult ICU and PICU, to review evidence-based delirium screening implementation, and to discuss common pitfalls encountered during delirium screening in the ICU., Data Sources: Review of delirium screening literature and expert opinion., Results: Over the past decade, tools specifically designed for use in critically ill adults and children have been developed and validated. Delirium screening has been effectively implemented across many ICU settings. Keys to effective implementation include addressing barriers to routine screening, multifaceted training such as lectures, case-based scenarios, one-on-one teaching, and real-time feedback of delirium screening, and interdisciplinary communication through discussion of a patient's delirium status during bedside rounds and through documentation systems. If delirium is present, clinicians should search for reversible or treatable causes because it is often multifactorial., Conclusion: Implementation of effective delirium screening is feasible but requires attention to implementation methods, including a change in the current ICU culture that believes delirium is inevitable or a normal part of a critical illness, to a future culture that views delirium as a dangerous syndrome which portends poor clinical outcomes and which is potentially modifiable depending on the individual patients circumstances.

The management of pain, agitation, and delirium in critically ill patients can be complicated by multiple factors. Decisions to administer opioids, sedatives, and antipsychotic medications are frequently driven by a desire to facilitate patients' comfort and their tolerance of invasive procedures or other interventions within the ICU. Despite accumulating evidence supporting new strategies to optimize pain, sedation, and delirium practices in the ICU, many critical care practitioners continue to embrace false perceptions regarding appropriate management in these critically ill patients. This article explores these perceptions in more detail and offers new evidence-based strategies to help critical care practitioners better manage sedation and delirium, particularly in ICU patients.

It has been 10 years since the last publication of the clinical practice guidelines for pain, agitation/sedation, and delirium (PAD). The results of new studies have directed significant changes in critical care practice. Using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology, the guidelines were revised, resulting in 32 recommendations and 22 summary statements. This article provides guidance toward guideline implementation strategies and outlines 10 key points to consider. Compared with its predecessor, the 2013 PAD guidelines are less prescriptive in that they recommend approaches to patient care rather than giving specific medication recommendations. This will help focus care teams on the process and structure of patient management and result in more flexibility when choosing specific medications. This article outlines approaches to guideline implementation that take into account the changes in philosophy surrounding medication selection. The manuscript focuses on the areas anticipated to generate the most change such as lighter sedation targets, avoidance of benzodiazepines, and early mobility. A gap analysis grid is provided. The release of any guideline should prompt reevaluation of current institutional practice standards. This manuscript uses the PAD guidelines as an example of how to approach the interprofessional work of guideline implementation., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)