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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: 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. 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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: 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.)

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.

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).

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.

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: 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.)

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.)

Delirium in the intensive care unit (ICU) is associated with many negative outcomes, including increased length of stay in both the ICU and the hospital, increased duration of mechanical ventilation, increased mortality, worse long-term cognitive impairment, and increased costs. The 2013 American College of Critical Care Medicine (ACCM)/Society of Critical Care Medicine (SCCM) clinical practice guidelines for pain, agitation, and delirium (PAD), based on available evidence, strongly recommend that critically ill patients be routinely monitored for delirium in the ICU using a validated tool. After conducting a thorough psychometric review of available delirium assessment tools, the 2013 PAD guideline group concluded that the Confusion Assessment Method for the ICU (CAM-ICU) and the Intensive Care Delirium Screening Checklist (ICDSC) are the ICU delirium screening tools with the strongest validity and reliability. This article discusses the importance and feasibility of delirium screening in the ICU and compares the most commonly used critical care delirium screening instruments. Strategies needed to implement and sustain delirium screening efforts in different critically ill populations are introduced and discussed. Accurate detection is the first step in managing ICU patients who develop delirium in an attempt to reduce the negative sequelae of delirium in this population., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objectives: To describe the reliability and sustainability of delirium and sedation measurements of bedside intensive care unit (ICU) nurses., Design: Prospective cohort study., Setting: A tertiary care academic medical center., Participants: Five hundred ten ICU patients from 2007 to 2010; 627 bedside nurses., Measurements: Bedside nurses and well-trained reference-rater research nurses independently measured delirium and sedation levels in routine care. Bedside nurses were instructed to use the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) every 12 hours to measure delirium and the Richmond Agitation-Sedation Scale (RASS) every 4 hours to measure sedation. CAM-ICU and RASS assessment agreement were computed using weighted kappa statistics across the entire population and subgroups (e.g., ICU type). Sensitivity and specificity of bedside nurse identification of delirium were calculated to understand sources of discordance., Results: Six thousand one hundred ninety-eight CAM-ICU and 6,880 RASS measurement pairs obtained on 3,846 patient-days. For CAM-ICU measurements, agreement between bedside and research nurses was substantial (weighted kappa = 0.67, 95% confidence interval (CI) = 0.66-0.70) and stable over 3 years of data collection. RASS measures also demonstrated substantial agreement (weighted kappa = 0.66, 95% CI = 0.64-0.68), which was stable across all years of data collection. The sensitivity of delirium nurse assessments was 0.81 (95% CI = 0.78-0.83), and the specificity was 0.81 (95% CI = 0.78-0.85)., Conclusion: Bedside nurse measurements of delirium and sedation are sustainable and reliable sources of information. These measures can be used for clinical decision-making, quality improvement, and quality measurement activities., (© 2011, Copyright the Authors Journal compilation © 2011, The American Geriatrics Society.)

A significant portion of critical care patients experience delirium. This form of acute brain dysfunction is associated with increased hospital stay, increased mortality, and greater long-term cognitive deficits. Critical care nurses are on the frontline with these patients and can make a significant impact on patient outcomes, including reducing the negative outcomes and experience of delirium. It is, therefore, imperative that nurses be equipped with a solid knowledge base of understanding delirium, which includes what has been reported specifically unique to delirium in the intensive care unit. This article will provide an overview of delirium and describe an interdisciplinary model of care combining multiple evidence-based practice strategies that nurses can and should use to help systematically reduce modifiable delirium risk factors. In addition, this article will provide an overview of recent reports concerning pharmacologic management of delirium in the intensive care unit.

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.

Delirium affects 60 to 80% of ventilated patients and is associated with worse clinical outcomes including death. Unfortunately, there are limited data regarding the prevalence and risk factors of delirium in critically ill burn patients. The objectives of this study were to evaluate the prevalence of delirium in ventilated burn patients, using validated instruments, and to identify its risk factors. Adult ventilated burn patients at two tertiary centers were prospectively evaluated for delirium using the Confusion Assessment Method in the Intensive Care Unit (CAM-ICU) for 30 days or until intensive care unit discharge. Patients with neurologic injuries, severe dementia, and those not expected to survive >24 hours were excluded. Markov logistic regression was used to identify the risk factors of delirium, adjusting for clinically relevant covariates. The 82 ventilated burn patients had a median (interquartile range) age of 48 (38-62) years, Acute Physiology and Chronic Health Evaluation II scores 27 (21-30), and percent burns of 20 (7-32). Prevalence of delirium was 77% with a median duration of 3 (1-6) days. Exposure to benzodiazepines was an independent risk factor for the development of delirium (odds ratio: 6.8 [confidence interval: 3.1-15], P < .001), whereas exposure to both intravenous opiates (0.5 [0.4-0.6], P < .001) and methadone (0.7 [0.5-0.9], P = .02) was associated with a lower risk of delirium. In conclusion, delirium occurred at least once in approximately 80% of ventilated burn patients. Exposure to benzodiazepines was an independent risk factor for delirium, whereas opiates and methadone reduced the risk of developing delirium, possibly through reduction of pain in these patients.

Objective: To test the hypothesis that duration of delirium in the intensive care unit is an independent predictor of long-term cognitive impairment after critical illness requiring mechanical ventilation., Design: Prospective cohort study., Setting: Medical intensive care unit in a large community hospital in the United States., Patients: Mechanically ventilated medical intensive care unit patients who were assessed daily for delirium while in the intensive care unit and who underwent comprehensive cognitive assessments 3 and 12 mos after discharge., Measurements and Main Results: Of 126 eligible patients, 99 survived>or=3 months after critical illness; long-term cognitive outcomes were obtained for 77 (78%) patients. Median age was 61 yrs, 51% were admitted with sepsis/acute respiratory distress syndrome, and median duration of delirium was 2 days. At 3-mo and 12-mo follow-up, 79% and 71% of survivors had cognitive impairment, respectively (with 62% and 36% being severely impaired). After adjusting for age, education, preexisting cognitive function, severity of illness, severe sepsis, and exposure to sedative medications in the intensive care unit, increasing duration of delirium was an independent predictor of worse cognitive performance-determined by averaging age-adjusted and education-adjusted T-scores from nine tests measuring seven domains of cognition-at 3-mo (p=.02) and 12-mo follow-up (p=.03). Duration of mechanical ventilation, alternatively, was not associated with long-term cognitive impairment (p=.20 and .58)., Conclusions: In this study of mechanically ventilated medical intensive care unit patients, duration of delirium (which is potentially modifiable) was independently associated with long-term cognitive impairment, a common public health problem among intensive care unit survivors.

Objective: To demonstrate the feasibility of a placebo-controlled trial of antipsychotics for delirium in the intensive care unit and to test the hypothesis that antipsychotics would improve days alive without delirium or coma., Design: Randomized, double-blind, placebo-controlled trial., Setting: Six tertiary care medical centers in the US., Patients: One hundred one mechanically ventilated medical and surgical intensive care unit patients., Intervention: Patients were randomly assigned to receive haloperidol or ziprasidone or placebo every 6 hrs for up to 14 days. Twice each day, frequency of study drug administration was adjusted according to delirium status, level of sedation, and side effects., Measurements and Main Outcomes: The primary end point was the number of days patients were alive without delirium or coma. During the 21-day study period, patients in the haloperidol group spent a similar number days alive without delirium or coma (median [interquartile range], 14.0 [6.0-18.0] days) as did patients in the ziprasidone (15.0 [9.1-18.0] days) and placebo groups (12.5 [1.2-17.2] days; p = 0.66). No differences were found in secondary clinical outcomes, including ventilator-free days (p = .25), hospital length of stay (p = .68), and mortality (p = .81). Ten (29%) patients in the haloperidol group reported symptoms consistent with akathisia, compared with six (20%) patients in the ziprasidone group and seven (19%) patients in the placebo group (p = .60), and a global measure of extrapyramidal symptoms was similar between treatment groups (p = .46)., Conclusions: A randomized, placebo-controlled trial of antipsychotics for delirium in mechanically ventilated intensive care unit patients is feasible. Treatment with antipsychotics in this limited pilot trial did not improve the number of days alive without delirium or coma, nor did it increase adverse outcomes. Thus, a large trial is needed to determine whether use of antipsychotics for intensive care unit delirium is appropriate.

Objective: A 2001 survey found that most healthcare professionals considered intensive care unit (ICU) delirium as a serious problem, but only 16% used a validated delirium screening tool. Our objective was to assess beliefs and practices regarding ICU delirium and sedation management., Design and Setting: Between October 2006 and May 2007, a survey was distributed to ICU practitioners in 41 North American hospitals, seven international critical care meetings and courses, and the American Thoracic Society e-mail database., Study Participants: A convenience sample of 1384 healthcare professionals including 970 physicians, 322 nurses, 23 respiratory care practitioners, 26 pharmacists, 18 nurse practitioners and physicians' assistants, and 25 others., Results: A majority [59% (766 of 1300)] estimated that more than one in four adult mechanically ventilated patients experience delirium. More than half [59% (774 of 1302)] screen for delirium, with 33% of those respondents (258 of 774) using a specific screening tool. A majority of respondents use a sedation protocol, but 29% (396 of 1355) still do not. A majority (76%, 990 of 1309) has a written policy on spontaneous awakening trials (SATs), but the minority of respondents (44%, 446 of 1019) practice spontaneous awakening trials on more than half of ICU days., Conclusions: Delirium is considered a serious problem by a majority of healthcare professionals, and the percent of practitioners using a specific screening tool has increased since the last published survey data. Although most respondents have adopted specific sedation protocols and have an approved approach to stopping sedation daily, few report even modest compliance with daily cessation of sedation.

Background: Although known to be an independent predictor of poor outcomes in medical intensive care unit (ICU) patients, limited data exist regarding the prevalence of and risk factors for delirium among surgical (SICU) and trauma ICU (TICU) patients. The purpose of this study was to analyze the prevalence of and risk factors for delirium in surgical and trauma ICU patients., Methods: SICU and TICU patients requiring mechanical ventilation (MV) >24 hours were prospectively evaluated for delirium using the Richmond Agitation Sedation Scale (RASS) and the Confusion Assessment Method for the ICU (CAM-ICU). Those with baseline dementia, intracranial injury, or ischemic/hemorrhagic strokes that would confound the evaluation of delirium were excluded. Markov models were used to analyze predictors for daily transition to delirium., Results: One hundred patients (46 SICU and 54 TICU) were enrolled. Prevalence of delirium was 73% in the SICU and 67% in the TICU. Multivariable analyses identified midazolam [OR 2.75 (CI 1.43-5.26, p = 0.002)] exposure as the strongest independent risk factor for transitioning to delirium. Opiate exposure showed an inconsistent message such that fentanyl was a risk factor for delirium in the SICU (p = 0.007) but not in the TICU (p = 0.936), whereas morphine exposure was associated with a lower risk of delirium (SICU, p = 0.069; TICU p = 0.024)., Conclusion: Approximately 7 of 10 SICU and TICU patients experience delirium. In keeping with other recent data on benzodiazepines, exposure to midazolam is an independent and potentially modifiable risk factor for the transitioning to delirium.

Context: Lorazepam is currently recommended for sustained sedation of mechanically ventilated intensive care unit (ICU) patients, but this and other benzodiazepine drugs may contribute to acute brain dysfunction, ie, delirium and coma, associated with prolonged hospital stays, costs, and increased mortality. Dexmedetomidine induces sedation via different central nervous system receptors than the benzodiazepine drugs and may lower the risk of acute brain dysfunction., Objective: To determine whether dexmedetomidine reduces the duration of delirium and coma in mechanically ventilated ICU patients while providing adequate sedation as compared with lorazepam., Design, Setting, Patients, and Intervention: Double-blind, randomized controlled trial of 106 adult mechanically ventilated medical and surgical ICU patients at 2 tertiary care centers between August 2004 and April 2006. Patients were sedated with dexmedetomidine or lorazepam for as many as 120 hours. Study drugs were titrated to achieve the desired level of sedation, measured using the Richmond Agitation-Sedation Scale (RASS). Patients were monitored twice daily for delirium using the Confusion Assessment Method for the ICU (CAM-ICU)., Main Outcome Measures: Days alive without delirium or coma and percentage of days spent within 1 RASS point of the sedation goal., Results: Sedation with dexmedetomidine resulted in more days alive without delirium or coma (median days, 7.0 vs 3.0; P = .01) and a lower prevalence of coma (63% vs 92%; P < .001) than sedation with lorazepam. Patients sedated with dexmedetomidine spent more time within 1 RASS point of their sedation goal compared with patients sedated with lorazepam (median percentage of days, 80% vs 67%; P = .04). The 28-day mortality in the dexmedetomidine group was 17% vs 27% in the lorazepam group (P = .18) and cost of care was similar between groups. More patients in the dexmedetomidine group (42% vs 31%; P = .61) were able to complete post-ICU neuropsychological testing, with similar scores in the tests evaluating global cognitive, motor speed, and attention functions. The 12-month time to death was 363 days in the dexmedetomidine group vs 188 days in the lorazepam group (P = .48)., Conclusion: In mechanically ventilated ICU patients managed with individualized targeted sedation, use of a dexmedetomidine infusion resulted in more days alive without delirium or coma and more time at the targeted level of sedation than with a lorazepam infusion., Trial Registration: clinicaltrials.gov Identifier: NCT00095251.

ICU delirium represents a form of brain dysfunction that in many cohorts has been diagnosed in 60 to 85% of patients receiving mechanical ventilation. This organ dysfunction is grossly underrecognized because a majority of patients have hypoactive or "quiet" delirium characterized by "negative" symptoms (eg, inattention and a flat affect) not alarming the treating team. Hyperactive delirium, formerly called ICU psychosis, stands out because of symptoms such as agitation that may cause harm to self or staff, but is actually rare relative to hypoactive delirium and associated with a better prognosis. Delirium is often incorrectly thought to be transient and of little consequence. After adjusting for numerous covariates, delirium is a strong, independent predictor of prolonged length of stay, reintubation, higher mortality, and cost of care. Expanded work on patient safety and recommendations by professional societies have established the importance of delirium monitoring and recommended it as standard practice in ICUs all over the world. This evidence-based review for physicians, nurses, respiratory therapists, and pharmacists will outline why it is imperative that patients be routinely monitored for delirium. This review will discuss modifiable risk factors for delirium, such as metabolic disturbances or potent sedative and analgesic medications. Attention to mitigating risk factors, along with recommended pharmacologic approaches such as antipsychotic medications, may provide resolution of delirium in some patients, while others will persist with refractory brain dysfunction and long-term cognitive impairment following critical illness.

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.

The prevention or treatment of pain, anxiety, and delirium in the ICU is an important goal. But achieving a balance between sedation and analgesia, especially in critically ill patients on mechanical ventilation, can be challenging. Both under- and oversedation carry serious risks. 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 that relate to sedation assessment and management, as well as the current literature. This month Part 1 also reviews pertinent recommendations concerning pain and delirium and discusses tools for assessing pain, delirium, and sedation. In August Part 2 will explore pharmacologic and nonpharmacologic management of anxiety and agitation in critically ill patients. The prevention or treatment of pain, anxiety, and delirium in the ICU is an important goal. But achieving a balance between sedation and analgesia, especially in critically ill patients on mechanical ventilation, can be challenging. Both under- and oversedation carry serious risks. 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 that relate to sedation assessment and management, as well as the current literature. This month Part 1 also reviews pertinent recommendations concerning pain and delirium and discusses tools for assessing pain, delirium, and sedation. In August Part 2 will explore pharmacologic and nonpharmacologic management of anxiety and agitation in critically ill patients.

Objective: To test for an association between apolipoprotein E (APOE) genotypes and duration of intensive care unit delirium., Design: Prospective, observational cohort study., Setting: A 541-bed, community-based teaching hospital., Patients: Fifty-three mechanically ventilated intensive care unit patients., Interventions: None., Measurements and Main Results: All patients were managed with standardized sedation and ventilator weaning protocols as part of an ongoing clinical trial and were evaluated prospectively for delirium with the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). DNA was extracted from whole blood samples obtained on enrollment, and APOE genotype was determined using polymerase chain reaction followed by restriction enzyme digestion by investigators blinded to the clinical information. Delirium occurred in 47 (89%) patients at some point during the intensive care unit stay. Of the 53 patients, 12 (23%) had an APOE4 allele (APOE4+) and 41 (77%) had only APOE2 or APOE3 alleles (APOE4-). APOE4+ patients were younger (53.2 +/- 21.9 vs. 65.4 +/- 13.4, p = .08) and less often admitted for pneumonia (0% vs. 29.3%, p = .05) compared with APOE4- patients, yet they had a duration of delirium that was twice as long: median (interquartile range), 4 (3, 4.5) vs. 2 (1, 4) days (p = .05). No other clinical outcomes were significantly different between the APOE4+ and APOE4- patients. Using multivariable regression analysis to adjust for age, admission diagnosis of sepsis or acute respiratory distress syndrome or pneumonia, severity of illness, and duration of coma, the presence of APOE4 allele was the strongest predictor of delirium duration (odds ratio, 7.32; 95% confidence interval, 1.82-29.51, p = .005)., Conclusions: APOE4 allele represents the first demonstrated genetic predisposition to longer duration of delirium in humans.

Objectives: To describe the motoric subtypes of delirium in critically ill patients and compare patients aged 65 and older with a younger cohort., Design: Prospective cohort study., Setting: The medical intensive care unit (MICU) of a tertiary care academic medical center., Participants: Six hundred fourteen MICU patients admitted during a process improvement initiative to monitor levels of sedation and delirium., Measurements: MICU nursing staff assessed delirium and level of consciousness in all MICU patients at least once per 12-hour shift using the Confusion Assessment Method for the Intensive Care Unit and the Richmond Agitation-Sedation Scale. Delirium episodes were categorized as hypoactive, hyperactive, and mixed type., Results: Delirium was detected in 112 of 156 (71.8%) subjects aged 65 and older and 263 of 458 (57.4%) subjects younger than 65. Mixed type was most common (54.9%), followed by hypoactive delirium (43.5%) and purely hyperactive delirium (1.6%). Patients aged 65 and older experienced hypoactive delirium at a greater rate than younger patients (41.0% vs 21.6%, P<.001) and never experienced hyperactive delirium. Older age was strongly and independently associated with hypoactive delirium (adjusted odds ratio=3.0, 95% confidence interval=1.7-5.3), compared with no delirium in a model that adjusted for other important determinants of delirium including severity of illness, sedative medication use, and ventilation status., Conclusion: Older age is a strong predictor of hypoactive delirium in MICU patients, and this motoric subtype of delirium may be missed in the absence of active monitoring.

Background: Delirium has recently been shown as a predictor of death, increased cost, and longer duration of stay in ventilated patients. Sedative and analgesic medications relieve anxiety and pain but may contribute to patients' transitioning into delirium., Methods: In this cohort study, the authors designed a priori an investigation to determine whether sedative and analgesic medications independently increased the probability of daily transition to delirium. Markov regression modeling (adjusting for 11 covariates) was used in the evaluation of 198 mechanically ventilated patients to determine the probability of daily transition to delirium as a function of sedative and analgesic dose administration during the previous 24 h., Results: Lorazepam was an independent risk factor for daily transition to delirium (odds ratio, 1.2 [95% confidence interval, 1.1-1.4]; P = 0.003), whereas fentanyl, morphine, and propofol were associated with higher but not statistically significant odds ratios. Increasing age and Acute Physiology and Chronic Health Evaluation II scores were also independent predictors of transitioning to delirium (multivariable P values < 0.05)., Conclusions: Lorazepam administration is an important and potentially modifiable risk factor for transitioning into delirium even after adjusting for relevant covariates.

Introduction: Delirium occurs in most ventilated patients and is independently associated with more deaths, longer stay, and higher cost. Guidelines recommend monitoring of delirium in all intensive care unit (ICU) patients, though few data exist in non-ventilated patients. The study objective was to determine the relationship between delirium and outcomes among non-ventilated ICU patients., Method: A prospective cohort investigation of 261 consecutively admitted medical ICU patients not requiring invasive mechanical ventilation during hospitalization at a tertiary-care, university-based hospital between February 2002 and January 2003. ICU nursing staff assessed delirium and level of consciousness at least twice per day using the Confusion Assessment Method for the ICU (CAM-ICU) and Richmond Agitation-Sedation Scale (RASS). Cox regression with time-varying covariates was used to determine the independent relationship between delirium and clinical outcomes., Results: Of 261 patients, 125 (48%) experienced at least one episode of delirium. Patients who experienced delirium were older (mean +/- SD: 56 +/- 18 versus 49 +/- 17 years; p = 0.002) and more severely ill as measured by Acute Physiology and Chronic Health Evaluation II (APACHE II) scores (median 15, interquartile range (IQR) 10-21 versus 11, IQR 6-16; p < 0.001) compared to their non-delirious counterparts. Patients who experienced delirium had a 29% greater risk of remaining in the ICU on any given day (compared to patients who never developed delirium) even after adjusting for age, gender, race, Charlson co-morbidity score, APACHE II score, and coma (hazard ratio (HR) 1.29; 95% confidence interval (CI) 0.98-1.69, p = 0.07). Similarly, patients who experienced delirium had a 41% greater risk of remaining in the hospital after adjusting for the same covariates (HR 1.41; 95% CI 1.05-1.89, p = 0.023). Hospital mortality was higher among patients who developed delirium (24/125, 19%) versus patients who never developed delirium (8/135, 6%), p = 0.002; however, time to in-hospital death was not significant the adjusted (HR 1.27; 95% CI 0.55-2.98, p = 0.58)., Conclusion: Delirium occurred in nearly half of the non-ventilated ICU patients in this cohort. Even after adjustment for relevant covariates, delirium was found to be an independent predictor of longer hospital stay.

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.