Long-term outcomes after treatment of delirium during critical illness with antipsychotics (MIND-USA): a randomised, placebo-controlled, phase 3 trial.

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.

An Exploration of Critical Care Professionals' 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: A Group Concept Mapping Study.

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.

Interprofessional Team Collaboration and Work Environment Health in 68 US Intensive Care Units.

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.

Factors Associated With Spontaneous Awakening Trial and Spontaneous Breathing Trial Performance in Adults With Critical Illness: Analysis of a Multicenter, Nationwide, Cohort Study.

BACKGROUND: Broad-scale adoption of spontaneous awakening trials (SATs) and spontaneous breathing trials (SBTs) into everyday practice has been slow, and uncertainty exists regarding what factors facilitate or impede their routine delivery. RESEARCH QUESTION: What patient, practice, and pharmacologic factors are associated with SAT and SBT performance and to what extent do they predict overall SAT/SBT performance? STUDY DESIGN AND METHODS: This secondary analysis used data collected from a national quality improvement collaborative composed of 68 diverse ICUs. Adults with critical illness adults who received mechanical ventilation and/or continuously infused sedative medications were included. We performed mixed-effects logistic regression modeling, created receiver operating characteristic curves, and calculated the area under the curve (AUC). RESULTS: Included in the SAT and SBT analysis were 4,847 and 4,938 patients, respectively. In multivariable models controlling for admitting patient characteristics, factors independently associated with higher odds of a next-day SAT and SBT included physical restraint use (adjusted odds ratio [AOR], 1.63; 95% CI, 1.42-1.87; AOR, 1.83; 95% CI, 1.60-2.09), documented target sedation level (AOR, 1.68; 95% CI, 1.41-2.01; AOR, 1.46; 95% CI, 1.24-1.72), more frequent level of arousal assessments (AOR, 1.22; 95% CI, 1.03-1.43; AOR, 1.32; 95% CI, 1.13-1.54), and dexmedetomidine administration (AOR, 1.23; 95% CI, 1.05-1.45; AOR, 1.52; 95% CI, 1.27-1.80). Factors independently associated with lower odds of a next-day SAT and SBT included deep sedation/coma (AOR, 0.69; 95% CI, 0.60-0.80; AOR, 0.33; 95% CI, 0.28-0.37) and benzodiazepine (AOR, 0.83; 95% CI, 0.72-0.95; AOR, 0.67; 95% CI, 0.59-0.77) or ketamine (AOR, 0.34; 95% CI, 0.16-0.71; AOR, 0.40; 95% CI, 0.18-0.88) administration. Models incorporating admitting, daily, and unit variations displayed moderate discriminant accuracy in predicting next-day SAT (AUC, 0.73) and SBT (AUC, 0.72) performance. INTERPRETATION: There are a number of modifiable factors associated with SAT/SBT performance that are amenable to the development and testing of implementation interventions.

Effects of a National Quality Improvement Collaborative on ABCDEF Bundle Implementation.

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.

Quantitative EEG During Critical Illness Correlates with Patterns of Long-Term Cognitive Impairment.

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.

Delirium in critical illness: clinical manifestations, outcomes, and management.

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.

ICU Survivorship-The Relationship of Delirium, Sedation, Dementia, and Acquired Weakness.

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.

Dexmedetomidine or Propofol for Sedation in Mechanically Ventilated Adults with Sepsis.

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.).

Prevalence and risk factors for delirium in critically ill patients with COVID-19 (COVID-D): a multicentre cohort study.

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.

Organizational Characteristics Associated With ICU Liberation (ABCDEF) Bundle Implementation by Adult ICUs in Michigan.

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.

A multisite study of nurse-reported perceptions and practice of ABCDEF bundle components.

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 (rs = 0.05-0.28) or sedation plan discussion during rounds and Awakening and Breathing trial Coordination (rs = 0.19). Delirium is more likely to be discussed during rounds when ICU physicians and nurse managers facilitate delirium reduction (rs = 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 (rs = 0.36-0.47). Physician leadership had the strongest correlation with reporting an ICU environment that facilitates ABCDEF bundle implementation (rs = 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.

COVID-19: What do we need to know about ICU delirium during the SARS-CoV-2 pandemic?

In March 2020, the World Health Organisation announced the COVID-19 pandemic caused by the SARS-CoV-2 virus. As well as respiratory failure, the SARS-CoV-2 may cause central nervous system (CNS) involvement, including delirium occurring in critically ill patients (ICU delirium). Due attention must be paid to this subject in the face of the COVID-19 pandemic. Delirium, the detection of which takes less than two minutes, is frequently underestimated during daily routine ICU care, but it may be a prodromal symptom of infection or hypoxia associated with severe respiratory failure. During the COVID-19 pandemic, systematic delirium monitoring using validated tests (CAM-ICU or ICDSC) may be sacrificed. This is likely to be due to the fact that the main emphasis is placed on organisational issues, i.e. the lack of ventilators, setting priorities for limited mechanical ventilation options, and a shortage of personal protective equipment. Early identification of patients with delirium is critical in patients with COVID-19 because the occurrence of delirium may be an early symptom of worsening respiratory failure or of infectious spread to the CNS mediated by potential neuroinvasive mechanisms of the coronavirus. The purpose of this review is to identify problems related to the development of delirium during the COVID-19 epidemic, which are presented in three areas: i) factors contributing to delirium in COVID-19, ii) potential pathophysiological factors of delirium in COVID-19, and iii) long-term consequences of delirium in COVID-19. This article discusses how healthcare workers can reduce the burden of delirium by identifying potential risk factors and difficulties during challenges associated with SARS-CoV-2 infection.

COVID-19: ICU delirium management during SARS-CoV-2 pandemic.

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.

Early Identification of Delirium in Intensive Care Unit Patients: Improving the Quality of Care.

BACKGROUND: Delirium has long-term consequences for intensive care unit patients. The project site, an urban academic hospital, did not previously use a validated delirium screening tool, and patients commonly received sedative medications to treat agitation. OBJECTIVE: To minimize the risk of delirium by implementing the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) as the standard-of-care delirium assessment tool in the intensive care unit and by decreasing use of high-risk medications (ie, opioids and benzodiazepines). METHODS: An observational pretest-posttest design was used to analyze deidentified patient data from electronic health records. The evidence-based practice intervention focused on educating nurses on high-risk medications and CAM-ICU implementation. Control charts, χ2 tests, and mixed regression models were used to evaluate the effectiveness of the intervention in reducing delirium risk by decreasing use of high-risk medications. RESULTS: High-risk medication use significantly decreased after intervention among patients at low risk for delirium (before intervention, 7.37%; after intervention, 3.92%; P < .001) and at high risk for delirium (before intervention, 4.73%; after intervention, 2.99%; P < .001). Hospital stays were significantly shorter in patients at low risk than at high risk for delirium (P < .001) but increased by a mean of 0.13 days with each additional high-risk medication used (P < .001). CONCLUSIONS: The variation of high-risk medication use was significantly controlled with the implementation of CAM-ICU and education. Nurses felt that hands-on training with the CAM-ICU increased their comfort in identifying patients at risk for delirium. Future work will focus on assessment accuracy.

Best Practices for Conducting Interprofessional Team Rounds to Facilitate Performance of the ICU Liberation (ABCDEF) Bundle.

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.

Statistical analysis plan for the Maximizing the Efficacy of Sedation and Reducing Neurological Dysfunction and Mortality in Septic Patients with Acute Respiratory Failure trial.

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).

Assessment of Variability in End-of-Life Care Delivery in Intensive Care Units in the United States.

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.