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The article presents a study which tested the hypothesis that the hyperinflammatory subphenotype is associated with worse acute brain dysfunction in patients who are in mechanically ventilated intensive care units (ICUs). Topics include baseline characteristics of the overall cohort and by subphenotype, associations between hyperinflammatory subphenotype and acute brain dysfunction and death, and strengths of the study.

Purpose: The purpose of this study was to determine associations between markers of inflammation and endogenous anticoagulant activity with delirium and coma during critical illness. Methods: In this prospective cohort study, we enrolled adults with respiratory failure and/or shock treated in medical or surgical intensive care units (ICUs) at 5 centers. Twice per day in the ICU, and daily thereafter, we assessed mental status using the Richmond Agitation Sedation Scale (RASS) and the Confusion Assessment Method-Intensive Care Unit (CAM-ICU). We collected blood samples on study days 1, 3, and 5, measuring levels of C-reactive protein (CRP), interferon gamma (IFN-γ), interleukin (IL)-1 beta (IL-1β), IL-6, IL-8, IL-10, IL-12, matrix metalloproteinase-9 (MMP-9), tumor necrosis factor-alpha (TNF-α), tumor necrosis factor receptor 1 (TNFR1), and protein C using validated protocols. We used multinomial logistic regression to analyze associations between biomarkers and the odds of delirium or coma versus normal mental status the following day, adjusting for age, sepsis, Sequential Organ Failure Assessment (SOFA), study day, corticosteroids, and sedatives. Results: Among 991 participants with a median age (interquartile range, IQR) of 62 [53–72] years and enrollment SOFA of 9 [7–11], higher concentrations of IL-6 (odds ratio [OR] [95% CI]: 1.8 [1.4–2.3]), IL-8 (1.3 [1.1–1.5]), IL-10 (1.5 [1.2–1.8]), TNF-α (1.2 [1.0–1.4]), and TNFR1 (1.3 [1.1–1.6]) and lower concentrations of protein C (0.7 [0.6–0.8])) were associated with delirium the following day. Higher concentrations of CRP (1.4 [1.1–1.7]), IFN-γ (1.3 [1.1–1.5]), IL-6 (2.3 [1.8–3.0]), IL-8 (1.8 [1.4–2.3]), and IL-10 (1.5 [1.2–2.0]) and lower concentrations of protein C (0.6 [0.5–0.8]) were associated with coma the following day. IL-1β, IL-12, and MMP-9 were not associated with mental status. Conclusion: Markers of inflammation and possibly endogenous anticoagulant activity are associated with delirium and coma during critical illness. [ABSTRACT FROM AUTHOR]

The article discusses ventilator-associated brain injury (VABI) as a potential complication of mechanical ventilation, presenting evidence from preclinical studies and observational data. It defines VABI as brain injury resulting directly from positive pressure mechanical ventilation, independent of other factors like sedation. It highlights the need for further research to understand the mechanisms of VABI and evaluate potential therapeutic strategies.

Purpose of review: The A2F intensive care unit (ICU) liberation bundle is a multi-component management strategy that has been shown to improve hospital survival and reduce rates of delirium and ICU readmission. In this review, we aim to highlight the potential role of the A2F bundle in neurocritical care settings while further delineating its individual components. Recent findings: The A2F bundle and its components are supported by a robust evidence base that continues to develop regarding the management of critically ill patients. Recent additions include the DEXACET trial, which found that scheduled intravenous acetaminophen reduced delirium, breakthrough analgesia, and ICU length of stay for post-operative patients. Meanwhile, although previous trials indicated that dexmedetomidine for light sedation reduces delirium when compared with benzodiazepine sedation, the MENDS2 and SPICE-III trials did not find that dexmedetomidine as a first-line sedative for mechanically ventilated ICU patients improved outcomes compared with propofol. Trials of family engagement support more frequent goals of care discussions and improvements in quality of communication and patient-centered care. However, evidence specific to neurocritically ill patients remains limited. A small trial found utility for goals of care decision aids to support shared decision-making in patients with severe acute brain injury. Recent studies have also suggested that delirium may have a unique impact on outcomes in neurocritically ill patients, and new tools may have utility in delirium identification in patients with acute neurological injury. Finally, there is accumulating evidence to suggest that early mobilization is safe and feasible in neurocritically ill patients, even those with external ventricular drains, and that it may improve outcomes. Summary: Although the A2F bundle in its entirety has not been specifically studied in neurocritically ill patients, many of its goals overlap with contemporary neurocritical care practices. Future studies are needed to determine optimal ICU liberation strategies that can be safely and effectively implemented in patients with acute neurological injury. [ABSTRACT FROM AUTHOR]

Delirium is a common condition in intensive care unit (ICU) patients and is associated with negative outcomes. While non-pharmacologic treatments have shown some success in reducing delirium, there is currently no recommended pharmacologic treatment. Haloperidol, a commonly used medication, has not been found to be more effective than a placebo in reducing delirium. However, a recent study found that haloperidol may have a positive effect on long-term mortality in ICU patients. Further research is needed to determine the optimal dose of haloperidol and to explore other factors that may influence long-term outcomes. ICU clinicians should not increase their use of haloperidol until more research is conducted. [Extracted from the article]

Delirium is a common condition in the ICU, and while non-pharmacological interventions are recommended, pharmacological treatment with haloperidol is often used despite recommendations against it. Two recent trials, the MIND-USA Study and the AID-ICU trial, examined the effectiveness and safety of haloperidol for delirium treatment in ICU patients. Both trials found no significant difference in their primary outcomes, but the AID-ICU trial did find lower mortality rates in the haloperidol group. The trials were well-designed and had low bias, but the difference in mortality outcomes is surprising and requires further investigation. Table 1 in the document provides detailed information on the trials' characteristics, interventions, and outcomes. While there were some differences in definitions and participant characteristics, subgroup analyses found no evidence of treatment effect heterogeneity. Differences in exposure to open-label antipsychotics may explain some of the differences in mortality outcomes. The AID-ICU trial showed potential benefits of haloperidol for days alive and out of the hospital, days alive without delirium or coma, and mortality. However, there is still uncertainty about the effects of haloperidol in delirious ICU patients, and more research is needed to understand its mechanisms of action and long-term outcomes. [Extracted from the article]

Background: Patients with acute respiratory failure have multiple risk factors for disability following their intensive care unit stay. Interventions to facilitate independence at hospital discharge may be more effective if personalized for patient subtypes. Objectives: To identify subtypes of patients with acute respiratory failure requiring mechanical ventilation and compare post–intensive care functional disability and intensive care unit mobility level among subtypes. Methods: Latent class analysis was conducted in a cohort of adult medical intensive care unit patients with acute respiratory failure receiving mechanical ventilation who survived to hospital discharge. Demographic and clinical medical record data were collected early in the stay. Clinical characteristics and outcomes were compared among subtypes by using Kruskal-Wallis tests and χ2 tests of independence. Results: In a cohort of 934 patients, the 6-class model provided the optimal fit. Patients in class 4 (obesity and kidney impairment) had worse functional impairment at hospital discharge than patients in classes 1 through 3. Patients in class 3 (alert patients) had the lowest magnitude of functional impairment (P <.001) and achieved the earliest out-of-bed mobility and highest mobility level of all subtypes (P <.001). Conclusions: Acute respiratory failure survivor subtypes identified from clinical data available early in the intensive care unit stay differ in post–intensive care functional disability. Future research should target high-risk patients in early rehabilitation trials in the intensive care unit. Additional investigation of contextual factors and mechanisms of disability is critical to improving quality of life in acute respiratory failure survivors. [ABSTRACT FROM AUTHOR]

Background: Sleep and circadian disruption (SCD) is common and severe in the ICU. On the basis of rigorous evidence in non)ICU populations and emerging evidence in ICU populations, SCD is likely to have a profound negative impact on patient outcomes. Thus, it is urgent that we establish research priorities to advance understanding of ICU SCD. Methods: We convened a multidisciplinary group with relevant expertise to participate in an American Thoracic Society Workshop. Workshop objectives included identifying ICU SCD subtopics of interest, key knowledge gaps, and research priorities. Members attended remote sessions from March to November 2021. Recorded presentations were prepared and viewed by members before Workshop sessions. Workshop discussion focused on key gaps and related research priorities. The priorities listed herein were selected on the basis of rank as established by a series of anonymous surveys. Results: We identified the following research priorities: establish an ICU SCD definition, further develop rigorous and feasible ICU SCD measures, test associations between ICU SCD domains and outcomes, promote the inclusion of mechanistic and patient-centered outcomes within large clinical studies, leverage implementation science strategies to maximize intervention fidelity and sustainability, and collaborate among investigators to harmonize methods and promote multisite investigation. Conclusions: ICU SCD is a complex and compelling potential target for improving ICU outcomes. Given the influence on all other research priorities, further development of rigorous, feasible ICU SCD measurement is a key next step in advancing the field. [ABSTRACT FROM AUTHOR]

Background: Sleep and circadian disruption (SCD) is common and severe in the ICU. On the basis of rigorous evidence in non-ICU populations and emerging evidence in ICU populations, SCD is likely to have a profound negative impact on patient outcomes. Thus, it is urgent that we establish research priorities to advance understanding of ICU SCD. Methods: We convened a multidisciplinary group with relevant expertise to participate in an American Thoracic Society Workshop. Workshop objectives included identifying ICU SCD subtopics of interest, key knowledge gaps, and research priorities. Members attended remote sessions from March to November 2021. Recorded presentations were prepared and viewed by members before Workshop sessions. Workshop discussion focused on key gaps and related research priorities. The priorities listed herein were selected on the basis of rank as established by a series of anonymous surveys. Results: We identified the following research priorities: establish an ICU SCD definition, further develop rigorous and feasible ICU SCD measures, test associations between ICU SCD domains and outcomes, promote the inclusion of mechanistic and patient-centered outcomes within large clinical studies, leverage implementation science strategies to maximize intervention fidelity and sustainability, and collaborate among investigators to harmonize methods and promote multisite investigation. Conclusions: ICU SCD is a complex and compelling potential target for improving ICU outcomes. Given the influence on all other research priorities, further development of rigorous, feasible ICU SCD measurement is a key next step in advancing the field. [ABSTRACT FROM AUTHOR]

Importance: Agitation is common in mechanically ventilated ICU patients, but little is known about physician attitudes regarding agitation in this setting. Objectives: To characterize physician attitudes regarding agitation in mechanically ventilated ICU patients. Design, Setting, and Participants: We surveyed critical care physicians within a multicenter health system in Western Pennsylvania, assessing attitudes regarding agitation during mechanical ventilation and use of and confidence in agitation management options. We used quantitative clinical vignettes to determine whether agitation influences confidence regarding readiness for extubation. We sent our survey to 332 critical care physicians, of whom 80 (24%) responded and 69 were eligible (had cared for a mechanically ventilated patient in the preceding three months). Main Outcomes and Measures: Respondent confidence in patient readiness for extubation (0–100%, continuous) and frequency of use and confidence in management options (1–5, Likert). Results: Of 69 eligible responders, 61 (88%) agreed agitation is common and 49 (71%) agreed agitation is a barrier to extubation, but only 27 (39%) agreed their approach to agitation is evidence-based. Attitudes regarding agitation did not differ much by practice setting or physician demographics, though respondents working in medical ICUs were more likely (P =.04) and respondents trained in surgery or emergency medicine were less likely (P =.03) than others to indicate that agitation is an extubation barrier. Fifty-three (77%) respondents reported they frequently use non-pharmacologic measures to treat agitation, and 42 (70%) of those who reported they used non-pharmacologic measures during the prior 3 months indicated confidence in their effectiveness. In responses to clinical vignettes, confidence in patient's readiness for extubation was significantly lower if the patient was agitated (P <.001) or tachypneic (P <.001), but the presence of both agitation and tachypnea did not reduce confidence compared with tachypnea alone (P =.24). Conclusions and Relevance: Most critical care physicians consider agitation during mechanical ventilation a common problem and agreed that agitation is a barrier to extubation. Treatment practice varies widely. [ABSTRACT FROM AUTHOR]

Background: Delirium is a frequent manifestation of acute brain dysfunction and is associated with cognitive impairment. The hypothesized mechanism of brain dysfunction during critical illness is centered on neuroinflammation, regulated in part by the cholinergic system. Point-of-care serum cholinesterase enzyme activity measurements serve as a real-time index of cholinergic activity. We hypothesized that cholinesterase activity during critical illness would be associated with delirium in the intensive care unit (ICU) and cognitive impairment after discharge. Methods: We enrolled adults with respiratory failure and/or shock and measured plasma acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity on days 1, 3, 5, and 7 after enrollment. AChE values were also normalized per gram of hemoglobin (AChE/Hgb). We assessed for coma and delirium twice daily using the Richmond Agitation Sedation Scale and the Confusion Assessment Method for the ICU to evaluate daily mental status (delirium, coma, normal) and days alive without delirium or coma. Cognitive impairment, disability, and health-related quality of life were assessed at up to 6 months post-discharge. We used multivariable regression to determine whether AChE, AChE/Hgb, and BChE activity were associated with outcomes after adjusting for relevant covariates. Results: We included 272 critically ill patients who were a median (IQR) age 56 (39–67) years and had a median Sequential Organ Failure Assessment score at enrollment of 8 (5–11). Higher daily AChE levels were associated with increased odds of being delirious versus normal mental status on the same day (Odds Ratio [95% Confidence Interval] 1.64 [1.11, 2.43]; P = 0.045). AChE/Hgb and BChE activity levels were not associated with delirious mental status. Lower enrollment BChE was associated with fewer days alive without delirium or coma (P = 0.048). AChE, AChE/Hgb, and BChE levels were not significantly associated with cognitive impairment, disability, or quality of life after discharge. Conclusion: Cholinesterase activity during critical illness is associated with delirium but not with outcomes after discharge, findings that may reflect mechanisms of acute brain organ dysfunction. Trial Registration: NCT03098472. Registered 31 March 2017. [ABSTRACT FROM AUTHOR]

This document is a response to a previous viewpoint on negative pressure ventilation (NPV) and raises several points in response. Firstly, it argues that NPV can cause lung stress, contrary to the claim made by the previous authors. Secondly, it disputes the notion that NPV guarantees the absence of sedation and delirium, stating that sedation may still be necessary for distress control. Thirdly, it highlights that the method of applying NPV can impact hemodynamics, potentially reducing cardiac output. Lastly, it acknowledges that the concept of ventilator-associated brain injury is still a hypothesis and suggests that it is premature to claim that NPV can prevent it. [Extracted from the article]

Background: Intensive care unit (ICU) delirium is associated with a proinflammatory state and poor outcomes. An epigenetic mechanism may modify inflammation. Objective: To identify inflammatory gene methylation trajectory groups and explore their clinical and demographic variability. Methods: Patients were at least 18 years old; received mechanical ventilation for at least 24 hours; had no brain disorder/injury, preexisting dementia, or positive toxicology screen; and were admitted to a medical or surgical/trauma ICU. Delirium was assessed (Confusion Assessment Method for the ICU) and blood samples were collected daily for up to 10 days. Methylation of 3 genes in the inflammatory pathway was quantified. Latent class analysis identified gene methylation trajectories, and variables (including delirium) were compared between trajectory groups. Results: Of 68 patients (53% female, 88% White), 65% developed delirium. Of 3 methylation trajectories for IL6ST, the group with low initial methylation increasing over time included younger male patients who were less likely to have delirium, and the group with high initial methylation decreasing over time included older (P =.01) female (P =.05) patients who more often had delirium (P =.05). IL17C had 2 methylation trajectories without significant differences in delirium, age, or sex. IL13RA1 had 2 methylation trajectories without differences in delirium or age; the group with sustained high methylation had more female patients (P =.003). Conclusions: Temporal variability in inflammatory gene methylation occurs after ICU admission. Delirium, female sex, and older age were more common with higher IL6ST methylation that decreased over time. Larger studies are needed to further elucidate these relationships. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this Intensive Care Medicine Rapid Practice Guideline (ICM‑RPG) was to formulate evidence‑based guidance for the use of dexmedetomidine for sedation in invasively mechanically ventilated adults in the intensive care unit (ICU). Methods: We adhered to the methodology for trustworthy clinical practice guidelines, including use of the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the certainty of evidence, and the Evidence-to-Decision framework to generate recommendations. The guideline panel comprised 28 international panelists, including content experts, ICU clinicians, methodologists, and patient representatives. Through teleconferences and web‑based discussions, the panel provided input on the balance and magnitude of the desirable and undesirable effects, the certainty of evidence, patients' values and preferences, costs and resources, feasibility, acceptability, and research priorities. Results: The ICM‑RPG panel issued one weak recommendation (suggestion) based on overall moderate certainty of evidence: "In invasively mechanically ventilated adult ICU patients, we suggest using dexmedetomidine over other sedative agents, if the desirable effects including a reduction in delirium are valued over the undesirable effects including an increase in hypotension and bradycardia". Conclusion: This ICM-RPG provides updated evidence-based guidance on the use of dexmedetomidine for sedation in mechanically ventilated adults, and outlines uncertainties and research priorities. [ABSTRACT FROM AUTHOR]

A substantial proportion of critically ill patients require ventilator support with the majority requiring invasive mechanical ventilation. Timely and safe liberation from invasive mechanical ventilation is a critical aspect of patient care in the intensive care unit (ICU) and is a top research priority for patients and clinicians. In this article, we discuss how to (1) identify candidates for liberation from mechanical ventilation, (2) conduct spontaneous breathing trials (SBTs), and (3) optimize patients for liberation from mechanical ventilation. We also discuss the roles for (4) extubation to noninvasive ventilation and (5) newer modes of mechanical ventilation during liberation from mechanical ventilation. We conclude that, though substantial progress has been made in identifying patients who are likely to be liberated (e.g., through the use of SBTs) and management strategies that speed liberation from the ventilator (e.g., protocolized SBTs, lighter sedation, and early mobilization), many important questions regarding liberation from mechanical ventilation in clinical practice remain unanswered. [ABSTRACT FROM AUTHOR]

Background: Several studies have previously reported the presence of altered cerebral perfusion during sepsis. However, the role of non-invasive neuromonitoring, and the impact of altered cerebral perfusion, in sepsis patients with delirium remains unclear. Methods: We performed a systematic review of studies that used near-infrared spectroscopy (NIRS) and/or transcranial Doppler (TCD) to assess adults (-18 years) with sepsis and delirium. From study inception to July 28, 2020, we searched the following databases: Ovid MedLine, Embase, Cochrane Library, and Web of Science. Results: Of 1546 articles identified, 10 met our inclusion criteria. Although NIRS-derived regional cerebral oxygenation was consistently lower, this difference was only statistically significant in one study. TCD-derived cerebral blood flow velocity was inconsistent across studies. Importantly, both impaired cerebral autoregulation during sepsis and increased cerebrovascular resistance were associated with delirium during sepsis. However, the heterogeneity in NIRS and TCD devices, duration of recording (from 10 seconds to 72 hours), and delirium assessment methods (e.g., electronic medical records, confusion assessment method for the intensive care unit), precluded meta-analysis. Conclusion: The available literature demonstrates that cerebral perfusion disturbances may be associated with delirium in sepsis. However, future investigations will require consistent definitions of delirium, delirium assessment training, harmonized NIRS and TCD assessments (e.g., consistent measurement site and length of recording), as well as the quantification of secondary and tertiary variables (i.e., Cox, Mxa, MAPOPT), in order to fully assess the relationship between cerebral perfusion and delirium in patients with sepsis. [ABSTRACT FROM AUTHOR]

Rationale: Mechanically ventilated patients in the intensive care unit (ICU) are often managed to maximize oxygenation, yet hyperoxemia may be deleterious to some. Little is known about how ICU providers weigh tradeoffs between hypoxemia and hyperoxemia when managing acute respiratory failure. Objectives: To define ICU providers' mental models for managing oxygenation for patients with acute respiratory failure and identify barriers and facilitators to conservative oxygen therapy. Methods: In two large U.S. tertiary care hospitals, we performed semistructured interviews with a purposive sample of ICU nurses, respiratory therapists, and physicians. We assessed perceptions of oxygenation management, hyperoxemia, and conservative oxygen therapies through interviews, which we audio recorded and transcribed verbatim. We analyzed transcripts for representative themes using an iterative thematic-analysis approach. Results: We interviewed 10 nurses, 10 respiratory therapists, 4 fellows, and 5 attending physicians before reaching thematic saturation. Major themes included perceptions of hyperoxemia, attitudes toward conservative oxygen therapy, and aspects of titrated-oxygen-therapy implementation. Many providers did not recognize the term "hyperoxemia," whereas others described a poor understanding; several stated they never encounter hyperoxemia clinically. Concerns about hyperoxemia varied: some providers believed that typical ventilation strategies emphasizing progressive lowering of the fraction of inspired oxygen mitigated worries about excess oxygen administration, whereas others maintained that hyperoxemia is harmful only to patients with chronic lung disease. Almost all interviewees expressed familiarity with lower oxygen saturations in chronic obstructive pulmonary disease. Cited barriers to conservative oxygen therapy included concerns about hypoxemia, particularly among nurses and respiratory therapists; perceptions that hyperoxemia is not harmful; and a lack of clear evidence supporting conservative oxygen therapy. Interviewees suggested that interprofessional education and convincing clinical trial evidence could facilitate uptake of conservative oxygenation. Conclusions: This study describes attitudes toward hyperoxemia and conservative oxygen therapy. These preferences and uncertain benefits and risks of conservative oxygen therapy should be considered during future implementation efforts. Successful oxygen therapy implementation most likely will require 1) improving awareness of hyperoxemia's effects, 2) normalizing lower saturations in patients without chronic lung disease, 3) addressing ingrained beliefs regarding oxygen management and oxygen's safety, and 4) using interprofessional education to obtain buy-in across providers and inform the ICU team. [ABSTRACT FROM AUTHOR]

Rationale: The biological mechanisms of long-term cognitive impairment and disability after critical illness are unclear.Objectives: To test the hypothesis that markers of acute inflammation and coagulation are associated with subsequent long-term cognitive impairment and disability.Methods: We obtained plasma samples from adults with respiratory failure or shock on Study Days 1, 3, and 5 and measured concentrations of CRP (C-reactive protein), IFN-γ, IL-1β, IL-6, IL-8, IL-10, IL-12, MMP-9 (matrix metalloproteinase-9), TNF-α (tumor necrosis factor-α), soluble TNF receptor 1, and protein C. At 3 and 12 months after discharge, we assessed global cognition, executive function, and activities of daily living. We analyzed associations between markers and outcomes using multivariable regression, adjusting for age, sex, education, comorbidities, baseline cognition, doses of sedatives and opioids, stroke risk (in cognitive models), and baseline disability scores (in disability models).Measurements and Main Results: We included 548 participants who were a median (interquartile range) of 62 (53-72) years old, 88% of whom were mechanically ventilated, and who had an enrollment Sequential Organ Failure Assessment score of 9 (7-11). After adjusting for covariates, no markers were associated with long-term cognitive function. Two markers, CRP and MMP-9, were associated with greater disability in basic and instrumental activities of daily living at 3 and 12 months. No other markers were consistently associated with disability outcomes.Conclusions: Markers of systemic inflammation and coagulation measured early during critical illness are not associated with long-term cognitive outcomes and demonstrate inconsistent associations with disability outcomes. Future studies that pair longitudinal measurement of inflammation and related pathways throughout the course of critical illness and during recovery with long-term outcomes are needed. [ABSTRACT FROM AUTHOR]

The article presents the discussion on Inflammation and Coagulation during critical illness and long-term cognitive impairment and disability. Topics include invasive mechanical ventilation, noninvasive positive pressure ventilation, continuous positive airway pressure, supplemental oxygen through a nonrebreather mask; and mental illness requiring institutionalization acquiring congenital mental retardation knowing brain lesions and traumatic brain injury.

The authors comment on a study on post-extubation respiratory support in the pediatric intensive care unit (PICU). They note the differences between high flow nasal cannula (HFNC) and continuous positive airway pressure (CPAP) as first-line support for assistance in breathing in children. They identify potential limitations of the study including non-adherence of respiratory support switch events to study procedures and differences in patient inclusion criteria in the HFNC and CPAP cohorts.

Background: The Randomized Embedded Multifactorial Adaptive Platform for COVID-19 (REMAP-COVID) trial is a global adaptive platform trial of hospitalized patients with COVID-19. We describe implementation at the first US site, the UPMC health system, and offer recommendations for implementation at other sites. Methods: To implement REMAP-COVID, we focused on six major areas: engaging leadership, trial embedment, remote consent and enrollment, regulatory compliance, modification of traditional trial management procedures, and alignment with other COVID-19 studies. Results: We recommend aligning institutional and trial goals and sharing a vision of REMAP-COVID implementation as groundwork for learning health system development. Embedment of trial procedures into routine care processes, existing institutional structures, and the electronic health record promotes efficiency and integration of clinical care and clinical research. Remote consent and enrollment can be facilitated by engaging bedside providers and leveraging institutional videoconferencing tools. Coordination with the central institutional review board will expedite the approval process. Protocol adherence, adverse event monitoring, and data collection and export can be facilitated by building electronic health record processes, though implementation can start using traditional clinical trial tools. Lastly, establishment of a centralized institutional process optimizes coordination of COVID-19 studies. Conclusions: Implementation of the REMAP-COVID trial within a large US healthcare system is feasible and facilitated by multidisciplinary collaboration. This investment establishes important groundwork for future learning health system endeavors. Trial registration: NCT02735707. Registered on 13 April 2016. [ABSTRACT FROM AUTHOR]

Background: The Randomized Embedded Multifactorial Adaptive Platform for COVID-19 (REMAP-COVID) trial is a global adaptive platform trial of hospitalized patients with COVID-19. We describe implementation at the first US site, the UPMC health system, and offer recommendations for implementation at other sites.Methods: To implement REMAP-COVID, we focused on six major areas: engaging leadership, trial embedment, remote consent and enrollment, regulatory compliance, modification of traditional trial management procedures, and alignment with other COVID-19 studies.Results: We recommend aligning institutional and trial goals and sharing a vision of REMAP-COVID implementation as groundwork for learning health system development. Embedment of trial procedures into routine care processes, existing institutional structures, and the electronic health record promotes efficiency and integration of clinical care and clinical research. Remote consent and enrollment can be facilitated by engaging bedside providers and leveraging institutional videoconferencing tools. Coordination with the central institutional review board will expedite the approval process. Protocol adherence, adverse event monitoring, and data collection and export can be facilitated by building electronic health record processes, though implementation can start using traditional clinical trial tools. Lastly, establishment of a centralized institutional process optimizes coordination of COVID-19 studies.Conclusions: Implementation of the REMAP-COVID trial within a large US healthcare system is feasible and facilitated by multidisciplinary collaboration. This investment establishes important groundwork for future learning health system endeavors.Trial Registration: NCT02735707 . Registered on 13 April 2016. [ABSTRACT FROM AUTHOR]

Acute Respiratory Distress Syndrome (ARDS) is one of the most demanding conditions in an Intensive Care Unit (ICU). Management of analgesia and sedation in ARDS is particularly challenging. An expert panel was convened to produce a "state-of-the-art" article to support clinicians in the optimal management of analgesia/sedation in mechanically ventilated adults with ARDS, including those with COVID-19. Current ICU analgesia/sedation guidelines promote analgesia first and minimization of sedation, wakefulness, delirium prevention and early rehabilitation to facilitate ventilator and ICU liberation. However, these strategies cannot always be applied to patients with ARDS who sometimes require deep sedation and/or paralysis. Patients with severe ARDS may be under-represented in analgesia/sedation studies and currently recommended strategies may not be feasible. With lightened sedation, distress-related symptoms (e.g., pain and discomfort, anxiety, dyspnea) and patient-ventilator asynchrony should be systematically assessed and managed through interprofessional collaboration, prioritizing analgesia and anxiolysis. Adaptation of ventilator settings (e.g., use of a pressure-set mode, spontaneous breathing, sensitive inspiratory trigger) should be systematically considered before additional medications are administered. Managing the mechanical ventilator is of paramount importance to avoid the unnecessary use of deep sedation and/or paralysis. Therefore, applying an "ABCDEF-R" bundle (R = Respiratory-drive-control) may be beneficial in ARDS patients. Further studies are needed, especially regarding the use and long-term effects of fast-offset drugs (e.g., remifentanil, volatile anesthetics) and the electrophysiological assessment of analgesia/sedation (e.g., electroencephalogram devices, heart-rate variability, and video pupillometry). This review is particularly relevant during the COVID-19 pandemic given drug shortages and limited ICU-bed capacity. [ABSTRACT FROM AUTHOR]

The article discusses Sex Disparities and Functional Outcomes after a Critical Illness. Topics include Enhanced identification of patients at risk of post-ICU morbidity is essential to improve care delivery and outcomes; Females are at higher risk than males for worse health, function, and healthcare-use outcomes in a variety of health conditions; and the main limitation of this study is that it was a secondary analysis.

The article reports on providing mechanical ventilation for acute respiratory failure in the U.S. Topics include offers information on multiple randomized trials that demonstrate treatment of high-risk patients with preventive noninvasive ventilation (NIV) after planned extubation prevent these events; and on basis of data the clinical practice guidelines recommends that high-risk patients extubated directly to NIV to prevent post extubation respiratory failure.

Rationale: Although survival during critical illness is improving, little evidence exists to guide post-intensive care unit (ICU) care. Understanding patients' needs and priorities is fundamental to improving care quality.Objectives: To describe the evolution of patients' priorities for recovery across the spectrum of post-ICU care.Methods: This was a secondary analysis of 39 semistructured interviews conducted from 2005 to 2006 in participants' homes 19 days to 11 years after hospital discharge after critical illness. Adult critical illness survivors (N = 39) aged 20 years or older from multiple ICUs across the United Kingdom were purposively selected to maximize diversity with respect to time since diagnosis, disease severity, sex, age, ethnicity, socioeconomic group/status, region. age, ICU admitting diagnoses, and length of stay. We used the method of qualitative description to characterize patients' priorities for recovery and their evolution within and between individual patients across three post-ICU periods: ICU transition to wards, early period (approximately the first 2 mo) after discharge to home, and late period (>2 mo) after discharge to home.Results: The analysis revealed 12 core patient priorities during recovery: feeling safe, being comfortable, engaging in mobility, participating in self-care, asserting personhood, connecting with people, ensuring family well-being, going home, restoring psychological health, restoring physical health, resuming previous roles and routines, and seeking new life experiences. In general, priorities evolved from those pertaining to basic survival during the stay on wards to being broader and more aspirational by the late postdischarge period.Conclusions: Understanding patients' priorities for post-ICU care is critical for developing stakeholder-driven clinical guidelines. Engaging other stakeholders (e.g., family members, healthcare providers, and institutionalized and frail older adults) to inform the development of clinical guidelines for post-ICU care, together with the barriers and facilitators faced in achieving patient- and family-centered care, is an important next step. [ABSTRACT FROM AUTHOR]

Background/Aim: The diagnostic accuracy of brief informant screening instruments to detect dementia in critically ill adults is unknown. We sought to determine the diagnostic accuracy of the 2- to 3-min Ascertain Dementia 8 (AD8) completed by surrogates in detecting dementia among critically ill adults suspected of having pre-existing dementia by comparing it to the Clinical Dementia Rating Scale (CDR). Methods: This substudy of BRAIN-ICU included a subgroup of 75 critically ill medical/surgical patients determined to be at medium risk of having pre-existing dementia (Informant Questionnaire on Cognitive Decline in the Elderly [IQCODE] score ≥3.3). We calculated the sensitivity, specificity, positive and negative predictive values (PPV and NPV), and AUC for the standard AD8 cutoff of ≥2 versus the reference standard CDR score of ≥1 for mild dementia. Results: By the CDR, 38 patients had very mild or no dementia and 37 had mild dementia or greater. For diagnosing mild dementia, the AD8 had a sensitivity of 97% (95% CI 86–100), a specificity of 16% (6–31), a PPV of 53% (40–65), an NPV of 86% (42–100), and an AUC of 0.738 (0.626–0.850). Conclusions: Among critically ill patients judged at risk for pre-existing dementia, the 2- to 3-min AD8 is highly sensitive and has a high NPV. These data indicate that the brief tool can serve to rule out dementia in a specific patient population. [ABSTRACT FROM AUTHOR]

An estimated 14.1 million patients survive sepsis each year. Many survivors experience poor long-term outcomes, including new or worsened neuropsychological impairment; physical disability; and vulnerability to further health deterioration, including recurrent infection, cardiovascular events, and acute renal failure. However, clinical trials and guidelines have focused on shorter-term survival, so there are few data on promoting longer-term recovery. To address this unmet need, the International Sepsis Forum convened a colloquium in February 2018 titled "Understanding and Enhancing Sepsis Survivorship." The goals were to identify gaps and limitations of current research and shorter- and longer-term priorities for understanding and enhancing sepsis survivorship. Twenty-six experts from eight countries participated. The top short-term priorities identified by nominal group technique culminating in formal voting were to better leverage existing databases for research, develop and disseminate educational resources on postsepsis morbidity, and partner with sepsis survivors to define and achieve research priorities. The top longer-term priorities were to study mechanisms of long-term morbidity through large cohort studies with deep phenotyping, build a harmonized global sepsis registry to facilitate enrollment in cohorts and trials, and complete detailed longitudinal follow-up to characterize the diversity of recovery experiences. This perspective reviews colloquium discussions, the identified priorities, and current initiatives to address them. [ABSTRACT FROM AUTHOR]

Background: Patterns of inpatient opioid use and their associations with postdischarge opioid use are poorly understood.Objective: To measure patterns in timing, duration, and setting of opioid administration in opioid-naive hospitalized patients and to examine associations with postdischarge use.Design: Retrospective cohort study using electronic health record data from 2010 to 2014.Setting: 12 community and academic hospitals in Pennsylvania.Patients: 148 068 opioid-naive patients (191 249 admissions) with at least 1 outpatient encounter within 12 months before and after admission.Measurements: Number of days and patterns of inpatient opioid use; any outpatient use (self-report and/or prescription orders) 90 and 365 days after discharge.Results: Opioids were administered in 48% of admissions. Patients were given opioids for a mean of 67.9% (SD, 25.0%) of their stay. Location of administration of first opioid on admission, timing of last opioid before discharge, and receipt of nonopioid analgesics varied substantially. After adjustment for potential confounders, 5.9% of inpatients receiving opioids had outpatient use at 90 days compared with 3.0% of those without inpatient use (difference, 3.0 percentage points [95% CI, 2.8 to 3.2 percentage points]). Opioid use at 90 days was higher in inpatients receiving opioids less than 12 hours before discharge than in those with at least 24 opioid-free hours before discharge (7.5% vs. 3.9%; difference, 3.6 percentage points [CI, 3.3 to 3.9 percentage points]). Differences based on proportion of the stay with opioid use were modest (opioid use at 90 days was 6.4% and 5.4%, respectively, for patients with opioid use for ≥75% vs. ≤25% of their stay; difference, 1.0 percentage point [CI, 0.4 to 1.5 percentage points]). Associations were similar for opioid use 365 days after discharge.Limitation: Potential unmeasured confounders related to opioid use.Conclusion: This study found high rates of opioid administration to opioid-naive inpatients and associations between specific patterns of inpatient use and risk for long-term use after discharge.Primary Funding Source: UPMC Health System and University of Pittsburgh. [ABSTRACT FROM AUTHOR]

Background: Adults hospitalized with community-acquired pneumonia (CAP) are at high risk for short-term mortality. However, it is unclear whether improvements in in-hospital pneumonia care could substantially lower this risk. We extensively reviewed all in-hospital deaths in a large prospective CAP study to assess the cause of each death and assess the extent of potentially preventable mortality.Methods: We enrolled adults hospitalized with CAP at five tertiary-care hospitals in the United States. Five physician investigators reviewed the medical record and study database for each patient who died to identify the cause of death, the contribution of CAP to death, and any preventable factors potentially contributing to death.Results: Among 2,320 enrolled patients, 52 (2.2%) died during initial hospitalization. Among these 52 patients, 33 (63.4%) were ≥ 65 years old, and 32 (61.5%) had ≥ two chronic comorbidities. CAP was judged to be the direct cause of death in 27 patients (51.9%). Ten patients (19.2%) had do-not-resuscitate orders prior to admission. Four patients were identified in whom a lapse in quality of care potentially contributed to death; preexisting end-of-life limitations were present in two of these patients. Two patients seeking full medical care experienced a lapse in in-hospital quality of pneumonia care that potentially contributed to death.Conclusions: In this study of adults with CAP at tertiary-care hospitals with a low mortality rate, most in-hospital deaths did not appear to be preventable with improvements in in-hospital pneumonia care. Preexisting end-of-life limitations in care, advanced age, and high comorbidity burden were common among those who died. [ABSTRACT FROM AUTHOR]