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Objectives: Surges in demand for sedatives for mechanical ventilation during the COVID-19 pandemic caused shortages of sedatives globally. Propranolol, a nonselective beta-adrenergic blocker, has been associated with reduced agitation and sedative needs in observational studies. We aimed to test whether propranolol could reduce the dose of sedatives needed in mechanically ventilated patients., Design: Open-label randomized controlled trial., Setting: Three academic hospitals., Subjects: Any nonparalyzed patient receiving mechanical ventilation and requiring high-dose sedatives., Interventions: Enteral propranolol 20-60 mg every 6 hours titrated to effect in the intervention group; all participants received protocol-titrated sedation with propofol or midazolam., Measurements and Main Results: Mean change in 24 hours dose of sedative from baseline to day 3, proportion of sedation scores within target, and occurrence rate of adverse events. We enrolled a planned 72 patients between January 2021 and October 2022. Sixty-nine percent were male with a mean (sd) age of 54 years (15.91 yr). Most were admitted for COVID or non-COVID pneumonia. Intervention participants received propranolol for a mean of 10 days (mean daily dose, 90 mg). There was a significantly larger decrease in sedative dose from baseline (54% vs. 34%; p = 0.048) and more sedation assessments within target range (48% vs. 35%; p < 0.0001) in the intervention group compared with controls. There were no differences in mortality or adverse events., Conclusions: Propranolol is an inexpensive drug that effectively lowered the need for sedatives in critically ill patients managed in the COVID-19 pandemic. Propranolol may help preserve limited supplies of sedatives while achieving target sedation., Competing Interests: Dr. Downar, Ms. Lapenskie, Dr. Kanji, Ms. Saeed, Mr. Anderson, and Dr. Fox-Robichaud disclosed off-label use of propranolol. Ms. Lapenskie’s, Ms. Saeed’s, Dr. Polskaia’s, Mr. Anderson’s, and Dr. Fox-Robichaud’s institutions received funding from the Hamilton Academic Health Sciences Organization (HAHSO). Ms. Lapenskie, Ms. Saeed, Dr. Polskaia, and Mr. Anderson received support for article research from the HAHSO. Ms. Haines received support for article research from the Canadian Institutes of Health Research (CIHR); she disclosed government work. Ms. Porteous received support for article research from Hamilton Health. Dr. Fox-Robichaud’s institution received funding from the CIHR; she received funding from Hamilton Health Sciences and McMaster University. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Objectives: To compare the safety and efficacy of ketamine and etomidate as induction agents to facilitate emergent endotracheal intubation., Data Sources: We searched MEDLINE, Embase, Cochrane Clinical Trials Register, and ClinicalTrials.gov from inception to April 3, 2024., Study Selection: We included randomized controlled trials (RCTs) that compared ketamine to etomidate to facilitate emergent endotracheal intubation in adults., Data Extraction: Reviewers screened abstracts, full texts, and extracted data independently and in duplicate. We pooled data using a random-effects model, assessed risk of bias using the modified Cochrane tool and certainty of evidence using the Grading Recommendations Assessment, Development, and Evaluation approach. We pre-registered the protocol on PROSPERO (CRD42023472450)., Data Synthesis: We included seven RCTs ( n = 2384 patients). Based on pooled analysis, compared with etomidate, ketamine probably increases hemodynamic instability in the peri-intubation period (relative risk [RR], 1.29; 95% CI, 1.07-1.57; moderate certainty) but probably decreases the need for initiation of continuous infusion vasopressors (RR, 0.75; 95% CI, 0.57-1.00; moderate certainty) and results in less adrenal suppression (RR, 0.54; 95% CI, 0.45-0.66; moderate certainty). Ketamine probably has no effect on successful intubation on the first attempt (RR, 1.01; 95% CI, 0.97-1.05; moderate certainty) or organ dysfunction measured as the maximum Sequential Organ Failure Assessment (SOFA) score during the first 3 days in ICU (mean difference, 0.55 SOFA points lower; 95% CI, 1.12 lower to 0.03 higher; moderate certainty) and may have no effect on mortality (RR, 1.00; 95% CI, 0.83-1.21; low certainty) when compared with etomidate., Conclusions: Compared with etomidate, ketamine probably results in more hemodynamic instability during the peri-intubation period and appears to have no effect on successful intubation on the first attempt or mortality. However, ketamine results in decreased need for the initiation of vasopressor use and decreases adrenal suppression compared with etomidate., Competing Interests: Dr. Semler received support for article research from the National Institutes of Health. Dr. Sharif received funding from the McMaster University Department of Medicine Internal Career Research Award. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Purpose: We performed a systematic review with meta-analysis examining the relationship between pain or pain medications and delirium occurence, duration, and severity., Methods: We searched MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials from inception to May 15, 2023. We included randomised or observational studies among critically ill adults, that reported data on pain or exposure to analgesics, and reported delirium presence, duration, or severity with no language or region restrictions., Prospero Id: CRD42022367715. Two authors independently screened records and extracted data. Risk of bias was evaluated using Risk of Bias 2 or the Risk of Bias In Non-randomized Studies of Interventions. We pooled data using the Hartung-Knapp Sidik-Jonkmann random effects model. PRISMA was followed., Results: From 8,054 citations, 90 studies (119,230 patients) published between 2001 and 2023 were included in the systematic review. 41 studies were included in the primary meta-analysis examining prevalent delirium: seven studies evaluated pain; 12 studies evaluated fentanyl; and five studies evaluated morphine. There was a trend to association between pain and delirium occurrence (OR 2.49, 95% CI 0.98-6.30), and a significant association between pain and incident delirium (OR 3.70, 95% CI 1.73-7.93). Fentanyl (OR 2.49, 95% CI 1.45-4.27) and morphine (OR 2.13, 95% CI 1.21-3.75) were associated with delirium occurrence. Risk of bias was critical for many studies., Conclusions: We observed an association between pain and incident delirium among critically ill adults. Exposure to morphine or fentanyl (but no other pain medications) was associated with increased risk of delirium occurrence., Competing Interests: Declarations. Conflicts of interest: All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/disclosure-of-interest/ and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© 2025. Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The use of patient/family-centred written summaries to supplement verbal information may be useful to improve knowledge and reduce anxiety related to patient transfer from the intensive care unit (ICU) to a hospital ward. We aimed to identify essential elements to include in an ICU-specific patient-oriented discharge summary tool (PODS-ICU)., Methods: We conducted a mixed methods study. Participants were ICU patients who were transitioning to a hospital ward and clinicians. We used a validated questionnaire to measure the relocation stress of patients, and standardized questions to qualitatively explore patients' needs during the transition, as well as perspectives of clinician stakeholders. Inductive thematic analysis was used for the qualitative analysis., Results: We recruited 22 participants, including ten patients and 12 clinician stakeholders. Of ten patients, 50-100% reported positive experiences during the transition and 10-30% reported negative experiences. From all participants' perspectives, we identified the following essential elements for the PODS-ICU: the reason for transition, a summary of the ICU course, a clinical update, destination ward details, medication reconciliation, a future care plan, and the planned follow-up by the ICU outreach team. Family presence and earlier notification of an upcoming transfer were identified as support needs to help patients prepare mentally and reduce transfer anxiety. Moreover, using positive communication with patients when providing transfer details and using the brief standardized transfer tool were recommended to improve transition care., Conclusions: We identified informational gaps in patient and family knowledge at the time of transfer from the ICU to a ward, which informed essential elements for the PODS-ICU. The PODS-ICU may reduce transfer anxiety and improve care during the transition from the ICU., (© 2024. Canadian Anesthesiologists' Society.)

Objectives: To summarize the delirium treatment trial literature, identify the unique challenges in delirium treatment trials, and formulate recommendations to address each in older adults., Design: A 39-member interprofessional and international expert working group of clinicians (physicians, nurses, and pharmacists) and nonclinicians (biostatisticians, epidemiologists, and trial methodologists) was convened. Four expert panels were assembled to explore key subtopics (pharmacological/nonpharmacologic treatment, methodological challenges, and novel research designs)., Methods: To provide background and context, a review of delirium treatment randomized controlled trials (RCTs) published between 2003 and 2023 was conducted and evidence gaps were identified. The four panels addressed the identified subtopics. For each subtopic, research challenges were identified and recommendations to address each were proposed through virtual discussion before a live, full-day, and in-person conference. General agreement was reached for each proposed recommendation across the entire working group via moderated conference discussion. Recommendations were synthesized across panels and iteratively discussed through rounds of virtual meetings and draft reviews., Results: We identified key evidence gaps through a systematic literature review, yielding 43 RCTs of delirium treatments. From this review, eight unique challenges for delirium treatment trials were identified, and recommendations to address each were made based on panel input. The recommendations start with design of interventions that consider the multifactorial nature of delirium, include both pharmacological and nonpharmacologic approaches, and target pathophysiologic pathways where possible. Selecting appropriate at-risk patients with moderate vulnerability to delirium may maximize effectiveness. Targeting patients with at least moderate delirium severity and duration will include those most likely to experience adverse outcomes. Delirium severity should be the primary outcome of choice; measurement of short- and long-term clinical outcomes will maximize clinical relevance. Finally, plans for handling informative censoring and missing data are key., Conclusions: By addressing key delirium treatment challenges and research gaps, our recommendations may serve as a roadmap for advancing delirium treatment research in older adults., Competing Interests: Dr. Devlin received research funding from the National Institutes on Aging (NIA), the Agency for Healthcare Research and Quality, Sedana Medical, and BioXcel Therapeutics; he disclosed he has served as a consultant to Ceribell. Dr. Sieber disclosed he has received unrelated grant support from the NIA and the Claude D. Pepper Odler Americans Independence Center. Drs. Devlin, Sieber, Akeju, Khan, Marcantonio, Girard, Jones, Travison, and Inouye received support for article research from the National Institutes of Health (NIH). Drs. Khan’s and Girard’s institutions received funding from the NIH. Dr. Khan’s institution received funding from the National Heart, Lung, and Blood Institute (NHLBI), Centers for Disease Control and Prevention, Gilead Sciences, and the Showalter Trust. Dr. Marcantonio disclosed he has received unrelated grant support from the NIA. Dr. Agar disclosed she has received unrelated grant support from the National Health and Medical Research Council and National Breast Cancer Foundation and Cancer Australia. Dr. Berger disclosed he has received unrelated grant support from the NIA and the Alzheimer’s Drug Discovery Foundation; he has received private legal consulting fees related to postoperative neurocognitive function. Dr. Han has disclosed funding that he receives funding from the NIA, NHLBI, and Patient-Centered Outcomes Research Institute (PCORI). Dr. Girard’s institution received funding from the Department of Defense (DoD) and Ceribell; he received funding from the NIH, the DoD, and Ceribell; and he disclosed he served previously on an advisory board for Lungpacer Medical. Dr. Hosie’s institution received funding from the National Health and Medical Research Council; she received funding from the University of Notre Dame Australia. Dr. Hughes received funding from the NIH and Sedana Medical. Dr. Subramanian’s institution received funding from Masimo; they received funding from Masimo. Dr. Inouye’s institution received funding from the NIA; she received unrelated funding from the NIH and PCORI. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Objective: This proposed scoping review aims to examine studies assessing the impact of drug shortages on population-level drug utilization trends. The objectives of this review are to a) assess which drugs have been studied and describe associated drug characteristics, b) determine jurisdictions and healthcare settings that have conducted these studies, and c) describe how changes in drug use and the extent of shortage impacts are reported in literature., Introduction: Drug shortages continue to impair drug access and delivery of quality care across the world. However, the impact of drug supply disruptions on availability and drug use are understudied in current literature. This proposed scoping review will identify this gap and inform future research initiatives aimed at determining the real-world impacts of drug shortages., Inclusion Criteria: Published and unpublished observational studies reporting on the effects of drug supply chain disruptions (shortages, discontinuations, and safety-based withdrawals) on consequent utilization trends faced by pharmaceutical products (i.e. prescription drugs, over-the-counter drugs, vaccines, therapy products, pharmaceutical solutions). Literature reviews, meta-analyses, randomized control trials, case series, case reports, and opinion pieces will be excluded., Methods: The search strategy will combine two key search concepts: drug shortages and drug utilization. The search will be conducted in MEDLINE and EMBASE. This will be followed by an extensive grey literature search in grey literature databases, targeted websites and Google. Furthermore, reference lists of included articles will be searched. Articles will be independently screened, selected and extracted by two reviewers. Data will be descriptively analyzed and presented in tables., Trial Registration: Review registration number: Open Science Framework, https://osf.io/2p6e5., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Santhireswaran et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Rationale/objectives: Despite plausible pathophysiological mechanisms, research is needed to confirm the relationship between sleep, circadian rhythm and delirium in patients admitted to the intensive care unit (ICU). The objective of this review is to summarise existing studies promoting, in whole or in part, the normalisation of sleep and circadian biology and their impact on the incidence, prevalence, duration and/or severity of delirium in ICU., Methods: A sensitive search of electronic databases and conference proceedings was completed in March 2023. Inclusion criteria were English-language studies of any design that evaluated in-ICU non-pharmacological, pharmacological or mixed intervention strategies for promoting sleep or circadian biology and their association with delirium, as assessed at least daily. Data were extracted and independently verified., Results: Of 7886 citations, we included 50 articles. Commonly evaluated interventions include care bundles (n=20), regulation or administration of light therapy (n=5), eye masks and/or earplugs (n=5), one nursing care-focused intervention and pharmacological intervention (eg, melatonin and ramelteon; n=19). The association between these interventions and incident delirium or severity of delirium was mixed. As multiple interventions were incorporated in included studies of care bundles and given that there was variable reporting of compliance with individual elements, identifying which components might have an impact on delirium is challenging., Conclusions: This scoping review summarises the existing literature as it relates to ICU sleep and circadian disruption (SCD) and delirium in ICU. Further studies are needed to better understand the role of ICU SCD promotion interventions in delirium mitigation., Competing Interests: Competing interests: MPK is a member of Serca LLC (no conflict with this review)., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Hospital admission for a critical illness episode creates communication breakpoints and can lead to medication discrepancies during hospital stays. Due to the patient's underlying condition and the care setting, chronic medications such as cardiovascular medication are often held, discontinued, or changed to alternative administration routes. Unfortunately, data on the optimal timing of cardiovascular drug reinitiation among intensive care unit (ICU) survivors are lacking., Objective: The primary objective of this study was to describe the prevalence of chronic cardiovascular medication taken before hospital admission and discontinued at ICU discharge and hospital discharge for critically ill patients. A secondary objective was to assess factors associated with medication discontinuation., Design Setting and Participants: We conducted a multicentered retrospective cohort study at 2 tertiary academic hospitals in Canada. All adult patients taking cardiovascular medication before ICU admission and surviving to hospital discharge between April 1, 2016, and April 1, 2017, were eligible., Main Outcomes and Measures: The main outcome of the study was the discontinuation of cardiovascular medication prescribed before ICU admission. The outcome was assessed through participants' chart review., Results: We included 352 patients with a median age of 71.0 years. A total of 155 patients (44.03%) had at least 1 cardiovascular medication discontinued during their stay. Our adjusted model uncovered 3 factors associated with cardiovascular medication discontinuation: male sex (odds ratio [OR] = 0.564, 95% confidence interval [CI] = 0.346-0.919), number of cardiovascular medications taken preadmission (OR = 1.669, 95% CI = 1.003-2.777 for 2 medications and OR = 3.170, 95% CI = 1.325-7.583), and the use of vasopressors (OR = 1.770, 95% CI = 1.045-2.997)., Conclusion: Our study uncovered that cardiovascular medication discontinuation for ICU patients is frequent, especially for renin-angiotensin system (RAS) blockers. Data from our study could be used to reinforce site-specific protocols of medication reconciliation and optimization, as well as inform future protocols aimed at RAS blocker reinitiation follow-up., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: In traumatic brain injury patients (TBI) admitted to the intensive care unit (ICU), agitation can lead to accidental removal of catheters, devices as well as self-extubation and falls. Actigraphy could be a potential tool to continuously monitor agitation. The objectives of this study were to assess the feasibility of monitoring agitation with actigraphs and to compare activity levels in agitated and non-agitated critically ill TBI patients., Methods: Actigraphs were placed on patients' wrists; 24-hour monitoring was continued until ICU discharge or limitation of therapeutic efforts. Feasibility was assessed by actigraphy recording duration and missing activity count per day., Results: Data from 25 patients were analyzed. The mean number of completed day of actigraphy per patient was 6.5 ± 5.1. The mean missing activity count was 20.3 minutes (±81.7) per day. The mean level of activity measured by raw actigraphy counts per minute over 24 hours was higher in participants with agitation than without agitation., Conclusions: This study supports the feasibility of actigraphy use in TBI patients in the ICU. In the acute phase of TBI, agitated patients have higher levels of activity, confirming the potential of actigraphy to monitor agitation.

Traumatic brain injury (TBI) survivors often suffer from agitated behaviors and will most likely receive pharmacological treatments. Choosing an optimal and safe treatment that will not interfere with neurological recovery remains controversial. By interfering with dopaminergic circuits, antipsychotics may impede processes important to cognitive recovery. Despite their frequent use, there have been no large randomized controlled studies of antipsychotics for the management of agitated behaviors during the acute TBI recovery period. We conducted a systematic review and meta-analysis of pre-clinical studies evaluating the effects of antipsychotics post-TBI on both cognitive and motor recovery. MEDLINE and Embase databases were searched up to August 2, 2023. Pre-clinical studies evaluating the effects of antipsychotics on cognitive and motor functions post-TBI were considered. Risk of bias was evaluated with the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool. We identified 15 studies including a total of 1188 rodents, mostly conducted in male Sprague-Dawley rats using cortical impact injury. The analysis revealed no consistent effect of haloperidol on motor functions, but risperidone was associated with a significant impairment in motor function on day 5 post-injury (7.05 sec; 95% confidence interval [CI]: 1.47, 12.62; I 2  = 92%). Other atypical antipsychotics did not result in impaired motor function. When evaluating cognitive function, haloperidol- (23.00 sec; 95% CI: 17.42-28.59; I 2  = 7%) and risperidone-treated rats (24.27 sec; 95% CI: 16.18-32.36; I 2  = 0%) were consistently impaired when compared to controls. In studies evaluating atypical antipsychotics, no impairments were observed. Clinicians should avoid the regular use of haloperidol and risperidone, and future human studies should be conducted with atypical antipsychotics., Competing Interests: No competing financial interests exist., (© Gabrielle Cataford et al., 2024; Published by Mary Ann Liebert, Inc.)

Background: We aimed to evaluate the comparative effectiveness and safety of various i.v. pharmacologic agents used for procedural sedation and analgesia (PSA) in the emergency department (ED) and ICU. We performed a systematic review and network meta-analysis to enable direct and indirect comparisons between available medications., Methods: We searched Medline, EMBASE, Cochrane, and PubMed from inception to 2 March 2023 for RCTs comparing two or more procedural sedation and analgesia medications in all patients (adults and children >30 days of age) requiring emergent procedures in the ED or ICU. We focused on the outcomes of sedation recovery time, patient satisfaction, and adverse events (AEs). We performed frequentist random-effects model network meta-analysis and used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to rate certainty in estimates., Results: We included 82 RCTs (8105 patients, 78 conducted in the ED and four in the ICU) of which 52 studies included adults, 23 included children, and seven included both. Compared with midazolam-opioids, recovery time was shorter with propofol (mean difference 16.3 min, 95% confidence interval [CI] 8.4-24.3 fewer minutes; high certainty), and patient satisfaction was better with ketamine-propofol (mean difference 1.5 points, 95% CI 0.3-2.6 points, high certainty). Regarding AEs, compared with midazolam-opioids, respiratory AEs were less frequent with ketamine (relative risk [RR] 0.55, 95% CI 0.32-0.96; high certainty), gastrointestinal AEs were more common with ketamine-midazolam (RR 3.08, 95% CI 1.15-8.27; high certainty), and neurological AEs were more common with ketamine-propofol (RR 3.68, 95% CI 1.08-12.53; high certainty)., Conclusion: When considering procedural sedation and analgesia in the ED and ICU, compared with midazolam-opioids, sedation recovery time is shorter with propofol, patient satisfaction is better with ketamine-propofol, and respiratory adverse events are less common with ketamine., (Copyright © 2023 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Purpose: Antipsychotic agents, which may increase the risk of infection through dopaminergic dysregulation, are prescribed to a fraction of patients following critical illness. We compared the rate of recurrent sepsis among patients who filled a prescription for antipsychotics with high- or low-D 2 affinity., Methods: Population-based cohort with active comparator design. We included sepsis survivors older than 65 years with intensive care unit admission and new prescription of antipsychotics in Ontario 2008-2019. The primary outcome were recurrent sepsis episodes within 1 year of follow-up. Patients who filled a prescription within 30 days of hospital discharge for high-D 2 affinity antipsychotics (e.g., haloperidol) were compared with patients who filled a prescription within 30 days of hospital discharge for low-D 2 affinity antipsychotics (e.g., quetiapine). Multivariable zero-inflated Poisson regression models with robust standard errors adjusting for confounding at baseline were used to estimate incidence rate ratios (IRR) and 95% confidence intervals (CI)., Results: Overall, 1879 patients filled a prescription for a high-D 2, and 1446 patients filled a prescription for a low-D 2 affinity antipsychotic. Patients who filled a prescription for a high-D 2 affinity antipsychotic did not present a higher rate of recurrent sepsis during 1 year of follow-up, compared with patients who filled a prescription for a low-D 2 affinity antipsychotic (IRR: 1.12; 95% CI: 0.94, 1.35)., Conclusions: We did not find conclusive evidence of a higher rate of recurrent sepsis associated with the prescription of high-D 2 affinity antipsychotics (compared with low-D 2 affinity antipsychotics) by 1 year of follow-up in adult sepsis survivors with intensive care unit admission., (© 2023 John Wiley & Sons Ltd.)

Rationale: Outcomes for people with respiratory failure in the United States vary by patient race and ethnicity. Invasive ventilation is an important treatment initiated based on expert opinion. It is unknown whether the use of invasive ventilation varies by patient race and ethnicity. Objectives: To measure 1 ) the association between patient race and ethnicity and the use of invasive ventilation; and 2 ) the change in 28-day mortality mediated by any association. Methods: We performed a multicenter cohort study of nonintubated adults receiving oxygen within 24 hours of intensive care admission using the Medical Information Mart for Intensive Care IV (MIMIC-IV, 2008-2019) and Phillips eICU (eICU, 2014-2015) databases from the United States. We modeled the association between patient race and ethnicity (Asian, Black, Hispanic, White) and invasive ventilation rate using a Bayesian multistate model that adjusted for baseline and time-varying covariates, calculated hazard ratios (HRs), and estimated 28-day hospital mortality changes mediated by differential invasive ventilation use. We reported posterior means and 95% credible intervals (CrIs). Results: We studied 38,258 patients, 52% (20,032) from MIMIC-IV and 48% (18,226) from eICU: 2% Asian (892), 11% Black (4,289), 5% Hispanic (1,964), and 81% White (31,113). Invasive ventilation occurred in 9.2% (3,511), and 7.5% (2,869) died. The adjusted rate of invasive ventilation was lower in Asian (HR, 0.82; CrI, 0.70-0.95), Black (HR, 0.78; CrI, 0.71-0.86), and Hispanic (HR, 0.70; CrI, 0.61-0.79) patients compared with White patients. For the average patient, lower rates of invasive ventilation did not mediate differences in 28-day mortality. For a patient on high-flow nasal cannula with inspired oxygen fraction of 1.0, the odds ratios for mortality if invasive ventilation rates were equal to the rate for White patients were 0.97 (CrI, 0.91-1.03) for Asian patients, 0.96 (CrI, 0.91-1.03) for Black patients, and 0.94 (CrI, 0.89-1.01) for Hispanic patients. Conclusions: Asian, Black, and Hispanic patients had lower rates of invasive ventilation than White patients. These decreases did not mediate harm for the average patient, but we could not rule out harm for patients with more severe hypoxemia.

Purpose: Agitation is a common behavioural problem following traumatic brain injury (TBI). Intensive care unit (ICU) physicians' perspectives regarding TBI-associated agitation are unknown. Our objective was to describe physicians' beliefs and perceived importance of TBI-associated agitation in critically ill patients., Methods: Following current standard guidance, we built an electronic, self-administrated, 42-item survey, pretested it for reliability and validity, and distributed it to 219 physicians working in 18 ICU level-1 trauma centres in Canada. We report the results using descriptive statistics., Results: The overall response rate was 93/219 (42%), and 76/93 (82%) respondents completed the full survey. Most respondents were men with ten or more years of experience. Respondents believed that pre-existing dementia (90%) and regular recreational drug use (86%) are risk factors for agitation. Concerning management, 91% believed that the use of physical restraints could worsen agitation, 90% believed that having family at the bedside reduces agitation, and 72% believed that alpha-2 adrenergic agonists are efficacious for managing TBI agitation. Variability was observed in beliefs on epidemiology, sex, gender, age, socioeconomic status, and other pharmacologic options. Respondents considered TBI agitation frequent enough to justify the implementation of management protocols (87%), perceived the current level of clinical evidence on TBI agitation management to be insufficient (84%), and expressed concerns about acute and long-term detrimental outcomes and burden to patients, health care professionals, and relatives (85%)., Conclusion: Traumatic brain injury-associated agitation in critically ill patients was perceived as an important issue for most ICU physicians. Physicians agreed on multiple approaches to manage TBI-associated agitation although agreement on epidemiology and risk factors was variable., (© 2023. Canadian Anesthesiologists' Society.)

Background: Untreated pain is associated with short-term and long-term consequences, including post-traumatic stress disorder and insomnia. Side effects of some analgesic medications include dysphoria, hallucinations and delirium. Therefore, both untreated pain and analgesic medications may be risk factors for delirium. Delirium is associated with longer length of stay or cognitive impairment. Our systematic review and meta-analysis will examine the relationship between pain or analgesic medications with delirium occurrence, duration and severity among critically ill adults., Methods and Analysis: MEDLINE, EMBASE, CINAHL, the Cochrane Central Register of controlled trials and a review of recent conference abstracts will be searched without restriction from inception to 15 May 2023. Study inclusion criteria are: (1) age≥18 years admitted to intensive care; (2) report a measure of pain, analgesic medications and delirium; (3) study design-randomised controlled trial, quasiexperimental designs and observational cohort and case-control studies excluding case reports. Study exclusion criteria are: (1) alcohol withdrawal delirium or delirium tremens; or (2) general anaesthetic emergence delirium; or (3) lab or animal studies. Risk of bias will be assessed with the Risk of Bias V.2 and risk of bias in non-randomised studies tools. There is no language restriction. Occurrence estimates will be transformed using the Freeman-Tukey double arcsine. Point estimates will be pooled using Hartung-Knapp Sidik-Jonkman random effects meta-analysis to estimate a pooled risk ratio. Statistical heterogeneity will be estimated with the I 2 statistic. Risk of small study effects will be assessed using funnel plots and Egger test. Studies will be analysed for time-varying and unmeasured confounding using E values., Ethics and Dissemination: Ethical approval is not required as this is an analysis of published aggregated data. We will share our findings at conferences and in peer-reviewed journals., Prospero Registration Number: The finalised protocol was submitted to the International Prospective Register of Systematic Reviews (PROSPERO ID: CRD42022367715)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: We sought to understand the beliefs and practices of Canadian intensivists regarding their use of ketamine as a sedative in critically ill patients and to gauge their interest in a randomized controlled trial (RCT) examining its use in the intensive care unit (ICU)., Methods: We designed and validated an electronic self-administered survey examining the use of ketamine as a sedative infusion for ICU patients. We surveyed 400 physician members of the Canadian Critical Care Society (CCCS) via email between February and April 2022 and sent three reminders at two-week intervals. The survey was redistributed in January 2023 to improve the response rate., Results: We received 87/400 (22%) completed questionnaires. Most respondents reported they rarely use ketamine as a continuous infusion for sedation or analgesia in the ICU (52/87, 58%). Physicians reported the following conditions would make them more likely to use ketamine: asthma exacerbation (73/87, 82%), tolerance to opioids (68/87, 77%), status epilepticus (44/87, 50%), and severe acute respiratory distress syndrome (33/87, 38%). Concern for side-effects that limited respondents' use of ketamine include adverse psychotropic effects (61/87, 69%) and delirium (47/87, 53%). The majority of respondents agreed there is need for an RCT to evaluate ketamine as a sedative infusion in the ICU (62/87, 71%)., Conclusion: This survey of Canadian intensivists illustrates that use of ketamine as a continuous infusion for sedation is limited, and is at least partly driven by concerns of adverse psychotropic effects. Canadian physicians endorse the need for a trial investigating the safety and efficacy of ketamine as a sedative for critically ill patients., (© 2023. Canadian Anesthesiologists' Society.)

Background: This document updates previously published Clinical Practice Guidelines for the management of patients with acute respiratory distress syndrome (ARDS), incorporating new evidence addressing the use of corticosteroids, venovenous extracorporeal membrane oxygenation, neuromuscular blocking agents, and positive end-expiratory pressure (PEEP). Methods: We summarized evidence addressing four "PICO questions" (patient, intervention, comparison, and outcome). A multidisciplinary panel with expertise in ARDS used the Grading of Recommendations, Assessment, Development, and Evaluation framework to develop clinical recommendations. Results: We suggest the use of: 1 ) corticosteroids for patients with ARDS (conditional recommendation, moderate certainty of evidence), 2 ) venovenous extracorporeal membrane oxygenation in selected patients with severe ARDS (conditional recommendation, low certainty of evidence), 3 ) neuromuscular blockers in patients with early severe ARDS (conditional recommendation, low certainty of evidence), and 4 ) higher PEEP without lung recruitment maneuvers as opposed to lower PEEP in patients with moderate to severe ARDS (conditional recommendation, low to moderate certainty), and 5 ) we recommend against using prolonged lung recruitment maneuvers in patients with moderate to severe ARDS (strong recommendation, moderate certainty). Conclusions: We provide updated evidence-based recommendations for the management of ARDS. Individual patient and illness characteristics should be factored into clinical decision making and implementation of these recommendations while additional evidence is generated from much-needed clinical trials.

Background: To curb the growing impact of drug shortages, Health Canada developed the Tiered Notification and Communication Framework which assigns potential shortages a corresponding tiered status. Tier-3 is assigned to shortages with the greatest potential impact on the healthcare system. This study aims to describe drug purchasing trends in response to Tier-3 shortages using three case-examples., Methods: We conducted a time-series analysis of monthly purchasing data for three out of 17 Tier-3 drug shortages (hydralazine, sarilumab, and medroxyprogesterone acetate) with publicly available reports in July 2021 and available IQVIA MIDAS data from January 2016 to December 2021. We assessed percent changes in purchasing at 1-, 3-, and 6-months after the onset of each Tier-3 drug shortage and interventional ARIMA modelling was used to assess the statistical significance., Results: Medroxyprogesterone acetate experienced a significant shift (p = 0.0370) in purchasing following its shortage, and the 1-, 3-, and 6-month percent changes were +14.9%, +6.8% and -3.1%, respectively. Hydralazine and sarilumab did not show a significant shift. The 1-, 3-, and 6-month percent changes for hydralazine were +15.5%, +10.2%, and +9.6% respectively and +25.2%, +45.1% and +39.2 for sarilumab., Conclusions: These results indicate that drugs assigned a Tier-3 status may not show declines in purchasing in the months following status assignment, which may be due to policy responses following the assignment. However, more insight is needed into the mechanisms through which these policy measures impact shortages and whether they are functioning as intended., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Santhireswaran et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: This Rapid Practice Guideline provides an evidence-based recommendation to address the question: in adults with sepsis or septic shock, should we recommend using or not using intravenous vitamin C therapy?, Methods: The panel included 21 experts from 16 countries and used a strict policy for potential financial and intellectual conflicts of interest. Methodological support was provided by the Guidelines in Intensive Care, Development, and Evaluation (GUIDE) group. Based on an updated systematic review, and the grading of recommendations, assessment, development, and evaluation approach, we evaluated the certainty of evidence and developed recommendations using the evidence-to-decision framework. We conducted an electronic vote, requiring >80% agreement among the panel for a recommendation to be adopted., Results: At longest follow-up, 90 days, intravenous vitamin C probably does not substantially impact (relative risk 1.05, 95% confidence interval [CI] 0.94 to 1.17; absolute risk difference 1.8%, 95% CI -2.2 to 6.2; 6 trials, n = 2148, moderate certainty). Effects of vitamin C on mortality at earlier timepoints was of low or very low certainty due to risk of bias of the included studies and significant heterogeneity between study results. Few adverse events were reported with the use of vitamin C. The panel did not identify any major differences in other outcomes, including duration of mechanical ventilation, ventilator free days, hospital or intensive care unit length of stay, acute kidney injury, need for renal replacement therapy. Vitamin C may result in a slight reduction in duration of vasopressor support (MD -18.9 h, 95% CI -26.5 to -11.4; 21 trials, n = 2661, low certainty); but may not reduce sequential organ failure assessment scores (MD -0.69, 95% CI -1.55 to 0.71; 24 trials, n = 4002, low certainty). The panel judged the undesirable consequences of using IV vitamin C to probably outweigh the desirable consequences, and therefore issued a conditional recommendation against using IV vitamin C therapy in sepsis., Conclusions: The panel suggests against use of intravenous vitamin C in adult patients with sepsis, beyond that of standard nutritional supplementation. Small and single center trials on this topic should be discouraged., (© 2023 Acta Anaesthesiologica Scandinavica Foundation.)

Objectives: Iatrogenic withdrawal syndrome (IWS) associated with opioid and sedative use for medical purposes has a reported high prevalence and associated morbidity. This study aimed to determine the prevalence, utilization, and characteristics of opioid and sedative weaning and IWS policies/protocols in the adult ICU population., Design: International, multicenter, observational, point prevalence study., Setting: Adult ICUs., Patients: All patients aged 18 years and older in the ICU on the date of data collection who received parenteral opioids or sedatives in the previous 24 hours., Interventions: None., Measurements and Main Results: ICUs selected 1 day for data collection between June 1 and September 30, 2021. Patient demographic data, opioid and sedative medication use, and weaning and IWS assessment data were collected for the previous 24 hours. The primary outcome was the proportion of patients weaned from opioids and sedatives using an institutional policy/protocol on the data collection day. There were 2,402 patients in 229 ICUs from 11 countries screened for opioid and sedative use; 1,506 (63%) patients received parenteral opioids, and/or sedatives in the previous 24 hours. There were 90 (39%) ICUs with a weaning policy/protocol which was used in 176 (12%) patients, and 23 (10%) ICUs with an IWS policy/protocol which was used in 9 (0.6%) patients. The weaning policy/protocol for 47 (52%) ICUs did not define when to initiate weaning, and the policy/protocol for 24 (27%) ICUs did not specify the degree of weaning. A weaning policy/protocol was used in 34% (176/521) and IWS policy/protocol in 9% (9/97) of patients admitted to an ICU with such a policy/protocol. Among 485 patients eligible for weaning policy/protocol utilization based on duration of opioid/sedative use initiation criterion within individual ICU policies/protocols 176 (36%) had it used, and among 54 patients on opioids and/or sedatives ≥ 72 hours, 9 (17%) had an IWS policy/protocol used by the data collection day., Conclusions: This international observational study found that a small proportion of ICUs use policies/protocols for opioid and sedative weaning or IWS, and even when these policies/protocols are in place, they are implemented in a small percentage of patients., Competing Interests: Dr. Burry’s institution receives funding under the award Canadian Institutes of Health Research (CIHR) project grant (no. 159696). Dr. Gélinas’ institution receives funding under the award CIHR project grant (no. 169043), and CIHR project grant (no. 168983), the Fonds de recherche en santé du Québec, and the Nursing Collaborative—Jewish General Hospital; she received funding from the Office of the Federal Publish Defender. Dr. Eadie’s institution receives funding from HSC Public Health Agency Research and Development Division NI. Dr. Saltarelli received funding from Wilkes University Provost Research and Scholarship Grant. Dr. Riker’s institution receives funding under the award number National Institute of General Medical Sciences 1P20GM139745; he and Dr. Fraser serve on the data and safety monitoring board for a sedation study but receive no payment. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Context: Delirium is a serious neurocognitive syndrome which is highly prevalent in people approaching the end of life. Existing trials of interventions to prevent or treat delirium in adults receiving palliative care report heterogeneous outcomes., Objectives: To undertake an international consensus process to develop a core outcome set for trials of interventions, designed to prevent and/or treat delirium, for adults receiving palliative care., Methods: The core outcome set development process included a systematic review, qualitative interviews, modified Delphi method and virtual consensus meetings using nominal group technique (Registration http://www.comet-initiative.org/studies/details/796). Participants included family members, clinicians, and researchers with experience of delirium in palliative care., Results: Forty outcomes were generated from the systematic review and interviews informing the Delphi Round one survey. The international Delphi panel comprised 92 participants including clinicians (n = 71, 77%), researchers (n = 13, 14%), and family members (n = 8, 9%). Delphi Round two was completed by 77 (84%) participants from Round one. Following the consensus meetings, four outcomes were selected for the core outcome set: 1) delirium occurrence (incidence and prevalence); 2) duration of delirium until resolution defined as either no further delirium in this episode of care or death; 3) overall delirium symptom profile (agitation, delusions or hallucinations, delirium symptoms and delirium severity); 4) distress due to delirium (person with delirium, and/or family and/or carers [including healthcare professionals])., Conclusion: Using a rigorous consensus process, we developed a core outcome set comprising four delirium-specific outcomes for inclusion in future trials of interventions to prevent and/or treat delirium in palliative care., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Sedation of critically ill patients with inhaled anaesthetics may reduce lung inflammation, time to extubation, and ICU length of stay compared with intravenous (i.v.) sedatives. However, the impact of inhaled anaesthetics on cognitive and psychiatric outcomes in this population is unclear. In this systematic review, we aimed to summarise the effect of inhaled anaesthetics on cognitive and psychiatric outcomes in critically ill adults., Methods: We searched MEDLINE, EMBASE, and PsycINFO for case series, retrospective, and prospective studies in critically ill adults sedated with inhaled anaesthetics. Outcomes included delirium, psychomotor and neurological recovery, long-term cognitive dysfunction, ICU memories, anxiety, depression, post-traumatic stress disorder (PTSD), and instruments used for assessment., Results: Thirteen studies were included in distinct populations of post-cardiac arrest survivors (n=4), postoperative noncardiac patients (n=3), postoperative cardiac patients (n=2), and mixed medical-surgical patients (n=4). Eight studies reported delirium incidence, two neurological recovery, and two ICU memories. One study reported on psychomotor recovery, long-term cognitive dysfunction, anxiety, depression, and PTSD. A meta-analysis of five trials found no difference in delirium incidence between inhaled and i.v. sedatives (relative risk 0.95 [95% confidence interval: 0.59-1.54]). Compared with i.v. sedatives, inhaled anaesthetics were associated with fewer hallucinations and faster psychomotor recovery but no differences in other outcomes. There was heterogeneity in the instruments used and timing of these assessments., Conclusions: Based on the limited evidence available, there is no difference in cognitive and psychiatric outcomes between adults exposed to volatile sedation or intravenous sedation in the ICU. Future studies should incorporate outcome assessment with validated tools during and after hospital stay., Systematic Review Protocol: PROSPERO CRD42021236455., (Copyright © 2023 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

To describe the eligibility and enrollment of pregnant and breastfeeding women in psychiatry randomized controlled trials (RCTs). We screened citations published 2017-2019 in the three highest impact psychiatry and five highest impact general medicine journals. We excluded male, pediatric, geriatric, and postmenopausal-focused RCTs and publications reporting subgroup, pooled, or secondary analyses of RCTs. We reviewed appendices, protocols, and registries for additional data. In total 108 RCTs were included. Three (2.8%) permitted enrollment of pregnant women; 59/108 (55%) and 46/108 (43%) explicitly excluded pregnant women or did not report pregnancy inclusion criteria, respectively. All RCTs including pregnant women evaluated non-pharmacological interventions for depression during pregnancy or postpartum. Among RCTs excluding pregnant women, 5/59 (8.5%) provided a rationale for exclusion. Contraception and/or negative pregnancy testing were required for women with reproductive capacity in 31/59 (53%). Three (2.8%) RCTs permitted enrollment of breastfeeding women and 3/41 (7.3%) RCTs excluding breastfeeding women provided a rationale for exclusion. This study demonstrates a major gap in psychiatry research involving pregnant and breastfeeding women. A shift from exclusion by default to inclusion and integration of this population into the clinical research agenda is needed to ensure they receive evidence-based care for mental illness., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)