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Objective: We evaluated the cost-effectiveness of a bundled intervention including an antimicrobial stewardship program (ASP), procalcitonin (PCT) testing, and rapid blood culture identification (BCID), compared with pre-implementation standard care in critically ill adult patients with sepsis., Methods: We conducted a decision tree model-based cost-effectiveness analysis alongside a previously published pre- and post-implementation quality improvement study. We adopted a public Canadian healthcare payer's perspective. Two intensive care units in Alberta with 727 adult critically ill patients were included. Our bundled intervention was compared with pre-implementation standard care. We collected healthcare resource use and estimated unit costs in 2022 Canadian dollars (CAD) over a time horizon from study entry to hospital discharge or death. We calculated the incremental net monetary benefit (iNMB) of the intervention group compared with the pre-intervention group. The primary outcome was cost per sepsis case. Secondary outcomes included readmission rates, Clostridioides difficile infections, mortality, and lengths of stay. Uncertainty was investigated using cost-effectiveness acceptability curves, cost-effectiveness plane scatterplots, and sensitivity analyses., Results: Mean (standard deviation [SD]) cost per index hospital admission was CAD $83,251 ($107,926) for patients in the intervention group and CAD $87,044 ($104,406) for the pre-intervention group, though the difference ($3,793 [$7,897]) was not statistically significant. Costs were higher in the pre-intervention group for antibiotics, readmissions, and C. difficile infections. The intervention group had a lower mean expected cost; $110,580 ($108,917) compared with pre-intervention ($125,745 [$113,210]), with a difference of $15,165 ($8278). There were no statistically significant differences in quality adjusted life years (QALYs) between groups. The iNMB of the intervention group compared with pre-intervention was greater than $15,000 for willingness-to-pay (WTP) per QALY values of between $0 and $100,000. In our sensitivity analysis, the intervention was most likely to be cost-effective in roughly 56% of simulations at all WTP thresholds., Conclusions: Our bundled intervention of ASP, PCT, and BCID among adult critically ill patients with sepsis was potentially cost-effective, but with substantial decision uncertainty., Competing Interests: Declarations. Funding: Funding was provided through a partnership grant between Alberta Innovates, Alberta Health Services, and bioMérieux. The investigators designed the study, wrote the manuscript, and vouch for the accuracy and completeness of the data and analyses. The funding organizations and partners were not involved in implementation or management of the study, in the analysis of data, or in the decision to submit the manuscript for publication. Competing Interests: Jeff Round is an editorial board member of PharmacoEconomics Open. He was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions. John Conly was an invited speaker at a symposium on antimicrobial resistance co-hosted by the University of Toronto and bioMérieux Canada in 2022. All other authors have no relevant conflicts to declare. Availability of Data and Material: The data that support the findings of this study are available upon reasonable request if permitted by Alberta Health Services; restrictions may apply. The anonymized model is publicly available on request. Ethics Approval and Consent to Participate: The study was approved by the Institutional Review Boards (IRBs) at the University of Alberta (Pro00101420) and the University of Calgary (REB17-2244). Individual patient consent was waived by both IRBs given the study was classified as a quality improvement initiative. Consent for Publication: Not applicable. Code Availability: The decision tree model was conducted using TreeAge software and the statistical analysis was conducted in R. Both files are included as supplementary material. Author Contributions: Conceptualization: C.D., D.Z., D.O., J.M.C., J.C., S.B., J.R., V.L., W.S. Data curation: K.C., C.B., M.G., C.C., T.D., C.P., A.T., D.G., D.O., J.M.C., J.C., K.F., W.S. Formal Analysis: X.W., C.Y., C.D., D.O., J.M.C., J.C., S.B., J.R., V.L., W.S. Funding acquisition: D.Z., D.O., S.B., W.S. Investigation: K.C., C.B., M.G., C.C., T.D., C.P., C.Y., G.C., A.T., D.G., C.D., D.Z., D.O., J.M.C., J.C., K.F., J.R., V.L., S.B., W.S. Methodology: X.W., C.Y., G.C., C.D., J.M.C., J.C., S.B., J.R., V.L., W.S. Project administration: D.Z., D.O., S.B., W.S. Resources: D.Z., D.O., S.B., W.S. Software: D.O., J.C., X.W. Supervision: S.B., W.S. Validation: S.B., W.S. Visualization: S.B., W.S. Writing—original draft: C.Y., C.D., J.M.C., S.B., J.R., V.L., S.B., W.S. Writing—reviewing and editing: K.C., C.B., M.G., C.C., T.D., C.P., C.Y., G.C., A.T., D.G., C.D., D.Z., D.O., J.M.C., J.C., K.F., J.R., V.L., S.B., W.S., (© 2024. The Author(s).)

Objectives: To summarize the efficacy of midodrine as an adjunctive therapy in critically ill patients. Safety of midodrine was assessed as a secondary outcome., Data Sources: We performed a systematic review and meta-analysis using a peer-reviewed search strategy combining the themes of vasopressor-dependent shock, critical care, and midodrine and including MEDLINE, Ovid Embase, CINAHL, and Cochrane library databases until September 14, 2023., Study Selection: We included studies if they: 1) included patients with vasopressor-dependent shock, 2) were performed in the ICU, 3) evaluated oral midodrine therapy compared with placebo or usual care, and 4) evaluated one of the outcomes of interest., Data Extraction: We extracted data independently in duplicate using standardized data abstraction forms, which included the following specific variables: patient characteristics, age, sex, type of ICU, etiology of shock, number of patients, study inclusion and exclusion criteria, and geographical location. We also captured the type, dose, and duration of IV vasopressors, any cointervention used, and outcome data., Data Synthesis: We identified seven randomized controlled trials (six included in the pooled analysis) and ten observational studies (four included in the pooled analysis) that met eligibility criteria. Adjunctive midodrine may decrease ICU length of stay (LOS) and there is low certainty of effect on hospital LOS. Midodrine may decrease IV vasopressor support duration, ICU mortality, and hospital mortality. Pooled observational data was based on very low certainty data for all outcomes of interest. The trial sequential analysis-informed required sample size was not met for ICU LOS or IV vasopressor duration and this contributed to Grading of Recommendations, Assessment, Development, and Evaluations assessments of imprecision for both outcomes., Conclusions: Adjunctive midodrine may decrease ICU LOS, duration of IV vasopressor therapy, and mortality in critically ill patients. However, required sample sizes was not met to determine our outcomes of interest. Midodrine may increase risk of bradycardia. While midodrine may provide benefit for patient-centered outcomes, due to increased risk of adverse events, further large-scale studies are needed to inform and guide its routine use in the ICU., Competing Interests: Mr. Kilcommons and Dr. Rewa disclosed the off-label product use of midodrine used for orthostatic hypotension and intradialytic hypotension. Dr. Bagshaw received funding from Baxter, Novartis, Sea Star Medical, BioPorto, and bioMerieux. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Background: Intravenous (IV) vasopressors are the mainstay of physiological support for hemodynamically unstable patients. However, the role of oral vasopressors remains unclear. The objective of our study was to evaluate the feasibility of evaluating midodrine for critically ill patients with IV vasopressor-dependent shock., Methods: We conducted a single-center, concealed-allocation, parallel-group, blinded feasibility randomized controlled trial (RCT) evaluating the effect of oral midodrine versus placebo on IV vasopressor-dependent shock in the intensive care unit (ICU). The study was performed in a medical-surgical ICU at the University of Alberta Hospital from April 2021 to July 2022. We included patients aged 18 years or older admitted to the ICU with ongoing vasopressor support with decreasing vasopressor dose(s). Patients were randomly assigned 1:1 to midodrine or a placebo for the duration of their IV vasopressor therapy. The primary outcome was study feasibility and secondary outcomes included patient-centered outcomes. Feasibility was assessed through rate of recruitment, adherence to study protocol, and patient safety., Results: Twenty patients were enrolled in the study and underwent randomization (n = 11 midodrine, n = 9 control). Recruitment was recorded at 1.2 participants per month, protocol adherence was 90%, and allocation remained concealed. No adverse events were reported in either group. Sepsis was the most common cause of shock in both groups. The midodrine group had a shorter length of ICU stay of 9.6 (SD 8.7) vs 10.4 (SD 14.5) days. Hospital mortality was lower for the midodrine group (n = 2, 18.2% vs n = 4, 37.5%). Vasopressor re-initiation after 24 h was more frequent in the midodrine group (n = 4, 36.4% vs n = 2, 25%). There were no readmissions to the ICU following discharge in either group., Conclusions: The evaluation of midodrine for patients in the ICU is feasible and safe. This trial will inform future large-scale RCTs regarding the utility of midodrine in critically ill patients with IV vasopressor-dependent shock., Trial Registration: This pilot RCT was registered at clinicaltrials.gov (NCT04489589). Registered July 27, 2020. https://clinicaltrials.gov/study/NCT04489589., Competing Interests: Declarations. Ethics approval and consent to participate: This trial was approved by the local Research Ethics Board (REB) in August 2020 (Pro00096716). Informed consent was obtained from the patient or surrogate decision-maker (SDM) prior to being enrolled in the study. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Purpose: The COVID-19 pandemic has resulted in increased job vacancies in Canadian intensive care units (ICUs). We aimed to identify, explore, and describe factors contributing to the decisions of health care workers to leave, or strongly consider leaving their ICU positions during the peri-COVID-19 pandemic era., Methods: We undertook a qualitative descriptive study between June and August 2022. We conducted semistructured interviews with 19 registered nurses and one respiratory therapist from a single ICU in Alberta, Canada who had left, or had strongly considered leaving their ICU position since the beginning of the pandemic. We used Braun and Clarke's thematic analysis to generate themes from these interviews., Results: We identified five themes to describe the factors that contributed to participants' decisions to leave, or strongly consider leaving, their ICU positions. These were: 1) toxic workplace, 2) inadequate staffing, 3) distress from providing nonbeneficial care, 4) caring for patients with COVID-19 and their families, and 5) paradoxical responses to COVID-19 outside of the ICU. Some of these factors existed before the pandemic and were exacerbated by it, while others were novel to COVID-19., Conclusions: Participants described as key factors in their decision or desire to leave their ICU positions the impacts of the COVID-19 pandemic on workplace culture, staffing, and patient interactions, as well as the discourse surrounding COVID-19 outside of work. Strategies that target workplace culture and ensure adequate staffing should be prioritized to promote staff retention following the pandemic., (© 2024. Canadian Anesthesiologists' Society.)

Objective: To determine the impact of point-of-care ultrasound (POCUS)-guided resuscitation on clinical outcomes in adult patients with shock., Data Source: We searched MEDLINE, Embase, and unpublished sources from inception to December 2023., Study Selection: We included randomized controlled trials (RCTs) that examined the use of POCUS to guide resuscitation in patients with shock., Data Extraction: We collected data regarding study and patient characteristics, POCUS protocol, control group interventions, and outcomes., Data Synthesis: We identified 18 eligible RCTs. POCUS slightly influences physicians' plans for IV fluid (IVF) and vasoactive medication prescription (moderate certainty), but results in little to no changes in the administration of IVF (low to high certainty) or inotropes (high certainty). POCUS may result in no change in the number of CT scans performed (low certainty) but probably reduces the number of diagnostic echocardiograms performed (moderate certainty). POCUS-guided resuscitation probably reduces 28-day mortality (relative risk [RR] 0.88; 95% CI, 0.78-0.99), the duration of vasoactive medication (mean difference -0.73 d; 95% CI, -1.16 to -0.30), and the need for renal replacement therapy (RRT) (RR 0.80; 95% CI, 0.63-1.02) (low to moderate certainty evidence), and lactate clearance (high certainty evidence). POCUS-guided resuscitation may results in little to no difference in ICU or hospital admissions, ICU and hospital length of stay, and the need for mechanical ventilation (MV) (low to moderate certainty evidence). There is an uncertain effect on the risk of acute kidney injury and the duration of MV or RRT (very low certainty evidence)., Conclusions: POCUS-guided resuscitation in shock may yield important patient and health system benefits. Due to lack of sufficient evidence, we were unable to explore how the thresholds of operator competency, frequency, and timing of POCUS scans impact patient outcomes., Competing Interests: Dr. Slessarev’s institution received funding from the Canadian Institutes of Health Research (CIHR) project grant for randomized controlled trial related to ICU sedation; he received support for article research from the CIHR. 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: Opioids remain the mainstay of analgesia for critically ill patients, but its exposure is associated with negative effects including persistent use after discharge. Nonsteroidal anti-inflammatory drugs (NSAIDs) may be an effective alternative to opioids with fewer adverse effects. We aimed to describe beliefs and attitudes towards the use of NSAIDs in adult intensive care units (ICUs)., Methods: Our survey of Canadian ICU physicians was conducted using a web-based platform and distributed through the Canadian Critical Care Society (CCCS) email distribution list. We used previously described survey development methodology including question generation and reduction, pretesting, and clinical sensibility and pilot testing., Results: We received 115 completed surveys from 321 CCCS members (36%). Nonsteroidal anti-inflammatory drugs use was most described as "rarely" (59 respondents, 51%) with the primary concern being adverse events (acute kidney injury [108 respondents, 94%] and gastrointestinal bleeding [92 respondents, 80%]). The primary preferred analgesic was acetaminophen (75 respondents, 65%) followed by opioids (40 respondents, 35%). Most respondents (91 respondents, 80%) would be willing to participate in a randomized controlled trial examining NSAID use in critical care., Conclusions: In our survey, Canadian critical care physicians did not mention commonly using NSAIDs primarily because of concerns about adverse events. Nevertheless, respondents were interested in further studying ketorolac, a commonly used NSAID outside of the ICU, in critically ill patients., (© 2024. Canadian Anesthesiologists' Society.)

Objective: To characterise sex and gender-based analysis (SGBA) and diversity metric reporting, representation of female/women participants in acute care trials and temporal changes in reporting before and after publication of the 2016 Sex and Gender Equity in Research guideline., Design: Systematic review., Data Sources: We searched MEDLINE for trials published in five leading medical journals in 2014, 2018 and 2020., Study Selection: Trials that enrolled acutely ill adults, compared two or more interventions and reported at least one clinical outcome., Data Abstraction and Synthesis: 4 reviewers screened citations and 22 reviewers abstracted data, in duplicate. We compared reporting differences between intensive care unit (ICU) and cardiology trials., Results: We included 88 trials (75 (85.2%) ICU and 13 (14.8%) cardiology) (n=111 428; 38 140 (34.2%) females/women). Of 23 (26.1%) trials that reported an SGBA, most used a forest plot (22 (95.7%)), were prespecified (21 (91.3%)) and reported a sex-by-intervention interaction with a significance test (19 (82.6%)). Discordant sex and gender terminology were found between headings and subheadings within baseline characteristics tables (17/32 (53.1%)) and between baseline characteristics tables and SGBA (4/23 (17.4%)). Only 25 acute care trials (28.4%) reported race or ethnicity. Participants were predominantly white (78.8%) and male/men (65.8%). No trial reported gendered-social factors. SGBA reporting and female/women representation did not improve temporally. Compared with ICU trials, cardiology trials reported significantly more SGBA (15/75 (20%) vs 8/13 (61.5%) p=0.005)., Conclusions: Acute care trials in leading medical journals infrequently included SGBA, female/women and non-white trial participants, reported race or ethnicity and never reported gender-related factors. Substantial opportunity exists to improve SGBA and diversity metric reporting and recruitment of female/women participants in acute care trials., Prospero Registration Number: CRD42022282565., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/disclosure-of-interest/. EB-C has received investigator-initiated grant funding from Bayer, BMS-Pfizer and Roche Diagnostics and consulting honoraria from Trimedic Therapeutics, which were unrelated to the current work. JR is a co-methodologist on the Society of Critical Care Medicine Guideline Committee–End of Life Care in the ICU Guidelines. VP is a member of the Canadian Critical Care Society–Equity, Diversity, Decolonisation and Inclusion Committee. KEAB is President of the Canadian Critical Care Society and an Ex-officio member of the Canadian Critical Care Trials Group Executive Committee. There are no other relationships or activities that could appear to have influenced the submitted work., (© 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: Critical care research in Canada is conducted primarily in academically affiliated intensive care units (ICUs) with established research infrastructure. Efforts are made to engage community hospital ICUs in research, although the impacts of their inclusion in clinical research have never been explicitly quantified. We therefore sought to determine the number of additional eligible patients that could be recruited into critical care trials and the change in time to study completion if community ICUs were included in clinical research., Methods: We conducted a decision tree analysis using 2018 Alberta Health Services data. Patient demographics and clinical characteristics for all ICU patients were compared against eligibility criteria from ten landmark, randomized, multicentre critical care trials. Individual patients from academic and community ICUs were assessed for eligibility in each of the ten studies, and decision tree analysis models were built based on prior inclusion and exclusion criteria from those trials., Results: The number of potentially eligible patients for the ten trials ranged from 2,082 to 10,157. Potentially eligible participants from community ICUs accounted for 40.0% of total potentially eligible participants. The recruitment of community ICU patients in trials would have increased potential enrolment by an average of 64.0%. The inclusion of community ICU patients was predicted to decrease time to trial completion by a mean of 14 months (43% reduction)., Conclusion: Inclusion of community ICU patients in critical care research trials has the potential to substantially increase enrolment and decrease time to trial completion., (© 2023. Canadian Anesthesiologists' Society.)

Introduction: Organ congestion may be a mediator of adverse outcomes in critically ill patients with severe acute kidney injury (AKI). The presence of abnormal venous Doppler waveforms could identify patients with clinically significant organ congestion who may benefit from a decongestive strategy., Methods: This prospective multicenter cohort study enrolled patients with severe AKI defined as Kidney Disease: Improving Global Outcomes stage 2 or higher. Patients were not eligible if they received renal replacement therapy (RRT) for more than 72 hours at the time of screening. Participants underwent serial Doppler ultrasound examinations of the portal, hepatic and intrarenal veins during the week following enrolment. We calculated the venous excess ultrasound (VExUS) score based on these data. The primary outcome studied was major adverse kidney events at 30 days (MAKE30) defined as death, RRT dependence, or a persistent decrease in kidney function., Results: A total of 125 patients were included for whom 291 ultrasound assessments were performed. Severely abnormal venous waveforms were documented in 14.4% of portal vein assessments, 6.5% of intrarenal venous assessments, and 14.4% of hepatic vein assessments. The individual ultrasound markers were not associated with MAKE30. The VExUS score (grade 0-1: reference; grade 2: adjusted hazard ratio [aHR]: 4.03, confidence interval [CI]: 1.81-8.99; grade 3: aHR: 2.70, CI: 1.10-6.65; P  = 0.03), as well as severely abnormal portal, hepatic and intrarenal vein Doppler were each independently associated with mortality., Conclusion: Although not significantly associated with MAKE30, venous Doppler abnormalities suggestive of venous congestion were associated with higher mortality in critically ill patients with severe AKI., (© 2023 International Society of Nephrology. Published by Elsevier Inc.)

Background: Children are increasingly discharged directly from the PICU. Transitions have been recognized as a period of increased patient and caregiver stress and risk of adverse events. No study has evaluated patient and caregiver outcomes after direct discharge from the PICU. This study aimed to explore the family's experiences with discharge directly home (DDH) from the PICU., Methods: This exploratory mixed-methods study was conducted in the PICU of the Institution is Sainte-Justine Hospital from February to July 2021. We included families of children expected to be DDH within 12 hours. Semistructured interviews were conducted at discharge, followed by telephone interviews 7 and 28 days post-PICU discharge. We measured comfort on a 5-point Likert scale and screened for anxiety using the Generalized Anxiety Disorder-7 tool., Results: Families of 25 patients were interviewed. Thematic analysis of the interviews revealed several themes, such as feeling stress and anxiety, feeling confident, anticipating home care, and needing support. These findings complemented the quantitative findings; the median comfort score was 4 (comfortable) (interquartile range 4-5) and 8 (interquartile range 4-12) for the Generalized Anxiety Disorder-7 on the day of discharge, with 16 reporting clinically significant anxiety. In the 28-day study period, 2 patients were readmitted and 6 had visited the emergency department., Conclusions: Despite feelings of anxiety, many families felt comfortable with DDH from the PICU. Increasing our understanding of the patient and family experiences of discharge from the PICU will help to better support these patients and their families during transition., (Copyright © 2023 by the American Academy of Pediatrics.)

Objectives: Studies have suggested intrapulmonary shunts may contribute to hypoxemia in COVID-19 acute respiratory distress syndrome (ARDS) with worse associated outcomes. We evaluated the presence of right-to-left (R-L) shunts in COVID-19 and non-COVID ARDS patients using a comprehensive hypoxemia workup for shunt etiology and associations with mortality., Design: Prospective, observational cohort study., Setting: Four tertiary hospitals in Edmonton, Alberta, Canada., Patients: Adult critically ill, mechanically ventilated, ICU patients admitted with COVID-19 or non-COVID (November 16, 2020, to September 1, 2021)., Interventions: Agitated-saline bubble studies with transthoracic echocardiography/transcranial Doppler ± transesophageal echocardiography assessed for R-L shunts presence., Measurements and Main Results: Primary outcomes were shunt frequency and association with hospital mortality. Logistic regression analysis was used for adjustment. The study enrolled 226 patients (182 COVID-19 vs 42 non-COVID). Median age was 58 years (interquartile range [IQR], 47-67 yr) and Acute Physiology and Chronic Health Evaluation II scores of 30 (IQR, 21-36). In COVID-19 patients, the frequency of R-L shunt was 31 of 182 COVID patients (17.0%) versus 10 of 44 non-COVID patients (22.7%), with no difference detected in shunt rates (risk difference [RD], -5.7%; 95% CI, -18.4 to 7.0; p = 0.38). In the COVID-19 group, hospital mortality was higher for those with R-L shunt compared with those without (54.8% vs 35.8%; RD, 19.0%; 95% CI, 0.1-37.9; p = 0.05). This did not persist at 90-day mortality nor after adjustment with regression., Conclusions: There was no evidence of increased R-L shunt rates in COVID-19 compared with non-COVID controls. R-L shunt was associated with increased in-hospital mortality for COVID-19 patients, but this did not persist at 90-day mortality or after adjusting using logistic regression., Competing Interests: Dr. Lau’s institution received funding from the University Hospital Foundation, the Royal Alexandra Hospital Foundation, and the Covenant Health Foundation. Dr. Shaw received funding from Edwards Lifesciences, Novartis, and Astellas. Dr. Opgenorth disclosed that she is an employee of the University of Alberta. Dr. Bagshaw received funding from Baxter and BioPorto; he is supported by a Canada Research Chair in Critical Care Outcomes and Systems Evaluation. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

While opioids are part of usual care for analgesia in the ICU, there are concerns regarding excess use. This is a systematic review of nonsteroidal anti-inflammatory drugs (NSAIDs) use in postoperative critical care adult patients., Data Sources: We searched Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, trial registries, Google Scholar, and relevant systematic reviews through March 2023., Study Selection: Titles, abstracts, and full texts were reviewed independently and induplicate by two investigators to identify eligible studies. We included randomized control trials (RCTs) that compared NSAIDs alone or as an adjunct to opioids for systemic analgesia. The primary outcome was opioid utilization., Data Extraction: In duplicate, investigators independently extracted study characteristics, patient demographics, intervention details, and outcomes of interest using predefined abstraction forms. Statistical analyses were conducted using Review Manager software Version 5.4. (The Cochrane Collaboration, Copenhagen, Denmark)., Data Synthesis: We included 15 RCTs ( n = 1,621 patients) for admission to the ICU for postoperative management after elective procedures. Adjunctive NSAID therapy to opioids reduced 24-hour oral morphine equivalent consumption by 21.4 mg (95% CI, 11.8-31.0 mg reduction; high certainty) and probably reduced pain scores (measured by Visual Analog Scale) by 6.1 mm (95% CI, 12.2 decrease to 0.1 increase; moderate certainty). Adjunctive NSAID therapy probably had no impact on the duration of mechanical ventilation (1.6 hr reduction; 95% CI, 0.4 hr to 2.7 reduction; moderate certainty) and may have no impact on ICU length of stay (2.1 hr reduction; 95% CI, 6.1 hr reduction to 2.0 hr increase; low certainty). Variability in reporting adverse outcomes (e.g., gastrointestinal bleeding, acute kidney injury) precluded their meta-analysis., Conclusions: In postoperative critical care adult patients, systemic NSAIDs reduced opioid use and probably reduced pain scores. However, the evidence is uncertain for the duration of mechanical ventilation or ICU length of stay. Further research is required to characterize the prevalence of NSAID-related adverse outcomes., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

A man in his 30s with alpha thalassaemia (four-alpha globin gene deletion) presented with 1 week of shortness of breath and 1 month of general malaise. Pulse oximetry monitoring revealed low peripheral oxygen saturation of approximately 80% despite maximal high-flow nasal cannula oxygen (fractional inspired oxygen 1.0-60 L/min flow). Arterial blood gas samples were chocolate brown in colour, with a low arterial partial pressure of oxygen of 197 mm Hg. This large oxygen saturation gap raised suspicion for methaemoglobinaemia. However, the patient's co-oximetry results were suppressed by the blood gas analyser and delayed a definitive diagnosis. A methaemalbumin screen was sent instead, which was positive at 65 mg/L (reference interval: <3 mg/L). Treatment with methylene blue was initiated but did not result in complete resolution of cyanosis. This patient had been red cell exchange dependent since childhood for thalassaemia. Therefore, an urgent red cell exchange was initiated overnight, leading to an improvement in symptoms and interpretability of co-oximetry results. This resulted in rapid improvement without residual sequelae or complications. We conclude that a methaemalbumin screen can be used as a surrogate test for prompt confirmation of diagnosis in lieu of co-oximetry in cases of severe methaemoglobinaemia or in cases with underlying haemoglobinopathy. Red cell exchange can allow prompt methaemoglobinaemia reversal, especially if methylene blue is only partially effective., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate the impact of direct discharge home (DDH) from ICUs compared with ward transfer on safety outcomes of readmissions, emergency department (ED) visits, and mortality., Data Sources: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing and Allied Health Literature from inception until March 28, 2022., Study Selection: Randomized and nonrandomized studies of DDH patients compared with ward transfer were eligible., Data Extraction: We screened and extracted studies independently and in duplicate. We assessed risk of bias using the Newcastle-Ottawa Scale for observational studies. A random-effects meta-analysis model and heterogeneity assessment was performed using pooled data (inverse variance) for propensity-matched and unadjusted cohorts. We assessed the overall certainty of evidence for each outcome using the Grading Recommendations Assessment, Development and Evaluation approach., Data Synthesis: Of 10,228 citations identified, we included six studies. Of these, three high-quality studies, which enrolled 49,376 patients in propensity-matched cohorts, could be pooled using meta-analysis. For DDH from ICU, compared with ward transfers, there was no difference in the risk of ED visits at 30-day (22.4% vs 22.7%; relative risk [RR], 0.99; 95% CI, 0.95-1.02; p = 0.39; low certainty); hospital readmissions at 30-day (9.8% vs 9.6%; RR, 1.02; 95% CI, 0.91-1.15; p = 0.71; very low-to-low certainty); or 90-day mortality (2.8% vs 2.6%; RR, 1.06; 95% CI, 0.95-1.18; p = 0.29; very low-to-low certainty). There were no important differences in the unmatched cohorts or across subgroup analyses., Conclusions: Very low-to-low certainty evidence from observational studies suggests that DDH from ICU may have no difference in safety outcomes compared with ward transfer of selected ICU patients. In the future, this research question could be further examined by randomized control trials to provide higher certainty data., Competing Interests: Dr. Parvez received funding from the University of Saskatchewan College of Medicine Dean’s Summer Student 2020 Award. Dr. Bagshaw received funding from Baxter and BioPorto. Dr. Scales’ institution received funding from the Canadian Institute for Health Research. Dr. Sy received funding from the Saskatchewan Health Research Foundation Establishment Grant. Dr. Bagshaw is supported by a Canada Research Chair in Critical Care Outcomes and Systems Evaluation. Dr. Fowler is the H. Barrie Fairley Professor of Critical Care Medicine at the University Health Network and the Interdepartmental Division of Critical Care Medicine at the University of Toronto. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Background and Aim: With the Coronavirus Disease 2019 (COVID-19) pandemic continuing to impact healthcare systems around the world, healthcare providers are attempting to balance resources devoted to COVID-19 patients while minimizing excess mortality overall (both COVID-19 and non-COVID-19 patients). To this end, we conducted a systematic review (SR) to describe the effect of the COVID-19 pandemic on all-cause excess mortality (COVID-19 and non-COVID-19) during the pandemic timeframe compared to non-pandemic times., Methods: We searched EMBASE, Cochrane Database of SRs, MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Cochrane Controlled Trials Register (CENTRAL), from inception (1948) to December 31, 2020. We used a two-stage review process to screen/extract data. We assessed risk of bias using Newcastle-Ottawa Scale (NOS). We used Critical Appraisal and Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology., Results: Of 11,581 citations, 194 studies met eligibility. Of these studies, 31 had mortality comparisons ( n = 433,196,345 participants). Compared to pre-pandemic times, during the COVID-19 pandemic, our meta-analysis demonstrated that COVID-19 mortality had an increased risk difference (RD) of 0.06% (95% CI: 0.06-0.06% p < 0.00001). All-cause mortality also increased [relative risk (RR): 1.53, 95% confidence interval (CI): 1.38-1.70, p < 0.00001] alongside non-COVID-19 mortality (RR: 1.18, 1.07-1.30, p < 0.00001). There was "very low" certainty of evidence through GRADE assessment for all outcomes studied, demonstrating the evidence as uncertain., Interpretation: The COVID-19 pandemic may have caused significant increases in all-cause excess mortality, greater than those accounted for by increases due to COVID-19 mortality alone, although the evidence is uncertain., Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/#recordDetails], identifier [CRD42020201256]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lu, Dhanoa, Cheema, Lewis, Geeraert, Merrick, Vander Leek, Sebastianski, Kula, Chaudhuri, Basmaji, Agrawal, Niven, Fiest, Stelfox, Zuege, Rewa, Bagshaw and Lau.)

Purpose: We sought to compare the cost-effectiveness of probiotics and usual care with usual care without probiotics in mechanically ventilated, intensive care unit patients alongside the Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial (PROSPECT)., Methods: We conducted a health economic evaluation alongside the PROSPECT randomized control trial (October 2013-March 2019). We adopted a public healthcare payer's perspective. Forty-four intensive care units in three countries (Canada/USA/Saudi Arabia) with adult critically ill, mechanically ventilated patients (N = 2,650) were included. Interventions were probiotics (Lactobacillus rhamnosus GG) vs placebo administered enterally twice daily. We collected healthcare resource use and estimated unit costs in 2019 United States dollars (USD) over a time horizon from randomization to hospital discharge/death. We calculated incremental cost-effectiveness ratios (ICERs) comparing probiotics vs usual care. The primary outcome was incremental cost per ventilator-associated pneumonia (VAP) event averted; secondary outcomes were costs per Clostridioides difficile-associated diarrhea (CDAD), antibiotic-associated diarrhea (AAD), and mortality averted. Uncertainty was investigated using nonparametric bootstrapping and sensitivity analyses., Results: Mean (standard deviation [SD]) cost per patient was USD 66,914 (91,098) for patients randomized to probiotics, with a median [interquartile range (IQR)] of USD 42,947 [22,239 to 76,205]. By comparison, for those not receiving probiotics, mean (SD) cost per patient was USD 62,701 (78,676) (median [IQR], USD 41,102 [23,170 to 75,140]; incremental cost, USD 4,213; 95% confidence interval [CI], -2,269 to 10,708). Incremental cost-effectiveness ratios for VAP or AAD events averted, probiotics were dominated by usual care (more expensive, with similar effectiveness). The ICERs were USD 1,473,400 per CDAD event averted (95% CI, undefined) and USD 396,764 per death averted (95% CI, undefined). Cost-effectiveness acceptability curves reveal that probiotics were not cost-effective across wide ranges of plausible willingness-to-pay thresholds. Sensitivity analyses did not change the conclusions., Conclusions: Probiotics for VAP prevention among critically ill patients were not cost-effective. Study registration data www., Clinicaltrials: gov (NCT01782755); registered 4 February 2013., (© 2022. Canadian Anesthesiologists' Society.)

Acute respiratory distress syndrome (ARDS) is a life-threatening respiratory injury with multiple physiological sequelae. Shunting of deoxygenated blood through intra- and extrapulmonary shunts may complicate ARDS management. Therefore, we conducted a systematic review to determine the prevalence of sonographically detected shunts, and their association with oxygenation and mortality in patients with ARDS., Data Sources: Medical literature analysis and retrieval system online, Excerpta Medica dataBASE, Cochrane Library, and database of abstracts of reviews of effects databases on March 26, 2021., Study Selection: Articles relating to respiratory failure and sonographic shunt detection., Data Extraction: Articles were independently screened and extracted in duplicate. Data pertaining to study demographics and shunt detection were compiled for mortality and oxygenation outcomes. Risk of bias was appraised using the Joanna-Briggs Institute and the Newcastle-Ottawa Scale tools with evidence rating certainty using Grading of Recommendations Assessment, Development and Evaluation methodology., Data Synthesis: From 4,617 citations, 10 observational studies met eligibility criteria. Sonographic detection of right-to-left shunt was present in 21.8% of patients (range, 14.4-30.0%) among included studies using transthoracic, transesophageal, and transcranial bubble Doppler ultrasonographies. Shunt prevalence may be associated with increased mortality (risk ratio, 1.22; 95% CI, 1.01-1.49; p = 0.04, very low certainty evidence) with no difference in oxygenation as measured by Pao 2 :Fio 2 ratio (mean difference, -0.7; 95% CI, -18.6 to 17.2; p = 0.94, very low certainty)., Conclusions: Intra- and extrapulmonary shunts are detected frequently in ARDS with ultrasound techniques. Shunts may increase mortality among patients with ARDS, but its association with oxygenation is uncertain., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Purpose: To evaluate the long-term safety of directly discharging intensive care unit (ICU) survivors to their home. Methods: A retrospective observational cohort of 341 ICU survivors who were directly discharged home from the ICU ("direct discharge") or discharged home ≤72 hours after ICU transfer to the ward ("ward transfer") was conducted in Regina, Saskatchewan ICUs between September 1, 2016 and September 30, 2018. The primary outcome was 90-day hospital readmission. Secondary outcomes included 30-day, 90-day, and 365-day emergency department (ED) visits, 30-day and 365-day hospital readmissions, and 365-day mortality. All outcomes were evaluated by multivariable Cox regression after adjustment for demographic and clinical characteristics. Results: Of 341 survivors (25.5% of total ICU visits), 148 (43.4%) patients were direct discharges and 193 (56.6%) were ward transfers. The median age was 46 years (interquartile range, 34-62), 38.4% were female, and 61.8% resided in Regina. Compared to the ward transfer cohort, more patients in the direct discharge cohort had at least one 90-day hospital readmission (30.4% versus 17.1% of patients, adjusted hazard ratio 2.09, 95% confidence interval 1.28-3.40, P  = .003), after adjustment. Additionally, there were more 90-day ED visits ( P  = .045), and 30-day ( P  = .049) and 365-day hospital readmissions ( P  = .03), after adjustment. Conclusions: In Saskatchewan, direct discharge compared to ward transfer was associated with an increase in 90-day hospital readmissions, and potentially other clinical outcomes. Further study is necessary.

Background: Critical care research in Canada is conducted primarily in academically-affiliated intensive care units with established research infrastructure, including research coordinators (RCs). Recently, efforts have been made to engage community hospital ICUs in research albeit with barriers. Automation or artificial intelligence (AI) could aid the performance of routine research tasks. It is unclear which research study processes might be improved through AI automation., Methods: We conducted a cross-sectional survey of Canadian ICU research personnel. The survey contained items characterizing opinions regarding research processes that may be amenable to AI automation. We distributed the questionnaire via email distribution lists of 3 Canadian research societies. Open-ended questions were analyzed using a thematic content analysis approach., Results: A total of 49 survey responses were received (response rate: 8%). Tasks that respondents felt were time-consuming/tedious/tiresome included: screening for potentially eligible patients (74%), inputting data into case report forms (65%), and preparing internal tracking logs (53%). Tasks that respondents felt could be performed by AI automation included: screening for eligible patients (59%), inputting data into case report forms (55%), preparing internal tracking logs (51%), and randomizing patients into studies (45%). Open-ended questions identified enthusiasm for AI automation to improve information accuracy and efficiency while freeing up RCs to perform tasks that require human interaction. This enthusiasm was tempered by the need for proper AI education and oversight., Conclusions: There were balanced supportive (increased efficiency and re-allocation of tasks) and challenges (informational accuracy and oversight) with regards to AI automation in ICU research.

Background: The role of remdesivir in the treatment of hospitalized patients with COVID-19 remains ill-defined. We conducted a cost-effectiveness analysis alongside the Canadian Treatments for COVID-19 (CATCO) open-label, randomized clinical trial evaluating remdesivir., Methods: Patients with COVID-19 in Canadian hospitals from Aug. 14, 2020, to Apr. 1, 2021, were randomly assigned to receive remdesivir plus usual care versus usual care alone. Taking a public health care payer's perspective, we collected in-hospital outcomes and health care resource utilization alongside estimated unit costs in 2020 Canadian dollars over a time horizon from randomization to hospital discharge or death. Data from 1281 adults admitted to 52 hospitals in 6 Canadian provinces were analyzed., Results: The total mean cost per patient was $37 918 (standard deviation [SD] $42 413; 95% confidence interval [CI] $34 617 to $41 220) for patients randomly assigned to the remdesivir group and $38 026 (SD $46 021; 95% CI $34 480 to $41 573) for patients receiving usual care (incremental cost -$108 [95% CI -$4953 to $4737], p > 0.9). The difference in proportions of in-hospital deaths between remdesivir and usual care groups was -3.9% (18.7% v. 22.6%, 95% CI -8.3% to 1.0%, p = 0.09). The difference in proportions of incident invasive mechanical ventilation events between groups was -7.0% (8.0% v. 15.0%, 95% CI -10.6% to -3.4%, p = 0.006), whereas the difference in proportions of total mechanical ventilation events between groups was -5.7% (16.4% v. 22.1%, 95% CI -10.0% to -1.4%, p = 0.01). Remdesivir was the dominant intervention (but only marginally less costly, with mildly lower mortality) with an incalculable incremental cost effectiveness ratio; we report results of incremental costs and incremental effects separately. For willingness-to-pay thresholds of $0, $20 000, $50 000 and $100 000 per death averted, a strategy using remdesivir was cost-effective in 60%, 67%, 74% and 79% of simulations, respectively. The remdesivir costs were the fifth highest cost driver, offset by shorter lengths of stay and less mechanical ventilation., Interpretation: From a health care payer perspective, treating patients hospitalized with COVID-19 with remdesivir and usual care appears to be preferrable to treating with usual care alone, albeit with marginal incremental cost and small clinical effects. The added cost of remdesivir was offset by shorter lengths of stay in the intensive care unit and less need for ventilation., Study Registration: ClinicalTrials. gov, no. NCT04330690., Competing Interests: Competing interests: Robert Fowler is the H. Barrie Fairley Professor of Critical Care Medicine at the University Health Network and the University of Toronto Interdepartmental Division of Critical Care Medicine. Robert Fowler declares a Canadian Institutes of Health Research (CIHR) operating grant. John Conly declares grants from the CIHR, Pfizer and the World Health Organization (WHO). He declares a peer-reviewed research grant on acute and primary care preparedness for COVID-19 in Alberta, Canada; he was a primary local investigator for the STRIVE Staphylococcus aureus vaccine randomized controlled trial in vertebral spinal surgery with instrumentation for which all funding was provided only to the University of Calgary; he was a co-investigator on a WHO-funded study using integrated human factors and ethnography approaches to identify and scale innovative infection prevention and control (IPC) guidance implementation supports in primary care with a focus on low-resource settings and using drone aerial systems to deliver medical supplies and personal protective equipment to remote First Nations communities during the COVID-19 pandemic. John Conly also reports receiving accommodations and airfare from the Centers for Disease Control and Prevention to attend a meeting in 2019. He is a member and chair of the WHO Infection Prevention and Control Research and Development Expert Group for COVID-19 and a member of the WHO Health Emergencies Programme Ad-hoc COVID-19 IPC Guidance Development Group, both of which provide multidisciplinary advice to the WHO, for which no funding is received and from which no funding recommendations are made for any WHO contracts or grants. He is also a member of the Cochrane Acute Respiratory Infections Group. Darrell Tan is supported by a Tier 2 Canada Research Chair in HIV Prevention and STI Research. Ryan Zarychanski reports grants from the CIHR, the Peter Munk Cardiac Centre, the Thistledown Foundation and the National Institutes of Health. He is a WHO thrombostasis technical advisory member. Ryan Zarychanski is the recipient of the Lyonel G. Israels Research Chair in Hematology at the University of Manitoba. Todd Lee reports a CATCO operating grant from the CIHR as a co–principal investigator and a co-investigator. He reports various operating grants from the CIHR, a technical development grant from the Centre for Aging + Brain Health Innovation and research salary support from the Fonds de recherche du Québec — Santé. He is the co-owner of a company that is bringing Med-Safer to market. Srinivas Murthy is the Innovative Medicines Canada and Health Research Foundation Chair in Pandemic Preparedness Research. Srinivas Murthy reports a grants from the CIHR and Health Research Foundation and Innovative Medicines Canada., (© 2022 CMA Impact Inc. or its licensors.)

Mortality is a well-established patient-important outcome in critical care studies. In contrast, morbidity is less uniformly reported (given the myriad of critical care illnesses and complications of each) but may have a common end-impact on a patient's functional capacity and health-related quality-of-life (HRQoL). Survival with a poor quality-of-life may not be acceptable depending on individual patient values and preferences. Hence, as mortality decreases within critical care, it becomes increasingly important to measure intensive care unit (ICU) survivor HRQoL. HRQoL measurements with a preference-based scoring algorithm can be converted into health utilities on a scale anchored at 0 (representing death) and 1 (representing full health). They can be combined with survival to calculate quality-adjusted life-years (QALY), which are one of the most widely used methods of combining morbidity and mortality into a composite outcome. Although QALYs have been use for health-technology assessment decision-making, an emerging and novel role would be to inform clinical decision-making for patients, families and healthcare providers about what expected HRQoL may be during and after ICU care. Critical care randomized control trials (RCTs) have not routinely measured or reported HRQoL (until more recently), likely due to incapacity of some patients to participate in patient-reported outcome measures. Further differences in HRQoL measurement tools can lead to non-comparable values. To this end, we propose the validation of a gold-standard HRQoL tool in critical care, specifically the EQ-5D-5L. Both combined health-utility and mortality (disaggregated) and QALYs (aggregated) can be reported, with disaggregation allowing for determination of which components are the main drivers of the QALY outcome. Increased use of HRQoL, health-utility, and QALYs in critical care RCTs has the potential to: (1) Increase the likelihood of finding important effects if they exist; (2) improve research efficiency; and (3) help inform optimal management of critically ill patients allowing for decision-making about their HRQoL, in additional to traditional health-technology assessments., Competing Interests: Conflict-of-interest statement: Drs. Lau, Xie and Johnson have received funding from EuroQoL Foundation. All other authors declare that they have no conflict of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: As the Coronavirus Disease-2019 (COVID-19) pandemic continues, healthcare providers struggle to manage both COVID-19 and non-COVID patients while still providing high-quality care. We conducted a systematic review/meta-analysis to describe the effects of the COVID-19 pandemic on patients with non-COVID illness and on healthcare systems compared to non-pandemic epochs., Methods: We searched Ovid MEDLINE/EMBASE/Cochrane Database of Systematic Reviews/CENTRAL/CINAHL (inception to December 31, 2020). All study types with COVID-pandemic time period (after December 31, 2019) with comparative non-pandemic time periods (prior to December 31, 2019). Data regarding study characteristics/case-mix/interventions/comparators/ outcomes (primary: mortality; secondary: morbidity/hospitalizations/disruptions-to-care. Paired reviewers conducted screening and abstraction, with conflicts resolved by discussion. Effect sizes for specific therapies were pooled using random-effects models. Risk of bias was assessed by Newcastle-Ottawa Scale, with evidence rating using GRADE methodology., Results: Of 11,581 citations, 167 studies met eligibility. Our meta-analysis showed an increased mortality of 16% during the COVID pandemic for non-COVID illness compared with 11% mortality during the pre-pandemic period (RR 1.38, 95% CI: 1.28-1.50; absolute risk difference: 5% [95% CI: 4-6%], p<0.00001, very low certainty evidence). Twenty-eight studies (17%) reported significant changes in morbidity (where 93% reported increases), while 30 studies (18%) reported no significant change (very low certainty). Thirty-nine studies (23%) reported significant changes in hospitalizations (97% reporting decreases), while 111 studies (66%) reported no significant change (very low certainty). Sixty-two studies (37%) reported significant disruptions in standards-to-care (73% reporting increases), while 62 studies (37%) reported no significant change (very low certainty)., Conclusions: There was a significant increase in mortality during the COVID pandemic compared to pre-pandemic times for non-COVID illnesses. When significant changes were reported, there was increased morbidity, decreased hospitalizations and increased disruptions in standards-of-care., Systematic Review Registration: PROSPERO CRD42020201256 (Sept 2, 2020)., Competing Interests: NO authors have competing interests.

Background: Severe infections are characterized by inflammation and oxidative damage. Ascorbic acid (vitamin C) administration may attenuate oxidative damage and, in turn, reduce vascular endothelial injury in pulmonary and systemic vasculature., Objective: We aim to describe a protocol for a living systematic review that will evaluate the effectiveness and safety of parenteral vitamin C administration in adults with severe infections, including those with COVID-19., Methods: We searched Ovid MEDLINE, Embase, CINAHL, the Centers for Disease Control and Prevention COVID-19 database, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to March 30, 2021, for randomized controlled trials evaluating parenteral vitamin C versus no parenteral vitamin C in hospitalized adults with severe infection. Eligible studies will include at least 1 arm involving any dose of parenteral vitamin C alone or in combination with other cointerventions and at least 1 arm not involving parenteral vitamin C. The primary outcomes of interest will include in-hospital, 30-day, and 90-day mortality. Title and abstract screening, full-text screening, data extraction, and risk of bias evaluation via a modified Risk of Bias 2.0 tool will be conducted independently and in pairs. We will perform random effects modeling for meta-analyses, in which study weights will be generated by using the inverse variance method. We will assess certainty in effect estimates by using the Grading of Recommendations Assessment, Development and Evaluation methodology. Meta-analyses will be updated iteratively as new trial evidence becomes available., Results: Among the 1386 citations identified as of March 30, 2021, a total of 17 eligible randomized controlled trials have been identified as of September 2021. We are in the process of updating the search strategy and associated data analyses., Conclusions: The results will be of importance to critical care physicians and hospitalists who manage severe infection and COVID-19 in daily practice, and they may directly inform international clinical guidance. Although our systematic review will incorporate the most recent trial evidence, ongoing trials may change our confidence in the estimates of effects, thereby necessitating iterative updates in the form of a living review., Trial Registration: PROSPERO CRD42020209187; https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=209187., International Registered Report Identifier (irrid): RR1-10.2196/33989., (©Arnav Agarwal, John Basmaji, Shannon M Fernando, Fang Zhou Ge, Yingqi Xiao, Haseeb Faisal, Kimia Honarmand, Mathieu Hylands, Vincent I Lau, Kimberley Lewis, Rachel Couban, François Lamontagne, Neill KJ Adhikari. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 06.01.2022.)

Objectives: Cost utility analyses compare the costs and health outcome of interventions, with a denominator of quality-adjusted life year, a generic health utility measure combining both quality and quantity of life. Cost utility analyses are difficult to compare when methods are not standardized. It is unclear how cost utility analyses are measured/reported in critical care and what methodologic challenges cost utility analyses pose in this setting. This may lead to differences precluding cost utility analyses comparisons. Therefore, we performed a systematic review of cost utility analyses conducted in critical care. Our objectives were to understand: 1) methodologic characteristics, 2) how health-related quality-of-life was measured/reported, and 3) what costs were reported/measured., Design: Systematic review., Data Sources: We systematically searched for cost utility analyses in critical care in MEDLINE, Embase, American College of Physicians Journal Club, CENTRAL, Evidence-Based Medicine Reviews' selected subset of archived versions of UK National Health Service Economic Evaluation Database, Database of Abstracts of Reviews of Effects, and American Economic Association electronic databases from inception to April 30, 2020., Setting: Adult ICUs., Patients: Adult critically ill patients., Interventions: None., Measurements and Main Results: Of 8,926 citations, 80 cost utility analyse studies were eligible. The time horizon most commonly reported was lifetime (59%). For health utility reporting, health-related quality-of-life was infrequently measured (29% reported), with only 5% of studies reporting baseline health-related quality-of-life. Indirect utility measures (generic, preference-based health utility measurement tools) were reported in 85% of studies (majority Euro-quality-of-life-5 Domains, 52%). Methods of estimating health-related quality-of-life were seldom used when the patient was incapacitated: imputation (19%), assigning fixed utilities for incapacitation (19%), and surrogates reporting on behalf of incapacitated patients (5%). For cost utility reporting transparency, separate incremental costs and quality-adjusted life years were both reported in only 76% of studies. Disaggregated quality-adjusted life years (reporting separate health utility and life years) were described in only 34% of studies., Conclusions: We identified deficiencies which warrant recommendations (standardized measurement/reporting of resource use/unit costs/health-related quality-of-life/methodological preferences) for improved design, conduct, and reporting of future cost utility analyses in critical care., Competing Interests: Dr. Xie receives a Career Scientist Award from Ontario Ministry of Health and Long-Term Care and a Canadian Institutes of Health Research (CIHR) New Investigator Award. Dr. Cook holds a Chair of the CIHR. Dr. Sirotich received funding from Board membership of the Canadian Arthritis Patient Alliance and Coronavirus Disease 2019 Global Rheumatology Alliance. Dr. Bagshaw received funding from Baxter and CNA Diagnostics, and he holds a Canada Research Chair in Critical Care Nephrology. Dr. Lamontagne holds a Canadian Research Chair in Patient-Centered Research in Acute Care. Dr. Ferguson received funding from Getinge and Xenios. Dr. Rochwerg is supported by a Hamilton Health Sciences Early Career Research Award. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Purpose: To describe factors (demographics and clinical characteristics) that predict patients who are at an increased risk of adverse events or unplanned return visits to a health-care facility following discharge direct to home (DDH) from intensive care units (ICUs)., Methods: Prospective cohort study of all adult patients who survived their stay in our medical-surgical-trauma ICU between February 2016 and 2017 and were discharged directly home. Patients were followed for 8 weeks postdischarge. Univariable and multivariable logistic regression analyses were performed to identify factors associated with adverse events or unplanned return visits to a health-care facility following DDH from ICU., Results: A total of 129 DDH patients were enrolled and completed the 8-week follow-up. We identified 39 unplanned return visits (URVs). There was 0% mortality at 8 weeks postdischarge. Eight potential predictors of hospital URVs ( P < .2) were identified in the univariable analysis: prior substance abuse (odds ratio [OR] of URV of 2.50 [95% confidence interval: 1.08-5.80], hepatitis (OR: 6.92 [1.68-28.48]), sepsis (OR: 11.03 [1.19-102.29]), admission nine equivalents of nursing manpower score (NEMS) <24 (OR: 2.28 [1.03-5.04], no fixed address (OR: 22.9 [1.2-437.3]), ICU length of stay (LOS) <2 days (OR: 2.95 [1.28-6.78]), home discharge within London, Ontario (OR: 2.44 [1.00-5.92]), and left against medical advice (AMA; OR: 6.06 [2.04-17.98])., Conclusions: Our study identified 8 covariates that were potential predictors of URV: prior substance abuse, hepatitis, sepsis, admission NEMS <24, no fixed address, ICU LOS <2 days, home discharge within London, Ontario, and left AMA. The practice of direct discharges home from the ICU would benefit from adequately powered multicenter study in order to construct a clinical prediction model (that would require further testing and validation).

Introduction: Ventilator-associated pneumonia (VAP) is a common healthcare-associated infection in the intensive care unit (ICU). Probiotics are defined as live microorganisms that may confer health benefits when ingested. Prior randomised trials suggest that probiotics may prevent infections such as VAP and Clostridioides difficile -associated diarrhoea (CDAD). PROSPECT (Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial) is a multicentre, double-blinded, randomised controlled trial comparing the efficacy of the probiotic Lactobacillus rhamnosus GG with usual care versus usual care without probiotics in preventing VAP and other clinically important outcomes in critically ill patients admitted to the ICU., Methods and Analysis: The objective of E-PROSPECT is to determine the incremental cost-effectiveness of L. rhamnosus GG plus usual care versus usual care without probiotics in critically ill patients. E-PROSPECT will be performed from the public healthcare payer's perspective over a time horizon from ICU admission to hospital discharge.We will determine probabilities of in-ICU and in-hospital events from all patients alongside PROSPECT. We will retrieve unit costs for each resource use item using jurisdiction-specific public databases, supplemented by individual site unit costs if such databases are unavailable. Direct costs will include medications, personnel costs, radiology/laboratory testing, operative/non-operative procedures and per-day hospital 'hoteling' costs not otherwise encompassed. The primary outcome is the incremental cost per VAP prevented between the two treatment groups. Other clinical events such as CDAD, antibiotic-associated diarrhoea and in-hospital mortality will be included as secondary outcomes. We will perform pre-specified subgroup analyses (medical/surgical/trauma; age; frailty status; antibiotic use; prevalent vs no prevalent pneumonia) and probabilistic sensitivity analyses for VAP, then generate confidence intervals using the non-parametric bootstrapping approach., Ethics and Dissemination: Study approval for E-PROSPECT was granted by the Hamilton Integrated Research Ethics Board of McMaster University on 29 July 2019. Informed consent was obtained from the patient or substitute decision-maker in PROSPECT. The findings of this study will be published in peer-reviewed journals., Trial Registration Number: NCT01782755; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Probiotics may prevent healthcare-associated infections, such as ventilator-associated pneumonia, Clostridioides difficile-associated diarrhea, and other adverse outcomes. Despite their potential benefits, there are no summative data examining the cost-effectiveness of probiotics in hospitalized patients. This systematic review summarized studies evaluating the economic impact of using probiotics in hospitalized adult patients., Methods: We searched MEDLINE, EMBASE, CENTRAL, ACP Journal Club, and other EBM reviews (inception to January 31, 2019) for health economics evaluations examining the use of probiotics in hospitalized adults. Independently and in duplicate, we extracted data study characteristics, risk of bias, effectiveness and total costs (medications, diagnostics/procedures, devices, personnel, hospital) associated with healthcare-associated infections (ventilator-associated pneumonia, Clostridioides difficile-associated diarrhea and antibiotic-associated diarrhea). We used Grading of Recommendations Assessment, Development and Evaluation methods to assess certainty in the overall cost-effectiveness evidence., Results: Of 721 citations identified, we included seven studies. For the clinical outcomes of interest, there was one randomized-controlled trial (RCT)-based health economic evaluation, and six model-based health economic evaluations. Probiotics showed favourable cost-effectiveness in six of seven (86%) economic evaluations. Three of the seven studies were manufacturer-supported, all which suggested cost-effectiveness. Certainty of cost-effectiveness evidence was very low because of risk of bias, imprecision, and inconsistency., Conclusion: Probiotics may be an economically attractive intervention for preventing ventilator-associated pneumonia, Clostridioides difficile-associated diarrhea, and antibiotic-associated diarrhea in hospitalized adult patients. Nevertheless, certainty about their cost-effectiveness evidence is very low. Future RCTs examining probiotics should incorporate cost data to inform bedside practice, clinical guidelines, and healthcare policy., Trial Registration: PROSPERO CRD42019129929; Registered 25 April, 2019.

Transcranial Doppler (TCD) ultrasound is a noninvasive method of obtaining bedside neurologic information that can supplement the physical examination. In critical care, this can be of particular value in patients who are unconscious with an equivocal neurologic examination because TCD findings can help the physician in decisions related to more definitive imaging studies and potential clinical interventions. Although TCD is traditionally the domain of sonographers and radiologists, there is increasing adoption of goal-directed TCD at the bedside in the critical care environment. The value of this approach includes round-the-clock availability and a goal-directed approach allowing for repeatability, immediate interpretation, and quick clinical integration. This paper presents a systematic approach to incorporating the highest yield TCD techniques into critical care bedside practice, and includes a series of illustrative figures and narrated video presentations to demonstrate the techniques described., (Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: In the new era of decreasing hospital bed availability, there is an increasing rate of direct discharge to home (DDH) from intensive care units (ICUs), despite sparse literature informing this practice., Objectives: To evaluate patient, family, and ICU attending physician satisfaction with planning for DDH from the ICU and intensivists' current DDH practices and perceptions., Methods: Prospective cohort study, using convenience sampling, of adult patients undergoing DDH from an ICU between February 2016 and February 2017 using a modified FS-ICU 24 satisfaction survey completed by patients, family members, and attending physicians at the time of patient discharge to home from the ICU., Results: Seventy-two percent of patients, 37% of family members, and 100% of ICU physicians recruited completed the survey. A majority of patients (89%) and families (78%) were satisfied or very satisfied with DDH. Only 6% of patients and 8% of families were dissatisfied to very dissatisfied with DDH. Conversely, ICU physician satisfaction varied, with only 5% being very comfortable with DDH and the majority (50%) only somewhat comfortable. Twenty percent of staff consultants were uncomfortable to very uncomfortable with the practice of DDH. Thirty-one percent of staff physician respondents felt that patient and family discomfort would be barriers to DDH. Compared to physicians and other allied health professionals, nurses were identified as the most helpful members of the health-care team in preparation for DDH by 98% of patients and 92% of family members. The DDH rates have increased for the past 12 years in our ICUs but declined during the study period (February 2016 to February 2017)., Conclusions: Patients and family members are satisfied with the practice of DDH from ICU, although ICU physician satisfaction is more variable. Physician comfort may be improved by data informing which patients may be safely DDH from the ICU.

Objectives: Evaluate outcomes (mortality, morbidity, unplanned return visits) of patients who are discharged directly to home from the ICU., Design: Prospective cohort study., Setting: Two tertiary care medical-surgical-trauma ICUs at Canadian hospitals over 1 year (February 2016-2017)., Subjects: All adult patients who were either discharged directly to home (Recruited and Nonrecruited cohorts) from ICU or discharged home within 24 hours after ward transfer (Ward Transfer cohort)., Interventions: Direct discharge home from ICU or discharge home within 24 hours of ward transfer from ICU., Measurements and Main Results: One-hundred ninety-eight patients were in the study, 100 patients in the discharged directly to home Recruited arm, 37 patients in the discharged directly to home Nonrecruited arm, and 61 patients in the Ward cohort. All three patient cohorts had 0% mortality at 8 weeks post discharge. The unplanned return visit rate for the Recruited cohort was 24% (emergency department 18%, Ward 4%, ICU 1%), whereas the rate for the Nonrecruited cohort was 52% (emergency department 34%, Ward 14%, ICU 3%) and the Ward Transfer cohort was 46% (emergency department 17%, Ward 26%, ICU 3%) (p = 0.005). No home support was available for 7% of the discharged directly to home Recruited cohort. Twenty-four percent of patients had funded home care nursing, but the majority of patients (81%) relied on help from friends/family., Conclusions: Recruited discharged directly to home patients experienced very good 8-week postdischarge outcomes with 0% mortality and a low rate of ICU readmission (1%) or ward readmission (4%), but not an insignificant rate of emergency department visits (18%). Recruited discharged directly to home patients had better outcomes compared with nonrecruited discharged directly to home patients and patients transferred briefly to the ward prior to discharge home. Future work should include derivation of a clinical prediction tool to identify patient characteristics that make discharged directly to home safe and a randomized control trial to compare discharged directly to home with short stay ward transfers.

Objectives: To evaluate the relationship between rates of discharge directly to home (DDH) from the intensive care unit (ICU) and bed availability (ward and ICU). Also to identify patient characteristics that make them candidates for safe DDH and describe transfer delay impact on length of stay (LOS)., Methods: Retrospective cohort study of all adult patients who survived their stay in our medical-surgical-trauma ICU between April 2003 and March 2015., Results: Median age was 49 years (interquartile range [IQR]: 33.5-60.4), and the majority of the patients were males (54.8%). Median number of preexisting comorbidities was 5 (IQR: 2-7) diagnoses. Discharge directly to home increased from 28 (3.1% of all survivors) patients in 2003 to 120 (12.5%) patients in 2014. The mean annual rate of DDH was between 11% and 12% over the last 6 years. Approximately 62% (n = 397) of patients waited longer than 4 hours for a ward bed, with a median delay of 2.0 days (IQR: 0.5-4.7) before being DDH. There was an inverse correlation between ICU occupancy and DDH rates ( r P = -.55, P < .0001, 95% confidence interval [CI] = -0.36 to -0.69, R 2 = .29). There was no correlation with ward occupancy and DDH rates ( r s = -.055, P = .64, 95% CI = -0.25 to 0.21)., Conclusions: The DDH rates have been increasing over time at our institution and were inversely correlated with ICU bed occupancy but were not associated with ward occupancy. The DDH patients are young, have few comorbidities on admission, and few discharge diagnoses, which are usually reversible single system problems with low disease burden. Transfers to the ward are delayed in a majority of cases, leading to increased ICU LOS and likely increased overall hospital LOS as well.

In the unconscious patient, there is a diagnostic void between the neurologic physical exam, and more invasive, costly and potentially harmful investigations. Transcranial color-coded sonography and two-dimensional transcranial Doppler imaging of the brain have the potential to be a middle ground to bridge this gap for certain diagnoses. With the increasing availability of point-of-care ultrasound devices, coupled with the need for rapid diagnosis of deteriorating neurologic patients, intensivists may be trained to perform point-of-care transcranial Doppler at the bedside. The feasibility and value of this technique in the intensive care unit to help rule-in specific intra-cranial pathologies will form the focus of this article. The proposed scope for point-of-care transcranial Doppler for the intensivist will be put forth and illustrated using four representative cases: presence of midline shift, vasospasm, raised intra-cranial pressure, and progression of cerebral circulatory arrest. We will review the technical details, including methods of image acquisition and interpretation. Common pitfalls and limitations of point-of-care transcranial Doppler will also be reviewed, as they must be understood for accurate diagnoses during interpretation, as well as the drawbacks and inadequacies of the modality in general.