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Rationale: Acute respiratory distress syndrome (ARDS) is a life-threatening critical care syndrome commonly associated with infections such as COVID-19, influenza, and bacterial pneumonia. Ongoing research aims to improve our understanding of ARDS, including its molecular mechanisms, individualized treatment options, and potential interventions to reduce inflammation and promote lung repair., Objective: To map and compare metabolic phenotypes of different infectious causes of ARDS to better understand the metabolic pathways involved in the underlying pathogenesis., Methods: We analyzed metabolic phenotypes of 3 ARDS cohorts caused by COVID-19, H1N1 influenza, and bacterial pneumonia compared to non-ARDS COVID-19-infected patients and ICU-ventilated controls. Targeted metabolomics was performed on plasma samples from a total of 150 patients using quantitative LC-MS/MS and DI-MS/MS analytical platforms., Results: Distinct metabolic phenotypes were detected between different infectious causes of ARDS. There were metabolomics differences between ARDSs associated with COVID-19 and H1N1, which include metabolic pathways involving taurine and hypotaurine, pyruvate, TCA cycle metabolites, lysine, and glycerophospholipids. ARDSs associated with bacterial pneumonia and COVID-19 differed in the metabolism of D-glutamine and D-glutamate, arginine, proline, histidine, and pyruvate. The metabolic profile of COVID-19 ARDS (C19/A) patients admitted to the ICU differed from COVID-19 pneumonia (C19/P) patients who were not admitted to the ICU in metabolisms of phenylalanine, tryptophan, lysine, and tyrosine. Metabolomics analysis revealed significant differences between C19/A, H1N1/A, and PNA/A vs ICU-ventilated controls, reflecting potentially different disease mechanisms., Conclusion: Different metabolic phenotypes characterize ARDS associated with different viral and bacterial infections., (© 2024. The Author(s).)

Objectives: Among patients with severe acute kidney injury (AKI) admitted to the ICU in high-income countries, regional practice variations for fluid balance (FB) management, timing, and choice of renal replacement therapy (RRT) modality may be significant., Design: Secondary post hoc analysis of the STandard vs. Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial (ClinicalTrials.gov number NCT02568722)., Setting: One hundred-fifty-three ICUs in 13 countries., Patients: Altogether 2693 critically ill patients with AKI, of whom 994 were North American, 1143 European, and 556 from Australia and New Zealand (ANZ)., Interventions: None., Measurements and Main Results: Total mean FB to a maximum of 14 days was +7199 mL in North America, +5641 mL in Europe, and +2211 mL in ANZ ( p < 0.001). The median time to RRT initiation among patients allocated to the standard strategy was longest in Europe compared with North America and ANZ ( p < 0.001; p < 0.001). Continuous RRT was the initial RRT modality in 60.8% of patients in North America and 56.8% of patients in Europe, compared with 96.4% of patients in ANZ ( p < 0.001). After adjustment for predefined baseline characteristics, compared with North American and European patients, those in ANZ were more likely to survive to ICU ( p < 0.001) and hospital discharge ( p < 0.001) and to 90 days (for ANZ vs. Europe: risk difference [RD], -11.3%; 95% CI, -17.7% to -4.8%; p < 0.001 and for ANZ vs. North America: RD, -10.3%; 95% CI, -17.5% to -3.1%; p = 0.007)., Conclusions: Among STARRT-AKI trial centers, significant regional practice variation exists regarding FB, timing of initiation of RRT, and initial use of continuous RRT. After adjustment, such practice variation was associated with lower ICU and hospital stay and 90-day mortality among ANZ patients compared with other regions., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: Critically ill children must often be transported long distances for access to critical care resources in Canada. This study aims to describe and compare characteristics and outcomes in patients presenting in the community and requiring inter-facility transport and admission to a Pediatric Intensive Care Unit (PICU)., Methods: This is a retrospective cohort study of children admitted to the ICU at the Hospital for Sick Children from 2016 to 2019 after inter-facility transport. Characteristics and outcomes were compared between children admitted to the PICU within 24 h from their initial critical care transport request, and children admitted after initial redirection to a non-ICU care setting, 24-72 h from request. The primary outcome was severity of illness at PICU admission. Secondary outcomes included duration of mechanical ventilation, organ dysfunction, PICU length of stay and mortality., Results: A total of 2,730 patients were admitted after inter-facility transport to either the medical/surgical or cardiac ICU within 72 h of initial critical care transport request. Of these children, 2,559 (94%) were admitted within 24 h and 171 (6%) were admitted between 24 and 72 h. Children admitted after initial redirection were younger and residing in more rural centers. Children who were initially redirected had lower severity of illness (PRISM-IV median score 3 vs. 5, p  = 0.047) and lower risk of mortality., Interpretation: Initial redirection to a non-ICU care setting rather than directly admitting to the PICU did not result in increased severity of illness or mortality. This study highlights the need to better understand which factors influence disposition decision-making at the time of initial transport request. Further research should focus on the impact of transport factors on clinical outcomes after PICU admission., 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., (© 2024 Halgren, Annich and Maratta.)

Lung cancer is a prevalent and highly lethal disease often complicated by lower respiratory tract infections. Microbial patterns in these infections vary based on treatment modalities. The present study explored the impact of lung cancer treatments on pathogens and clinical characteristics in the presence of lower respiratory tract infections to inform antimicrobial drug selection. A retrospective analysis was performed that included data from 93 patients diagnosed with advanced lung cancer and lower respiratory tract infections between January 2019 and December 2021. Patients were divided into the targeted therapy and chemoradiotherapy groups. Clinical, nutritional, biochemical, infection and pathogenetic indicators were compared. Of the 93 cases, 24 were in the targeted therapy group and 69 were in the chemoradiotherapy group. Pathological type and hospitalization duration differed significantly (P<0.05), but age, sex, smoking history, alcohol consumption and underlying diseases did not (P>0.05). Lymphocyte counts differed (P<0.05), while body mass index, albumin, hemoglobin, alanine aminotransferase and creatinine levels, erythrocyte sedimentation rate, hypersensitive C-reactive protein and procalcitonin levels, and the percentage of neutrophils did not (P>0.05). Pathogenetic testing was negative in 15 patients and positive in 78 patients, with Gram-negative bacteria (61.77%), fungi (17.65%) and viruses (11.76%) predominant in the targeted therapy group. In the chemoradiotherapy group, Gram-negative bacteria (47.46%), fungi (28.81%) and viruses (16.95%) were also more prevalent. Candida albicans was the most frequent fungal infection in both groups, and mixed infections were common (50% in targeted therapy and 73.92% in chemoradiotherapy). The chemoradiotherapy group had significantly more mixed infections (P<0.05). Overall, common pathogens in both groups included Gram-negative bacteria, fungi and viruses. Chemoradiotherapy patients experienced longer hospital stays and a higher incidence of mixed infections, predominantly involving Gram-negative bacteria and fungi. The results provide valuable insights into the rational selection of empirical antibiotics and antifungals for critically ill patients with lung cancer and lower respiratory tract infections in targeted therapy or chemoradiotherapy., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Zhang et al.)

Background: Airway closure, which refers to the complete collapse of the airway, has been described under mechanical ventilation during anesthesia and more recently in adult patients with acute respiratory distress syndrome (ARDS). A ventilator maneuver can be used to identify airway closure and measure the pressure required for the airway to reopen, known as the airway opening pressure (AOP). Without that maneuver, AOP is unknown to clinicians., Objective: This study aims to demonstrate the technical adaptation of the adult maneuver for children and illustrate its application in two cases of pediatric ARDS (p-ARDS)., Methods: A bench study was performed to adapt the maneuver for 3-50 kg patients. Four maneuvers were performed for each simulated patient, with 1, 2, 3, and 4 s of insufflation time to deliver a tidal volume (Vt) of 6 ml/kg by a continuous flow., Results: Airway closure was simulated, and AOP was visible at 15 cmH 2 O with a clear inflection point, except for the 3 kg simulated patient. Regarding insufflation time, a 4 s maneuver exhibited a better performance in 30 and 50 kg simulated patients since shorter insufflation times had excessive flowrates (>10 L/min). Below 20 kg, the difference in resistive pressure between a 3 s and a 4 sec maneuver was negligible; therefore, prolonging the maneuver beyond 3 s was not useful. Airway closure was identified in two p-ARDS patients, with the pediatric maneuver being employed in the 28 kg patient., Conclusions: We propose a pediatric AOP maneuver delivering 6 ml/kg of Vt at a continuous low-flow inflation for 3 s for patients weighing up to 20 kg and for 4 s for patients weighing beyond 20 kg., 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., (© 2024 Rodriguez Guerineau, Vieira, Rodrigues, Reise, Todd, Guerguerian and Brochard.)

Importance: Considerable controversy exists regarding the best spontaneous breathing trial (SBT) technique to use., Objective: To summarize trials comparing alternative SBTs., Data Sources: Several databases (MEDLINE [from inception to February 2023], the Cochrane Central Register of Controlled Trials [in February 2023], and Embase [from inception to February 2023] and 5 conference proceedings (from January 1990 to April 2023) were searched in this systematic review and meta-analysis., Study Selection: Randomized trials directly comparing SBT techniques in critically ill adults or children and reporting at least 1 clinical outcome were selected., Data Extraction and Synthesis: Paired reviewers independently screened citations, abstracted data, and assessed quality for the systematic review and meta-analysis using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA guidelines). Data were pooled using random-effects models., Main Outcomes and Measures: Primary outcomes included SBT success, extubation success, and reintubation., Results: The systematic review and meta-analysis identified 40 trials that included 6716 patients. Low-quality evidence (14 trials [n = 4459]) suggested that patients were not more likely to pass a pressure support (PS) compared with a T-piece SBT (risk ratio [RR], 1.04; 95% CI, 0.97-1.11; P = .31; I2 = 73%), unless 1 outlier trial accounting for all heterogeneity was excluded (RR, 1.09; 95% CI, 1.06-1.12; P < .001; I2 = 0% [13 trials; n = 3939]; moderate-quality evidence), but were significantly more likely to be successfully extubated (RR, 1.07; 95% CI, 1.04-1.10; P < .001; I2 = 0%; 16 trials [n = 4462]; moderate-quality evidence). Limited data (5 trials [n = 502]) revealed that patients who underwent automatic tube compensation/continuous positive airway pressure compared with PS SBTs had a significantly higher successful extubation rate (RR, 1.10; 95% CI, 1.00-1.21; P = .04; I2 = 0% [low-quality evidence]). Compared with T-piece SBTs, high-flow oxygen SBTs (3 trials [n = 386]) had significantly higher successful extubation (RR, 1.06; 95% CI, 1.00-1.11; P = .04; I2 = 0%) and lower reintubation (RR, 0.37; 95% CI, 0.21-0.65; P = <.001; I2 = 0% [both low-quality evidence]) rates. Credible subgroup effects were not found., Conclusions and Relevance: In this systematic review and meta-analysis, the findings suggest that patients undergoing PS compared with T-piece SBTs were more likely to be extubated successfully and more likely to pass an SBT, after exclusion of an outlier trial. Pressure support SBTs were not associated with increased risk of reintubation. Future trials should compare SBT techniques that maximize differences in inspiratory support.

Importance: The COVID-19 pandemic had a profound impact on the delivery of cancer care, but less is known about its association with place of death and delivery of specialized palliative care (SPC) and potential disparities in these outcomes., Objective: To evaluate the association of the COVID-19 pandemic with death at home and SPC delivery at the end of life and to examine whether disparities in socioeconomic status exist for these outcomes., Design, Setting, and Participants: In this cohort study, an interrupted time series analysis was conducted using Ontario Cancer Registry data comprising adult patients aged 18 years or older who died with cancer between the pre-COVID-19 (March 16, 2015, to March 15, 2020) and COVID-19 (March 16, 2020, to March 15, 2021) periods. The data analysis was performed between March and November 2023., Exposure: COVID-19-related hospital restrictions starting March 16, 2020., Main Outcomes and Measures: Outcomes were death at home and SPC delivery at the end of life (last 30 days before death). Socioeconomic status was measured using Ontario Marginalization Index area-based material deprivation quintiles, with quintile 1 (Q1) indicating the least deprivation; Q3, intermediate deprivation; and Q5, the most deprivation. Segmented linear regression was used to estimate monthly trends in outcomes before, at the start of, and in the first year of the COVID-19 pandemic., Results: Of 173 915 patients in the study cohort (mean [SD] age, 72.1 [12.5] years; males, 54.1% [95% CI, 53.8%-54.3%]), 83.7% (95% CI, 83.6%-83.9%) died in the pre-COVID-19 period and 16.3% (95% CI, 16.1%-16.4%) died in the COVID-19 period, 54.5% (95% CI, 54.2%-54.7%) died at home during the entire study period, and 57.8% (95% CI, 57.5%-58.0%) received SPC at the end of life. In March 2020, home deaths increased by 8.3% (95% CI, 7.4%-9.1%); however, this increase was less marked in Q5 (6.1%; 95% CI, 4.4%-7.8%) than in Q1 (11.4%; 95% CI, 9.6%-13.2%) and Q3 (10.0%; 95% CI, 9.0%-11.1%). There was a simultaneous decrease of 5.3% (95% CI, -6.3% to -4.4%) in the rate of SPC at the end of life, with no significant difference among quintiles. Patients who received SPC at the end of life (vs no SPC) were more likely to die at home before and during the pandemic. However, there was a larger immediate increase in home deaths among those who received no SPC at the end of life vs those who received SPC (Q1, 17.5% [95% CI, 15.2%-19.8%] vs 7.6% [95% CI, 5.4%-9.7%]; Q3, 12.7% [95% CI, 10.8%-14.5%] vs 9.0% [95% CI, 7.2%-10.7%]). For Q5, the increase in home deaths was significant only for patients who did not receive SPC (13.9% [95% CI, 11.9%-15.8%] vs 1.2% [95% CI, -1.0% to 3.5%])., Conclusions and Relevance: These findings suggest that the COVID-19 pandemic was associated with amplified socioeconomic disparities in death at home and SPC delivery at the end of life. Future research should focus on the mechanisms of these disparities and on developing interventions to ensure equitable and consistent SPC access.

The demographic shift, together with financial constraint, justify a re-evaluation of the trajectory of care of very old critically ill patients (VIP), defined as older than 80 years. We must avoid over- as well as under-utilisation of critical care interventions in this patient group and ensure the inclusion of health care professionals, the patient and their caregivers in the decision process. This new integrative approach mobilises expertise at each step of the process beginning prior to intensive care unit (ICU) admission and extending to long-term follow-up. In this review, several international experts have contributed to provide recommendations that can be universally applied. Our aim is to define a minimum core dataset of information to be shared and discussed prior to ICU admission and to facilitate the shared-decision-making process with the patient and their caregivers, throughout the patient journey. Documentation of uncertainty may contribute to a tailored level of care and ultimately to discussions around possible limitations of life sustaining treatments. The goal of ICU care is not only to avoid death, but more importantly to maintain an acceptable quality of life and functional autonomy after hospital discharge. Societal consideration is important to highlight, together with alternatives to ICU admission. We discuss challenges for the future and potential areas of research. In summary, this review provides a state-of-the-art current overview and aims to outline future directions to address the challenges in the treatment of VIP., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The aim of this study was to describe the incidence of venous thromboembolism (VTE) and major bleeding among hospitalized patients with hematologic malignancy, assessing its association with critical illness and other baseline characteristics., Methods: We conducted a population-based cohort study of hospitalized adults with a new diagnosis of hematologic malignancy in Ontario, Canada, between 2006 and 2017. The primary outcome was VTE (pulmonary embolism or deep venous thrombosis). Secondary outcomes were major bleeding and in-hospital mortality. We compared the incidence of VTE between intensive care unit (ICU) and non-ICU patients and described the association of other baseline characteristics and VTE., Results: Among 76,803 eligible patients (mean age 67 years [standard deviation, SD, 15]), 20,524 had at least one ICU admission. The incidence of VTE was 3.7% in ICU patients compared to 1.2% in non-ICU patients (odds ratio [OR] 3.08; 95% confidence interval [CI] 2.77-3.42). The incidence of major bleeding was 7.6% and 2.4% (OR 3.33; 95% CI 3.09-3.58), respectively. The association of critical illness and VTE remained significant after adjusting for potential confounders (OR 2.92; 95% CI 2.62-3.25). We observed a higher incidence of VTE among specific subtypes of hematologic malignancy and patients with prior VTE (OR 6.64; 95% CI 5.42-8.14). Admission more than 1 year after diagnosis of hematologic malignancy (OR 0.64; 95% CI 0.56-0.74) and platelet count ≤ 50 × 10 9 /L at the time of hospitalization (OR 0.63; 95% CI 0.48-0.84) were associated with a lower incidence of VTE., Conclusion: Among patients with hematologic malignancy, critical illness and certain baseline characteristics were associated with a higher incidence of VTE., (© 2023. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Bloodstream infections (BSIs) are associated with significant mortality and morbidity, including multiple organ dysfunction. We explored if delayed adequate antimicrobial treatment for children with BSIs is associated with change in organ dysfunction as measured by PELOD-2 scores., Methods: We conducted a multicenter, retrospective cohort study of critically ill children <18 years old with BSIs. The primary outcome was change in PELOD-2 score between days 1 (index blood culture) and 5. The exposure variable was delayed administration of adequate antimicrobial therapy by ≥3 h from blood culture collection. We compared PELOD-2 score changes between those who received early and delayed treatment., Results: Among 202 children, the median (interquartile range) time to adequate antimicrobial therapy was 7 (0.8-20.1) hours; 124 (61%) received delayed antimicrobial therapy. Patients who received early and delayed treatment had similar baseline characteristics. There was no significant difference in PELOD-2 score changes from days 1 and 5 between groups (PELOD-2 score difference -0.07, 95% CI -0.92 to 0.79, p = 0.88)., Conclusions: We did not find an association between delayed adequate antimicrobial therapy and PELOD-2 score changes between days 1 and 5 from detection of BSI. PELOD-2 score was not sensitive for clinical effects of delayed antimicrobial treatment., Impact: In critically ill children with bloodstream infections, there was no significant change in organ dysfunction as measured by PELOD-2 scores between patients who received adequate antimicrobial therapy within 3 h of their initial positive blood culture and those who started after 3 h. Higher PELOD-2 scores on day 1 were associated with larger differences in PELOD-2 scores between days 1 and 5 from index positive blood cultures. Further study is required to determine if PELOD-2 or alternative measures of organ dysfunction could be used as primary outcome measures in trials of antimicrobial interventions in pediatric critical care research., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Objective: To measure tidal volume delivery during nasal intermittent positive pressure ventilation with two nasal interfaces: infant cannula and nasal prongs., Study Design: A single-center crossover study of neonates with mild respiratory distress. Fifteen preterm neonates were randomized to initial interface of infant cannula or nasal prongs and monitored on a sequence of pressure settings first on the initial interface, then repeated on the alternate interface. We compared relative tidal volumes between the two interfaces with two-way repeated measures ANOVA during three breath types: synchronized (I), patient effort without ventilator breaths (II), and ventilator breaths without patient effort (III). Clinical trial #NCT04326270., Results: Type III breaths delivered no significant tidal volume. No significant difference was measured in relative tidal volume delivery between the interfaces when breath types were matched., Conclusions: Nasal intermittent positive pressure ventilation delivers neither clinically nor statistically significant tidal volume with either infant cannula or nasal prongs., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Introduction: To our knowledge, this study is the first to identify and describe current sepsis policies, clinical practice guidelines, and health professional training standards in Canada to inform evidence-based policy recommendations., Methods and Analysis: This study will be designed and reported according to the Arksey and O'Malley framework for scoping reviews and the Preferred Reporting Items for Systematic Review and Meta-Analyses Extension for Scoping Reviews. EMBASE, CINAHL, Medline, Turning Research Into Practice and Policy Commons will be searched for policies, clinical practice guidelines and health professional training standards published or updated in 2010 onwards, and related to the identification, management or reporting of sepsis in Canada. Additional sources of evidence will be identified by searching the websites of Canadian organisations responsible for regulating the training of healthcare professionals and reporting health outcomes. All potentially eligible sources of evidence will be reviewed for inclusion, followed by data extraction, independently and in duplicate. The included policies will be collated and summarised to inform future evidence-based sepsis policy recommendations., Ethics and Dissemination: The proposed study does not require ethics approval. The results of the study will be submitted for publication in a peer-reviewed journal and presented at local, national and international forums., Competing Interests: Competing interests: GG is an employee of the Canadian Medical Protective Association. LS is funded by the Arnold L. Johnson Chair in Health Care Ethics, an endowed Chair at McMaster University. AFR is the Scientific Director of Sepsis Canada, a CIHR-funded network. KB has consulted for Fresenius Medical Care., (© 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 of Review: Determining the optimal positive end-expiratory pressure (PEEP) setting remains a central yet debated issue in the management of acute respiratory distress syndrome (ARDS).The 'best compliance' strategy set the PEEP to coincide with the peak respiratory system compliance (or 2 cmH 2 O higher) during a decremental PEEP trial, but evidence is conflicting., Recent Findings: The physiological rationale that best compliance is always representative of functional residual capacity and recruitment has raised serious concerns about its efficacy and safety, due to its association with increased 28-day all-cause mortality in a randomized clinical trial in ARDS patients.Moreover, compliance measurement was shown to underestimate the effects of overdistension, and neglect intra-tidal recruitment, airway closure, and the interaction between lung and chest wall mechanics, especially in obese patients. In response to these concerns, alternative approaches such as recruitment-to-inflation ratio, the nitrogen wash-in/wash-out technique, and electrical impedance tomography (EIT) are gaining attention to assess recruitment and overdistention more reliably and precisely., Summary: The traditional 'best compliance' strategy for determining optimal PEEP settings in ARDS carries risks and overlooks some key physiological aspects. The advent of new technologies and methods presents more reliable strategies to assess recruitment and overdistention, facilitating personalized approaches to PEEP optimization., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Concise definitive review of the use of venopulmonary arterial extracorporeal membrane oxygenation (V-PA ECMO) support in patients with cardiopulmonary failure., Data Sources: Original investigations identified through a PubMed search with search terms "percutaneous right ventricular assist device," "oxy-RVAD," "V-PA ECMO," and "veno-pulmonary arterial ECMO" were reviewed and evaluated for relevance., Study Selection: Studies that included more than three patients supported with V-PA ECMO were included., Data Extraction: Clinically relevant data from included studies, including patient-important outcomes, were summarized and discussed., Data Synthesis: We identified four groups of patients where V-PA ECMO has been studied: acute respiratory distress syndrome, right ventricular dysfunction after left ventricular assist device placement, bridge to lung transplantation, and pulmonary embolism. Most identified works are small, single center, and retrospective in nature, precluding definitive conclusions regarding the efficacy of V-PA ECMO. There have been no clinical trials evaluating the efficacy of V-PA ECMO for any indication., Conclusions: V-PA ECMO is a promising form of extracorporeal support for patients with right ventricular dysfunction. Future work should focus on identifying the optimal timing and populations for the use of V-PA ECMO., Competing Interests: Dr. Fan reports personal fees from ALung Technologies, Baxter, Getinge, Inspira, Vasomune, and Zoll Medical outside the submitted work. He also receives research support from Abbott, Medtronic, and LivaNova through his institution. Dr. Hockstein has disclosed that he does not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. 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.

Background: Acute respiratory distress syndrome (ARDS) is an important pulmonary complication in brain-injured patients receiving invasive mechanical ventilation (IMV). We aimed to evaluate the incidence and association between ARDS and clinical outcomes in patients with different forms of acute brain injury requiring IMV in the intensive care unit (ICU). Methods: This was a preplanned secondary analysis of a prospective, multicenter, international cohort study (NCT03400904). We included brain-injured patients receiving IMV for ≥ 24 h. ARDS was the main exposure of interest and was identified during index ICU admission using the Berlin definition. We examined the incidence and adjusted association of ARDS with ICU mortality, ICU length of stay, duration of IMV, and extubation failure. Outcomes were evaluated using mixed-effect logistic regression and cause-specific Cox proportional hazards models. Results: 1492 patients from 67 hospitals and 16 countries were included in the analysis, of whom 137 individuals developed ARDS (9.2% of overall cohort). Across countries, the median ARDS incidence was 5.1% (interquartile range [IQR] 0-10; range 0-27.3). ARDS was associated with increased ICU mortality (adjusted odds ratio (OR) 2.66; 95% confidence interval [CI], 1.29-5.48), longer ICU length of stay (adjusted hazard ratio [HR] 0.59; 95% CI, 0.48-0.73), and longer duration of IMV (adjusted HR 0.54; 95% CI, 0.44-0.67). The association between ARDS and extubation failure approached statistical significance (adjusted HR 1.48; 95% CI 0.99-2.21). Higher ARDS severity was associated with incrementally longer ICU length of stay and longer cumulative duration of IMV. Findings remained robust in a sensitivity analysis evaluating the magnitude of unmeasured confounding. Conclusions: In this cohort of acutely brain-injured patients, the incidence of ARDS was similar to that reported in other mixed cohorts of critically ill patients. Development of ARDS was associated with worse outcomes., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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.)

Objective: Percutaneous tracheostomy is routinely performed in adult patients but is seldomly used in the pediatric population due to concerns regarding safety and limited available evidence. This study aims to consolidate the current literature on percutaneous tracheostomy in the pediatric population., Methods: A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted. MEDLINE, EMBASE, CINAHL, and Web of Science were searched for studies on pediatric percutaneous tracheostomy (age ≤18). The Joanna Briggs Institute and ROBINS-I tools were used for quality appraisal., Results: Twenty-one articles were included resulting in 143 patients. Patient age ranged from 2 days to 17 years, with the largest subpopulation of patients (n = 57, 40 %) being adolescents (age between 12 and 17 years old). Main indications for percutaneous tracheostomy included prolonged ventilation (n = 6), respiratory insufficiency (n = 5), and upper airway obstruction (n = 5). One-third (n = 47) of percutaneous tracheostomies were completed at the bedside in an intensive care unit. Select studies reported on surgical time and time from intubation to tracheostomy with a mean of 13.8 (SD = 7.8) minutes (n = 27) and 8.9 (SD = 2.8) days (n = 35), respectively. Major postoperative complications included tracheoesophageal fistula (n = 4, 2.8 %) and pneumothorax (n = 3, 2.1 %). There were four conversions to open tracheostomy., Conclusion: Percutaneous tracheostomy had a similar risk of complications to open surgical tracheostomy in children and adolescents and can be performed at the bedside in a select group of patients if necessary. However, we feel that consideration must be given to the varying anatomical considerations in children and adolescents compared with adults, and therefore suggest that this procedure be reserved for adolescent patients with a thin body habitus and clearly demarcated and palpable anatomical landmarks who require a tracheostomy. When performed, we strongly support using endoscopic guidance and a surgeon who has the ability to convert to an open tracheostomy if required., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Virtual reality (VR) simulators have revolutionized training in bronchoscopy, offering unrestricted availability in a low-stakes learning environment and frequent assessments represented by automatic scoring. The VR assessments can be used to monitor and support learners' progression. How trainees perceive these assessments needs to be clarified., Objective: The objective of this study was to examine what assessments learners select to document and receive feedback on and what influences their decisions., Methods: We used a sequential explanatory mixed methods strategy. All participants were pediatric critical care medicine trainees requiring competency in bronchoscopy skills. During independent simulation practice, we collected the number of learning-focused practice attempts (scores not recorded), assessment-focused practice (scores recorded and reviewed by the instructor for feedback), and the amount of time each attempt lasted. After simulation training, we conducted interviews to explore learners' perceptions of assessment., Results: There was no significant difference in the number of attempts for each practice type. The average time per learning-focused attempt was almost three times longer than the assessment-focused attempt (mean [standard deviation] 16 ± 1 min vs. 6 ± 3 min, respectively; P  < 0.05). Learners perceived documentation of their scores as high stakes and only recorded their better scores. Learners felt safer experimenting if their assessments were not recorded., Conclusion: During independent practice, learners took advantage of automatic assessments generated by the VR simulator to monitor their progression. However, the recording of scores from the simulation program to document learners' trajectory to a set goal was perceived as high stakes, discouraging learners from seeking supervisor feedback., (Copyright © 2024 by the American Thoracic Society.)

Background: Jet nebulizers are commonly used for bronchodilator therapy in COPD. High-flow nasal cannula with vibrating mesh nebulizer (HFNC-VMN) is a recently developed system; however, few studies have compared the efficacy of bronchodilator administration via HFNC-VMN to jet nebulizer in stable COPD. This study aimed to compare the effect of salbutamol administered via HFNC-VMN versus jet nebulizer on airway and lung function in subjects with stable COPD., Methods: This randomized non-inferiority crossover physiologic study enrolled subjects with stable COPD. Salbutamol was nebulized via HFNC-VMN or jet nebulizer in random order with a 4-h washout period between crossover sequences. Spirometry, lung volume, and impulse oscillometry were performed at baseline and after each intervention. The primary outcome was change in FEV 1 from baseline. Secondary outcomes included changes in other respiratory-related parameters and nebulization time compared between the 2 devices., Results: Seventeen subjects were enrolled. HFNC-VMN and jet nebulizer both significantly improved FEV 1 from baseline ( P = .005 and P = .002, respectively). The difference between respiratory resistance at 5 Hz and 20 Hz significantly decreased after HFNC-VMN compared to baseline ( P = .02), while no significant change was observed after jet nebulizer ( P = .056). Area of reactance and resonant frequency of reactance were both significantly decreased ( P = .035 and P = .03, respectively), and respiratory reactance at 5 Hz significantly increased ( P = .02) in the HFNC-VMN group compared to baseline indicating improved lung mechanics, with no significant changes with the jet nebulizer. HFNC-VMN had a shorter nebulization time (6 [5-9] min vs 20 [16-22] min, respectively, P < .001)., Conclusions: Bronchodilator therapy via HFNC-VMN was not inferior to jet nebulizer for subjects with stable COPD and can significantly improve airway oscillometry mechanics and decrease nebulization time compared to jet nebulizer., Competing Interests: Dr Brochard discloses relationships with Medtronic Covidien, Fisher & Paykel, Philips, Sentec, Air Liquide Medical Systems, GE Healthcare, and St. Michael's Hospital. Dr Chow discloses relationships with Thorasys Thoracic Medical Systems and AstraZeneca Canada. The remaining authors have disclosed no conflicts of interest., (Copyright © 2024 by Daedalus Enterprises.)

Background: Subarachnoid hemorrhage (SAH) is associated with neurocognitive impairment. Recent data suggest that sevoflurane attenuates edema formation after SAH in rats. However, so far, no information is available about the long-term repair phase, nor if sevoflurane impacts functionality by increasing vascularity. This study tested whether sevoflurane postconditioning would improve long-term neurologic deficit through increased formation of new vessels close to the hemorrhage area., Methods: Fifty-three animals were subjected to SAH or sham surgery with or without a 2-hour sevoflurane postconditioning (versus propofol anesthesia). Animal survival, including dropout animals due to death or reaching termination criteria, as well as neurologic deficit, defined by the Garcia score, were assessed 2 hours after recovery until postoperative day 14. On day 14, blood samples and brain tissue were harvested. Vessel density was determined by the number of cluster of differentiation 31 (CD31)-positive vessels, and activated glial cells by glial fibrillary acidic protein (GFAP)-positive astrocytes per field of view., Results: The survival rate for sham animals was 100%, 69% in the SAH-propofol and 92% in the SAH-sevoflurane groups. According to the log-rank Mantel-Cox test, survival curves were significantly different (P = .024). The short-term neurologic deficit was higher in SAH-propofol versus SAH-sevoflurane animals 2 hours after recovery and on postoperative day 1 (propofol versus sevoflurane: 14. 6 ± 3.4 vs 15. 9 ± 2.7 points, P = .034, and 16. 2 ± 3.5 vs 17. 8 ± 0.9 points, P = .015). Overall complete recovery from neurologic deficit was observed on day 7 in both SAH groups (18. 0 ± 0.0 vs 18. 0 ± 0.0 points, P = 1.000). Cortical vascular density increased to 80. 6 ± 15.0 vessels per field of view in SAH-propofol animals (vs 71. 4 ± 10.1 in SAH-sevoflurane, P < .001). Activation of glial cells, an indicator of neuroinflammation, was assessed by GFAP-positive astrocytes GFAP per field of view. Hippocampal GFAP-positive cells were 201 ± 68 vs 179 ± 84 cells per field of view in SAH-propofol versus SAH-sevoflurane animals (P < .001)., Conclusions: Sevoflurane postconditioning improves survival by 23% (SAH-sevoflurane versus SAH-propofol). The sevoflurane intervention could attenuate the early neurologic deficit, while the long-term outcome was similar across the groups. A higher vascular density close to the SAH area in the propofol group was not associated with improved outcomes., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2024 International Anesthesia Research Society.)

Background: Post-operative acute kidney injury (PO-AKI) is a common surgical complication consistently associated with subsequent morbidity and mortality. Prior kidney dysfunction is a major risk factor for PO-AKI, however it is unclear whether serum creatinine, the conventional kidney function marker, is optimal in this population. Serum cystatin C is a kidney function marker less affected by body composition and might provide better prognostic information in surgical patients., Methods: This was a pre-defined, secondary analysis of a multi-centre prospective cohort study of pre-operative functional capacity. Participants were aged ≥40 years, undergoing non-cardiac surgery. We assessed the association of pre-operative estimated glomerular filtration rate (eGFR) calculated using both serum creatinine and serum cystatin C with PO-AKI within 3 days after surgery, defined by KDIGO creatinine changes. The adjusted analysis accounted for established AKI risk factors., Results: A total of 1347 participants were included (median age 65 years, interquartile range 56-71), of whom 775 (58%) were male. A total of 82/1347 (6%) patients developed PO-AKI. These patients were older, had higher prevalence of cardiovascular disease and related medication, were more likely to have intra-abdominal procedures, had more intraoperative transfusion, and were more likely to be dead at 1 year after surgery 6/82 (7.3%) vs 33/1265 (2.7%) ( P  = .038). Pre-operative eGFR was lower in AKI than non-AKI patients using both creatinine and cystatin C. When both measurements were considered in a single age- and sex-adjusted model, eGFR-Cysc was strongly associated with PO-AKI, with increasing risk of AKI as eGFR-Cysc decreased below 90, while eGFR-Cr was no longer significantly associated., Conclusions: Data from over 1000 prospectively recruited surgical patients confirms pre-operative kidney function as major risk factor for PO-AKI. Of the kidney function markers available, compared with creatinine, cystatin C had greater strength of association with PO-AKI and merits further assessment in pre-operative assessment of surgical risk., Competing Interests: J.R.P. has received honoraria from Paion Ltd, Baxter Inc., Biomerieux SA and Nikkiso Europe GmbH; he is a scientific advisor for Mission Therapeutics Ltd, Jafron Biomedical Co. Ltd and Nephrolyx GmbH, and serves on a Data Monitoring and Safety Board for Novartis Inc.; he is a specialty editor for the Clinical Kidney Journal and Blood Purification. B.H.C. and D.N.W. are supported in part by Merit Awards from the Department of Anesthesiology and Pain Medicine at the University of Toronto. D.N.W. is supported in part by the Endowed Chair in Translational Anesthesiology Research at St Michael's Hospital and the University of Toronto. D.N.W. has received honoraria from Edwards Lifesciences within the last 5 years and is a member of the Scientific Advisory Board for Surgical Safety Technologies Inc. T.E.F.A. is an NIHR Clinical Lecturer, an editor of the British Journal of Anaesthesia, has received research funding from the Medical Research Council, the National Institute of Academic Anaesthesia and Barts Charity, and has received consultancy fees from MSD and Edwards Life Sciences unrelated to this work. All other authors report no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years, and no other relationships or activities that could appear to have influenced the submitted work., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Introduction: Furosemide is the most commonly used medication in pediatric intensive care. Growing data indicates improved hemodynamic stability and efficacy of furosemide infusions compared to intermittent injections, thereby suggesting furosemide infusions might be considered as first line therapy in critically ill, paediatric patients. The objective of this study is to examine furosemide treatment as either continuous infusions or intermittent injections and subsequent patient outcomes., Methods: This is a retrospective cohort analysis of patients treated in a pediatric intensive care unit (ICU) over a nine year period (July 31st 2006 and July 31, 2015). Eligible patients were admitted to either the general pediatric or cardiac specific ICU for a duration of at least 6 hours and who received intravenous furosemide treatment., Results: A total of 7,478 patients were identified who received a total of 118,438 furosemide administrations for a total of 113,951 (96%) intermittent doses and 4,487 (4%) infusions running for a total of 1,588,750 hours. A total of 5,996 (80%) patients received exclusively furosemide injections and 1,482 (20%) patients received at least one furosemide infusion. A total of 193 patients died during ICU admission, amounting to 87 (6%) of the 1,482 patients who received an infusion and 106 (2%) of the 5,996 who received intermittent injections. Multivariable regression analysis showed no statistically significant decrease in adjusted mortality for patients who received furosemide injections compared to furosemide infusions (aOR 1.20, CI 0.76-1.89)., Discussion: This retrospective study observed similar mortality for patients who received furosemide infusions compared to furosemide injections. More research on furosemide in the ICU could provide insights on fluid management, drug effectiveness, and pharmacologic stewardship for critically ill children., 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., (© 2024 Gaetani, Parshuram and Redelmeier.)

Background: Sedation management has a major impact on outcomes in mechanically ventilated patients, but sedation strategies do not generally consider the differential effects of different sedatives on respiration and respiratory pattern. A systematic review was undertaken to quantitatively summarize the known effects of different classes of drugs used for sedation on respiratory pattern during both spontaneous breathing and assisted mechanical ventilation., Methods: This was a systematic review and meta-analysis conducted using Ovid MEDLINE, Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials up to June 2020 to retrieve studies that measured respiratory parameters before and after the administration of opioids, benzodiazepines, intravenous and inhaled anaesthetic agents, and other hypnotic agents (PROSPERO #CRD42020190017). A random-effects meta-analytic model was employed to estimate the mean percentage change in each of the respiratory indices according to medication exposure with and without mechanical ventilation. Risk of bias was assessed using the Cochrane risk of bias assessment tools., Findings: Fifty-one studies were included in the analysis. Risk of bias was generally deemed to be low for most studies. Respiratory rate decreased with the administration of opioids in both non-ventilated patients (18% decrease, 95% CI 12-24%) and ventilated patients (26% decrease, 95% CI 15-37%) and increased with inhaled anaesthetics in non-ventilated patients (83% increase, 95% CI 49-118%) and ventilated patients (50% increase, 28-72%). In non-ventilated patients, tidal volume decreased following administration of inhaled aesthetics (55% decrease, 95% CI 25-86%), propofol (36% decrease, 95% CI 20-52%), and benzodiazepines (28% decrease, 95% CI 17-40%); in patients receiving assisted mechanical ventilation, tidal volume was not significantly affected by sedation. Administration of other hypnotic agents was not associated with changes in respiratory rate or tidal volume., Interpretation: Different classes of drugs used for sedation exert differential effects on respiratory pattern, and this may influence weaning and outcomes in mechanically ventilated patients., Funding: This study did not receive any funding support., Competing Interests: Dr. Goligher reports receiving grants from the Canadian Institutes of Health Research and National Sanitarium Association; consulting fees from Lungpacer Medical, Stimit LLC, and Bioage; honoraria for lectures from Vyaire, Draeger, and Getinge; advisory board participation for Getinge (current) and Lungpacer (previous); and receipt of equipment for research from Timpel and Lungpacer., (© 2023 The Author(s).)

Background: Approximately 50% of patients with interstitial lung disease (ILD) experience frailty, which remains unexplored in acute exacerbations of ILD (AE-ILD). A better understanding may help with prognostication and resource planning. We evaluated the association of frailty with clinical characteristics, physical function, hospital outcomes, and post-AE-ILD recovery., Methods: Retrospective cohort study of AE-ILD patients (01/2015-10/2019) with frailty (proportion ≥0.25) on a 30-item cumulative-deficits index. Frail and non-frail patients were compared for pre- and post-hospitalization clinical characteristics, adjusted for age, sex, and ILD diagnosis. One-year mortality, considering transplantation as a competing risk, was analysed adjusting for age, frailty, and Charlson Comorbidity Index (CCI)., Results: 89 AE-ILD patients were admitted (median: 67 years, 63% idiopathic pulmonary fibrosis). 31 were frail, which was associated with older age, greater CCI, lower 6-min walk distance, and decreased independence pre-hospitalization. Frail patients had more major complications (32% vs 10%, p = .01) and required more multidisciplinary support during hospitalization. Frailty was not associated with 1-year mortality (HR: 0.97, 95%CI: [0.45-2.10]) factoring transplantation as a competing risk., Conclusions: Frailty was associated with reduced exercise capacity, increased comorbidities and hospital complications. Identifying frailty may highlight those requiring additional multidisciplinary support, but further study is needed to explore whether frailty is modifiable with AE-ILD., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Lee Fidler has received a grant from the Canadian Pulmonary Fibrosis Foundation and honoraria for speaking/lecturing from Boehringer Ingelheim, AstraZeneca, and Pfizer. Jolene Fisher acknowledges grants from Boehringer Ingelheim (for the Canadian Registry for Pulmonary Fibrosis) and payments made to the University of British Columbia, with subsequent support for the University of Toronto. She has received consulting fees and honoraria from AstraZeneca and Boehringer Ingelheim, as well as honoraria from Boehringer Ingelheim for a presentation. She serves as an unpaid Medical Advisory Board Member for the Canadian Pulmonary Fibrosis Foundation. W. Darlene Reid and Dmitry Rozenberg received a grant from the Canadian Institutes of Health Research for their project “Translating the interplay of cognition and physical performance to daily activities in COPD and ILD: Identifying Needs and Advancing Research Priorities. “Shane Shapera acknowledges a grant from Boehringer Ingelheim Canada and honoraria for speaking at CME events from AstraZeneca, Boehringer Ingelheim, and Hoffman La-Roche. All other authors have no conflicts of interest to declare.

Evidence suggests system-level norms and care processes influence individual patients' medical decisions, including end-of-life decisions for patients with critical illnesses like acute respiratory failure. Yet, little is known about how these processes unfold over the course of a patient's critical illness in the intensive care unit (ICU). Our objective was to map current-state ICU care delivery processes for patients with acute respiratory failure and to identify opportunities to improve the process. We conducted a process mapping study at two academic medical centers, using focus groups and semi-structured interviews. The 70 participants represented 17 distinct roles in ICU care, including interprofessional medical ICU and palliative care clinicians, surrogate decision makers, and patient survivors. Participants refined and endorsed a process map of current-state care delivery for all patients admitted to the ICU with acute respiratory failure requiring mechanical ventilation. The process contains four critical periods for active deliberation about the use of life-sustaining treatments. However, active deliberation steps are inconsistently performed and frequently disrupted, leading to prolongation of life-sustaining treatment by default, without consideration of patients' individual goals and priorities. Interventions to standardize active deliberation in the ICU may improve treatment decisions for ICU patients with acute respiratory failure., Competing Interests: Disclosure of Interest The first author’s spouse receives honoraria for lectures and speakers bureaus from Astra Zeneca. The remaining authors report no conflict of interest.

Background: Wide interhospital variations exist in cardiovascular intensive care unit (CICU) admission practices and the use of critical care restricted therapies (CCRx), but little is known about the differences in patient acuity, CCRx utilization, and the associated outcomes within tertiary centers., Methods: The Critical Care Cardiology Trials Network is a multicenter registry of tertiary and academic CICUs in the United States and Canada that captured consecutive admissions in 2-month periods between 2017 and 2022. This analysis included 17 843 admissions across 34 sites and compared interhospital tertiles of CCRx (eg, mechanical ventilation, mechanical circulatory support, continuous renal replacement therapy) utilization and its adjusted association with in-hospital survival using logistic regression. The Pratt index was used to quantify patient-related and institutional factors associated with CCRx variability., Results: The median age of the study population was 66 (56-77) years and 37% were female. CCRx was provided to 62.2% (interhospital range of 21.3%-87.1%) of CICU patients. Admissions to CICUs with the highest tertile of CCRx utilization had a greater burden of comorbidities, had more diagnoses of ST-elevation myocardial infarction, cardiac arrest, or cardiogenic shock, and had higher Sequential Organ Failure Assessment scores. The unadjusted in-hospital mortality (median, 12.7%) was 9.6%, 11.1%, and 18.7% in low, intermediate, and high CCRx tertiles, respectively. No clinically meaningful differences in adjusted mortality were observed across tertiles when admissions were stratified by the provision of CCRx. Baseline patient-level variables and institutional differences accounted for 80% and 5.3% of the observed CCRx variability, respectively., Conclusions: In a large registry of tertiary and academic CICUs, there was a >4-fold interhospital variation in the provision of CCRx that was primarily driven by differences in patient acuity compared with institutional differences. No differences were observed in adjusted mortality between low, intermediate, and high CCRx utilization sites., Competing Interests: Disclosures Dr Barnett reports clinical trial enrollment for Acceleron, Merck, Merck Shape & Dohme, and Aerovate Therapeutics. Dr Bohula, Dr Morrow, and J. Guo are members of the TIMI study group, which has received institutional research grant support through Brigham and Women’s Hospital from Abbott, Abiomed, Amgen, Anthos Therapeutics, ARCA Biopharma, Inc, AstraZeneca, Bayer HealthCare Pharmaceuticals, Inc, Daiichi Sankyo, Eisai, Intarcia, Ionis Pharmaceuticals, Inc, Janssen Research and Development, LLC, MedImmune, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron Pharmaceuticals, Inc, Roche, Siemens Healthcare Diagnostics, Inc, Softcell Medical Limited, The Medicines Company, and Zora Biosciences. Dr Morrow has received consulting fees from Abbott Laboratories, ARCA Biopharma, InCarda, Inflammatix, Merck, Novartis, and Roche Diagnostics. Dr Daniels reports consulting income from Roche Diagnostics and QuidelOrtho serves on clinical end point adjudication committees for Abbottand Applied Therapeutics. Dr Prasad reports advisory board for Abiomed and NIH R01 grant. Dr Teuteberg reports consulting with Abbott, Abiomed advisory board, CareDx advisory board and speaking fees, Cytokinetics speaking fees, Medtronic advisory board, speaking and consulting fees, Paragonix speaking fees, and Takeda advisory board. The other authors report no conflicts.

Objectives: The Berlin definition of acute respiratory distress syndrome (ARDS) was constructed for patients receiving invasive mechanical ventilation (IMV) with consideration given to issues related to reliability, feasibility, and validity. Notwithstanding, patients with acute respiratory failure (ARF) may be treated with high-flow nasal oxygen (HFNO) and may not fall within the scope of the original definition. We aimed to evaluate the predictive validity of the Berlin definition in HFNO-treated patients with COVID-19-related respiratory failure who otherwise met ARDS criteria., Design: Multicenter, prospective cohort study., Setting: Five ICUs of five centers in Argentina from March 2020 to September 2021., Patients: We consecutively included HFNO-treated patients older than 18 years with confirmed COVID-19-related ARF, a Pa o2 /F io2 of less than 300 mm Hg, bilateral infiltrates on imaging, and worsening respiratory symptoms for less than 1 week., Interventions: None., Measurements and Main Results: We evaluated the predictive validity of mortality at day 28 using the area under the receiver operating characteristics curve (AUC), compared the predictive validity across subgroups, and characterized relevant clinical outcomes. We screened 1,231 patients and included 696 ARDS patients [30 (4%) mild, 380 (55%) moderate, and 286 (41%) severe]. For the study cohort, the AUC for mortality at day 28 was 0.606 (95% CI, 0.561-0.651) with the AUC for subgroups being similar to that of the overall cohort. Two hundred fifty-six patients (37%) received IMV. By day 28, 142 patients (21%) had died, of whom 81 (57%) had severe ARDS. Mortality occurred primarily in patients who were transitioned to IMV., Conclusions: The predictive validity of the Berlin ARDS definition was similar for HFNO-treated patients as compared with the original population of invasively ventilated patients. Our findings support the extension of the Berlin definition to HFNO-treated patients with ARDS., Competing Interests: The 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.)

Introduction: Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar syndrome (HHS) are life-threatening complications of diabetes mellitus. Their clinical profiles have not been fully investigated., Methods: A multicenter retrospective cohort study was conducted in 21 acute care hospitals in Japan. Patients included were adults aged 18 or older who had been hospitalized from January 1, 2012, to December 31, 2016 due to DKA or HHS. The data were extracted from patient medical records. A four-group comparison (mild DKA, moderate DKA, severe DKA, and HHS) was performed to evaluate outcomes., Results: A total of 771 patients including 545 patients with DKA and 226 patients with HHS were identified during the study period. The major precipitating factors of disease episodes were poor medication compliance, infectious diseases, and excessive drinking of sugar-sweetened beverages. The median hospital stay was 16 days [IQR 10-26 days]. The intensive care unit (ICU) admission rate was 44.4% (mean) and the rate at each hospital ranged from 0 to 100%. The in-hospital mortality rate was 2.8% in patients with DKA and 7.1% in the HHS group. No significant difference in mortality was seen among the three DKA groups., Conclusions: The mortality rate of patients with DKA in Japan is similar to other studies, while that of HHS was lower. The ICU admission rate varied among institutions. There was no significant association between the severity of DKA and mortality in the study population., Trial Registration: This study is registered in the UMIN clinical Trial Registration System (UMIN000025393, Registered 23th December 2016)., (© 2023. Springer-Verlag Italia S.r.l., part of Springer Nature.)

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: Since publication of the 2012 Berlin definition of acute respiratory distress syndrome (ARDS), several developments have supported the need for an expansion of the definition, including the use of high-flow nasal oxygen, the expansion of the use of pulse oximetry in place of arterial blood gases, the use of ultrasound for chest imaging, and the need for applicability in resource-limited settings. Methods: A consensus conference of 32 critical care ARDS experts was convened, had six virtual meetings (June 2021 to March 2022), and subsequently obtained input from members of several critical care societies. The goal was to develop a definition that would 1 ) identify patients with the currently accepted conceptual framework for ARDS, 2 ) facilitate rapid ARDS diagnosis for clinical care and research, 3 ) be applicable in resource-limited settings, 4 ) be useful for testing specific therapies, and 5 ) be practical for communication to patients and caregivers. Results: The committee made four main recommendations: 1 ) include high-flow nasal oxygen with a minimum flow rate of ⩾30 L/min; 2 ) use Pa O 2 :Fi O 2  ⩽ 300 mm Hg or oxygen saturation as measured by pulse oximetry Sp O 2 :Fi O 2  ⩽ 315 (if oxygen saturation as measured by pulse oximetry is ⩽97%) to identify hypoxemia; 3 ) retain bilateral opacities for imaging criteria but add ultrasound as an imaging modality, especially in resource-limited areas; and 4 ) in resource-limited settings, do not require positive end-expiratory pressure, oxygen flow rate, or specific respiratory support devices. Conclusions: We propose a new global definition of ARDS that builds on the Berlin definition. The recommendations also identify areas for future research, including the need for prospective assessments of the feasibility, reliability, and prognostic validity of the proposed global definition.

Background: Guidelines advocate for minimization of physical restraint (PR) use in intensive care units (ICU). Interprofessional team perspectives on PR practices can inform the design and implementation of successful PR minimization interventions., Aim: To identify ICU staff perspectives of contextual influences on PR practices and minimization strategies., Study Design: A qualitative descriptive study in a single ICU in Toronto, Canada. One-on-one semi-structured interviews were conducted with 14 ICU staff. A deductive content analysis of interviews was undertaken using the integrated-Promoting Action on Research Implementation in Health Services (i-PARIHS) framework., Results: Five themes were developed: risk-averse culture, leadership, practice monitoring and feedback processes, environmental factors, and facilitation. Participants described a risk-averse culture where prophylactic application of PR for intubated patients was used to prevent unplanned extubation thereby avoiding blame from colleagues. Perceived absence of leadership and interprofessional team involvement situated nurses as the primary decision-maker for restraint application and removal. Insufficient monitoring of restraint practices, lack of access to restraint alternatives, and inability to control environmental contributors to delirium and agitation further increased PR use. Recommendations as to how to minimize restraint use included a nurse facilitator to advance leadership-team collaboration, availability of restraints alternatives, and guidance on situations for applying and removing restraints., Conclusions: This analysis of contextual influences on PR practices and minimization using the i-PARIHS framework revealed potentially modifiable barriers to successful PR minimization, including a lack of leadership involvement, gaps in practice monitoring, and collaborative decision-making processes. A team approach to changing behaviour and culture should be considered for successful implementation and sustainability of PR minimization., Relevance to Practice: The establishment of an interprofessional facilitation team that addresses risk-averse culture and promotes collaboration among ICU stakeholders will be crucial to the success of any approach to restraint minimization., (© 2022 British Association of Critical Care Nurses.)

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: Clogging is characterized by a progressive impairment of transmembrane patency in renal replacement devices and occurs due to obstruction of pores by unknown molecules. If citrate-based anti-coagulation is used, clogging can manifest as a metabolic alkalosis accompanied by hypernatremia and hypercalcemia, primarily a consequence of Na 3 Citrate infusion. An increased incidence of clogging has been observed during the COVID-19 pandemic. However, precise factors contributing to the formation remain uncertain. This investigation aimed to analyze its incidence and assessed time-varying trajectories of associated factors in critically ill patients on continuous renal replacement therapy (CRRT)., Methods: In this retrospective, single-center data analysis, we evaluated COVID-19 patients undergoing CRRT and admitted to critical care between March 2020 and December 2021. We assessed the proportional incidence of clogging surrogates in the overall population and subgroups based on the specific CRRT devices employed at our institution, including multiFiltrate (Fresenius Medical Care) and Prismaflex System (Baxter). Moderate and severe clogging were defined as Na > 145 or ≥ 150 mmol/l and HCO 3  > 28.0 or ≥ 30 mmol/l, respectively, with a total albumin-corrected calcium > 2.54 mmol/l. A mixed effect model was introduced to investigate factors associated with development of clogging.-  > 28.0 or ≥ 30 mmol/l, respectively, with a total albumin-corrected calcium > 2.54 mmol/l. A mixed effect model was introduced to investigate factors associated with development of clogging., Results: Fifty-three patients with 240 CRRT runs were analyzed. Moderate and severe clogging occurred in 15% (8/53) and 19% (10/53) of patients, respectively. Twenty-seven percent (37/136) of CRRTs conducted with a multiFiltrate device met the criteria for clogging, whereas no clogging could be observed in patients dialyzed with the Prismaflex System. Occurrence of clogging was associated with elevated triglyceride plasma levels at filter start (p = 0.013), amount of enteral nutrition (p = 0.002) and an increasing white blood cell count over time (p = 0.002)., Conclusions: Clogging seems to be a frequently observed phenomenon in critically ill COVID-19 patients. The presence of hypertriglyceridemia, combined with systemic inflammation, may facilitate the development of an impermeable secondary membrane within filters, thereby contributing to compromised membrane patency., (© 2023. The Author(s).)

Background: The efficacy of simvastatin in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear., Methods: In an ongoing international, multifactorial, adaptive platform, randomized, controlled trial, we evaluated simvastatin (80 mg daily) as compared with no statin (control) in critically ill patients with Covid-19 who were not receiving statins at baseline. The primary outcome was respiratory and cardiovascular organ support-free days, assessed on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support through day 21 in survivors; the analyis used a Bayesian hierarchical ordinal model. The adaptive design included prespecified statistical stopping criteria for superiority (>99% posterior probability that the odds ratio was >1) and futility (>95% posterior probability that the odds ratio was <1.2)., Results: Enrollment began on October 28, 2020. On January 8, 2023, enrollment was closed on the basis of a low anticipated likelihood that prespecified stopping criteria would be met as Covid-19 cases decreased. The final analysis included 2684 critically ill patients. The median number of organ support-free days was 11 (interquartile range, -1 to 17) in the simvastatin group and 7 (interquartile range, -1 to 16) in the control group; the posterior median adjusted odds ratio was 1.15 (95% credible interval, 0.98 to 1.34) for simvastatin as compared with control, yielding a 95.9% posterior probability of superiority. At 90 days, the hazard ratio for survival was 1.12 (95% credible interval, 0.95 to 1.32), yielding a 91.9% posterior probability of superiority of simvastatin. The results of secondary analyses were consistent with those of the primary analysis. Serious adverse events, such as elevated levels of liver enzymes and creatine kinase, were reported more frequently with simvastatin than with control., Conclusions: Although recruitment was stopped because cases had decreased, among critically ill patients with Covid-19, simvastatin did not meet the prespecified criteria for superiority to control. (REMAP-CAP ClinicalTrials.gov number, NCT02735707.)., (Copyright © 2023 Massachusetts Medical Society.)

Background: Internal redistribution of gas, referred to as pendelluft, is a new potential mechanism of effort-dependent lung injury. Neurally-adjusted ventilatory assist (NAVA) and proportional assist ventilation (PAV +) follow the patient's respiratory effort and improve synchrony compared with pressure support ventilation (PSV). Whether these modes could prevent the development of pendelluft compared with PSV is unknown. We aimed to compare pendelluft magnitude during PAV + and NAVA versus PSV in patients with resolving acute respiratory distress syndrome (ARDS)., Methods: Patients received either NAVA, PAV + , or PSV in a crossover trial for 20-min using comparable assistance levels after controlled ventilation (> 72 h). We assessed pendelluft (the percentage of lost volume from the non-dependent lung region displaced to the dependent region during inspiration), drive (as the delta esophageal swing of the first 100 ms [ΔP es 100 ms ]) and inspiratory effort (as the esophageal pressure-time product per minute [PTP min ]). We performed repeated measures analysis with post-hoc tests and mixed-effects models., Results: Twenty patients mechanically ventilated for 9 [5-14] days were monitored. Despite matching for a similar tidal volume, respiratory drive and inspiratory effort were slightly higher with NAVA and PAV + compared with PSV (ΔP es 100 ms of -2.8 [-3.8--1.9] cm H 2 O, -3.6 [-3.9--2.4] cm H 2 O and -2.1 [-2.5--1.1] cm H 2 O, respectively, p < 0.001 for both comparisons; PTP min of 155 [118-209] cm H 2 O s/min, 197 [145-269] cm H 2 O s/min, and 134 [93-169] cm H 2 O s/min, respectively, p < 0.001 for both comparisons). Pendelluft magnitude was higher in NAVA (12 ± 7%) and PAV + (13 ± 7%) compared with PSV (8 ± 6%), p < 0.001. Pendelluft magnitude was strongly associated with respiratory drive (β = -2.771, p-value < 0.001) and inspiratory effort (β = 0.026, p  < 0.001), independent of the ventilatory mode. A higher magnitude of pendelluft in proportional modes compared with PSV existed after adjusting for PTP min (β = 2.606, p = 0.010 for NAVA, and β = 3.360, p = 0.004 for PAV +), and only for PAV + when adjusted for respiratory drive (β = 2.643, p = 0.009 for PAV +)., Conclusions: Pendelluft magnitude is associated with respiratory drive and inspiratory effort. Proportional modes do not prevent its occurrence in resolving ARDS compared with PSV., (© 2023. The Author(s).)

Background: The unsuccessful extubation in patients with traumatic cervical spinal cord injuries (CSCI) may result from impairment diaphragm function and monitoring of diaphragm electrical activity (EAdi) can be informative in guiding extubation. We aimed to evaluate whether the change of EAdi during a single maximal maneuver can predict extubation outcomes in CSCI patients., Methods: This is a retrospective study of CSCI patients requiring mechanical ventilation in the ICU of a tertiary hospital. A single maximal maneuver was performed by asking each patient to inhale with maximum strength during the first spontaneous breathing trial (SBT). The baseline (during SBT before maximal maneuver), maximum (during the single maximal maneuver), and the increase of EAdi (ΔEAdi, equal to the difference between baseline and maximal) were measured. The primary outcome was extubation success, defined as no reintubation after the first extubation and no tracheostomy before any extubation during the ICU stay., Results: Among 107 patients enrolled, 50 (46.7%) were extubated successfully at the first SBT. Baseline EAdi, maximum EAdi, and ΔEAdi were significantly higher, and the rapid shallow breathing index was lower in patients who were extubated successfully than in those who failed. By multivariable logistic analysis, ΔEAdi was independently associated with successful extubation (OR 2.03, 95% CI 1.52-3.17). ΔEAdi demonstrated high diagnostic accuracy in predicting extubation success with an AUROC 0.978 (95% CI 0.941-0.995), and the cut-off value was 7.0 μV., Conclusions: The increase of EAdi from baseline SBT during a single maximal maneuver is associated with successful extubation and can help guide extubation in CSCI patients., (© 2023. The Author(s).)

Exposure to crystalline silica leads to health effects beyond occupational silicosis. Exercise training's potential benefits on pulmonary diseases yield inconsistent outcomes. In this study, we utilized experimental silicotic mice subjected to exercise training and pharmacological interventions, including interleukin-17A (IL-17A) neutralizing antibody or clodronate liposome for macrophage depletion. Findings reveal exercise training's ability to mitigate silicosis progression in mice by suppressing scavenger receptor B (SRB)/NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and Toll-like receptor 4 (TLR4) pathways. Macrophage-derived IL-17A emerges as primary source and trigger for silica-induced pulmonary inflammation and fibrosis. Exercise training effectively inhibits IL-17A-CXC motif chemokine ligand 5 (CXCL5)-Chemokine (C-X-C motif) Receptor 2 (CXCR2) axis in silicotic mice. Our study evidences exercise training's potential to reduce collagen deposition, preserve elastic fibers, slow pulmonary fibrosis advancement, and enhance pulmonary function post silica exposure by impeding macrophage-derived IL-17A-CXCL5-CXCR2 axis., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

In some patients with acute respiratory distress syndrome (ARDS), a paradoxical improvement in respiratory system compliance (C RS ) has been observed when assuming a supine (head of bed [HOB] 0°) compared with semirecumbent (HOB 35-40°) posture. We sought to test the hypothesis that mechanically ventilated patients with ARDS would have improved C RS , due to changes in ventilation distribution, when moving from the semirecumbent to supine position. We conducted a prospective, observational ICU study including 14 mechanically ventilated patients with ARDS. For each patient, ventilation distribution (assessed by electrical impedance tomography) and pulmonary mechanics were compared in supine versus semirecumbent postures. Compared with semirecumbent, in the supine posture C RS increased (33 ± 21 vs. 26 ± 14 mL/cm H 2 O, p = 0.005), driving pressure was reduced (14 ± 6 vs. 17 ± 7 cm H 2 O, p < 0.001), and dorsal fraction of ventilation was decreased (48.5 ± 14.1% vs. 54.5 ± 12.0%, p = 0.003). Posture change from semirecumbent to supine resulted in a favorable physiologic response in terms of improved C RS and reduced driving pressure-with a corresponding increase in ventral ventilation, possibly related to reduced ventral overdistension., Competing Interests: Drs. Pearce and McGuire received funding from the National Institutes of Health- National Heart Lung and Blood Institute (NIH-NHLBI) T32. Dr. Malhotra has received funding from the National Institutes of Health (NIH). Dr. Malhotra also reports income related to medical education from Livanova, Jazz, Zoll, and Eli Lilly. ResMed gave a philanthropic donation to University of California San Diego (UCSD). Dr. Malhotra is a co-founder of Healcisio which is a startup related to predictive analytics in sepsis. The remaining authors have disclosed that they do not have any conflicts of interest related to this work., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Objectives: To describe international variation in ethics and contract processes, identify predictors of approval times, and reasons for nonparticipation in an international observational study of ventilation discontinuation practices., Study Design and Setting: A nested cross-sectional survey of research personnel at 111 participating sites (representing 142 intensive care units [ICUs]) from six geographic regions (Canada, India, the United Kingdom, Europe, Australia/New Zealand, and the United States)., Results: We analyzed responses from 80 sites (72.1% response rate). A single local or central approval was required at 34/80 (42.5%) and 23/80 (28.75%), respectively. Of those requiring central ethics approval, 20/23 (87.0%) sites required an additional approval. Sites with central vs. other ethics approval processes had significantly longer times to ethics approval (176 vs. 42 days; P < 0.0001). The median time to contract execution was 140 days (range: 11-1,215) with sites in India and the United States having the shortest and longest times to contract execution, respectively. We did not identify independent predictors of approval times. Of 190 sites that initially agreed to participate, 78 (41%) sites (89 ICUs) were ultimately unable to participate., Conclusion: International ethics and contract approval times were lengthy and highly variable. Central ethics review processes significantly increased approval times., Competing Interests: Declaration of competing interest All authors affirm that they have no financial or nonfinancial conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Wearable consumer technology allows for the collection of a growing amount of personal health data. Through the analysis of reflected LED light on the skin, heart rate measurement and arrhythmia detection can be performed. Given that melanin alters skin light absorption, this study seeks to summarize the accuracy of cardiac data from wrist-worn wearable devices for participants of varying skin tones., Methods: We conducted a systematic review, searching Embase, MEDLINE, CINAHL, and Cochrane for original studies that stratified heart rate and rhythm data for consumer wearable technology according to participant race and/or skin tone., Results: A total of 10 studies involving 469 participants met inclusion criteria. The frequency-weighted Fitzpatrick score for skin tone was reported in six studies (n = 293), with a mean participant score of 3.5 (range 1-6). Overall, four of the ten studies reported a significant reduction in accuracy of heart rate measurement with wearable devices in darker-skinned individuals, compared to participants with lighter skin tones. Four studies noted no effect of user skin tone on accuracy. The remaining two studies showed mixed results., Conclusions: Preliminary evidence is inconclusive, but some studies suggest that wearable devices may be less accurate for detecting heart rate in participants with darker skin tones. Higher quality evidence is necessary, with larger sample sizes and more objective stratification of participants by skin tone, in order to characterize potential racial bias in consumer devices., (© 2022. W. Montague Cobb-NMA Health Institute.)