Sex and gender-based analysis and diversity metric reporting in acute care trials published in high-impact journals: a systematic review.

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.

Incidence and risk factors of chronic postoperative pain in same-day surgery: A prospective cohort study.

BACKGROUND: The amount of same-day surgery has increased markedly worldwide in recent decades, but there remains limited evidence on chronic postsurgical pain in this setting. METHODS: We assessed pain 90 days after ambulatory surgery in an international, multicentre prospective cohort study of patients ≥45 years old with comorbidities or ≥65 years old. Pain was assessed using the Brief Pain Inventory. Chronic postsurgical pain was defined as a change ≥1 in self-rated average pain at the surgical site between baseline and 90 days, and moderate to severe chronic postsurgical pain as a score ≥4 in self-rated average pain at the surgical site at 90 days. Risk factors for chronic postsurgical pain were identified using multivariable logistic regression. RESULTS: Between November 2021 and January 2023, a total of 2054 participants were included, and chronic postsurgical pain occurred in 12% of participants, of whom 93.1% had new chronic pain at the surgical site (i.e., participants without pain prior to surgery). Moderate to severe chronic postsurgical pain occurred in 9% of overall participants. Factors associated with chronic postsurgical pain were: active smoking (OR 1.82; 95% CI 1.20 to 2.76), orthopaedic surgery (OR 4.7; 95% CI 2.24 to 9.7), plastic surgery (OR 4.3; 95% CI 1.97 to 9.2), breast surgery (OR 2.74; 95% CI 1.29 to 5.8), vascular surgery (OR 2.71; 95% CI 1.09 to 6.7), and ethnicity (i.e., Hispanic/Latino ethnicity OR 3.41; 95% CI 1.68 to 6.9 and First Nations/Native persons OR 4.0; 95% CI 1.05 to 15.4). CONCLUSIONS: Persistent postsurgical pain after same-day surgery is common, usually moderate to severe in nature, and occurs mostly in patients without chronic pain prior to surgery.

Developing Guidance for Donor Intervention Randomized Controlled Trials: Initial Discussions From the Canada-United Kingdom 2022 Workshop.

BACKGROUND: Donor interventions, including medications, protocols, and medical devices administered to donors, can enhance transplantable organ quality and quantity and maximize transplantation success. However, there is paucity of high-quality evidence about their effectiveness, in part because of ethical, practical, and regulatory challenges, and lack of guidance about conduct of donor intervention randomized controlled trials (RCTs). METHODS: With the vision to develop authoritative guidance for conduct of donor intervention RCTs, we convened a workshop of Canadian-United Kingdom experts in organ donation and transplantation ethics, research, and policy to identify stakeholders, explore unique challenges, and develop research agenda to inform future work in this promising field. RESULTS: Donor intervention trials should consider perspectives of broad group of stakeholders including donors, transplant recipients, and their families; researchers in donation and transplantation; research ethics boards; and healthcare providers and administrators involved in donation and transplantation. Unique challenges include (1) research ethics (living versus deceased status of the donor at the time of intervention, intervention versus outcomes assessment in different individuals, harm-benefit analysis in donors versus recipients, consent, and impact on research bystanders); (2) outcome data standardization and linkage; and (3) regulatory and governance considerations. CONCLUSIONS: Donor intervention RCTs hold potential to benefit organ transplantation outcomes but face unique research ethics, outcome data, and regulatory challenges. By developing research agenda to address these challenges, our workshop was an important first step toward developing Canada-United Kingdom guidance for donor intervention RCTs that are poised to improve the quality and availability of transplantable organs.

The impact of COVID-19 workload on psychological distress amongst Canadian intensive care unit healthcare workers during the 1st wave of the COVID-19 pandemic: A longitudinal cohort study.

Intensive care unit healthcare workers (ICU HCW) are at risk of mental health disorders during emerging disease outbreaks. Numerous cross-sectional studies have reported psychological distress, anxiety, and depression amongst ICU HCW during the COVID-19 pandemic. However, few studies have followed HCW longitudinally, and none of these have examined the association between COVID-19 workload and mental health. We conducted a longitudinal cohort study of 309 Canadian ICU HCW from April 2020 to August 2020, during the 1st wave of the COVID-19 pandemic. Psychological distress was assessed using the General Health Questionnaire 12-item scale (GHQ-12) at 3 timepoints: during the acceleration phase of the 1st wave (T1), the deceleration phase of the 1st wave (T2), and after the 1st wave had passed (T3). Clinically relevant psychological distress, defined as a GHQ-12 score ≥ 3, was identified in 64.7% of participants at T1, 41.0% at T2, and 34.6% at T3. Psychological distress was not associated with COVID-19 workload at T1. At T2, psychological distress was associated with the number of COVID-19 patients in the ICU (odds ratio [OR]: 1.06, 95% confidence interval [CI]: 1.00, 1.13) while at T3, when COVID-19 patient numbers were low, it was associated with the number of weekly hospital shifts with COVID-19 exposure (OR: 1.33, 95% CI: 1.09, 1.64). When analyzed longitudinally in a mixed effects model, pandemic timepoint was a stronger predictor of psychological distress (OR: 0.24, 95% CI: 0.15, 0.40 for T2 and OR: 0.16, 95% CI: 0.09, 0.27 for T3) than COVID-19 workload. Participants who showed persistent psychological distress at T3 were compared with those who showed recovery at T3. Persistent psychological distress was associated with a higher number of weekly shifts with COVID-19 exposure (OR: 1.97, 95% CI:1.33, 3.09) but not with a higher number of COVID-19 patients in the ICU (OR: 0.86, 95% CI: 0.76, 0.95). In summary, clinically relevant psychological distress was observed in a majority of ICU HCW during the acceleration phase of the 1st wave of the COVID-19 pandemic but decreased rapidly as the 1st wave progressed. Persistent psychological distress was associated with working more weekly shifts with COVID-19 exposure but not with higher numbers of COVID-19 patients in the ICU. In future emerging disease outbreaks, minimizing shifts with direct disease exposure may help alleviate symptoms for individuals with persistent psychological distress.

Development and Validation Process of the Intensive Care Unit Omitted Nursing Care (ICU-ONC) Instrument Among French Canadian Nurses.

Background and Purpose: The purpose of this article is to document the development and validation process of an instrument adapted for French-speaking nurses and to measure the occurrence of omitted nursing care (ONC) in the intensive care unit (ICU). Methods: An electronic Delphi panel, involving ICU nursing experts from the province of Quebec (Canada), was used to develop the intensive care unit omitted nursing care (ICU-ONC) instrument. For the validation process, an electronic cross-sectional survey was conducted. Results: A total of 564 nurses participated in the validation study. Exploratory factor analysis performed on 478 complete observations supports the presence of a single-factor structure for the 22-item ICU-ONC instrument. Coefficient alpha for the scale was .93, 95% confidence interval (CI) was [0.92, 0.94], item-partial total correlations ranged from .49 and .68, and the mean/median interitem correlations were .38 and .37, respectively. Moderate negative correlations were found between the ICU-ONC instrument overall score and two related constructs: nurses' perception of the quality as well as the safety of care. Conclusions: Our current understanding of ONC in the ICU is based on the results drawn from the administration of generic instruments to ICU nurses. The novel 22-item ICU-ONC instrument can help better estimate the occurrence of the phenomena in the ICU.

Functional recovery of wrist surgery with regional versus general anesthesia: a prospective observational study.

PURPOSE: Regional anesthesia may favour postoperative rehabilitation by inhibiting peripheral sensitization and secondary hyperalgesia. The literature on this subject is limited. In the present FUNCTION study, we sought to compare the functional recovery post orthopedic wrist surgery with regional versus general anesthesia. METHODS: We conducted a single-centre prospective observational cohort study in adult patients with a distal radial fracture. Functional recovery was assessed with validated psychometrics questionnaires (Quick Disabilities of Arm, Shoulder and Hand [QuickDASH] and Patient-Rated Wrist Evaluation [PRWE]), range of motion, and grip strength. We used a linear mixed regression model to assess the impact of the anesthesia technique on functional recovery. Postoperative pain and patient satisfaction were evaluated using a visual analog scale. RESULTS: We recruited 76 patients. At 12 weeks post surgery, there was no difference between the type of anesthesia and functional recovery with the QuickDASH (higher scores worse; regional anesthesia [RA], 22.7 vs general anesthesia [GA], 19.3; adjusted mean difference [aMD], -0.3; 95% confidence interval [CI], -9.6 to 9.0; P = 0.9) and PRWE (higher scores worse; RA group, 21.0 vs GA group, 20.5; aMD, -3.3; 95% CI, -12.1 to 5.6; P = 0.93) questionnaires. Range of motion, satisfaction, and postoperative pain were similar between groups. Right-hand grip strength was higher in the GA group. CONCLUSION: Regional anesthesia was not associated with improved functional recovery compared with general anesthesia. The dominance of the operated limb was a confusion factor in all evaluation modalities. Further research taking into account the dominance of the hand is necessary to establish the effects of regional anesthesia on functional recovery. STUDY REGISTRATION: ClinicalTrials.gov (NCT04541745); registered 9 September 2020.

RéSUMé: OBJECTIF: L'anesthésie régionale pourrait favoriser la rééducation postopératoire en inhibant la sensibilisation périphérique et l'hyperalgésie secondaire. La littérature à ce sujet est limitée. Dans la présente étude nommée FUNCTION, nous avons cherché à comparer la récupération fonctionnelle après une chirurgie orthopédique du poignet réalisée sous anesthésie régionale vs sous anesthésie générale. MéTHODE: Nous avons réalisé une étude de cohorte observationnelle prospective monocentrique auprès de patient·es adultes présentant une fracture radiale distale. La récupération fonctionnelle a été évaluée à l'aide de questionnaires psychométriques validés (questionnaires QuickDASH [Quick Disabilities of Arm, Shoulder and Hand] et PRWE [Patient-Rated Wrist Evaluation]), de l'amplitude des mouvements et de la force de préhension. Nous avons utilisé un modèle de régression linéaire mixte pour évaluer l'impact de la technique d'anesthésie sur la récupération fonctionnelle. La douleur postopératoire et la satisfaction des patient·es ont été évaluées à l'aide d'une échelle visuelle analogique. RéSULTATS: Nous avons recruté 76 personnes. Douze semaines après la chirurgie, il n'y avait aucune différence entre le type d'anesthésie et la récupération fonctionnelle selon le questionnaire QuickDASH (scores plus élevés les pires; anesthésie régionale [AR], 22,7 vs anesthésie générale [AG], 19,3; différence moyenne ajustée [DMa], −0,3; intervalle de confiance [IC] à 95 %, −9,6 à 9,0; P = 0,9) et PRWE (scores plus élevés les pires; groupe AR, 21,0 vs groupe AG, 20,5; DMa, −3,3; IC 95 %, −12,1 à 5,6; P = 0,93). L'amplitude des mouvements, la satisfaction et la douleur postopératoire étaient similaires entre les groupes. La force de préhension de la main droite était plus élevée dans le groupe AG. CONCLUSION: L'anesthésie régionale n'a pas été associée à une amélioration de la récupération fonctionnelle par rapport à l'anesthésie générale. La prédominance du membre opéré était un facteur de confusion dans toutes les modalités d'évaluation. D'autres recherches tenant compte du côté dominant au niveau des mains sont nécessaires pour déterminer les effets de l'anesthésie régionale sur la récupération fonctionnelle. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT04541745); enregistrée le 9 septembre 2020.

Frequency of screening and SBT Technique Trial-North American Weaning Collaboration (FAST-NAWC): an update to the protocol and statistical analysis plan.

BACKGROUND: This update summarizes key changes made to the protocol for the Frequency of Screening and Spontaneous Breathing Trial (SBT) Technique Trial-North American Weaning Collaborative (FAST-NAWC) trial since the publication of the original protocol. This multicenter, factorial design randomized controlled trial with concealed allocation, will compare the effect of both screening frequency (once vs. at least twice daily) to identify candidates to undergo a SBT and SBT technique [pressure support + positive end-expiratory pressure vs. T-piece] on the time to successful extubation (primary outcome) in 760 critically ill adults who are invasively ventilated for at least 24 h in 20 North American intensive care units. METHODS/DESIGN: Protocols for the pilot, factorial design trial and the full trial were previously published in J Clin Trials ( https://doi.org/10.4172/2167-0870.1000284 ) and Trials (https://doi: 10.1186/s13063-019-3641-8). As planned, participants enrolled in the FAST pilot trial will be included in the report of the full FAST-NAWC trial. In response to the onset of the coronavirus disease of 2019 (COVID-19) pandemic when approximately two thirds of enrollment was complete, we revised the protocol and consent form to include critically ill invasively ventilated patients with COVID-19. We also refined the statistical analysis plan (SAP) to reflect inclusion and reporting of participants with and without COVID-19. This update summarizes the changes made and their rationale and provides a refined SAP for the FAST-NAWC trial. These changes have been finalized before completion of trial follow-up and the commencement of data analysis. TRIAL REGISTRATION: Clinical Trials.gov NCT02399267.

Small-Volume Blood Collection Tubes to Reduce Transfusions in Intensive Care: The STRATUS Randomized Clinical Trial.

Importance: Blood collection for laboratory testing in intensive care unit (ICU) patients is a modifiable contributor to anemia and red blood cell (RBC) transfusion. Most blood withdrawn is not required for analysis and is discarded. Objective: To determine whether transitioning from standard-volume to small-volume vacuum tubes for blood collection in ICUs reduces RBC transfusion without compromising laboratory testing procedures. Design, Setting, and Participants: Stepped-wedge cluster randomized trial in 25 adult medical-surgical ICUs in Canada (February 5, 2019 to January 21, 2021). Interventions: ICUs were randomized to transition from standard-volume (n = 10 940) to small-volume tubes (n = 10 261) for laboratory testing. Main Outcomes and Measures: The primary outcome was RBC transfusion (units per patient per ICU stay). Secondary outcomes were patients receiving at least 1 RBC transfusion, hemoglobin decrease during ICU stay (adjusted for RBC transfusion), specimens with insufficient volume for testing, length of stay in the ICU and hospital, and mortality in the ICU and hospital. The primary analysis included patients admitted for 48 hours or more, excluding those admitted during a 5.5-month COVID-19-related trial hiatus. Results: In the primary analysis of 21 201 patients (mean age, 63.5 years; 39.9% female), which excluded 6210 patients admitted during the early COVID-19 pandemic, there was no significant difference in RBC units per patient per ICU stay (relative risk [RR], 0.91 [95% CI, 0.79 to 1.05]; P = .19; absolute reduction of 7.24 RBC units/100 patients per ICU stay [95% CI, -3.28 to 19.44]). In a prespecified secondary analysis (n = 27 411 patients), RBC units per patient per ICU stay decreased after transition from standard-volume to small-volume tubes (RR, 0.88 [95% CI, 0.77 to 1.00]; P = .04; absolute reduction of 9.84 RBC units/100 patients per ICU stay [95% CI, 0.24 to 20.76]). Median decrease in transfusion-adjusted hemoglobin was not statistically different in the primary population (mean difference, 0.10 g/dL [95% CI, -0.04 to 0.23]) and lower in the secondary population (mean difference, 0.17 g/dL [95% CI, 0.05 to 0.29]). Specimens with insufficient quantity for analysis were rare (≤0.03%) before and after transition. Conclusions and Relevance: Use of small-volume blood collection tubes in the ICU may decrease RBC transfusions without affecting laboratory analysis. Trial Registration: ClinicalTrials.gov Identifier: NCT03578419.

Benzodiazepine-Free Cardiac Anesthesia for Reduction of Postoperative Delirium (B-Free): A Protocol for a Multi-centre Randomized Cluster Crossover Trial.

Delirium is common after cardiac surgery and is associated with adverse outcomes. Administration of benzodiazepines before and after cardiac surgery is associated with delirium; guidelines recommend minimizing their use. Benzodiazepine administration during cardiac surgery remains common because of its recognized benefits. The Benzodiazepine-Free Cardiac Anesthesia for Reduction of Postoperative Delirium (B-Free) trial is a randomized cluster crossover trial evaluating whether an institutional policy of restricting intraoperative benzodiazepine administration (ie, ≥ 90% of patients do not receive benzodiazepines during cardiac surgery), as compared with a policy of liberal intraoperative benzodiazepine administration (ie, ≥ 90% of patients receive ≥ 0.03 mg/kg midazolam equivalent), reduces delirium. Hospitals performing ≥ 250 cardiac surgeries a year are included if their cardiac anesthesia group agrees to apply both benzodiazepine policies per their randomization, and patients are assessed for postoperative delirium every 12 hours in routine clinical care. Hospitals apply the restricted or liberal benzodiazepine policy during 12 to 18 crossover periods of 4 weeks each. Randomization for all periods takes place in advance of site startup; sites are notified of their allocated policy during the last week of each crossover period. Policies are applied to all patients undergoing cardiac surgery during the trial period. The primary outcome is the incidence of delirium at up to 72 hours after surgery. The B-Free trial will enroll ≥ 18,000 patients undergoing cardiac surgery at 20 hospitals across North America. Delirium is common after cardiac surgery, and benzodiazepines are associated with the occurrence of delirium. The B-Free trial will determine whether an institutional policy restricting the administration of benzodiazepines during cardiac surgery reduces the incidence of delirium after cardiac surgery. Clinicaltrials.gov registration number: NCT03928236 (First registered April 26, 2019).

L'état confusionnel est fréquent après une chirurgie cardiaque et il est associé à des complications. L'administration de benzodiazépines avant et après une chirurgie cardiaque est associée à l'état confusionnel; dans les lignes directrices, on recommande de réduire leur utilisation au minimum. L'administration de benzodiazépines pendant une chirurgie cardiaque demeure fréquente, en raison des leurs bienfaits reconnus. L'essai B-Free (Benzodiazepine-Free Cardiac Anesthesia for Reduction of Postoperative Delirium ou l'anesthésie sans benzodiazépine en contexte de chirurgie cardiaque pour la réduction de l'état confusionnel postopératoire) est un essai à répartition aléatoire par grappes et avec permutation, visant à évaluer si une politique institutionnelle de restriction de l'administration peropératoire de benzodiazépines (c.-à-d. que ≥ 90 % des patients ne reçoivent pas de benzodiazépines durant une chirurgie cardiaque) réduit l'état confusionnel, comparativement à une politique d'administration peropératoire libérale de benzodiazépines (c.-à-d. que ≥ 90 % des patients reçoivent ≥ 0,03 mg/kg d'équivalent du midazolam). Des hôpitaux effectuant au moins 250 chirurgies cardiaques par année sont inclus dans l'essai si leurs équipes d'anesthésie cardiaque acceptent d'appliquer les deux politiques relatives aux benzodiazépines en vertu de la répartition aléatoire et si les patients sont évalués toutes les 12 heures, en ce qui a trait à l'état confusionnel postopératoire, dans le cadre des soins cliniques habituels. Les hôpitaux mettent en œuvre la politique d'administration restreinte ou libérale de benzodiazépines durant 12 à 18 périodes de permutation de 4 semaines chacune. La répartition aléatoire de l'ensemble des périodes a lieu avant le début de l'essai à l'hôpital; les établissements sont avisés de la politique qui leur est attribuée au cours de la dernière semaine de chaque période de permutation. Les politiques sont appliquées à tous les patients qui subissent une chirurgie cardiaque durant la période de l'essai. Le critère d'évaluation principal est l'incidence de l'état confusionnel dans les 72 heures suivant l'intervention chirurgicale. L'étude B-Free inclura au moins 18 000 patients qui subiront une chirurgie cardiaque dans 20 hôpitaux en l'Amérique du Nord. L'état confusionnel est fréquent après une chirurgie cardiaque, et les benzodiazépines sont associées à la survenue de l'état confusionnel. L'essai B-Free permettra de déterminer si une politique institutionnelle de restriction de l'administration de benzodiazépines durant une chirurgie cardiaque réduit l'incidence de l'état confusionnel après une telle chirurgie.Clinicaltrials.gov registration number: NCT03928236 (First registered April 26, 2019).

Calcineurin Inhibition in Deceased Organ Donors: A Systematic Review and Meta-analysis of Preclinical Studies.

Background: Preconditioning deceased organ donors with calcineurin inhibitors (CNIs) may reduce ischemia-reperfusion injury to improve transplant outcomes. Methods: We searched MEDLINE, EMBASE, Cochrane Library, and conference proceedings for animal models of organ donation and transplantation, comparing donor treatment with CNIs with either placebo or no intervention, and evaluating outcomes for organ transplantation. Reviewers independently screened and selected studies, abstracted data, and assessed the risk of bias and clinical relevance of included studies. Where possible, we pooled results using meta-analysis; otherwise, we summarized findings descriptively. Results: Eighteen studies used various animals and a range of CNI agents and doses and evaluated their effects on a variety of transplant outcomes. The risk of bias and clinical applicability were poorly reported. Pooled analyses suggested benefit of CNI treatment on early graft function in renal transplants (3 studies; serum creatinine: ratio of means [RoM] 0.54; 95% confidence interval [CI], 0.34-0.86) but not for liver transplants (2 studies; serum alanine transaminase: RoM 0.61; 95% CI, 0.30-1.26; and serum aspartate aminotransferase: RoM 0.58; 95% CI, 0.26-1.31). We found no reduction in graft loss at 7 d (2 studies; risk ratio 0.54; 95% CI, 0.08-3.42). CNI treatment was associated with reduced transplant recipient levels of interleukin-6 (4 studies; RoM 0.36; 95% CI, 0.19-0.70), tumor necrosis factor-alpha (5 studies; RoM 0.36; 95% CI, 0.12-1.03), and cellular apoptosis (4 studies; RoM 0.30; 95% CI, 0.19-0.47). Conclusions: Although this compendium of animal experiments suggests that donor preconditioning with CNIs may improve early kidney graft function, the limited ability to reproduce a true clinical environment in animal experiments and to assess for risk of bias in these experiments is a serious weakness that precludes current clinical application.

Transplant Recipient Preferences Regarding Organ Donor Research: Their Role in Consent and use of Their Data.

Research on deceased organ donors has been hindered by concerns related to seeking research consent from transplant recipients. We undertook this qualitative study to elucidate solid organ transplant recipients views on organ donor research, their role in the consent for such research, and their preferences related to providing their data. We conducted interviews with 18 participants and three themes emerged from the data. The first centered around participant research literacy. The second described practical preferences of participating in research, and the third related to the connection between donor and recipient. We concluded that previously held views about the requirement for transplant recipients to have a consenting role in donor research is not always suitable.

Critical Care Cycling to Improve Lower Extremity Strength (CYCLE): protocol for an international, multicentre randomised clinical trial of early in-bed cycling for mechanically ventilated patients.

INTRODUCTION: In-bed leg cycling with critically ill patients is a promising intervention aimed at minimising immobility, thus improving physical function following intensive care unit (ICU) discharge. We previously completed a pilot randomised controlled trial (RCT) which supported the feasibility of a large RCT. In this report, we describe the protocol for an international, multicentre RCT to determine the effectiveness of early in-bed cycling versus routine physiotherapy (PT) in critically ill, mechanically ventilated adults. METHODS AND ANALYSIS: We report a parallel group RCT of 360 patients in 17 medical-surgical ICUs and three countries. We include adults (≥18 years old), who could ambulate independently before their critical illness (with or without a gait aid), ≤4 days of invasive mechanical ventilation and ≤7 days ICU length of stay, and an expected additional 2-day ICU stay, and who do not fulfil any of the exclusion criteria. After obtaining informed consent, patients are randomised using a web-based, centralised system to either 30 min of in-bed cycling in addition to routine PT, 5 days per week, up to 28 days maximum, or routine PT alone. The primary outcome is the Physical Function ICU Test-scored (PFIT-s) at 3 days post-ICU discharge measured by assessors blinded to treatment allocation. Participants, ICU clinicians and research coordinators are not blinded to group assignment. Our sample size estimate was based on the identification of a 1-point mean difference in PFIT-s between groups. ETHICS AND DISSEMINATION: Critical Care Cycling to improve Lower Extremity (CYCLE) is approved by the Research Ethics Boards of all participating centres and Clinical Trials Ontario (Project 1345). We will disseminate trial results through publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT03471247 (Full RCT); NCT02377830 (CYCLE Vanguard 46 patient internal pilot).

Neurologic Physiology after Removal of Therapy (NeuPaRT) study: study protocol of a multicentre, prospective, observational, pilot feasibility study of neurophysiology after withdrawal of life-sustaining measures.

INTRODUCTION: In donation after circulatory determination of death, death is declared 5 min after circulatory arrest. This practice assumes, but does not explicitly confirm, permanent loss of brain activity. While this assumption is rooted a strong physiological rationale, paucity of direct human data regarding temporal relationship between cessation of brain activity and circulatory arrest during the dying process threatens public and healthcare provider trust in deceased organ donation. METHODS AND ANALYSIS: In this cohort study, we will prospectively record cerebral and brainstem electrical activity, cerebral blood flow velocity and arterial blood pressure using electroencephalography (EEG), brainstem evoked potentials, transcranial doppler and bedside haemodynamic monitors in adult patients undergoing planned withdrawal of life sustaining measures in the intensive care units at five hospital sites for 18 months. We will use MATLAB to synchronise waveform data and compute the time of cessation of each signal relative to circulatory arrest. Our primary outcome is the feasibility of patient accrual, while secondary outcomes are (a) proportion of patients with complete waveform recordings and data transfer to coordinating site and (b) time difference between cessation of neurophysiological signals and circulatory arrest. We expect to accrue 1 patient/site/month for a total of 90 patients. ETHICS AND DISSEMINATION: We have ethics approval from Clinical Trials Ontario (protocol #3862, version 1.0, date 19 January 2022.) and the relevant Research Ethics Board for each site. We will obtain written informed consent from legal substitute decision makers. We will present study results at research conferences including donor family partner forum and in peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT05306327.

Vasopressin Use in the Support of Organ Donors: Physiological Rationale and Review of the Literature.

The objective of this review was to depict the physiological and clinical rationale for the use of vasopressin in hemodynamic support of organ donors. After summarizing the physiological, pharmacological concepts and preclinical findings, regarding vasopressin's pathophysiological impacts, we will present the available clinical data. DATA SOURCES: Detailed search strategies in PubMed, OVID Medline, and EMBASE were undertaken using Medical Subject Headings and Key Words. STUDY SELECTION: Physiological articles regarding brain death, and preclinical animal and human studies about the use of vasopressin or analogs, as an intervention in organ support for donation, were considered. DATA EXTRACTION: Two authors independently screened titles, abstracts, and full text of articles to determine eligibility. Data encompassing models, population, methodology, outcomes, and relevant concepts were extracted. DATA SYNTHESIS: Following brain death, profound reduction in sympathetic outflow is associated with reduced cardiac output, vascular tone, and hemodynamic instability in donors. In addition to reducing catecholamine needs and reversing diabetes insipidus, vasopressin has been shown to limit pulmonary injury and decrease systemic inflammatory response in animals. Several observational studies show the benefit of vasopressin on hemodynamic parameters and catecholamine sparing in donors. Small trials suggest that vasopressin increase organ procurement and have some survival benefit for recipients. However, the risk of bias is overall concerning, and therefore the quality of the evidence is deemed low. CONCLUSIONS: Despite potential impact on graft outcome and a protective effect through catecholamine support sparing, the benefit of vasopressin use in organ donors is based on low evidence. Well-designed observational and randomized controlled trials are warranted.

A randomized controlled trial comparing three supraglottic airway devices used as a conduit to facilitate tracheal intubation with flexible bronchoscopy.

PURPOSE: Once difficult ventilation and intubation are declared, guidelines suggest the use of a supraglottic airway (SGA) as a rescue device to ventilate and, if oxygenation is restored, subsequently as an intubation conduit. Nevertheless, few trials have formally studied recent SGA devices in patients. Our objective was to compare the efficacy of three second-generation SGA devices as conduits for bronchoscopy-guided endotracheal intubation. METHODS: In this prospective, single-blinded three-arm randomized controlled trial, patients with an American Society of Anesthesiologists Physical Status of I-III undergoing general anesthesia were randomized to bronchoscopy-guided endotracheal intubation using AuraGain™, Air-Q® Blocker, or i-gel® devices. We excluded patients with contraindications to an SGA or drugs and who were pregnant or had a neck, spine, or respiratory anomaly. The primary outcome was intubation time, measured from SGA circuit disconnection to CO2 measurement. Secondary outcomes included ease, time, and success of SGA insertion; success of intubation on first attempt; overall intubation success; number of attempts to intubate; ease of intubation; and ease of SGA removals. RESULTS: One hundred and fifty patients were enrolled from March 2017 to January 2018. Median intubation times were similar across the three groups (Air-Q Blocker, 44 sec; AuraGain, 45 sec; i-gel, 36 sec; P = 0.08). The i-gel was faster to insert (i-gel: 10 sec; Air-Q Blocker, 16 sec; AuraGain, 16 sec; P < 0.001) and easier to insert (Air-Q Blocker vs i-gel, P = 0.001; AuraGain vs i-gel, P = 0.002). Success of SGA insertion, success of intubation, and number of attempts were similar. The Air-Q Blocker was easier to remove than the i-gel (P < 0.001). CONCLUSION: All three second-generation SGA devices performed similarly regarding intubation. Despite minor benefits of the i-gel, clinicians should select their SGA based on clinical experience. STUDY REGISTRATION: ClinicalTrials.gov (NCT02975466); registered on 29 November 2016.

RéSUMé: OBJECTIF: Une fois qu'une ventilation et une intubation difficiles sont déclarées, les lignes directrices préconisent le recours à un dispositif supraglottique comme modalité de sauvetage pour ventiler le patient et, si l'oxygénation est rétablie, être ensuite utilisé comme conduit d'intubation. Toutefois, peu d'études ont formellement analysé l'utilisation des dispositifs supraglottiques récents chez de véritbales patients. Notre objectif était de comparer l'efficacité de trois dispositifs supraglottiques de deuxième génération utilisés comme conduits pour l'intubation endotrachéale guidée par bronchoscopie. MéTHODE: Dans cette étude prospective randomisée contrôlée à trois bras et à simple insu, les patients de statut physique I-III selon l'American Society of Anesthesiologists bénéficiant d'une anesthésie générale ont été randomisés à recevoir une intubation endotrachéale guidée par bronchoscopie via les dispositifs AuraGain™, Air-Q® Blocker ou i-gel®. Nous avons exclu les patients présentant des contre-indications à l'utilisation d'un dispositif supraglottique ou aux médicaments, ainsi que les patientes enceintes et les patients présentant une anomalie au niveau du cou, de la colonne vertébrale ou des voies aériennes. Le critère d'évaluation principal était le temps d'intubation mesuré entre le moment de déconnexion du dispositif supraglottique du circuit et le moment de mesure du CO2. Les critères d'évaluation secondaires comprenaient la facilité, le délai et la réussite de l'insertion du dispositif supraglottique; la réussite de l'intubation à la première tentative; la réussite globale de l'intubation; le nombre de tentatives d'intubation; la facilité d'intubation; et la facilité de retrait du dispositif supraglottique. RéSULTATS: Cent cinquante patients ont été recrutés de mars 2017 à janvier 2018. Les délais d'intubation médians étaient similaires dans les trois groupes (Air-Q Blocker : 44 sec; AuraGain : 45 sec; i-gel : 36 sec; P = 0,08). L'i-gel était plus rapide à insérer (i-gel : 10 sec; Air-Q Blocker : 16 sec; AuraGain : 16 sec; P < 0,001) et plus facile à insérer (Air-Q Blocker vs i-gel : P = 0,001; AuraGain vs i-gel : P = 0,002). La réussite de l'insertion du dispositif supraglottique, la réussite de l'intubation et le nombre de tentatives étaient similaires. L'Air-Q Blocker était plus facile à retirer que l'i-gel (P < 0,001). CONCLUSION: Les trois dispositifs supraglottiques de deuxième génération ont tous affiché une performance similaire en matière d'intubation. Malgré des avantages mineurs de l'i-gel, les cliniciens devraient choisir leur dispositif supraglottique en fonction de leur expérience clinique. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT02975466); enregistrée le 29 novembre 2016.

Self-perceived role and knowledge of community pharmacists in organ donation.

BACKGROUND: Although a majority of North Americans is in favor of organ donation, registration remains challenging. Community pharmacists are highly accessible frontline health care professionals that could contribute to a new common registration donation consent system. AIM: The objective of the study was to assess self-perceived professional role and organ donation knowledge of community pharmacists in Quebec. METHOD: We designed a telephone interview survey using a three round modified Delphi process. Following questionnaires testing, we randomly sampled 329 community pharmacists in Quebec. Following administration, we validated the questionnaire by conducting an exploratory factorial analysis using principal component followed by a varimax rotation and rearranging domains and items accordingly. RESULTS: A total of 443 pharmacists were contacted, 329 provided answers to the self-perception role and 216 of them completed the knowledge questionnaire. Overall, community pharmacists of Quebec had a positive view on organ donation and demonstrated interest in acquiring knowledge. Respondents have identified lack of time and high pharmacy attendance as non-limiting barriers to implementing the intervention. The average score on the knowledge questionnaire was 61.2%. CONCLUSION: With the implementation of an appropriate education program to address this knowledge gap, we believe that community pharmacists could be key players in registered organ donation consent.

Functional recovery with peripheral nerve block versus general anesthesia for upper limb surgery: a systematic review.

BACKGROUND: Peripheral nerve block is a common anesthetic technique used during orthopedic upper limb surgery. Injection of local anesthetics around the target nerve inhibits the action of voltage-dependent sodium channels, inhibiting neurotransmission of pain impulses and providing motor immobility. Compared to general anesthesia, it could improve functional recovery by inhibiting nociceptive impulses and inflammation, thus reducing postoperative pain and immobilization and improving postoperative rehabilitation. This systematic review evaluates the impact of peripheral nerve block versus general anesthesia on postoperative functional recovery following orthopedic upper limb surgery. METHODS: We searched CENTRAL, MEDLINE, CINHAL, EMBASE, and Scopus trial databases from inception until September 2021 for studies comparing peripheral nerve block to general anesthesia. We collected data on functional recovery, range of motion, patient satisfaction, quality of life, and return to work. We pooled studies using a random-effects model and summarized the quality of evidence with the GRADE approach. RESULTS: We assessed 373 citations and 19 full-text articles for eligibility, and included six studies. Six studies reported on functional recovery, but failed to detect a significant superiority of peripheral nerve block over general anesthesia (3 RCT studies, N = 160; SMD -0.15; CI at 95% -0.60-0.3; I2 = 45%; p = 0.07; low quality of evidence and 3 observational studies, N = 377; SMD -0.35; CI at 95% -0.71-0.01; I2 = 64%; p = 0.06; very low quality of evidence). CONCLUSIONS: Current literature is limited and fails to identify the benefit of peripheral nerve block on functional recovery. More studies are needed to assess the impact on long-term recovery. Considering the potential impact on clinical practice and training, a prospective study on functional recovery is ongoing (NCT04541745). TRIAL REGISTRATION: PROSPERO ID CRD42018116298. Registered on December 4, 2018.

Effect of perioperative benzodiazepine use on intraoperative awareness and postoperative delirium: a systematic review and meta-analysis of randomised controlled trials and observational studies.

BACKGROUND: Benzodiazepine use is associated with delirium, and guidelines recommend avoiding them in older and critically ill patients. Their perioperative use remains common because of perceived benefits. METHODS: We searched CENTRAL, MEDLINE, CINAHL, PsycInfo, and Web of Science from inception to June 2021. Pairs of reviewers identified randomised controlled trials and prospective observational studies comparing perioperative use of benzodiazepines with other agents or placebo in patients undergoing surgery. Two reviewers independently abstracted data, which we combined using a random-effects model. Our primary outcomes were delirium, intraoperative awareness, and mortality. RESULTS: We included 34 randomised controlled trials (n=4354) and nine observational studies (n=3309). Observational studies were considered separately. Perioperative benzodiazepines did not increase the risk of delirium (n=1352; risk ratio [RR] 1.43; 95% confidence interval [CI]: 0.9-2.27; I2=72%; P=0.13; very low-quality evidence). Use of benzodiazepines instead of dexmedetomidine did, however, increase the risk of delirium (five studies; n=429; RR 1.83; 95% CI: 1.24-2.72; I2=13%; P=0.002). Perioperative benzodiazepine use decreased the risk of intraoperative awareness (n=2245; RR 0.26; 95% CI: 0.12-0.58; I2=35%; P=0.001; very low-quality evidence). When considering non-events, perioperative benzodiazepine use increased the probability of not having intraoperative awareness (RR 1.07; 95% CI: 1.01-1.13; I2=98%; P=0.03; very low-quality evidence). Mortality was reported by one randomised controlled trial (n=800; RR 0.90; 95% CI: 0.20-3.1; P=0.80; very low quality). CONCLUSIONS: In this systematic review and meta-analysis, perioperative benzodiazepine use did not increase postoperative delirium and decreased intraoperative awareness. Previously observed relationships of benzodiazepine use with delirium could be explained by comparisons with dexmedetomidine. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42019128144.