Liberal or Restrictive Transfusion Strategy in Patients with Traumatic Brain Injury.

BACKGROUND: The effect of a liberal transfusion strategy as compared with a restrictive strategy on outcomes in critically ill patients with traumatic brain injury is unclear. METHODS: We randomly assigned adults with moderate or severe traumatic brain injury and anemia to receive transfusion of red cells according to a liberal strategy (transfusions initiated at a hemoglobin level of ≤10 g per deciliter) or a restrictive strategy (transfusions initiated at ≤7 g per deciliter). The primary outcome was an unfavorable outcome as assessed by the score on the Glasgow Outcome Scale-Extended at 6 months, which we categorized with the use of a sliding dichotomy that was based on the prognosis of each patient at baseline. Secondary outcomes included mortality, functional independence, quality of life, and depression at 6 months. RESULTS: A total of 742 patients underwent randomization, with 371 assigned to each group. The analysis of the primary outcome included 722 patients. The median hemoglobin level in the intensive care unit was 10.8 g per deciliter in the group assigned to the liberal strategy and 8.8 g per deciliter in the group assigned to the restrictive strategy. An unfavorable outcome occurred in 249 of 364 patients (68.4%) in the liberal-strategy group and in 263 of 358 (73.5%) in the restrictive-strategy group (adjusted absolute difference, restrictive strategy vs. liberal strategy, 5.4 percentage points; 95% confidence interval, -2.9 to 13.7). Among survivors, a liberal strategy was associated with higher scores on some but not all the scales assessing functional independence and quality of life. No association was observed between the transfusion strategy and mortality or depression. Venous thromboembolic events occurred in 8.4% of the patients in each group, and acute respiratory distress syndrome occurred in 3.3% and 0.8% of patients in the liberal-strategy and restrictive-strategy groups, respectively. CONCLUSIONS: In critically ill patients with traumatic brain injury and anemia, a liberal transfusion strategy did not reduce the risk of an unfavorable neurologic outcome at 6 months. (Funded by the Canadian Institutes of Health Research and others; HEMOTION ClinicalTrials.gov number, NCT03260478.).

Effect of Donor Sex on Recipient Mortality in Transfusion.

BACKGROUND: Conflicting observational evidence exists regarding the association between the sex of red-cell donors and mortality among transfusion recipients. Evidence to inform transfusion practice and policy is limited. METHODS: In this multicenter, double-blind trial, we randomly assigned patients undergoing red-cell transfusion to receive units of red cells from either male donors or female donors. Patients maintained their trial-group assignment throughout the trial period, including during subsequent inpatient and outpatient encounters. Randomization was conducted in a 60:40 ratio (male donor group to female donor group) to match the historical allocation of red-cell units from the blood supplier. The primary outcome was survival, with the male donor group as the reference group. RESULTS: A total of 8719 patients underwent randomization before undergoing transfusion; 5190 patients were assigned to the male donor group, and 3529 to the female donor group. At baseline, the mean (±SD) age of the enrolled patients was 66.8±16.4 years. The setting of the first transfusion was as an inpatient in 6969 patients (79.9%), of whom 2942 (42.2%) had been admitted under a surgical service. The baseline hemoglobin level before transfusion was 79.5±19.7 g per liter, and patients received a mean of 5.4±10.5 units of red cells in the female donor group and 5.1±8.9 units in the male donor group (difference, 0.3 units; 95% confidence interval [CI], -0.1 to 0.7). Over the duration of the trial, 1141 patients in the female donor group and 1712 patients in the male donor group died. In the primary analysis of overall survival, the adjusted hazard ratio for death was 0.98 (95% CI, 0.91 to 1.06). CONCLUSIONS: This trial showed no significant difference in survival between a transfusion strategy involving red-cell units from female donors and a strategy involving red-cell units from male donors. (Funded by the Canadian Institutes of Health Research; iTADS ClinicalTrials.gov number, NCT03344887.).

Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit.

BACKGROUND: Studies that have evaluated the use of intravenous vitamin C in adults with sepsis who were receiving vasopressor therapy in the intensive care unit (ICU) have shown mixed results with respect to the risk of death and organ dysfunction. METHODS: In this randomized, placebo-controlled trial, we assigned adults who had been in the ICU for no longer than 24 hours, who had proven or suspected infection as the main diagnosis, and who were receiving a vasopressor to receive an infusion of either vitamin C (at a dose of 50 mg per kilogram of body weight) or matched placebo administered every 6 hours for up to 96 hours. The primary outcome was a composite of death or persistent organ dysfunction (defined by the use of vasopressors, invasive mechanical ventilation, or new renal-replacement therapy) on day 28. RESULTS: A total of 872 patients underwent randomization (435 to the vitamin C group and 437 to the control group). The primary outcome occurred in 191 of 429 patients (44.5%) in the vitamin C group and in 167 of 434 patients (38.5%) in the control group (risk ratio, 1.21; 95% confidence interval [CI], 1.04 to 1.40; P = 0.01). At 28 days, death had occurred in 152 of 429 patients (35.4%) in the vitamin C group and in 137 of 434 patients (31.6%) in the placebo group (risk ratio, 1.17; 95% CI, 0.98 to 1.40) and persistent organ dysfunction in 39 of 429 patients (9.1%) and 30 of 434 patients (6.9%), respectively (risk ratio, 1.30; 95% CI, 0.83 to 2.05). Findings were similar in the two groups regarding organ-dysfunction scores, biomarkers, 6-month survival, health-related quality of life, stage 3 acute kidney injury, and hypoglycemic episodes. In the vitamin C group, one patient had a severe hypoglycemic episode and another had a serious anaphylaxis event. CONCLUSIONS: In adults with sepsis receiving vasopressor therapy in the ICU, those who received intravenous vitamin C had a higher risk of death or persistent organ dysfunction at 28 days than those who received placebo. (Funded by the Lotte and John Hecht Memorial Foundation; LOVIT ClinicalTrials.gov number, NCT03680274.).

Resumption of Cardiac Activity after Withdrawal of Life-Sustaining Measures.

BACKGROUND: The minimum duration of pulselessness required before organ donation after circulatory determination of death has not been well studied. METHODS: We conducted a prospective observational study of the incidence and timing of resumption of cardiac electrical and pulsatile activity in adults who died after planned withdrawal of life-sustaining measures in 20 intensive care units in three countries. Patients were intended to be monitored for 30 minutes after determination of death. Clinicians at the bedside reported resumption of cardiac activity prospectively. Continuous blood-pressure and electrocardiographic (ECG) waveforms were recorded and reviewed retrospectively to confirm bedside observations and to determine whether there were additional instances of resumption of cardiac activity. RESULTS: A total of 1999 patients were screened, and 631 were included in the study. Clinically reported resumption of cardiac activity, respiratory movement, or both that was confirmed by waveform analysis occurred in 5 patients (1%). Retrospective analysis of ECG and blood-pressure waveforms from 480 patients identified 67 instances (14%) with resumption of cardiac activity after a period of pulselessness, including the 5 reported by bedside clinicians. The longest duration after pulselessness before resumption of cardiac activity was 4 minutes 20 seconds. The last QRS complex coincided with the last arterial pulse in 19% of the patients. CONCLUSIONS: After withdrawal of life-sustaining measures, transient resumption of at least one cycle of cardiac activity after pulselessness occurred in 14% of patients according to retrospective analysis of waveforms; only 1% of such resumptions were identified at the bedside. These events occurred within 4 minutes 20 seconds after a period of pulselessness. (Funded by the Canadian Institutes for Health Research and others.).

Quality of life and cost-effectiveness of convalescent plasma compared to standard care for hospitalized COVID-19 patients in the CONCOR-1 trial.

BACKGROUND: The CONvalescent Plasma for Hospitalized Adults With COVID-19 Respiratory Illness (CONCOR-1) trial was a multicenter randomized controlled trial assessing convalescent plasma in hospitalized COVID-19 patients. This study evaluates the cost-effectiveness of convalescent plasma and its impact on quality-of-life to provide insight into its potential as an alternative treatment in resource-constrained settings. METHODS: Individual patient data on health outcomes and resource utilization from the CONCOR-1 trial were used to conduct the analysis from the Canadian public payer's perspective with a time horizon of 30 days post-randomization. Baseline and 30-day EQ-5D-5L were measured to calculate quality-adjusted survival. All costs are presented in 2021 Canadian dollars. The base case assessed the EQ-5D-5L scores of hospitalized inpatients reporting at both timepoints, and a utility score of 0 was assigned for patients who died within 30 days. Costs for all patients enrolled were used. The sensitivity analysis utilizes EQ-5D-5L scores from the same population but only uses costs from this population. RESULTS: 940 patients were randomized: 627 received CCP and 313 received standard care. The total costs were $28,716 (standard deviation, $25,380) and $24,258 ($22,939) for the convalescent plasma and standard care arms respectively. EQ-5D-5L scores were 0.61 in both arms (p = .85) at baseline. At 30 days, EQ-5D-5L scores were 0.63 and 0.64 for patients in the convalescent plasma and standard care arms, respectively (p = .46). The incremental cost was $4458 and the incremental quality-adjusted life day was -0.078. DISCUSSION: Convalescent plasma was less effective and more costly than standard care in treating hospitalized COVID-19.

Transbronchial Lung Cryobiopsies, Transbronchial Forceps Lung Biopsies, and Surgical Lung Biopsies in Mechanically Ventilated Patients with Acute Hypoxemic Respiratory Failure: A Retrospective Cohort Study.

IMPORTANCE: Lung biopsies are sometimes performed in mechanically ventilated patients with acute hypoxemic respiratory failure (AHRF) of unknown etiology to guide patient management. While surgical lung biopsies (SLB) offer high diagnostic rates, they may also cause significant complications. Transbronchial forceps lung biopsies (TBLB) are less invasive but often produce non-contributive specimens. Transbronchial lung cryobiopsies (TBLC) yield specimens of potentially better quality than TBLB, but due to their novel implementation in the intensive care unit (ICU), their accuracy and safety are still unclear. OBJECTIVES: Our main objective was to evaluate the risk of adverse events in patients with AHRF following the three biopsy techniques. Our secondary objectives were to assess the diagnostic yield and associated modifications of patient management of each technique. DESIGN, SETTINGS AND PARTICIPANTS: We conducted a retrospective cohort study comparing TBLC, TBLB, and SLB in mechanically ventilated patients with AHRF. MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of patients with at least one complication, and secondary outcomes included complication rates, diagnostic yields, treatment modifications, and mortality. RESULTS: Of the 26 patients who underwent lung biopsies from 2018 to 2022, all TBLC and SLB patients and 60% of TBLB patients had at least one complication. TBLC patients had higher unadjusted numbers of total and severe complications, but also worse Sequential Organ Failure Assessment scores and P/F ratios. A total of 25 biopsies (25/26, 96%) provided histopathological diagnoses, 88% (22/25) of which contributed to patient management. ICU mortality was high for all modalities (63% for TBLC, 60% for TBLB and 50% for SLB). CONCLUSIONS AND RELEVANCE: All biopsy methods had high diagnostic yields and the great majority contributed to patient management; however, complication rates were elevated. Further research is needed to determine which patients may benefit from lung biopsies and to determine the best biopsy modality.

Comparison of Radiologists and Deep Learning for US Grading of Hepatic Steatosis.

Background Screening for nonalcoholic fatty liver disease (NAFLD) is suboptimal due to the subjective interpretation of US images. Purpose To evaluate the agreement and diagnostic performance of radiologists and a deep learning model in grading hepatic steatosis in NAFLD at US, with biopsy as the reference standard. Materials and Methods This retrospective study included patients with NAFLD and control patients without hepatic steatosis who underwent abdominal US and contemporaneous liver biopsy from September 2010 to October 2019. Six readers visually graded steatosis on US images twice, 2 weeks apart. Reader agreement was assessed with use of κ statistics. Three deep learning techniques applied to B-mode US images were used to classify dichotomized steatosis grades. Classification performance of human radiologists and the deep learning model for dichotomized steatosis grades (S0, S1, S2, and S3) was assessed with area under the receiver operating characteristic curve (AUC) on a separate test set. Results The study included 199 patients (mean age, 53 years ± 13 [SD]; 101 men). On the test set (n = 52), radiologists had fair interreader agreement (0.34 [95% CI: 0.31, 0.37]) for classifying steatosis grades S0 versus S1 or higher, while AUCs were between 0.49 and 0.84 for radiologists and 0.85 (95% CI: 0.83, 0.87) for the deep learning model. For S0 or S1 versus S2 or S3, radiologists had fair interreader agreement (0.30 [95% CI: 0.27, 0.33]), while AUCs were between 0.57 and 0.76 for radiologists and 0.73 (95% CI: 0.71, 0.75) for the deep learning model. For S2 or lower versus S3, radiologists had fair interreader agreement (0.37 [95% CI: 0.33, 0.40]), while AUCs were between 0.52 and 0.81 for radiologists and 0.67 (95% CI: 0.64, 0.69) for the deep learning model. Conclusion Deep learning approaches applied to B-mode US images provided comparable performance with human readers for detection and grading of hepatic steatosis. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Tuthill in this issue.

Trajectories of health-related quality of life and their predictors in adult COVID-19 survivors: A longitudinal analysis of the Biobanque Québécoise de la COVID-19 (BQC-19).

PURPOSE: A significant number of people will experience prolonged symptoms after COVID-19 infection that will greatly impact functional capacity and quality of life. The aim of this study was to identify trajectories of health-related quality of life (HRQOL) and their predictors among adults diagnosed with COVID-19. METHODS: This is a retrospective analysis of an ongoing prospective cohort study (BQC-19) including adults (≥18y) recruited from April 2020 to March 2022. Our primary outcome is HRQOL using the EQ-5D-5L scale. Sociodemographic, acute disease severity, vaccination status, fatigue, and functional status at onset of the disease were considered as potential predictors. The latent class mixed model was used to identify the trajectories over an 18-month period in the cohort as a whole, as well as in the inpatient and outpatient subgroups. Multivariable and univariable regressions models were undertaken to detect predictors of decline. RESULTS: 2163 participants were included. Thirteen percent of the outpatient subgroup (2 classes) and 28% in the inpatient subgroup (3 classes) experienced a more significant decline in HRQOL over time than the rest of the participants. Among all patients, age, sex, disease severity and fatigue, measured on the first assessment visit or on the first day after hospital admission (multivariable models), were identified as the most important predictors of HRQOL decline. Each unit increase in the SARC-F and CFS scores increase the likelihood of belonging to the declining trajectory (univariable models). CONCLUSION: Although to different degrees, similar factors explain the decline in HRQOL over time among the overall population, people who have been hospitalized or not. Clinical functional capacity scales could help to determine the risk of HRQOL decline.

The reticular activating system: a narrative review of discovery, evolving understanding, and relevance to current formulations of brain death.

A series of landmark experiments conducted throughout the 20th century progressively localized the regions involved in consciousness to the reticular activating system (RAS) and its ascending projections. The first description of the RAS emerged in 1949 through seminal experiments performed by Moruzzi and Magoun in feline brainstems; additional experiments in the 1950s revealed connections between the RAS and the thalamus and neocortical structures. This knowledge has allowed for the explanation of disorders of consciousness with exquisite anatomic precision. The clinical relevance of the RAS is further apparent in modern definitions of brain death/death by neurologic criteria (BD/DNC), which require demonstration of the complete and permanent loss of capacity for consciousness as one of their core criteria. BD/DNC is currently understood across jurisdictions in terms of "whole brain" and "brainstem" formulations. Although their clinical examination between formulations is indistinguishable, policies for BD/DNC declaration may differ in the rare scenario of patients with isolated infratentorial brain injuries, in which ancillary testing is advised in the whole brain formulation but not the brainstem formulation. Canadian guidelines acknowledge that the distinction between whole brain and brainstem formulations is unclear with respect to clinical implications for patients with isolated infratentorial injuries. This has led to variability in Canadian clinicians' use of ancillary testing when the mechanism of BD/DNC is suspected to be an isolated infratentorial injury. The present narrative review highlights these concepts and explores implications for determination of BD/DNC in Canada, with specific emphasis on the RAS and its relevance to both formulations.

RéSUMé: Une série d'expériences marquantes menées tout au long du 20e siècle a progressivement permis de localiser les régions impliquées dans la conscience dans le système d'activation réticulaire (SAR) et ses projections ascendantes. La première description du SAR a vu le jour en 1949 grâce à des expériences fondatrices réalisées par Moruzzi et Magoun dans des troncs cérébraux félins; d'autres expériences menées au cours des années 1950 ont révélé des liens entre le SAR et le thalamus et les structures néocorticales. Ces connaissances ont permis d'expliquer les troubles de la conscience avec une précision anatomique extraordinaire. La pertinence clinique du SAR est encore plus évidente dans les définitions modernes de la mort cérébrale / du décès déterminé par des critères neurologiques (MC/DCN), qui exigent la démonstration de la perte complète et permanente de la capacité de conscience comme l'un de ses critères de base. La mort cérébrale est actuellement comprise partout en termes de formulations de « cerveau entier ¼ et de « tronc cérébral ¼. Bien que l'examen clinique ne fasse pas de distinction entre ces formulations, les politiques de déclaration de MC/DCN peuvent différer dans le rare cas de patients présentant des lésions cérébrales infratentorielles isolées, pour lesquels des examens auxiliaires sont conseillés lorsqu'on parle de cerveau entier mais pas lorsqu'on utilise la formulation de tronc cérébral. Les lignes directrices canadiennes reconnaissent que la distinction entre les termes de cerveau entier et de tronc cérébral n'est pas claire en ce qui concerne leurs implications cliniques pour les patients présentant des lésions infratentorielles isolées. Cela a entraîné une variabilité dans l'utilisation des examens auxiliaires par les cliniciens canadiens lorsqu'ils soupçonnent que le mécanisme de MC/DCN consiste en une lésion infratentorielle isolée. Ce compte rendu narratif met en lumière ces concepts et explore les implications pour la détermination de la MC/DCN au Canada, en mettant une emphase spécifique sur le SAR et sa pertinence pour les deux formulations.

Infratentorial brain injury and death by neurologic criteria in Canada: a narrative review.

There are two anatomic formulations of death by neurologic criteria accepted worldwide: whole-brain death and brainstem death. As part of the Canadian Death Definition and Determination Project, we convened an expert working group and performed a narrative review of the literature. Infratentorial brain injury (IBI) with an unconfounded clinical assessment consistent with death by neurologic criteria represents a nonrecoverable injury. The clinical determination of death cannot distinguish between IBI and whole-brain cessation of function. Current clinical, functional, and neuroimaging assessments cannot reliably confirm the complete and permanent destruction of the brainstem. No patient with isolated brainstem death has been reported to recover consciousness and all patients have died. Studies suggest a significant majority of isolated brainstem death will evolve into whole-brain death, influenced by time/duration of somatic support and impacted by ventricular drainage and/or posterior fossa decompressive craniectomy. Acknowledging variability in intensive care unit (ICU) physician opinion on this matter, a majority of Canadian ICU physicians would perform ancillary testing for death determination by neurologic criteria in the context of IBI. There is currently no reliable ancillary test to confirm complete destruction of the brainstem; ancillary testing currently includes evaluation of both infratentorial and supratentorial flow. Acknowledging international variability in this regard, the existing evidence reviewed does not provide sufficient confidence that the clinical exam in IBI represents a complete and permanent destruction of the reticular activating system and thus the capacity for consciousness. On this basis, IBI consistent with clinical signs of death by neurologic criteria without significant supratentorial involvement does not fulfill criteria for death in Canada and ancillary testing is required.

RéSUMé: Il existe deux formulations anatomiques du décès selon des critères neurologiques acceptés dans le monde entier : la mort du cerveau entier et la mort du tronc cérébral. Dans le cadre du Projet canadien de définition et de détermination du décès, nous avons réuni un groupe de travail composé d'experts et réalisé un compte rendu narratif de la littérature. Une lésion cérébrale infratentorielle (LCI) avec une évaluation clinique sans facteur confondant et compatible avec un décès selon des critères neurologiques représente une atteinte irrécupérable. La détermination clinique du décès ne permet pas de faire la distinction entre une LCI et l'arrêt de la fonction dans le cerveau entier. Les évaluations cliniques, fonctionnelles et de neuroimagerie actuelles ne peuvent pas confirmer de manière fiable la destruction complète et permanente du tronc cérébral. La récupération de la conscience n'a jamais été signalée chez aucun patient présentant une mort isolée du tronc cérébral, et tous les patients sont décédés. Des études suggèrent qu'une majorité significative des morts isolées du tronc cérébral évolueront vers la mort cérébrale entière, étant influencées par le temps et la durée de l'assistance somatique et impactées par le drainage ventriculaire et/ou la craniectomie décompressive de la fosse postérieure. Compte tenu de la variabilité des opinions des médecins intensivistes à ce sujet, la majorité des médecins intensivistes canadiens réaliseraient des examens auxiliaires pour déterminer le décès selon des critères neurologiques dans le contexte d'une LCI. Il n'existe actuellement aucun examen auxiliaire fiable pour confirmer la destruction complète du tronc cérébral; les examens auxiliaires comprennent actuellement l'évaluation de la circulation infratentorielle et supratentorielle. Reconnaissant la variabilité internationale à cet égard, les données probantes existantes passées en revue ne sont pas suffisamment fiables pour affirmer que l'examen clinique en cas de LCI représente une destruction complète et permanente du système d'activation réticulaire et donc de la capacité de conscience. En se fondant sur cette base, une LCI compatible avec les signes cliniques d'un décès selon des critères neurologiques sans atteinte supratentorielle significative ne répond pas aux critères de décès au Canada et un examen auxiliaire est requis.

Ancillary investigations for death determination in infants and children: a systematic review and meta-analysis.

PURPOSE: We performed a systematic review and meta-analysis to determine the diagnostic test accuracy of ancillary investigations for declaration of death by neurologic criteria (DNC) in infants and children. SOURCE: We searched MEDLINE, EMBASE, Web of Science, and Cochrane databases from their inception to June 2021 for relevant randomized controlled trials, observational studies, and abstracts published in the last three years. We identified relevant studies using Preferred Reporting Items for Systematic Reviews and Meta-Analysis methodology and a two-stage review. We assessed the risk of bias using the QUADAS-2 tool, and applied Grading of Recommendations Assessment, Development, and Evaluation methodology to determine the certainty of evidence. A fixed-effects model was used to meta-analyze pooled sensitivity and specificity data for each ancillary investigation with at least two studies. PRINCIPAL FINDINGS: Thirty-nine eligible manuscripts assessing 18 unique ancillary investigations (n = 866) were identified. The sensitivity and specificity ranged from 0.00 to 1.00 and 0.50 to 1.00, respectively. The quality of evidence was low to very low for all ancillary investigations, with the exception of radionuclide dynamic flow studies for which it was graded as moderate. Radionuclide scintigraphy using the lipophilic radiopharmaceutical 99mTc-hexamethylpropyleneamine oxime (HMPAO) with or without tomographic imaging were the most accurate ancillary investigations with a combined sensitivity of 0.99 (95% highest density interval [HDI], 0.89 to 1.00) and specificity of 0.97 (95% HDI, 0.65 to 1.00). CONCLUSION: The ancillary investigation for DNC in infants and children with the greatest accuracy appears to be radionuclide scintigraphy using HMPAO with or without tomographic imaging; however, the certainty of the evidence is low. Nonimaging modalities performed at the bedside require further investigation. STUDY REGISTRATION: PROSPERO (CRD42021278788); registered 16 October 2021.

RéSUMé: OBJECTIF: Nous avons réalisé une revue systématique et une méta-analyse pour déterminer la précision des tests diagnostiques des examens auxiliaires pour la déclaration du décès selon des critères neurologiques (DCN) chez les nourrissons et les enfants. SOURCES: Nous avons effectué des recherches dans les bases de données MEDLINE, EMBASE, Web of Science et Cochrane de leur création jusqu'en juin 2021 pour trouver des études randomisées contrôlées, des études observationnelles et des résumés pertinents publiés au cours des trois dernières années. Nous avons identifié les études pertinentes utilisant la méthodologie PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) et une revue en deux étapes. Nous avons évalué le risque de biais en utilisant l'outil QUADAS-2 et appliqué la méthodologie GRADE (Grading of Recommendations Assessment, Development and Evaluation) afin d'évaluer la certitude des données probantes. Un modèle à effets fixes a été utilisé pour méta-analyser les données de sensibilité et de spécificité regroupées pour chaque examen auxiliaire avec au moins deux études. CONSTATATIONS PRINCIPALES: Trente-neuf manuscrits admissibles évaluant 18 examens auxiliaires uniques (n = 866) ont été identifiés. La sensibilité et la spécificité variaient de 0,00 à 1,00 et de 0,50 à 1,00, respectivement. La qualité des données probantes était faible à très faible pour tous les examens auxiliaires, à l'exception des études de circulation nucléaire dynamique, pour lesquelles elle a été classée comme modérée. La scintigraphie nucléaire à l'aide du produit radiopharmaceutique lipophile 99mTc- hexa-méthyl-propylène amine oxime (HMPAO) avec ou sans imagerie tomographique était à la base des examens auxiliaires les plus précis, avec une sensibilité combinée de 0,99 (intervalle de densité le plus élevé [IDE] à 95 %, 0,89 à 1,00) et une spécificité de 0,97 (IDE à 95 %, 0,65 à 1,00). CONCLUSION: L'examen auxiliaire pour un DCN chez les nourrissons et les enfants offrant la plus grande précision semble être la scintigraphie nucléaire utilisant le HMPAO avec ou sans imagerie tomographique; cependant, la certitude des données probantes est faible. Les modalités sans imagerie réalisées au chevet du patient nécessitent un examen plus approfondi. Enregistrement de l'étude: PROSPERO (CRD42021278788); enregistrée le 16 octobre 2021.

Diagnostic accuracy of ancillary tests for death by neurologic criteria: a systematic review and meta-analysis.

PURPOSE: Ancillary tests are frequently used in death determination by neurologic criteria (DNC), particularly when the clinical neurologic examination is unreliable. Nevertheless, their diagnostic accuracy has not been extensively studied. Our objective was to synthesize the sensitivity and specificity of commonly used ancillary tests for DNC. SOURCE: We performed a systematic review and meta-analysis by searching MEDLINE, EMBASE, Cochrane databases, and CINAHL Ebsco from their inception to 4 February 2022. We selected cohort and case-control studies including patients with 1) clinically diagnosed death by neurologic criteria or 2) clinically suspected death by neurologic criteria who underwent ancillary testing for DNC. We excluded studies without a priori diagnostic criteria and studies conducted solely on pediatric patients. Accepted reference standards were clinical examination, four-vessel conventional angiography, and radionuclide imaging. Data were directly extracted from published reports. We assessed the methodological quality of studies with the QUADAS-2 tool and estimated ancillary test sensitivities and specificities using hierarchical Bayesian models with diffuse priors. PRINCIPAL FINDINGS: Overall, 137 records met the selection criteria. One study (0.7%) had a low risk of bias in all QUADAS-2 domains. Among clinically diagnosed death by neurologic criteria patients (n = 8,891), ancillary tests had similar pooled sensitivities (range, 0.82-0.93). Sensitivity heterogeneity was greater within (σ = 0.10-0.15) than between (σ = 0.04) ancillary test types. Among clinically suspected death by neurologic criteria patients (n = 2,732), pooled ancillary test sensitivities ranged between 0.81 and 1.00 and specificities between 0.87 and 1.00. Most estimates had high statistical uncertainty. CONCLUSION: Studies assessing ancillary test diagnostic accuracy have an unclear or high risk of bias. High-quality studies are required to thoroughly validate ancillary tests for DNC. STUDY REGISTRATION: PROSPERO (CRD42013005907); registered 7 October 2013.

RéSUMé: OBJECTIF: Les examens auxiliaires sont fréquemment utilisés dans la détermination du décès selon des critères neurologiques (DCN), en particulier lorsque l'examen neurologique clinique n'est pas fiable. Néanmoins, leur précision diagnostique n'a pas été étudiée de manière approfondie. Notre objectif était de synthétiser la sensibilité et la spécificité des examens auxiliaires couramment utilisés pour la DCN. SOURCES: Nous avons réalisé une revue systématique et une méta-analyse en effectuant des recherches dans les bases de données MEDLINE, EMBASE, Cochrane et CINAHL Ebsco de leur création jusqu'au 4 février 2022. Nous avons sélectionné des études de cohorte et cas témoins incluant des patients présentant 1) un décès selon des critères neurologiques diagnostiqué cliniquement ou 2) un décès selon des critères neurologiques soupçonné cliniquement qui ont été soumis à des examens auxiliaires pour un DCN. Nous avons exclu les études sans critères diagnostiques a priori et les études menées uniquement auprès de patients pédiatriques. Les normes de référence acceptées étaient l'examen clinique, l'angiographie conventionnelle à quatre vaisseaux et l'imagerie nucléaire. Les données ont été directement extraites de comptes rendus publiés. Nous avons évalué la qualité méthodologique des études avec l'outil QUADAS-2 et estimé les sensibilités et les spécificités des examens auxiliaires à l'aide de modèles hiérarchiques bayésiens avec des distributions préalables diffuses. CONSTATATIONS PRINCIPALES: Au total, 137 études répondaient aux critères de sélection. Une étude (0,7 %) présentait un faible risque de biais dans tous les domaines de QUADAS-2. Parmi les patients ayant reçu un diagnostic clinique de décès selon des critères neurologiques (n = 8891), les examens auxiliaires présentaient des sensibilités combinées similaires (intervalle de 0,82 à 0,93). L'hétérogénéité de sensibilité était plus grande au sein (σ = 0,10-0,15) plutôt qu'entre (σ = 0,04) les types d'examens auxiliaires. Parmi les patients cliniquement soupçonnés de décès selon des critères neurologiques (n = 2732), les sensibilités combinées des examens auxiliaires variaient entre 0,81 et 1,00 et les spécificités entre 0,87 et 1,00. La plupart des estimations comportaient une grande incertitude statistique. CONCLUSION: Les études évaluant la précision diagnostique des examens auxiliaires présentent un risque de biais incertain ou élevé. Des études de haute qualité sont nécessaires pour valider en profondeur les examens auxiliaires pour la DCN. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42013005907); enregistrée le 7 octobre 2013.

Perioperative clinical practice in liver transplantation: a cross-sectional survey.

PURPOSE: The objective of this study was to describe some components of the perioperative practice in liver transplantation as reported by clinicians. METHODS: We conducted a cross-sectional clinical practice survey using an online instrument containing questions on selected themes related to the perioperative care of liver transplant recipients. We sent email invitations to Canadian anesthesiologists, Canadian surgeons, and French anesthesiologists specialized in liver transplantation. We used five-point Likert-type scales (from "never" to "always") and numerical or categorical answers. Results are presented as medians or proportions. RESULTS: We obtained answers from 130 participants (estimated response rate of 71% in Canada and 26% in France). Respondents reported rarely using transesophageal echocardiography routinely but often using it for hemodynamic instability, often using an intraoperative goal-directed hemodynamic management strategy, and never using a phlebotomy (medians from ordinal scales). Fifty-nine percent of respondents reported using a restrictive fluid management strategy to manage hemodynamic instability during the dissection phase. Forty-two percent and 15% of respondents reported using viscoelastic tests to guide intraoperative and postoperative transfusions, respectively. Fifty-four percent of respondents reported not pre-emptively treating preoperative coagulations disturbances, and 91% reported treating them intraoperatively only when bleeding was significant. Most respondents (48-64%) did not have an opinion on the maximal graft ischemic times. Forty-seven percent of respondents reported that a piggyback technique was the preferred vena cava anastomosis approach. CONCLUSION: Different interventions were reported to be used regarding most components of perioperative care in liver transplantation. Our results suggest that significant equipoise exists on the optimal perioperative management of this population.

RéSUMé: OBJECTIF: L'objectif de cette étude était de décrire certaines composantes de la pratique périopératoire en transplantation hépatique telles que rapportées par les cliniciens. MéTHODE: Nous avons mené un sondage transversal sur la pratique clinique à l'aide d'un instrument en ligne comportant des questions sur des thèmes sélectionnés liés aux soins périopératoires des receveurs de greffe du foie. Nous avons envoyé des invitations par courriel à des anesthésiologistes canadiens, des chirurgiens canadiens et des anesthésiologistes français spécialisés en transplantation hépatique. Nous avons utilisé des échelles de type Likert à cinq points (de « jamais ¼ à « toujours ¼) et des réponses numériques ou catégorielles. Les résultats sont présentés sous forme de médianes ou de proportions. RéSULTATS: Nous avons obtenu des réponses de 130 participants (taux de réponse estimé à 71 % au Canada et à 26 % en France). Les répondants ont déclaré utiliser rarement l'échocardiographie transœsophagienne de routine, mais l'utiliser fréquemment pour l'instabilité hémodynamique, souvent en utilisant une stratégie de prise en charge hémodynamique peropératoire axée sur les objectifs, et jamais en utilisant une phlébotomie (médianes des échelles ordinales). Cinquante-neuf pour cent des répondants ont déclaré utiliser une stratégie restrictive de gestion liquidienne pour prendre en charge l'instabilité hémodynamique pendant la phase de dissection. Quarante-deux pour cent et 15 % des répondants ont déclaré utiliser des tests viscoélastiques pour guider les transfusions peropératoires et postopératoires, respectivement. Cinquante-quatre pour cent des répondants ont déclaré ne pas traiter préventivement les troubles préopératoires de la coagulation, et 91 % ont déclaré les traiter en peropératoire uniquement lorsque les saignements étaient importants. La plupart des répondants (48-64 %) n'avaient pas d'opinion sur les temps ischémiques maximaux du greffon. Quarante-sept pour cent des répondants ont déclaré qu'une technique de 'piggyback' (anastomose latéroterminale) était l'approche préférée pour l'anastomose de la veine cave. CONCLUSION: Différentes interventions ont été signalées pour la plupart des composantes des soins périopératoires dans la transplantation hépatique. Nos résultats suggèrent qu'il existe une incertitude significative concernant la prise en charge périopératoire optimale de cette population.

Death determination by neurologic criteria-what do families understand?

PURPOSE: Currently, there is little empirical data on family understanding about brain death and death determination. The purpose of this study was to describe family members' (FMs') understanding of brain death and the process of determining death in the context of organ donation in Canadian intensive care units (ICUs). METHODS: We conducted a qualitative study using semistructured, in-depth interviews with FMs who were asked to make an organ donation decision on behalf of adult or pediatric patients with death determination by neurologic criteria (DNC) in Canadian ICUs. RESULTS: From interviews with 179 FMs, six main themes emerged: 1) state of mind, 2) communication, 3) DNC may be counterintuitive, 4) preparation for the DNC clinical assessment, 5) DNC clinical assessment, and 6) time of death. Recommendations on how clinicians can help FMs to understand and accept DNC through communication at key moments were described including preparing FMs for death determination, allowing FMs to be present, and explaining the legal time of death, combined with multimodal strategies. For many FMs, understanding of DNC unfolded over time, facilitated with repeated encounters and explanation, rather than during a single meeting. CONCLUSION: Family members' understanding of brain death and death determination represented a journey that they reported in sequential meeting with health care providers, most notably physicians. Modifiable factors to improve communication and bereavement outcomes during DNC include attention to the state of mind of the family, pacing and repeating discussions according to families' expressed understanding, and preparing and inviting families to be present for the clinical determination including apnea testing. We have provided family-generated recommendations that are pragmatic and can be easily implemented.

RéSUMé: OBJECTIF: À l'heure actuelle, il y a peu de données empiriques sur la compréhension des familles de la mort cérébrale et de la détermination du décès. Le but de cette étude était de décrire la compréhension des membres de la famille de la mort cérébrale et du processus de détermination du décès dans le contexte du don d'organes dans les unités de soins intensifs (USI) canadiennes. MéTHODE: Nous avons mené une étude qualitative à l'aide d'entrevues semi-structurées et approfondies avec des membres de la famille à qui on a demandé de prendre une décision de don d'organes au nom de patients adultes ou pédiatriques dont le décès avait été déterminé selon des critères neurologiques (DCN) dans les unités de soins intensifs canadiennes. RéSULTATS: Sur la base d'entrevues avec 179 membres de la famille, six thèmes principaux ont émergé : 1) l'état d'esprit, 2) la communication, 3) le DCN peut être contre-intuitif, 4) la préparation à l'évaluation clinique pour un DCN, 5) l'évaluation clinique pour un DCN et 6) le moment du décès. Des recommandations sur la façon dont les cliniciens peuvent aider les membres de la famille à comprendre et à accepter un DCN par la communication à des moments clés ont été décrites, y compris la préparation des membres de la famille à la détermination du décès, l'autorisation de la présence des membres de la famille et l'explication de l'heure légale du décès, combinées à des stratégies multimodales. Pour de nombreux membres de la famille, la compréhension du DCN s'est développée au fil du temps et a été facilitée par des rencontres et des explications répétées plutôt qu'au cours d'une seule rencontre. CONCLUSION: La compréhension qu'ont les membres de la famille de la mort cérébrale et de la détermination du décès représente un parcours qu'ils ont décrit lors de rencontres successives avec des acteurs de soins de santé, et particulièrement avec des médecins. Les facteurs modifiables pour améliorer la communication et les issues du deuil pendant un DCN comprennent l'attention portée à l'état d'esprit de la famille, le rythme et la répétition des discussions en fonction de la compréhension exprimée par les familles, ainsi que la préparation et l'invitation des familles à être présentes pour la détermination clinique, y compris pendant le test d'apnée. Nous avons fourni des recommandations familiales qui sont pragmatiques et peuvent être facilement mises en œuvre.

A brain-based definition of death and criteria for its determination after arrest of circulation or neurologic function in Canada: a 2023 clinical practice guideline.

This 2023 Clinical Practice Guideline provides the biomedical definition of death based on permanent cessation of brain function that applies to all persons, as well as recommendations for death determination by circulatory criteria for potential organ donors and death determination by neurologic criteria for all mechanically ventilated patients regardless of organ donation potential. This Guideline is endorsed by the Canadian Critical Care Society, the Canadian Medical Association, the Canadian Association of Critical Care Nurses, Canadian Anesthesiologists' Society, the Canadian Neurological Sciences Federation (representing the Canadian Neurological Society, Canadian Neurosurgical Society, Canadian Society of Clinical Neurophysiologists, Canadian Association of Child Neurology, Canadian Society of Neuroradiology, and Canadian Stroke Consortium), Canadian Blood Services, the Canadian Donation and Transplantation Research Program, the Canadian Association of Emergency Physicians, the Nurse Practitioners Association of Canada, and the Canadian Cardiovascular Critical Care Society.

RéSUMé: Ces Lignes directrices de pratique clinique 2023 Lignes directrices de pratique clinique dicale du décès basée sur l'arrêt permanent de la fonction cérébrale qui s'applique à toute personne, ainsi que des recommandations pour la détermination du décès par des critères circulatoires pour des donneurs d'organes potentiels et des recommandations pour la détermination du décès par des critères neurologiques pour tous les patients sous ventilation mécanique, indépendamment de leur potentiel de donneur d'organes. Les présentes Lignes directrices sont approuvées par la Société canadienne de soins intensifs, l'Association médicale canadienne, l'Association canadienne des infirmiers/infirmières en soins intensifs, la Société canadienne des anesthésiologistes, la Fédération des sciences neurologiques du Canada (représentant la Société canadienne de neurologie, la Société canadienne de neurochirurgie, la Société canadienne de neurophysiologie clinique, l'Association canadienne de neurologie pédiatrique, la Société canadienne de neuroradiologie et le Consortium neurovasculaire canadien), la Société canadienne du sang, le Programme de recherche en don et transplantation du Canada, l'Association canadienne des médecins d'urgence, l'Association des infirmières et infirmiers praticiens du Canada, et la Société canadienne de soins intensifs cardiovasculaires (CANCARE) et la Société canadienne de pédiatrie.

Immunosuppressant Medication Use in Patients with Kidney Allograft Failure: A Prospective Multicenter Canadian Cohort Study.

BACKGROUND: Patients with kidney transplant failure have a high risk of hospitalization and death due to infection. The optimal use of immunosuppressants after transplant failure remains uncertain and clinical practice varies widely. METHODS: This prospective cohort study enrolled patients within 21 days of starting dialysis after transplant failure in 16 Canadian centers. Immunosuppressant medication use, death, hospitalized infection, rejection of the failed allograft, and anti-HLA panel reactive antibodies were determined at 1, 3, 6, and 12 months and and then twice yearly until death, repeat transplantation, or loss to follow-up. RESULTS: The 269 study patients were followed for a median of 558 days. There were 33 deaths, 143 patients hospitalized for infection, and 21 rejections. Most patients (65%) continued immunosuppressants, 20% continued prednisone only, and 15% discontinued all immunosuppressants. In multivariable models, patients who continued immunosuppressants had a lower risk of death (hazard ratio [HR], 0.40; 95% confidence interval [CI], 0.17 to 0.93) and were not at increased risk of hospitalized infection (HR, 1.81; 95% CI, 0.82 to 4.0) compared with patients who discontinued all immunosuppressants or continued prednisone only. The mean class I and class II panel reactive antibodies increased from 11% to 27% and from 25% to 47%, respectively, but did not differ by immunosuppressant use. Continuation of immunosuppressants was not protective of rejection of the failed allograft (HR, 0.81; 95% CI, 0.22 to 2.94). CONCLUSIONS: Prolonged use of immunosuppressants >1 year after transplant failure was not associated with a higher risk of death or hospitalized infection but was insufficient to prevent higher anti-HLA antibodies or rejection of the failed allograft.

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.

Automated APACHE II and SOFA score calculation using real-world electronic medical record data in a single center.

The integration of illness severity and organ dysfunction scores into clinical practice, including the APACHE II and SOFA scores, has been challenging due to constraints associated to manual score calculation. With electronic medical records (EMR), score calculation automation using data extraction scripts has emerged as a solution. We aimed to demonstrate that APACHE II and SOFA scores calculated with an automated EMR-based data extraction script predict important clinical endpoints. In this retrospective cohort study, every adult patient admitted to one of our three ICUs, between July 1, 2019, and December 31, 2020, were enrolled. For every patient, an automated ICU admission APACHE II score was calculated using EMR data and minimal clinician input. Fully automated daily SOFA scores were calculated for every patient. 4 794 ICU admissions met our selection criteria. Of these ICU admissions, 522 deaths were recorded (10.9% in-hospital mortality rate). The automated APACHE II was discriminant for in-hospital mortality (AU-ROC = 0.83 (95% CI 0.81-0.85)). We observed an association between the APACHE II score and ICU LOS, with a statistically significant mean increase of 1.1 days of ICU LOS (1.1 [1-1.2]; p = < .0001) for each 10 units increase in APACHE score. SOFA score curves did not discrimate significantly between survivors and non-survivors. A partially automated APACHE II score, calculated with real-world EMR data using an extraction script, is associated with in-hospital mortality risk. The automated APACHE II score could potentially constitute an acceptable surrogate of ICU acuity to be used in resource allocation and triaging, especially in time of high demand for ICU beds.

Association of age with death and withdrawal of life-sustaining therapy after severe traumatic brain injury.

BACKGROUND: Compared to younger age, older age (≥ 65 yr) is associated with worse outcomes after severe traumatic brain injury (TBI). We sought to describe the association of older age with in-hospital death and aggressiveness of intervention. METHODS: We conducted a retrospective cohort study of adult (age ≥ 16 yr) patients with severe TBI admitted to a single academic tertiary care neurotrauma centre between January 2014 and December 2015. We collected data through chart review as well as from our institutional administrative database. We provided descriptive statistics and used multivariable logistic regression to evaluate the independent association of age with the primary outcome, in-hospital death. The secondary outcome was early withdrawal of life-sustaining therapy. RESULTS: There were 126 adult patients (median age 67 yr [Q1-Q3, 33-80 yr]) with severe TBI during the study period who met our eligibility criteria. The most common mechanism was high-velocity blunt injury (55 patients [43.6%]). The median Marshall score was 4 (Q1-Q3, 2-6), and the median Injury Severity Score was 26 (Q1-Q3, 25-35). After controlling for confounders including clinical frailty, pre-existing comorbidity, injury severity, Marshall score and neurologic examination at admission, we observed that older patients were more likely than younger patients to die in hospital (odds ratio 5.10, 95% confidence interval 1.65-15.78). Older patients were also more likely to experience early withdrawal of life-sustaining therapy and less likely to receive invasive interventions. CONCLUSION: After controlling for confounding factors relevant to older patients, we observed that age was an important and independent predictor of in-hospital death and early withdrawal of life-sustaining therapy. The mechanism by which age influences clinical decision-making independent of global and neurologic injury severity, clinical frailty and comorbidities remains unclear.

The association of venous thromboembolism with blood transfusion in kidney transplant patients.

BACKGROUND: Red blood cell transfusion (RBCT) is common after kidney transplantation and could have pro-thrombotic effects predisposing to venous thromboembolism (VTE). The risks for developing of VTE after RBCT in kidney transplant patients are unknown. STUDY DESIGN AND METHODS: This was a retrospective cohort study of adult kidney transplant recipients from 2002 to 2018. The exposure of interest was receipt of RBCT after transplant. Cox proportional hazards models were used to calculate hazard ratios (HR) for the outcomes of venous thromboembolism [VTE] (deep venous thrombosis [DVT] or pulmonary embolism [PE]) using RBCT as a time-varying, cumulative exposure. RESULTS: Out of 1258 kidney transplants recipients, 468 (37%) were transfused during the study period. Seventy-nine study participants (6.3%) developed VTE, 72 DVT (5.7%), and 22 PE (1.8%). For the receipt of 1, 2, 3-5, and >5 RBCT, compared to individuals never transfused, the number of events and adjusted HR (95%CI) for VTE were 6 (6.2%) HR 1.57 (0.69-3.58), 9 (7.6%) HR 2.54 (1.30-4.96), 15 (11.9%) HR 2.73 (1.38-5.41), and 23 (18.1%) HR 5.77 (2.99-11.14) respectively; for DVT, it was 6 (6.2%) HR 1.94 (0.84-4.48), 9 (7.6%) HR 2.92 (1.44-5.94), 14 (11.1%) HR 3.29 (1.63-6.65), and 21 (16.5%) HR 6.97 (3.53-13.76), respectively. For PE, among transfused individuals, there were 14 events (3.0%) and the HR was 2.40 (1.02-5.61). CONCLUSION: The risks for developing VTE, DVT, and PE were significantly increased in kidney transplant patients receiving RBCT after transplant. Receipt of RBCT should prompt considerations for judicious monitoring and assessment for thrombosis.