Evaluating the Sum of Eye and Motor Components of the Glasgow Coma Score As a Predictor of Extubation Failure in Patients With Acute Brain Injury.

OBJECTIVES: To evaluate the association between the pre-extubation sum of eye and motor components of the Glasgow Coma Score (GCS-EM) and odds of extubation failure in patients with acute brain injury being liberated from mechanical ventilation. DESIGN: Secondary analysis of a prospective, multicenter observational study ( ClinicalTrials.gov identifier NCT03400904). SETTING: Sixty-three hospital sites worldwide, with patient recruitment from January 2018 to November 2020. PATIENTS: One thousand one hundred fifty-two critically ill patients with acute brain injury, with a median age of 54 years, of whom 783 (68.0%) were male, 559 (48.5%) had traumatic brain injury, and 905 (78.6%) had a GCS-EM greater than 8 before extubation (scores range from 2 to 10). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: GCS-EM was computed in intubated patients on the day of extubation. The main outcome was extubation failure, defined as unplanned reintubation within 5 days of extubation. Analyses used multilevel logistic regression with adjustment for patient characteristics and a random intercept for hospital site. In the primary analysis, GCS-EM was not associated with extubation failure (odds ratio, 1.07 per additional point; 95% CI, 0.87-1.31). Findings were consistent in sensitivity analyses that: 1) used different adjustment covariates, 2) included a verbal estimate to derive an overall GCS, 3) accounted for missing data, 4) considered a 2-day time interval to define extubation failure, 5) accounted for competing risks, and 6) used a propensity score-based model. There was no association between GCS-EM and extubation outcome in subgroups defined by brain injury diagnosis or age. CONCLUSIONS: In this large, contemporary, multicenter cohort of patients with acute brain injury, we found no association between the GCS-EM and odds of extubation failure. However, few patients had a pre-extubation GCS-EM less than or equal to 8, and the possibility of a true prognostic association in patients with low scores is not excluded.

Influence of health insurance on withdrawal of life sustaining treatment for patients with isolated traumatic brain injury: a retrospective multi-center observational cohort study.

BACKGROUND: Healthcare inequities for patients with traumatic brain injury (TBI) represent a major priority area for trauma quality improvement. We hypothesized a relationship between health insurance status and timing of withdrawal of life sustaining treatment (WLST) for adults with severe TBI. METHODS: This multicenter retrospective observational cohort study utilized data collected between 2017 and 2020. We identified adult (age ≥ 16) patients with isolated severe TBI admitted participating Trauma Quality Improvement Program centers. We determined the relationship between insurance status (public, private, and uninsured) and the timing of WLST using a competing risk survival analysis framework adjusting for baseline, clinical, injury and trauma center characteristics. Multivariable cause-specific Cox regressions were used to compute adjusted hazard ratios (HR) reflecting timing of WLST, accounting for mortality events. We also quantified the between-center residual variability in WLST using the median odds ratio (MOR) and measured insurance status association with access to rehabilitation at discharge. RESULTS: We identified 42,111 adults with isolated severe TBI treated across 509 trauma centers across North America. There were 10,771 (25.6%) WLST events in the cohort and a higher unadjusted incidence of WLST events was evident in public insurance patients compared to private or uninsured groups. After adjustment, WLST occurred earlier for publicly insured (HR 1.07, 95% CI 1.02-1.12) and uninsured patients (HR 1.29, 95% CI 1.18-1.41) compared to privately insured patients. Access to rehabilitation was lower for both publicly insured and uninsured patients compared to patients with private insurance. Accounting for case-mix, the MOR was 1.49 (95% CI 1.43-1.55), reflecting significant residual between-center variation in WLST decision-making. CONCLUSIONS: Our findings highlight the presence of disparate WLST practices independently associated with health insurance status. Additionally, these results emphasize between-center variability in WLST, persisting despite adjustments for measurable patient and trauma center characteristics.

Incidence and Outcomes of Acute Respiratory Distress Syndrome in Brain-Injured Patients Receiving Invasive Ventilation: A Secondary Analysis of the ENIO Study.

Background: Acute respiratory distress syndrome (ARDS) is an important pulmonary complication in brain-injured patients receiving invasive mechanical ventilation (IMV). We aimed to evaluate the incidence and association between ARDS and clinical outcomes in patients with different forms of acute brain injury requiring IMV in the intensive care unit (ICU). Methods: This was a preplanned secondary analysis of a prospective, multicenter, international cohort study (NCT03400904). We included brain-injured patients receiving IMV for ≥ 24 h. ARDS was the main exposure of interest and was identified during index ICU admission using the Berlin definition. We examined the incidence and adjusted association of ARDS with ICU mortality, ICU length of stay, duration of IMV, and extubation failure. Outcomes were evaluated using mixed-effect logistic regression and cause-specific Cox proportional hazards models. Results: 1492 patients from 67 hospitals and 16 countries were included in the analysis, of whom 137 individuals developed ARDS (9.2% of overall cohort). Across countries, the median ARDS incidence was 5.1% (interquartile range [IQR] 0-10; range 0-27.3). ARDS was associated with increased ICU mortality (adjusted odds ratio (OR) 2.66; 95% confidence interval [CI], 1.29-5.48), longer ICU length of stay (adjusted hazard ratio [HR] 0.59; 95% CI, 0.48-0.73), and longer duration of IMV (adjusted HR 0.54; 95% CI, 0.44-0.67). The association between ARDS and extubation failure approached statistical significance (adjusted HR 1.48; 95% CI 0.99-2.21). Higher ARDS severity was associated with incrementally longer ICU length of stay and longer cumulative duration of IMV. Findings remained robust in a sensitivity analysis evaluating the magnitude of unmeasured confounding. Conclusions: In this cohort of acutely brain-injured patients, the incidence of ARDS was similar to that reported in other mixed cohorts of critically ill patients. Development of ARDS was associated with worse outcomes.

Association of Noninvasive Respiratory Support with Extubation Outcomes in Brain-injured Patients Receiving Mechanical Ventilation: A Secondary Analysis of the ENIO Prospective Observational Study.

Rationale: Noninvasive respiratory support using a high-flow nasal cannula (HFNC) or noninvasive positive pressure ventilation (NIPPV) can decrease the risk of reintubation in patients being liberated from mechanical ventilation, but effects in patients with acute brain injury (ABI) are unknown. Objectives: To evaluate the association between postextubation noninvasive respiratory support and reintubation in patients with ABI being liberated from mechanical ventilation. Methods: This was a secondary analysis of a prospective, observational study of mechanically ventilated patients with ABI (clinicaltrials.gov identifier NCT03400904). The primary endpoint was reintubation during ICU admission. We used mixed-effects logistic regression models with patient-level covariates and random intercepts for hospital and country to evaluate the association between prophylactic (i.e., planned) HFNC or NIPPV and reintubation. Measurements and Main Results: 1,115 patients were included from 62 hospitals and 19 countries, of whom 267 received HFNC or NIPPV following extubation (23.9%). Compared with conventional oxygen therapy, neither prophylactic HFNC nor NIPPV was associated with decreased odds of reintubation (respectively, odds ratios of 0.97 [95% confidence interval, 0.54-1.73] and 0.63 [0.30-1.32]). Findings remained consistent in sensitivity analyses accounting for alternate adjustment procedures, missing data, shorter time frames of the primary endpoint, and competing risks precluding reintubation. In a Bayesian analysis using skeptical and data-driven priors, the probabilities of reduced reintubation ranged from 17% to 34% for HFNC and from 46% to 74% for NIPPV. Conclusions: In a large cohort of brain-injured patients undergoing liberation from mechanical ventilation, prophylactic use of HFNC and NIPPV were not associated with reintubation. Prospective trials are needed to confirm treatment effects in this population. Primary study registered with www.clinicaltrials.gov (NCT03400904).

Prognostic Factors Associated With Extubation Failure in Acutely Brain-Injured Patients: A Systematic Review and Meta-Analysis.

OBJECTIVE: Extubation failure in brain-injured patients is associated with increased morbidity. Our objective was to systematically review prognostic factors associated with extubation failure in acutely brain-injured adult patients receiving invasive ventilation in an ICU. DATA SOURCES: MEDLINE, Embase, and Cochrane Central were searched from inception to January 31, 2022. STUDY SELECTION: Two reviewers independently screened citations and selected English-language cohort studies and randomized trials examining the association of prognostic factors with extubation failure. Studies were considered if they included greater than or equal to 80% adult patients with acute brain injury admitted to the ICU and mechanically ventilated for greater than or equal to 24 hours. DATA EXTRACTION: Two reviewers extracted data on population, prognostic factors, extubation outcomes, and risk of bias (using the quality in prognostic factors tool). DATA SYNTHESIS: In the primary analysis, adjusted odds ratios (aOR) for each prognostic factor were pooled using random-effects models. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. The search identified 7,626 citations, of which 21 studies met selection criteria. Moderate-certainty evidence suggested increased risk of extubation failure with older age (aOR, 3.0 for upper vs lower tertile; 95% CI, 1.78-5.07) and longer duration of mechanical ventilation (aOR, 3.47 for upper vs lower tertile; 95% CI, 1.68-7.19). Presence of cough (aOR, 0.40; 95% CI, 0.28-0.57) and intact swallow (aOR, 0.34; 95% CI, 0.21-0.54) probably decreased risk of extubation failure (moderate certainty). Associations of other factors with extubation failure were informed by low or very low certainty evidence. CONCLUSIONS: Patient age, duration of mechanical ventilation, and airway reflexes were associated with extubation failure in brain-injured patients with moderate certainty. Future studies are needed to determine the optimal application of these variables in clinical practice.

Lower Versus Higher Exposure to Vasopressor Therapy in Vasodilatory Hypotension: A Systematic Review With Meta-Analysis.

OBJECTIVES: Balancing the risks of hypotension and vasopressor-associated adverse effects is a daily challenge in ICUs. We conducted a systematic review with meta-analysis to examine the effect of lower versus higher exposure to vasopressor therapy on mortality among adult ICU patients with vasodilatory hypotension. DATA SOURCES: We searched Ovid Medline, Embase, and the Cochrane Central Register of Controlled Trials for studies published from inception to October 15, 2021. STUDY SELECTION: We included randomized controlled trials of lower versus higher exposure to vasopressor therapy in adult ICU patients with vasodilatory hypotension without language or publication status limits. DATA EXTRACTION: The primary outcome was 90-day all-cause mortality, with seven prespecified subgroups. Secondary outcomes included shorter- and longer-term mortality, use of life-sustaining therapies, vasopressor-related complications, neurologic outcome, and quality of life at longest reported follow-up. We conducted random-effects meta-analyses to calculate summary effect measures across individual studies (risk ratio [RR] for dichotomous variables, mean difference for continuous variables, both with 95% CIs). The certainty of the evidence was assessed using Grading of Recommendations, Assessment, Development, and Evaluation. We registered this review on the International Prospective Register of Systematic Reviews (CRD42021224434). DATA SYNTHESIS: Of 3,403 records retrieved, 68 full-text articles were reviewed and three eligible studies included. Lower exposure to vasopressors probably lowers 90-day mortality but this is based on moderate-certainty evidence, lowered for imprecision (RR, 0.94; 95% CI, 0.87-1.02). There was no credible subgroup effect. Lower vasopressor exposure may also decrease the risk of supraventricular arrhythmia (odds ratio, 0.55; 95% CI, 0.36-0.86; low certainty). CONCLUSIONS: In patients with vasodilatory hypotension who are started on vasopressors, moderate-certainty evidence from three randomized trials showed that lower vasopressor exposure probably lowers mortality. However, additional trial data are needed to reach an optimal information size to detect a clinically important 10% relative reduction in mortality with this approach.

Ventilatory targets following brain injury.

PURPOSE OF REVIEW: Recent studies have focused on identifying optimal targets and strategies of mechanical ventilation in patients with acute brain injury (ABI). The present review will summarize these findings and provide practical guidance to titrate ventilatory settings at the bedside, with a focus on managing potential brain-lung conflicts. RECENT FINDINGS: Physiologic studies have elucidated the impact of low tidal volume ventilation and varying levels of positive end expiratory pressure on intracranial pressure and cerebral perfusion. Epidemiologic studies have reported the association of different thresholds of tidal volume, plateau pressure, driving pressure, mechanical power, and arterial oxygen and carbon dioxide concentrations with mortality and neurologic outcomes in patients with ABI. The data collectively make clear that injurious ventilation in this population is associated with worse outcomes; however, optimal ventilatory targets remain poorly defined. SUMMARY: Although direct data to guide mechanical ventilation in brain-injured patients is accumulating, the current evidence base remains limited. Ventilatory considerations in this population should be extrapolated from high-quality evidence in patients without brain injury - keeping in mind relevant effects on intracranial pressure and cerebral perfusion in patients with ABI and individualizing the chosen strategy to manage brain-lung conflicts where necessary.

Utilization of mechanical power and associations with clinical outcomes in brain injured patients: a secondary analysis of the extubation strategies in neuro-intensive care unit patients and associations with outcome (ENIO) trial.

BACKGROUND: There is insufficient evidence to guide ventilatory targets in acute brain injury (ABI). Recent studies have shown associations between mechanical power (MP) and mortality in critical care populations. We aimed to describe MP in ventilated patients with ABI, and evaluate associations between MP and clinical outcomes. METHODS: In this preplanned, secondary analysis of a prospective, multi-center, observational cohort study (ENIO, NCT03400904), we included adult patients with ABI (Glasgow Coma Scale ≤ 12 before intubation) who required mechanical ventilation (MV) ≥ 24 h. Using multivariable log binomial regressions, we separately assessed associations between MP on hospital day (HD)1, HD3, HD7 and clinical outcomes: hospital mortality, need for reintubation, tracheostomy placement, and development of acute respiratory distress syndrome (ARDS). RESULTS: We included 1217 patients (mean age 51.2 years [SD 18.1], 66% male, mean body mass index [BMI] 26.3 [SD 5.18]) hospitalized at 62 intensive care units in 18 countries. Hospital mortality was 11% (n = 139), 44% (n = 536) were extubated by HD7 of which 20% (107/536) required reintubation, 28% (n = 340) underwent tracheostomy placement, and 9% (n = 114) developed ARDS. The median MP on HD1, HD3, and HD7 was 11.9 J/min [IQR 9.2-15.1], 13 J/min [IQR 10-17], and 14 J/min [IQR 11-20], respectively. MP was overall higher in patients with ARDS, especially those with higher ARDS severity. After controlling for same-day pressure of arterial oxygen/fraction of inspired oxygen (P/F ratio), BMI, and neurological severity, MP at HD1, HD3, and HD7 was independently associated with hospital mortality, reintubation and tracheostomy placement. The adjusted relative risk (aRR) was greater at higher MP, and strongest for: mortality on HD1 (compared to the HD1 median MP 11.9 J/min, aRR at 17 J/min was 1.22, 95% CI 1.14-1.30) and HD3 (1.38, 95% CI 1.23-1.53), reintubation on HD1 (1.64; 95% CI 1.57-1.72), and tracheostomy on HD7 (1.53; 95%CI 1.18-1.99). MP was associated with the development of moderate-severe ARDS on HD1 (2.07; 95% CI 1.56-2.78) and HD3 (1.76; 95% CI 1.41-2.22). CONCLUSIONS: Exposure to high MP during the first week of MV is associated with poor clinical outcomes in ABI, independent of P/F ratio and neurological severity. Potential benefits of optimizing ventilator settings to limit MP warrant further investigation.

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.

Mechanical Ventilation in Patients with Traumatic Brain Injury: Is it so Different?

Patients with traumatic brain injury (TBI) frequently require invasive mechanical ventilation and admission to an intensive care unit. Ventilation of patients with TBI poses unique clinical challenges, and careful attention is required to ensure that the ventilatory strategy (including selection of appropriate tidal volume, plateau pressure, and positive end-expiratory pressure) does not cause significant additional injury to the brain and lungs. Selection of ventilatory targets may be guided by principles of lung protection but with careful attention to relevant intracranial effects. In patients with TBI and concomitant acute respiratory distress syndrome (ARDS), adjunctive strategies include sedation optimization, neuromuscular blockade, recruitment maneuvers, prone positioning, and extracorporeal life support. However, these approaches have been largely extrapolated from studies in patients with ARDS and without brain injury, with limited data in patients with TBI. This narrative review will summarize the existing evidence for mechanical ventilation in patients with TBI. Relevant literature in patients with ARDS will be summarized, and where available, direct data in the TBI population will be reviewed. Next, practical strategies to optimize the delivery of mechanical ventilation and determine readiness for extubation will be reviewed. Finally, future directions for research in this evolving clinical domain will be presented, with considerations for the design of studies to address relevant knowledge gaps.

Optimizing oxygen delivery to the injured brain.

PURPOSE OF REVIEW: The principle of optimizing oxygen delivery to the injured brain rests on the premise that both hypoxia and hyperoxia are important mediators of secondary brain injury and should be avoided. This rationale has prompted a move towards incorporating oxygenation endpoints into the management of neurocritical care patients, particularly those with traumatic brain injury. The present review will seek to describe clinical strategies to optimize oxygenation in the acutely brain-injured patient, drawing upon relevant physiologic principles and clinical data, where it exists. RECENT FINDINGS: A phase II randomized trial found that a protocolized approach to improving oxygen delivery resulted in less duration of brain hypoxia and a trend towards lower mortality among patients with severe traumatic brain injury. Recent clinical protocols have been published to guide oxygen delivery based on core physiologic principles: increasing oxygen supply via modulation of mean arterial pressure and intracranial pressure, blood oxygen carrying capacity, and cerebral vasoreactivity; and decreasing oxygen demand via sedation, pharmacologic coma, and hypothermia. SUMMARY: Although there is growing interest in the use of brain tissue oxygenation as a resuscitative endpoint, many of these therapies are based on physiologic principles with little robust clinical evidence to guide their application. Clinicians must be mindful of this and balance the putative benefits of improving oxygenation against the risks associated with the use of such therapies.

Discordances Between Factors Associated With Withholding Extubation and Extubation Failure After a Successful Spontaneous Breathing Trial.

OBJECTIVES: To identify whether factors associated with withholding extubation in the ICU also predict the risk of extubation failure. DESIGN: Retrospective cohort study. SETTING: Eight medical-surgical ICUs in Toronto. PATIENTS: Adult patients receiving invasive mechanical ventilation, with a first successful spontaneous breathing trial within 28 days of initial ICU admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary end point had three mutually exclusive levels, including: 1) withholding extubation after a successful spontaneous breathing trial, 2) extubation failure within 48 hours, and 3) successful extubation. Among 9,910 patients, 38% of patients were not extubated within 24 hours of their first successful spontaneous breathing trial. A total of 12.9% of patients who were promptly extubated failed within the next 48 hours. Several discrepancies were evident in the association of factors with risk of withholding extubation and extubation failure. Specifically, both age and female sex were associated with withholding extubation (odds ratio, 1.07; 95% CI, 1.03-1.11; and odds ratio, 1.13; 95% CI, 1.02-1.26, respectively) but not a higher risk of failed extubation (odds ratio, 0.99; 95% CI, 0.93-1.05; and odds ratio, 0.93; 95% CI, 0.77-1.11, respectively). Conversely, both acute cardiovascular conditions and intubation for hypoxemic respiratory failure were associated with a higher risk of failed extubation (odds ratio, 1.32; 95% CI, 1.06-1.66; and odds ratio, 1.46; 95% CI, 1.16-1.82, respectively) but not a higher odds of a withheld extubation attempt (odds ratio, 0.79; 95% CI, 0.68-0.91; and odds ratio, 1.07; 95% CI, 0.93-1.23, respectively). CONCLUSIONS: Several factors showed discordance between the decision to withhold extubation and the risk of extubation failure. This discordance may lead to longer duration of mechanical ventilation or higher reintubation rates. Improving the decision-making behind extubation may help to reduce both exposure to invasive mechanical ventilation and extubation failure.

Educational initiatives for electroencephalography in the critical care setting: a systematic review and meta-analysis.

PURPOSE: We systematically reviewed existing critical care electroencephalography (EEG) educational programs for non-neurologists, with the primary goal of reporting the content covered, methods of instruction, overall duration, and participant experience. Our secondary goals were to assess the impact of EEG programs on participants' core knowledge, and the agreement between non-experts and experts for seizure identification. SOURCE: Major databases were searched from inception to 30 August 2020. Randomized controlled trials, cohort studies, and descriptive studies were all considered if they reported an EEG curriculum for non-neurologists in a critical care setting. Data were presented thematically for the qualitative primary outcome and a meta-analysis using a random effects model was performed for the quantitative secondary outcomes. PRINCIPAL FINDINGS: Twenty-nine studies were included after reviewing 7,486 citations. Twenty-two studies were single centre, 17 were from North America, and 16 were published after 2016. Most EEG studies were targeted to critical care nurses (17 studies), focused on processed forms of EEG with amplitude-integrated EEG being the most common (15 studies), and were shorter than one day in duration (24 studies). In pre-post studies, EEG programs significantly improved participants' knowledge of tested material (standardized mean change, 1.79; 95% confidence interval [CI], 0.86 to 2.73). Agreement for seizure identification between non-experts and experts was moderate (Cohen's kappa = 0.44; 95% CI, 0.27 to 0.60). CONCLUSIONS: It is feasible to teach basic EEG to participants in critical care settings from different clinical backgrounds, including physicians and nurses. Brief training programs can enable bedside providers to recognize high-yield abnormalities such as non-convulsive seizures.

RéSUMé: OBJECTIF: Nous avons réalisé une revue systématique des programmes éducatifs d'électroencéphalographie (EEG) en soins intensifs s'adressant aux non-neurologues, avec pour but principal de rapporter le contenu couvert, les méthodes d'enseignement, la durée globale et l'expérience des participants. Nos objectifs secondaires étaient d'évaluer l'impact des programmes d'EEG sur les connaissances de base des participants, et l'accord entre non-experts et experts pour l'identification des convulsions. MéTHODE: Les principales bases de données ont été consultées depuis leur création jusqu'au 30 août 2020. Les études randomisées contrôlées, les études de cohorte et les études descriptives ont toutes été prises en compte si elles décrivaient un programme de formation en EEG pour les non-neurologues en milieu de soins intensifs. Les données ont été présentées thématiquement en ce qui touchait notre critère d'évaluation principal qualitatif, et une méta-analyse utilisant un modèle à effets aléatoires a été exécutée pour les critères secondaires quantitatifs. CONSTATATIONS PRINCIPALES: Vingt-neuf études ont été incluses après avoir examiné 7486 citations. Vingt-deux études étaient monocentriques, 17 provenaient d'Amérique du Nord et 16 avaient été publiées après 2016. La plupart des études sur l'EEG visaient le personnel infirmier en soins intensifs (17 études); elles se concentraient sur les formes analysées d'EEG; l'EEG à amplitude intégrée était le thème le plus fréquemment abordé (15 études), et la plupart duraient moins d'un jour (24 études). Dans les études avant-après, les programmes d'EEG ont considérablement amélioré les connaissances des participants du matériel testé (changement moyen normalisé, 1,79; intervalle de confiance [IC] à 95 %, 0,86 à 2,73). L'accord en matière d''identification des convulsions entre non-experts et experts était modéré (kappa de Cohen = 0,44; IC 95 %, 0,27 à 0,60). CONCLUSION: Il est possible d'enseigner l'EEG de base dans des milieux de soins intensifs à des participants provenant de différents milieux cliniques, y compris les médecins et le personnel infirmier. De brefs programmes de formation peuvent permettre aux fournisseurs de soins au chevet de reconnaître les anomalies à haut impact comme par exemple des crises épileptiques non convulsives.

Organ donation in patients on extracorporeal membrane oxygenation: considerations for determination of death and withdrawal of life support.

The use of extracorporeal membrane oxygenation (ECMO) is increasing globally, although mortality in this setting remains high. Patients on ECMO may be potential organ donors in the context of withdrawal of life-sustaining measures (WLSM) or neurologic determination of death (NDD). Nevertheless, there are currently no Canadian standards to guide clinicians on NDD or WLSM for the purposes of organ donation in this patient population. Apnea testing remains fundamental to determining NDD and is an area where ECMO may alter routine procedures. In this review, we outline protocols for the performance of apnea testing and WLSM for patients supported with ECMO, highlighting important technical and physiologic considerations that may affect the determination of death. In addition, we review important considerations for NDD in ECMO, including management of potential confounders, strategies for controlling oxygen and carbon dioxide levels during apnea testing, and the appropriate use of ancillary tests to support NDD. In the context of ECMO support, there is limited evidence to guide NDD and WLSM for the purposes of organ donation. Drawing upon extensive clinical experience, we provide protocols for these processes and review other important considerations in an effort to maximize donor potential in this growing patient population.

RéSUMé: L'utilisation de l'oxygénation extracorporelle (ECMO) augmente dans le monde, malgré le fait que la mortalité associée demeure élevée. Les patients sous ECMO pourraient être des donneurs d'organes potentiels dans le cadre d'une interruption des mesures de maintien des fonctions vitales ou d'un diagnostic de décès neurologique (DDN). À l'heure actuelle il n'existe cependant aucune norme canadienne pour guider les cliniciens en matière de DDN ou d'interruption des mesures de maintien des fonctions vitales aux fins de dons d'organes dans cette population de patients. Le test d'apnée demeure fondamental pour poser un DDN mais il s'agit d'un domaine dans lequel l'ECMO pourrait modifier les interventions de routine. Dans ce compte rendu, nous décrivons des protocoles pour la réalisation d'un test d'apnée et l'interruption des mesures de maintien des fonctions vitales chez des patients sous ECMO. Nous soulignons certaines considérations techniques et physiologiques importantes qui pourraient avoir un impact sur le diagnostic de décès. En outre, nous passons en revue certaines considérations importantes pour le DDN sous ECMO, notamment la prise en charge de facteurs confondants potentiels, les stratégies pour contrôler les niveaux d'oxygène et de dioxyde de carbone pendant le test d'apnée, et l'utilisation adaptée de tests complémentaires pour appuyer le DDN. Dans le cadre d'un maintien des fonctions vitales sous ECMO, il n'existe que peu de données probantes pour guider le DDN et l'interruption des mesures de maintien des fonctions vitales aux fins d'un don d'organes. En nous fondant sur notre vaste expérience clinique, nous proposons des protocoles pour ces processus et passons en revue d'autres considérations importantes afin de maximiser le potentiel de dons dans cette population de patients grandissante.

The Use of Standardized Management Protocols for Critically Ill Patients with Non-traumatic Subarachnoid Hemorrhage: A Systematic Review.

The use of standardized management protocols (SMPs) may improve patient outcomes for some critical care diseases. Whether SMPs improve outcomes after subarachnoid hemorrhage (SAH) is currently unknown. We aimed to study the effect of SMPs on 6-month mortality and neurologic outcomes following SAH. A systematic review of randomized control trials (RCTs) and observational studies was performed by searching multiple indexing databases from their inception through January 2019. Studies were limited to adult patients (age ≥ 18) with non-traumatic SAH reporting mortality, neurologic outcomes, delayed cerebral ischemia (DCI) and other important complications. Data on patient and SMP characteristics, outcomes and methodologic quality were extracted into a pre-piloted collection form. Methodologic quality of observational studies was assessed using the Newcastle-Ottawa scale, and RCT quality was reported as per the Cochrane risk of bias tool. A total of 11,260 studies were identified, of which 37 (34 full-length articles and 3 abstracts) met the criteria for inclusion. Two studies were RCTs and 35 were observational. SMPs were divided into four broad domains: management of acute SAH, early brain injury, DCI and general neurocritical care. The most common SMP design was control of DCI, with 22 studies assessing this domain of care. Overall, studies were of low quality; most described single-center case series with small patient sizes. Definitions of key terms and outcome reporting practices varied significantly between studies. DCI and neurologic outcomes in particular were defined inconsistently, leading to significant challenges in their interpretation. Given the substantial heterogeneity in reporting practices between studies, a meta-analysis for 6-month mortality and neurologic outcomes could not be performed, and the effect of SMPs on these measures thus remains inconclusive. Our systematic review highlights the need for large, rigorous RCTs to determine whether providing standardized, best-practice management through the use of a protocol impacts outcomes in critically ill patients with SAH.Trial registration Registration number: CRD42017069173.