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.

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.

The Thinker-A Work by Rodin With a Message for Clinicians.

This essay describes the author's experience of viewing The Thinker in Paris and being reminded that clinicians too need to stop and think.

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.

Factors associated with acute respiratory distress syndrome in brain-injured patients: A systematic review and meta-analysis.

PURPOSE: Acute respiratory distress syndrome (ARDS) is common in patients with acute brain injury admitted to the ICU. We aimed to identify factors associated with ARDS in this population. METHODS: We searched MEDLINE, Embase, Cochrane Central, Scopus, and Web of Science from inception to January 14, 2022. Three reviewers independently screened articles and selected English-language studies reporting risk factors for ARDS in brain-injured adult patients. Data were extracted on ARDS incidence, adjusted and unadjusted risk factors, and clinical outcomes. Risk of bias was reported using the Quality in Prognostic Studies tool. Certainty of evidence was assessed using GRADE. RESULTS: We selected 23 studies involving 6,961,284 patients with acute brain injury. The pooled cumulative incidence of ARDS after brain injury was 17.0% (95%CI 10.7-25.8). In adjusted analysis, factors associated with ARDS included sepsis (odds ratio (OR) 4.38, 95%CI 2.37-8.10; high certainty), history of hypertension (OR 3.11, 95%CI 2.31-4.19; high certainty), pneumonia (OR 2.69, 95%CI 2.35-3.10; high certainty), acute kidney injury (OR 1.44, 95%CI 1.30-1.59; moderate certainty), admission hypoxemia (OR 1.67, 95%CI 1.29-2.17; moderate certainty), male sex (OR 1.30, 95%CI 1.06-1.58; moderate certainty), and chronic obstructive pulmonary disease (OR 1.27, 95%CI 1.13-1.44; moderate certainty). Development of ARDS was independently associated with increased odds of in-hospital mortality (OR 3.12, 95% CI 1.39-7.00). CONCLUSIONS: Multiple risk factors are associated with ARDS in brain-injured patients. These findings could be used to develop prognostic models for ARDS or as prognostic enrichment strategies for patient enrolment in future clinical trials.

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.

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).

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.

Association of Days Alive and at Home at Day 90 After Intensive Care Unit Admission With Long-term Survival and Functional Status Among Mechanically Ventilated Patients.

Importance: Many conventional end points in randomized clinical trials of interventions for critically ill patients do not account for patient-centered concerns such as time at home, physical function, and quality of life after critical illness. Objective: To establish whether days alive and at home at day 90 (DAAH90) is associated with long-term survival and functional outcomes in mechanically ventilated patients. Design, Setting, and Participants: The RECOVER prospective cohort study was conducted from February 2007 to March 2014, using data from 10 intensive care units (ICUs) in Canada. Patients were included in the baseline cohort if they were aged 16 years or older and underwent invasive mechanical ventilation for 7 or more days. The follow-up cohort analyzed here comprised RECOVER patients who were alive and had functional outcomes ascertained at 3, 6, and 12 months. Secondary data analysis occurred from July 2021 to August 2022. Exposures: Composite of survival and days alive and at home at day 90 after ICU admission (DAAH90). Main Outcomes and Measures: Functional outcomes at 3, 6, and 12 months were evaluated with the Functional Independence Measure (FIM), the 6-Minute Walk Test (6MWT), the Medical Research Council (MRC) Scale for Muscle Strength, and the 36-Item Short Form Health Survey physical component summary (SF-36 PCS). Mortality was evaluated at 1 year from ICU admission. Ordinal logistic regression was used to describe the association between DAAH90 tertiles and outcomes. Cox proportional hazards regression models were used to examine the independent association of DAAH90 tertiles with mortality. Results: The baseline cohort comprised 463 patients. Their median age was 58 years (IQR, 47-68 years), and 278 patients (60.0%) were men. In these patients, Charlson Comorbidity Index score, Acute Physiology and Chronic Health Evaluation II score, ICU intervention (eg, kidney replacement therapy or tracheostomy), and ICU length of stay were independently associated with lower DAAH90. The follow-up cohort comprised 292 patients. Their median age was 57 years (IQR, 46-65 years), and 169 patients (57.9%) were men. Among patients who survived to day 90, lower DAAH90 was associated with higher mortality at 1 year after ICU admission (tertile 1 vs tertile 3: adjusted hazard ratio [HR], 0.18 [95% CI, 0.07-0.43]; P < .001). At 3 months of follow-up, lower DAAH90 was independently associated with lower median scores on the FIM (tertile 1 vs tertile 3, 76 [IQR, 46.2-101] vs 121 [IQR, 112-124.2]; P = .04), 6MWT (tertile 1 vs tertile 3, 98 [IQR, 0-239] vs 402 [IQR, 300-494]; P < .001), MRC (tertile 1 vs tertile 3, 48 [IQR, 32-54] vs 58 [IQR, 51-60]; P < .001), and SF-36 PCS (tertile 1 vs tertile 3, 30 [IQR, 22-38] vs 37 [IQR, 31-47]; P = .001) measures. Among patients who survived to 12 months, being in tertile 3 vs tertile 1 for DAAH90 was associated with higher FIM score at 12 months (estimate, 22.4 [95% CI, 14.8-30.0]; P < .001), but this association was not present for ventilator-free days (estimate, 6.0 [95% CI, -2.2 to 14.1]; P = .15) or ICU-free days (estimate, 5.9 [95% CI, -2.1 to 13.8]; P = .15) at day 28. Conclusions and Relevance: In this study, lower DAAH90 was associated with greater long-term mortality risk and worse functional outcomes among patients who survived to day 90. These findings suggest that the DAAH90 end point reflects long-term functional status better than standard clinical end points in ICU studies and may serve as a patient-centered end point in future clinical trials.

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.

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.

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.

Noninvasive and invasive mechanical ventilation for neurologic disorders.

Patients with acute neurologic injuries frequently require mechanical ventilation due to diminished airway protective reflexes, cardiopulmonary failure secondary to neurologic insults, or to facilitate gas exchange to precise targets. Mechanical ventilation enables tight control of oxygenation and carbon dioxide levels, enabling clinicians to modulate cerebral hemodynamics and intracranial pressure with the goal of minimizing secondary brain injury. In patients with acute spinal cord injuries, neuromuscular conditions, or diseases of the peripheral nerve, mechanical ventilation enables respiratory support under conditions of impending or established respiratory failure. Noninvasive ventilatory approaches may be carefully considered for certain disease conditions, including myasthenia gravis and amyotrophic lateral sclerosis, but may be inappropriate in patients with Guillain-Barré syndrome or when relevant contra-indications exist. With regard to discontinuing mechanical ventilation, considerable uncertainty persists about the best approach to wean patients, how to identify patients ready for extubation, and when to consider primary tracheostomy. Recent consensus guidelines highlight these and other knowledge gaps that are the focus of active research efforts. This chapter outlines important general principles to consider when initiating, titrating, and discontinuing mechanical ventilation in patients with acute neurologic injuries. Important disease-specific considerations are also reviewed where appropriate.

Prophylactic acid suppressants in patients with primary neurologic injury: A systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Neurocritical care patients are at risk of stress-induced gastrointestinal ulceration. We performed a systematic review and meta-analysis of stress ulcer prophylaxis (SUP) in critically ill adults admitted with a primary neurologic injury. MATERIALS AND METHODS: We included randomized controlled trials (RCTs) comparing SUP with histamine-2-receptor antagonists (H2RAs) or proton pump inhibitors (PPIs) to placebo/no prophylaxis, as well as to each other. The primary outcome was in-ICU gastrointestinal bleeding (GIB). Predefined secondary outcomes were all-cause 30-day mortality, ICU length of stay (LOS), nosocomial pneumonia, and other complications. RESULTS: We identified 14 relevant trials enrolling 1036 neurocritical care patients; 11 trials enrolling 930 patients were included in the meta-analysis. H2RAs resulted in a lower incidence of GIB as compared to placebo or no prophylaxis (Risk ratio [RR] 0.42, 95% CI 0.30-0.58; p < 0.001); PPIs with a lower risk of GIB compared to placebo/no prophylaxis (RR 0.37, 95% CI 0.23-0.59; p < 0.001). No significant difference was observed in GIB comparing PPIs with H2RAs (RR 0.53, 95% CI 0.26-1.06; p = 0.07; I2 = 0%). CONCLUSIONS: In neurocritical care patients, the overall high or unclear risk of bias of individual trials, the low event rates, and modest sample sizes preclude strong clinical inferences about the utility of SUP.