Balancing Patient Needs With Environmental Impacts for Best Practices in General Anesthesia: Narrative Review and Clinical Perspective.

Discussions of the environmental impacts of general anesthetics have focused on greenhouse gas (GHG) emissions from inhaled agents, with those of total intravenous anesthesia (TIVA) recently coming to the forefront. Clinical experts are calling for the expansion of research toward life cycle assessment (LCA) to comprehensively study the impact of general anesthetics. We provide an overview of proposed environmental risks, including direct GHG emissions from inhaled anesthetics and non-GHG impacts and indirect GHG emissions from propofol. A practical description of LCA methodology is also provided, as well as how it applies to the study of general anesthesia. We describe available LCA studies comparing the environmental impacts of a lower carbon footprint inhaled anesthetic, sevoflurane, to TIVA/propofol and discuss their life cycle steps: manufacturing, transport, clinical use, and disposal. Significant hotspots of GHG emission were identified as the manufacturing and disposal of sevoflurane and use (attributed to the manufacture of the required syringes and syringe pumps) for propofol. However, the focus of these studies was solely on GHG emissions, excluding other environmental impacts of wasted propofol, such as water/soil toxicity. Other LCA gaps included a lack of comprehensive GHG emission estimates related to the manufacturing of TIVA plastic components, high-temperature incineration of propofol, and gas capture technologies for inhaled anesthetics. Considering that scarce LCA evidence does not allow for a definite conclusion to be drawn regarding the overall environmental impacts of sevoflurane and TIVA, we conclude that current anesthetic practice involving these agents should focus on patient needs and established best practices as more LCA research is accumulated.

Early management of adult traumatic spinal cord injury in patients with polytrauma: a consensus and clinical recommendations jointly developed by the World Society of Emergency Surgery (WSES) & the European Association of Neurosurgical Societies (EANS).

BACKGROUND: The early management of polytrauma patients with traumatic spinal cord injury (tSCI) is a major challenge. Sparse data is available to provide optimal care in this scenario and worldwide variability in clinical practice has been documented in recent studies. METHODS: A multidisciplinary consensus panel of physicians selected for their established clinical and scientific expertise in the acute management of tSCI polytrauma patients with different specializations was established. The World Society of Emergency Surgery (WSES) and the European Association of Neurosurgical Societies (EANS) endorsed the consensus, and a modified Delphi approach was adopted. RESULTS: A total of 17 statements were proposed and discussed. A consensus was reached generating 17 recommendations (16 strong and 1 weak). CONCLUSIONS: This consensus provides practical recommendations to support a clinician's decision making in the management of tSCI polytrauma patients.

Clinical practice and effect of carbon dioxide on outcomes in mechanically ventilated acute brain-injured patients: a secondary analysis of the ENIO study.

PURPOSE: The use of arterial partial pressure of carbon dioxide (PaCO2) as a target intervention to manage elevated intracranial pressure (ICP) and its effect on clinical outcomes remain unclear. We aimed to describe targets for PaCO2 in acute brain injured (ABI) patients and assess the occurrence of abnormal PaCO2 values during the first week in the intensive care unit (ICU). The secondary aim was to assess the association of PaCO2 with in-hospital mortality. METHODS: We carried out a secondary analysis of a multicenter prospective observational study involving adult invasively ventilated patients with traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), intracranial hemorrhage (ICH), or ischemic stroke (IS). PaCO2 was collected on day 1, 3, and 7 from ICU admission. Normocapnia was defined as PaCO2 > 35 and to 45 mmHg; mild hypocapnia as 32-35 mmHg; severe hypocapnia as 26-31 mmHg, forced hypocapnia as < 26 mmHg, and hypercapnia as > 45 mmHg. RESULTS: 1476 patients (65.9% male, mean age 52 ± 18 years) were included. On ICU admission, 804 (54.5%) patients were normocapnic (incidence 1.37 episodes per person/day during ICU stay), and 125 (8.5%) and 334 (22.6%) were mild or severe hypocapnic (0.52 and 0.25 episodes/day). Forced hypocapnia and hypercapnia were used in 40 (2.7%) and 173 (11.7%) patients. PaCO2 had a U-shape relationship with in-hospital mortality with only severe hypocapnia and hypercapnia being associated with increased probability of in-hospital mortality (omnibus p value = 0.0009). Important differences were observed across different subgroups of ABI patients. CONCLUSIONS: Normocapnia and mild hypocapnia are common in ABI patients and do not affect patients' outcome. Extreme derangements of PaCO2 values were significantly associated with increased in-hospital mortality.

Targeted Temperature Management for Patients with Acute Ischemic Stroke: A Literature Review.

Despite significant advances in medical imaging, thrombolytic therapy, and mechanical thrombectomy, acute ischemic strokes (AIS) remain a major cause of mortality and morbidity globally. Targeted temperature management (TTM) has emerged as a potential therapeutic intervention, aiming to mitigate neuronal damage and improve outcomes. This literature review examines the efficacy and challenges of TTM in the context of an AIS. A comprehensive literature search was conducted using databases such as PubMed, Cochrane, Web of Science, and Google Scholar. Studies were selected based on relevance and quality. We identified key factors influencing the effectiveness of TTM such as its timing, depth and duration, and method of application. The review also highlighted challenges associated with TTM, including increased pneumonia rates. The target temperature range was typically between 32 and 36 °C, with the duration of cooling from 24 to 72 h. Early initiation of TTM was associated with better outcomes, with optimal results observed when TTM was started within the first 6 h post-stroke. Emerging evidence indicates that TTM shows considerable potential as an adjunctive treatment for AIS when implemented promptly and with precision, thereby potentially mitigating neuronal damage and enhancing overall patient outcomes. However, its application is complex and requires the careful consideration of various factors.

Effect of aging on the human myometrium at single-cell resolution.

Age-associated myometrial dysfunction can prompt complications during pregnancy and labor, which is one of the factors contributing to the 7.8-fold increase in maternal mortality in women over 40. Using single-cell/single-nucleus RNA sequencing and spatial transcriptomics, we have constructed a cellular atlas of the aging myometrium from 186,120 cells across twenty perimenopausal and postmenopausal women. We identify 23 myometrial cell subpopulations, including contractile and venous capillary cells as well as immune-modulated fibroblasts. Myometrial aging leads to fewer contractile capillary cells, a reduced level of ion channel expression in smooth muscle cells, and impaired gene expression in endothelial, smooth muscle, fibroblast, perivascular, and immune cells. We observe altered myometrial cell-to-cell communication as an aging hallmark, which associated with the loss of 25 signaling pathways, including those related to angiogenesis, tissue repair, contractility, immunity, and nervous system regulation. These insights may contribute to a better understanding of the complications faced by older individuals during pregnancy and labor.

Individualized Thresholds of Hypoxemia and Hyperoxemia and their Effect on Outcome in Acute Brain Injured Patients: A Secondary Analysis of the ENIO Study.

BACKGROUND: In acute brain injury (ABI), the effects of hypoxemia as a potential cause of secondary brain damage and poor outcome are well documented, whereas the impact of hyperoxemia is unclear. The primary aim of this study was to assess the episodes of hypoxemia and hyperoxemia in patients with ABI during the intensive care unit (ICU) stay and to determine their association with in-hospital mortality. The secondary aim was to identify the optimal thresholds of arterial partial pressure of oxygen (PaO2) predicting in-hospital mortality. METHODS: We conducted a secondary analysis of a prospective multicenter observational cohort study. Adult patients with ABI (traumatic brain injury, subarachnoid aneurysmal hemorrhage, intracranial hemorrhage, ischemic stroke) with available data on PaO2 during the ICU stay were included. Hypoxemia was defined as PaO2 < 80 mm Hg, normoxemia was defined as PaO2 between 80 and 120 mm Hg, mild/moderate hyperoxemia was defined as PaO2 between 121 and 299 mm Hg, and severe hyperoxemia was defined as PaO2 levels ≥ 300 mm Hg. RESULTS: A total of 1,407 patients were included in this study. The mean age was 52 (±18) years, and 929 (66%) were male. Over the ICU stay, the fractions of patients in the study cohort who had at least one episode of hypoxemia, mild/moderate hyperoxemia, and severe hyperoxemia were 31.3%, 53.0%, and 1.7%, respectively. PaO2 values below 92 mm Hg and above 156 mm Hg were associated with an increased probability of in-hospital mortality. Differences were observed among subgroups of patients with ABI, with consistent effects only seen in patients without traumatic brain injury. CONCLUSIONS: In patients with ABI, hypoxemia and mild/moderate hyperoxemia were relatively frequent. Hypoxemia and hyperoxemia during ICU stay may influence in-hospital mortality. However, the small number of oxygen values collected represents a major limitation of the study.

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Extremely missing numerical data in Electronic Health Records for machine learning can be managed through simple imputation methods considering informative missingness: A comparative of solutions in a COVID-19 mortality case study.

BACKGROUND AND OBJECTIVE: Reusing Electronic Health Records (EHRs) for Machine Learning (ML) leads on many occasions to extremely incomplete and sparse tabular datasets, which can hinder the model development processes and limit their performance and generalization. In this study, we aimed to characterize the most effective data imputation techniques and ML models for dealing with highly missing numerical data in EHRs, in the case where only a very limited number of data are complete, as opposed to the usual case of having a reduced number of missing values. METHODS: We used a case study including full blood count laboratory data, demographic and survival data in the context of COVID-19 hospital admissions and evaluated 30 processing pipelines combining imputation methods with ML classifiers. The imputation methods included missing mask, translation and encoding, mean imputation, k-nearest neighbors' imputation, Bayesian ridge regression imputation and generative adversarial imputation networks. The classifiers included k-nearest neighbors, logistic regression, random forest, gradient boosting and deep multilayer perceptron. RESULTS: Our results suggest that in the presence of highly missing data, combining translation and encoding imputation-which considers informative missingness-with tree ensemble classifiers-random forest and gradient boosting-is a sensible choice when aiming to maximize performance, in terms of area under curve. CONCLUSIONS: Based on our findings, we recommend the consideration of this imputer-classifier configuration when constructing models in the presence of extremely incomplete numerical data in EHR.

Impact of Stepwise Recruitment Maneuvers on Cerebral Hemodynamics: Experimental Study in Neonatal Model.

BACKGROUND: Lung recruitment maneuvers (LRMs) have been demonstrated to be effective in avoiding atelectasis during general anesthesia in the pediatric population. Performing these maneuvers is safe at the systemic hemodynamic and respiratory levels. AIMS: We aimed to evaluate the impact of a stepwise LRM and individualized positive end-expiratory pressure (PEEP) on cerebral hemodynamics in an experimental neonatal model. METHODS: Eleven newborn pigs (less than 72 h old, 2.56 ± 0.18 kg in weight) were included in the study. The LRM was performed under pressure-controlled ventilation with a constant driving pressure (15 cmH2O) in a stepwise increasing PEEP model. The target peak inspiratory pressure (PIP) was 30 cmH2O and the PEEP was 15 cmH2O. The following hemodynamic variables were monitored using the PICCO® system: mean arterial pressure (MAP), central venous pressure (CVP), and cardiac output (CO). The cerebral hemodynamics variables monitored were intracranial pressure (ICP) (with an intraparenchymal Camino® catheter) and cerebral oxygen saturation (rSO2) (with the oximetry monitor INVOS 5100® system). The following respiratory parameters were monitored: oxygen saturation, fraction of inspired oxygen, partial pressure of oxygen, end-tidal carbon dioxide pressure, Pmean, PEEP, static compliance (Cstat), and dynamic compliance (Cdyn). RESULTS: All LRMs were safely performed as scheduled without any interruptions. Systemic hemodynamic stability was maintained during the lung recruitment maneuver. No changes in ICP occurred. We observed an improvement in rSO2 after the maneuver (+5.8%). CONCLUSIONS: Stepwise LRMs are a safe tool to avoid atelectasis. We did not observe an impairment in cerebral hemodynamics but an improvement in cerebral oxygenation.

Cocaine and Ischemic or Hemorrhagic Stroke: A Systematic Review and Meta-Analysis of Clinical Evidence.

Cocaine consumption has increased over the last decade. The potent sympathomimetic effects of the drug can lead to serious neurovascular complications in the form of ischemic stroke (IS), intracerebral hemorrhage (ICH), or subarachnoid hemorrhage (SAH). This systematic review and meta-analysis were designed to describe the clinical features and outcomes of patients suffering from IS, ICH, or SAH occurring in the context of cocaine use. The PubMed, Embase, Cochrane, and Web of Science libraries were queried in December 2022. Studies were included if they provided information regarding the epidemiology, clinical presentation, or outcomes in cocaine-associated strokes. Odds ratios (OR) were pooled using a random-effects model. A total of 36 papers were included. Strokes associated with cocaine use were more prevalent in younger populations and those of African American descent. Cocaine use increased the odds of IS, ICH, or SAH (OR = 5.05, p < 0.001). The odds of mortality (OR = 1.77, p = 0.0021), vasospasm (OR = 2.25, p = 0.0037), and seizures (OR = 1.61, p < 0.001) were also worse when strokes were associated with cocaine use. In addition to counseling patients on the benefits of drug cessation, clinicians should remain vigilant of the potential complications in patients who are hospitalized with cocaine-associated strokes.

The Neurological Pupil index for outcome prognostication in people with acute brain injury (ORANGE): a prospective, observational, multicentre cohort study.

BACKGROUND: Improving the prognostication of acute brain injury is a key element of critical care. Standard assessment includes pupillary light reactivity testing with a hand-held light source, but findings are interpreted subjectively; automated pupillometry might be more precise and reproducible. We aimed to assess the association of the Neurological Pupil index (NPi)-a quantitative measure of pupillary reactivity computed by automated pupillometry-with outcomes of patients with severe non-anoxic acute brain injury. METHODS: ORANGE is a multicentre, prospective, observational cohort study at 13 hospitals in eight countries in Europe and North America. Patients admitted to the intensive care unit after traumatic brain injury, aneurysmal subarachnoid haemorrhage, or intracerebral haemorrhage were eligible for the study. Patients underwent automated infrared pupillometry assessment every 4 h during the first 7 days after admission to compute NPi, with values ranging from 0 to 5 (with abnormal NPi being <3). The co-primary outcomes of the study were neurological outcome (assessed with the extended Glasgow Outcome Scale [GOSE]) and mortality at 6 months. We used logistic regression to model the association between NPi and poor neurological outcome (GOSE ≤4) at 6 months and Cox regression to model the relation of NPi with 6-month mortality. This study is registered with ClinicalTrials.gov, NCT04490005. FINDINGS: Between Nov 1, 2020, and May 3, 2022, 514 patients (224 with traumatic brain injury, 139 with aneurysmal subarachnoid haemorrhage, and 151 with intracerebral haemorrhage) were enrolled. The median age of patients was 61 years (IQR 46-71), and the median Glasgow Coma Scale score on admission was 8 (5-11). 40 071 NPi measurements were taken (median 40 per patient [20-50]). The 6-month outcome was assessed in 497 (97%) patients, of whom 160 (32%) patients died, and 241 (47%) patients had at least one recording of abnormal NPi, which was associated with poor neurological outcome (for each 10% increase in the frequency of abnormal NPi, adjusted odds ratio 1·42 [95% CI 1·27-1·64]; p<0·0001) and in-hospital mortality (adjusted hazard ratio 5·58 [95% CI 3·92-7·95]; p<0·0001). INTERPRETATION: NPi has clinically and statistically significant prognostic value for neurological outcome and mortality after acute brain injury. Simple, automatic, repeat automated pupillometry assessment could improve the continuous monitoring of disease progression and the dynamics of outcome prediction at the bedside. FUNDING: NeurOptics.

Ventilation Targets for Patients Undergoing Mechanical Thrombectomy for Acute Ischemic Stroke: A Systematic Review.

Mechanical thrombectomy (MT) has become a standard treatment for acute ischemic stroke (AIS) caused by large vessel occlusion (LVO). Recent evidence suggests that general anesthesia (GA) and mechanical ventilation do not lead to inferior neurologic outcomes if compared to non-GA. However, the guidelines lack specific recommendations for ventilation targets during MT under GA. This systematic review aims to identify ventilation strategies correlating with better neurological outcomes in AIS patients undergoing MT, particularly focusing on oxygenation and carbon dioxide (CO2) targets. A systematic search of multiple databases was conducted to identify human studies reporting the correlation between ventilation strategies and neurological outcomes in MT for AIS. Eligible studies included clinical trials, observational studies, and case-control studies. Out of 157 studies assessed, 11 met the inclusion criteria. Five studies investigated oxygenation targets, while six studies explored CO2 targets. The published studies highlighted the controversial role of supplemental normobaric oxygen therapy and its potential association with worse outcomes. Regarding CO2 targets, the studies identified a potential association between end tidal CO2 levels and functional outcomes, with hypocapnia being unfavorable. This systematic review demonstrates that the current available evidence still lacks strength to suggest specific ventilation targets, but it highlights the potential risks of hyperoxia and hypocapnia in this specific cohort of patients.

Effect of Ketamine on Postoperative Neurocognitive Disorders: A Systematic Review and Meta-Analysis.

BACKGROUND: Neurocognitive alterations in the perioperative period might be caused by a wide variety of factors including pain, blood loss, hypotension, hypoxia, micro- and macroemboli, cardiopulmonary bypass (CPB), reperfusion damage, and surgery itself, and all are risk factors for developing postoperative delirium (POD) and postoperative cognitive dysfunction (POCD). The objective of this study was to evaluate the effect of ketamine on neurocognitive dysfunction after anesthesia. METHODS: We conducted a meta-analysis of randomized controlled trials (RCTs) comparing ketamine use (experimental group) with placebo (controls). RESULTS: The model favors the control group over the experimental group in terms of frequency of hallucinations (the risk ratio with 95% CI is 1.54 [1.09, 2.19], p-value = 0.02), the number of patients readmitted within 30 days (RR with 95% CI is 0.25 [0.09, 0.70]), and the number of adverse events (overall RR with 95% CI is 1.31 [1.06, 1.62]). In terms of morphine consumption, the model favors the experimental group. CONCLUSION: There was no statistically significant difference in incidences of postoperative delirium, vasopressor requirement, and fentanyl consumption between the ketamine and control groups. However, hallucinations were more frequently reported in the ketamine group.

Heart Rate Variability for Outcome Prediction in Intracerebral and Subarachnoid Hemorrhage: A Systematic Review.

This systematic review presents clinical evidence on the association of heart rate variability with outcome prediction in intracerebral and subarachnoid hemorrhages. The literature search led to the retrieval of 19 significant studies. Outcome prediction included functional outcome, cardiovascular complications, secondary brain injury, and mortality. Various aspects of heart rate recording and analysis, based on linear time and frequency domains and a non-linear entropy approach, are reviewed. Heart rate variability was consistently associated with poor functional outcome and mortality, while controversial results were found regarding the association between heart rate variability and secondary brain injury and cardiovascular complications.

Sedation with Sevoflurane versus Propofol in COVID-19 Patients with Acute Respiratory Distress Syndrome: Results from a Randomized Clinical Trial.

BACKGROUND: Acute respiratory distress syndrome (ARDS) related to COVID-19 (coronavirus disease 2019) led to intensive care units (ICUs) collapse. Amalgams of sedative agents (including volatile anesthetics) were used due to the clinical shortage of intravenous drugs (mainly propofol and midazolam). METHODS: A multicenter, randomized 1:1, controlled clinical trial was designed to compare sedation using propofol and sevoflurane in patients with ARDS associated with COVID-19 infection in terms of oxygenation and mortality. RESULTS: Data from a total of 17 patients (10 in the propofol arm and 7 in the sevoflurane arm) showed a trend toward PaO2/FiO2 improvement and the sevoflurane arm's superiority in decreasing the likelihood of death (no statistical significance was found). CONCLUSIONS: Intravenous agents are the most-used sedative agents in Spain, even though volatile anesthetics, such as sevoflurane and isoflurane, have shown beneficial effects in many clinical conditions. Growing evidence demonstrates the safety and potential benefits of using volatile anesthetics in critical situations.

Postoperative Delirium and Cognitive Dysfunction after General and Regional Anesthesia: A Systematic Review and Meta-Analysis.

Background: Perioperative disorders of neurocognitive function are a set of heterogeneous conditions, which include transient post-operative delirium (POD) and more prolonged post-operative cognitive dysfunction (POCD). Since the number of annually performed surgical procedures is growing, we should identify which type of anesthesia is safer for preserving neurocognitive function. The purpose of this study was to compare the effect of general anesthesia (GA) and regional anesthesia (RA) in patients undergoing surgical procedures under general anesthesia and regional anesthesia. Material and methods: We searched for randomized controlled studies, which studied post-operative cognitive outcomes after general and regional anesthesia in the adult patient population. Results: Thirteen articles with 3633 patients: the RA group consisted of 1823 patients, and the GA group of 1810 patients, who were selected for meta-analysis. The overall effect of the model shows no difference between these two groups in terms of risk for post-operative delirium. The result is insensitive to the exclusion of any study. There was no difference between RA and GA in terms of post-operative cognitive dysfunction. Conclusions: There was no statistically significant difference between GA and RA in the incidence of POD. There was no statistically significant difference in the incidence of POCD per-protocol analysis, psychomotor/attention tests (preoperative/baseline, post-operative), memory tests (postoperatively, follow up), mini-mental state examination score 24 h postoperatively, post-operative reaction time three months postoperatively, controlled oral word association test, and digit copying test. There were no differences in the incidence of POCD in general and regional anesthesia at one week postoperatively, three months postoperatively, or total events (one week or three months). The incidence of post-operative mortality also did not differ between two groups.

Neurological Pupil Index and Delayed Cerebral Ischemia after Subarachnoid Hemorrhage: A Retrospective Multicentric Study.

BACKGROUND: Delayed cerebral ischemia (DCI) occurs in around 30% of patients suffering from nontraumatic subarachnoid hemorrhage (SAH) and is associated with poor neurological outcome. Whether the Neurological Pupil index (NPi) derived from the automated pupillometry could help to diagnose the occurrence of DCI remains unknown. The aim of this study was to investigate the association of NPi with the occurrence of DCI in patients with SAH. METHODS: This was a multicenter, retrospective cohort study of consecutive patients with SAH admitted to the intensive care units of five hospitals between January 2018 and December 2020 who underwent daily NPi recordings (every 8 h) during the first 10 days of admission. DCI was diagnosed according to standard definitions (in awake patients) or based on neuroimaging and neuromonitoring (in sedated or unconscious patients). An NPi < 3 was defined as abnormal. The primary outcome of the study was to assess the time course of daily NPi between patients with DCI and patients without DCI. Secondary outcome included the number of patients who had an NPi < 3 before DCI. RESULTS: A total of 210 patients were eligible for the final analysis; DCI occurred in 85 (41%) patients. Patients who developed DCI had similar values of mean and worst daily NPi over time when compared with patients without DCI. Patients with DCI had a higher proportion of at least one NPi < 3 at any moment before DCI when compared with others (39/85, 46% vs. 35/125, 38%, p = 0.009). Similarly, the worst NPi before DCI diagnosis was lower in the DCI group when compared with others (3.1 [2.5-3.8] vs. 3.7 [2.7-4.1], p = 0.05). In the multivariable logistic regression analysis, the presence of NPi < 3 was not independently associated with the development of DCI (odds ratio 1.52 [95% confidence interval 0.80-2.88]). CONCLUSIONS: In this study, NPi measured three times a day and derived from the automated pupillometry had a limited value for the diagnosis of DCI in patients with SAH.

Outcomes in Patients With COVID-19 With Acute Encephalopathy and Coma: An International Prospective Study.

BACKGROUND AND OBJECTIVES: To report the prevalence of acute encephalopathy and outcomes in patients with severe coronavirus disease 2019 (COVID-19) and to identify determinants of 90-day outcomes. METHODS: Data from adults with severe COVID-19 and acute encephalopathy were prospectively collected for patients requiring intensive care unit management in 31 university or university-affiliated intensive care units in 6 countries (France, United States, Colombia, Spain, Mexico, and Brazil) between March and September of 2020. Acute encephalopathy was defined, as recently recommended, as subsyndromal delirium or delirium or as a comatose state in case of severely decreased level of consciousness. Logistic multivariable regression was performed to identify factors associated with 90-day outcomes. A Glasgow Outcome Scale-Extended (GOS-E) score of 1-4 was considered a poor outcome (indicating death, vegetative state, or severe disability). RESULTS: Of 4,060 patients admitted with COVID-19, 374 (9.2%) experienced acute encephalopathy at or before the intensive care unit (ICU) admission. A total of 199/345 (57.7%) patients had a poor outcome at 90-day follow-up as evaluated by the GOS-E (29 patients were lost to follow-up). On multivariable analysis, age older than 70 years (odds ratio [OR] 4.01, 95% CI 2.25-7.15), presumed fatal comorbidity (OR 3.98, 95% CI 1.68-9.44), Glasgow coma scale score <9 before/at ICU admission (OR 2.20, 95% CI 1.22-3.98), vasopressor/inotrope support during ICU stay (OR 3.91, 95% CI 1.97-7.76), renal replacement therapy during ICU stay (OR 2.31, 95% CI 1.21-4.50), and CNS ischemic or hemorrhagic complications as acute encephalopathy etiology (OR 3.22, 95% CI 1.41-7.82) were independently associated with higher odds of poor 90-day outcome. Status epilepticus, posterior reversible encephalopathy syndrome, and reversible cerebral vasoconstriction syndrome were associated with lower odds of poor 90-day outcome (OR 0.15, 95% CI 0.03-0.83). DISCUSSION: In this observational study, we found a low prevalence of acute encephalopathy at ICU admission in patients with COVID-19. More than half of patients with COVID-19 presenting with acute encephalopathy had poor outcomes as evaluated by GOS-E. Determinants of poor 90-day outcome were dominated by older age, comorbidities, degree of impairment of consciousness before/at ICU admission, association with other organ failures, and acute encephalopathy etiology. TRIAL REGISTRATION INFORMATION: The study is registered with ClinicalTrials.gov, number NCT04320472.