Variability of oxygen requirements in critically ill COVID-19 patients.

Background: The global scarcity of medical oxygen has proven to be catastrophic during the surges in COVID-19 cases over the past two years, with the heaviest burden felt in low- and middle-income countries. Despite its criticality, data and analyses of oxygen consumption, even for typical clinical cases, are missing. Consequently, planning oxygen needs, particularly with variable surges in COVID-19 cases, has presented a substantial challenge to policymakers and hospital decision-makers. Methods: We performed a sub-analysis of the COVID-19 Critical Care Consortium database assessing the oxygen consumption requirements of COVID-19 patients admitted to intensive care units between February 2020 and October 2021. We calculated descriptive statistics for oxygen flow-rates, stratified by oxygen supplementation method, and developed a multi-state model for estimating the frequency, therapy duration, probability of transition, and number of oxygen therapy modes per patient. Results: Overall, 12 429 patients from 35 countries received oxygen support on at least one day of their hospitalisation. Of the patients with measurable flow rates, 6142 received invasive mechanical ventilation, 838 received high-flow nasal oxygen, and 257 received both modalities. The median flow rate for mechanical ventilation was 3.2 L per minute (interquartile range (IQR) = 2.0-4.9), with a median duration of 12 days (IQR = 6-24), while the median flow rate for high-flow nasal cannula was 40 L per minute (IQR = 15-55), with a median duration of three days (IQR = 2-6). Conclusions: Oxygen consumption among critical COVID-19 patients varies by mode of delivery (invasive ventilation vs high-flow nasal cannula), across patients, and over treatment duration. Therefore, it is essential that health facilities routinely monitor oxygen utilization to better inform oxygen delivery system design and regular supply planning. Registration: ClinicalTrials.gov: CTG2021-01 ACTRN12620000421932.

Characteristics and outcomes of patients with severe COVID-19 in Indonesia: Lessons from the first wave.

BACKGROUND: Indonesia's national response to COVID-19 evolved rapidly throughout 2020. Understanding pandemic response and outcomes is crucial for better mitigation strategies ahead. This study describes the characteristics and outcomes of patients admitted to ICU during the early stages of the pandemic. METHODS: This is a multi-centre prospective observational study including patients from twelve collaborating hospitals in Indonesia. All patients were clinically suspected or laboratory-confirmed COVID-19 cases admitted to ICU between January 2020 and March 2021. The primary outcome was monthly ICU mortality. Descriptive statistics of patient characteristics and treatment were generated as secondary outcomes. RESULTS: From 559 subjects, the overall mortality was 68% and decreased over the study period, while the mortality of patients that received mechanical ventilation was 92%, consistently high over the study period. Fatal cases showed 2- and 4-day delays from symptoms onset to hospital admissions and ICU admissions, respectively. Evidence-backed approaches which could influence patient outcome, such as extracorporeal membrane oxygenation, prone positioning, renal replacement therapy, and neuromuscular blockade were scarcely administered. CONCLUSIONS: The mortality rate of COVID-19 patients in Indonesia was extremely high during the first major outbreak of disease, particularly in those mechanically ventilated. Delayed admission and unavailability of evidence-based approaches due to high burden on health facility during COVID-19 crisis could be addressed by efficient public health measures and enhancing health infrastructure to improve the future pandemic response.

The Use of Noninvasive Multimodal Neuromonitoring in Adult Critically Ill Patients With COVID-19 Infection.

INTRODUCTION: Noninvasive neuromonitoring could be a valuable option for bedside assessment of cerebral dysfunction in patients with coronavirus disease-2019 (COVID-19) admitted to intensive care units (ICUs). This systematic review aims to investigate the use of noninvasive multimodal neuromonitoring in critically ill adult patients with COVID-19 infection. METHODS: MEDLINE/PubMed, Scopus, Cochrane, and EMBASE databases were searched for studies investigating noninvasive neuromonitoring in patients with COVID-19 admitted to ICUs. The monitoring included transcranial Doppler ultrasonography (TCD), the Brain4care Corp. cerebral compliance monitor (B4C), optic nerve sheath diameter (ONSD), near infrared spectroscopy, automated pupillometry, and electroencephalography (EEG). RESULTS: Thirty-two studies that investigated noninvasive neuromonitoring techniques in patients with COVID-19 in the ICU were identified from a systematic search of 7001 articles: 1 study investigating TCD, ONSD and pupillometry; 2 studies investigating the B4C device and TCD; 3 studies investigating near infrared spectroscopy and TCD; 4 studies investigating TCD; 1 case series investigating pupillometry, and 21 studies investigating EEG. One hundred and nineteen patients underwent TCD monitoring, 47 pupillometry, 49 ONSD assessment, 50 compliance monitoring with the B4C device, and 900 EEG monitoring. Alterations in cerebral hemodynamics, brain compliance, brain oxygenation, pupillary response, and brain electrophysiological activity were common in patients with COVID-19 admitted to the ICU; these abnormalities were not clearly associated with worse outcome or the development of new neurological complications. CONCLUSIONS: The use of noninvasive multimodal neuromonitoring in critically ill COVID-19 patients could be considered to facilitate the detection of neurological derangements. Determining whether such findings allow earlier detection of neurological complications or guide appropriate therapy requires additional studies.

Neurological Manifestations of SARS-CoV-2 Infection: Protocol for a Sub-analysis of the COVID-19 Critical Care Consortium Observational Study.

Introduction: Neurological manifestations and complications in coronavirus disease-2019 (COVID-19) patients are frequent. Prior studies suggested a possible association between neurological complications and fatal outcome, as well as the existence of potential modifiable risk factors associated to their occurrence. Therefore, more information is needed regarding the incidence and type of neurological complications, risk factors, and associated outcomes in COVID-19. Methods: This is a pre-planned secondary analysis of the international multicenter observational study of the COVID-19 Critical Care Consortium (which collected data both retrospectively and prospectively from the beginning of COVID-19 pandemic) with the aim to describe neurological complications in critically ill COVID-19 patients and to assess the associated risk factors, and outcomes. Adult patients with confirmed COVID-19, admitted to Intensive Care Unit (ICU) will be considered for this analysis. Data collected in the COVID-19 Critical Care Consortium study includes patients' pre-admission characteristics, comorbidities, severity status, and type and severity of neurological complications. In-hospital mortality and neurological outcome were collected at discharge from ICU, and at 28-days. Ethics and Dissemination: The COVID-19 Critical Care Consortium main study and its amendments have been approved by the Regional Ethics Committee of participating sites. No further approval is required for this secondary analysis. Trial Registration Number: ACTRN12620000421932.

Non-Invasive Multimodal Neuromonitoring in Non-Critically Ill Hospitalized Adult Patients With COVID-19: A Systematic Review and Meta-Analysis.

Introduction: Neurological complications are frequent in patients with coronavirus disease-2019 (COVID-19). The use of non-invasive neuromonitoring in subjects without primary brain injury but with potential neurological derangement is gaining attention outside the intensive care unit (ICU). This systematic review and meta-analysis investigates the use of non-invasive multimodal neuromonitoring of the brain in non-critically ill patients with COVID-19 outside the ICU and quantifies the prevalence of abnormal neuromonitoring findings in this population. Methods: A structured literature search was performed in MEDLINE/PubMed, Scopus, Cochrane, and EMBASE to investigate the use of non-invasive neuromonitoring tools, including transcranial doppler (TCD); optic nerve sheath diameter (ONSD); near-infrared spectroscopy (NIRS); pupillometry; and electroencephalography (EEG) inpatients with COVID-19 outside the ICU. The proportion of non-ICU patients with CVOID-19 and a particular neurological feature at neuromonitoring at the study time was defined as prevalence. Results: A total of 6,593 records were identified through literature searching. Twenty-one studies were finally selected, comprising 368 non-ICU patients, of whom 97 were considered for the prevalence of meta-analysis. The pooled prevalence of electroencephalographic seizures, periodic and rhythmic patterns, slow background abnormalities, and abnormal background on EEG was.17 (95% CI 0.04-0.29), 0.42 (95% CI 0.01-0.82), 0.92 (95% CI 0.83-1.01), and.95 (95% CI 0.088-1.09), respectively. No studies investigating NIRS and ONSD outside the ICU were found. The pooled prevalence for abnormal neuromonitoring findings detected using the TCD and pupillometry were incomputable due to insufficient data. Conclusions: Neuromonitoring tools are non-invasive, less expensive, safe, and bedside available tools with a great potential for both diagnosis and monitoring of patients with COVID-19 at risk of brain derangements. However, extensive literature searching reveals that they are rarely used outside critical care settings.Systematic Review Registration: www.crd.york.ac.uk/prospero/display_record.php?RecordID=265617, identifier: CRD42021265617.

Advances in Neuroimaging and Monitoring to Defend Cerebral Perfusion in Noncardiac Surgery.

Noncardiac surgery conveys a substantial risk of secondary organ dysfunction and injury. Neurocognitive dysfunction and covert stroke are emerging as major forms of perioperative organ dysfunction, but a better understanding of perioperative neurobiology is required to identify effective treatment strategies. The likelihood and severity of perioperative brain injury may be increased by intraoperative hemodynamic dysfunction, tissue hypoperfusion, and a failure to recognize complications early in their development. Advances in neuroimaging and monitoring techniques, including optical, sonographic, and magnetic resonance, have progressed beyond structural imaging and now enable noninvasive assessment of cerebral perfusion, vascular reserve, metabolism, and neurologic function at the bedside. Translation of these imaging methods into the perioperative setting has highlighted several potential avenues to optimize tissue perfusion and deliver neuroprotection. This review introduces the methods, metrics, and evidence underlying emerging optical and magnetic resonance neuroimaging methods and discusses their potential experimental and clinical utility in the setting of noncardiac surgery.

Neurological Manifestations of Coronavirus Disease 2019: A Comprehensive Review and Meta-Analysis of the First 6 Months of Pandemic Reporting.

Background: There is growing evidence that SARS-Cov-2 infection is associated with severe neurological complications. Understanding the nature and prevalence of these neurologic manifestations is essential for identifying higher-risk patients and projecting demand for ongoing resource utilisation. This review and meta-analysis report the neurologic manifestations identified in hospitalised COVID-19 patients and provide a preliminary estimate of disease prevalence. Methods: MEDLINE, Embase and Scopus were searched for studies reporting the occurrence of neurological complications in hospitalised COVID-19 patients. Results: A total of 2,207 unique entries were identified and screened, among which 14 cohort studies and 53 case reports were included, reporting on a total of 8,577 patients. Central nervous system manifestations included ischemic stroke (n = 226), delirium (n = 79), intracranial haemorrhage (ICH, n = 57), meningoencephalitis (n = 13), seizures (n = 3), and acute demyelinating encephalitis (n = 2). Peripheral nervous system manifestations included Guillain-Barrè Syndrome (n = 21) and other peripheral neuropathies (n = 3). The pooled period prevalence of ischemic stroke from identified studies was 1.3% [95%CI: 0.9-1.8%, 102/7,715] in all hospitalised COVID-19 patients, and 2.8% [95%CI: 1.0-4.6%, 9/318] among COVID-19 patients admitted to ICU. The pooled prevalence of ICH was estimated at 0.4% [95%CI: 0-0.8%, 6/1,006]. Conclusions: The COVID-19 pandemic exerts a substantial neurologic burden which may have residual effects on patients and healthcare systems for years. Low quality evidence impedes the ability to accurately predict the magnitude of this burden. Robust studies with standardised screening and case definitions are required to improve understanding of this disease and optimise treatment of individuals at higher risk for neurologic sequelae.

Ischemic and Hemorrhagic Stroke Among Critically Ill Patients With Coronavirus Disease 2019: An International Multicenter Coronavirus Disease 2019 Critical Care Consortium Study.

OBJECTIVES: Stroke has been reported in observational series as a frequent complication of coronavirus disease 2019, but more information is needed regarding stroke prevalence and outcomes. We explored the prevalence and outcomes of acute stroke in an international cohort of patients with coronavirus disease 2019 who required ICU admission. DESIGN: Retrospective analysis of prospectively collected database. SETTING: A registry of coronavirus disease 2019 patients admitted to ICUs at over 370 international sites was reviewed for patients diagnosed with acute stroke during their stay. PATIENTS: Patients older than 18 years old with acute coronavirus disease 2019 infection in ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 2,699 patients identified (median age 59 yr; male 65%), 59 (2.2%) experienced acute stroke: 0.7% ischemic, 1.0% hemorrhagic, and 0.5% unspecified type. Systemic anticoagulant use was not associated with any stroke type. The frequency of diabetes, hypertension, and smoking was higher in patients with ischemic stroke than in stroke-free and hemorrhagic stroke patients. Extracorporeal membrane oxygenation support was more common among patients with hemorrhagic (56%) and ischemic stroke (16%) than in those without stroke (10%). Extracorporeal membrane oxygenation patients had higher cumulative 90-day probabilities of hemorrhagic (relative risk = 10.5) and ischemic stroke (relative risk = 1.7) versus nonextracorporeal membrane oxygenation patients. Hemorrhagic stroke increased the hazard of death (hazard ratio = 2.74), but ischemic stroke did not-similar to the effects of these stroke types seen in noncoronavirus disease 2019 ICU patients. CONCLUSIONS: In an international registry of ICU patients with coronavirus disease 2019, stroke was infrequent. Hemorrhagic stroke, but not ischemic stroke, was associated with increased mortality. Further, both hemorrhagic stroke and ischemic stroke were associated with traditional vascular risk factors. Extracorporeal membrane oxygenation use was strongly associated with both stroke and death.

Predicting Neurological Recovery after Traumatic Brain Injury in Children: A Systematic Review of Prognostic Models.

Predictive modeling is foundational to treatment and long-term management of children with traumatic brain injury (TBI). Assessment of injury severity in the acute-care setting enables early stratification of patients based on their risk of death, lifelong disability, or unfavorable outcome. This review evaluates predictive models that have been developed or validated for pediatric TBI patients. The predictive accuracy of these models, the outcomes and time points predicted, and the variables and statistical methods utilized in model development were compared. Embase, Scopus, MEDLINE®, and Web of Science were searched for studies that developed statistical models for predicting patient outcomes following pediatric TBI. Studies were excluded if they focused on adults or non-traumatic brain injury, or if they did not assess classification accuracy. A total of 4538 entries were identified and screened, with 7 studies included for analysis. This included five studies in which adult predictive models were validated for use in the pediatric setting, and two in which new models were derived from a pediatric cohort. Trials of adult prediction tools in pediatric cohorts, including the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) and Corticoid Randomisation After Significant Head Injury (CRASH)-TBI models, showed comparable accuracy between classification of adults and children. Models derived from pediatric cohorts showed improved accuracy. Most studies solely focused on clinical variables, with two studies incorporating biochemical and imaging variables. Predictive models for pediatric TBI are primarily based on methods and variables identified in adult studies. Although adult models have proven effective in select pediatric cohorts, they may be suboptimal when compared with models derived or adjusted for children.

NFIB Haploinsufficiency Is Associated with Intellectual Disability and Macrocephaly.

The nuclear factor I (NFI) family of transcription factors play an important role in normal development of multiple organs. Three NFI family members are highly expressed in the brain, and deletions or sequence variants in two of these, NFIA and NFIX, have been associated with intellectual disability (ID) and brain malformations. NFIB, however, has not previously been implicated in human disease. Here, we present a cohort of 18 individuals with mild ID and behavioral issues who are haploinsufficient for NFIB. Ten individuals harbored overlapping microdeletions of the chromosomal 9p23-p22.2 region, ranging in size from 225 kb to 4.3 Mb. Five additional subjects had point sequence variations creating a premature termination codon, and three subjects harbored single-nucleotide variations resulting in an inactive protein as determined using an in vitro reporter assay. All individuals presented with additional variable neurodevelopmental phenotypes, including muscular hypotonia, motor and speech delay, attention deficit disorder, autism spectrum disorder, and behavioral abnormalities. While structural brain anomalies, including dysgenesis of corpus callosum, were variable, individuals most frequently presented with macrocephaly. To determine whether macrocephaly could be a functional consequence of NFIB disruption, we analyzed a cortex-specific Nfib conditional knockout mouse model, which is postnatally viable. Utilizing magnetic resonance imaging and histology, we demonstrate that Nfib conditional knockout mice have enlargement of the cerebral cortex but preservation of overall brain structure and interhemispheric connectivity. Based on our findings, we propose that haploinsufficiency of NFIB causes ID with macrocephaly.

Intraoperative Cerebral Perfusion Disturbances During Transcatheter Aortic Valve Replacement.

BACKGROUND: Transcatheter aortic valve replacement entails profound and unavoidable hemodynamic perturbations that may contribute to the neurological injury associated with the procedure. METHODS: Thirty-one patients were monitored with cerebral oximetry as a surrogate marker of perfusion while undergoing transcatheter aortic valve replacement via a transfemoral approach under general anesthesia to detect intraoperative hypoperfusion insult. Serial neurologic, cognitive, and cerebral magnetic resonance imaging assessments were administered to objectively quantify perioperative neurologic injury and ascertain any association with significant cerebral oximetry disturbances. RESULTS: Cerebral oximetry reacted promptly to rapid ventricular pacing with significant cerebral desaturation, relative to baseline, of greater than 12% and greater than 20% in 12 of 31 (68%) and 9 of 31 (29%) patients, respectively; or to an absolute measurement of less than 50% in 10 of 31 (33%) patients. Hyperemia occurred immediately following relief of aortic stenosis exceeding baseline by greater than 10% and greater than 20% in 14 of 31 (45%) and 5 of 31 (16%) patients. Postoperative cognitive dysfunction was evident in 3 of 31 (10%) patients and new magnetic resonance imaging-defined ischemic lesions were seen in 17 of 28 (61%) patients. No patient experienced clinically apparent stroke. CONCLUSIONS: Cerebral oximetry reacted promptly to rapid ventricular pacing with significant desaturation and hyperemia a common occurrence. However, no association between this intraoperative insult and objective neurologic injury was detected.