Hyperosmolar therapy for acute brain injury: study protocol for an umbrella review of meta-analyses and an evidence mapping

Introduction Acute brain injury is a challenging public health problem worldwide. Elevated intracranial pressure is a common complication after acute brain injury. Hyperosmolar therapy is one of the main therapeutic strategies for the management of intracranial hypertension. This study protocol outlines an umbrella review of meta-analyses which will investigate the benefits and harms of hyperosmolar therapy routinely used for the management of acute brain injury in the intensive care. Methods and analysis We will search PubMed/MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews. We will include meta-analyses of primary research studies (eg, randomised controlled trials, observat…

Prevalence and risk factors for delirium in critically ill patients with COVID-19 (COVID-D): a multicentre cohort study

Background: To date, 750 000 patients with COVID-19 worldwide have required mechanical ventilation and thus are at high risk of acute brain dysfunction (coma and delirium). We aimed to investigate the prevalence of delirium and coma, and risk factors for delirium in critically ill patients with COVID-19, to aid the development of strategies to mitigate delirium and associated sequelae. Methods: This multicentre cohort study included 69 adult intensive care units (ICUs), across 14 countries. We included all patients (aged ≥18 years) admitted to participating ICUs with severe acute respiratory syndrome coronavirus 2 infection before April 28, 2020. Patients who were moribund or had life-suppo…

Acute respiratory distress syndrome in traumatic brain injury: how do we manage it?

Abstract: Traumatic brain injury (TBI) is an important cause of morbidity and mortality worldwide. TBI patients frequently suffer from lung complications and acute respiratory distress syndrome (ARDS), which is associated with poor clinical outcomes. Moreover, the association between TBI and ARDS in trauma patients is well recognized. Mechanical ventilation of patients with a concomitance of acute brain injury and lung injury can present significant challenges. Frequently, guidelines recommending management strategies for patients with traumatic brain injuries come into conflict with what is now considered best ventilator practice. In this review, we will explore the strategies of the best …

Usefulness of Cerebral Oximetry in TBI by NIRS

Measurement of cerebral oximetry by near-infrared spectroscopy provides continuous and non-invasive information about the oxygen saturation of haemoglobin in the central nervous system. This is especially important in the case of patients with traumatic brain injuries. Monitoring of cerebral oximetry in these patients could allow for the diagnosis of inadequate cerebral oxygenation caused by disturbances in cerebral blood flow. It could enable identification of episodes of hypoxia and cerebral ischemia. Continuous bedside measurement could facilitate the rapid diagnosis of intracranial bleeding or cerebrovascular autoregulation disorders and accelerate the implementation of treatment. Howev…

Hyperventilation in Severe Traumatic Brain Injury Has Something Changed in the Last Decade or Uncertainty Continues? A Brief Review

The role of noninvasive brain oximetry in adult critically ill patients without primary non-anoxic brain injury.

A primary objective in intensive care and perioperative settings is to promote an adequate supply and delivery of oxygen to tissues and organs, particularly to the brain. Cerebral near infrared spectroscopy (NIRS) is a noninvasive, continuous monitoring technique, that can be used to assess cerebral oxygenation. Using NIRS to monitor cerebral oximetry is not new and has been in widespread use in neonates and cardiac surgery for decades. In addition, it has become common to see NIRS being used in adult and pediatric cardiac surgery, acute neurological diseases, neurosurgical procedures, vascular surgery, severe trauma and other acute medical diseases. Furthermore, recent evidence suggests a …

Extubation in neurocritical care patients: the ENIO international prospective study

Purpose: Neurocritical care patients receive prolonged invasive mechanical ventilation (IMV), but there is poor specific information in this high-risk population about the liberation strategies of invasive mechanical ventilation. Methods: ENIO (NCT03400904) is an international, prospective observational study, in 73 intensive care units (ICUs) in 18 countries from 2018 to 2020. Neurocritical care patients with a Glasgow Coma Score (GCS) ≤ 12, receiving IMV ≥ 24 h, undergoing extubation attempt or tracheostomy were included. The primary endpoint was extubation failure by day 5. An extubation success prediction score was created, with 2/3 of patients randomly allocated to the training cohort …

Neuro-ICU patient disposition

This article revises the recent evidence on ICU admission criteria for acute neurological patients [traumatic brain injury (TBI) patients, postoperative neurosurgical procedures and stroke].The appropriate utilization of ICU beds is essential, but it is complex and a challenge to attain. To date there are no widely accepted international guidelines for managing these acute brain-injured patients (stroke, TBI, postneurosurgery) in the ICU. The criteria for ICU admission after neurological acute injury, high-dependency unit or a specialized neurosurgical ward vary from institution to institution depending on local structures and characteristics of the available resources. Better evidence to s…

ISARIC-COVID-19 dataset: A Prospective, Standardized, Global Dataset of Patients Hospitalized with COVID-19

The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide. Patient data are available from acute hospital admissions with COVID-19 and outpatient follow-ups. The data include signs and symptoms, pre-existing como…

Ketamine in acute phase of severe traumatic brain injury “an old drug for new uses?”

AbstractMaintaining an adequate level of sedation and analgesia plays a key role in the management of traumatic brain injury (TBI). To date, it is unclear which drug or combination of drugs is most effective in achieving these goals. Ketamine is an agent with attractive pharmacological and pharmacokinetics characteristics. Current evidence shows that ketamine does not increase and may instead decrease intracranial pressure, and its safety profile makes it a reliable tool in the prehospital environment. In this point of view, we discuss different aspects of the use of ketamine in the acute phase of TBI, with its potential benefits and pitfalls.

Cerebral Autoregulation in Non-Brain Injured Patients: A Systematic Review.

Introduction: Cerebral autoregulation (CA) plays a fundamental role in the maintenance of adequate cerebral blood flow (CBF). CA monitoring, through direct and indirect techniques, may guide an appropriate therapeutic approach aimed at improving CBF and reducing neurological complications; so far, the role of CA has been investigated mainly in brain-injured patients. The aim of this study is to investigate the role of CA in non-brain injured patients.Methods: A systematic consultation of literature was carried out. Search terms included: “CA and sepsis,” “CA and surgery,” and “CA and non-brain injury.”Results: Our research individualized 294 studies and after screening, 22 studies were anal…

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study

Invasive mechanical ventilation; COVID-19; Critical care Ventilación mecánica invasiva; COVID-19; Cuidado crítico Ventilació mecànica invasiva; COVID-19; Atenció crítica Background Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). Methods This is a multin…

Arterial and Venous Cerebral Blood Flow Velocities and Their Correlation in Healthy Volunteers and Traumatic Brain Injury Patients.

Few studies have explored the cerebral venous compartment or the correlation between venous and arterial cerebral blood flows. We aimed to correlate cerebral blood flow velocities in the arterial (middle cerebral artery) and venous (straight sinus) compartments in healthy volunteers and traumatic brain injury (TBI) patients. In addition, we determined the normative range of these parameters.A total of 122 healthy volunteers and 95 severe TBI patients of both sexes were included and stratified into 3 age groups as follows: group 1 (aged, 18 to 44 y); group 2 (aged, 45 to 64 y); group 3 (older than 65 y). Transcranial Doppler systolic cerebral blood flow velocity, diastolic cerebral blood flo…

Hemodynamic Monitoring in Patients With Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis

Aneurysmal subarachnoid hemorrhage (aSAH) often causes cardiopulmonary dysfunction. Therapeutic strategies can be guided by standard (invasive arterial/central venous pressure measurements, fluid balance assessment), and/or advanced (pulse index continuous cardiac output, pulse dye densitometry, pulmonary artery catheterization) hemodynamic monitoring. We conducted a systematic review and meta-analysis of the literature to determine whether standard compared with advanced hemodynamic monitoring can improve patient management and clinical outcomes after aSAH. A literature search was performed for articles published between January 1, 2000 and January 1, 2019. Studies involving aSAH patients …

Intracranial pressure monitoring in patients with acute brain injury in the intensive care unit (SYNAPSE-ICU): an international, prospective observational cohort study

Background: The indications for intracranial pressure (ICP) monitoring in patients with acute brain injury and the effects of ICP on patients’ outcomes are uncertain. The aims of this study were to describe current ICP monitoring practises for patients with acute brain injury at centres around the world and to assess variations in indications for ICP monitoring and interventions, and their association with long-term patient outcomes. Methods: We did a prospective, observational cohort study at 146 intensive care units (ICUs) in 42 countries. We assessed for eligibility all patients aged 18 years or older who were admitted to the ICU with either acute brain injury due to primary haemorrhagic…

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, suba…

Suppression of Electrographic Seizures Is Associated with Amelioration of QTc Interval Prolongation in Patients with Traumatic Brain Injury.

Introduction: Disorders in electroencephalography (EEG) are commonly noted in patients with traumatic brain injury (TBI) and may be associated with electrocardiographic disturbances. Electrographic seizures (ESz) are the most common features in these patients. This study aimed to explore the relationship between ESz and possible changes in QTc interval and spatial QRS-T angle both during ESz and after ESz resolution. Methods: Adult patients with TBI were studied. Surface 12-lead ECGs were recorded using a Cardiax device during ESz events and 15 min after their effective suppression using barbiturate infusion. The ESz events were diagnosed using Masimo Root or bispectral index (BIS) devices.…

Characteristics and outcomes of an international cohort of 600 000 hospitalized patients with COVID-19

Abstract Background We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, one of the world's largest international, standardized data sets concerning hospitalized patients. Methods The data set analysed includes COVID-19 patients hospitalized between January 2020 and January 2022 in 52 countries. We investigated how symptoms on admission, co-morbidities, risk factors and treatments varied by age, sex and other characteristics. We used Cox regression models to investigate associations between demographics, symptoms, co-morbidities and other factors with risk of death, admiss…

Additional file 4 of Ketamine in acute phase of severe traumatic brain injury “an old drug for new uses?”

Additional file 4: Table S1. Comparative cost of 24 hours intravenous infusion of sedative and analgesic drugs. mg: milligrams; kg: kilograms; h: hour; min: minute; mcg: micrograms

Potentially Detrimental Effects of Hyperosmolality in Patients Treated for Traumatic Brain Injury

Hyperosmotic therapy is commonly used to treat intracranial hypertension in traumatic brain injury patients. Unfortunately, hyperosmolality also affects other organs. An increase in plasma osmolality may impair kidney, cardiac, and immune function, and increase blood–brain barrier permeability. These effects are related not only to the type of hyperosmotic agents, but also to the level of hyperosmolality. The commonly recommended osmolality of 320 mOsm/kg H2O seems to be the maximum level, although an increase in plasma osmolality above 310 mOsm/kg H2O may already induce cardiac and immune system disorders. The present review focuses on the adverse effects of hyperosmolality on the function…

Effects of Age and Sex on Optic Nerve Sheath Diameter in Healthy Volunteers and Patients With Traumatic Brain Injury.

The measurement of optic nerve sheath diameter (ONSD) has been reported as a non-invasive marker for intracranial pressure (ICP). Nevertheless, it is uncertain whether possible ONSD differences occur with age and sex in healthy and brain-injured populations. The aim of this study was to investigate the effects of sex and age on ONSD in healthy volunteers and patients with traumatic brain injury. We prospectively included 122 healthy adult volunteers (Galliera Hospital, Genova, Italy), and compared age/sex dependence of ONSD to 95 adult patients (Addenbrooke's Hospital, Cambridge, UK) with severe traumatic brain injury (TBI) requiring intubation and invasive ICP monitoring. The two groups we…

Association of country income level with the characteristics and outcomes of critically ill patients hospitalized with acute kidney injury and COVID-19

Introduction Acute kidney injury (AKI) has been identified as one of the most common and significant problems in hospitalized patients with COVID-19. However, studies examining the relationship between COVID-19 and AKI in low- and low-middle income countries (LLMIC) are lacking. Given that AKI is known to carry a higher mortality rate in these countries, it is important to understand differences in this population. Methods This prospective, observational study examines the AKI incidence and characteristics of 32,210 patients with COVID-19 from 49 countries across all income levels who were admitted to an intensive care unit during their hospital stay. Results Among patients with COVID-19 ad…

Changes in Subendocardial Viability Ratio in Traumatic Brain Injury Patients

Background: Traumatic brain injury (TBI) is often associated with cardiac dysfunction, which is a consequence of the brain–heart cross talk. The subendocardial viability ratio (SEVR) is an estimate...

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Additional file 1 of Intraoperative ventilator settings and their association with postoperative pulmonary complications in neurosurgical patients: post-hoc analysis of LAS VEGAS study

Additional file 1.

Treatments for intracranial hypertension in acute brain-injured patients: grading, timing, and association with outcome. Data from the SYNAPSE-ICU study

Purpose: Uncertainties remain about the safety and efficacy of therapies for managing intracranial hypertension in acute brain injured (ABI) patients. This study aims to describe the therapeutical approaches used in ABI, with/without intracranial pressure (ICP) monitoring, among different pathologies and across different countries, and their association with six months mortality and neurological outcome. Methods: A preplanned subanalysis of the SYNAPSE-ICU study, a multicentre, prospective, international, observational cohort study, describing the ICP treatment, graded according to Therapy Intensity Level (TIL) scale, in patients with ABI during the first week of intensive care unit (ICU) a…

Lung Injury Is a Predictor of Cerebral Hypoxia and Mortality in Traumatic Brain Injury

Background: A major contributor to unfavorable outcome after traumatic brain injury (TBI) is secondary brain injury. Low brain tissue oxygen tension (PbtO2) has shown to be an independent predictor of unfavorable outcome. Although PbtO2 provides clinicians with an understanding of the ischemic and non-ischemic derangements of brain physiology, its value does not take into consideration systemic oxygenation that can influence patients' outcomes. This study analyses brain and systemic oxygenation and a number of related indices in TBI patients: PbtO2, partial arterial oxygenation pressure (PaO2), PbtO2/PaO2, ratio of PbtO2 to fraction of inspired oxygen (FiO2), and PaO2/FiO2. The primary aim …

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 (H…

Plasma Hyperosmolality Prolongs QTc Interval and Increases Risk for Atrial Fibrillation in Traumatic Brain Injury Patients

Introduction: Hyperosmotic therapy with mannitol is frequently used for treatment cerebral edema, and 320 mOsm/kg H2O has been recommended as a high limit for therapeutic plasma osmolality. However, plasma hyperosmolality may impair cardiac function, increasing the risk of cardiac events. The aim of this study was to analyze the relation between changes in plasma osmolality and electrocardiographic variables and cardiac arrhythmia in patients treated for isolated traumatic brain injury (iTBI). Methods: Adult iTBI patients requiring mannitol infusion following cerebral edema, and with a Glasgow Coma Score below 8, were included. Plasma osmolality was measured with Osmometr 800 CLG. Spatial Q…

Decompressive Craniectomy Improves QTc Interval in Traumatic Brain Injury Patients

Background: Traumatic brain injury (TBI) is commonly associated with cardiac dysfunction, which may be reflected by abnormal electrocardiograms (ECG) and/or contractility. TBI-related cardiac disorders depend on the type of cerebral injury, the region of brain damage and the severity of the intracranial hypertension. Decompressive craniectomy (DC) is commonly used to reduce intra-cranial hypertension (ICH). Although DC decreases ICH rapidly, its effect on ECG has not been systematically studied. The aim of this study was to analyze the changes in ECG in patients undergoing DC. Methods: Adult patients without previously known cardiac diseases treated for isolated TBI with DC were studied. EC…

Authors' reply-multi-organ ultrasonography: a stethoscope for the body

We read with great interest the letter from Sakka et al . (1) commenting our article (2) on comprehensive haemodynamic monitoring in patients with acute respiratory distress syndrome (ARDS) and traumatic brain injury (TBI). We agree with the authors that haemodynamic monitoring has to be implemented in patients with ARDS complicating TBI.

Additional file 5 of Ketamine in acute phase of severe traumatic brain injury “an old drug for new uses?”

Additional file 5: Figure S5. Potential indications of ketamine continuous infusion in traumatic brain injury.

Additional file 1 of Ketamine in acute phase of severe traumatic brain injury “an old drug for new uses?”

Additional file 1: Figure S1. Systemic and cerebral consequences of pain and agitation. SIRS: systemic inflammatory response syndrome; Tº: central temperature; HR: heart rate; pa02: oxygen arterial pressure; paCO2: carbon dioxide arterial pressure; coagul: coagulation alterations; IAP: intraabdominal pressure; UO: urinary output; Hypovol: hypovolemia; Hypergly: hyperglycemia; ICP: intracranial pressure; CBF: cerebral blood flow; CPP: cerebral perfusion pressure; CMO2: cerebral metabolic rate of oxygen; CMGl: cerebral metabolic rate of glycemia; CBV: cerebral blood volume.

Additional file 2 of Ketamine in acute phase of severe traumatic brain injury “an old drug for new uses?”

Additional file 2: Figure S2. Sedation and Analgesia ideal level.

Additional file 3 of Ketamine in acute phase of severe traumatic brain injury “an old drug for new uses?”

Additional file 3: Figure S3. Mechanisms of neuroprotection by ketamine. Ketamine is a “glutamate modulator.” It exerts its effect basically at two levels: a) presynaptic, inhibiting the release of glutamate and b) post-synaptic, acting as a competitive blocker of N-Methyl-D-Aspartate receptors, thereby excitotoxic injury through inhibiting the entry of calcium into cells, the formation of nitric oxide and oxygen free radicals. Modulates glucose metabolism and the generation of mitochondrial ATP. Inhibits the apoptotic phenomenon. Additionally, it inhibits spreading depolarizations and acts as an antithrombotic and anti-inflammatory by inhibiting platelet aggregation and the production and …