Role of brain tissue oxygenation (PbtO₂) in the management of subarachnoid haemorrhage: a scoping review protocol.

In patients with subarachnoid haemorrhage (SAH), the initial brain oedema and increased blood volume can cause an increase in intracranial pressure (ICP) leading to impaired cerebral perfusion and tissue hypoxia. However, ICP monitoring may not be enough to detect tissue hypoxia, which can also occur in the absence of elevated ICP. Moreover, some patients will experience tissue hypoxia in a later phase after admission due to the occurrence of delayed cerebral ischaemia. Therefore, the measurement of brain oxygenation using invasive techniques has become of great interest. This scoping review seeks to examine the role of brain tissue oxygenation in the management of patients with SAH, mapping the existing literature to identify areas for future research. This scoping review has been planned following the Joanna Briggs Institute recommendations and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The literature search will be performed using several databases: Medline, EMBASE, the Cochrane Central Register of Controlled Trials and Grey literature. The database searches are planned from the inception to May 2020. Two reviewers will independently screen titles and abstracts, followed by full-text screening of potentially relevant articles with a standardised data extraction. Articles eligible for the inclusion will be discussed with a third reviewer. This paper does not require ethics approval. The results of our evaluation will be disseminated on author's web sites. Additional dissemination will occur through presentations at conferences, such as courses and science education conferences, regionally and nationally, and through articles published in peer-reviewed journals. Open Science Framework Registration: https://doi.org/10.17605/OSF.IO/ZYJ7R.Trial registration numberClinicalTrials.gov Identifier: NCT03754114

Hemoglobin concentrations and RBC transfusion thresholds in patients with acute brain injury: an international survey.

The optimal hemoglobin (Hb) threshold at which to initiate red blood cell (RBC) transfusion in patients with acute brain injury is unknown. The aim of this survey was to investigate RBC transfusion practices used with these patients. We conducted a web-based survey within various societies of critical care medicine for intensive care unit (ICU) physicians who currently manage patients with primary acute brain injury. A total of 868 responses were obtained from around the world, half of which (n = 485) were from European centers; 204 (24%) respondents had a specific certificate in neurocritical care, and most were specialists in anesthesiology or intensive care and had less than 15 years of practice experience. Four hundred sixty-six respondents (54%) said they used an Hb threshold of 7-8 g/dl to initiate RBC transfusion after acute brain injury, although half of these respondents used a different threshold (closer to 9 g/dl) in patients with traumatic brain injury, subarachnoid hemorrhage, or ischemic stroke. Systemic and cerebral factors were reported as influencing the need for higher Hb thresholds. Most respondents agreed that a randomized clinical trial was needed to compare two different Hb thresholds for RBC transfusion, particularly in patients with traumatic brain injury, subarachnoid hemorrhage, and ischemic stroke. The Hb threshold used for RBC transfusion after acute brain injury was less than 8 g/dl in half of the ICU clinicians who responded to our survey. However, more than 50% of these physicians used higher Hb thresholds in certain conditions

The Association Between Peri-Hemorrhagic Metabolites and Cerebral Hemodynamics in Comatose Patients With Spontaneous Intracerebral Hemorrhage: An International Multicenter Pilot Study Analysis.

Background and Objective: Cerebral microdialysis (CMD) enables monitoring brain tissue metabolism and risk factors for secondary brain injury such as an imbalance of consumption, altered utilization, and delivery of oxygen and glucose, frequently present following spontaneous intracerebral hemorrhage (SICH). The aim of this study was to evaluate the relationship between lactate/pyruvate ratio (LPR) with hemodynamic variables [mean arterial blood pressure (MABP), intracranial pressure (ICP), cerebral perfusion pressure (CPP), and cerebrovascular pressure reactivity (PRx)] and metabolic variables (glutamate, glucose, and glycerol), within the cerebral peri-hemorrhagic region, with the hypothesis that there may be an association between these variables, leading to a worsening of outcome in comatose SICH patients. Methods: This is an international multicenter cohort study regarding a retrospective dataset analysis of non-consecutive comatose patients with supratentorial SICH undergoing invasive multimodality neuromonitoring admitted to neurocritical care units pertaining to three different centers. Patients with SICH were included if they had an indication for invasive ICP and CMD monitoring, were >18 years of age, and had a Glasgow Coma Scale (GCS) score of ≤8. Results: Twenty-two patients were included in the analysis. A total monitoring time of 1,558 h was analyzed, with a mean (SD) monitoring time of 70.72 h (66.25) per patient. Moreover, 21 out of the 22 patients (95%) had disturbed cerebrovascular autoregulation during the observation period. When considering a dichotomized LPR for a threshold level of 25 or 40, there was a statistically significant difference in all the measured variables (PRx, glucose, glutamate), but not glycerol. When dichotomized PRx was considered as the dependent variable, only LPR was related to autoregulation. A lower PRx was associated with a higher survival [27.9% (23.1%) vs. 56.0% (31.3%), p = 0.03]. Conclusions: According to our results, disturbed autoregulation in comatose SICH patients is common. It is correlated to deranged metabolites within the peri-hemorrhagic region of the clot and is also associated with poor outcome

Incidence and prognosis of dysnatraemia in critically ill patients: Analysis of a large prevalence study

Background: The objective of this study is to assess the impact of dysnatraemia on mortality among intensive care unit (ICU) patients in a large, international cohort. Material and methods: Analysis of the Extended Prevalence of Infection in Intensive Care (EPIC II) study, a 1-day (8 May 2007) worldwide multicenter, prospective point prevalence study. Hyponatraemia was categorized as mild (130-134 mM/L), moderate (125-129 mM/L) or severe ( 155 mM/L). Patients with normal serum sodium (135-145 mM/L) constituted the reference group. The main outcome was hospital mortality. Analysis was conducted separately for patients admitted on the study day (25·8%) and those already present on the ICU (74·2%). Results: Serum sodium was measured in 13 276 of the 13 796 patients (96·2%). A total of 3815 patients (28·7%) had dysnatraemia: 12·9% with hyponatraemia and 15·8% with hypernatraemia. The prevalence of dysnatraemia was significantly greater in patients already present on the ICU prior to the study day than for those just admitted (13·1% vs. 12·3% for hyponatraemia and 17·1% vs. 12·1% for hypernatraemia, both P < 0·001). Hospital mortality rates were higher in patients with dysnatraemia than in those with normal sodium levels and were directly related to the severity of hypo- and hypernatraemia. This association between dysnatraemia and mortality was similar in infected and noninfected patients (P = 0·061). Conclusions: Dysnatraemia is more frequent during the ICU stay than on the day of admission. Dysnatraemia in the ICU - even mild - is an independent predictor of increased hospital mortality

Prediction of poor neurological outcome in comatose survivors of cardiac arrest: a systematic review.

To assess the ability of clinical examination, blood biomarkers, electrophysiology, or neuroimaging assessed within 7 days from return of spontaneous circulation (ROSC) to predict poor neurological outcome, defined as death, vegetative state, or severe disability (CPC 3-5) at hospital discharge/1 month or later, in comatose adult survivors from cardiac arrest (CA). PubMed, EMBASE, Web of Science, and the Cochrane Database of Systematic Reviews (January 2013-April 2020) were searched. Sensitivity and false-positive rate (FPR) for each predictor were calculated. Due to heterogeneities in recording times, predictor thresholds, and definition of some predictors, meta-analysis was not performed. Ninety-four studies (30,200 patients) were included. Bilaterally absent pupillary or corneal reflexes after day 4 from ROSC, high blood values of neuron-specific enolase from 24 h after ROSC, absent N20 waves of short-latency somatosensory-evoked potentials (SSEPs) or unequivocal seizures on electroencephalogram (EEG) from the day of ROSC, EEG background suppression or burst-suppression from 24 h after ROSC, diffuse cerebral oedema on brain CT from 2 h after ROSC, or reduced diffusion on brain MRI at 2-5 days after ROSC had 0% FPR for poor outcome in most studies. Risk of bias assessed using the QUIPS tool was high for all predictors. In comatose resuscitated patients, clinical, biochemical, neurophysiological, and radiological tests have a potential to predict poor neurological outcome with no false-positive predictions within the first week after CA. Guidelines should consider the methodological concerns and limited sensitivity for individual modalities. (PROSPERO CRD42019141169)

Quantitative versus standard pupillary light reflex for early prognostication in comatose cardiac arrest patients: an international prospective multicenter double-blinded study.

To assess the ability of quantitative pupillometry [using the Neurological Pupil index (NPi)] to predict an unfavorable neurological outcome after cardiac arrest (CA). We performed a prospective international multicenter study (10 centers) in adult comatose CA patients. Quantitative NPi and standard manual pupillary light reflex (sPLR)-blinded to clinicians and outcome assessors-were recorded in parallel from day 1 to 3 after CA. Primary study endpoint was to compare the value of NPi versus sPLR to predict 3-month Cerebral Performance Category (CPC), dichotomized as favorable (CPC 1-2: full recovery or moderate disability) versus unfavorable outcome (CPC 3-5: severe disability, vegetative state, or death). At any time between day 1 and 3, an NPi ≤ 2 (n = 456 patients) had a 51% (95% CI 49-53) negative predictive value and a 100% positive predictive value [PPV; 0% (0-2) false-positive rate], with a 100% (98-100) specificity and 32% (27-38) sensitivity for the prediction of unfavorable outcome. Compared with NPi, sPLR had significantly lower PPV and significantly lower specificity (p  &lt; 0.001 at day 1 and 2; p  = 0.06 at day 3). The combination of NPi ≤ 2 with bilaterally absent somatosensory evoked potentials (SSEP; n = 188 patients) provided higher sensitivity [58% (49-67) vs. 48% (39-57) for SSEP alone], with comparable specificity [100% (94-100)]. Quantitative NPi had excellent ability to predict an unfavorable outcome from day 1 after CA, with no false positives, and significantly higher specificity than standard manual pupillary examination. The addition of NPi to SSEP increased sensitivity of outcome prediction, while maintaining 100% specificity

Extracorporeal membrane oxygenation during pregnancy and peripartal. An international retrospective multicenter study

Introduction Extracorporeal Membrane Oxygenation (ECMO) may be used in the setting of pregnancy or the peripartal period, however its utility has not been well-characterized. This study aims to give an overview on the prevalence of peripartel ECMO cases and further assess the indications and outcomes of ECMO in this setting across multiple centers and countries. Methods A retrospective, multicenter, international cohort study of pregnant and peripartum ECMO cases was performed. Data were collected from six ECMO centers across three continents over a 10-year period. Results A total of 60 pregnany/peripartal ECMO cases have been identified. Most frequent indications are acute respiratory distress syndrome (n = 30) and pulmonary embolism (n = 5). Veno-venous ECMO mode was applied more often (77%). ECMO treatment during pregnancy was performed in 17 cases. Maternal and fetal survival was high with 87% (n = 52), respectively 73% (n = 44). Conclusions Various emergency scenarios during pregnancy and at time of delivery may require ECMO treatment. Peripartal mortality in a well-resourced setting is rare, however emergencies in the labor room occur and knowledge of available rescue therapy is essential to improve outcome. Obstetricians and obstetric anesthesiologists should be aware of the availability of ECMO resource at their hospital or region to ensure immediate contact when needed

Acute liver transplantation in a 41-year-old male patient presenting symptoms of adult-onset Still's disease

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Vancomycin Pharmacokinetics Throughout Life: Results from a Pooled Population Analysis and Evaluation of Current Dosing Recommendations

Abstract Background and Objectives Uncertainty exists regarding the optimal dosing regimen for vancomycin in diferent patient populations, leading to a plethora of subgroup-specifc pharmacokinetic models and derived dosing regimens. We aimed to investigate whether a single model for vancomycin could be developed based on a broad dataset covering the extremes of patient characteristics. Furthermore, as a benchmark for current dosing recommendations, we evaluated and optimised the expected vancomycin exposure throughout life and for specifc patient subgroups. Methods A pooled population-pharmacokinetic model was built in NONMEM based on data from 14 diferent studies in diferent patient populations. Steady-state exposure was simulated and compared across patient subgr

Variation in Structure and Process of Care in Traumatic Brain Injury: Provider Profiles of European Neurotrauma Centers Participating in the CENTER-TBI Study.

INTRODUCTION: The strength of evidence underpinning care and treatment recommendations in traumatic brain injury (TBI) is low. Comparative effectiveness research (CER) has been proposed as a framework to provide evidence for optimal care for TBI patients. The first step in CER is to map the existing variation. The aim of current study is to quantify variation in general structural and process characteristics among centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. METHODS: We designed a set of 11 provider profiling questionnaires with 321 questions about various aspects of TBI care, chosen based on literature and expert opinion. After pilot testing, questionnaires were disseminated to 71 centers from 20 countries participating in the CENTER-TBI study. Reliability of questionnaires was estimated by calculating a concordance rate among 5% duplicate questions. RESULTS: All 71 centers completed the questionnaires. Median concordance rate among duplicate questions was 0.85. The majority of centers were academic hospitals (n = 65, 92%), designated as a level I trauma center (n = 48, 68%) and situated in an urban location (n = 70, 99%). The availability of facilities for neuro-trauma care varied across centers; e.g. 40 (57%) had a dedicated neuro-intensive care unit (ICU), 36 (51%) had an in-hospital rehabilitation unit and the organization of the ICU was closed in 64% (n = 45) of the centers. In addition, we found wide variation in processes of care, such as the ICU admission policy and intracranial pressure monitoring policy among centers. CONCLUSION: Even among high-volume, specialized neurotrauma centers there is substantial variation in structures and processes of TBI care. This variation provides an opportunity to study effectiveness of specific aspects of TBI care and to identify best practices with CER approaches