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BackgroundAugmented renal clearance (ARC) might lead to subtherapeutic plasma levels of drugs with predominant renal clearance. Early identification of ARC remains challenging for the intensive care unit (ICU) physician. We developed and validated the ARC predictor, a clinical prediction model for ARC on the next day during ICU stay, and made it available via an online calculator. Its predictive performance was compared with that of two existing models for ARC.MethodsA large multicenter database including medical, surgical and cardiac ICU patients (n = 33258 ICU days) from three Belgian tertiary care academic hospitals was used for the development of the prediction model. Development was based on clinical information available during ICU stay. We assessed performance by measuring discrimination, calibration and net benefit. The final model was externally validated (n = 10259 ICU days) in a single-center population.ResultsARC was found on 19.6% of all ICU days in the development cohort. Six clinical variables were retained in the ARC predictor: day from ICU admission, age, sex, serum creatinine, trauma and cardiac surgery. External validation confirmed good performance with an area under the curve of 0.88 (95% CI 0.87 – 0.88), and a sensitivity and specificity of 84.1 (95% CI 82.5 – 85.7) and 76.3 (95% CI 75.4 – 77.2) at the default threshold probability of 0.2, respectively.ConclusionARC on the next day can be predicted with good performance during ICU stay, using routinely collected clinical information that is readily available at bedside. The ARC predictor is available at www.arcpredictor.com.

Supplemental Digital Content is available in the text., Objectives: Cerebral oximetry by near-infrared spectroscopy is used frequently in critically ill children but guidelines on its use for decision making in the PICU are lacking. We investigated cerebral near-infrared spectroscopy oximetry in its ability to predict severe acute kidney injury after pediatric cardiac surgery and assessed its additional predictive value to routinely collected data. Design: Prospective observational study. The cerebral oximeter was blinded to clinicians. Setting: Twelve-bed tertiary PICU, University Hospitals Leuven, Belgium, between October 2012 and November 2015. Patients: Critically ill children with congenital heart disease, younger than 12 years old, were monitored with cerebral near-infrared spectroscopy oximetry from PICU admission until they were successfully weaned off mechanical ventilation. Interventions: None. Measurements and Main Results: The primary outcome was prediction of severe acute kidney injury 6 hours before its occurrence during the first week of intensive care. Near-infrared spectroscopy-derived predictors and routinely collected clinical data were compared and combined to assess added predictive value. Of the 156 children included in the analysis, 55 (35%) developed severe acute kidney injury. The most discriminant near-infrared spectroscopy-derived predictor was near-infrared spectroscopy variability (area under the receiver operating characteristic curve, 0.68; 95% CI, 0.67–0.68), but was outperformed by a clinical model including baseline serum creatinine, cyanotic cardiopathy pre-surgery, blood pressure, and heart frequency (area under the receiver operating characteristic curve, 0.75; 95% CI, 0.75–0.75; p < 0.001). Combining clinical and near-infrared spectroscopy information improved model performance (area under the receiver operating characteristic curve, 0.79; 95% CI, 0.79–0.80; p < 0.001). Conclusions: After pediatric cardiac surgery, near-infrared spectroscopy variability combined with clinical information improved discrimination for acute kidney injury. Future studies are required to identify whether supplementary, timely clinical interventions at the bedside, based on near-infrared spectroscopy variability analysis, could improve outcome.

Objectives: To assess whether near-infrared cerebral tissue oxygen saturation, measured with the FORESIGHT cerebral oximeter (CAS Medical Systems, Branford, CT) predicts PICU length of stay, duration of invasive mechanical ventilation, and mortality in critically ill children after pediatric cardiac surgery. Design: Single-center prospective, observational study. Setting: Twelve-bed PICU of a tertiary academic hospital. Patients: Critically ill children and infants with congenital heart disease, younger than 12 years old, admitted to the PICU between October 2012 and November 2015. Children were monitored with the FORESIGHT cerebral oximeter from PICU admission until they were weaned off mechanical ventilation. Clinicians were blinded to cerebral tissue oxygen saturation data. Interventions: None. Measurements and Main Results: Primary outcome was the predictive value of the first 24 hours of postoperative cerebral tissue oxygen saturation for duration of PICU stay (median [95% CI], 4 d [3–8 d]) and duration of mechanical ventilation (median [95% CI], 111.3 hr (69.3–190.4 hr]). We calculated predictors on the first 24 hours of cerebral tissue oxygen saturation monitoring. The association of each individual cerebral tissue oxygen saturation predictor and of a combination of predictors were assessed using univariable and multivariable bootstrap analyses, adjusting for age, weight, gender, Pediatric Index of Mortality 2, Risk Adjustment in Congenital Heart Surgery 1, cyanotic heart defect, and time prior to cerebral tissue oxygen saturation monitoring. The most important risk factors associated with worst outcomes were an increased SD of a smoothed cerebral tissue oxygen saturation signal and an elevated cerebral tissue oxygen saturation desaturation score. Conclusions: Increased SD of a smoothed cerebral tissue oxygen saturation signal and increased depth and duration of desaturation below the 50% saturation threshold were associated with longer PICU and hospital stays and with longer duration of mechanical ventilation after pediatric cardiac surgery. ispartof: Pediatric Critical Care Medicine vol:19 issue:5 pages:433-441 ispartof: location:United States status: published

The definition of cerebral perfusion pressure (CPP) secondary insults in severe traumatic brain injury remains unclear. The purpose of the present study is to visualize the association of intensity and duration of episodes below or above cerebral perfusion pressure thresholds and outcome. The analysis was based on prospectively collected minute-by-minute intracranial pressure (ICP) and blood pressure data and outcome from 259 adult patients. The relationship of episodes of CPP below or above a certain threshold for certain duration with the 6-month Glasgow Outcome Score was visualized, separately for episodes of active or deficient autoregulation (AR). In adults ≤ 65y, an almost exponential transition curve separates the episodes of CPP associated with better outcomes from the episodes of low CPP associated with worse outcomes, indicating that lower CPP could only be tolerated for a brief time. Analysis of episodes of high CPP again showed a time-intensity dependent association with outcome. When combining the two plots, a safe CPP zone between 60 and 70 mmHg could be delineated, however only for AR active insults. AR status predominantly affected the transition curve for insults of low CPP. Episodes with ICP > 25 mmHg were associated with poor outcome regardless of CPP. In conclusion, in the present study the CPP pressure-time burden associated with poor outcome was visualized. A safe zone between 60 and 70 mmHg could be identified for adults ≤ 65y, provided AR was active and ICP was ≤ 25 mmHg. Deficient AR reduces the tolerability for low CPP. ispartof: Journal of Neurotrauma vol:34 issue:16 pages:2425-2431 ispartof: location:United States status: published

ispartof: Intensive Care Medicine vol:43 issue:6 pages:870-873 ispartof: location:United States status: published

Objective: A model for early detection of episodes of increased intracranial pressure in traumatic brain injury patients has been previously developed and validated based on retrospective adult patient data from the multicenter Brain-IT database. The purpose of the present study is to validate this early detection model in different cohorts of recently treated adult and pediatric traumatic brain injury patients. Design: Prognostic modeling. Noninterventional, observational, retrospective study. Setting and Patients: The adult validation cohort comprised recent traumatic brain injury patients from San Gerardo Hospital in Monza (n = 50), Leuven University Hospital (n = 26), Antwerp University Hospital (n = 19), Tübingen University Hospital (n = 18), and Southern General Hospital in Glasgow (n = 8). The pediatric validation cohort comprised patients from neurosurgical and intensive care centers in Edinburgh and Newcastle (n = 79). Interventions: None. Measurements and Main Results: The model's performance was evaluated with respect to discrimination, calibration, overall performance, and clinical usefulness. In the recent adult validation cohort, the model retained excellent performance as in the original study. In the pediatric validation cohort, the model retained good discrimination and a positive net benefit, albeit with a performance drop in the remaining criteria. Conclusions: The obtained external validation results confirm the robustness of the model to predict future increased intracranial pressure events 30 minutes in advance, in adult and pediatric traumatic brain injury patients. These results are a large step toward an early warning system for increased intracranial pressure that can be generally applied. Furthermore, the sparseness of this model that uses only two routinely monitored signals as inputs (intracranial pressure and mean arterial blood pressure) is an additional asset.

ispartof: BRITISH JOURNAL OF ANAESTHESIA vol:126 issue:1 pages:E15-E17 ispartof: location:England status: published

OBJECTIVE: To assess the predictive value of JC virus (JCV) PCR in cerebrospinal fluid (CSF) in the diagnosis of progressive multifocal leukoencephalopathy (PML). METHODS: We conducted a retrospective database query to identify patients with positive CSF JCV PCR. Clinical features, final diagnosis and quantitative PCR results were obtained. RESULTS: A positive CSF JCV PCR had a PPV of 10.4% for the diagnosis of PML. A weakly positive PCR had a PPV of 1.6%, whereas a moderately to highly positive PCR had a PPV of 92.3%. A PPV of 0.0% was observed in immunocompetent patients and in patients without compatible clinical or radiological features. CONCLUSIONS: A false-positive CSF JCV PCR is highly prevalent in our clinical practice. This test should be reserved for patients with a clinical suspicion of PML and the quantitative result of the PCR should be taken into account when making the diagnosis of PML. ispartof: DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE vol:95 issue:3 ispartof: location:United States status: published

Brain injury; Head trauma; Algorithm Daño cerebral; Trauma en la cabeza; Algoritmo Lesió cerebral; Trauma al cap; Algoritme Background: Management algorithms for adult severe traumatic brain injury (sTBI) were omitted in later editions of the Brain Trauma Foundation’s sTBI Management Guidelines, as they were not evidence-based. Methods: We used a Delphi-method-based consensus approach to address management of sTBI patients undergoing intracranial pressure (ICP) monitoring. Forty-two experienced, clinically active sTBI specialists from six continents comprised the panel. Eight surveys iterated queries and comments. An in-person meeting included whole- and small-group discussions and blinded voting. Consensus required 80% agreement. We developed heatmaps based on a traffic-light model where panelists’ decision tendencies were the focus of recommendations. Results: We provide comprehensive algorithms for ICP-monitor-based adult sTBI management. Consensus established 18 interventions as fundamental and ten treatments not to be used. We provide a three-tier algorithm for treating elevated ICP. Treatments within a tier are considered empirically equivalent. Higher tiers involve higher risk therapies. Tiers 1, 2, and 3 include 10, 4, and 3 interventions, respectively. We include inter-tier considerations, and recommendations for critical neuroworsening to assist the recognition and treatment of declining patients. Novel elements include guidance for autoregulation-based ICP treatment based on MAP Challenge results, and two heatmaps to guide (1) ICP-monitor removal and (2) consideration of sedation holidays for neurological examination. Conclusions: Our modern and comprehensive sTBI-management protocol is designed to assist clinicians managing sTBI patients monitored with ICP-monitors alone. Consensus-based (class III evidence), it provides management recommendations based on combined expert opinion. It reflects neither a standard-of-care nor a substitute for thoughtful individualized management. We thank our financial supporters who include Adler/Geirsch Attorney at Law, the American Association of Neurological Surgeons/Congress of Neurological Surgeons Section on Neurotrauma and Critical Care, Bard, the Brain Trauma Foundation, DePuy, Hemedex, Integra, the Neurointensive Care Section of the European Society of Intensive Care Medicine, Neurosurgical Society of Australasia, Medtronic, Moberg Research, Natus, Neuroptics, Raumedic, Sophysa, Stryker, and Zoll.

IntroductionIndividualising therapy is an important challenge for intensive care of patients with severe traumatic brain injury (TBI). Targeting a cerebral perfusion pressure (CPP) tailored to optimise cerebrovascular autoregulation has been suggested as an attractive strategy on the basis of a large body of retrospective observational data. The objective of this study is to prospectively assess the feasibility and safety of such a strategy compared with fixed thresholds which is the current standard of care from international consensus guidelines.Methods and analysisCPPOpt Guided Therapy: Assessment of Target Effectiveness (COGiTATE) is a prospective, multicentre, non-blinded randomised, controlled trial coordinated from Maastricht University Medical Center, Maastricht (The Netherlands). The other original participating centres are Cambridge University NHS Foundation Trust, Cambridge (UK), and University Hospitals Leuven, Leuven (Belgium). Adult severe TBI patients requiring intracranial pressure monitoring are randomised within the first 24 hours of admission in neurocritical care unit. For the control arm, the CPP target is the Brain Trauma Foundation guidelines target (60–70 mm Hg); for the intervention group an automated CPP target is provided as the CPP at which the patient’s cerebrovascular reactivity is best preserved (CPPopt). For a maximum of 5 days, attending clinicians review the CPP target 4-hourly. The main hypothesis of COGiTATE are: (1) in the intervention group the percentage of the monitored time with measured CPP within a range of 5 mm Hg above or below CPPopt will reach 36%; (2) the difference in between groups in daily therapy intensity level score will be lower or equal to 3.Ethics and disseminationEthical approval has been obtained for each participating centre. The results will be presented at international scientific conferences and in peer-reviewed journals.Trial registration numberNCT02982122

Impairment of cerebrovascular autoregulation (CAR) is common after brain injury, although the pathophysiology remains elusive. The mechanisms of vascular dysregulation, their impact on brain function, and potential therapeutic implications are still incompletely understood. Clinical assessment of CAR remains challenging. Observational studies suggest that CAR impairment is associated with worse outcomes, and that optimization of cerebral blood flow (CBF) by individual arterial blood pressure (ABP) targets could potentially improve outcome. We present a porcine closed cranial window model that measures the hemodynamic response of pial arterioles, the main site of CBF control, based on changes in their diameter and red blood cell velocity. This quantitative direct CAR assessment is compared to laser Doppler flow (LDF). CAR breakpoints are determined by segmented regression analysis and validated using LDF and brain tissue oxygen pressure. Using a standardized cortical impact, CAR impairment in traumatic brain injury can be studied using our method of combining pial arteriolar diameter and RBC velocity to quantify RBC flux in a large animal model. The model has numerous potential applications to investigate CAR physiology and pathophysiology of CAR impairment after brain injury, the impact of therapeutic interventions, drugs, and other confounders, or to develop personalized ABP management strategies. ispartof: SCIENTIFIC REPORTS vol:9 issue:1 ispartof: location:England status: published

ispartof: INTENSIVE CARE MEDICINE vol:45 issue:9 pages:1292-1294 ispartof: location:United States status: published

Background Early diagnosis of acute kidney injury (AKI) is a major challenge in the intensive care unit (ICU). The AKIpredictor is a set of machine-learning-based prediction models for AKI using routinely collected patient information, and accessible online. In order to evaluate its clinical value, the AKIpredictor was compared to physicians’ predictions. Methods Prospective observational study in five ICUs of a tertiary academic center. Critically ill adults without end-stage renal disease or AKI upon admission were considered for enrollment. Using structured questionnaires, physicians were asked upon admission, on the first morning, and after 24 h to predict the development of AKI stages 2 or 3 (AKI-23) during the first week of ICU stay. Discrimination, calibration, and net benefit of physicians’ predictions were compared against the ones by the AKIpredictor. Results Two hundred fifty-two patients were included, 30 (12%) developed AKI-23. In the cohort of patients with predictions by physicians and AKIpredictor, the performance of physicians and AKIpredictor were respectively upon ICU admission, area under the receiver operating characteristic curve (AUROC) 0.80 [0.69–0.92] versus 0.75 [0.62–0.88] (n = 120, P = 0.25) with net benefit in ranges 0–26% versus 0–74%; on the first morning, AUROC 0.94 [0.89–0.98] versus 0.89 [0.82–0.97] (n = 187, P = 0.27) with main net benefit in ranges 0–10% versus 0–48%; after 24 h, AUROC 0.95 [0.89–1.00] versus 0.89 [0.79–0.99] (n = 89, P = 0.09) with main net benefit in ranges 0–67% versus 0–50%. Conclusions The machine-learning-based AKIpredictor achieved similar discriminative performance as physicians for prediction of AKI-23, and higher net benefit overall, because physicians overestimated the risk of AKI. This suggests an added value of the systematic risk stratification by the AKIpredictor to physicians’ predictions, in particular to select high-risk patients or reduce false positives in studies evaluating new and potentially harmful therapies. Due to the low event rate, future studies are needed to validate these findings. Trial registration ClinicalTrials.gov, NCT03574896 registration date: July 2nd, 2018 Electronic supplementary material The online version of this article (10.1186/s13054-019-2563-x) contains supplementary material, which is available to authorized users.

PURPOSE OF REVIEW: In this article, the specific and general indications for sedatives in the neurocritical care unit are discussed, together with an overview on current insights in sedative protocols for these patients. In addition, physiological effects of sedative agents on the central nervous system are reviewed. RECENT FINDINGS: In the general ICU population, a large body of evidence supports light protocolized sedation over indiscriminate deep sedation. Unfortunately, in patients with severe acute brain injury, the evidence from randomized controlled trials is scarce to nonexistent, and practice is supported by expert opinion, physiological studies and observational or small interventional trials. The different sedatives each have different beneficial effects and side-effects. SUMMARY: Extrapolating the findings from studies in the general ICU population suggests to reserve deep continuous sedation in the neuro-ICU for specific indications. Although an improved understanding of cerebral physiological changes in patients with brain injury may be helpful to guide individualized sedation, we still lack the evidence base to make broad recommendations for specific patient groups. ispartof: CURRENT OPINION IN CRITICAL CARE vol:25 issue:2 pages:97-104 ispartof: location:United States status: published

ispartof: CRITICAL CARE vol:23 issue:1 ispartof: location:England status: published

Objective To report on the currently available prediction models for the development of acute kidney injury in heterogeneous adult intensive care units. Methods A systematic review of clinical prediction models for acute kidney injury in adult intensive care unit populations was carried out. PubMed® was searched for publications reporting on the development of a novel prediction model, validation of an established model, or impact of an existing prediction model for early acute kidney injury diagnosis in intensive care units. Results We screened 583 potentially relevant articles. Among the 32 remaining articles in the first selection, only 5 met the inclusion criteria. The nonstandardized adaptations that were made to define baseline serum creatinine when the preadmission value was missing led to heterogeneous definitions of the outcome. Commonly included predictors were sepsis, age, and serum creatinine level. The final models included between 5 and 19 risk factors. The areas under the Receiver Operating Characteristic curves to predict acute kidney injury development in the internal validation cohorts ranged from 0.78 to 0.88. Only two studies were externally validated. Conclusion Clinical prediction models for acute kidney injury can help in applying more timely preventive interventions to the right patients. However, in intensive care unit populations, few models have been externally validated. In addition, heterogeneous definitions for acute kidney injury and evaluation criteria and the lack of impact analysis hamper a thorough comparison of existing models. Future research is needed to validate the established models and to analyze their clinical impact before they can be applied in clinical practice.

It is difficult to make a distinction between inflammation and infection. Therefore, new strategies are required to allow accurate detection of infection. Here, we hypothesize that we can distinguish infected from non-infected ICU patients based on dynamic features of serum cytokine concentrations and heart rate time series. Serum cytokine profiles and heart rate time series of 39 patients were available for this study. The serum concentration of ten cytokines were measured using blood sampled every 10 min between 2100 and 0600 hours. Heart rate was recorded every minute. Ten metrics were used to extract features from these time series to obtain an accurate classification of infected patients. The predictive power of the metrics derived from the heart rate time series was investigated using decision tree analysis. Finally, logistic regression methods were used to examine whether classification performance improved with inclusion of features derived from the cytokine time series. The AUC of a decision tree based on two heart rate features was 0.88. The model had good calibration with 0.09 Hosmer-Lemeshow p value. There was no significant additional value of adding static cytokine levels or cytokine time series information to the generated decision tree model. The results suggest that heart rate is a better marker for infection than information captured by cytokine time series when the exact stage of infection is not known. The predictive value of (expensive) biomarkers should always be weighed against the routinely monitored data, and such biomarkers have to demonstrate added value. ispartof: Journal of Clinical Monitoring and Computing vol:31 issue:2 pages:407-415 ispartof: location:Netherlands status: published

There are different patterns in the COVID-19 outbreak in the general population and amongst nursing home patients. We investigate the time from symptom onset to diagnosis and hospitalization or the length of stay (LoS) in the hospital, and whether there are differences in the population. Sciensano collected information on 14,618 hospitalized patients with COVID-19 admissions from 114 Belgian hospitals between 14 March and 12 June 2020. The distributions of different event times for different patient groups are estimated accounting for interval censoring and right truncation of the time intervals. The time between symptom onset and hospitalization or diagnosis are similar, with median length between symptom onset and hospitalization ranging between 3 and 10.4 days, depending on the age of the patient (longest delay in age group 20&ndash, 60 years) and whether or not the patient lives in a nursing home (additional 2 days for patients from nursing home). The median LoS in hospital varies between 3 and 10.4 days, with the LoS increasing with age. The hospital LoS for patients that recover is shorter for patients living in a nursing home, but the time to death is longer for these patients. Over the course of the first wave, the LoS has decreased.

ispartof: ACTA NEUROLOGICA BELGICA vol:118 issue:3 pages:513-515 ispartof: location:Italy status: published

ispartof: INTENSIVE CARE MEDICINE vol:44 issue:8 pages:1318-1320 ispartof: location:United States status: published

No consensus exists on the exact method for measuring mean arterial blood pressure (MAP) in the definition of cerebral perfusion pressure (CPP). The aim of the current study is to investigate how different MAP measurement methods have influenced the CPP recommendations in the Brain Trauma Foundation (BTF) guidelines.All papers on which the chapter on CPP thresholds in the 2007 version of the BTF guidelines is based, were reviewed. If accurate descriptions of head of bed elevation and arterial pressure transducer height were lacking, the authors were emailed for clarification. Additionally, the effect of choosing the radial artery for MAP measurement and the potential effect of gravity were studied in the literature.Thresholds of CPP in the BTF guidelines are based on 11 studies. Head of bed elevation at 30° was part of the protocol in 5 studies, patients were nursed flat in 1 study, and this variable remained unknown for 5 studies. The arterial pressure transducer was at heart level in 5 studies, at ear level in 3 studies, and height was unknown in 3 studies. Measuring MAP in the radial artery underestimates carotid artery MAP by approximately 10 mmHg in the flat position, and in a nonflat position gravity influences MAP of the internal carotid artery.There is no uniform definition for CPP, which may affect conclusions on proposed CPP targets in severe traumatic brain injury by ±10 mmHg.

The aim of this study is to assess visually the impact of duration and intensity of cerebrovascular autoregulation insults on 6-month neurological outcome in severe traumatic brain injury.Retrospective analysis of prospectively collected minute-by-minute intracranial pressure (ICP) and mean arterial blood pressure data of 259 adult and 99 paediatric traumatic brain injury (TBI) patients from multiple European centres. The relationship of the 6-month Glasgow Outcome Scale with cerebrovascular autoregulation insults (defined as the low-frequency autoregulation index above a certain threshold during a certain time) was visualized in a colour-coded plot. The analysis was performed separately for autoregulation insults occurring with cerebral perfusion pressure (CPP) below 50 mmHg, with ICP above 25 mmHg and for the subset of adult patients that did not undergo decompressive craniectomy.The colour-coded plots showed a time-intensity-dependent association with outcome for cerebrovascular autoregulation insults in adult and paediatric TBI patients. Insults with a low-frequency autoregulation index above 0.2 were associated with worse outcomes and below -0.6 with better outcomes, with and approximately exponentially decreasing transition curve between the two intensity thresholds. All insults were associated with worse outcomes when CPP was below 50 mmHg or ICP was above 25 mmHg.The colour-coded plots indicate that cerebrovascular autoregulation is disturbed in a dynamic manner, such that duration and intensity play a role in the determination of a zone associated with better neurological outcome.

The aim of this analysis was to investigate to what extent median cerebral perfusion pressure (CPP) differs between severe traumatic brain injury (TBI) patients and between centres, and whether the 2007 change in CPP threshold in the Brain Trauma Foundation guidelines is reflected in patient data collected at several centres over different time periods.Data were collected from the Brain-IT database, a multi-centre project between 2003 and 2005, and from a recent project in four centres between 2009 and 2013. For patients nursed with their head up at 30° and with the blood pressure transducer at atrium level, CPP was corrected by 10 mmHg. Median CPP, interquartile ranges and total CPP ranges over the monitoring time were calculated per patient and per centre.Per-centre medians pre-2007 were situated between 50 and 70 mmHg in 6 out of 16 centres, while 10 centres had medians above 70 mmHg and 4 above 80 mmHg. Post-2007, three out of four centres had medians between 60 and 70 mmHg and one above 80 mmHg. One out of two centres with data pre- and post-2007 shifted from a median CPP of 76 mmHg to 60 mmHg, while the other remained at 68-67 mmHg.CPP data are characterised by a high inter-individual variability, but the data also suggest differences in CPP policies between centres. The 2007 guideline change may have affected policies towards lower CPP in some centres. Deviations from the guidelines occur in the direction of CPP70 mmHg.

Objective: The aim of this study is to assess visually the impact of duration and intensity of cerebrovascular autoregulation insults on 6-month neurological outcome in severe traumatic brain injury. Material and methods: Retrospective analysis of prospectively collected minute-by-minute intracranial pressure (ICP) and mean arterial blood pressure data of 259 adult and 99 paediatric traumatic brain injury (TBI) patients from multiple European centres. The relationship of the 6-month Glasgow Outcome Scale with cerebrovascular autoregulation insults (defined as the low-frequency autoregulation index above a certain threshold during a certain time) was visualized in a colour-coded plot. The analysis was performed separately for autoregulation insults occurring with cerebral perfusion pressure (CPP) below 50 mmHg, with ICP above 25 mmHg and for the subset of adult patients that did not undergo decompressive craniectomy. Results: The colour-coded plots showed a time-intensity-dependent association with outcome for cerebrovascular autoregulation insults in adult and paediatric TBI patients. Insults with a low-frequency autoregulation index above 0.2 were associated with worse outcomes and below -0.6 with better outcomes, with and approximately exponentially decreasing transition curve between the two intensity thresholds. All insults were associated with worse outcomes when CPP was below 50 mmHg or ICP was above 25 mmHg. Conclusions: The colour-coded plots indicate that cerebrovascular autoregulation is disturbed in a dynamic manner, such that duration and intensity play a role in the determination of a zone associated with better neurological outcome.

Introduction: No consensus exists on the exact method for measuring mean arterial blood pressure (MAP) in the definition of cerebral perfusion pressure (CPP). The aim of the current study is to investigate how different MAP measurement methods have influenced the CPP recommendations in the Brain Trauma Foundation (BTF) guidelines.

Objectives: Validated optimal cerebral perfusion pressure (CPP) treatment thresholds in children do not exist. To improve the intensive care unit (ICU) management of the paediatric traumatic brain injury (TBI) population, we are forming a new paediatric multi-centre collaboration to recruit standardised ICU data for running and reporting upon models for assessing autoregulation and optimal CCP (CPPopt).

Introduction: The aim of this analysis was to investigate to what extent median cerebral perfusion pressure (CPP) differs between severe traumatic brain injury (TBI) patients and between centres, and whether the 2007 change in CPP threshold in the Brain Trauma Foundation guidelines is reflected in patient data collected at several centres over different time periods. Methods: Data were collected from the Brain-IT database, a multi-centre project between 2003 and 2005, and from a recent project in four centres between 2009 and 2013. For patients nursed with their head up at 30 degrees and with the blood pressure transducer at atrium level, CPP was corrected by 10 mmHg. Median CPP, interquartile ranges and total CPP ranges over the monitoring time were calculated per patient and per centre. Results: Per-centre medians pre-2007 were situated between 50 and 70 mmHg in 6 out of 16 centres, while 10 centres had medians above 70 mmHg and 4 above 80 mmHg. Post-2007, three out of four centres had medians between 60 and 70 mmHg and one above 80 mmHg. One out of two centres with data pre- and post-2007 shifted from a median CPP of 76 mmHg to 60 mmHg, while the other remained at 68-67 mmHg. Conclusions: CPP data are characterised by a high inter-individual variability, but the data also suggest differences in CPP policies between centres. The 2007 guideline change may have affected policies towards lower CPP in some centres. Deviations from the guidelines occur in the direction of CPP > 70 mmHg.

OBJECTIVE: To report the ESICM consensus and clinical practice recommendations on fluid therapy in neurointensive care patients. DESIGN: A consensus committee comprising 22 international experts met in October 2016 during ESICM LIVES2016. Teleconferences and electronic-based discussions between the members of the committee subsequently served to discuss and develop the consensus process. METHODS: Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles generated. The consensus focused on three main topics: (1) general fluid resuscitation and maintenance in neurointensive care patients, (2) hyperosmolar fluids for intracranial pressure control, (3) fluid management in delayed cerebral ischemia after subarachnoid haemorrhage. After an extensive literature search, the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system were applied to assess the quality of evidence (from high to very low), to formulate treatment recommendations as strong or weak, and to issue best practice statements when applicable. A modified Delphi process based on the integration of evidence provided by the literature and expert opinions-using a sequential approach to avoid biases and misinterpretations-was used to generate the final consensus statement. RESULTS: The final consensus comprises a total of 32 statements, including 13 strong recommendations and 17 weak recommendations. No recommendations were provided for two statements. CONCLUSIONS: We present a consensus statement and clinical practice recommendations on fluid therapy for neurointensive care patients.

ispartof: INTENSIVE CARE MEDICINE vol:46 issue:3 pages:564-565 ispartof: location:United States status: published

ispartof: Intensive Care Medicine vol:44 issue:9 pages:1524-1527 ispartof: location:United States status: published

ispartof: Intensive Care Medicine vol:42 issue:8 pages:1282-1285 ispartof: location:United States status: published

Although rare, central nervous system (CNS) infections are increasingly being recognized in immunocompromised patients. The goal of the present review is to provide a practical diagnostic approach for the intensivist, and to briefly discuss some of the most prevalent conditions.Immunocompromised patients presenting with new neurological symptoms should always be suspected of a CNS infection. These infections carry a poor prognosis, especially if intracranial hypertension, severely altered mental status or seizures are present. Clinical examination and serum blood tests should be followed by brain imaging, and when no contra-indications are present, a lumbar puncture including cerebrospinal fluid PCR to identify causative organisms. Empirical therapy depends on the type of immunodeficiency. In HIV-infected patients, the most common CNS infection is cerebral toxoplasmosis, whereas in other immunocompromised patients, aspergillosis, cryptococcal meningitis and tuberculous meningitis are more prevalent. Multiple pathogens can be detected in up to 15% of patients. The diagnostic value of fast multiplex PCR has yet to be evaluated in this setting.CNS infections represent a rare but severe complication in immunocompromised patients. A systematic approach including early diagnosis, appropriate antimicrobial treatment, early ICU admission and aggressive measures to reduce intracranial pressure may improve outcome.

ispartof: Neurosurgery vol:81 issue:1 pages:E1-E1 ispartof: location:United States status: published

The prognosis of patients who are admitted to the hospital after cardiac arrest often relies on neurological examination, which could be significantly influenced by the use of sedative drugs or the implementation of targeted temperature management. The need for early and accurate prognostication is crucial as up to 15-20% of patients could be considered as having a poor outcome and may undergo withdrawal of life-sustaining therapies while a complete neurological recovery is still possible. As current practice in Belgium is still based on a very early assessment of neurological function in these patients, the Belgian Society of Intensive Care Medicine created a multidisciplinary Task Force to provide an optimal approach for monitoring and refine prognosis of CA survivors. This Task Force underlined the importance to use a multimodal approach using several additional tools (e.g., electrophysiological tests, neuroimaging, biomarkers) and to refer cases with uncertain prognosis to specialized centers to better evaluate the extent of brain injury in these patients.

Object In severe traumatic brain injury, a universal target for cerebral perfusion pressure (CPP) has been abandoned. Attempts to identify a dynamic CPP target based on the patient's cerebrovascular autoregulatory capacity have been promising so far. Bedside monitoring of pressure autoregulatory capacity has become possible by a number of methods, Czosnyka's pressure reactivity index (PRx) being the most frequently used. The PRx is calculated as the moving correlation coefficient between 40 consecutive 5-second averages of intracranial pressure (ICP) and mean arterial blood pressure (MABP) values. Plotting PRx against CPP produces a U-shaped curve in roughly two-thirds of monitoring time, with the bottom of this curve representing a CPP range corresponding with optimal autoregulatory capacity (CPPopt). In retrospective series, keeping CPP close to CPPopt corresponded with better outcomes. Monitoring of PRx requires high-frequency signal processing. The aim of the present study is to investigate how the processing of the information on cerebrovascular pressure reactivity that can be obtained from routine minute-by-minute ICP and MABP data can be enhanced to enable CPPopt recommendations that do not differ from those obtained by the PRx method, show the same associations with outcome, and can be generated in more than two-thirds of monitoring time. Methods The low-frequency autoregulation index (LAx) was defined as the moving minute-by-minute ICP/MABP correlation coefficient calculated over time intervals varying from 3 to 120 minutes. The CPPopt calculation was based on LAx-CPP plots and done for time windows between 1 and 24 hours and for each LAx type. The resulting matrix of CPPopts were then averaged in a weighted manner, with the weight based on the goodness of fit of a U-shape and the lower value of the LAx corresponding to the U-bottom, to result in a final CPPopt recommendation. The association between actual CPP/CPPopt and outcome was assessed in the multicenter Brain Monitoring with Information Technology Research Group (BrainIT) database (n = 180). In the Leuven-Tübingen database (60-Hz waveform data, n = 21), LAx- and PRx-based CPPopts were compared. Results In the BrainIT database, CPPopt recommendations were generated in 95% of monitoring time. Actual CPP being close to LAx-based CPPopt was associated with increased survival. In a multivariate model using the Corticosteroid Randomization After Significant Head Injury (CRASH) model as covariates, the average absolute difference between actual CPP and CPPopt was independently associated with increased mortality. In the high-frequency data set no significant difference was observed between PRx-based and LAx-based CPPopts. The new method issued a CPPopt recommendation in 97% of monitoring time, as opposed to 44% for PRx-based CPPopt. Conclusions Minute-by-minute ICP/MABP data contain relevant information for autoregulation monitoring. In this study, the authors' new method based on minute-by-minute data resolution allowed for CPPopt calculation in nearly the entire monitoring time. This will facilitate the use of pressure reactivity monitoring in all ICUs.

A substantial minority of patients who survive an acquired brain injury develop a state of sympathetic hyperactivity that can persist for weeks or months, consisting of periodic episodes of increased heart rate and blood pressure, sweating, hyperthermia, and motor posturing, often in response to external stimuli. The unifying term for the syndrome-paroxysmal sympathetic hyperactivity (PSH)-and clear diagnostic criteria defined by expert consensus were only recently established. PSH has predominantly been described after traumatic brain injury (TBI), in which it is associated with worse outcomes. The pathophysiology of the condition is not completely understood, although most researchers consider it to be a disconnection syndrome with paroxysms driven by a loss of inhibitory control over excitatory autonomic centres. Although therapeutic strategies to alleviate sympathetic outbursts have been proposed, their effects on PSH are inconsistent between patients and their influence on outcome is unknown. Combinations of drugs are frequently used and are chosen on the basis of local custom, rather than on objective evidence. New rigorous tools for diagnosis could allow better characterisation of PSH to enable stratification of patients for future therapeutic trials. ispartof: The Lancet Neurology vol:16 issue:9 pages:721-729 ispartof: location:England status: published

Introduction Intracranial pressure (ICP) monitoring is commonly used in neurocritical care patients with acute brain injury (ABI). Practice about indications and use of ICP monitoring in patients with ABI remains, however, highly variable in high-income countries, while data on ICP monitoring in low and middle-income countries are scarce or inconsistent. The aim of the SYNAPSE-ICU study is to describe current practices of ICP monitoring using a worldwide sample and to quantify practice variations in ICP monitoring and management in neurocritical care ABI patients. Methods and analysis The SYNAPSE-ICU study is a large international, prospective, observational cohort study. From March 2018 to March 2019, all patients fulfilling the following inclusion criteria will be recruited: age >18 years; diagnosis of ABI due to primary haemorrhagic stroke (subarachnoid haemorrhage or intracranial haemorrhage) or traumatic brain injury; Glasgow Coma Score (GCS) with no eye opening (Eyes response=1) and Motor score ≤5 (not following commands) at ICU admission, or neuro-worsening within the first 48 hours with no eye opening and a Motor score decreased to ≤5. Data related to clinical examination (GCS, pupil size and reactivity, Richmond Agitation-Sedation Scale score, neuroimaging) and to ICP interventions (Therapy Intensity Levels) will be recorded on admission, and at day 1, 3 and 7. The Glasgow Outcome Scale Extended (GOSE) will be collected at discharge from ICU and from hospital and at 6-month follow-up. The impact of ICP monitoring and ICP-driven therapy on GOSE will be analysed at both patient and ICU level. Ethics and dissemination The study has been approved by the Ethics Committee 'Brianza' at the Azienda Socio Sanitaria Territoriale (ASST)-Monza (approval date: 21 November 2017). Each National Coordinator will notify the relevant ethics committee, in compliance with the local legislation and rules. Data will be made available to the scientific community by means of abstracts submitted to the European Society of Intensive Care Medicine annual conference and by scientific reports and original articles submitted to peer-reviewed journals., SCOPUS: ar.j, info:eu-repo/semantics/published

Since their widespread introduction more than half a century ago, intensive care units (ICUs) have become an integral part of the health care system. Although most ICUs are found in high-income countries, they are increasingly a feature of health care systems in low- and middle-income countries. The World Federation of Societies of Intensive and Critical Care Medicine convened a task force whose objective was to answer the question “What is an ICU?” in an internationally meaningful manner and to develop a system for stratifying ICUs on the basis of the intensity of the care they provide. We undertook a scoping review of the peer-reviewed and gray literature to assemble existing models for ICU stratification. Based on these and on discussions among task force members by teleconference and 2 face-to-face meetings, we present a proposed definition and classification of ICUs. An ICU is an organized system for the provision of care to critically ill patients that provides intensive and specialized medical and nursing care, an enhanced capacity for monitoring, and multiple modalities of physiologic organ support to sustain life during a period of life-threatening organ system insufficiency. Although an ICU is based in a defined geographic area of a hospital, its activities often extend beyond the walls of the physical space to include the emergency department, hospital ward, and follow-up clinic. A level 1 ICU is capable of providing oxygen, noninvasive monitoring, and more intensive nursing care than on a ward, whereas a level 2 ICU can provide invasive monitoring and basic life support for a short period. A level 3 ICU provides a full spectrum of monitoring and life support technologies, serves as a regional resource for the care of critically ill patients, and may play an active role in developing the specialty of intensive care through research and education. A formal definition and descriptive framework for ICUs can inform health care decision-makers in planning and measuring capacity and provide clinicians and patients with a benchmark to evaluate the level of resources available for clinical care.

The concept of CPPopt, a variable cerebral perfusion pressure (CPP) target based on cerebrovascular autoregulatory capacity in severe traumatic brain injury (TBI), is promising. CPPopt calculation is based on the continuous plotting of the pressure reactivity Index (PRx) against CPP and requires processing of waveform quality data. The aim of this study is to investigate whether CPPopt can also be calculated based on minute-by-minute data.A low-resolution autoregulation index (LAx) was defined as the minute-by-minute intracranial pressure-mean arterial pressure correlation over varying time intervals. A matrix of LAx-CPP plots was built using different LAx values and varying time windows. CPPopt was calculated as the weighted average of the CPPopt values resulting from each plot. The method was assessed in a database of 21 patients with TBI with 60-Hz data.No significant difference was observed between PRx-based and LAx-based CPPopt values. The new method was able to issue a CPPopt recommendation throughout almost the entire monitoring time. The absolute difference between CPP and CPPopt was inversely associated with survival.CPPopt calculation based on standard resolution data compared well with PRx-based CPPopt and may represent a promising alternative method, avoiding the need for waveform quality data capture. Further validation of this new method is required.

This paper describes the use of minute-by-minute monitoring data to determine continuous optimal cerebral perfusion pressure (CPP) recommendations based on the autoregulatory status of pediatric patients with traumatic brain injury. Data from 79 children were retrospectively studied. Optimal CPP recommendations were obtained for the majority of the first 72 h of monitoring time. Actual CPP close to recommended CPP values was significantly associated with better outcome and was a significant independent predictor of better outcome when considering IMPACT model covariates in multivariate logistic regression.

Background: The concept of CPPopt, a variable cerebral perfusion pressure (CPP) target based on cerebrovascular autoregulatory capacity in severe traumatic brain injury (TBI), is promising. CPPopt calculation is based on the continuous plotting of the pressure reactivity Index (PRx) against CPP and requires processing of waveform quality data. The aim of this study is to investigate whether CPPopt can also be calculated based on minute-by-minute data. Methods: A low-resolution autoregulation index (LAx) was defined as the minute-by-minute intracranial pressure–mean arterial pressure correlation over varying time intervals. A matrix of LAx-CPP plots was built using different LAx values and varying time windows. CPPopt was calculated as the weighted average of the CPPopt values resulting from each plot. The method was assessed in a database of 21 patients with TBI with 60-Hz data. Results: No significant difference was observed between PRx-based and LAx-based CPPopt values. The new method was able to issue a CPPopt recommendation throughout almost the entire monitoring time. The absolute difference between CPP and CPPopt was inversely associated with survival. Conclusion: CPPopt calculation based on standard resolution data compared well with PRx-based CPPopt and may represent a promising alternative method, avoiding the need for waveform quality data capture. Further validation of this new method is required.

This paper describes the use of minute-by-minute monitoring data to determine continuous optimal cerebral perfusion pressure (CPP) recommendations based on the autoregulatory status of pediatric patients with traumatic brain injury. Data from 79 children were retrospectively studied. Optimal CPP recommendations were obtained for the majority of the first 72 h of monitoring time. Actual CPP close to recommended CPP values was significantly associated with better outcome and was a significant independent predictor of better outcome when considering IMPACT model covariates in multivariate logistic regression.

The widespread implementation of computerized medical files in intensive care units (ICUs) over recent years has made available large databases of clinical data for the purpose of developing clinical prediction models. The typical intensive care unit has several information sources from which data is electronically collected as time series of varying time resolutions. We present an overview of research questions studied in the ICU setting that have been addressed through the automatic analysis of these large databases. We focus on automatic learning methods, specifically data mining approaches for predictive modeling based on these time series of clinical data. On the one hand we examine short and medium term predictions, which have as ultimate goal the development of early warning or decision support systems. On the other hand we examine long term outcome prediction models and evaluate their performance with respect to established scoring systems based on static admission and demographic data. ispartof: Journal of clinical monitoring and computing vol:27 issue:4 pages:449-453 ispartof: location:GERMANY, Bonn status: published

BACKGROUND: Augmented renal clearance in critically ill patients can result in underdosing of life-saving drugs, potentially leading to therapeutic failure. To detect this phenomenon, correct assessment of the kidney function is essential. Currently, little is known about the validity of mathematical formulas to estimate renal function in this subset of patients. OBJECTIVE: To evaluate the validity of different methods to estimate kidney function in critically ill patients with augmented renal clearance by comparing measured renal clearance with estimated clearance using different formulas. METHODS: An observational, retrospective, single-center study was conducted in a 34-bed surgical intensive care unit (SICU) of the University Hospitals Leuven, Leuven, Belgium. Adults admitted to the SICU in 2010 with a measured creatinine clearance (CrCl) of 120 mL/min or more (based on 24-hour urinary collection) were included. The measured clearance values were compared with estimated clearance values as calculated by the Cockcroft-Gault (CrClCG) method and the re-expressed 4-variable Modification of Diet in Renal Disease estimated glomerular filtration rate (eGFR) formula. Spearman rank order correlation was performed to determine the relationship between measured and estimated clearances. Bland-Altman plots were evaluated to assess bias and limits of agreement between the 2 methods. RESULTS: Records on 1317 patients were screened. Augmented renal clearance was present in 390 patients. Spearman correlation showed fair correlation between measured and estimated clearances (rs = 0.343; p < 0.001 [CrClCG] and rs = 0.290; p < 0.001 [eGFR]). Bias was −11.2 mL/min with limits of agreement (–131.7; 109.3 mL/min [CrClCG]) and −19.9 mL/min with limits of agreement (–170.4; 130.7 mL/min [eGFR]). CONCLUSIONS: Estimated renal clearances, such as the eGFR estimated by the MDRD formula or CrCl estimated by CG, showed poor agreement with measured CrCl values in our critically ill population displaying augmented renal clearance. Clinicians should be cautious when interpreting kidney function based on estimating equations in this subset of patients. Instead, measured CrCl using urinary collection is recommended in patients suspected of displaying augmented renal clearance.

Caspofungin is the first echinocandin approved for the treatment of invasive fungal infections (IFI). As it is also well tolerated in patients with liver cirrhosis, caspofungin is an alternative for azoles in the treatment of IFI in patients with hepatic insufficiency.We report, for the first time, the pharmacokinetics (PK) of caspofungin in a patient with Child A cirrhosis and a transjugular intrahepatic portosystemic shunt (TIPS) and compare values to previously published results.Caspofungin plasma levels were determined on days 14 (before TIPS reduction) and 29 (after TIPS reduction) of treatment. Troughs and peaks were 3.55 and 3.34 mg/l on day 14 and 9.28 and 9.49 mg/l on day 29, resulting in, (1) PK parameters only slightly higher than previously reported results in healthy volunteers and patients with Child A liver cirrhosis without TIPS and (2) similar exposures before versus after TIPS reduction. This limited increase in exposure is not expected to be correlated to toxicity.Caspofungin is a safe alternative for azoles when treating patients with TIPS suffering from IFI.