While the discussion on the optimal blood glucose (BG) level target in critically ill patients is on-going, attention shifts towards other aspects of the BG signal, such as hypoglycemia and blood ...glucose amplitude variability (BGAV). A large number of observational and mostly retrospective studies have demonstrated an association between increased BGAV and worse outcomes. This observed association could partially be explained by endogenous factors such as changes in the status of the patient that cannot be externally influenced. On the other hand, exogenous factors such as insulin and caloric infusions could play a role in increasing or decreasing BGAV. In this review article, intuitive concept of "variability" will be clarified, and possible metrics to quantify BGAV are discussed. Whether it is feasible to actively minimize BGAV in order to improve the outcome of critically ill patients, is questionable.
Background
Several methods have been proposed to measure cerebrovascular autoregulation (CA) in traumatic brain injury (TBI), but the lack of a gold standard and the absence of prospective clinical ...data on risks, impact on care and outcomes of implementation of CA-guided management lead to uncertainty.
Aim
To formulate statements using a Delphi consensus approach employing a group of expert clinicians, that reflect current knowledge of CA, aspects that can be implemented in TBI management and CA research priorities.
Methods
A group of 25 international academic experts with clinical expertise in the management of adult severe TBI patients participated in this consensus process. Seventy-seven statements and multiple-choice questions were submitted to the group in two online surveys, followed by a face-to-face meeting and a third online survey. Participants received feedback on average scores and the rationale for resubmission or rephrasing of statements. Consensus on a statement was defined as agreement of more than 75% of participants.
Results
Consensus amongst participants was achieved on the importance of CA status in adult severe TBI pathophysiology, the dynamic non-binary nature of CA impairment, its association with outcome and the inadvisability of employing universal and absolute cerebral perfusion pressure targets. Consensus could not be reached on the accuracy, reliability and validation of any current CA assessment method. There was also no consensus on how to implement CA information in clinical management protocols, reflecting insufficient clinical evidence.
Conclusion
The Delphi process resulted in 25 consensus statements addressing the pathophysiology of impaired CA, and its impact on cerebral perfusion pressure targets and outcome. A research agenda was proposed emphasizing the need for better validated CA assessment methods as well as the focused investigation of the application of CA-guided management in clinical care using prospective safety, feasibility and efficacy studies.
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.
HTS use, on the other hand, can expose to an important risk of hypernatremia and osmotic variation 15 compared to mannitol. Since these variations could also be detrimental in some patients, HTS ...cannot be promoted as being the preferred agent in all brain injured patients. ...based on the literature, no recommendation suggesting a superiority of one hyperosmolar agent over the other can currently be made, and it appears that both HTS and mannitol have a demonstrated effect on ICP, but not on outcome. Li, M; Chen, T; Chen, S; Cai, J. Comparison of equimolar doses of mannitol and hypertonic saline for the treatment of elevated intracranial pressure after traumatic brain injury: a systematic review and meta-analysis.
The complement system is an essential part of our innate immune system. Three enzymatic activation pathways are described, all converging into a common terminal pathway which causes lysis of the ...target cell. Late complement deficiencies (LCDs) are typically diagnosed in children or adolescents with invasive meningococcal disease (IMD). However, IMD can also be a first manifestation in adulthood and should prompt for the evaluation of the LCD. We report the case of a young adult with IMD who was found to have a LCD, caused by a compound heterozygous mutation in C6. His vaccination status was optimized and prophylactic antibiotic treatment was initiated. By means of this case, we would like to raise awareness of underlying LCD in (young) adults presenting with IMD by N. meningitidis. Screening for complement deficiencies after IMD, followed by genetic testing, can be lifesaving and allows for genetic counselling. In addition, we discuss the diagnosis and treatment of LCD.
Acute bacterial meningitis (ABM) is a rare but disabling infectious condition that requires a performant multidisciplinary management approach. Between 70 and 90 adult patients are diagnosed with ...community-acquired ABM in Belgium annually, and reported case fatality rates range from 17 to 40%. The currently available guidelines provide evidence-based guidance on how to manage this disease. However, these guidelines do not translate the evidence to the daily practice at the emergency department in a Belgian healthcare context. We created a taskforce in University Hospitals Leuven consisting of experts with complementary expertise in managing this disease: neurology, neurosurgery, intensive care medicine, microbiology and infectious diseases. The taskforce agreed upon a flowchart containing seven management steps encompassing all relevant phases in emergency ABM management. In addition to the focus on timely and adequate initiation of antimicrobial treatment, the flowchart and protocol also provide guidance on practical hurdles such as how to assess the safety of performing a lumbar puncture and when to refer patients to the intensive care department. This protocol was implemented in University Hospitals Leuven and fosters inter-disciplinary coordination of ABM care.
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).
We are adapting the adult BrainIT group's approach to develop a new Paediatric Brain Monitoring and Information Technology Group (KidsBrainIT), which will include a repository to store prospectively collected high-resolution physiological, clinical, and outcome data. In the first phase of this project there are 7 UK Paediatric Intensive Care Units, 1 Spanish, 1 Belgium, and 1 Romanian Centre interested in participating. In subsequent phases, we plan to open recruitment to other centres both within Europe, US and abroad. We are collaborating with the Leuven Group and plan to use their LAx (low-frequency autoregulation index), DATACAR (dynamic adaptive target of active cerebral autoregulation), CPPopt and visualisation methodologies. We also plan to use the continuous diffuse optical monitoring and tomography technology developed in Barcelona as an acute surrogate end-point for optimising brain perfusion. This technology allows non-invasive continuous monitoring of deep tissue perfusion and oxygenation in adults but its clinical application in infants and children with TBI has not been studied previously.
We report on the current status of setting up this new collaboration and also on pilot analyses in two centres which are the basis of our rationale for the need for a prospective validation study of CPPopt in children. Specifically, we demonstrated that CPPopt varied with time for each patient during their paediatric intensive care unit (PICU) stay, and the median overall CPPopt levels for children aged 2-6 years, 7-11 years and 12-16 years were 68.83, 68.09, and 72.17 mmHg respectively. Among survivors and patients with favourable outcome (GOS 4 and 5), there were significantly higher proportions with CPP monitoring time within CPPopt (p = 0.04 and p = 0.01 respectively).
There is a need and an interest in forming a multi-centre PICU collaboration for acquiring data and performing analyses for determining validated CPPopt thresholds in the paediatric TBI population. KidsBrainIT is being formed to meet that need.
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