Cerebral microcirculation and histological mapping after severe head injury: a contusion and acceleration experimental model

Background: Cerebral microcirculation after severe head injury is heterogeneous and temporally variable. Microcirculation is dependent upon the severity of injury, and it is unclear how histology relates to cerebral regional blood flow. Objective: This study assesses the changes of cerebral microcirculation blood flow over time after an experimental brain injury model in sheep and contrasts these findings with the histological analysis of the same regions with the aim of mapping cerebral flow and tissue changes after injury. Methods: Microcirculation was quantified using flow cytometry of color microspheres injected under intracardiac ultrasound to ensure systemic and homogeneous distribution. Histological analysis used amyloid precursor protein staining as a marker of axonal injury. A mapping of microcirculation and axonal staining was performed using adjacent layers of tissue from the same anatomical area, allowing flow and tissue data to be available from the same anatomical region. A mixed effect regression model assessed microcirculation during 4 h after injury, and those results were then contrasted to the amyloid staining qualitative score. results: Microcirculation values for each subject and tissue region over time, including baseline, ranged between 20 and 80 ml/100 g/min with means that did not differ statistically from baseline flows. However, microcirculation values for each subject and tissue region were reduced from baseline, although their confidence intervals crossing the horizontal ratio of 1 indicated that such reduction was not statistically significant. Histological analysis demonstrated the presence of moderate and severe score on the amyloid staining throughout both hemispheres. conclusion: Microcirculation at the ipsilateral and contralateral site of a contusion and the ipsilateral thalamus and medulla showed a consistent decline over time. Our data suggest that after severe head injury, microcirculation in predefined areas of the brain is reduced from baseline with amyloid staining in those areas reflecting the early establishment of axonal injuryJudith Bellapart, Kylie Cuthbertson, Kimble Dunster, Sara Diab, David G. Platts, Owen Christopher Raffel, Levon Gabrielian, Adrian Barnett, Jenifer Paratz, Rob Boots and John F. Frase

Effects of brain tissue oxygen (PbtO2) guided management on patient outcomes following severe traumatic brain injury: A systematic review and meta-analysis.

Monitoring and optimisation of brain tissue oxygen tension (PbtO2) has been associated with improved neurological outcome and survival in observational studies of severe traumatic brain injury (TBI). We carried out a systematic review of randomized controlled trials to determine if PbtO2-guided management is associated with differential neurological outcomes, survival, and adverse events. Searches were carried out to 10 February 2022 in Medline (OvidSP), 11 February in EMBASE (OvidSP) and 8 February in Cochrane library. Randomized controlled trials comparing PbtO2 and ICP-guided management to ICP-guided management alone were included. The primary outcome was survival with favourable neurological outcome at 6-months post injury. Data were extracted by two independent authors and GRADE certainty of evidence assessed. There was no difference in the proportion of patients with favourable neurological outcomes with PbtO2-guided management (relative risk [RR] 1.42, 95% CI 0.97 to 2.08; p = 0.07; I2 = 0%, very low certainty evidence) but PbtO2-guided management was associated with reduced mortality (RR 0.54, 95% CI 0.31 to 0.93; p = 0.03; I2 = 42%; very low certainty evidence) and ICP (mean difference (MD) - 4.62, 95% CI - 8.27 to - 0.98; p = 0.01; I2 = 63%; very low certainty evidence). There was no significant difference in the risk of adverse respiratory or cardiovascular events. PbtO2-guided management in addition to ICP-based care was not significantly associated with increased favourable neurological outcomes, but was associated with increased survival and reduced ICP, with no difference in respiratory or cardiovascular adverse events. However, based on GRADE criteria, the certainty of evidence provided by this meta-analysis was consistently very low. MESH: Brain Ischemia; Intensive Care; Glasgow Outcome Scale; Randomized Controlled Trial; Craniocerebral Trauma

Prophylactic Melatonin for Delirium in Intensive Care (Pro-MEDIC): Study protocol for a randomised controlled trial

Background: Delirium is an acute state of brain dysfunction characterised by fluctuating inattention and cognitive disturbances, usually due to illness. It occurs commonly in the intensive care unit (ICU), and it is associated with greater morbidity and mortality. It is likely that disturbances of sleep and of the day-night cycle play a significant role. Melatonin is a naturally occurring, safe and cheap hormone that can be administered to improve sleep. The main aim of this trial will be to determine whether prophylactic melatonin administered to critically ill adults, when compared with placebo, decreases the rate of delirium. Methods: This trial will be a multi-centre, randomised, placebo-controlled study conducted in closed ICUs in Australia. Our aim is to enrol 850 adult patients with an expected ICU length of stay (LOS) of 72h or more. Eligible patients for whom there is consent will be randomised to receive melatonin 4mg enterally or placebo in a 1:1 ratio according to a computer-generated randomisation list, stratified by site. The study drug will be indistinguishable from placebo. Patients, doctors, nurses, investigators and statisticians will be blinded. Melatonin or placebo will be administered once per day at 21:00 until ICU discharge or 14days after enrolment, whichever occurs first. Trained staff will assess patients twice daily to determine the presence or absence of delirium using the Confusion Assessment Method for the ICU score. Data will also be collected on demographics, the overall prevalence of delirium, duration and severity of delirium, sleep quality, participation in physiotherapy sessions, ICU and hospital LOS, morbidity and mortality, and healthcare costs. A subgroup of 100 patients will undergo polysomnographic testing to further evaluate the quality of sleep. Discussion: Delirium is a significant issue in ICU because of its frequency and associated poorer outcomes. This trial will be the largest evaluation of melatonin as a prophylactic agent to prevent delirium in the critically ill population. This study will also provide one of the largest series of polysomnographic testing done in ICU. Trial registration: Australian New Zealand Clinical Trial Registry (ANZCTR) number: ACTRN12616000436471. Registered on 20 December 2015

Intraaortic Balloon Pump Counterpulsation and Cerebral Autoregulation: an observational study

The use of Intra-aortic counterpulsation is a well established supportive therapy for patients in cardiac failure or after cardiac surgery. Blood pressure variations induced by counterpulsation are transmitted to the cerebral arteries, challenging cerebral autoregulatory mechanisms in order to maintain a stable cerebral blood flow. This study aims to assess the effects on cerebral autoregulation and variability of cerebral blood flow due to intra-aortic balloon pump and inflation ratio weaning

Vampires in the village Žrnovo on the island of Korčula: following an archival document from the 18th century

Središnja tema rada usmjerena je na raščlambu spisa pohranjenog u Državnom arhivu u Mlecima (fond: Capi del Consiglio de’ Dieci: Lettere di Rettori e di altre cariche) koji se odnosi na događaj iz 1748. godine u korčulanskom selu Žrnovo, kada su mještani – vjerujući da su se pojavili vampiri – oskvrnuli nekoliko mjesnih grobova. U radu se podrobno iznose osnovni podaci iz spisa te rečeni događaj analizira u širem društvenom kontekstu i prate se lokalna vjerovanja.The main interest of this essay is the analysis of the document from the State Archive in Venice (file: Capi del Consiglio de’ Dieci: Lettere di Rettori e di altre cariche) which is connected with the episode from 1748 when the inhabitants of the village Žrnove on the island of Korčula in Croatia opened tombs on the local cemetery in the fear of the vampires treating. This essay try to show some social circumstances connected with this event as well as a local vernacular tradition concerning superstitions

Transcranial doppler assessment of cerebral autoregulation

Cerebral autoregulation describes the process by which cerebral blood flow is maintained despite fluctuations in cerebral perfusion pressure. The assessment of cerebral autoregulation is a key to the optimisation of cerebral perfusion pressure in patients with brain injury. This review evaluates the current evidence for transcranial Doppler in the assessment of cerebral autoregulation. The study of cerebral autoregulation classically assesses changes in cerebral perfusion pressure secondary to changes in systemic blood pressure. It is defined static autoregulation if blood pressure changes are progressive, thereby allowing a steady-state autoregulatory response to be completed. For sudden changes in blood pressure, the autoregulatory response is defined as dynamic. The static and dynamic components of cerebral autoregulation have been approached using linear mathematical models (models based in direct correlations). Over the past decade, demonstration of the nonstationary (the property of changing over time or space) behaviour of cerebral autoregulation has emphasised the benefit obtained in using nonlinear statistical models (models based on changeable functions), suggesting that these methods may improve the mathematical representation of cerebral autoregulation. Despite the multiple determinants involved in cerebral autoregulation, it appears feasible to reliably assess cerebral autoregulation through the combination of linear and nonlinear methods. Nonlinear methods appear attractive in the research setting, but the challenge is how to adopt these methods to the clinical setting

Copper removal strategies for Wilson's disease crisis in the ICU

Wilson's disease is a rare, inherited, autosomal recessive disorder of copper metabolism which leads to an accumulation of copper in body tissues. If a patient develops a Wilson's crisis, mortality can approach 100%. The treatment of such patients is mostly organ support but a possible treatment goal is to try to rapidly remove copper from their system. We performed a literature search on methods for de-coppering strategies for patients in intensive care with known Wilson's disease. We found 11 case reports where therapeutic plasma exchange was used and six case reports where various forms of albumin dialysis were used as techniques for rapidly reducing serum copper levels. To date, the case reports are encouraging that therapeutic plasma exchange and albumin dialysis can either delay or prevent the need for liver transplantation in patients with fulminant hepatic failure due to Wilson's disease. However, these case reports are mainly in the paediatric or young adult population, thus further studies in adults are warranted