Enlighten-Research publications by members of the University of Glasgow http://eprints.gla.ac.uk Minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label phase 3 trial with blinded endpoint

The risk of death from venous thromboembolism (VTE) is high in intensive care unit patients with neurological diagnoses. This is due to an increased risk of venous stasis secondary to paralysis as well as an increased prevalence of underlying pathologies that cause endothelial activation and create an increased risk of embolus formation. In many of these diseases, there is an associated risk from bleeding because of standard VTE prophylaxis. There is a paucity of prospective studies examining different VTE prophylaxis strategies in the neurologically ill. The lack of a solid evidentiary base has posed challenges for the establishment of consistent and evidence-based clinical practice standards. In response to this need for guidance, the Neurocritical Care Society set out to develop and evidence-based guideline using GRADE to safely reduce VTE and its associated complications.

Devastating brain injuries (DBIs) profoundly damage cerebral function and frequently cause death. DBI survivors admitted to critical care will suffer both intracranial and extracranial effects from their brain injury. The indicators of quality care in DBI are not completely defined, and despite best efforts many patients will not survive, although others may have better outcomes than originally anticipated. Inaccuracies in prognostication can result in premature termination of life support, thereby biasing outcomes research and creating a self-fulfilling cycle where the predicted course is almost invariably dismal. Because of the potential complexities and controversies involved in the management of devastating brain injury, the Neurocritical Care Society organized a panel of expert clinicians from neurocritical care, neuroanesthesia, neurology, neurosurgery, emergency medicine, nursing, and pharmacy to develop an evidence-based guideline with practice recommendations. The panel intends for this guideline to be used by critical care physicians, neurologists, emergency physicians, and other health professionals, with specific emphasis on management during the first 72-h post-injury. Following an extensive literature review, the panel used the GRADE methodology to evaluate the robustness of the data. They made actionable recommendations based on the quality of evidence, as well as on considerations of risk: benefit ratios, cost, and user preference. The panel generated recommendations regarding prognostication, psychosocial issues, and ethical considerations.

Simple bedside tests and somatosensory-evoked potentials predict poor neurologic outcome for survivors of cardiac arrest treated with targeted temperature management, and specificity improves when performed beyond 72 hours. Clinicians should use caution with these predictors as they carry the inherent risk of becoming self-fulfilling.

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BACKGROUND:Minimally invasive surgery procedures, including stereotactic catheter aspiration and clearance of intracerebral hemorrhage (ICH) with recombinant tissue plasminogen activator hold a promise to improve outcome of supratentorial brain hemorrhage, a morbid and disabling type of stroke. A recently completed Phase III randomized trial showed improved mortality but was neutral on the primary outcome (modified Rankin scale score 0 to 3 at 1 yr). OBJECTIVE: To assess surgical performance and its impact on the extent of ICH evacuation and functional outcomes. METHODS: Univariate and multivariate models were used to assess the extent of hematoma evacuation efficacy in relation to mRS 0 to 3 outcome and postulated factors related to patient, disease, and protocol adherence in the surgical arm (n = 242) of the MISTIE trial. RESULTS: Greater ICH reduction has a higher likelihood of achieving mRS of 0 to 3 with a minimum evacuation threshold of ≤15 mL end of treatment ICH volume or ≥70% volume reduction when controlling for disease severity factors. Mortality benefit was achieved at ≤30 mL end of treatment ICH volume, or >53% volume reduction. Initial hematoma volume, history of hypertension, irregular-shaped hematoma, number of alteplase doses given, surgical protocol deviations, and catheter manipulation problems were significant factors in failing to achieve ≤15 mL goal evacuation. Greater surgeon/site experiences were associated with avoiding poor hematoma evacuation. CONCLUSION: This is the first surgical trial reporting thresholds for reduction of ICH volume correlating with improved mortality and functional outcomes. To realize the benefit of surgery, protocol objectives, surgeon education, technical enhancements, and case selection should be focused on this goal.

Levetiracetam, a pyrrolidine, the racemically pure Senantiomer of pyrrolidineacetamide, is an antiepileptic medication with a novel mechanism, related to a specific binding site in the brain for the synaptic vesicle protein 2A 1 . In contrast to the mechanism of traditional antiepileptics, there is no evidence for action on voltage-gated sodium channel, gammaamino butyric acid, or glutamate-mediated synaptic transmission 2 . Levetiracetam has a linear pharmacokinetic profile, high oral bioavailability (close to 100%), and is not bound to proteins, with 95% being metabolized and excreted in urine 3 . Plasma concentrations peak within one hour, with steady- épilepsie réfractaire au traitement, 1 comme médicament de première intention chez des patients au moment du diagnostic de l'épilepsie et 1 comme monothérapie en prophylaxie. Huit des essais cliniques randomisés évaluant le lévétiracétam comme médicament d'appoint étaient de qualité moyenne (critères GRADE), dont 2 où le traitement n'était pas en aveugle. Les méta-analyses ont montré que le lévétiracétam comme traitement d'appoint était plus efficace que le placebo pour diminuer d'au moins 50% la fréquence des crises quand il était ajouté au régime posologique de base (RR global 2,15 [1,82] ; 12 = 45%, p (hétérogénéité) = 0,08 ; p effet global < 0,01). La probabilité que des incidents thérapeutiques sérieux entraînent le retrait du patient de l'étude n'était pas significativement différente entre le groupe recevant le lévétiracétam et le groupe témoin (RR global 1,37 [0,13] ; 12 = 0% ; p (hétérogénéité) = 0,84 ; p effet global = 0,17). Selon les analyses de sous-groupes, les effets seraient les mêmes, quelle que soit la posologie. Les analyses de sensibilité des études bien menées à l'insu ont montré des effets similaires. Conclusions : Le lévétiracétam est un médicament d'appoint efficace dans l'épilepsie réfractaire au traitement. Il devra faire l'objet de nouvelles études pour établir son efficacité en monothérapie chez les patients dont le diagnostic est récent et en prophylaxie chez les patients qui ont subi un traumatisme crânien. common side effects of levetiracetam include somnolence, asthenia and dizziness 5 . Meta-analysis suggests that the extended release version of this medication, when compared to placebo, may be associated with lower incidence of nervous system, psychiatric, nutritional and metabolic adverse effects 2-5 . So far, only four systematic reviews 2-5 have been conducted verifying its efficacy as a sole agent in refractory partial-onset seizures, as well as adjunctive agent in epilepsy. These studies were limited by lack of clarity in selection criteria, exclusion of potentially relevant trials, lack of critical appraisal of primary studies, and for-profit funding of most trials. OBJECTIVESThe purpose of this review and meta-analysis is to systematically collect, critically appraise, and synthesize current evidence regarding the efficacy and tolerability of levetiracetam as a first line or adjunctive agent for adults suffering from i...

A multicenter quality intervention improved rates of appropriate neurologic prognostication after OHCA but did not increase survival with good neurologic outcome. Clinical trial registered with www.clinicaltrials.gov (NCT 01472458).