Monisha A. Kumar

Guideline for Reversal of Antithrombotics in Intracranial Hemorrhage : A Statement for Healthcare Professionals from the Neurocritical Care Society and Society of Critical Care Medicine.

BackgroundThe use of antithrombotic agents, including anticoagulants, antiplatelet agents, and thrombolytics has increased over the last decade and is expected to continue to rise. Although antithrombotic-associated intracranial hemorrhage can be devastating, rapid reversal of coagulopathy may help limit hematoma expansion and improve outcomes.MethodsThe Neurocritical Care Society, in conjunction with the Society of Critical Care Medicine, organized an international, multi-institutional committee with expertise in neurocritical care, neurology, neurosurgery, stroke, hematology, hemato-pathology, emergency medicine, pharmacy, nursing, and guideline development to evaluate the literature and develop an evidence-based practice guideline. Formalized literature searches were conducted, and studies meeting the criteria established by the committee were evaluated.ResultsUtilizing the GRADE methodology, the committee developed recommendations for reversal of vitamin K antagonists, direct factor Xa antagonists, direct thrombin inhibitors, unfractionated heparin, low-molecular weight heparin, heparinoids, pentasaccharides, thrombolytics, and antiplatelet agents in the setting of intracranial hemorrhage.ConclusionsThis guideline provides timely, evidence-based reversal strategies to assist practitioners in the care of patients with antithrombotic-associated intracranial hemorrhage.

Consensus summary statement of the International Multidisciplinary Consensus Conference on Multimodality Monitoring in Neurocritical Care: A statement for healthcare professionals from the Neurocritical Care Society and the European Society of Intensive Care Medicine

Neurocritical care depends, in part, on careful patient monitoring but as yet there are little data on what processes are the most important to monitor, how these should be monitored, and whether monitoring these processes is cost-effective and impacts outcome. At the same time, bioinformatics is a rapidly emerging field in critical care but as yet there is little agreement or standardization on what information is important and how it should be displayed and analyzed. The Neurocritical Care Society in collaboration with the European Society of Intensive Care Medicine, the Society for Critical Care Medicine, and the Latin America Brain Injury Consortium organized an international, multidisciplinary consensus conference to begin to address these needs. International experts from neurosurgery, neurocritical care, neurology, critical care, neuroanesthesiology, nursing, pharmacy, and informatics were recruited on the basis of their research, publication record, and expertise. They undertook a systematic literature review to develop recommendations about specific topics on physiologic processes important to the care of patients with disorders that require neurocritical care. This review does not make recommendations about treatment, imaging, and intraoperative monitoring. A multidisciplinary jury, selected for their expertise in clinical investigation and development of practice guidelines, guided this process. The GRADE system was used to develop recommendations based on literature review, discussion, integrating the literature with the participants’ collective experience, and critical review by an impartial jury. Emphasis was placed on the principle that recommendations should be based on both data quality and on trade-offs and translation into clinical practice. Strong consideration was given to providing pragmatic guidance and recommendations for bedside neuromonitoring, even in the absence of high quality data.

Consensus Summary Statement of the International Multidisciplinary Consensus Conference on Multimodality Monitoring in Neurocritical Care: A statement for healthcare professionals from the Neurocritical Care Society and the European Society of Intensive Care Medicine

Neurocritical care depends, in part, on careful patient monitoring but as yet there are little data on what processes are the most important to monitor, how these should be monitored, and whether monitoring these processes is cost-effective and impacts outcome. At the same time, bioinformatics is a rapidly emerging field in critical care but as yet there is little agreement or standardization on what information is important and how it should be displayed and analyzed. The Neurocritical Care Society in collaboration with the European Society of Intensive Care Medicine, the Society for Critical Care Medicine, and the Latin America Brain Injury Consortium organized an international, multidisciplinary consensus conference to begin to address these needs. International experts from neurosurgery, neurocritical care, neurology, critical care, neuroanesthesiology, nursing, pharmacy, and informatics were recruited on the basis of their research, publication record, and expertise. They undertook a systematic literature review to develop recommendations about specific topics on physiologic processes important to the care of patients with disorders that require neurocritical care. This review does not make recommendations about treatment, imaging, and intraoperative monitoring. A multidisciplinary jury, selected for their expertise in clinical investigation and development of practice guidelines, guided this process. The GRADE system was used to develop recommendations based on literature review, discussion, integrating the literature with the participants’ collective experience, and critical review by an impartial jury. Emphasis was placed on the principle that recommendations should be based on both data quality and on trade-offs and translation into clinical practice. Strong consideration was given to providing pragmatic guidance and recommendations for bedside neuromonitoring, even in the absence of high quality data.

Anti–N-methyl-D-aspartate Receptor Encephalitis During Pregnancy

OBJECTIVE To report 3 patients who developed anti-N-methyl-d-aspartate receptor encephalitis during pregnancy. DESIGN Case reports. SETTING University hospitals. Patients Three young women developed at 14, 8, and 17 weeks of gestation acute change of behavior, prominent psychiatric symptoms, progressive decrease of consciousness, seizures, dyskinesias, and autonomic dysfunction. MAIN OUTCOME MEASURES Clinical, radiological, and immunological findings. RESULTS The 3 patients had cerebrospinal fluid pleocytosis, normal magnetic resonance imaging, and electroencephalogram showing slow activity. All had higher antibody titers in cerebrospinal fluid than in serum and 2 had ovarian teratomas that were removed. The pregnancy was terminated in 1 patient with recurrent bilateral teratomas. All patients had substantial neurological recoveries, and the 2 newborns were normal. Results of extensive antibody testing in 1 of the babies were negative. CONCLUSION The current study shows that anti-NMDAR encephalitis during pregnancy can have a good outcome for the mother and newborn.

A Comparison of Clinical and Research Practices in Measuring Cerebral Perfusion Pressure: A Literature Review and Practitioner Survey

BACKGROUND:Our objective was to determine whether there is variability in the foundational literature and across centers in how mean arterial blood pressure is measured to calculate cerebral perfusion pressure. METHODS:We reviewed foundational literature and sent an e-mail survey to members of the Neurocritical Care Society. RESULTS:Of 32 articles reporting cerebral perfusion pressure data, the reference point for mean arterial blood pressure was identified in 16: 10 heart and 6 midbrain. The overall survey response rate was 14.3%. Responses from 31 of 34 (91%) United Council for Neurologic Subspecialties fellowship-accredited Neurointensive Care Units indicated the reference point was most often the heart (74%), followed by the midbrain (16%). Conflicting answers were received from 10%. CONCLUSIONS:There is substantive heterogeneity in both research reports and clinical practice in how mean arterial blood pressure is measured to determine cerebral perfusion pressure.

Anemia and hematoma volume in acute intracerebral hemorrhage

Objective: Anemia increases risk of bleeding complications in the critically ill. In primary intracerebral hemorrhage (ICH), the most fatal type of stroke, outcome is largely dependent on the volume of hemorrhage into the brain. We investigated the relationship between anemia and clinical course of acute ICH. Methods: Six hundred ninety-four consecutive subjects were identified from an ongoing single-center prospective cohort study of nontraumatic ICH during a 6-year period. Anemia was defined according to World Health Organization criteria. Study end points were ICH volume, as measured on the baseline computed tomography scan, and 30-day mortality. Results: Anemia was present in 177 (25.8%) patients on admission. Patients with anemia were older (p = 0.005) and more likely to have coronary artery disease (p < 0.0001). In multivariable analysis, anemia (p = 0.009), lobar location of ICH (p < 0.001), white blood cell count (p < 0.001), and admission diastolic blood pressure (p < 0.001) were associated with larger ICH volume. Although after accounting for ICH volume, none of these variables was a significant predictor of 30-day mortality in multivariable analysis, the size of the marginal reduction in the odds ratio for anemia suggests that it may have a small effect on mortality through mechanisms in addition to ICH volume. Conclusions: Anemia is common in acute ICH and its presence at admission is an independent predictor of larger volume of ICH. Given the central role of ICH volume in outcome, clarification of the mechanisms underlying this relationship may offer novel therapeutic targets for reducing ICH morbidity and mortality.

Evidence that a Panel of Neurodegeneration Biomarkers Predicts Vasospasm, Infarction, and Outcome in Aneurysmal Subarachnoid Hemorrhage

Biomarkers for neurodegeneration could be early prognostic measures of brain damage and dysfunction in aneurysmal subarachnoid hemorrhage (aSAH) with clinical and medical applications. Recently, we developed a new panel of neurodegeneration biomarkers, and report here on their relationships with pathophysiological complications and outcomes following severe aSAH. Fourteen patients provided serial cerebrospinal fluid samples for up to 10 days and were evaluated by ultrasonography, angiography, magnetic resonance imaging, and clinical examination. Functional outcomes were assessed at hospital discharge and 6–9 months thereafter. Eight biomarkers for acute brain damage were quantified: calpain-derived α-spectrin N- and C-terminal fragments (CCSntf and CCSctf), hypophosphorylated neurofilament H, 14-3-3 β and ζ, ubiquitin C-terminal hydrolase L1, neuron-specific enolase, and S100β. All 8 biomarkers rose up to 100-fold in a subset of patients. Better than any single biomarker, a set of 6 correlated significantly with cerebral vasospasm, brain infarction, and poor outcome. Furthermore, CSF levels of 14-3-3β, CCSntf, and NSE were early predictors of subsequent moderate-to-severe vasospasm. These data provide evidence that a panel of neurodegeneration biomarkers may predict lasting brain dysfunction and the pathophysiological processes that lead to it following aSAH. The panel may be valuable as surrogate endpoints for controlled clinical evaluation of treatment interventions and for guiding aSAH patient care.

The International Multidisciplinary Consensus Conference on Multimodality Monitoring in Neurocritical Care: Evidentiary Tables: A Statement for Healthcare Professionals from the Neurocritical Care Society and the European Society of Intensive Care Medicine

A variety of technologies have been developed to assist decision-making during the management of patients with acute brain injury who require intensive care. A large body of research has been generated describing these various technologies. The Neurocritical Care Society (NCS) in collaboration with the European Society of Intensive Care Medicine (ESICM), the Society for Critical Care Medicine (SCCM), and the Latin America Brain Injury Consortium (LABIC) organized an international, multidisciplinary consensus conference to perform a systematic review of the published literature to help develop evidence-based practice recommendations on bedside physiologic monitoring. This supplement contains a Consensus Summary Statement with recommendations and individual topic reviews on physiologic processes important in the care of acute brain injury. In this article we provide the evidentiary tables for select topics including systemic hemodynamics, intracranial pressure, brain and systemic oxygenation, EEG, brain metabolism, biomarkers, processes of care and monitoring in emerging economies to provide the clinician ready access to evidence that supports recommendations about neuromonitoring.

Temporal dynamics of microparticle elevation following subarachnoid hemorrhage

OBJECT Microparticles (MPs), small membrane fragments shed from various cell types, have been implicated in thrombosis, inflammation, and endothelial dysfunction. Their involvement in subarachnoid hemorrhage (SAH) and the development of cerebral infarction and clinical deterioration caused by delayed cerebral ischemia (DCI) remain ill defined. The authors sought to quantify the magnitude of elevations in MPs, delineate the temporal dynamics of elevation, and analyze the correlation between MPs and DCI in patients with SAH. METHODS On the day of hemorrhage and on Days 1, 3, 5, 7, and 10 after hemorrhage, peripheral blood samples were drawn from 22 patients with SAH. Plasma samples were labeled with Annexin V and CD142, CD41a, CD235a, CD146, CD66b, or von Willebrand factor (vWF) and were quantified by flow cytometry. Clinical data, including the 3-month extended Glasgow Outcome Scale (GOS-E) scores, infarction as measured on MRI at 14 days after SAH, and vasospasm as measured by transcranial Doppler ultrasonography and angiography, were collected and compared with the MP burden. RESULTS When averaged over time, all MP subtypes were elevated relative to controls. The CD235a+(erythrocyte)-, CD66b+(neutrophil)-, and vWF-associated MPs peaked on the day of hemorrhage and quickly declined. The CD142+(tissue factor [TF])-associated MPs and CD146+(endothelial cell)-associated MPs were significantly elevated throughout the study period. There was a strong negative correlation between TF-expressing and endothelial-derived MPs at Day 1 after SAH and the risk of infarction at Day 14 after SAH. CONCLUSIONS Microparticles of various subtypes are elevated following SAH; however, the temporal profile of this elevation varies by subtype. Those subtypes closely associated with thrombosis and endothelial dysfunction, for example, CD145+(TF)-associated MPs and CD146+(endothelial cell)-associated MPs, had the most durable response and demonstrated a significant negative correlation with radiographic infarction at 14 days after SAH. Levels of these MPs predict infarction as early as Day 1 post-SAH.

Multimodal Monitoring in Subarachnoid Hemorrhage

In severely injured patients, the immediate goal of resuscitation is restoration and maintenance of adequate tissue metabolism by ensuring sufficient delivery of fuel, typically oxygen and glucose, to meet cellular metabolic demands. In neurocritical care, traditional goals of resuscitation—intracranial pressure (ICP), cerebral perfusion pressure (CPP), and the clinical examination—have been extrapolated from those of general critical care. These variables are analogous to central venous pressure, mean arterial pressure, and urine output and are similarly crude. These distant surrogates for cerebral perfusion do not account for dynamic changes in cerebral autoregulation, tissue metabolic rate, cellular fuel use, and microcirculatory dysfunction, all of which impact tissue metabolic health. Although standard, it seems intuitively obvious that a uniform approach of maintaining ICP 60 mm Hg is overly simplistic. This approach does not address either significant baseline differences in patient physiology nor the complex, dynamic, and variable pathophysiological changes that ensue after severe brain injury. A more tailored therapeutic strategy that responds to multiple simultaneously measured and more relevant physiological variables is logically appealing. Until recently, however, the requisite individual patient physiology was inaccessible at the bedside. The emergence of technology that allows for continuous real-time bedside monitoring of cerebral physiology marks a new era in neurocritical care. These monitors facilitate assessment of therapeutic efficacy and may provide more relevant physiological end points for resuscitation. Combining these monitors in a multimodal approach allows for the practice of goal-directed cerebral resuscitation that emphasizes the individual patients unique neurological and systemic physiology. Aneurysmal subarachnoid hemorrhage (SAH) is an example of a disease in which individualized goal-directed cerebral resuscitation using multimodality neuromonitoring might influence therapy and outcome. After initial patient stabilization and aneurysm exclusion from the circulation, care focuses on prevention of secondary neuronal injury. Of those who survive the initial hemorrhage, …