Keith Dombrowski

Andexanet alfa for the reversal of Factor Xa inhibitor related anticoagulation

ABSTRACT Andexanet alfa is a specific reversal agent for Factor Xa inhibitors. The molecule is a recombinant protein analog of factor Xa that binds to Factor Xa inhibitors and antithrombin:LMWH complex but does not trigger prothrombotic activity. In ex vivo, animal, and volunteer human studies, andexanet alfa (AnXa) was able to dose-dependently reverse Factor Xa inhibition and restore thrombin generation for the duration of drug administration. Further trials are underway to examine its safety and efficacy in the population of patients experiencing FXa inhibitor-related bleeding.

Cerebrospinal Fluid Catecholamine Levels as Predictors of Outcome in Subarachnoid Hemorrhage

Objective: Subarachnoid hemorrhage (SAH) is associated with marked sympathetic activation at the time of ictus. The purpose of this study is to determine whether early central catecholamine levels measured from cerebrospinal fluid (CSF) relate to outcome in patients with SAH. Methods: Observational study of consecutive SAH grade 3–5 patients who underwent ventriculostomy placement, but did not undergo open craniotomy for aneurysm obliteration. CSF samples were obtained during the first 48 h following symptom onset and assayed for catecholamine levels. Statistical analyses were performed to determine whether the levels predicted mortality by day 15 or mortality/disability by day 30. Results: For the 102 patients included, mean age was 58, and 73% were female – 21% experienced day-15 mortality, and 32% experienced mortality/disability by day 30. Early mortality was related to Hunt-Hess (H/H) grade (p < 0.001), neurogenic cardiomyopathy (NC) (p = 0.003), cerebral infarction (p = 0.001), elevated intracranial pressure (ICP) (p = 0.029), epinephrine (EPI) level (p = 0.002) and norepinephrine/3,4-dihydroxyphenylglycol (NE/DHPG) ratio (p = 0.003). Mortality/disability was related to H/H grade (p < 0.001), NC (p = 0.018), infarction (p < 0.001), elevated ICP (p = 0.002), EPI (p = 0.004) and NE/DHPG (p = 0.014). Logistic regression identified age [OR 1.09 (95% CI 1.01–1.17)], H/H grade [9.52 (1.19–77)], infarction [10.87 (1.22–100)], ICP elevation [32.26 (2–500)], EPI [1.06 (1.01–1.10)], and (inversely) DHPG [0.99 (0.99–1.00)] as independent predictors of early mortality. For mortality/disability, H/H grade [OR 21.74 (95% CI 5.62–83)], ICP elevation [18.52 (1.93–166)], and EPI [1.05 (1.02–1.09)] emerged as independent predictors. Proportional-hazards analysis revealed age [HR 1.041 (95% CI 1.003–1.08)], H/H grade [6.9 (1.54–31.25)], NC [4.31 (1.5–12.35)], and EPI [1.032 (1.009–1.054)] independently predicted early mortality. Conclusions: CSF catecholamine levels are elevated in SAH patients who experience early mortality or disability. EPI may potentially serve as useful index of outcome in this population of patients with SAH.

Diagnostic Accuracy of Electrographic Seizure Detection by Neurophysiologists and Non-Neurophysiologists in the Adult ICU Using a Panel of Quantitative EEG Trends.

Purpose: To evaluate the sensitivity and specificity of a panel of quantitative EEG (qEEG) trends for seizure detection in adult intensive care unit (ICU) patients when reviewed by neurophysiologists and non-neurophysiologists. Methods: One hour qEEG panels (n = 180) were collected retrospectively from 45 ICU patients and were distributed to 5 neurophysiologists, 7 EEG technologists, and 5 Neuroscience ICU nurses for evaluation of seizures. Each panel consisted of the following qEEG tools, displayed separately for left and right hemisphere electrodes: rhythmicity spectrogram (rhythmic run detection and display; Persyst Inc), color density spectral array, EEG asymmetry index, and amplitude integrated EEG. The reviewers did not have access to the raw EEG data. Results: For the reviewers ability to detect the presence of seizures on qEEG panels when compared with the gold standard of independent raw EEG review, the sensitivities and specificities are as follows: neurophysiologists 0.87 and 0.61, EEG technologists 0.80 and 0.80, and Neuroscience ICU nurses 0.87 and 0.61, respectively. There was no statistical difference among the three groups regarding sensitivity. Conclusions: Quantitative EEG display panels are a promising tool to aid detection of seizures by non-neurophysiologists as well as by neurophysiologists. However, even when used as a panel, qEEG trends do not appear to be adequate as the sole method for reviewing continuous EEG data.

Development and Feasibility Testing of a Critical Care EEG Monitoring Database for Standardized Clinical Reporting and Multicenter Collaborative Research.

Purpose: The rapid expansion of the use of continuous critical care electroencephalogram (cEEG) monitoring and resulting multicenter research studies through the Critical Care EEG Monitoring Research Consortium has created the need for a collaborative data sharing mechanism and repository. The authors describe the development of a research database incorporating the American Clinical Neurophysiology Society standardized terminology for critical care EEG monitoring. The database includes flexible report generation tools that allow for daily clinical use. Methods: Key clinical and research variables were incorporated into a Microsoft Access database. To assess its utility for multicenter research data collection, the authors performed a 21-center feasibility study in which each center entered data from 12 consecutive intensive care unit monitoring patients. To assess its utility as a clinical report generating tool, three large volume centers used it to generate daily clinical critical care EEG reports. Results: A total of 280 subjects were enrolled in the multicenter feasibility study. The duration of recording (median, 25.5 hours) varied significantly between the centers. The incidence of seizure (17.6%), periodic/rhythmic discharges (35.7%), and interictal epileptiform discharges (11.8%) was similar to previous studies. The database was used as a clinical reporting tool by 3 centers that entered a total of 3,144 unique patients covering 6,665 recording days. Conclusions: The Critical Care EEG Monitoring Research Consortium database has been successfully developed and implemented with a dual role as a collaborative research platform and a clinical reporting tool. It is now available for public download to be used as a clinical data repository and report generating tool.

Life-saving hemicraniectomy for fulminant acute disseminated encephalomyelitis

Fulminant acute disseminated encephalomyelitis (ADEM) is a rare demyelinating disorder, which most often occurs after an infection or vaccination. It frequently presents with focal neurologic signs and an altered sensorium. Patients often require critical care for airway management but are typically treated with medical therapy alone, including intravenous steroids and other immunotherapies. We present a case of dominant hemisphere fulminant ADEM in a patient who required neurosurgical intervention and a life-saving hemicraniectomy despite maximum medical therapy.

Skin and gland but not urine odours elicit conspicuous investigation by female grey short-tailed opossums, Monodelphis domestica

Chemical communication plays a major role in mammalian behaviour. One mammal with well-developed chemical senses is the grey short-tailed opossum, a small, South American marsupial that has become common in laboratory research. Male and female opossums scent-mark with different body parts, but apparently not with urine, and females enter oestrus following their exposure to male odours. To elucidate the effects of body odours on the behaviour of female opossums, we investigated their ability to discriminate between conspecific odours originating from different body parts. We simultaneously presented female opossums with two cotton balls smeared either with skin and glandular secretions or urine of conspecifics, or with distilled water or blank controls, and we analysed the time females spent investigating each stimulus. Odours of the male suprasternal gland elicited intensive investigation by the test females. Male flank and submandible odours, and female submandible odours, were also attractive to the females. Investigation of male and female urine was comparable to investigation of water and blank controls. We suggest that in this species, which inhabits semiarid areas, urine marking is avoided to reduce dehydration, and consequently urine has lost its biological significance as a chemosignal. On the other hand, glandular and skin secretions, which are more stable than aqueous deposits in dry conditions, allow the opossums to communicate with each other effectively and also to retain body fluids.

Association between acute sympathetic response, early onset vasospasm, and delayed vasospasm following spontaneous subarachnoid hemorrhage

Subarachnoid hemorrhage (SAH) is accompanied by a marked acute sympathetic response, and evidence exists for sympathetic participation in the development of cerebral vasospasm (VS). The purpose of this observational investigation was to assess the association between acute central catecholaminergic activity, early VS and delayed VS following SAH. SAH grade 3-5 patients who received ventriculostomy, and in whom bilateral temporal transcranial insonation was performed, were enrolled. Cerebrospinal fluid (CSF) was sampled (<48 hours) and assayed for catecholamines, which were correlated to measures of early and delayed sonographic anterior circulation VS. Clinical independent predictors of early VS included age (odds ratio .946 [95% confidence interval .902-.991]), CT scan score (4.27 [1.30-14.0]) and neurogenic cardiomyopathy (6.5 [1.24-34.1]). Age (.925 [.859-.996]) and CT scan score (8.30 [1.33-5.17]) also independently predicted delayed VS. Any early VS independently predicted conventionally defined delayed VS (10.9 [2.64-45.0]), and severe delayed VS was independently predicted by any early VS (9.87 [2.45-39.7]) and by conventionally defined early VS (12.3 [2.80-54.1]). The norepinephrine:3,4-dihydroxyphenylglycol ratio (NE/DHPG) independently predicted severe delayed VS (3.38 [1.01-11.35]), for which DHPG was a negative predictor (.356 [.151-.839]). Epinephrine was a negative predictor of any early VS (.574 [.357-.921]), any delayed VS (.372 [.158-.875]), and delayed conventional VS (.402 [.200-.807]). Early and delayed VS appear to be related processes that are generally unrelated to the acute central sympathetic response following SAH. The one exception may be severe delayed VS which may be associated with noradrenergic activation.

Cardiovascular manifestations of neurologic disease

Cardiac manifestations of neurologic diseases are common in clinical practice. There are numerous anatomic and pathophysiologic links between the normal and abnormal function of both systems. There are a number of brain-heart interactions which affect the care of patients as well as help guide therapeutic development. This is exemplified in the area of vascular neurology where knowledge of the brain-heart connection is essential not only for bedside management but where collaborative efforts between neurology and cardiology are key in developing new strategies for ischemic stroke prevention and treatment, atrial fibrillation, and interventional techniques. This chapter will focus on cardiac manifestations of neurologic disease, with special emphasis on vascular and intensive care neurology, epilepsy, and neurodegenerative and peripheral nervous system diseases.

The Evidence Base for Nursing Care and Monitoring of Patients During Therapeutic Temperature Management

Therapeutic temperature management (TTM) is fast becoming a primary management strategy for a variety of medical conditions treated in critical care settings throughout the world. Nurses who provide direct care and who are tasked with developing multidisciplinary protocols and pathways are struggling to collate evidence from which to support specific nursing interventions. The aim of this project was to create the first comprehensive set of evidence-based guidelines specific to nursing care of the patient for whom TTM is medically necessary. Evidence-based nursing practice summaries are provided for nine nursing content areas: interventions to manage temperature, monitoring temperature, neurologic, cardiac, pulmonary, skin care, gastrointestinal/endocrine, laboratory findings, and general considerations for nursing care.

Focal neuronal dysfunction resulting in subclinical status epilepticus in von gierke's disease

Glycogen storage disease type I (GSD I) is an uncommon GSD that is associated with a defect of the glucose-6-phosphatase complex. Defects in this enzyme interfere with glycogenolysis and gluconeogenesis, often resulting in severe fasting hypoglycemia, lactic acidosis, hyperuricemia and hyperlipidemia. Clinical manifestations include hepatomegaly, small stature and delayed pubertal development [1–4]. Severe hypoglycemia is known to cause generalized seizures [1]. However, focal seizures have rarely been reported. In this brief communication, we report a case of a woman with GSD I who presented with focal status epilepticus of the parietooccipital lobe manifesting as intermittent visual obscuration, illusions and sensory neglect.