Publications by authors named "Gretchen M Brophy"

71 Publications

Principles of Pharmacotherapy of Seizures and Status Epilepticus.

Semin Neurol 2020 Dec 11;40(6):681-695. Epub 2020 Nov 11.

Pharmacotherapy and Outcomes Science and Neurosurgery, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia.

Status epilepticus is a neurological emergency with an outcome that is highly associated with the initial pharmacotherapy management that must be administered in a timely fashion. Beyond first-line therapy of status epilepticus, treatment is not guided by robust evidence. Optimal pharmacotherapy selection for individual patients is essential in the management of seizures and status epilepticus with careful evaluation of pharmacokinetic and pharmacodynamic factors. With the addition of newer antiseizure agents to the market, understanding their role in the management of status epilepticus is critical. Etiology-guided therapy should be considered in certain patients with drug-induced seizures, alcohol withdrawal, or autoimmune encephalitis. Some patient populations warrant special consideration, such as pediatric, pregnant, elderly, and the critically ill. Seizure prophylaxis is indicated in select patients with acute neurological injury and should be limited to the acute postinjury period.
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http://dx.doi.org/10.1055/s-0040-1718721DOI Listing
December 2020

Stress-Related Gastrointestinal Bleeding in Patients with Aneurysmal Subarachnoid Hemorrhage: A Multicenter Retrospective Observational Study.

Neurocrit Care 2020 Nov 4. Epub 2020 Nov 4.

University of Kentucky HealthCare, Lexington, USA.

Background/objective: Stress-related mucosal bleeding (SRMB) occurs in approximately 2-4% of critically ill patients. Patients with aneurysmal subarachnoid hemorrhage (aSAH) have a (diffuse) space-occupying lesion, are critically ill, often require mechanical ventilation, and frequently receive anticoagulation or antiplatelet therapy after aneurysm embolization, all of which may be risk factors for SRMB. However, no studies have evaluated SRMB in patients with aSAH. Aims of the study were to determine the incidence of SRMB in aSAH patients, evaluate the effect of acid suppression on SRMB, and identify specific risk factors for SRMB.

Methods: This was a multicenter, retrospective, observational study conducted across 17 centers. Each center reviewed up to 50 of the most recent cases of aSAH. Patients with length of stay (LOS) < 48 h or active GI bleeding on admission were excluded. Variables related to demographics, aSAH severity, gastrointestinal (GI) bleeding, provision of SRMB prophylaxis, adverse events, intensive care unit (ICU), and hospital LOS were collected for the first 21 days of admission or until hospital discharge, whichever came first. Descriptive statistics were used to analyze the data. A multivariate logistic regression modeling was utilized to examine the relationship between specific risk factors and the incidence of clinically important GI bleeding in patients with aSAH.

Results: A total of 627 patients were included. The overall incidence of clinically important GI bleeding was 4.9%. Of the patients with clinically important GI bleeding, 19 (61%) received pharmacologic prophylaxis prior to evidence of GI bleeding, while 12 (39%) were not on pharmacologic prophylaxis at the onset of GI bleeding. Patients who received an acid suppressant agent were less likely to experience GI bleeding than patients who did not receive pharmacologic prophylaxis prior to evidence of bleeding (OR 0.39, 95% CI 0.18-0.83). The multivariate regression analysis identified any instance of elevated intracranial pressure, creatinine clearance < 60 ml/min and the incidence of cerebral vasospasm as specific risk factors associated with GI bleeding. Cerebral vasospasm has not previously been described as a risk for GI bleeding (OR 2.5 95% CI 1.09-5.79).

Conclusions: Clinically important GI bleeding occurred in 4.9% of patients with aSAH, similar to the general critical care population. Risk factors associated with GI bleeding were prolonged mechanical ventilation (> 48 h), creatinine clearance < 60 ml/min, presence of coagulopathy, elevation of intracranial pressure, and cerebral vasospasm. Further prospective research is needed to confirm this observation within this patient population.
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http://dx.doi.org/10.1007/s12028-020-01137-5DOI Listing
November 2020

Anticoagulation reversal for intracranial hemorrhage in the era of the direct oral anticoagulants.

Curr Opin Crit Care 2020 04;26(2):122-128

Virginia Commonwealth University, School of Pharmacy, Richmond, Virginia.

Purpose Of Review: This review focuses on recent relevant literature that examines the reversal of direct oral anticoagulants (DOACs) in patients with intracranial hemorrhage (ICH). The aim of this review is to provide an insightful description of available reversal agents and their clinical utility.

Recent Findings: Increases in prescribing of DOACs has led to the introduction of drug-specific reversal agents. The clinical trials that evaluated these agents did not include a comparator arm making it difficult to determine if they are clinically superior to nonspecific reversal agents.

Summary: Numerous options for reversal of DOAC-associated ICH are currently available. Recent clinical trials have demonstrated drug-specific reversal agents are effective in this setting, but additional research is needed to determine whether these agents should be routinely preferred over nonspecific reversal agents.
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http://dx.doi.org/10.1097/MCC.0000000000000706DOI Listing
April 2020

Early Acute Ischemic Stroke Management for Pharmacists.

Hosp Pharm 2020 Feb 7;55(1):12-25. Epub 2018 Aug 7.

Virginia Commonwealth University, Richmond, USA.

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http://dx.doi.org/10.1177/0018578718791504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6961150PMC
February 2020

Unique Uses of Cooling Strategies.

Ther Hypothermia Temp Manag 2019 09 27;9(3):168-172. Epub 2019 Aug 27.

Department of Surgery, University of Maryland, Baltimore, Maryland.

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http://dx.doi.org/10.1089/ther.2019.29064.mjkDOI Listing
September 2019

High-Dose Intravenous Ascorbic Acid: Ready for Prime Time in Traumatic Brain Injury?

Neurocrit Care 2020 02;32(1):333-339

Department of Pharmacotherapy and Outcomes Sciences, Virginia Commonwealth University School of Pharmacy, Richmond, USA.

Traumatic brain injury (TBI) is one of the leading public health problems in the USA and worldwide. It is the number one cause of death and disability in children and adults between ages 1-44. Despite efforts to prevent TBIs, the incidence continues to rise. Secondary brain injury occurs in the first hours and days after the initial impact and is the most effective target for intervention. Inflammatory processes and oxidative stress play an important role in the pathomechanism of TBI and are exacerbated by impaired endogenous defense mechanisms, including depletion of antioxidants. As a reducing agent, free radical scavenger, and co-factor in numerous biosynthetic reactions, ascorbic acid (AA, vitamin C) is an essential nutrient that rapidly becomes depleted in states of critical illness. The administration of high-dose intravenous (IV) AA has demonstrated benefits in numerous preclinical models in the areas of trauma, critical care, wound healing, and hematology. A safe and inexpensive treatment, high-dose IV AA administration gained recent attention in studies demonstrating an associated mortality reduction in septic shock patients. High-quality data on the effects of high-dose IV AA on TBI are lacking. Historic data in a small number of patients demonstrate acute and profound AA deficiency in patients with central nervous system pathology, particularly TBI, and a strong correlation between low AA concentrations and poor outcomes. While replenishing deficient AA stores in TBI patients should improve the brain's ability to tolerate oxidative stress, high-dose IV AA may prove an effective strategy to prevent or mitigate secondary brain injury due to its ability to impede lipid peroxidation, scavenge reactive oxygen species, suppress inflammatory mediators, stabilize the endothelium, and reduce brain edema. The existing preclinical data and limited clinical data suggest that high-dose IV AA may be effective in lowering oxidative stress and decreasing cerebral edema. Whether this translates into improved clinical outcomes will depend on identifying the ideal target patient population and possible treatment combinations, factors that need to be evaluated in future clinical studies. With its excellent safety profile and low cost, high-dose IV AA is ready to be evaluated in the early treatment of TBI patients to mitigate secondary brain injury and improve outcomes.
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http://dx.doi.org/10.1007/s12028-019-00829-xDOI Listing
February 2020

Targeted Temperature Management in Nursing Care.

Ther Hypothermia Temp Manag 2019 09 22;9(3):173-176. Epub 2019 Aug 22.

Air Methods/Life Evac of Virginia, Richmond, Virginia.

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http://dx.doi.org/10.1089/ther.2019.29062.gmbDOI Listing
September 2019

Prevention, Treatment, and Monitoring of Seizures in the Intensive Care Unit.

J Clin Med 2019 Aug 7;8(8). Epub 2019 Aug 7.

Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond, VA 23298-0533, USA.

The diagnosis and management of seizures in the critically ill patient can sometimes present a unique challenge for practitioners due to lack of exposure and complex patient comorbidities. The reported incidence varies between 8% and 34% of critically ill patients, with many patients often showing no overt clinical signs of seizures. Outcomes in patients with unidentified seizure activity tend to be poor, and mortality significantly increases in those who have seizure activity longer than 30 min. Prompt diagnosis and provision of medical therapy are crucial in order to attain successful seizure termination and prevent poor outcomes. In this article, we review the epidemiology and pathophysiology of seizures in the critically ill, various seizure monitoring modalities, and recommended medical therapy.
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http://dx.doi.org/10.3390/jcm8081177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722541PMC
August 2019

Common Data Elements for Unruptured Intracranial Aneurysms and Aneurysmal Subarachnoid Hemorrhage: Recommendations from the Working Group on Hospital Course and Acute Therapies-Proposal of a Multidisciplinary Research Group.

Neurocrit Care 2019 06;30(Suppl 1):36-45

Departments of Anesthesiology and Critical Care Medicine, Neurology, and Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, USA.

Introduction: The Common Data Elements (CDEs) initiative is a National Institute of Health/National Institute of Neurological Disorders and Stroke (NINDS) effort to standardize naming, definitions, data coding, and data collection for observational studies and clinical trials in major neurological disorders. A working group of experts was established to provide recommendations for Unruptured Aneurysms and Aneurysmal Subarachnoid Hemorrhage (SAH) CDEs.

Methods: This paper summarizes the recommendations of the Hospital Course and Acute Therapies after SAH working group. Consensus recommendations were developed by assessment of previously published CDEs for traumatic brain injury, stroke, and epilepsy. Unruptured aneurysm- and SAH-specific CDEs were also developed. CDEs were categorized into "core", "supplemental-highly recommended", "supplemental" and "exploratory".

Results: We identified and developed CDEs for Hospital Course and Acute Therapies after SAH, which included: surgical and procedure interventions; rescue therapy for delayed cerebral ischemia (DCI); neurological complications (i.e. DCI; hydrocephalus; rebleeding; seizures); intensive care unit therapies; prior and concomitant medications; electroencephalography; invasive brain monitoring; medical complications (cardiac dysfunction; pulmonary edema); palliative comfort care and end of life issues; discharge status. The CDEs can be found at the NINDS Web site that provides standardized naming, and definitions for each element, and also case report form templates, based on the CDEs.

Conclusion: Most of the recommended Hospital Course and Acute Therapies CDEs have been newly developed. Adherence to these recommendations should facilitate data collection and data sharing in SAH research, which could improve the comparison of results across observational studies, clinical trials, and meta-analyses of individual patient data.
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http://dx.doi.org/10.1007/s12028-019-00726-3DOI Listing
June 2019

Prevention Strategies to Improve Outcomes in Critically Ill Adults.

Pharmacotherapy 2019 03 15;39(3):212-214. Epub 2019 Mar 15.

Department of Pharmacotherapy & Outcomes Science and Neurosurgery, Virginia Commonwealth University, Richmond, Virginia.

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http://dx.doi.org/10.1002/phar.2232DOI Listing
March 2019

Platelets retain inducible alpha granule secretion by P-selectin expression but exhibit mechanical dysfunction during trauma-induced coagulopathy.

J Thromb Haemost 2019 05 18;17(5):771-781. Epub 2019 Mar 18.

Department of Emergency Medicine, University of Washington, Seattle, WA, USA.

Essentials Platelets in trauma-induced coagulopathy (TIC) are impaired, but the mechanism is not known. We performed comprehensive longitudinal platelet function testing in trauma patient samples. Platelets in TIC are widely impaired early after injury, but platelet activatability is intact. This suggests a mechanism of transient platelet cytoskeletal/integrin dysfunction during TIC. SUMMARY: Background Trauma-induced coagulopathy (TIC) is a common and deadly bleeding disorder. Platelet dysfunction is present during TIC, but its mechanisms remain unclear. Platelets are currently thought to become "exhausted," a state in which they have released their granule contents and can no longer aggregate or contract. Methods This prospective observational cohort study tested the hypothesis that platelet exhaustion is present during TIC and characterized the early time course of platelet dysfunction. Blood was collected from 95 adult trauma patients at a Level I trauma center at time of Emergency Department arrival and several time points over 72 h. Platelet activation state and function were characterized using CD62P (P-selectin) and PAC-1 surface membrane staining, platelet function analyzer (PFA-100), aggregometry, viscoelastic platelet mapping, and, to test for exhaustion, their ability to express CD62P after ex vivo adenosine diphosphate (ADP) agonism. Platelet function was compared between patients with and without TIC, defined by prothrombin time ≥18 s. Results Platelets in TIC showed no initial increase in their level of surface activation markers or impairment of their capacity to express CD62P in response to ADP stimulation. However, TIC platelets were impaired in nearly all functional assays, spanning adhesion, aggregation, and contraction. These effects largely remained after controlling for platelet count and fibrinogen concentration and resolved after 8 h. Conclusion The TIC platelets exhibit early impairment of adhesion, aggregation, and contraction with retained alpha granule secretion ability, suggesting a specific mechanism of cytoskeletal or integrin dysfunction that is not a result of more general platelet exhaustion.
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http://dx.doi.org/10.1111/jth.14414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494686PMC
May 2019

Periprocedural Neuroendovascular Antiplatelet Strategies for Thrombosis Prevention in Clopidogrel-Hyporesponsive Patients.

Pharmacotherapy 2019 03 11;39(3):317-334. Epub 2019 Mar 11.

Virginia Commonwealth University, Richmond, Virginia.

Patients undergoing neuroendovascular procedures such as cerebral aneurysm coiling and intracranial stent deployment are frequently treated with antiplatelet agents to prevent thrombotic complications. The combination of aspirin and a P2Y12 inhibitor such as clopidogrel is often initiated days before elective procedures or as loading doses for emergent procedures; however, some patients may still experience thrombotic complications. Patients identified as clopidogrel hyporesponders are more likely to experience poor outcomes and may require changes to their regimens. Historically, high-dose clopidogrel regimens were used in response to subtherapeutic results of platelet function assays and point-of-care testing despite limited supporting data. Recently, more data have emerged using alternative P2Y12 inhibitors such as prasugrel and ticagrelor. Dosing for neuroendovascular conditions is often extrapolated from the cardiac literature, although outcomes in cardiac patients may not be relevant to neurologic patients, making prophylactic treatment recommendations challenging for these patients. This review summarizes the literature for antiplatelet prophylaxis in patients undergoing neuroendovascular device placement, focusing on alternative regimens for clopidogrel hyporesponders.
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http://dx.doi.org/10.1002/phar.2228DOI Listing
March 2019

Current Practices of Intraventricular Antibiotic Therapy in the Treatment of Meningitis and Ventriculitis: Results from a Multicenter Retrospective Cohort Study.

Neurocrit Care 2019 06;30(3):609-616

Departments of Neurology and Anesthesiology & Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, USA.

Background: Central nervous system (CNS) infections are particularly prevalent in the adult neurocritical care patient population and are associated with significant morbidity and mortality. Factors relevant to the nature of CNS infections pose significant challenges to clinicians treating afflicted patients. Intraventricular (IVT) administration of antibiotics may offer several benefits over systemic therapy; however, the outcomes and current practices of such treatments are poorly described in the literature.

Objective: To describe current practices and outcomes of patients receiving intraventricular antibiotic treatment for CNS infections in neurological intensive care units of academic medical centers nationwide.

Methods: A retrospective cohort study was conducted on patients admitted to intensive care units who received IVT antibiotic treatment at participating centers in the USA between January 01, 2003, and December 31, 2013. Clinical and laboratory parameters, microbiology, surgical and antimicrobial management, and treatment outcomes were collected and described.

Results: Of the 105 patients included, all received systemic antimicrobial therapy along with at least one dose of IVT antimicrobial agents. Intraventricular vancomycin was used in 52.4% of patients. The average dose was 12.2 mg/day for a median duration of 5 days. Intraventricular aminoglycosides were used in 47.5% of the patients, either alone or in combination with IVT vancomycin. The average dose of gentamicin/tobramycin was 6.7 mg/day with a median duration of 6 days. Overall mortality was 18.1%. Cerebrospinal fluid (CSF) culture sterilization occurred in 88.4% of the patients with a rate of recurrence or persistence of positive cultures of 9.5%.

Conclusion: Intraventricular antimicrobial agents resulted in a high CSF sterilization rate. Contemporary use of this route typically results in a treatment duration of less than a week. Prospective studies are needed to establish the optimal patient population, as well as the efficacy and safety of this route of administration.
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http://dx.doi.org/10.1007/s12028-018-0647-0DOI Listing
June 2019

Metabolomics and Precision Medicine in Trauma: The State of the Field.

Shock 2018 07;50(1):5-13

Department of Surgery, Division of Acute Care Surgical Services, School of Medicine, Virginia Commonwealth University, Richmond, Virginia.

Trauma is a major problem in the United States. Mortality from trauma is the number one cause of death under the age of 45 in the United States and is the third leading cause of death for all age groups. There are approximately 200,000 deaths per year due to trauma in the United States at a cost of over $671 billion in combined healthcare costs and lost productivity. Unsurprisingly, trauma accounts for approximately 30% of all life-years lost in the United States. Due to immense development of trauma systems, a large majority of trauma patients survive the injury, but then go on to die from complications arising from the injury. These complications are marked by early and significant metabolic changes accompanied by inflammatory responses that lead to progressive organ failure and, ultimately, death. Early resuscitative and surgical interventions followed by close monitoring to identify and rescue treatment failures are key to successful outcomes. Currently, the adequacy of resuscitation is measured using vital signs, noninvasive methods such as bedside echocardiography or stroke volume variation, and other laboratory endpoints of resuscitation, such as lactate and base deficit. However, these methods may be too crude to understand cellular and subcellular changes that may be occurring in trauma patients. Better diagnostic and therapeutic markers are needed to assess the adequacy of interventions and monitor responses at a cellular and subcellular level and inform clinical decision-making before complications are clinically apparent. The developing field of metabolomics holds great promise in the identification and application of biochemical markers toward the clinical decision-making process.
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http://dx.doi.org/10.1097/SHK.0000000000001093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5995639PMC
July 2018

Pharmacotherapy Pearls for Emergency Neurological Life Support.

Neurocrit Care 2017 Sep;27(Suppl 1):51-73

Department of Clinical Pharmacy, Barnes-Jewish Hospital, Washington University in St. Louis, St. Louis, MO, USA.

The appropriate use of medications during Emergency Neurological Life Support (ENLS) is essential to optimize patient care. Important considerations when choosing the appropriate agent include the patient's organ function and medication allergies, potential adverse drug effects, drug interactions and critical illness and aging pathophysiologic changes. Critical medications used during ENLS include hyperosmolar therapy, anticonvulsants, antithrombotics, anticoagulant reversal and hemostatic agents, anti-shivering agents, neuromuscular blockers, antihypertensive agents, sedatives, vasopressors and inotropes, and antimicrobials. This article focuses on the important pharmacokinetic and pharmacodynamics characteristics, advantages and disadvantages and clinical pearls of these therapies, providing practitioners with essential drug information to optimize pharmacotherapy in acutely ill neurocritical care patients.
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http://dx.doi.org/10.1007/s12028-017-0456-xDOI Listing
September 2017

Temporal Profile of Microtubule-Associated Protein 2: A Novel Indicator of Diffuse Brain Injury Severity and Early Mortality after Brain Trauma.

J Neurotrauma 2018 01 3;35(1):32-40. Epub 2017 Nov 3.

10 Department of Neurosurgery, Baylor College of Medicine , Houston, Texas.

This study compared cerebrospinal fluid (CSF) levels of microtubule-associated protein 2 (MAP-2) from adult patients with severe traumatic brain injury (TBI) with uninjured controls over 10 days, and examined the relationship between MAP-2 concentrations and acute clinical and radiologic measures of injury severity along with mortality at 2 weeks and over 6 months. This prospective study, conducted at two Level 1 trauma centers, enrolled adults with severe TBI (Glasgow Coma Scale [GCS] score ≤8) requiring a ventriculostomy, as well as controls. Ventricular CSF was sampled from each patient at 6, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 h following TBI and analyzed via enzyme-linked immunosorbent assay for MAP-2 (ng/mL). Injury severity was assessed by the GCS score, Marshall Classification on computed tomography (CT), Rotterdam CT score, and mortality. There were 151 patients enrolled-130 TBI and 21 control patients. MAP-2 was detectable within 6 h of injury and was significantly elevated compared with controls (p < 0.001) at each time-point. MAP-2 was highest within 72 h of injury and decreased gradually over 10 days. The area under the receiver operating characteristic curve for deciphering TBI versus controls at the earliest time-point CSF was obtained was 0.96 (95% CI 0.93-0.99) and for the maximal 24-h level was 0.98 (95% CI 0.97-1.00). The area under the curve for initial MAP-2 levels predicting 2-week mortality was 0.80 at 6 h, 0.81 at 12 h, 0.75 at 18 h, 0.75 at 24 h, and 0.80 at 48 h. Those with Diffuse Injury III-IV had much higher initial (p = 0.033) and maximal (p = 0.003) MAP-2 levels than those with Diffuse Injury I-II. There was a graded increase in the overall levels and peaks of MAP-2 as the degree of diffuse injury increased within the first 120 h post-injury. These data suggest that early levels of MAP-2 reflect severity of diffuse brain injury and predict 2-week mortality in TBI patients. These findings have implications for counseling families and improving clinical decision making early after injury and guiding multidisciplinary care. Further studies are needed to validate these findings in a larger sample.
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http://dx.doi.org/10.1089/neu.2017.4994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5757083PMC
January 2018

Guidelines for Family-Centered Care in Neuro-ICU Populations: Caveats for Routine Palliative Care.

Crit Care Med 2017 06;45(6):e620-e621

Departments of Neurology and Neurological Surgery, Ohio State University, Columbus, OH; Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University, Richmond, VA; Departments of Neurology and Neurosurgery, Henry Ford Hospital, Detroit, MI; Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany; Department of Neurology, Northwestern Medical Group, Chicago, IL; Nursing Center of Excellence, Mission Hospital, Mission Viejo, CA; Section of Vascular Neurology and Neurocritical Care, Baylor College of Medicine, Houston, TX; Neurocritical Care Division, Department of Neurosurgery, Maine Medical Center, Portland, ME; Mayo Clinic, Jacksonville, FL.

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http://dx.doi.org/10.1097/CCM.0000000000002344DOI Listing
June 2017

Development of the Critical Care Pharmacotherapy Trials Network.

Am J Health Syst Pharm 2017 03;74(5):287-293

Rush University Medical Center, Chicago, IL.

Purpose: The development of the Critical Care Pharmacotherapy Trials Network (CCPTN) as a model for practice-based pharmacotherapy research is described.

Summary: The CCPTN was formed in 2010 as a collaborative research network dedicated to scientific investigation in the field of critical care pharmacotherapy. The CCPTN organizational structure is consistent with many professional pharmacy and interdisciplinary organizations and organized into 3 primary domains: executive committee, working committees, and network membership. The network membership consists of critical care investigators dedicated to the mission and vision of the CCPTN and is open to anyone expressing an interest in contributing to high-level research. Network member sites represent the breadth of U.S. critical care practice environments. In addition, network members include individuals with demonstrated expertise in patient safety, administration, research design, grantsmanship, database management, peer review, and scientific writing. In 2015, there were more than 100 site investigators from around the United States and Canada. Projects to date have yielded numerous abstracts, platform presentations, and peer-reviewed publications in high-impact journals. The CCPTN has expanded to form collaborations with researchers in the United Kingdom, Australia, and New Zealand. The CCPTN has identified new potential partnerships and field-based areas for inquiry. Numerous opportunities for continued growth and scientific inquiry in the field of critical care pharmacotherapy research exist for the CCPTN to foster in the coming years.

Conclusion: The CCPTN has been a successful model for practice-based pharmacotherapy research and assists its members in expanding critical care pharmacotherapy knowledge.
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http://dx.doi.org/10.2146/ajhp160028DOI Listing
March 2017

Clevidipine Versus Nicardipine for Acute Blood Pressure Reduction in a Neuroscience Intensive Care Population.

Neurocrit Care 2017 04;26(2):167-173

Department of Pharmacotherapy & Outcomes Science and Neurosurgery, Virginia Commonwealth University, Richmond, VA, USA.

Background: Currently, a lack of published literature exists regarding the use of clevidipine in the neuroscience population. This agent may be preferred in some patients because of its short half-life, potentially leading to more narrow blood pressure (BP) control in comparison with other agents. The purpose of this study was to compare the difference in time to achieve target systolic blood pressure (SBP) goals with clevidipine versus nicardipine infusions in patients admitted to the neuroscience intensive care unit (NSICU) at our institution.

Methods: A retrospective review was performed on patients receiving clevidipine or nicardipine infusions while in the NSICU between July 1, 2011 and June 30, 2014. Patients were matched based on indication for BP lowering and target SBP. Primary endpoints included time to target SBP and percentage of time within target BP range.

Results: Of the 57 patients included in the study, the median time to target SBP was 30 min in the clevidipine group and 46 min in the nicardipine group (p = 0.13). The percentage of time spent within target BP range was 79 versus 78% (p = 0.64). Clevidipine administration resulted in significantly less volume administered per patient versus nicardipine (530 vs. 1254 mL, p = 0.02).

Conclusions: There were no statistically significant differences in acute BP management between the two agents; however, there was a trend toward shorter time to target and significantly less volume administered in the clevidipine group. Either agent should be considered a viable option in a NSICU population.
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http://dx.doi.org/10.1007/s12028-016-0349-4DOI Listing
April 2017

Temperature Management in Neurological and Neurosurgical Intensive Care Unit.

Ther Hypothermia Temp Manag 2016 Dec 9;6(4):164-168. Epub 2016 Nov 9.

4 Wellstar Health System, Kennestone Hospital , Marietta, Georgia .

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http://dx.doi.org/10.1089/ther.2016.29020.pjlDOI Listing
December 2016

Clinical Q & A: Translating Therapeutic Temperature Management from Theory to Practice.

Ther Hypothermia Temp Manag 2016 Dec 3;6(4):218-222. Epub 2016 Nov 3.

1 Mission Hospital , Mission Viejo, California.

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http://dx.doi.org/10.1089/ther.2016.29018.mkbDOI Listing
December 2016

What's new in refractory status epilepticus?

Intensive Care Med 2017 04 20;43(4):543-546. Epub 2016 Aug 20.

Virginia Commonwealth University, Medical College of Virginia Campus, 410 N. 12th Street, Richmond, VA, 23298-0533, USA.

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http://dx.doi.org/10.1007/s00134-016-4501-6DOI Listing
April 2017

Clinical Q & A: Translating Therapeutic Temperature Management from Theory to Practice.

Ther Hypothermia Temp Manag 2016 Aug 9;6(3):146-9. Epub 2016 Aug 9.

5 Harborview Medical Center , Seattle, Washington.

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http://dx.doi.org/10.1089/ther.2016.29016.mkbDOI Listing
August 2016

Intravenous Versus Oral Acetaminophen for Pain Control in Neurocritical Care Patients.

Neurocrit Care 2016 12;25(3):400-406

Virginia Commonwealth University School of Pharmacy, Richmond, VA, USA.

Background: Acetaminophen (APAP) is used in neurocritical care (NCC) patients for analgesia without sedation or antiplatelet activity. Research suggests that intravenous (IV) APAP produces earlier and higher serum levels compared to oral (PO) APAP. This retrospective study evaluates the associated analgesic effects of IV and PO APAP and use of adjunctive opioids in NCC patients with moderate-severe pain.

Methods: Patients admitted to the neuroscience intensive care unit (NSICU) between May 2012 and April 2013 who received ≥1 dose of IV APAP were included in the study. IV and PO APAP doses administered with a predose pain score ≥4 within 1 h of dosing were compared. Pain intensity difference (PID) was calculated as the change between the pain score prior to each dose and scores at 30 min, 1, 2, 3, and 6 h postdose. Pre- and postdose morphine milligram equivalents (MME) were also calculated.

Results: 309 NSICU patients received 459 doses of IV and 440 doses of PO APAP meeting our inclusion criteria. The PID at 30 min postdosing was significantly higher among those receiving IV APAP compared to those receiving PO APAP (p = 0.003). No significant difference in PID was seen at 1, 2, 3, and 6 h; and there was no significant difference in pre- or postdose MME between the two groups.

Conclusion: IV APAP was more effective than PO APAP at relieving pain within 30 min of dosing, but this difference was not sustained over 6 h. Further studies are needed to assess the benefits of this rapid onset of action.
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http://dx.doi.org/10.1007/s12028-016-0289-zDOI Listing
December 2016

Managing Status Epilepticus in the Older Adult.

J Clin Med 2016 May 11;5(5). Epub 2016 May 11.

Virginia Commonwealth University, Medical College of Virginia Campus, 410 N. 12th Street, Richmond, VA 23298-0533, USA.

The aim of this systematic review was to describe particularities in epidemiology, outcome, and management modalities in the older adult population with status epilepticus. There is a higher incidence of status epilepticus in the older adult population, and it commonly has a nonconvulsive presentation. Diagnosis in this population may be difficult and requires an unrestricted use of EEG. Short and long term associated-mortality are high, and age over 60 years is an independent factor associated with poor outcome. Stroke (acute or remote symptomatic), miscellaneous metabolic causes, dementia, infections hypoxemia, and brain injury are among the main causes of status epilepticus occurrence in this age category. The use of anticonvulsive agents can be problematic as well. Thus, it is important to take into account the specific aspects related to the pharmacokinetic and pharmacodynamic changes in older critically-ill adults. Beyond these precautions, the management may be identical to that of the younger adult, including prompt initiation of symptomatic and anticonvulsant therapies, and a broad and thorough etiological investigation. Such management strategies may improve the vital and functional prognosis of these patients, while maintaining a high overall quality of care.
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http://dx.doi.org/10.3390/jcm5050053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4882482PMC
May 2016

Time Course and Diagnostic Accuracy of Glial and Neuronal Blood Biomarkers GFAP and UCH-L1 in a Large Cohort of Trauma Patients With and Without Mild Traumatic Brain Injury.

JAMA Neurol 2016 05;73(5):551-60

Brain Health, Harpers Ferry, West Virginia.

Importance: Glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) have been widely studied and show promise for clinical usefulness in suspected traumatic brain injury (TBI) and concussion. Understanding their diagnostic accuracy over time will help translate them into clinical practice.

Objectives: To evaluate the temporal profiles of GFAP and UCH-L1 in a large cohort of trauma patients seen at the emergency department and to assess their diagnostic accuracy over time, both individually and in combination, for detecting mild to moderate TBI (MMTBI), traumatic intracranial lesions on head computed tomography (CT), and neurosurgical intervention.

Design, Setting, And Participants: This prospective cohort study enrolled adult trauma patients seen at a level I trauma center from March 1, 2010, to March 5, 2014. All patients underwent rigorous screening to determine whether they had experienced an MMTBI (blunt head trauma with loss of consciousness, amnesia, or disorientation and a Glasgow Coma Scale score of 9-15). Of 3025 trauma patients assessed, 1030 met eligibility criteria for enrollment, and 446 declined participation. Initial blood samples were obtained in 584 patients enrolled within 4 hours of injury. Repeated blood sampling was conducted at 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180 hours after injury.

Main Outcomes And Measures: Diagnosis of MMTBI, presence of traumatic intracranial lesions on head CT scan, and neurosurgical intervention.

Results: A total of 1831 blood samples were drawn from 584 patients (mean [SD] age, 40 [16] years; 62.0% [362 of 584] male) over 7 days. Both GFAP and UCH-L1 were detectible within 1 hour of injury. GFAP peaked at 20 hours after injury and slowly declined over 72 hours. UCH-L1 rose rapidly and peaked at 8 hours after injury and declined rapidly over 48 hours. Over the course of 1 week, GFAP demonstrated a diagnostic range of areas under the curve for detecting MMTBI of 0.73 (95% CI, 0.69-0.77) to 0.94 (95% CI, 0.78-1.00), and UCH-L1 demonstrated a diagnostic range of 0.30 (95% CI, 0.02-0.50) to 0.67 (95% CI, 0.53-0.81). For detecting intracranial lesions on CT, the diagnostic ranges of areas under the curve were 0.80 (95% CI, 0.67-0.92) to 0.97 (95% CI, 0.93-1.00)for GFAP and 0.31 (95% CI, 0-0.63) to 0.77 (95% CI, 0.68-0.85) for UCH-L1. For distinguishing patients with and without a neurosurgical intervention, the range for GFAP was 0.91 (95% CI, 0.79-1.00) to 1.00 (95% CI, 1.00-1.00), and the range for UCH-L1 was 0.50 (95% CI, 0-1.00) to 0.92 (95% CI, 0.83-1.00).

Conclusions And Relevance: GFAP performed consistently in detecting MMTBI, CT lesions, and neurosurgical intervention across 7 days. UCH-L1 performed best in the early postinjury period.
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http://dx.doi.org/10.1001/jamaneurol.2016.0039DOI Listing
May 2016

Medical management of epileptic seizures: challenges and solutions.

Neuropsychiatr Dis Treat 2016 24;12:467-85. Epub 2016 Feb 24.

Departments of Pharmacotherapy & Outcomes Science and Neurosurgery, Virginia Commonwealth University, Richmond, VA, USA.

Epilepsy is one of the most common neurologic illnesses. This condition afflicts 2.9 million adults and children in the US, leading to an economic impact amounting to $15.5 billion. Despite the significant burden epilepsy places on the population, it is not very well understood. As this understanding continues to evolve, it is important for clinicians to stay up to date with the latest advances to provide the best care for patients. In the last 20 years, the US Food and Drug Administration has approved 15 new antiepileptic drugs (AEDs), with many more currently in development. Other advances have been achieved in terms of diagnostic modalities like electroencephalography technology, treatment devices like vagal nerve and deep-brain stimulators, novel alternate routes of drug administration, and improvement in surgical techniques. Specific patient populations, such as the pregnant, elderly, those with HIV/AIDS, and those with psychiatric illness, present their own unique challenges, with AED side effects, drug interactions, and medical-psychiatric comorbidities adding to the conundrum. The purpose of this article is to review the latest literature guiding the management of acute epileptic seizures, focusing on the current challenges across different practice settings, and it discusses studies in various patient populations, including the pregnant, geriatric, those with HIV/AIDS, comatose, psychiatric, and "pseudoseizure" patients, and offers possible evidence-based solutions or the expert opinion of the authors. Also included is information on newer AEDs, routes of administration, and significant AED-related drug-interaction tables. This review has tried to address only some of these issues that any practitioner who deals with the acute management of seizures may encounter. The document also highlights the numerous avenues for new research that would help practitioners optimize epilepsy management.
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http://dx.doi.org/10.2147/NDT.S80586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4771397PMC
March 2016

Emergency Neurological Life Support: Pharmacotherapy.

Neurocrit Care 2015 Dec;23 Suppl 2:S48-68

Departments of Critical Care Medicine, Neurology & Neurosurgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

The appropriate use of medications during Emergency Neurological Life Support (ENLS) is essential to optimize patient care. Important considerations when choosing the appropriate agent include the patient's organ function and medication allergies, potential adverse drug effects, drug interactions, and critical illness and aging pathophysiologic changes. Critical medications used during ENLS include hyperosmolar therapy, anticonvulsants, antithrombotics, anticoagulant reversal and hemostatic agents, anti-shivering agents, neuromuscular blockers, antihypertensive agents, sedatives, vasopressors and inotropes, and antimicrobials. This article focuses on the important pharmacokinetic and pharmacodynamics characteristics, advantages and disadvantages, and clinical pearls of these therapies, providing practitioners with essential drug information to optimize pharmacotherapy in acutely ill neurocritical care patients.
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http://dx.doi.org/10.1007/s12028-015-0158-1DOI Listing
December 2015

Treatment of Super-Refractory Status Epilepticus.

Curr Neurol Neurosci Rep 2015 Oct;15(10):66

Department of Neurology, Virginia Commonwealth University, P.O. Box 980599, Richmond, VA, 23298, USA,

Super-refractory status epilepticus (SRSE) is a devastating neurological condition with limited treatment options. We conducted an extensive literature search to identify and summarize the therapeutic options for SRSE. The search mainly resulted in case reports of various pharmacologic and non-pharmacologic treatments. The success rate of each of the following agents, ketamine, inhaled anesthetics, intravenous immunoglobulin G (IVIG), IV steroids, ketogenic diet, hypothermia, electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), and vagal nerve stimulation (VNS), are discussed in greater detail. The choice of appropriate treatment options for a given patient is based on clinical presentation. This review focuses on evidence-based, pharmacotherapeutic strategies for patients in SRSE.
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http://dx.doi.org/10.1007/s11910-015-0589-2DOI Listing
October 2015