Publications by authors named "Neeraj Badjatia"

169 Publications

Relationship Between Nutrition Intake and Outcome After Subarachnoid Hemorrhage: Results From the International Nutritional Survey.

J Intensive Care Med 2021 Oct;36(10):1141-1148

Clinical Evaluation Research Unit, Kingston General Hospital, Kingston, ON, USA.

Background: A previous study suggested an association between low caloric intake(CI), negative nitrogen balance, and poor outcome after subarachnoid hemorrhage(SAH). Objective of this multinational, multicenter study was to investigate whether clinical outcomes vary by protein intake(PI) or CI in SAH patients adjusting for the nutritional risk as judged by the modified NUTrition Risk in the Critically Ill (mNUTRIC) score.

Methods: The International Nutrition Survey(INS) 2007-2014 was utilized to describe the characteristics, outcomes and nutrition use. A subgroup of patients from 2013 and 2014(when NUTRIC score was captured) examined the association between CI and PI and time to discharge alive(TTDA) from hospital using Cox regression models, adjusting for nutrition risk classified by the mNUTRIC score as low(0-4) or high(5-9).

Results: There were 489 SAH patients(57% female with a mean ± SD age 57.5 ± 13.9 years, BMI of 25.9 ± 5.3 kg/m and APACHE-2 score 19.4 ± 7.0. Majority(85%) received enteral nutrition(EN) only, with a time to initiation of EN of 35.4 ± 35.2 hours. 64% had EN interrupted. Patients received a CI of 14.6 ± 7.1 calories/kg/day and PI 0.7 ± 0.3 grams/kg/day corresponding to 59% and 55% of total prescribed CI and PI respectively. In the 2013 and 2014 subgroup there were 226 SAH patients with a mNUTRIC score of 3.4 ± 1.8. Increased CI and PI were associated with faster TTDA among high mNUTRIC patients(HR per 20% of prescription received = 1.34[95% CI,1.03 -1.76] for CI and 1.44[1.07 -1.93] for PI), but not low mNUTRIC patients(CI: HR = 0.95[0.77 -1.16] PI:0.95[0.78 -1.16]).

Conclusions: Results from this multicenter study found that SAH patients received under 60% of their prescribed CI and PI. Further, achieving greater CI and PI in hi risk SAH patients was associated with improved TTDA. mNUTRIC serves to identify SAH patients that benefit most from artificial nutrition and efforts to optimize protein and caloric delivery in this subpopulation should be maximized.
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http://dx.doi.org/10.1177/0885066620966957DOI Listing
October 2021

Verticalization for Refractory Intracranial Hypertension: A Case Series.

Neurocrit Care 2021 Aug 17. Epub 2021 Aug 17.

Program in Trauma, Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.

Background: Severe intracranial hypertension is strongly associated with mortality. Guidelines recommend medical management involving sedation, hyperosmotic agents, barbiturates, hypothermia, and surgical intervention. When these interventions are maximized or are contraindicated, refractory intracranial hypertension poses risk for herniation and death. We describe a novel intervention of verticalization for treating intracranial hypertension refractory to aggressive medical treatment.

Methods: This study was a single-center retrospective review of six cases of refractory intracranial hypertension in a tertiary care center. All patients were treated with a standard-of-care algorithm for lowering intracranial pressure (ICP) yet maintained an ICP greater than 20 mmHg. They were then treated with verticalization for at least 24 h. We compared the median ICP, the number of ICP spikes greater than 20 mmHg, and the percentage of ICP values greater than 20 mmHg in the 24 h before verticalization vs. after verticalization. We assessed the use of hyperosmotic therapies and any changes in the mean arterial pressure and cerebral perfusion pressure related with the intervention.

Results: Five patients were admitted with subarachnoid hemorrhage and one with intracerebral hemorrhage. All patients had ICP monitoring by external ventricular drain. The median opening pressure was 30 mmHg (25th-75th interquartile range 22.5-30 mmHg). All patients demonstrated a reduction in ICP after verticalization, with a significant decrease in the median ICP (12 vs. 8 mmHg; p < 0.001), the number of ICP spikes (12 vs. 2; p < 0.01), and the percentage of ICP values greater than 20 mmHg (50% vs. 8.3%; p < 0.01). There was a decrease in total medical interventions after verticalization (79 vs. 41; p = 0.05) and a lower total therapy intensity level score after verticalization. The most common adverse effects included asymptomatic bradycardia (n = 3) and pressure wounds (n = 4).

Conclusions: Verticalization is an effective noninvasive intervention for lowering ICP in intracranial hypertension that is refractory to aggressive standard management and warrants further study.
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http://dx.doi.org/10.1007/s12028-021-01323-zDOI Listing
August 2021

Dynamic Intracranial Pressure Waveform Morphology Predicts Ventriculitis.

Neurocrit Care 2021 Jul 30. Epub 2021 Jul 30.

Department of Neurology, Columbia University Vagelos College of Physicians and Surgeons, 177 Fort Washington Ave, 8 Milstein - 300 Center, New York, NY, USA.

Background: Intracranial pressure waveform morphology reflects compliance, which can be decreased by ventriculitis. We investigated whether morphologic analysis of intracranial pressure dynamics predicts the onset of ventriculitis.

Methods: Ventriculitis was defined as culture or Gram stain positive cerebrospinal fluid, warranting treatment. We developed a pipeline to automatically isolate segments of intracranial pressure waveforms from extraventricular catheters, extract dominant pulses, and obtain morphologically similar groupings. We used a previously validated clinician-supervised active learning paradigm to identify metaclusters of triphasic, single-peak, or artifactual peaks. Metacluster distributions were concatenated with temperature and routine blood laboratory values to create feature vectors. A L2-regularized logistic regression classifier was trained to distinguish patients with ventriculitis from matched controls, and the discriminative performance using area under receiver operating characteristic curve with bootstrapping cross-validation was reported.

Results: Fifty-eight patients were included for analysis. Twenty-seven patients with ventriculitis from two centers were identified. Thirty-one patients with catheters but without ventriculitis were selected as matched controls based on age, sex, and primary diagnosis. There were 1590 h of segmented data, including 396,130 dominant pulses in patients with ventriculitis and 557,435 pulses in patients without ventriculitis. There were significant differences in metacluster distribution comparing before culture-positivity versus during culture-positivity (p < 0.001) and after culture-positivity (p < 0.001). The classifier demonstrated good discrimination with median area under receiver operating characteristic 0.70 (interquartile range 0.55-0.80). There were 1.5 true alerts (ventriculitis detected) for every false alert.

Conclusions: Intracranial pressure waveform morphology analysis can classify ventriculitis without cerebrospinal fluid sampling.
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http://dx.doi.org/10.1007/s12028-021-01303-3DOI Listing
July 2021

Repetitive Traumatic Brain Injury Among Older Adults.

J Head Trauma Rehabil 2021 Jul 26. Epub 2021 Jul 26.

Departments of Epidemiology and Public Health (Drs Chauhan, Guralnik, and Albrecht) and Neurology (Dr Badjatia), University of Maryland School of Medicine, Baltimore; Department of Pharmaceutical Health Services Research, University of Maryland School of Pharmacy, Baltimore (Dr dosReis); Baltimore VA Geriatric Research, Education and Clinical Center (Dr Sorkin); and Department of Medicine, Division of Gerontology and Geriatrics, University of Maryland School of Medicine, Baltimore (Dr Sorkin).

Objective: To determine the incidence of and assess risk factors for repetitive traumatic brain injury (TBI) among older adults in the United States.

Design: Retrospective cohort study.

Setting: Administrative claims data obtained from the Centers for Medicare & Medicaid Services' Chronic Conditions Data Warehouse.

Participants: Individuals 65 years or older and diagnosed with TBI between July 2008 and September 2012 drawn from a 5% random sample of US Medicare beneficiaries.

Main Measures: Repetitive TBI was identified as a second TBI occurring at least 90 days after the first occurrence of TBI following an 18-month TBI-free period. We identified factors associated with repetitive TBI using a log-binomial model.

Results: A total of 38 064 older Medicare beneficiaries experienced a TBI. Of these, 4562 (12%) beneficiaries sustained at least one subsequent TBI over up to 5 years of follow-up. The unadjusted incidence rate of repetitive TBI was 3022 (95% CI, 2935-3111) per 100 000 person-years. Epilepsy was the strongest predictor of repetitive TBI (relative risk [RR] = 1.44; 95% CI, 1.25-1.56), followed by Alzheimer disease and related dementias (RR = 1.32; 95% CI 1.20-1.45), and depression (RR = 1.30; 95% CI, 1.21-1.38).

Conclusions: Injury prevention and fall-reduction interventions could be targeted to identify groups of older adults at an increased risk of repetitive head injury. Future work should focus on injury-reduction initiatives to reduce the risk of repetitive TBI as well as assessment of outcomes related to repetitive TBI.
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http://dx.doi.org/10.1097/HTR.0000000000000719DOI Listing
July 2021

Pathological Computed Tomography Features Associated With Adverse Outcomes After Mild Traumatic Brain Injury: A TRACK-TBI Study With External Validation in CENTER-TBI.

JAMA Neurol 2021 Sep;78(9):1137-1148

University of Washington, Seattle.

Importance: A head computed tomography (CT) with positive results for acute intracranial hemorrhage is the gold-standard diagnostic biomarker for acute traumatic brain injury (TBI). In moderate to severe TBI (Glasgow Coma Scale [GCS] scores 3-12), some CT features have been shown to be associated with outcomes. In mild TBI (mTBI; GCS scores 13-15), distribution and co-occurrence of pathological CT features and their prognostic importance are not well understood.

Objective: To identify pathological CT features associated with adverse outcomes after mTBI.

Design, Setting, And Participants: The longitudinal, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study enrolled patients with TBI, including those 17 years and older with GCS scores of 13 to 15 who presented to emergency departments at 18 US level 1 trauma centers between February 26, 2014, and August 8, 2018, and underwent head CT imaging within 24 hours of TBI. Evaluations of CT imaging used TBI Common Data Elements. Glasgow Outcome Scale-Extended (GOSE) scores were assessed at 2 weeks and 3, 6, and 12 months postinjury. External validation of results was performed via the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Data analyses were completed from February 2020 to February 2021.

Exposures: Acute nonpenetrating head trauma.

Main Outcomes And Measures: Frequency, co-occurrence, and clustering of CT features; incomplete recovery (GOSE scores <8 vs 8); and an unfavorable outcome (GOSE scores <5 vs ≥5) at 2 weeks and 3, 6, and 12 months.

Results: In 1935 patients with mTBI (mean [SD] age, 41.5 [17.6] years; 1286 men [66.5%]) in the TRACK-TBI cohort and 2594 patients with mTBI (mean [SD] age, 51.8 [20.3] years; 1658 men [63.9%]) in an external validation cohort, hierarchical cluster analysis identified 3 major clusters of CT features: contusion, subarachnoid hemorrhage, and/or subdural hematoma; intraventricular and/or petechial hemorrhage; and epidural hematoma. Contusion, subarachnoid hemorrhage, and/or subdural hematoma features were associated with incomplete recovery (odds ratios [ORs] for GOSE scores <8 at 1 year: TRACK-TBI, 1.80 [95% CI, 1.39-2.33]; CENTER-TBI, 2.73 [95% CI, 2.18-3.41]) and greater degrees of unfavorable outcomes (ORs for GOSE scores <5 at 1 year: TRACK-TBI, 3.23 [95% CI, 1.59-6.58]; CENTER-TBI, 1.68 [95% CI, 1.13-2.49]) out to 12 months after injury, but epidural hematoma was not. Intraventricular and/or petechial hemorrhage was associated with greater degrees of unfavorable outcomes up to 12 months after injury (eg, OR for GOSE scores <5 at 1 year in TRACK-TBI: 3.47 [95% CI, 1.66-7.26]). Some CT features were more strongly associated with outcomes than previously validated variables (eg, ORs for GOSE scores <5 at 1 year in TRACK-TBI: neuropsychiatric history, 1.43 [95% CI .98-2.10] vs contusion, subarachnoid hemorrhage, and/or subdural hematoma, 3.23 [95% CI 1.59-6.58]). Findings were externally validated in 2594 patients with mTBI enrolled in the CENTER-TBI study.

Conclusions And Relevance: In this study, pathological CT features carried different prognostic implications after mTBI to 1 year postinjury. Some patterns of injury were associated with worse outcomes than others. These results support that patients with mTBI and these CT features need TBI-specific education and systematic follow-up.
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http://dx.doi.org/10.1001/jamaneurol.2021.2120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290344PMC
September 2021

Regionalization of Critical Care in the United States: Current State and Proposed Framework From the Academic Leaders in Critical Care Medicine Task Force of the Society of the Critical Care Medicine.

Crit Care Med 2021 Jul 1. Epub 2021 Jul 1.

1 Office of the Medical Director, Montefiore Health System, Albert Einstein College of Medicine, Bronx, NY. 2 Department of Anesthesiology and Critical Care Medicine, Memorial Sloan Kettering Cancer Center, New York, NY. 3 Division of Critical Care Medicine, Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY. 4 Departments of Medicine, Anesthesiology and Surgery, University of Massachusetts Medical School, Worchester, MA. 5 Department of Anesthesiology, University of Maryland, Maryland Critical Care Network, Baltimore, MD. 6 Department of Neurology, University of Maryland, Maryland Critical Care Network, Baltimore, MD. 7 Department of Pharmacy, Indiana University Medical Center, Indianapolis, IN. 8 Department of Surgery, University of Maryland, Maryland Critical Care Network, Baltimore, MD. 9 Department of Finance, Montefiore Health System, Bronx, NY.

Objectives: The Society of Critical Care Medicine convened its Academic Leaders in Critical Care Medicine taskforce on February 22, 2016, during the 45th Critical Care Congress to develop a series of consensus papers with toolkits for advancing critical care organizations in North America. The goal of this article is to propose a framework based on the expert opinions of critical care organization leaders and their responses to a survey, for current and future critical care organizations, and their leadership in the health system to design and implement successful regionalization for critical care in their regions.

Data Sources And Study Selection: Members of the workgroup convened monthly via teleconference with the following objectives: to 1) develop and analyze a regionalization survey tool for 23 identified critical care organizations in the United States, 2) assemble relevant medical literature accessed using Medline search, 3) use a consensus of expert opinions to propose the framework, and 4) create groups to write the subsections and assemble the final product.

Data Extraction And Synthesis: The most prevalent challenges for regionalization in critical care organizations remain a lack of a strong central authority to regulate and manage the system as well as a lack of necessary infrastructure, as described more than a decade ago. We provide a framework and outline a nontechnical approach that the health system and their critical care medicine leadership can adopt after considering their own structure, complexity, business operations, culture, and the relationships among their individual hospitals. Transforming the current state of regionalization into a coordinated, accountable system requires a critical assessment of administrative and clinical challenges and barriers. Systems thinking, business planning and control, and essential infrastructure development are critical for assisting critical care organizations.

Conclusions: Under the value-based paradigm, the goals are operational efficiency and patient outcomes. Health systems that can align strategy and operations to assist the referral hospitals with implementing regionalization will be better positioned to regionalize critical care effectively.
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http://dx.doi.org/10.1097/CCM.0000000000005147DOI Listing
July 2021

Admission Features Associated With Paroxysmal Sympathetic Hyperactivity After Traumatic Brain Injury: A Case-Control Study.

Crit Care Med 2021 Apr 26. Epub 2021 Apr 26.

1 R. Adams Cowley Shock Trauma Center, Baltimore, MD. 2 University of Maryland Medical Center, Baltimore, MD. 3 University of Maryland School of Medicine, Baltimore, MD. 4 Hartford Hospital, University of Connecticut School of Medicine, Hartford, CT.

Objectives: Paroxysmal sympathetic hyperactivity occurs in a subset of critically ill traumatic brain injury patients and has been associated with worse outcomes after traumatic brain injury. The goal of this study was to identify admission risk factors for the development of paroxysmal sympathetic hyperactivity in traumatic brain injury patients.

Design: Retrospective case-control study of age- and Glasgow Coma Scale-matched traumatic brain injury patients.

Setting: Neurotrauma ICU at the R. Adams Cowley Shock Trauma Center of the University of Maryland Medical System, January 2016 to July 2018.

Patients: Critically ill adult traumatic brain injury patients who underwent inpatient monitoring for at least 14 days were included. Cases were identified based on treatment for paroxysmal sympathetic hyperactivity with institutional first-line therapies and were confirmed by retrospective tabulation of established paroxysmal sympathetic hyperactivity diagnostic and severity criteria. Cases were matched 1:1 by age and Glasgow Coma Scale to nonparoxysmal sympathetic hyperactivity traumatic brain injury controls, yielding 77 patients in each group.

Interventions: None.

Measurements And Main Results: Admission characteristics independently predictive of paroxysmal sympathetic hyperactivity included male sex, higher admission systolic blood pressure, and initial CT evidence of diffuse axonal injury, intraventricular hemorrhage/subarachnoid hemorrhage, complete cisternal effacement, and absence of contusion. Paroxysmal sympathetic hyperactivity cases demonstrated significantly worse neurologic outcomes upon hospital discharge despite being matched for injury severity at admission.

Conclusions: Several anatomical, epidemiologic, and physiologic risk factors for clinically relevant paroxysmal sympathetic hyperactivity can be identified on ICU admission. These features help characterize paroxysmal sympathetic hyperactivity as a clinical-pathophysiologic phenotype associated with worse outcomes after traumatic brain injury.
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http://dx.doi.org/10.1097/CCM.0000000000005076DOI Listing
April 2021

Functional Outcomes Over the First Year After Moderate to Severe Traumatic Brain Injury in the Prospective, Longitudinal TRACK-TBI Study.

JAMA Neurol 2021 Aug;78(8):982-992

University of Cincinnati, Cincinnati, Ohio.

Importance: Moderate to severe traumatic brain injury (msTBI) is a major cause of death and disability in the US and worldwide. Few studies have enabled prospective, longitudinal outcome data collection from the acute to chronic phases of recovery after msTBI.

Objective: To prospectively assess outcomes in major areas of life function at 2 weeks and 3, 6, and 12 months after msTBI.

Design, Setting, And Participants: This cohort study, as part of the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study, was conducted at 18 level 1 trauma centers in the US from February 2014 to August 2018 and prospectively assessed longitudinal outcomes, with follow-up to 12 months postinjury. Participants were patients with msTBI (Glasgow Coma Scale scores 3-12) extracted from a larger group of patients with mild, moderate, or severe TBI who were enrolled in TRACK-TBI. Data analysis took place from October 2019 to April 2021.

Exposures: Moderate or severe TBI.

Main Outcomes And Measures: The Glasgow Outcome Scale-Extended (GOSE) and Disability Rating Scale (DRS) were used to assess global functional status 2 weeks and 3, 6, and 12 months postinjury. Scores on the GOSE were dichotomized to determine favorable (scores 4-8) vs unfavorable (scores 1-3) outcomes. Neurocognitive testing and patient reported outcomes at 12 months postinjury were analyzed.

Results: A total of 484 eligible patients were included from the 2679 individuals in the TRACK-TBI study. Participants with severe TBI (n = 362; 283 men [78.2%]; median [interquartile range] age, 35.5 [25-53] years) and moderate TBI (n = 122; 98 men [80.3%]; median [interquartile range] age, 38 [25-53] years) were comparable on demographic and premorbid variables. At 2 weeks postinjury, 36 of 290 participants with severe TBI (12.4%) and 38 of 93 participants with moderate TBI (41%) had favorable outcomes (GOSE scores 4-8); 301 of 322 in the severe TBI group (93.5%) and 81 of 103 in the moderate TBI group (78.6%) had moderate disability or worse on the DRS (total score ≥4). By 12 months postinjury, 142 of 271 with severe TBI (52.4%) and 54 of 72 with moderate TBI (75%) achieved favorable outcomes. Nearly 1 in 5 participants with severe TBI (52 of 270 [19.3%]) and 1 in 3 with moderate TBI (23 of 71 [32%]) reported no disability (DRS score 0) at 12 months. Among participants in a vegetative state at 2 weeks, 62 of 79 (78%) regained consciousness and 14 of 56 with available data (25%) regained orientation by 12 months.

Conclusions And Relevance: In this study, patients with msTBI frequently demonstrated major functional gains, including recovery of independence, between 2 weeks and 12 months postinjury. Severe impairment in the short term did not portend poor outcomes in a substantial minority of patients with msTBI. When discussing prognosis during the first 2 weeks after injury, clinicians should be particularly cautious about making early, definitive prognostic statements suggesting poor outcomes and withdrawal of life-sustaining treatment in patients with msTBI.
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http://dx.doi.org/10.1001/jamaneurol.2021.2043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261688PMC
August 2021

Development of a Resting Energy Expenditure Estimation in Patients Undergoing Targeted Temperature Management with a Surface Gel Pad Temperature Modulating Device.

Ther Hypothermia Temp Manag 2021 Jun 29. Epub 2021 Jun 29.

Program in Trauma, Department of Neurology, University of Maryland School of Medicine, Baltimore, Maryland, USA.

Targeted temperature management (TTM) directly impacts energy expenditure via temperature modulation and shivering associated with temperature modulating devices. We hypothesized that resting energy expenditure (REE) can be accurately estimated utilizing data obtained from a surface gel pad temperature modulating device (TMD) and demographic factors. Baseline demographic data, along with concurrent temperature, sedation, and shivering data, and indirect calorimetry (IDC) were collected from patients undergoing TTM. The data from the IDC and temperature modulation device (TMD) were synchronized and averaged over 60-second intervals to provide simultaneous comparisons. Heat transfer (calories) was calculated from the TMD by an equation that assessed water temperature from the TMD to the patient, water temperature returning to the TMD, water flow rates, and device mode. A linear regression model was used to determine factors associated with REE as measured by IDC. A difference in the mean between REE and estimated REE was used to assess accuracy. There were 48 assessments conducted in 40 subjects [mean (standard deviation)] age: 58 (14) years, 60% female, body surface area (BSA): 2.0 ± 0.3 who underwent simultaneous assessments. Target temperature was 36-37°C in 75%, with a median Bedside Shivering Assessment Score of 0 (range 0-2). Factors associated with REE on multivariable linear regression included older age ( < 0.001), male sex ( = 0.004), higher BSA ( < 0.001), higher patient temperature ( < 0.001), and lower heat transfer ( = 0.003). Adjusted prediction coefficients from this model were then tested against REE by a Bland-Altman analysis. The difference between difference in resting energy estimation (REEdiff) and measured REE by IDC was 6.2 calories/min (REEdiff: 95% confidence interval: -14.1 calories, 26.5 calories,  = 0.5). We believe that the heat transfer data from the TMD coupled with clinical characteristics of patients can be utilized to calculate the REE for every minute of TTM. These data can be utilized to mitigate the consequences of shivering and malnutrition during TTM.
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http://dx.doi.org/10.1089/ther.2021.0005DOI Listing
June 2021

Pain Trajectories Following Subarachnoid Hemorrhage are Associated with Continued Opioid Use at Outpatient Follow-up.

Neurocrit Care 2021 Jun 9. Epub 2021 Jun 9.

Department of Neurology, School of Medicine, University of Maryland, Baltimore, MD, USA.

Background: Subarachnoid hemorrhage (SAH) is characterized by the worst headache of life and associated with long-term opioid use. Discrete pain trajectories predict chronic opioid use following other etiologies of acute pain, but it is unknown whether they exist following SAH. If discrete pain trajectories following SAH exist, it is uncertain whether they predict long-term opioid use. We sought to characterize pain trajectories after SAH and determine whether they are associated with persistent opioid use.

Methods: We reviewed pain scores from patients admitted to a single tertiary care center for SAH from November 2015 to September 2019. Group-based trajectory modeling identified discrete pain trajectories during hospitalization. We compared outcomes across trajectory groups using χ and Kruskal-Wallis tests. Multivariable regression determined whether trajectory group membership was an independent predictor of long-term opioid use, defined as continued use at outpatient follow-up.

Results: We identified five discrete pain trajectories among 305 patients. Group 1 remained pain free. Group 2 reported low scores with intermittent spikes and slight increase over time. Group 3 noted increasing pain severity through day 7 with mild improvement until day 14. Group 4 experienced maximum pain with steady decrement over time. Group 5 reported moderate pain with subtle improvement. In multivariable analysis, trajectory groups 3 (odds ratio [OR] 3.5; 95% confidence interval [CI] 1.5-8.3) and 5 (OR 8.0; 95% CI 3.1-21.1), history of depression (OR 3.6; 95% CI 1.3-10.0) and racial/ethnic minority (OR 2.3; 95% CI 1.3-4.1) were associated with continued opioid use at follow-up (median 62 days following admission, interquartile range 48-96).

Conclusions: Discrete pain trajectories following SAH exist. Recognition of pain trajectories may help identify those at risk for long-term opioid use.
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http://dx.doi.org/10.1007/s12028-021-01282-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189709PMC
June 2021

Evidence for Andexanet Alpha in Reversing Intracerebral Hemorrhage due to Factor Xa Inhibitors?

Stroke 2021 Jun 10;52(6):2106-2108. Epub 2021 May 10.

Program in Trauma, Department of Neurology, University of Maryland School of Medicine, Baltimore (N.B.).

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http://dx.doi.org/10.1161/STROKEAHA.120.031825DOI Listing
June 2021

Studies Utilizing Therapeutic Hypothermia and Targeted Temperature Management.

Ther Hypothermia Temp Manag 2021 Jun 22;11(2):71-75. Epub 2021 Apr 22.

Department of Emergency Medicine, University of Michigan, SIREN Emergency Clinical Trials Network and Neurological Emergencies Treatment, TrialsClinical Coordinating Centers, Ann Arbor, Michigan, USA.

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http://dx.doi.org/10.1089/ther.2021.29092.njbDOI Listing
June 2021

A prospective, real-world, clinical pharmacokinetic study to inform lacosamide dosing in critically ill patients undergoing continuous venovenous haemofiltration (PADRE-02).

Br J Clin Pharmacol 2021 Apr 14. Epub 2021 Apr 14.

Center for Translational Medicine, School of Pharmacy, University of Maryland, Baltimore, Maryland, United States.

Aims: Although the use of continuous renal replacement therapy (CRRT) has increased, limited dosing information exists on the effect of CRRT on antiepileptic drug pharmacokinetics. The objectives of this practice-based study are to evaluate the pharmacokinetics of lacosamide and recommend individualized dosing recommendations in critically ill patients receiving continuous venovenous haemofiltration (CVVH).

Methods: Seven patients receiving lacosamide and CVVH in a neurocritical care unit were enrolled. Pre-filter, post-filter and ultrafiltrate samples were obtained at baseline, right after the completion of the infusion, and up to six additional sampling time points post-administration. Patient-specific flow rates and clinical measures were also collected simultaneously at the time of sampling. Plasma concentrations were measured using a validated high-performance liquid chromatography with ultraviolet radiation detection (HPLC-UV) bioanalytical method. Non-compartmental analysis was utilized to characterize the pharmacokinetics of lacosamide.

Results: The observed mean sieving coefficient for lacosamide was 0.80 ± 0.10, suggesting high removal of lacosamide. Concentrations measured in six out of seven patients were observed to be outside the therapeutic range (5-12 mg/L). The estimated average volume of distribution was found to be similar to healthy patients (0.58 L/kg). The mean bias and precision of the estimated total clearance was -2.53% and 14.9%, respectively. Simulations of various doses suggest that effluent flow rate-based dosing regimens could be used to individualize lacosamide therapeutics.

Conclusions: CVVH clearance contributed a major fraction of the total lacosamide clearance in neurocritically ill patients. Given that drug clearance increases with higher effluent flow rates, lacosamide dosing regimens should be increased to match exposures observed in patients with normal renal function.
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http://dx.doi.org/10.1111/bcp.14858DOI Listing
April 2021

Early Stage Longitudinal Subcortical Volumetric Changes following Mild Traumatic Brain Injury.

Brain Inj 2021 05 6;35(6):725-733. Epub 2021 Apr 6.

Center for Advanced Imaging Research, Department of Diagnostic Radiology & Nuclear Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.

: To investigate early brain volumetric changes from acute to 6 months following mild traumatic brain injury (mTBI) in deep gray matter regions and their association with patient 6-month outcome.: Fifty-six patients with mTBI underwent MRI and behavioral evaluation at acute (<10 days) and approximately 1 and 6 months post injury. Regional volume changes were investigated in key gray matter regions: thalamus, hippocampus, putamen, caudate, pallidum, and amygdala, and compared with volumes from 34 healthy control subjects. In patients with mTBI, we further assessed associations between longitudinal regional volume changes with patient outcome measures at 6 months including post-concussive symptoms, cognitive performance, and overall satisfaction with life.: Reduction in thalamic and hippocampal volumes was observed at 1 month among patients with mTBI. Such volume reduction persisted in the thalamus until 6 months. Changes in thalamic volumes also correlated with multiple symptom and functional outcome measures in patients at 6 months.: Our results indicate that the thalamus may be differentially affected among patients with mTBI, resulting in both structural and functional deficits with subsequent post-concussive sequelae and may serve as a biomarker for the assessment of efficacy of novel therapeutic interventions.
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http://dx.doi.org/10.1080/02699052.2021.1906445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207827PMC
May 2021

Association of Sex and Age With Mild Traumatic Brain Injury-Related Symptoms: A TRACK-TBI Study.

JAMA Netw Open 2021 04 1;4(4):e213046. Epub 2021 Apr 1.

Virginia Commonwealth University, Richmond, Virginia.

Importance: Knowledge of differences in mild traumatic brain injury (mTBI) recovery by sex and age may inform individualized treatment of these patients.

Objective: To identify sex-related differences in symptom recovery from mTBI; secondarily, to explore age differences within women, who demonstrate poorer outcomes after TBI.

Design, Setting, And Participants: The prospective cohort study Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) recruited 2000 patients with mTBI from February 26, 2014, to July 3, 2018, and 299 patients with orthopedic trauma (who served as controls) from January 26, 2016, to July 27, 2018. Patients were recruited from 18 level I trauma centers and followed up for 12 months. Data were analyzed from August 19, 2020, to March 3, 2021.

Exposures: Patients with mTBI (defined by a Glasgow Coma Scale score of 13-15) triaged to head computed tomography in 24 hours or less; patients with orthopedic trauma served as controls.

Main Outcomes And Measures: Measured outcomes included (1) the Rivermead Post Concussion Symptoms Questionnaire (RPQ), a 16-item self-report scale that assesses postconcussion symptom severity over the past 7 days relative to preinjury; (2) the Posttraumatic Stress Disorder Checklist for the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (PCL-5), a 20-item test that measures the severity of posttraumatic stress disorder symptoms; (3) the Patient Health Questionnaire-9 (PHQ-9), a 9-item scale that measures depression based on symptom frequency over the past 2 weeks; and (4) the Brief Symptom Inventory-18 (BSI-18), an 18-item scale of psychological distress (split into Depression and Anxiety subscales).

Results: A total of 2000 patients with mTBI (1331 men [67%; mean (SD) age, 41.0 (17.3) years; 1026 White (78%)] and 669 women [33%; mean (SD) age, 43.0 (18.5) years; 505 (76%) White]). After adjustment of multiple comparisons, significant TBI × sex interactions were observed for cognitive symptoms (B = 0.76; 5% false discovery rate-corrected P = .02) and somatic RPQ symptoms (B = 0.80; 5% false discovery rate-corrected P = .02), with worse symptoms in women with mTBI than men, but no sex difference in symptoms in control patients with orthopedic trauma. Within the female patients evaluated, there was a significant TBI × age interaction for somatic RPQ symptoms, which were worse in female patients with mTBI aged 35 to 49 years compared with those aged 17 to 34 years (B = 1.65; P = .02) or older than 50 years (B = 1.66; P = .02).

Conclusions And Relevance: This study found that women were more vulnerable than men to persistent mTBI-related cognitive and somatic symptoms, whereas no sex difference in symptom burden was seen after orthopedic injury. Postconcussion symptoms were also worse in women aged 35 to 49 years than in younger and older women, but further investigation is needed to corroborate these findings and to identify the mechanisms involved. Results suggest that individualized clinical management of mTBI should consider sex and age, as some women are especially predisposed to chronic postconcussion symptoms even 12 months after injury.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.3046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025125PMC
April 2021

Latent Profile Analysis of Neuropsychiatric Symptoms and Cognitive Function of Adults 2 Weeks After Traumatic Brain Injury: Findings From the TRACK-TBI Study.

JAMA Netw Open 2021 03 1;4(3):e213467. Epub 2021 Mar 1.

TIRR Memorial Hermann, Houston, Texas.

Importance: Heterogeneity across patients with traumatic brain injury (TBI) presents challenges for clinical care and intervention design. Identifying distinct clinical phenotypes of TBI soon after injury may inform patient selection for precision medicine clinical trials.

Objective: To investigate whether distinct neurobehavioral phenotypes can be identified 2 weeks after TBI and to characterize the degree to which early neurobehavioral phenotypes are associated with 6-month outcomes.

Design, Setting, And Participants: This prospective cohort study included patients presenting to 18 US level 1 trauma centers within 24 hours of TBI from 2014 to 2019 as part of the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study. Data were analyzed from January 28, 2020, to January 11, 2021.

Exposures: TBI.

Main Outcomes And Measures: Latent profiles (LPs) were derived from common dimensions of neurobehavioral functioning at 2 weeks after injury, assessed through National Institutes of Health TBI Common Data Elements (ie, Brief Symptom Inventory-18, Patient Health Questionnaire-9 Depression checklist, Posttraumatic Stress Disorder Checklist for DSM-5, PROMIS Pain Intensity scale, Insomnia Severity Index, Rey Auditory Verbal Learning Test, Wechsler Adult Intelligence Scale-Fourth Edition Coding and Symbol Search subtests, Trail Making Test, and NIH Toolbox Cognitive Battery Pattern Comparison Processing Speed, Dimensional Change Card Sort, Flanker Inhibitory Control and Attention, and Picture Sequence Memory subtests). Six-month outcomes were the Satisfaction With Life Scale (SWLS), Quality of Life after Brain Injury-Overall Scale (QOLIBRI-OS), Glasgow Outcome Scale-Extended (GOSE), and Rivermead Post-Concussion Symptoms Questionnaire (RPQ).

Results: Among 1757 patients with TBI included, 1184 (67.4%) were men, and the mean (SD) age was 39.9 (17.0) years. LP analysis revealed 4 distinct neurobehavioral phenotypes at 2 weeks after injury: emotionally resilient (419 individuals [23.8%]), cognitively impaired (368 individuals [20.9%]), cognitively resilient (620 individuals [35.3%]), and neuropsychiatrically distressed (with cognitive weaknesses; 350 individuals [19.9%]). Adding LP group to models including demographic characteristics, medical history, Glasgow Coma Scale score, and other injury characteristics was associated with significantly improved estimation of association with 6-month outcome (GOSE R2 increase = 0.09-0.19; SWLS R2 increase = 0.12-0.22; QOLIBRI-OS R2 increase = 0.14-0.32; RPQ R2 = 0.13-0.34).

Conclusions And Relevance: In this cohort study of patients with TBI presenting to US level-1 trauma centers, qualitatively distinct profiles of symptoms and cognitive functioning were identified at 2 weeks after TBI. These distinct phenotypes may help optimize clinical decision-making regarding prognosis, as well as selection and stratification for randomized clinical trials.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.3467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010589PMC
March 2021

Association of Refractory Pain in the Acute Phase After Subarachnoid Hemorrhage With Continued Outpatient Opioid Use.

Neurology 2021 05 25;96(19):e2355-e2362. Epub 2021 Mar 25.

From the Departments of Neurology (M.N.J., J.E.P., A.K., W.-T.W.C., M.M., G.Y.P., N.B., N.A.M.), Emergency Medicine (W.-T.W.C.), Pharmacy Services (M.J.A.), Neurosurgery (J.M.S.), Pathology (J.M.S.), and Physiology (J.M.S.), and Program in Trauma, R. Adams Cowley Shock Trauma Center (M.N.J., J.E.P., W.-T.W.C., M.M., G.Y.P., N.B., N.A.M.), University of Maryland School of Medicine (M.C.S., A.F., A.K.), Baltimore; and Department of Neurology, Division of Neurocritical Care and Emergency Neurology (K.N.S.), Yale School of Medicine, New Haven, CT.

Objective: Little is known about the prevalence of continued opioid use following aneurysmal subarachnoid hemorrhage (aSAH) despite guidelines recommending their use during the acute phase of disease. We sought to determine prevalence of opioid use following aSAH and test the hypothesis that acute pain and higher inpatient opioid dose increased outpatient opioid use.

Methods: We reviewed consecutively admitted patients with aSAH from November 2015 through September 2019. We retrospectively collected pain scores and daily doses of analgesics. Pain burden was calculated as area under the pain-time curve. Univariate and multivariable regression models determined risk factors for continued opioid use at discharge and outpatient follow-up.

Results: We identified 234 patients with aSAH with outpatient follow-up. Continued opioid use was common at discharge (55% of patients) and follow-up (47% of patients, median 63 [interquartile range 49-96] days from admission). Pain burden, craniotomy, and racial or ethnic minority status were associated with discharge opioid prescription in multivariable analysis. At outpatient follow-up, pain burden (odds ratio [OR] 1.88, 95% confidence interval [CI] 1.5-2.4), depression (OR 3.1, 95% CI 1.1-8.8), and racial or ethnic minority status (OR 2.1, 95% CI 1.1-4.0) were independently associated with continued opioid use; inpatient opioid dose was not.

Conclusion: Continued opioid use following aSAH is prevalent and related to refractory pain during acute illness, but not inpatient opioid dose. More efficacious analgesic strategies are needed to reduce continued opioid use in patients following aSAH.

Classification Of Evidence: This study provides Class II evidence that continued opioid use following aSAH is associated with refractory pain during acute illness but not hospital opioid exposure.
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http://dx.doi.org/10.1212/WNL.0000000000011906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166442PMC
May 2021

Impact of Fever Prevention in Brain-Injured Patients (INTREPID): Study Protocol for a Randomized Controlled Trial.

Neurocrit Care 2021 Mar 24. Epub 2021 Mar 24.

Department of Neurology, Yale University School of Medicine, 15 York Street, LCI 1003, New Haven, CT, USA.

Background: Multiple studies demonstrate that fever/elevated temperature is associated with poor outcomes in patients with vascular brain injury; however, there are no conclusive studies that demonstrate that fever prevention/controlled normothermia is associated with better outcomes. The primary objective of the INTREPID (Impact of Fever Prevention in Brain-Injured Patients) trial is to test the hypothesis that fever prevention is superior to standard temperature management in patients with acute vascular brain injury.

Methods: INTREPID is a prospective randomized open blinded endpoint study of fever prevention versus usual care in patients with ischemic or hemorrhagic stroke. The fever prevention intervention utilizes the Arctic Sun System and will be compared to standard care patients in whom fever may spontaneously develop. Ischemic stroke, intracerebral hemorrhage or subarachnoid hemorrhage patients will be included within disease-specific time-windows. Both awake and sedated patients will be included, and treatment is initiated immediately upon enrollment. Eligible patients are expected to require intensive care for at least 72 h post-injury, will not be deemed unlikely to survive without severe disability, and will be treated for up to 14 days, or until deemed ready for discharge from the ICU, whichever comes first. Fifty sites in the USA and worldwide will participate, with a target enrollment of 1176 patients (1000 evaluable). The target temperature is 37.0 °C. The primary efficacy outcome is the total fever burden by °C-h, defined as the area under the temperature curve above 37.9 °C. The primary secondary outcome, on which the sample size is based, is the modified Rankin Scale Score at 3 months. All efficacy analyses including the primary and key secondary endpoints will be primarily based on an intention-to-treat population. Analysis of the as-treated and per protocol populations will also be performed on the primary and key secondary endpoints as sensitivity analyses.

Discussion: The INTREPID trial will provide the first results of the impact of a pivotal fever prevention intervention in patients with acute stroke ( www.clinicaltrials.gov ; NCT02996266; registered prospectively 05DEC2016).
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http://dx.doi.org/10.1007/s12028-021-01208-1DOI Listing
March 2021

Triage of Patients with Intracerebral Hemorrhage to Comprehensive Versus Primary Stroke Centers.

J Stroke Cerebrovasc Dis 2021 May 14;30(5):105672. Epub 2021 Mar 14.

Department of Neurology, Program in Trauma, University of Maryland School of Medicine, Baltimore, MD USA.

Objectives: The management of patients admitted with intracerebral hemorrhage (ICH) mostly occurs in an ICU. While guidelines recommend initial treatment of these patients in a neurocritical care or stroke unit, there is limited data on which patients would benefit most from transfer to a comprehensive stroke center where on-site neurosurgical coverage is available 24/7. As neurocritical units become more common in primary stroke centers, it is important to determine which patients are most likely to require neurosurgical intervention and transfer to comprehensive stroke centers.

Materials And Methods: This is a retrospective observational cohort study conducted at an academic comprehensive stroke center in the United States. Four-hundred-fifty-nine consecutive patients transferred or directly admitted to the neurocritical care unit from 2016-2018 with the primary diagnosis of ICH were included. Univariate statistics and multivariate regression were used to identify clinical characteristics associated with neurosurgical intervention, defined as undergoing craniotomy, ventriculostomy, or endovascular embolization of an arteriovenous malformation (AVM).

Results: The following variables were associated with neurosurgical intervention in multivariate analysis: age (OR 0.38, 95% CI 0.27-0.55), admission Glasgow Coma Scale (OR 0.29, 95% CI 0.18-0.48), the presence of intraventricular hemorrhage (OR 2.82, CI 1.71-4.65), infratentorial location of ICH (OR 2.28, 95% CI 1.20-4.31), previous antiplatelet use (OR 2.04, 95% CI 1.24-3.34), and an AVM indicated on CT Angiogram (OR 2.59, 95% CI 1.19-5.63) were independently associated with the need for neurosurgical intervention. This was translated into a scoring system to help make quick triage decisions, with high sensitivity (99%, 95% CI 97-99%) and negative predictive value (98%, 95% CI 89-99%).

Conclusions: Using previously well described predictors of severity in ICH patients, we were able to develop a scoring system to predict the need for neurosurgical intervention with high sensitivity and negative predictive value.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105672DOI Listing
May 2021

Temperature Management in Neurological and Neurosurgical Intensive Care Unit.

Ther Hypothermia Temp Manag 2021 03 16;11(1):7-9. Epub 2021 Feb 16.

Department of Neurology, University of Maryland School of Medicine, Baltimore, Maryland, USA.

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http://dx.doi.org/10.1089/ther.2021.29080.pjlDOI Listing
March 2021

An update on the pharmacological management and prevention of cerebral edema: current therapeutic strategies.

Expert Opin Pharmacother 2021 Jun 27;22(8):1025-1037. Epub 2021 Jan 27.

Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA.

: Cerebral edema is a common complication of multiple neurological diseases and is a strong predictor of outcome, especially in traumatic brain injury and large hemispheric infarction.: Traditional and current treatments of cerebral edema include treatment with osmotherapy or decompressive craniectomy at the time of clinical deterioration. The authors discuss preclinical and clinical models of a variety of neurological disease states that have identified receptors, ion transporters, and channels involved in the development of cerebral edema as well as modulation of these receptors with promising agents.: Further study is needed on the safety and efficacy of the agents discussed. IV glibenclamide has shown promise in preclinical and clinical trials of cerebral edema in large hemispheric infarct and traumatic brain injury. Consideration of underlying pathophysiology and pharmacodynamics is vital, as the synergistic use of agents has the potential to drastically mitigate cerebral edema and secondary brain injury thusly transforming our treatment paradigms.
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http://dx.doi.org/10.1080/14656566.2021.1876663DOI Listing
June 2021

Low-Dose Intravenous Heparin Infusion After Aneurysmal Subarachnoid Hemorrhage is Associated With Decreased Risk of Delayed Neurological Deficit and Cerebral Infarction.

Neurosurgery 2021 02;88(3):523-530

Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland.

Background: Patients who survive aneurysmal subarachnoid hemorrhage (aSAH) are at risk for delayed neurological deficits (DND) and cerebral infarction. In this exploratory cohort comparison analysis, we compared in-hospital outcomes of aSAH patients administered a low-dose intravenous heparin (LDIVH) infusion (12 U/kg/h) vs those administered standard subcutaneous heparin (SQH) prophylaxis for deep vein thrombosis (DVT; 5000 U, 3 × daily).

Objective: To assess the safety and efficacy of LDIVH in aSAH patients.

Methods: We retrospectively analyzed 556 consecutive cases of aSAH patients whose aneurysm was secured by clipping or coiling at a single institution over a 10-yr period, including 233 administered the LDIVH protocol and 323 administered the SQH protocol. Radiological and outcome data were compared between the 2 cohorts using multivariable logistic regression and propensity score-based inverse probability of treatment weighting (IPTW).

Results: The unadjusted rate of cerebral infarction in the LDIVH cohort was half that in SQH cohort (9 vs 18%; P = .004). Multivariable logistic regression showed that patients in the LDIVH cohort were significantly less likely than those in the SQH cohort to have DND (odds ratio (OR) 0.53 [95% CI: 0.33, 0.85]) or cerebral infarction (OR 0.40 [95% CI: 0.23, 0.71]). Analysis following IPTW showed similar results. Rates of hemorrhagic complications, heparin-induced thrombocytopenia and DVT were not different between cohorts.

Conclusion: This cohort comparison analysis suggests that LDIVH infusion may favorably influence the outcome of patients after aSAH. Prospective studies are required to further assess the benefit of LDIVH infusion in patients with aSAH.
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http://dx.doi.org/10.1093/neuros/nyaa473DOI Listing
February 2021

The Modified Fisher Scale Lacks Interrater Reliability.

Neurocrit Care 2021 08 16;35(1):72-78. Epub 2020 Nov 16.

Department of Neurology, Program in Trauma, University of Maryland School of Medicine, Baltimore, MD, USA.

Background: The modified Fisher scale (mFS) is a critical clinical and research tool for risk stratification of cerebral vasospasm. As such, the mFS is included as a common data element by the National Institute of Neurological Disorders and Stroke SAH Working Group. There are few studies assessing the interrater reliability of the mFS.

Methods: We distributed a survey to a convenience sample with snowball sampling of practicing neurointensivists and through the research survey portion of the Neurocritical Care Society Web site. The survey consisted of 15 scrollable CT scans of patients with SAH for mFS grading, two questions regarding the definitions of the scale criteria and demographics of the responding physician. Kendall's coefficient of concordance was used to determine the interrater reliability of mFS grading.

Results: Forty-six participants (97.8% neurocritical care fellowship trained, 78% UCNS-certified in neurocritical care, median 5 years (IQR 3-6.3) in practice, treating median of 80 patients (IQR 50-100) with SAH annually from 32 institutions) completed the survey. By mFS criteria, 30% correctly identified that there is no clear measurement of thin versus thick blood, and 42% correctly identified that blood in any ventricle is scored as "intraventricular blood." The overall interrater reliability by Kendall's coefficient of concordance for the mFS was moderate (W = 0.586, p < 0.0005).

Conclusions: Agreement among raters in grading the mFS is only moderate. Online training tools could be developed to improve mFS reliability and standardize research in SAH.
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http://dx.doi.org/10.1007/s12028-020-01142-8DOI Listing
August 2021

Neuromuscular Electrical Stimulation and High-Protein Supplementation After Subarachnoid Hemorrhage: A Single-Center Phase 2 Randomized Clinical Trial.

Neurocrit Care 2021 08 4;35(1):46-55. Epub 2020 Nov 4.

Department of Medicine, University of Maryland School of Medicine, Baltimore, USA.

Introduction: Aneurysmal subarachnoid hemorrhage (SAH) survivors live with long-term residual physical and cognitive disability. We studied whether neuromuscular electrical stimulation (NMES) and high-protein supplementation (HPRO) in the first 2 weeks after SAH could preserve neuromotor and cognitive function as compared to standard of care (SOC) for nutrition and mobilization.

Methods: SAH subjects with a Hunt Hess (HH) grade > 1,modified Fisher score > 1 and BMI < 40 kg/m were randomly assigned to SOC or NMES + HPRO. NMES was delivered to bilateral quadricep muscles daily during two 30-min sessions along with HPRO (goal:1.8 g/kg/day) between post-bleed day (PBD) 0 and 14. Primary endpoint was atrophy in the quadricep muscle as measured by the percentage difference in the cross-sectional area from baseline to PBD14 on CT scan. All subjects underwent serial assessments of physical (short performance physical battery, SPPB) cognitive (Montreal Cognitive Assessment Scale, MoCA) and global functional recovery (modified Rankin Scale, mRS) at PBD 14, 42, and 90.

Results: Twenty-five patients (SOC = 13, NMES + HPRO = 12) enrolled between December 2017 and January 2019 with no between-group differences in baseline characteristics (58 years old, 68% women, 50% HH > 3). Median duration of interventions was 12 days (range 9-14) with completion of 98% of NMES sessions and 83% of goal HPRO, and no reported serious adverse events. There was no difference in caloric intake between groups, but HPRO + NMES group received more protein (1.5 ± 0.5 g/kg/d v 0.9 ± 0.4 g/kg/d, P < 0.01). Muscle atrophy was less in NMES + HPRO than the SOC group (6.5 ± 4.1% vs 12.5 ± 6.4%, P 0.01). Higher atrophy was correlated with lower daily protein intake (ρ = - 0.45, P = 0.03) and lower nitrogen balance (ρ = 0.47, P  = 0.02); and worse 3 month SPPB (ρ = -  0.31, P = 0.1) and mRS (ρ = 0.4, P  = 0.04). NMES + HPRO patients had a better median [25%,75] SPPB (12[10, 12] v. 9 [4, 12], P = 0.01) and mRS (1[0,2] v.2[1, 3], P = 0.04) than SOC at PBD 90.

Conclusions: NMES + HPRO appears to be feasible and safe acutely after SAH and may reduce acute quadriceps muscle wasting with a lasting benefit on recovery after SAH.
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http://dx.doi.org/10.1007/s12028-020-01138-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093316PMC
August 2021

Safety and Feasibility of a Novel Transnasal Cooling Device to Induce Normothermia in Febrile Cerebrovascular Patients.

Neurocrit Care 2021 04;34(2):500-507

Department of Cardiology, The Johns Hopkins Hospital, Baltimore, USA.

Background: Inducing normothermia with surface cooling temperature modulating devices (TMDs) is cumbersome and often associated with significant shivering. We tested the safety and feasibility of a novel transnasal evaporative cooling device to induce and maintain normothermia in febrile patients following ischemic and hemorrhagic stroke.

Methods: A single-center study utilizing the CoolStat® transnasal cooling device was used to achieve core temperature reduction in mechanically ventilated stroke patients with fever (T ≥ 38.3 C) refractory to acetaminophen by inducing an evaporative cooling energy exchange in the nasal turbinates thru a high flow of dehumidified air into the nasal cavity and out through the mouth. Continuous temperature measurements were obtained from tympanic and core (esophageal or bladder) temperature monitors. Safety assessments included continuous monitoring for hypertension, tachycardia, and raised intracranial pressure (when monitored). Otolaryngology (ENT) evaluations were monitored for any device-related nasal mucosal injury with a pre- and post-visual examination. Shivering was assessed every 30 min using the Bedside Shivering Assessment Scale (BSAS). Duration of device use was limited to 8 h, at which time patients were transitioned to routine care for temperature management.

Results: Ten subjects (median age: 54 years, BMI: 32.5 kg/m, 60% men) were enrolled with normothermia achieved in 90% of subjects. One subject did not achieve normothermia and was later refractory to other TMDs. Median baseline temperature was 38.5 ± 0.1 C, with a reduction noted by 4 h (38.5 ± 0.1 vs 37.3 ± 0.8, P < 0.001) and sustained at 8 h (38.5 ± 0.1 vs 37.1 ± 0.7, P = 0.001). Time to normothermia was 2.6 ± 1.9 h. The median BSAS was 0 (range 0-1) with only 4 episodes necessitating meperidine across 76 h of study monitoring. No treatment was discontinued due to safety concerns. ENT evaluations noted no device-related adverse findings.

Conclusions: Inducing normothermia with a novel transnasal TMD appears to be safe, feasible and not associated with significant shivering. A multicenter trial testing the ability of the CoolStat to maintain normothermia for 24 h is currently underway.
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http://dx.doi.org/10.1007/s12028-020-01044-9DOI Listing
April 2021

Comparison of a Continuous Noninvasive Temperature to Monitor Core Temperature Measures During Targeted Temperature Management.

Neurocrit Care 2021 04;34(2):449-455

Program in Trauma, Department of Neurology, University of Maryland School of Medicine, Baltimore, USA.

Background: Temperature modulating devices (TMD) currently utilize core temperature measurements during targeted temperature management (TTM) that are currently limited to esophageal (Et), bladder (Bt), or rectal (Rt) temperatures. We assessed the ability of a continuous noninvasive temperature monitor to accurately approximate core temperature during TTM.

Methods: All patients undergoing TTM using a gel pad surface TMD and an existing core temperature monitoring device were eligible for this study. Core and continuous noninvasive temperature monitoring values were simultaneously recorded for up to 72 h of TTM. The two sets of temperature data were downloaded from a clinical data acquisition storage system at 1-min intervals. The Bland-Altman method assessed agreement between the core and continuous noninvasive temperature monitor values, by measuring the mean difference (± 2 SD) between these values.

Results: There were 20 subjects that underwent study between January 2018 and March 2018 (55% women, age: 57 ± 14 years old, BMI: 28.9 + 9.8 kg/m, 100% mechanically ventilated). The comparison patient temperature source was predominantly esophageal (n = 10) followed by bladder (n = 5) or rectal (n = 5). There were a total of 999 h of paired patient temperature data from esophageal (50%), bladder (25%), and rectal (25%) temperatures. Bland-Altman analysis demonstrated good agreement with the superficial temperature monitor and core temperature measures in all patients overall, with a difference mean of 0.06 ± 0.39 C (P = 0.99) and no proportional bias noted (β =0.002, P = 0.917).

Conclusions: Continuous noninvasive temperature monitoring is a suitable alternative method for assessing core temperature during TTM. Future studies should focus on developing connectivity with a continuous noninvasive temperature monitor to approximate core temperature during TTM.
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http://dx.doi.org/10.1007/s12028-020-01036-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338135PMC
April 2021

Factors associated with tracheostomy decannulation in patients with severe traumatic brain injury.

Brain Inj 2020 07 2;34(8):1106-1111. Epub 2020 Jul 2.

Section of Neurocritical Care and Emergency Neurology, Program in Trauma, Department of Neurology, University of Maryland School of Medicine , Baltimore, MD, USA.

Objective: To assess variables associated with decannulation in patients with traumatic brain injury (TBI).

Participants: 79 patients with TBI requiring tracheostomy and ICU admission from January 1 to December 31, 2014.

Design: Retrospective analysis.

Measures: Patients decannulated prior to 90 days were compared with patients who remained cannulated. Two Cox Proportional Hazards models were used to predict decannulation using variables prior to tracheostomy and throughout hospitalization.

Results: Median time to decannulation was 37 days (Interquartile Range [IQR] 29-67). Variables prior to tracheostomy associated with decannulation included diabetes (HR, 0.15; 95% CI, 0.03-0.84; =.03), craniotomy (HR, 0.25; 95% CI, 0.06-1.02; =.05) and acute kidney injury (AKI) (HR, 0.06; 95% CI, 0.01-0.48; =.01). Variables present throughout hospitalization included age (HR, 1.12; 95% CI, 1.01-1.21; =.03), ventilator days (HR, 0.74; 95% CI, 0.57-0.95; =.02), reintubation (HR, 0.07; 95% CI, 0.01-0.64; =.02), aspiration (HR, 0.01; 95% CI, 0.0-0.29, =.01), craniotomy (HR, 0.004; 95% CI, 0.0-0.39; =.02) and AKI (HR, 0.0; 95% CI, 0.0-0.21; =.01).

Conclusion: The presence of diabetes, craniotomy and acute kidney injury may inform the conversation surrounding chances for decannulation prior to tracheostomy.
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http://dx.doi.org/10.1080/02699052.2020.1786601DOI Listing
July 2020

Prognostic Significance of Sentinel Headache Preceding Aneurysmal Subarachnoid Hemorrhage.

World Neurosurg 2020 07 24;139:e672-e676. Epub 2020 Apr 24.

Departments of Neurology and Neurosurgery, New York Medical College, Westchester Medical Center Health Network, Valhalla, New York, USA. Electronic address:

Background: Sentinel headache (SH) is often assumed to portend an increased risk of delayed cerebral ischemia (DCI) and aneurysm rebleeding. This study aimed to re-evaluate the associations between SH and aneurysm rebleeding, DCI, and outcome after SAH.

Methods: We retrospectively analyzed 1102 patients with spontaneous SAH and available data regarding history of SH who were enrolled in the Columbia University SAH Outcomes Project between 1996 and 2009. Patients were asked whether they had experienced any episodes of acute, sudden-onset severe headache in the 2 weeks preceding the most recent bleeding event. DCI was defined as neurologic deterioration, infarction, or both due to vasospasm. Rebleeding was defined as the appearance of new hemorrhage on computed tomography. Outcome was assessed at 3 months by telephone interview using the modified Rankin Scale.

Results: SH was reported in 152 (14%) of 1102 patients. There were no significant differences between patients with and without SH with regard to admission Hunt-Hess grade or modified Fisher Scale. There was also no difference with regard to the frequency of aneurysm rebleeding (10% vs. 8%, P = 0.42), DCI (18% vs, 20%, P = 0.64), moderate-or-severe angiographic vasospasm on follow-up angiography (51% vs. 56%, P = 0.43), highest recorded mean middle cerebral artery flow velocity on transcranial Doppler (134 versus 128 cm/s, P = 0.30), or the distribution of modified Rankin Scale scores at 3 months.

Conclusions: A history of sentinel headache before the clinical diagnosis of SAH does not imply an increased risk of DCI or further rebleeding, and carries no prognostic significance.
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http://dx.doi.org/10.1016/j.wneu.2020.04.097DOI Listing
July 2020

A Practice-Based, Clinical Pharmacokinetic Study to Inform Levetiracetam Dosing in Critically Ill Patients Undergoing Continuous Venovenous Hemofiltration (PADRE-01).

Clin Transl Sci 2020 09 3;13(5):950-959. Epub 2020 Apr 3.

Center for Translational Medicine, University of Maryland School of Pharmacy, Baltimore, Maryland, USA.

Limited data exist on the effect of continuous renal replacement therapy (CRRT) methods on anti-epileptic drug pharmacokinetics (PK). This prospective practice-based PK study aims to assess the impact of continuous venovenous hemofiltration (CVVH), a modality of CRRT, on levetiracetam PK in critically ill patients and to derive individualized dosing recommendations. Eleven patients receiving oral or intravenous levetiracetam and CVVH in various intensive care units at a large academic medical center were enrolled to investigate the need for dosing adjustments. Prefilter, postfilter, and ultrafiltrate samples were obtained before dosing, after the completion of the infusion or 1-hour postoral dose, and up to 6 additional time points postinfusion or postoral administration. Patient-specific blood and ultrafiltrate flow rates and laboratory values were also collected at the time of sampling. The average sieving coefficient (SC) for levetiracetam was 0.89 ± 0.1, indicating high filter efficiency. Six of the 11 patients experienced concentrations outside the reported therapeutic range (12-46 mg/L). The average volume of distribution was 0.73 L/kg. CVVH clearance contributes a major fraction of the total levetiracetam clearance (36-73%) in neurocritically ill patients. The average bias and precision of the estimated vs. observed total clearance value was ~ 10.6% and 21.5%. Major dose determinants were identified to be SC and effluent flow rate. Patients with higher ultrafiltrate rates will have increased drug clearance and, therefore, will require higher doses in order to match exposures seen in patients with normal renal function.
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http://dx.doi.org/10.1111/cts.12782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485952PMC
September 2020
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