Publications

2023

Mazzu, Maria A, Margaret L Campbell, Richard M Schwartzstein, Douglas B White, Susan L Mitchell, and Corey R Fehnel. (2023) 2023. “Evidence Guiding Withdrawal of Mechanical Ventilation at the End of Life: A Review.”. Journal of Pain and Symptom Management. https://doi.org/10.1016/j.jpainsymman.2023.05.009.

OBJECTIVE: Distress at the end of life in the intensive care unit (ICU) is common. We reviewed the evidence guiding symptom assessment, withdrawal of mechanical ventilation (WMV) process, support for the ICU team, and symptom management among adults, and specifically older adults, at end of life in the ICU.

SETTING AND DESIGN: Systematic search of published literature (January 1990-December 2021) pertaining to WMV at end of life among adults in the ICU setting using PubMed, Embase, and Web of Science. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed.

PARTICIPANTS: Adults (age 18 and over) undergoing WMV in the ICU.

MEASUREMENTS: Study quality was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.

RESULTS: Out of 574 articles screened, 130 underwent full text review, and 74 were reviewed and assessed for quality. The highest quality studies pertained to use of validated symptom scales during WMV. Studies of the WMV process itself were generally lower quality. Support for the ICU team best occurs via structured communication and social supports. Dyspnea is the most distressing symptom, and while high quality evidence supports the use of opiates, there is limited evidence to guide implementation of their use for specific patients.

CONCLUSION: High quality studies support some practices in palliative WMV, while gaps in evidence remain for the WMV process, supporting the ICU team, and medical management of distress. Future studies should rigorously compare WMV processes and symptom management to reduce distress at end of life.

2022

Kumar, Amit, Indrakshi Roy, Pamela R Bosch, Corey R Fehnel, Nicholas Garnica, Jon Cook, Meghan Warren, and Amol M Karmarkar. (2022) 2022. “Medicare Claim-Based National Institutes of Health Stroke Scale to Predict 30-Day Mortality and Hospital Readmission.”. J Gen Intern Med 37 (11): 2719-26.

Background: The Centers for Medicare and Medicaid Services (CMS) penalizes hospitals for higher than expected 30-day mortality rates using methods without accounting for condition severity risk adjustment. For patients with stroke, CMS claims did not quantify stroke severity until recently, when the National Institutes of Health Stroke Scale (NIHSS) reporting began.

Objective: Examine the predictive ability of claim-based NIHSS to predict 30-day mortality and 30-day hospital readmission in patients with ischemic stroke.

Design: Retrospective cohort study of Medicare claims data.

Patients: Medicare beneficiaries with ischemic stroke (N=43,241) acute hospitalization between October 2016 and November 2017.

Measurements: All-cause 30-day mortality and 30-day hospital readmission. NIHSS score was derived from ICD-10 codes and stratified into the following: minor to moderate, moderate, moderate to severe, and severe categories.

Results: Among 43,241 patients with ischemic stroke with NIHSS from 2,659 US hospitals, 64.6% had minor to moderate stroke, 14.3% had moderate, 12.7% had moderate to severe, and 8.5% had a severe stroke,10.1% died within 30 days, 12.1% were readmitted within 30 days. The NIHSS exhibited stronger discriminant property (C-statistic 0.83, 95% CI: 0.82-0.84) for 30-day mortality compared to Elixhauser (0.74, 95% CI: 0.73-0.75). A monotonic increase in the adjusted 30-day mortality risk occurred relative to minor to moderate stroke category: hazard ratio [HR]=2.92 (95% CI=2.59-3.29) for moderate stroke, HR=5.49 (95% CI=4.90-6.15) for moderate to severe stroke, and HR=7.82 (95% CI=6.95-8.80) for severe stroke. After accounting for competing risk of mortality, there was a significantly higher readmission risk in the moderate stroke (HR=1.11, 95% CI=1.03-1.20), but significantly lower readmission risk in the severe stroke (HR=0.84, 95% CI=0.74-0.95) categories.

Limitation: Timing of NIHSS reporting during hospitalization is unknown.

Conclusions: Medicare claim-based NIHSS is significantly associated with 30-day mortality in Medicare patients with ischemic stroke and significantly improves discriminant property relative to the Elixhauser comorbidity index.

Keywords: CMS; Elixhauser; administrative data; competing risk; stroke severity; survival analysis.

Chua, Melissa M J, Alejandro Enríquez-Marulanda, Santiago Gomez-Paz, Yosuke Akamatsu, Mohamed M Salem, Georgios A Maragkos, Luis C Ascanio, et al. (2022) 2022. “Sodium Variability and Probability of Vasospasm in Patients With Aneurysmal Subarachnoid Hemorrhage.”. Journal of Stroke and Cerebrovascular Diseases : The Official Journal of National Stroke Association 31 (1): 106186. https://doi.org/10.1016/j.jstrokecerebrovasdis.2021.106186.

OBJECTIVES: Vasospasm is a well-known complication of aneurysmal subarachnoid hemorrhage (aSAH) that generally occurs 4-14 days post-hemorrhage. Based on American Heart Association guidelines, the current understanding is that hyponatremic episodes may lead to vasospasm. Therefore, we sought to determine the association between repeated serum sodium levels of aSAH patients and its relationship to radiographic vasospasm.

MATERIALS AND METHODS: A single-center retrospective analysis from 2007-2016 was conducted of aSAH patients. Daily serum sodium levels were recorded up to day 14 post-admission. Hyponatremia was defined as a serum sodium value of < 135 mEq/L. We evaluated the relationship to radiologic vasospasm, neurologic deterioration, functional status at discharge, and mortality. A repeated measures analysis using a mixed-effect regression model was performed to assess the interindividual relationship between serum sodium trends and outcomes.

RESULTS: A total of 271 aSAH patients were included. There were no significant differences in interindividual serum sodium values over time and occurrence of radiographic vasospasm, neurologic deterioration, functional, or mortality outcomes (p = .59, p = .42, p = .94, p = .99, respectively) using the mixed-effect regression model. However, overall mean serum sodium levels were significantly higher in patients who had neurologic deterioration, poor functional outcome (mRS 3-6), and mortality.

CONCLUSIONS: Serum sodium level variations are not associated with subsequent development of cerebral vasospasm in aSAH patients. These findings indicate that serum sodium may not have an impact on vasospasm, and avoiding hypernatremia may provide a neurologic, functional and survival benefit.

Kumar, Amit, Indrakshi Roy, Pamela R Bosch, Corey R Fehnel, Nicholas Garnica, Jon Cook, Meghan Warren, and Amol M Karmarkar. (2022) 2022. “Medicare Claim-Based National Institutes of Health Stroke Scale to Predict 30-Day Mortality and Hospital Readmission.”. Journal of General Internal Medicine 37 (11): 2719-26. https://doi.org/10.1007/s11606-021-07162-0.

BACKGROUND: The Centers for Medicare and Medicaid Services (CMS) penalizes hospitals for higher than expected 30-day mortality rates using methods without accounting for condition severity risk adjustment. For patients with stroke, CMS claims did not quantify stroke severity until recently, when the National Institutes of Health Stroke Scale (NIHSS) reporting began.

OBJECTIVE: Examine the predictive ability of claim-based NIHSS to predict 30-day mortality and 30-day hospital readmission in patients with ischemic stroke.

DESIGN: Retrospective cohort study of Medicare claims data.

PATIENTS: Medicare beneficiaries with ischemic stroke (N=43,241) acute hospitalization between October 2016 and November 2017.

MEASUREMENTS: All-cause 30-day mortality and 30-day hospital readmission. NIHSS score was derived from ICD-10 codes and stratified into the following: minor to moderate, moderate, moderate to severe, and severe categories.

RESULTS: Among 43,241 patients with ischemic stroke with NIHSS from 2,659 US hospitals, 64.6% had minor to moderate stroke, 14.3% had moderate, 12.7% had moderate to severe, and 8.5% had a severe stroke,10.1% died within 30 days, 12.1% were readmitted within 30 days. The NIHSS exhibited stronger discriminant property (C-statistic 0.83, 95% CI: 0.82-0.84) for 30-day mortality compared to Elixhauser (0.74, 95% CI: 0.73-0.75). A monotonic increase in the adjusted 30-day mortality risk occurred relative to minor to moderate stroke category: hazard ratio [HR]=2.92 (95% CI=2.59-3.29) for moderate stroke, HR=5.49 (95% CI=4.90-6.15) for moderate to severe stroke, and HR=7.82 (95% CI=6.95-8.80) for severe stroke. After accounting for competing risk of mortality, there was a significantly higher readmission risk in the moderate stroke (HR=1.11, 95% CI=1.03-1.20), but significantly lower readmission risk in the severe stroke (HR=0.84, 95% CI=0.74-0.95) categories.

LIMITATION: Timing of NIHSS reporting during hospitalization is unknown.

CONCLUSIONS: Medicare claim-based NIHSS is significantly associated with 30-day mortality in Medicare patients with ischemic stroke and significantly improves discriminant property relative to the Elixhauser comorbidity index.

Bosch, Pamela R, Amol M Karmarkar, Indrakshi Roy, Corey R Fehnel, Robert E Burke, and Amit Kumar. (2022) 2022. “Association of Medicare-Medicaid Dual Eligibility and Race and Ethnicity With Ischemic Stroke Severity.”. JAMA Network Open 5 (3): e224596. https://doi.org/10.1001/jamanetworkopen.2022.4596.

IMPORTANCE: Black and Hispanic US residents are disproportionately affected by stroke incidence, and patients with dual eligibility for Medicare and Medicaid may be predisposed to more severe strokes. Little is known about differences in stroke severity for individuals with dual eligibility, Black individuals, and Hispanic individuals, but understanding hospital admission stroke severity is the first important step for focusing strategies to reduce disparities in stroke care and outcomes.

OBJECTIVE: To examine whether dual eligibility and race and ethnicity are associated with stroke severity in Medicare beneficiaries admitted to acute hospitals with ischemic stroke.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cross-sectional study was conducted using Medicare claims data for patients with ischemic stroke admitted to acute hospitals in the United States from October 1, 2016, to November 30, 2017. Data were analyzed from July 2021 and January 2022.

EXPOSURES: Dual enrollment for Medicare and Medicaid; race and ethnicity categorized as White, Black, Hispanic, and other.

MAIN OUTCOMES AND MEASURES: Claim-based National Institutes of Health Stroke Scale (NIHSS) categorized into minor (0-7), moderate (8-13), moderate to severe (14-21), and severe (22-42) stroke.

RESULTS: Our sample included 45 459 Medicare fee-for-service patients aged 66 and older (mean [SD] age, 80.2 [8.4]; 25 303 [55.7%] female; 7738 [17.0%] dual eligible; 4107 [9.0%] Black; 1719 [3.8%] Hispanic; 37 715 [83.0%] White). In the fully adjusted models, compared with White patients, Black patients (odds ratio [OR], 1.21; 95% CI, 1.06-1.39) and Hispanic patients (OR, 1.54; 95% CI, 1.29-1.85) were more likely to have a severe stroke. Using White patients without dual eligibility as a reference group, White patients with dual eligibility were more likely to have a severe stroke (OR, 1.75; 95% CI, 1.56-1.95). Similarly, Black patients with dual eligibility (OR, 2.15; 95% CI, 1.78-2.60) and Hispanic patients with dual eligibility (OR, 2.50; 95% CI, 1.98-3.16) were more likely to have a severe stroke.

CONCLUSIONS AND RELEVANCE: In this cross-sectional study, Medicare fee-for-service patients with ischemic stroke admitted to acute hospitals who were Black or Hispanic had a higher likelihood of worse stroke severity. Additionally, dual eligibility status had a compounding association with stroke severity regardless of race and ethnicity. An urgent effort is needed to decrease disparities in access to preventive and poststroke care for dual eligible and minority patients.

2021

Goudarzi, Sogand, Shooka Esmaeeli, Juan D Valencia, Maegan E Lu, Riley R Hales, Corey R Fehnel, Christopher M Conley, Sadeq A Quraishi, and Ala Nozari. (2021) 2021. “Treatment Options for COVID-19-Related Guillain-Barré Syndrome: A Systematic Review of Literature.”. The Neurologist 26 (5): 196-224. https://doi.org/10.1097/NRL.0000000000000342.

BACKGROUND: Central nervous system complications are reported in an increasing number of patients with Coronavirus Disease 2019 (COVID-19). COVID-19-related Guillain-Barré syndrome (GBS) is of particular importance given its association with higher mortality rates and prolonged respiratory failure.

REVIEW SUMMARY: We conducted a systematic review of published cases for COVID-19-related GBS, and provide a summary of clinical management strategies for these cases. Sixty-three studies, including 86 patients, were included. Seventy-six cases with reported outcome data were eligible for the outcome analysis. Ninety-nine percent of patients were diagnosed with COVID-19 before diagnosis of GBS (median: 14 d prior, interquartile range: 7 to 20). Intravenous immunotherapy (intravenous immunoglobulin: 0.4 g/kg/d for 5 d) was the most frequently used treatment approach. The review indicated that the outcome was not favorable in 26% of cases (persistent neurological deficits). A mortality rate of 3.5% was observed in patients with COVID-19-related GBS.

CONCLUSIONS: Although evidence to support specific treatments is lacking, clinicians should consider the benefits of immunotherapy and plasma exchange in addition to the standard antimicrobial and supportive therapies for patients who meet the diagnostic criteria for acute sensory and motor polyradiculoneuritis. Intravenous immunoglobulin treatment alone is not shown to result in improved outcomes or mortality. More extensive studies aimed at exploring the neurological manifestations and complications of COVID-19 and distinctive treatment options for COVID-19-related GBS are warranted.

Esmaeeli, Shooka, Juan Valencia, Lauren K Buhl, Andres Brenes Bastos, Sogand Goudarzi, Matthias Eikermann, Corey Fehnel, et al. (2021) 2021. “Anesthetic Management of Unruptured Intracranial Aneurysms: A Qualitative Systematic Review.”. Neurosurgical Review 44 (5): 2477-92. https://doi.org/10.1007/s10143-020-01441-w.

Intracranial aneurysms (IA) occur in 3-5% of the general population and may require surgical or endovascular obliteration if the patient is symptomatic or has an increased risk of rupture. These procedures carry an inherent risk of neurological complications, and the outcome can be influenced by the physiological and pharmacological effects of the administered anesthetics. Despite the critical role of anesthetic agents, however, there are no current studies to systematically assess the intraoperative anesthetic risks, benefits, and outcome effects in this population. In this systematic review of the literature, we carefully examine the existing evidence on the risks and benefits of common anesthetic agents during IA obliteration, their physiological and clinical characteristics, and effects on neurological outcome. The initial search strategy captured a total of 287 published studies. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 28 studies were included in the final report. Our data showed that both volatile and intravenous anesthetics are commonly employed, without evidence that either is superior. Although no specific anesthetic regimens are promoted, their unique neurological, cardiovascular, and physiological properties may be critical to the outcome in vulnerable patients. In particular, patients at risk for perioperative ischemia may benefit from timely administration of anesthetic agents with neuroprotective properties and optimization of their physiological parameters. Further studies are warranted to examine if these anesthetic regimens can reduce the risk of neurological injury and improve the overall outcome in these patients.

2020

Fehnel, Corey R, Miguel Armengol de la Hoz, Leo A Celi, Margaret L Campbell, Khalid Hanafy, Ala Nozari, Douglas B White, and Susan L Mitchell. (2020) 2020. “Incidence and Risk Model Development for Severe Tachypnea Following Terminal Extubation.”. Chest 158 (4): 1456-63. https://doi.org/10.1016/j.chest.2020.04.027.

BACKGROUND: Palliative ventilator withdrawal (PVW) in the ICU is a common occurrence.

RESEARCH QUESTION: The goal of this study was to measure the rate of severe tachypnea as a proxy for dyspnea and to identify characteristics associated with episodes of tachypnea.

STUDY DESIGN AND METHODS: This study assessed a retrospective cohort of ICU patients from 2008 to 2012 mechanically ventilated at a single academic medical center who underwent PVW. The primary outcome of at least one episode of severe tachypnea (respiratory rate > 30 breaths/min) within 6 h after PVW was measured by using detailed physiologic and medical record data. Multivariable logistic regression was used to examine the association between patient and treatment characteristics with the occurrence of a severe episode of tachypnea post extubation.

RESULTS: Among 822 patients undergoing PVW, 19% and 30% had an episode of severe tachypnea during the 1-h and 6-h postextubation period, respectively. Within 1 h postextubation, patients with the following characteristics were more likely to experience tachypnea: no pre-extubation opiates (adjusted OR [aOR], 2.08; 95% CI, 1.03-4.19), lung injury (aOR, 3.33; 95% CI, 2.19-5.04), Glasgow Coma Scale score > 8 (aOR, 2.21; 95% CI, 1.30-3.77), and no postextubation opiates (aOR, 1.90; 95% CI, 1.19-3.00).

INTERPRETATION: Up to one-third of ICU patients undergoing PVW experience severe tachypnea. Administration of pre-extubation opiates (anticipatory dosing) represents a key modifiable factor that may reduce poor symptom control.

Caplan, Rachel A, Jonah P Zuflacht, Jed A Barash, and Corey R Fehnel. (2020) 2020. “Neurotoxicology Syndromes Associated With Drugs of Abuse.”. Neurologic Clinics 38 (4): 983-96. https://doi.org/10.1016/j.ncl.2020.08.005.

Substance use disorders-and their associated neurologic complications-are frequently encountered by neurologists as well as emergency room physicians, internists, psychiatrists, and medical intensivists. Prominent neurologic sequelae of drug abuse, such as seizure and stroke, are common and often result in patients receiving medical attention. However, less overt neurologic manifestations, such as dysautonomia and perceptual disturbances, may be initially misattributed to primary medical or psychiatric illness, respectively. This article focuses on the epidemiology, pharmacology, and complications associated with commonly used recreational drugs, including opioids, alcohol, marijuana, cocaine, and hallucinogens.