Clinical Focus

  • Neurology
  • Stroke
  • Traumatic Brain Injury
  • Cardiac Arrest
  • Coma
  • Brain Death
  • Hypoxic ischemic Brain Injury

Academic Appointments

Administrative Appointments

  • Division Chief, Neurocritical Care, Stanford University, Department of Neurology (2018 - Present)

Boards, Advisory Committees, Professional Organizations

  • Emergency Cardiovascular Care Committee, American Heart Association (2019 - Present)
  • Task Force Member, Adult Life Support, International Liaison Committee on Resuscitation (ILCOR) (2020 - Present)
  • Board of Directors, Neurocritical Care Society (2019 - Present)

Professional Education

  • Board Certification: American Board of Internal Medicine, Neurocritical Care (2021)
  • Board Certification: American Board of Psychiatry and Neurology, Neurology (2010)
  • Fellowship: UCSF Dept of Neurology (2012) CA
  • Residency, Johns Hopkins University, Neurology (2010)
  • Internship, Stanford University, Internal Medicine (2007)
  • MD, Stanford University (2006)
  • Board Certification: United Council for Neurologic Subspecialties, Neurocritical Care (2013)

Current Research and Scholarly Interests

Dr. Karen G. Hirsch cares for critically ill patients with neurologic disorders in the intensive care unit. Dr. Hirsch's research focuses on using continuous and discrete multi-modal data to develop phenotypes and identify signatures of treatment responsiveness in patients with coma after cardiac arrest. She is the Co-PI of PRECICECAP (PRecision Care In Cardiac ArrEst - ICECAP, NINDS R01 NS119825-01) and works closely with collaborators in data science at Stanford and with industry partners to apply machine learning analyses to the complex multi-modal ICU data. Dr. Hirsch also studies neuro-imaging in post-cardiac arrest coma and traumatic brain injury.

Additional research interests include a broad array of topics and Dr. Hirsch greatly appreciates the importance of team science and collaboration. Along with colleagues in Biomedical Ethics, Dr. Hirsch studies brain death and organ donation with a focus on ethical challenges and prediction models. Along with colleagues in Cardiac Anesthesia and Cardiothoracic Surgery, Dr. Hirsch studies neurologic outcomes in patients on mechanical circulatory support including ECMO.

Dr. Hirsch is broadly interested in improving neurologic outcomes after acute brain injury and identifying early phenotypes to guide precision medicine in neurocritical care, especially in patients with post-cardiac arrest brain injury.

All Publications

  • Proceedings of the Second Curing Coma Campaign NIH Symposium: Challenging the Future of Research for Coma and Disorders of Consciousness. Neurocritical care Mainali, S., Aiyagari, V., Alexander, S., Bodien, Y., Boerwinkle, V., Boly, M., Brown, E., Brown, J., Claassen, J., Edlow, B. L., Fink, E. L., Fins, J. J., Foreman, B., Frontera, J., Geocadin, R. G., Giacino, J., Gilmore, E. J., Gosseries, O., Hammond, F., Helbok, R., Claude Hemphill, J., Hirsch, K., Kim, K., Laureys, S., Lewis, A., Ling, G., Livesay, S. L., McCredie, V., McNett, M., Menon, D., Molteni, E., Olson, D., O'Phelan, K., Park, S., Polizzotto, L., Javier Provencio, J., Puybasset, L., Venkatasubba Rao, C. P., Robertson, C., Rohaut, B., Rubin, M., Sharshar, T., Shutter, L., Sampaio Silva, G., Smith, W., Stevens, R. D., Thibaut, A., Vespa, P., Wagner, A. K., Ziai, W. C., Zink, E., I Suarez, J., Curing Coma Campaign collaborators 2022


    This proceedings article presents actionable research targets on the basis of the presentations and discussions at the 2nd Curing Coma National Institutes of Health (NIH) symposium held from May 3 to May 5, 2021. Here, we summarize the background, research priorities, panel discussions, and deliverables discussed during the symposium across six major domains related to disorders of consciousness. The six domains include (1) Biology of Coma, (2) Coma Database, (3) Neuroprognostication, (4) Care of Comatose Patients, (5) Early Clinical Trials, and (6) Long-term Recovery. Following the 1st Curing Coma NIH virtual symposium held on September 9 to September 10, 2020, six workgroups, each consisting of field experts in respective domains, were formed and tasked with identifying gaps and developing key priorities and deliverables to advance the mission of the Curing Coma Campaign. The highly interactive and inspiring presentations and panel discussions during the 3-day virtual NIH symposium identified several action items for the Curing Coma Campaign mission, which we summarize in this article.

    View details for DOI 10.1007/s12028-022-01505-3

    View details for PubMedID 35534661

  • Moving towards precision medicine in post-cardiac arrest care: Using cerebrovascular autoregulation to individualize blood pressure. Resuscitation Rivera Lara, L., Genevieve Hirsch, K. 2022
  • Prognostication of ICU Patients by Providers with and without Neurocritical Care Training. Neurocritical care Finley Caulfield, A., Mlynash, M., Eyngorn, I., Lansberg, M. G., Afjei, A., Venkatasubramanian, C., Buckwalter, M. S., Hirsch, K. G. 2022


    BACKGROUND: Predictions of functional outcome in neurocritical care (NCC) patients impact care decisions. This study compared the predictive values (PVs) of good and poor functional outcome among health care providers with and without NCC training.METHODS: Consecutive patients who were intubated for≥72h with primary neurological illness or neurological complications were prospectively enrolled and followed for 6-month functional outcome. Medical intensive care unit (MICU) attendings, NCC attendings, residents (RES), and nurses (RN) predicted 6-month functional outcome on the modified Rankin scale (mRS). The primary objective was to compare these four groups' PVs of a good (mRS score 0-3) and a poor (mRS score 4-6) outcome prediction.RESULTS: Two hundred eighty-nine patients were enrolled. One hundred seventy-six had mRS scores predicted by a provider from each group and were included in the primary outcome analysis. At 6months, 54 (31%) patients had good outcome and 122 (69%) had poor outcome. Compared with other providers, NCC attendings expected better outcomes (p<0.001). Consequently, the PV of a poor outcome prediction by NCC attendings was higher (96%[95% confidence interval [CI] 89-99%]) than that by MICU attendings (88% [95% CI 80-93%]), RES (82% [95% CI 74-88%]), and RN (85% [95% CI 77-91%]) (p=0.047, 0.002, and 0.012, respectively). When patients who had withdrawal of life-sustaining therapy (n=67) were excluded, NCC attendings remained better at predicting poor outcome (NCC 90% [95% CI 75-97%] vs. MICU 73% [95% CI 59-84%], p=0.064). The PV of a good outcome prediction was similar among groups (MICU 65% [95% CI 52-76%], NCC 63% [95% CI 51-73%], RES 71% [95% CI 55-84%], and RN 64% [95% CI 50-76%]).CONCLUSIONS: Neurointensivists expected better outcomes than other providers and were better at predicting poor functional outcomes. The PV of a good outcome prediction was modest among all providers.

    View details for DOI 10.1007/s12028-022-01467-6

    View details for PubMedID 35314970

  • Prediction of good neurological outcome in comatose survivors of cardiac arrest: a systematic review. Intensive care medicine Sandroni, C., D'Arrigo, S., Cacciola, S., Hoedemaekers, C. W., Westhall, E., Kamps, M. J., Taccone, F. S., Poole, D., Meijer, F. J., Antonelli, M., Hirsch, K. G., Soar, J., Nolan, J. P., Cronberg, T. 2022


    PURPOSE: To assess the ability of clinical examination, blood biomarkers, electrophysiology or neuroimaging assessed within 7days from return of spontaneous circulation (ROSC) to predict good neurological outcome, defined as no, mild, or moderate disability (CPC 1-2 or mRS 0-3) at discharge from intensive care unit or later, in comatose adult survivors from cardiac arrest (CA).METHODS: PubMed, EMBASE, Web of Science and the Cochrane Database of Systematic Reviews were searched. Sensitivity and specificity for good outcome were calculated for each predictor. The risk of bias was assessed using the QUIPS tool.RESULTS: A total of 37 studies were included. Due to heterogeneities in recording times, predictor thresholds, and definition of some predictors, meta-analysis was not performed. A withdrawal or localisation motor response to pain immediately or at 72-96h after ROSC, normal blood values of neuron-specific enolase (NSE) at 24h-72h after ROSC, a short-latency somatosensory evoked potentials (SSEPs) N20 wave amplitude>4V or a continuous background without discharges on electroencephalogram (EEG) within 72h from ROSC, and absent diffusion restriction in the cortex or deep grey matter on MRI on days 2-7 after ROSC predicted good neurological outcome with more than 80% specificity and a sensitivity above 40% in most studies. Most studies had moderate or high risk of bias.CONCLUSIONS: In comatose cardiac arrest survivors, clinical, biomarker, electrophysiology, and imaging studies identified patients destined to a good neurological outcome with high specificity within the first week after cardiac arrest (CA).

    View details for DOI 10.1007/s00134-022-06618-z

    View details for PubMedID 35244745

  • Precision Care in Cardiac Arrest: ICECAP (PRECICECAP) Study Protocol and Informatics Approach. Neurocritical care Elmer, J., He, Z., May, T., Osborn, E., Moberg, R., Kemp, S., Stover, J., Moyer, E., Geocadin, R. G., Hirsch, K. G., PRECICECAP Study Team 2022


    BACKGROUND: Most trials in critical care have been neutral, in part because between-patient heterogeneity means not all patients respond identically to the same treatment. The Precision Care in Cardiac Arrest: Influence of Cooling duration on Efficacy in Cardiac Arrest Patients (PRECICECAP) study will apply machine learning to high-resolution, multimodality data collected from patients resuscitated from out-of-hospital cardiac arrest. We aim to discover novel biomarker signatures to predict the optimal duration of therapeutic hypothermia and 90-day functional outcomes. In parallel, we are developing a freely available software platform for standardized curation of intensive care unit-acquired data for machine learning applications.METHODS: The Influence of Cooling duration on Efficacy in Cardiac Arrest Patients (ICECAP) study is a response-adaptive, dose-finding trial testing different durations of therapeutic hypothermia. Twelve ICECAP sites will collect data for PRECICECAP from multiple modalities routinely used after out-of-hospital cardiac arrest, including ICECAP case report forms, detailed medication data, cardiopulmonary and electroencephalographic waveforms, and digital imaging and communications in medicine files (DICOMs). We partnered with Moberg Analytics to develop a freely available software platform to allow high-resolution critical care data to be used efficiently and effectively. We will use an autoencoder neural network to create low-dimensional representations of all raw waveforms and derivative features, censored at rewarming to ensure clinical usability to guide optimal duration of hypothermia. We will also consider simple features that are historically considered to be important. Finally, we will create a supervised deep learning neural network algorithm to directly predict 90-day functional outcome from large sets of novel features.RESULTS: PRECICECAP is currently enrolling and will be completed in late 2025.CONCLUSIONS: Cardiac arrest is a heterogeneous disease that causes substantial morbidity and mortality. PRECICECAP will advance the overarching goal of titrating personalized neurocritical care on the basis of robust measures of individual need and treatment responsiveness. The software platform we develop will be broadly applicable to hospital-based research after acute illness or injury.

    View details for DOI 10.1007/s12028-022-01464-9

    View details for PubMedID 35229231

  • 2021 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Neonatal Life Support; Education, Implementation, and Teams; First Aid Task Forces; and the COVID-19 Working Group CIRCULATION Wyckoff, M. H., Singletary, E. M., Soar, J., Olasveengen, T. M., Greif, R., Liley, H. G., Zideman, D., Bhanji, F., Andersen, L. W., Avis, S. R., Aziz, K., Bendall, J. C., Berry, D. C., Borra, V., Boettiger, B. W., Bradley, R., Bray, J. E., Breckwoldt, J., Carlson, J. N., Cassan, P., Castren, M., Chang, W., Charlton, N. P., Cheng, A., Chung, S., Considine, J., Costa-Nobre, D. T., Couper, K., Dainty, K. N., Davis, P. G., de Almeida, M., de Caen, A. R., de Paiva, E. F., Deakin, C. D., Djarv, T., Douma, M. J., Drennan, I. R., Duff, J. P., Eastwood, K. J., El-Naggar, W., Epstein, J. L., Escalante, R., Fabres, J. G., Fawke, J., Finn, J. C., Foglia, E. E., Folke, F., Freeman, K., Gilfoyle, E., Goolsby, C. A., Grove, A., Guinsburg, R., Hatanaka, T., Hazinski, M., Heriot, G. S., Hirsch, K. G., Holmberg, M. J., Hosono, S., Hsieh, M., Hung, K. C., Hsu, C. H., Ikeyama, T., Isayama, T., Kapadia, V. S., Kawakami, M., Kim, H., Kloeck, D. A., Kudenchuk, P. J., Lagina, A. T., Lauridsen, K. G., Lavonas, E. J., Lockey, A. S., Hansen, C., Markenson, D., Matsuyama, T., McKinlay, C. D., Mehrabian, A., Merchant, R. M., Meyran, D., Morley, P. T., Morrison, L. J., Nation, K. J., Nemeth, M., Neumar, R. W., Nicholson, T., Niermeyer, S., Nikolaou, N., Nishiyama, C., O'Neil, B. J., Orkin, A. M., Osemeke, O., Parr, M. J., Patocka, C., Pellegrino, J. L., Perkins, G. D., Perlman, J. M., Rabi, Y., Reynolds, J. C., Ristagno, G., Roehr, C. C., Sakamoto, T., Sandroni, C., Sawyer, T., Schmolzer, G. M., Schnaubelt, S., Semeraro, F., Skrifvars, M. B., Smith, C. M., Smyth, M. A., Soll, R. F., Sugiura, T., Taylor-Phillips, S., Trevisanuto, D., Vaillancourt, C., Wang, T., Weiner, G. M., Welsford, M., Wigginton, J., Wyllie, J. P., Yeung, J., Nolan, J. P., Berg, K. M. 2022; 145 (9): E645-E721


    The International Liaison Committee on Resuscitation initiated a continuous review of new, peer-reviewed published cardiopulmonary resuscitation science. This is the fifth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations; a more comprehensive review was done in 2020. This latest summary addresses the most recently published resuscitation evidence reviewed by International Liaison Committee on Resuscitation task force science experts. Topics covered by systematic reviews in this summary include resuscitation topics of video-based dispatch systems; head-up cardiopulmonary resuscitation; early coronary angiography after return of spontaneous circulation; cardiopulmonary resuscitation in the prone patient; cord management at birth for preterm and term infants; devices for administering positive-pressure ventilation at birth; family presence during neonatal resuscitation; self-directed, digitally based basic life support education and training in adults and children; coronavirus disease 2019 infection risk to rescuers from patients in cardiac arrest; and first aid topics, including cooling with water for thermal burns, oral rehydration for exertional dehydration, pediatric tourniquet use, and methods of tick removal. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, according to the Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations or good practice statements. Insights into the deliberations of the task forces are provided in Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces listed priority knowledge gaps for further research.

    View details for DOI 10.1161/CIR.0000000000001017

    View details for Web of Science ID 000768449900006

    View details for PubMedID 34813356

  • 2021 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations Summary From the Basic Life Support; Advanced Life Support; Neonatal Life Support; Education, Implementation, and Teams; First Aid Task Forces; and the COVID-19 Working Group RESUSCITATION Wyckoff, M. H., Singletary, E. M., Soar, J., Olasveengen, T. M., Greif, R., Liley, H. G., Zideman, D., Bhanji, F., Andersen, L. W., Avis, S. R., Aziz, K., Bendall, J. C., Berry, D. C., Borra, V., Bottiger, B. W., Bradley, R., Bray, J. E., Breckwoldt, J., Carlson, J. N., Cassan, P., Castren, M., Chang, W., Charlton, N. P., Cheng, A., Chung, S., Considine, J., Costa-Nobre, D. T., Couper, K., Dainty, K. N., Davis, P. G., Almeida, M., Caen, A., Paiva, E., Deakin, C. D., Djarv, T., Douma, M. J., Drennan, I. R., Duff, J. P., Eastwood, K. J., El-Naggar, W., Epstein, J. L., Escalante, R., Fabres, J. G., Fawke, J., Finn, J. C., Foglia, E. E., Folke, F., Freeman, K., Gilfoyle, E., Goolsby, C. A., Grove, A., Guinsburg, R., Hatanaka, T., Hazinski, M., Heriot, G. S., Hirsch, K. G., Holmberg, M. J., Hosono, S., Hsieh, M., Hung, K. C., Hsu, C. H., Ikeyama, T., Isayama, T., Kapadia, V. S., Kawakami, M., Kim, H., Kloeck, D. A., Kudenchuk, P. J., Lagina, A. T., Lauridsen, K. G., Lavonas, E. J., Lockey, A. S., Hansen, C., Markenson, D., Matsuyama, T., McKinlay, C. D., Mehrabian, A., Merchant, R. M., Meyran, D., Morley, P. T., Morrison, L. J., Nation, K. J., Nemeth, M., Neumar, R. W., Nicholson, T., Niermeyer, S., Nikolaou, N., Nishiyama, C., O'Neil, B. J., Orkin, A. M., Osemeke, O., Parr, M. J., Patocka, C., Pellegrino, J. L., Perkins, G. D., Perlman, J. M., Rabi, Y., Reynolds, J. C., Ristagno, G., Roehr, C. C., Sakamoto, T., Sandroni, C., Sawyer, T., Schmolzer, G. M., Schnaubelt, S., Semeraro, F., Skrifvars, M. B., Smith, C. M., Smyth, M. A., Soll, R. F., Sugiura, T., Taylor-Phillips, S., Trevisanuto, D., Vaillancourt, C., Wang, T., Weiner, G. M., Welsford, M., Wigginton, J., Wyllie, J. P., Yeung, J., Nolan, J. P., Berg, K. M., COVID-19 Working Grp 2021; 169: 229-311
  • Incidence of Cardiac Interventions and Associated Cardiac Arrest Outcomes in Patients with Nonshockable Initial Rhythms and No ST Elevation Post Resuscitation. Resuscitation Harhash, A. A., May, T., Hsu, C., Seder, D. B., Dankiewicz, J., Agarwal, S., Patel, N., McPherson, J., Riker, R., Soreide, E., Hirsch, K. G., Stammet, P., Dupont, A., Forsberg, S., Rubertsson, S., Friberg, H., Nielsen, N., Mooney, M. R., Kern, K. B. 2021


    BACKGROUND: Out of Hospital Cardiac arrest (OHCA) survivors with ST elevation (STE) with or without shockable rhythms often benefit from coronary angiography (CAG) and, if indicated, percutaneous coronary intervention (PCI). However, the benefits of CAG and PCI in OHCA survivors with nonshockable rhythms (PEA/asystole) and no STE are debated.METHODS: Using the International Cardiac Arrest Registry (INTCAR 2.0), representing 44 centers in the US and Europe, comatose OHCA survivors with known presenting rhythms and post resuscitation ECGs were identified. Survival to hospital discharge, neurological recovery on discharge, and impact of CAG with or without PCI on such outcome were assessed and compared with other groups (shockable rhythms with or without STE).RESULTS: Total of 2,113 OHCA survivors were identified and described as; nonshockable/no STE (Nsh-NST) (n=940, 44.5%), shockable/no STE (Sh-NST) (n=716, 33.9%), nonshockable/STE (Nsh-ST) (n=110, 5.2%), and shockable/STE (Sh-ST) (n=347, 16.4%). Of Nsh-NST, 13.7% (129) were previously healthy before CA and only 17.3% (161) underwent CAG; of those, 30.4% (52) underwent PCI. A total of 18.6% (174) Nsh-NST patients survived to hospital discharge, with 57.5% (100) of such survivors having good neurological recovery (cerebral performance category 1 or 2) on discharge. Coronary angiography was associated with improved odds for survival and neurological recovery among all groups, including those with NSh-NST.CONCLUSIONS: Nonshockable initial rhythms with no ST elevation post resuscitation was the most common presentation after OHCA. Although most of these patients did not undergo coronary angiography, among those who did, 1 in 4 patients had a culprit lesion and underwent revascularization. Invasive CAG should be at least considered for all OHCA survivors, including those with nonshockable rhythms and no ST elevation post resuscitation. Brief Abstract Out of hospital cardiac arrest (OHCA) survivors with ST elevation and/or shockable rhythms benefit from coronary angiography and revascularization. Nonshockable cardiac arrest survivors with no ST elevation have the worst prognosis and rarely undergo coronary angiography. Nonshockable rhythms with no ST elevation was the most common presentation after OHCA and among a small subgroup underwent coronary angiography, 1 in 4 patients with had culprit lesion and underwent revascularization. Coronary angiography was associated with high prevalence of acute culprit coronary lesions and should be considered for those with a probably cardiac cause for their arres.

    View details for DOI 10.1016/j.resuscitation.2021.08.026

    View details for PubMedID 34437992

  • Beyond the 'Good' in Good Neurologic Outcome: Recovery as a Critical Link in the Chain of Survival after Cardiac Arrest. Resuscitation Vogelsong, M. A., Hirsch, K. G. 2021
  • Proceedings of the First Curing Coma Campaign NIH Symposium: Challenging the Future of Research for Coma and Disorders of Consciousness. Neurocritical care Claassen, J., Akbari, Y., Alexander, S., Bader, M. K., Bell, K., Bleck, T. P., Boly, M., Brown, J., Chou, S. H., Diringer, M. N., Edlow, B. L., Foreman, B., Giacino, J. T., Gosseries, O., Green, T., Greer, D. M., Hanley, D. F., Hartings, J. A., Helbok, R., Hemphill, J. C., Hinson, H. E., Hirsch, K., Human, T., James, M. L., Ko, N., Kondziella, D., Livesay, S., Madden, L. K., Mainali, S., Mayer, S. A., McCredie, V., McNett, M. M., Meyfroidt, G., Monti, M. M., Muehlschlegel, S., Murthy, S., Nyquist, P., Olson, D. M., Provencio, J. J., Rosenthal, E., Sampaio Silva, G., Sarasso, S., Schiff, N. D., Sharshar, T., Shutter, L., Stevens, R. D., Vespa, P., Videtta, W., Wagner, A., Ziai, W., Whyte, J., Zink, E., Suarez, J. I., Curing Coma Campaign 2021; 35 (Suppl 1): 4-23


    Coma and disorders of consciousness (DoC) are highly prevalent and constitute a burden for patients, families, and society worldwide. As part of the Curing Coma Campaign, the Neurocritical Care Society partnered with the National Institutes of Health to organize a symposium bringing together experts from all over the world to develop research targets for DoC. The conference was structured along six domains: (1) defining endotype/phenotypes, (2) biomarkers, (3) proof-of-concept clinical trials, (4) neuroprognostication, (5) long-term recovery, and (6) large datasets. This proceedings paper presents actionable research targets based on the presentations and discussions that occurred at the conference. We summarize the background, main research gaps, overall goals, the panel discussion of the approach, limitations and challenges, and deliverables that were identified.

    View details for DOI 10.1007/s12028-021-01260-x

    View details for PubMedID 34236619

  • Risk Stratification Among Survivors of Cardiac Arrest Considered for CoronaryAngiography. Journal of the American College of Cardiology Harhash, A. A., May, T. L., Hsu, C., Agarwal, S., Seder, D. B., Mooney, M. R., Patel, N., McPherson, J., McMullan, P., Riker, R., Soreide, E., Hirsch, K. G., Stammet, P., Dupont, A., Rubertsson, S., Friberg, H., Nielsen, N., Rab, T., Kern, K. B. 2021; 77 (4): 360–71


    BACKGROUND: The American College of Cardiology Interventional Council published consensus-based recommendations to help identify resuscitated cardiac arrest patients with unfavorable clinical features in whom invasive procedures are unlikely to improve survival.OBJECTIVES: This study sought to identify how many unfavorable features are required before prognosis is significantly worsened and which features are most impactful in predicting prognosis.METHODS: Using the INTCAR (International Cardiac Arrest Registry), the impact of each proposed "unfavorable feature" on survival to hospital discharge was individually analyzed. Logistic regression was performed to assess the association of such unfavorable features with poor outcomes.RESULTS: Seven unfavorable features (of 10 total) were captured in 2,508 patients successfully resuscitated after cardiac arrest (ongoing cardiopulmonary resuscitation and noncardiac etiology were exclusion criteria in our registry). Chronic kidney disease was used in lieu of end-stage renal disease. In total, 39% survived to hospital discharge. The odds ratio (OR) of survival to hospital discharge for each unfavorable feature was as follows: age >85 years OR: 0.30 (95% CI: 0.15 to 0.61), time-to-ROSC >30min OR: 0.30 (95% CI: 0.23 to 0.39), nonshockable rhythm OR: 0.39 (95% CI: 0.29 to 0.54), no bystander cardiopulmonary resuscitation OR: 0.49 (95% CI: 0.38 to 0.64), lactate >7mmol/l OR: 0.50 (95% CI: 0.40 to 0.63), unwitnessed arrest OR: 0.58 (95% CI: 0.44 to 0.78), pH<7.2 OR: 0.78 (95% CI: 0.63 to 0.98), and chronic kidney disease OR: 0.96 (95% CI: 0.70 to 1.33). The presence of any 3 or more unfavorable features predicted<40% survival. Presence of the 3 strongest risk factors (age >85 years, time-to-ROSC >30min, and non-ventricular tachycardia/ventricular fibrillation) together or ≥6 unfavorable features predicted a≤10% chance of survival to discharge.CONCLUSIONS: Patients successfully resuscitated from cardiac arrest with 6 or more unfavorable features have a poor long-term prognosis. Delaying or even forgoing invasive procedures in such patients is reasonable.

    View details for DOI 10.1016/j.jacc.2020.11.043

    View details for PubMedID 33509392

  • Influence of sex on survival, neurologic outcomes, and neurodiagnostic testing after out-of-hospital cardiac arrest. Resuscitation Vogelsong, M. A., May, T., Agarwal, S., Cronberg, T., Dankiewicz, J., Dupont, A., Friberg, H., Hand, R., McPherson, J., Mlynash, M., Mooney, M., Nielsen, N., O'Riordan, A., Patel, N., Riker, R. R., Seder, D. B., Soreide, E., Stammet, P., Xiong, W., Hirsch, K. G. 2021


    Previous studies evaluating the relationship between sex and post-resuscitation care and outcomes following out-of-hospital cardiac arrest (OHCA) are conflicting. We investigated the association between sex and outcomes as well as neurodiagnostic testing in a prospective multicenter international registry of patients admitted to intensive care units following OHCA.OHCA survivors enrolled in the International Cardiac Arrest Registry (INTCAR) from 2012-2017 were included. We assessed the independent association between sex and survival to hospital discharge, good neurologic outcome (Cerebral Performance Category 1 or 2), neurodiagnostic testing, and withdrawal of life-sustaining therapy (WLST).Of 2,407 eligible patients, 809 (33.6%) were women. Baseline characteristics differed by sex, with less bystander CPR and initial shockable rhythms among women. Women were less likely to survive to hospital discharge, however significance abated following adjusted analysis (30.1% vs 42.7%, adjusted OR 0.85, 95% CI 0.67-1.08). Women were less likely to have good neurologic outcome at discharge (21.4% vs 34.0%, adjusted OR 0.74, 95% CI 0.57-0.96) and at six months post-arrest (16.7% vs 29.4%, adjusted OR 0.73, 95% CI 0.54-0.98) that persisted after adjustment. Neuroimaging (75.5% vs 74.3%, p=0.54) and other neurophysiologic testing (78.8% vs 78.6%, p=0.91) was similar across sex. Women were more likely to undergo WLST (55.6% vs 42.8%, adjusted OR 1.35, 95% CI 1.09-1.66).Women with cardiac arrest have lower odds of good neurologic outcomes and higher odds of WLST, despite comparable rates of neurodiagnostic testing and after controlling for baseline differences in clinical characteristics and cardiac arrest features.

    View details for DOI 10.1016/j.resuscitation.2021.07.037

    View details for PubMedID 34363853

  • Part 3: Adult Basic and Advanced Life Support 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care CIRCULATION Panchal, A. R., Bartos, J. A., Cabanas, J. G., Donnino, M. W., Drennan, I. R., Hirsch, K. G., Kudenchuk, P. J., Kurz, M. C., Lavonas, E. J., Morley, P. T., O'Neil, B. J., Peberdy, M., Rittenberger, J. C., Rodriguez, A. J., Sawyer, K. N., Berg, K. M., Adv Life Support Writing Grp 2020; 142: S366–S468

    View details for DOI 10.1161/CIR.0000000000000916

    View details for Web of Science ID 000589620700003

    View details for PubMedID 33081529

  • The association of partial pressures of oxygen and carbon dioxide with neurological outcome after out-of-hospital cardiac arrest: an explorative International Cardiac Arrest Registry 2.0 study. Scandinavian journal of trauma, resuscitation and emergency medicine Ebner, F., Riker, R. R., Haxhija, Z., Seder, D. B., May, T. L., Ullen, S., Stammet, P., Hirsch, K., Forsberg, S., Dupont, A., Friberg, H., McPherson, J. A., Soreide, E., Dankiewicz, J., Cronberg, T., Nielsen, N. 2020; 28 (1): 67


    BACKGROUND: Exposure to extreme arterial partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2) following the return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA) is common and may affect neurological outcome but results of previous studies are conflicting.METHODS: Exploratory study of the International Cardiac Arrest Registry (INTCAR) 2.0 database, including 2162 OHCA patients with ROSC in 22 intensive care units in North America and Europe. We tested the hypothesis that exposure to extreme PaO2 or PaCO2 values within 24h after OHCA is associated with poor neurological outcome at discharge. Our primary analyses investigated the association between extreme PaO2 and PaCO2 values, defined as hyperoxemia (PaO2>40kPa), hypoxemia (PaO2<8.0kPa), hypercapnemia (PaCO2>6.7kPa) and hypocapnemia (PaCO2<4.0kPa) and neurological outcome. The secondary analyses tested the association between the exposure combinations of PaO2>40kPa with PaCO2<4.0kPa and PaO2 8.0-40kPa with PaCO2>6.7kPa and neurological outcome. To define a cut point for the onset of poor neurological outcome, we tested a model with increasing and decreasing PaO2 levels and decreasing PaCO2 levels. Cerebral Performance Category (CPC), dichotomized to good (CPC 1-2) and poor (CPC 3-5) was used as outcome measure.RESULTS: Of 2135 patients eligible for analysis, 700 were exposed to hyperoxemia or hypoxemia and 1128 to hypercapnemia or hypocapnemia. Our primary analyses did not reveal significant associations between exposure to extreme PaO2 or PaCO2 values and neurological outcome (P=0.13-0.49). Our secondary analyses showed no significant associations between combinations of PaO2 and PaCO2 and neurological outcome (P=0.11-0.86). There was no PaO2 or PaCO2 level significantly associated with poor neurological outcome. All analyses were adjusted for relevant co-variates.CONCLUSIONS: Exposure to extreme PaO2 or PaCO2 values in the first 24h after OHCA was common, but not independently associated with neurological outcome at discharge.

    View details for DOI 10.1186/s13049-020-00760-7

    View details for PubMedID 32664989

  • Prognostic value of diffusion-weighted MRI for post-cardiac arrest coma. Neurology Hirsch, K. G., Fischbein, N., Mlynash, M., Kemp, S., Bammer, R., Eyngorn, I., Tong, J., Moseley, M., Venkatasubramanian, C., Caulfield, A. F., Albers, G. 2020


    OBJECTIVE: To validate quantitative diffusion-weighted imaging (DWI) MRI thresholds that correlate with poor outcome in comatose cardiac arrest survivors, we conducted a clinician-blinded study and prospectively obtained MRIs from comatose patients after cardiac arrest.METHODS: Consecutive comatose post-cardiac arrest adult patients were prospectively enrolled. MRIs obtained within 7 days after arrest were evaluated. The clinical team was blinded to the DWI MRI results and followed a prescribed prognostication algorithm. Apparent diffusion coefficient (ADC) values and thresholds differentiating good and poor outcome were analyzed. Poor outcome was defined as a Glasgow Outcome Scale score of ≤2 at 6 months after arrest.RESULTS: Ninety-seven patients were included, and 75 patients (77%) had MRIs. In 51 patients with MRI completed by postarrest day 7, the prespecified threshold of >10% of brain tissue with an ADC <650 *10-6 mm2/s was highly predictive for poor outcome with a sensitivity of 0.63 (95% confidence interval [CI] 0.42-0.80), a specificity of 0.96 (95% CI 0.77-0.998), and a positive predictive value (PPV) of 0.94 (95% CI 0.71-0.997). The mean whole-brain ADC was higher among patients with good outcomes. Receiver operating characteristic curve analysis showed that ADC <650 *10-6 mm2/s had an area under the curve of 0.79 (95% CI 0.65-0.93, p < 0.001). Quantitative DWI MRI data improved prognostication of both good and poor outcomes.CONCLUSIONS: This prospective, clinician-blinded study validates previous research showing that an ADC <650 *10-6 mm2/s in >10% of brain tissue in an MRI obtained by postarrest day 7 is highly specific for poor outcome in comatose patients after cardiac arrest.

    View details for DOI 10.1212/WNL.0000000000009289

    View details for PubMedID 32269116

  • A Standardized Checklist Improves the Transfer of Stroke Patients from the Neurocritical Care Unit to Hospital Ward. The Neurohospitalist Murray, N. M., Joshi, A. N., Kronfeld, K., Hobbs, K., Bernier, E., Hirsch, K. G., Gold, C. A. 2020; 10 (2): 100-108


    The transfer of patients with ischemic stroke from the intensive care unit (ICU) to noncritical care inpatient wards involves detailed information sharing between care teams. Our local transfer process was not standardized, leading to potential patient risk. We developed and evaluated an "ICU Transfer Checklist" to standardize communication between the neurocritical care team and the stroke ward team.Retrospective review of consecutive patients with ischemic stroke admitted to the neurocritical care unit who were transferred to the stroke ward was used to characterize transfer documentation. A multidisciplinary team developed and implemented an ICU Transfer Checklist that contained a synthesis of the patient's clinical course, immediate "to-do" action items, and a system-based review of active medical problems. Postintervention checklist utilization was recorded for 8 months, and quality metrics for the postintervention cohort were compared to the preintervention cohort. Providers were surveyed pre- and postintervention to characterize perceived workflow and quality of care.Patients before (n = 52) and after (n = 81) ICU Transfer Checklist implementation had similar demographic and clinical characteristics. In the postchecklist implementation period, the ICU Transfer Checklist was used in over 85% of patients and median hospital length of stay (LOS) decreased (8.6 days vs 5.4 days, P = .003), while ICU readmission rate remained low. The checklist was associated with improved perceptions of safety and decreased time needed to transfer patients.Use of the standardized ICU Transfer Checklist was associated with decreased hospital LOS and with improvements in providers' perceptions of patient safety.

    View details for DOI 10.1177/1941874419873810

    View details for PubMedID 32373272

    View details for PubMedCentralID PMC7191660

  • A Standardized Checklist Improves the Transfer of Stroke Patients from the Neurocritical Care Unit to Hospital Ward NEUROHOSPITALIST Murray, N. M., Joshi, A. N., Kronfeld, K., Hobbs, K., Bernier, E., Hirsch, K. G., Gold, C. A. 2020; 10 (2): 100–108
  • Global Survey of Outcomes of Neurocritical Care Patients: Analysis of the PRINCE Study Part 2 NEUROCRITICAL CARE Rao, C., Suarez, J., Martin, R. H., Bauza, C., Georgiadis, A., Calvillo, E., Hemphill, J., Sung, G., Oddo, M., Taccone, F., LeRoux, P. D., Domeniconi, G., Alberto Camputaro, L., Villalobos, M., Allasia, M., Goldenberg, F. D., Teran, M. D., Rosciani, F., Alvarez, H., Costilla, M., Videtta, W., Perez, D., Raffa, P., Seppelt, I., Rodgers, H., Paxton, J., Bhonagiri, D., Aneman, A., Jenkinson, E., Bradford, C., Finfer, S., Yarad, E., Bass, F., Hammond, N., O'Connor, A., Bird, S., Smith, R., Barge, D., Shilkin, J., Woods, W., Roberts, B., O'Leary, M., Vallance, S., Helbok, R., Beer, R., Pfaulser, B., Schiefecker, A., Almemari, A., Mukaddam, S., Taccone, F. S., Wittebole, X., Berghe, C., Dujardin, M., Renard, S., Hantson, P., Biston, P., Meyfroidt, G., Ferreira da Silva, I., de Oliveira, J., Reao Neto, A., Sala Domingues, J., de Azambuja Rodrigues, P., Teitelbaum, J., Chapman, M., McCredie, V., Marinoff, N., Perez, A., Kutsogiannis, D., Bernard, F., Kramer, A., Moretti, J., Aguilera, S., Poch, E. J., Romero, C., Wong, G. C., Song, J., Xu, G., Mejia-Mantilla, J. H., Madrinan-Navia, H., Martinez, J. E., Elena Ochoa, M., Bautista, D., Varga, M., Gomez, M., Diego Ciro, J., Gil, B., Murillo, R., Hernandez, O., Ramirez-Arce, J., Breitenfeld, T., Lacerda Gallardo, A. J., Lopez Delgado, H. J., Yunen Gonzalez, J., Hache-Marliere, M., Pinto, D., Llano, M., Salgado, E., Jibaja, M., Wright, J. C., Harvey, D., Verma, V., Hopkins, P., Chan, A., Welbourne, J., Dowling, S., Katila, A., Lasocki, S., Wartenberg, K., Hobohm, C., Poli, S., Schirotzek, I., Bosel, J., Schoenenberger, S., Francken, S., Shieber, S., Kern, A., Falla, J., Avalos Herrera, E., Gilvaz, P. C., Goyal, K., Sokhal, N., Sohal, J., Aggarwal, D. G., Ray, B., Pattnaik, S., Garg, S., Dixit, S., Rawal, R., Samavedam, S., Madhusudan, M., Paul, G., Mishra, S., Shushma, P., Shukla, U., Sinha, V., Vanamoorthy, P., Vadi, S., Mokhtari, M., Rasulo, F., Pegoli, M., Bilotta, F., Nagayama, M., Kobata, H., Vosylius, S., Malin Abdullah, J., Franco Granillo, J., Mijangos-Mendez, J., Horn, J., Muller, M. A., Kuiper, M., Abdo, W. F., McArthur, C., Newby, L., Hashmi, M., Shiraz, S., Castillo Abrego, G., Bautista Coronel, E., Saldarriaga Rivera, O., Cam Paucar, J., Gomez, O., Palo, J., Lokin, J., Misiewska-Kaczur, A., Dias, C., Amorim, P., Andre, S., Rodriguez-Vega, G., Gritsan, A., Titova, Y., Al Jabbary, A., Al Zahrani, A., Pelunkova, L., Zraiki, H., Deeb, A. M., Al Bshabshe, A., Al-Jehani, H., Al-Suwaidan, F., Svigelj, V., Ramos-Gomez, L. A., Aguilar, G., Badenes, R., Llopart Pou, J., Zavala, E., Bernal Julian, F., Galarza Barrachina, L., Vidal Tegedor, B., Altaba Tena, S., Romero Krauchi, O., Tamayo, G., Sanchez, B., Gonzalezluengo, R., Puvanendiran, S., Merlani, P., Laiwattana, D., Promsin, P., Nazliel, B., Eriksson, E., Chalela, J., Miller, D. W., Guisado, R., Gordon, E., Murthy, H. K., Paulson, A., Rajajee, V., Sheehan, K., Williamson, C., Ball, R., Allan, P., Berkeley, J., Muehlschlegel, S., Carandang, R., Hall, W., Sarwal, A., Damani, R., Maldonado, N., Tan, B., Gupta, P., Lazaridis, C., Bershad, E. M., Ansari, S., Martinez, J., Singares, E., Manno, E., Provencio, J., Chaudhry, B., McBride, M., Dhar, R., Roberts, D., Allen, M., Schumacher, H. C., Habre, W., Sheth, K., Greer, D., Kunze, K., Varelas, P., Tack, L., Porter, N., Junker, C., Rodricks, M., Tuppeny, M., Basignani, C., Napolitano, S., Anderson, G., Donaldson, K., Davis, R., Sternberg, S., Giraldo, E. A., Tran, H., Coplin, W. M., Badjatia, N., Fathy, A., Reshi, R. A., Bonomo, J., Seder, D., Connolyy, L. S., McCrum, B., Carter, T., Treggiari, M., Dickinson, M., Rison, R. A., Mirski, M., John, S., Bleck, T. P., Malek, A., Trim, T., Smith, M., Athar, M., Rincon, F., Altaweel, L., Vespa, P., Emanuel, B., Eskiogly, E., McNett, M., Sukumaran, A., Shutter, L., Milzman, D., Glassner, S., OPhelan, K., Rosenthal, E., Hemphill, J. C., Kottapally, M., Smith, W. S., Ko, N., Josephson, S. A., Kim, A., Singhal, N. S., Ahmad, A., Meeker, M., Hirsch, K. G., Nair, D., Chou, S., Santos, G., Clark, S., Feske, S., Henderson, G., Sorond, F., Vaitkevicius, H., Chung, D., Kim, J., Amatangelo, M., Kapinos, G., Torbey, M., Kahn, D., Chang, C., Koenig, M., Gorman, M., Langdon, J. R., Dissin, J., Cross, L., Peled, H., Claassen, J., Ali, A., Layon, A., Miller, A., Wilensky, E., Kumar, M., Levine, J. M., Maldonado, I. L., Schneck, M., Lele, A., Sarma, A. K., Yazbeck, M. F., Johnston, G., Jarquin-Valdivia, A. A., Johnson, L., Kuisle, L., Sajjad, R., Glickman, S., Garvin, R., Parra, A., DeFilippis, M., Fletcher, J. J., Freeman, W., Rao, V. A., Olmecah, H., Dugan, G., Medary, I. B., Hoesch, R., Brehaut, S. S., Afshinnik, A., Moreda, M., Graffagnino, C., Laskowitz, D. T., Naidech, A., Francis, B., Berman, M., Tesoro, E., Medow, J., Jordan, D., Aiyagari, V., Rosengart, A., De Georgia, M., Bowling, S., Sharaby, M., Nathan, B., Landry, R., Hebert, C., Hubner, K. E., Karanjia, N., Hightower, B., Cummings, K., Kirkwood, J., Frank, J., Hassan, A., Sanchez, O., Cordina, S., Mora, J., Tuan Van Bui, PRINCE Study Investigators 2020; 32 (1): 88–103


    Neurocritical care is devoted to the care of critically ill patients with acute neurological or neurosurgical emergencies. There is limited information regarding epidemiological data, disease characteristics, variability of clinical care, and in-hospital mortality of neurocritically ill patients worldwide. We addressed these issues in the Point PRevalence In Neurocritical CarE (PRINCE) study, a prospective, cross-sectional, observational study.We recruited patients from various intensive care units (ICUs) admitted on a pre-specified date, and the investigators recorded specific clinical care activities they performed on the subjects during their first 7 days of admission or discharge (whichever came first) from their ICUs and at hospital discharge. In this manuscript, we analyzed the final data set of the study that included patient admission characteristics, disease type and severity, ICU resources, ICU and hospital length of stay, and in-hospital mortality. We present descriptive statistics to summarize data from the case report form. We tested differences between geographically grouped data using parametric and nonparametric testing as appropriate. We used a multivariable logistic regression model to evaluate factors associated with in-hospital mortality.We analyzed data from 1545 patients admitted to 147 participating sites from 31 countries of which most were from North America (69%, N = 1063). Globally, there was variability in patient characteristics, admission diagnosis, ICU treatment team and resource allocation, and in-hospital mortality. Seventy-three percent of the participating centers were academic, and the most common admitting diagnosis was subarachnoid hemorrhage (13%). The majority of patients were male (59%), a half of whom had at least two comorbidities, and median Glasgow Coma Scale (GCS) of 13. Factors associated with in-hospital mortality included age (OR 1.03; 95% CI, 1.02 to 1.04); lower GCS (OR 1.20; 95% CI, 1.14 to 1.16 for every point reduction in GCS); pupillary reactivity (OR 1.8; 95% CI, 1.09 to 3.23 for bilateral unreactive pupils); admission source (emergency room versus direct admission [OR 2.2; 95% CI, 1.3 to 3.75]; admission from a general ward versus direct admission [OR 5.85; 95% CI, 2.75 to 12.45; and admission from another ICU versus direct admission [OR 3.34; 95% CI, 1.27 to 8.8]); and the absence of a dedicated neurocritical care unit (NCCU) (OR 1.7; 95% CI, 1.04 to 2.47).PRINCE is the first study to evaluate care patterns of neurocritical patients worldwide. The data suggest that there is a wide variability in clinical care resources and patient characteristics. Neurological severity of illness and the absence of a dedicated NCCU are independent predictors of in-patient mortality.

    View details for DOI 10.1007/s12028-019-00835-z

    View details for Web of Science ID 000512861100004

    View details for PubMedID 31486027

  • Will We Ever Make Headway in Severe Traumatic Brain Injury Treatment Trials? JAMA neurology Murray, N. M., Threlkeld, Z. D., Hirsch, K. G. 2020

    View details for DOI 10.1001/jamaneurol.2019.4672

    View details for PubMedID 31961381

  • Unsupervised learning of early post-arrest brain injury phenotypes. Resuscitation Elmer, J. n., Coppler, P. J., May, T. L., Hirsch, K. n., Faro, J. n., Solanki, P. n., Brown, M. n., Puyana, J. S., Rittenberger, J. C., Callaway, C. W. 2020


    Trials may be neutral when they do not appropriately target the experimental intervention. We speculated multimodality assessment of early hypoxic-ischemic brain injury would identify phenotypes likely to benefit from therapeutic interventions.We performed a retrospective study including comatose patients resuscitated from out-of-hospital cardiac arrest (OHCA) by one of 126 emergency medical services or in-hospital arrest at one of 26 hospitals from 2011 to 2019. All patients were ultimately transported to a single tertiary center for care including standardized initial neurological examination, brain imaging and electroencephalography; targeted temperature management (TTM); hemodynamic optimization targeting mean arterial pressure (MAP) >80mmHg; and, coronary angiography for clinical suspicion for acute coronary syndrome. We used unsupervised learning to identify brain injury phenotypes defined by admission neurodiagnostics. We tested for interactions between phenotype and TTM, hemodynamic management and cardiac catheterization in models predicting recovery.We included 1,086 patients with mean (SD) age 58 (17) years of whom 955 (88%) were resuscitated from OHCA. Survival to hospital discharge was 27%, and 248 (23%) were discharged with Cerebral Performance Category (CPC) 1-3. We identified 5 clusters defining distinct brain injury phenotypes, each comprising 14% to 30% of the cohort with discharge CPC 1-3 in 59% to<1%. We found significant interactions between cluster and TTM strategy (P=0.01), MAP (P<0.001) and coronary angiography (P=0.04) in models predicting outcomes.We identified patterns of early hypoxic-ischemic injury based on multiple diagnostic modalities that predict responsiveness to several therapeutic interventions recently tested in neutral clinical trials.

    View details for DOI 10.1016/j.resuscitation.2020.05.051

    View details for PubMedID 32531403

  • Early Head Computed Tomography Abnormalities Associated with Elevated Intracranial Pressure in Severe Traumatic Brain Injury. Journal of neuroimaging : official journal of the American Society of Neuroimaging Murray, N. M., Wolman, D. N., Mlynash, M. n., Threlkeld, Z. D., Christensen, S. n., Heit, J. J., Harris, O. A., Hirsch, K. G. 2020


    Intracranial pressure (ICP) monitoring is recommended in severe traumatic brain injury (sTBI), yet invasive monitoring has risks, and many patients do not develop elevated ICP. Tools to identify patients at risk for ICP elevation are limited. We aimed to identify early radiologic biomarkers of ICP elevation.In this retrospective study, we analyzed a prospectively enrolled cohort of patients with a sTBI at an academic level 1 trauma center. Inclusion criteria were nonpenetrating TBI, age ≥16 years, Glasgow Coma Scale (GCS) score ≤8, and presence of an ICP monitor. Two independent reviewers manually evaluated 30 prespecified features on serial head computed tomography (CTs). Patient characteristics and radiologic features were correlated with elevated ICP. The primary outcome was clinically relevant ICP elevation, defined as ICP ≥ 20 mm Hg on at least 5 or more hourly recordings during postinjury days 0-7 with concurrent administration of an ICP-lowering treatment.Among 111 sTBI patients, the median GCS was 6 (interquartile range 3-8), and 45% had elevated ICP. Features associated with elevated ICP were younger age (every 10-year decrease, odds ratio [OR] 1.4), modified Fisher scale (mFS) score at 0-4 hours postinjury (every 1 point, OR 1.8), and combined volume of contusional hemorrhage and peri-hematoma edema (10 ml, OR 1.2) at 4-18 hours postinjury.Younger age, mFS score, and volume of contusion are associated with ICP elevation in patients with a sTBI. Imaging features may stratify patients by their risk of subsequent ICP elevation.

    View details for DOI 10.1111/jon.12799

    View details for PubMedID 33146933

  • Guidelines for the Acute Treatment of Cerebral Edema in Neurocritical Care Patients. Neurocritical care Cook, A. M., Morgan Jones, G. n., Hawryluk, G. W., Mailloux, P. n., McLaughlin, D. n., Papangelou, A. n., Samuel, S. n., Tokumaru, S. n., Venkatasubramanian, C. n., Zacko, C. n., Zimmermann, L. L., Hirsch, K. n., Shutter, L. n. 2020


    Acute treatment of cerebral edema and elevated intracranial pressure is a common issue in patients with neurological injury. Practical recommendations regarding selection and monitoring of therapies for initial management of cerebral edema for optimal efficacy and safety are generally lacking. This guideline evaluates the role of hyperosmolar agents (mannitol, HTS), corticosteroids, and selected non-pharmacologic therapies in the acute treatment of cerebral edema. Clinicians must be able to select appropriate therapies for initial cerebral edema management based on available evidence while balancing efficacy and safety.The Neurocritical Care Society recruited experts in neurocritical care, nursing, and pharmacy to create a panel in 2017. The group generated 16 clinical questions related to initial management of cerebral edema in various neurological insults using the PICO format. A research librarian executed a comprehensive literature search through July 2018. The panel screened the identified articles for inclusion related to each specific PICO question and abstracted necessary information for pertinent publications. The panel used GRADE methodology to categorize the quality of evidence as high, moderate, low, or very low based on their confidence that the findings of each publication approximate the true effect of the therapy.The panel generated recommendations regarding initial management of cerebral edema in neurocritical care patients with subarachnoid hemorrhage, traumatic brain injury, acute ischemic stroke, intracerebral hemorrhage, bacterial meningitis, and hepatic encephalopathy.The available evidence suggests hyperosmolar therapy may be helpful in reducing ICP elevations or cerebral edema in patients with SAH, TBI, AIS, ICH, and HE, although neurological outcomes do not appear to be affected. Corticosteroids appear to be helpful in reducing cerebral edema in patients with bacterial meningitis, but not ICH. Differences in therapeutic response and safety may exist between HTS and mannitol. The use of these agents in these critical clinical situations merits close monitoring for adverse effects. There is a dire need for high-quality research to better inform clinicians of the best options for individualized care of patients with cerebral edema.

    View details for DOI 10.1007/s12028-020-00959-7

    View details for PubMedID 32227294

  • 2019 American Heart Association Focused Update on Systems of Care: Dispatcher-Assisted Cardiopulmonary Resuscitation and Cardiac Arrest Centers An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care CIRCULATION Panchal, A. R., Berg, K. M., Cabanas, J. G., Kurz, M. C., Link, M. S., Del Rios, M., Hirsch, K. G., Chan, P. S., Hazinski, M., Morley, P. T., Donnino, M. W., Kudenchuk, P. J. 2019; 140 (24): E895–E903


    Survival after out-of-hospital cardiac arrest requires an integrated system of care (chain of survival) between the community elements responding to an event and the healthcare professionals who continue to care for and transport the patient for appropriate interventions. As a result of the dynamic nature of the prehospital setting, coordination and communication can be challenging, and identification of methods to optimize care is essential. This 2019 focused update to the American Heart Association systems of care guidelines summarizes the most recent published evidence for and recommendations on the use of dispatcher-assisted cardiopulmonary resuscitation and cardiac arrest centers. This article includes the revised recommendations that emergency dispatch centers should offer and instruct bystanders in cardiopulmonary resuscitation during out-of-hospital cardiac arrest and that a regionalized approach to post-cardiac arrest care may be reasonable when comprehensive postarrest care is not available at local facilities.

    View details for DOI 10.1161/CIR.0000000000000733

    View details for Web of Science ID 000508367200005

    View details for PubMedID 31722563

  • 2019 American Heart Association Focused Update on Advanced Cardiovascular Life Support Use of Advanced Airways, Vasopressors, and Extracorporeal Cardiopulmonary Resuscitation During Cardiac Arrest An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care CIRCULATION Panchal, A. R., Berg, K. M., Hirsch, K. G., Kudenchuk, P. J., Del Rios, M., Cabanas, J. G., Link, M. S., Kurz, M. C., Chan, P. S., Morley, P. T., Hazinski, M., Donnino, M. W. 2019; 140 (24): E881–E894


    The fundamentals of cardiac resuscitation include the immediate provision of high-quality cardiopulmonary resuscitation combined with rapid defibrillation (as appropriate). These mainstays of therapy set the groundwork for other possible interventions such as medications, advanced airways, extracorporeal cardiopulmonary resuscitation, and post-cardiac arrest care, including targeted temperature management, cardiorespiratory support, and percutaneous coronary intervention. Since 2015, an increased number of studies have been published evaluating some of these interventions, requiring a reassessment of their use and impact on survival from cardiac arrest. This 2019 focused update to the American Heart Association advanced cardiovascular life support guidelines summarizes the most recent published evidence for and recommendations on the use of advanced airways, vasopressors, and extracorporeal cardiopulmonary resuscitation during cardiac arrest. It includes revised recommendations for all 3 areas, including the choice of advanced airway devices and strategies during cardiac arrest (eg, bag-mask ventilation, supraglottic airway, or endotracheal intubation), the training and retraining required, the administration of standard-dose epinephrine, and the decisions involved in the application of extracorporeal cardiopulmonary resuscitation and its potential impact on cardiac arrest survival.

    View details for DOI 10.1161/CIR.0000000000000732

    View details for Web of Science ID 000508367200004

    View details for PubMedID 31722552

  • Functional outcomes associated with varying levels of targeted temperature management after out-of-hospital cardiac arrest - An INTCAR2 registry analysis. Resuscitation Johnsson, J., Wahlstrom, J., Dankiewicz, J., Annborn, M., Agarwal, S., Dupont, A., Forsberg, S., Friberg, H., Hand, R., Hirsch, K. G., May, T., McPherson, J. A., Mooney, M. R., Patel, N., Riker, R. R., Stammet, P., Soreide, E., Seder, D. B., Nielsen, N. 2019


    INTRODUCTION: Targeted temperature management (TTM) after out-of-hospital cardiac arrest (OHCA) has been recommended in international guidelines since 2005. The TTM-trial published in 2013 showed no difference in survival or neurological outcome for patients randomised to 33°C or 36°C, and many hospitals have changed practice. The optimal utilization of TTM is still debated. This study aimed to analyse if a difference in temperature goal was associated with outcome in an unselected international registry population.METHODS: This is a retrospective observational study based on a prospective registry - the International Cardiac Arrest Registry 2. Patients were categorized as receiving TTM in the lower range at 32-34°C (TTM-low) or at 35-37°C (TTM-high). Primary outcome was good functional status defined as cerebral performance category (CPC) of 1-2 at hospital discharge and secondary outcome was adverse events related to TTM. A logistic regression model was created to evaluate the independent effect of temperature by correcting for clinical and demographic factors associated with outcome.RESULTS: Of 1710 patients included, 1242 (72,6%) received TTM-low and 468 (27,4%) TTM-high. In patients receiving TTM-low, 31.3% survived with good outcome compared to 28.8% in the TTM-high group. There was no significant association between temperature and outcome (p=0.352). In analyses adjusted for baseline differences the OR for a good outcome with TTM-low was 1.27, 95% CI (0.94-1.73). Haemodynamic instability leading to discontinuation of TTM was more common in TTM-low.CONCLUSIONS: No significant difference in functional outcome at hospital discharge was found in patients receiving lower- versus higher targeted temperature management.

    View details for DOI 10.1016/j.resuscitation.2019.10.020

    View details for PubMedID 31706964

  • Correction to: Variability in functional outcome and treatment practices by treatment center after out-of-hospital cardiac arrest: analysis of International Cardiac Arrest Registry. Intensive care medicine May, T. L., Lary, C. W., Riker, R. R., Friberg, H., Patel, N., Soreide, E., McPherson, J. A., Unden, J., Hand, R., Sunde, K., Stammet, P., Rubertsson, S., Belohlvaek, J., Dupont, A., Hirsch, K. G., Valsson, F., Kern, K., Sadaka, F., Israelsson, J., Dankiewicz, J., Nielsen, N., Seder, D. B., Agarwal, S. 2019


    The original version of this article unfortunately contained a mistake.

    View details for DOI 10.1007/s00134-019-05687-x

    View details for PubMedID 31317207

  • Early withdrawal of life support after resuscitation from cardiac arrest is common and may result in additional deaths RESUSCITATION Teresa, M. L., Robin, R., Richard, R. R., Hans, F., Nainesh, P., Eldar, S., Robert, H., Pascal, S., Allison, D., Karen, H. G., Sachin, A., Michael, W. J., Josef, D., Niklas, N., David, S. B., David, K. M. 2019; 139: 308–13
  • Translating Protective Hypothermia During Cardiac Arrest Into Clinical Practice JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Hirsch, K. G., Callaway, C. W. 2019; 321 (17): 1673–75
  • Variability in functional outcome and treatment practices by treatment center after out-of-hospital cardiac arrest: analysis of International Cardiac Arrest Registry INTENSIVE CARE MEDICINE May, T. L., Lary, C. W., Riker, R. R., Friberg, H., Patel, N., Soreide, E., McPherson, J. A., Unden, J., Hand, R., Sunde, K., Stammet, P., Rubertsson, S., Belohlvaek, J., Dupont, A., Hirsch, K. G., Valsson, F., Kern, K., Sadaka, F., Israelsson, J., Dankiewicz, J., Nielsen, N., Seder, D. B., Agarwal, S. 2019; 45 (5): 637–46
  • Variability in functional outcome and treatment practices by treatment center after out-of-hospital cardiac arrest: analysis of International Cardiac Arrest Registry. Intensive care medicine May, T. L., Lary, C. W., Riker, R. R., Friberg, H., Patel, N., Soreide, E., McPherson, J. A., Unden, J., Hand, R., Sunde, K., Stammet, P., Rubertsson, S., Belohlvaek, J., Dupont, A., Hirsch, K. G., Valsson, F., Kern, K., Sadaka, F., Israelsson, J., Dankiewicz, J., Nielsen, N., Seder, D. B., Agarwal, S. 2019


    PURPOSE: Functional outcomes vary between centers after out-of-hospital cardiac arrest (OHCA) and are partially explained by pre-existing health status and arrest characteristics, while the effects of in-hospital treatments on functional outcome are less understood. We examined variation in functional outcomes by center after adjusting for patient- and arrest-specific characteristics and evaluated how in-hospital management differs between high- and low-performing centers.METHODS: Analysis of observational registry data within the International Cardiac Arrest Registry was used to perform a hierarchical model of center-specific risk standardized rates for good outcome, adjusted for demographics, pre-existing functional status, and arrest-related factors with treatment center as a random effect variable. We described the variability in treatments and diagnostic tests that may influence outcome at centers with adjusted rates significantly above and below registry average.RESULTS: A total of 3855 patients were admitted to an ICU following cardiac arrest with return of spontaneous circulation. The overall prevalence of good outcome was 11-63% among centers. After adjustment, center-specific risk standardized rates for good functional outcome ranged from 0.47 (0.37-0.58) to 0.20 (0.12-0.26). High-performing centers had faster time to goal temperature, were more likely to have goal temperature of 33°C, more likely to perform unconscious cardiac catheterization and percutaneous coronary intervention, and had differing prognostication practices than low-performing centers.CONCLUSIONS: Center-specific differences in outcomes after OHCA after adjusting for patient-specific factors exist. This variation could partially be explained by in-hospital management differences. Future research should address the contribution of these factors to the differences in outcomes after resuscitation.

    View details for PubMedID 30848327

  • Early withdrawal of life support after resuscitation from cardiac arrest is common and may result in additional deaths. Resuscitation May, T. L., Ruthazer, R., Riker, R. R., Friberg, H., Patel, N., Soreide, E., Hand, R., Stammet, P., Dupont, A., Hirsch, K. G., Agarwal, S., Wanscher, M. J., Dankiewicz, J., Nielsen, N., Seder, D. B., Kent, D. M. 2019


    AIM: "Early" withdrawal of life support therapies (eWLST) within the first 3 calendar days after resuscitation from cardiac arrest (CA) is discouraged. We evaluated a prospective multicenter registry of patients admitted to hospitals after resuscitation from CA to determine predictors of eWLST and estimate its impact on outcomes.METHODS: CA survivors enrolled from 2012-2017 in the International Cardiac Arrest Registry (INTCAR) were included. We developed a propensity score for eWLST and matched a cohort with similar probabilities of eWLST who received ongoing care. The incidence of good outcome (Cerebral Performance Category of 1 or 2) was measured across deciles of eWLST in the matched cohort.RESULTS: 2688 patients from 24 hospitals were included. Median ischemic time was 20 (IQR 11, 30) minutes, and 1148 (43%) had an initial shockable rhythm. Withdrawal of life support occurred in 1162 (43%) cases, with 459 (17%) classified as eWLST. Older age, initial non-shockable rhythm, increased ischemic time, shock on admission, out-of-hospital arrest, and admission in the United States were each independently associated with eWLST. All patients with eWLST died, while the matched cohort, good outcome occurred in 21% of patients. 19% of patients within the eWLST group were predicted to have a good outcome, had eWLST not occurred.CONCLUSIONS: Early withdrawal of life support occurs frequently after cardiac arrest. Although the mortality of patients matched to those with eWLST was high, these data showed excess mortality with eWLST.

    View details for PubMedID 30836171

  • Translating Protective Hypothermia During Cardiac Arrest Into Clinical Practice. JAMA Hirsch, K. G., Callaway, C. W. 2019; 321 (17): 1673–75

    View details for PubMedID 31063554

  • The Prognostic Value of Quantitative Diffusion-Weighted MRI after Pediatric Cardiopulmonary Arrest. Resuscitation Yacoub, M., Birchansky, B., Mlynash, M., Berg, M., Knight, L., Hirsch, K. G., Su, F., Revive Initiative at Stanford Childrens Health 2018


    OBJECTIVES: The prognostic value of quantitative diffusion-weighted magnetic resonance imaging (DWI MRI) in predicting neurologic outcomes after pediatric cardiopulmonary arrest (CPA) has not been determined. The aim of this study was to identify a DWI MRI threshold for brain volume percent that correlates with neurologic outcome in children who remain comatose or display significant neurologic deficits immediately after resuscitation from CPA.METHODS: This single-center retrospective study analyzed DWI MRIs of pediatric patients who remained neurologically impaired after CPA. Any MRI obtained within 2 weeks after CPA was analyzed. The apparent diffusion coefficient (ADC) value of each voxel within the brain was determined. Percentage brain volume with voxels below each ADC threshold between 300-1200 * 10-6 mm2/s with a step of 50 were calculated. Area under the receiver operating characteristics curve (AUC) was used to identify optimal DWI MRI thresholds for brain volume percent most predictive of poor neurologic outcome. The primary outcome measure was neurologic outcome 6-months after CPA based on Pediatric Cerebral Performance Category (PCPC) score. Poor neurologic outcome was defined as PCPC score of 3-6, or a worsening from baseline score ≥ 1 if baseline PCPC score was ≥ 3.RESULTS: Twenty-six patients were included in this study. The median age was 8.5 years (2.2-14) and median time from CPA to MRI was 4 days (2-7). Two ADC thresholds for brain volume percent had the largest AUC for predicting poor neurologic outcome. An ADC threshold of < 600 * 10-6 mm2/s in ≥ 7% of brain volume; and < 650 * 10-6 mm2/s in ≥ 11% of brain volume both demonstrated a specificity of 1.0 (0.76-1.0, 95% CI) and a sensitivity of 0.8 (0.44- 0.96, 95% CI) for poor outcome.CONCLUSIONS: In pediatric patients who remain comatose or have significant neurologic deficits after CPA, quantitative DWI MRI correlates with neurologic outcome. Both an ADC threshold of < 600 * 10-6 mm2/s in ≥ 7% of brain volume and < 650 * 10-6 mm2/s in ≥ 11% of brain volume are highly specific for predicting poor neurologic outcome. A prospective trial to validate these thresholds is needed.

    View details for PubMedID 30576784

  • 2018 American Heart Association Focused Update on Advanced Cardiovascular Life Support Use of Antiarrhythmic Drugs During and Immediately After Cardiac Arrest: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care CIRCULATION Panchal, A. R., Berg, K. M., Kudenchuk, P. J., Del Rios, M., Hirsch, K. G., Link, M. S., Kurz, M. C., Chan, P. S., Cabanas, J. G., Morley, P. T., Hazinski, M., Donnino, M. W. 2018; 138 (23): E740–E749
  • The neuron specific enolase (NSE) ratio offers benefits over absolute value thresholds in post-cardiac arrest coma prognosis JOURNAL OF CLINICAL NEUROSCIENCE Chung-Esaki, H. M., Mui, G., Mlynash, M., Eyngorn, I., Catabay, K., Hirsch, K. G. 2018; 57: 99–104


    Serum neuron-specific enolase (NSE) levels have been shown to correlate with neurologic outcome in comatose survivors of cardiac arrest but use of absolute NSE thresholds is limited. This study describes and evaluates a novel approach to analyzing NSE, the NSE ratio, and evaluates the prognostic utility of NSE absolute value thresholds and trends over time.100 consecutive adult comatose cardiac arrest survivors were prospectively enrolled. NSE levels were assessed at 24, 48, and 72 h post-arrest. Primary outcome was the Glasgow Outcome Score (GOS) at 6 months post-arrest; good outcome was defined as GOS 3-5. Absolute and relative NSE values (i.e. the NSE ratio), peak values, and the trend in NSE over 72 h were analyzed.98 patients were included. 42 (43%) had a good outcome. Five good outcome patients had peak NSE >33 µg/L (34.9-46.4 µg/L). NSE trends between 24 and 48 h differed between outcome groups (decrease by 3.0 µg/L (0.9-7.0 µg/L) vs. increase by 13.4 µg/L (-3.7 to 69.4 µg/L), good vs. poor, p = 0.004). The 48:24 h NSE ratio differed between the good and poor outcome groups (0.8 (0.6-0.9) vs. 1.4 (0.8-2.5), p = 0.001), and a 48:24 h ratio of ≥1.7 was 100% specific for poor outcome.The NSE ratio is a unique method to quantify NSE changes over time. Values greater than 1.0 indicate increasing NSE and may be reflective of ongoing neuronal injury. The NSE ratio obviates the need for an absolute value cut-off.

    View details for PubMedID 30145080

    View details for PubMedCentralID PMC6191328

  • Variation in Sedation and Neuromuscular Blockade Regimens on Outcome After Cardiac Arrest CRITICAL CARE MEDICINE May, T. L., Riker, R. R., Fraser, G. L., Hirsch, K. G., Agarwal, S., Duarte, C., Friberg, H., Soreide, E., McPherson, J., Hand, R., Kent, D., Nielsen, N., Seder, D. B. 2018; 46 (10): E975–E980


    Sedation and neuromuscular blockade protocols in patients undergoing targeted temperature management after cardiac arrest address patient discomfort and manage shivering. These protocols vary widely between centers and may affect outcomes.Consecutive patients admitted to 20 centers after resuscitation from cardiac arrest were prospectively entered into the International Cardiac Arrest Registry between 2006 and 2016. Additional data about each center's sedation and shivering management practice were obtained via survey. Sedation and shivering practices were categorized as escalating doses of sedation and minimal or no neuromuscular blockade (sedation and shivering practice 1), sedation with continuous or scheduled neuromuscular blockade (sedation and shivering practice 2), or sedation with as-needed neuromuscular blockade (sedation and shivering practice 3). Good outcome was defined as Cerebral Performance Category score of 1 or 2. A logistic regression hierarchical model was created with two levels (patient-level data with standard confounders at level 1 and hospitals at level 2) and sedation and shivering practices as a fixed effect at the hospital level. The primary outcome was dichotomized Cerebral Performance Category at 6 months.Cardiac arrest receiving centers in Europe and the United states from 2006 to 2016 PATIENTS:: Four-thousand two-hundred sixty-seven cardiac arrest patients 18 years old or older enrolled in the International Cardiac Arrest Registry.None.The mean age was 62 ± 15 years, 36% were female, 77% out-of-hospital arrests, and mean ischemic time was 24 (± 18) minutes. Adjusted odds ratio (for age, return of spontaneous circulation, location of arrest, witnessed, initial rhythm, bystander cardiopulmonary resuscitation, defibrillation, medical history, country, and size of hospital) was 1.13 (0.74-1.73; p = 0.56) and 1.45 (1.00-2.13; p = 0.046) for sedation and shivering practice 2 and sedation and shivering practice 3, respectively, referenced to sedation and shivering practice 1.Cardiac arrest patients treated at centers using as-needed neuromuscular blockade had increased odds of good outcomes compared with centers using escalating sedation doses and avoidance of neuromuscular blockade, after adjusting for potential confounders. These findings should be further investigated in prospective studies.

    View details for PubMedID 29979225

    View details for PubMedCentralID PMC6138551

  • Quantitative EEG Metrics Differ Between Outcome Groups and Change Over the First 72 h in Comatose Cardiac Arrest Patients NEUROCRITICAL CARE Wiley, S., Razavi, B., Krishnamohan, P., Mlynash, M., Eyngorn, I., Meador, K. J., Hirsch, K. G. 2018; 28 (1): 51–59


    Forty to sixty-six percent of patients resuscitated from cardiac arrest remain comatose, and historic outcome predictors are unreliable. Quantitative spectral analysis of continuous electroencephalography (cEEG) may differ between patients with good and poor outcomes.Consecutive patients with post-cardiac arrest hypoxic-ischemic coma undergoing cEEG were enrolled. Spectral analysis was conducted on artifact-free contiguous 5-min cEEG epochs from each hour. Whole band (1-30 Hz), delta (δ, 1-4 Hz), theta (θ, 4-8 Hz), alpha (α, 8-13 Hz), beta (β, 13-30 Hz), α/δ power ratio, percent suppression, and variability were calculated and correlated with outcome. Graphical patterns of quantitative EEG (qEEG) were described and categorized as correlating with outcome. Clinical outcome was dichotomized, with good neurologic outcome being consciousness recovery.Ten subjects with a mean age = 50 yrs (range = 18-65) were analyzed. There were significant differences in total power (3.50 [3.30-4.06] vs. 0.68 [0.52-1.02], p = 0.01), alpha power (1.39 [0.66-1.79] vs 0.27 [0.17-0.48], p < 0.05), delta power (2.78 [2.21-3.01] vs 0.55 [0.38-0.83], p = 0.01), percent suppression (0.66 [0.02-2.42] vs 73.4 [48.0-97.5], p = 0.01), and multiple measures of variability between good and poor outcome patients (all values median [IQR], good vs. poor). qEEG patterns with high or increasing power or large power variability were associated with good outcome (n = 6). Patterns with consistently low or decreasing power or minimal power variability were associated with poor outcome (n = 4).These preliminary results suggest qEEG metrics correlate with outcome. In some patients, qEEG patterns change over the first three days post-arrest.

    View details for PubMedID 28646267

  • Practical Pearl: Use of MRI to Differentiate Pseudo-subarachnoid Hemorrhage from True Subarachnoid Hemorrhage. Neurocritical care Ho, A. L., Sussman, E. S., Pendharkar, A. V., Iv, M. n., Hirsch, K. G., Fischbein, N. J., Dodd, R. L. 2018

    View details for PubMedID 29948997

  • The author replies. Critical care medicine Hirsch, K. G. 2017; 45 (3): e339-e340

    View details for DOI 10.1097/CCM.0000000000002222

    View details for PubMedID 28212244

  • Functional Neurologic Outcomes Change Over the First 6 Months After Cardiac Arrest. Critical care medicine Tong, J. T., Eyngorn, I., Mlynash, M., Albers, G. W., Hirsch, K. G. 2016; 44 (12): e1202-e1207


    To determine the longitudinal changes in functional outcome and compare ordinal outcome scale assessments in comatose cardiac arrest survivors.Prospective observational study of comatose cardiac arrest survivors. Subjects who survived to 1 month were included.Academic medical center ICU.Ninety-eight consecutive patients who remained comatose after resuscitation from cardiac arrest; 45 patients survived to 1 month.None.Patients' functional neurologic outcomes were assessed by phone call or in-person clinic visit at 1, 3, 6, and 12 months postcardiac arrest using the modified Rankin Scale, Glasgow Outcome Scale, and Barthel Index. A "good" outcome was defined as modified Rankin Scale 0-3, Barthel Index 70-100, and Glasgow Outcome Scale 4-5. Changes in dichotomized outcomes and shifts on each outcome scale were analyzed. The mean age of survivors was 51 ± 19 years and 18 (40%) were women. Five (19%) out of 26 patients with data available at all timepoints improved to good modified Rankin Scale outcome and none worsened to poor outcome between postarrest months 1 and 6 (p = 0.06). Thirteen patients (50%) improved on the modified Rankin Scale by 1-3 points and four (15%) worsened by 1-2 points between months 1 and 6 (overall improvement by 0.5 points; 95% CI, 0-1; p = 0.04). From postarrest months 6 to 12, there was no change in the number of patients with good versus poor outcomes. The modified Rankin Scale and Barthel Index were more sensitive to detecting changes in outcome than the Glasgow Outcome Scale.In initially comatose cardiac arrest survivors, improvements in functional status occur over the first 6 months after the event. There was no significant change in outcome between postarrest months 6 and 12. The modified Rankin Scale is a sensitive outcome scale in this population.

    View details for PubMedID 27495816

  • Development of a Mobile Tool That Semiautomatically Screens Patients for Stroke Clinical Trials. Stroke; a journal of cerebral circulation Spokoyny, I., Lansberg, M., Thiessen, R., Kemp, S. M., Aksoy, D., Lee, Y., Mlynash, M., Hirsch, K. G. 2016; 47 (10): 2652-2655


    Despite several national coordinated research networks, enrollment in many cerebrovascular trials remains challenging. An electronic tool was needed that would improve the efficiency and efficacy of screening for multiple simultaneous acute clinical stroke trials by automating the evaluation of inclusion and exclusion criteria, improving screening procedures and streamlining the communication process between the stroke research coordinators and the stroke clinicians.A multidisciplinary group consisting of physicians, study coordinators, and biostatisticians designed and developed an electronic clinical trial screening tool on a HIPAA (Health Insurance Portability and Accountability Act)-compliant platform.A web-based tool was developed that uses branch logic to determine eligibility for simultaneously enrolling clinical trials and automatically notifies the study coordinator teams about eligible patients. After 12 weeks of use, 225 surveys were completed, and 51 patients were enrolled in acute stroke clinical trials. Compared with the 12 weeks before implementation of the tool, there was an increase in enrollment from 16.5% of patients screened to 23.4% of patients screened (P<0.05). Clinicians and coordinators reported increased satisfaction with the process and improved ease of screening.We created a semiautomated electronic screening tool that uses branch logic to screen patients for stroke clinical trials. The tool has improved efficiency and efficacy of screening, and it could be adapted for use at other sites and in other medical fields.

    View details for DOI 10.1161/STROKEAHA.116.013456

    View details for PubMedID 27608822

    View details for PubMedCentralID PMC5039105

  • Multi-Center Study of Diffusion-Weighted Imaging in Coma After Cardiac Arrest. Neurocritical care Hirsch, K. G., Mlynash, M., Eyngorn, I., Pirsaheli, R., Okada, A., Komshian, S., Chen, C., Mayer, S. A., Meschia, J. F., Bernstein, R. A., Wu, O., Greer, D. M., Wijman, C. A., Albers, G. W. 2016; 24 (1): 82-89


    The ability to predict outcomes in acutely comatose cardiac arrest survivors is limited. Brain diffusion-weighted magnetic resonance imaging (DWI MRI) has been shown in initial studies to be a simple and effective prognostic tool. This study aimed to determine the predictive value of previously defined DWI MRI thresholds in a multi-center cohort.DWI MRIs of comatose post-cardiac arrest patients were analyzed in this multi-center retrospective observational study. Poor outcome was defined as failure to regain consciousness within 14 days and/or death during the hospitalization. The apparent diffusion coefficient (ADC) value of each brain voxel was determined. ADC thresholds and brain volumes below each threshold were analyzed for their correlation with outcome.125 patients were included in the analysis. 33 patients (26 %) had a good outcome. An ADC value of less than 650 × 10(-6) mm(2)/s in ≥10 % of brain volume was highly specific [91 % (95 % CI 75-98)] and had a good sensitivity [72 % (95 % CI 61-80)] for predicting poor outcome. This threshold remained an independent predictor of poor outcome in multivariable analysis (p = 0.002). An ADC value of less than 650 × 10(-6) mm(2)/s in >22 % of brain volume was needed to achieve 100 % specificity for poor outcome.In patients who remain comatose after cardiac arrest, quantitative DWI MRI findings correlate with early recovery of consciousness. A DWI MRI threshold of 650 × 10(-6) mm(2)/s in ≥10 % of brain volume can differentiate patients with good versus poor outcome, though in this patient population the threshold was not 100 % specific for poor outcome.

    View details for DOI 10.1007/s12028-015-0179-9

    View details for PubMedID 26156112

  • Prognostic Value of Quantitative Diffusion-Weighted MRI in Patients with Traumatic Brain Injury. Journal of neuroimaging Shakir, A., Aksoy, D., Mlynash, M., Harris, O. A., Albers, G. W., Hirsch, K. G. 2016; 26 (1): 103-108


    Data about the predictive value of quantitative diffusion-weighted MRI in traumatic brain injury (TBI) patients is lacking. This study aimed to determine if specific apparent diffusion coefficient (ADC) thresholds could be determined that correlate with outcome in moderate-severe TBI.This retrospective observational study investigated patients with moderate-severe TBI. MRIs obtained post-injury days 1-13 were analyzed. MRIs were obtained on a 1.5T scanner; 20-23 contiguous diffusion-weighted imaging (DWI) sections with a spin-echo echo planar imaging DWI 256×256 reconstructed matrix; field of view 24×24 cm; slice thickness/gap of 5/1.5 or 5/2.5 mm. The ADC value of each brain tissue voxel was determined. The percentage of voxels below different ADC thresholds was calculated and correlated with outcome. A good outcome was defined as discharge to home or a rehabilitation facility.Seventy-six patients were analyzed. Thirty-five patients (46%) had a good outcome. The timing of MRI scans did not differ between groups, but the mean age did (42±18 years vs. 56±19 years, p<.01, good vs. poor outcome). Patients with poor outcome had significantly higher percentage of brain volume with ADC < 400×10(-6) mm2 /second (.85±.67% vs. .60±.29%, poor vs. good outcome, p<.05). Using a ROC curve analysis and Youden's index, an ADC <400×10(-6) mm2 /second in ≥.49% of brain was 85% sensitive and 46% specific for poor outcome (p<.05).Quantitative MRI offers additional prognostic information in acute TBI. A whole brain tissue ADC threshold of <400×10(-6) mm2 /second in ≥.49% of brain may be a novel prognostic biomarker.

    View details for DOI 10.1111/jon.12286

    View details for PubMedID 26296810

  • Prognostic Value of A Qualitative Brain MRI Scoring System After Cardiac Arrest JOURNAL OF NEUROIMAGING Hirsch, K. G., Mlynash, M., Jansen, S., Persoon, S., Eyngorn, I., Krasnokutsky, M. V., Wijman, C. A., Fischbein, N. J. 2015; 25 (3): 430-437


    To develop a qualitative brain magnetic resonance imaging (MRI) scoring system for comatose cardiac arrest patients that can be used in clinical practice.Consecutive comatose postcardiac arrest patients were prospectively enrolled. Routine MR brain sequences were scored by two independent blinded experts. Predefined brain regions were qualitatively scored on the fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted imaging (DWI) sequences according to the severity of the abnormality on a scale from 0 to 4. The mean score of the raters was used. Poor outcome was defined as death or vegetative state at 6 months.Sixty-eight patients with 88 brain MRI scans were included. Median time from the arrest to the initial MRI was 77 hours (IQR 58-144 hours). At 100% specificity, the "cortex score" performed best in predicting unfavorable outcome with a sensitivity of 55%-60% (95% CI 41-74) depending on time window selection. When comparing the "cortex score" with historically used predictors for poor outcome, MRI improved the sensitivity for poor outcome over conventional predictors by 27% at 100% specificity.A qualitative MRI scoring system helps assess hypoxic-ischemic brain injury severity following cardiac arrest and may provide useful prognostic information in comatose cardiac arrest patients.

    View details for DOI 10.1111/jon.12143

    View details for Web of Science ID 000354129000014

    View details for PubMedID 25040353

  • Very Early Administration of Progesterone for Acute Traumatic Brain Injury NEW ENGLAND JOURNAL OF MEDICINE Wright, D. W., Yeatts, S. D., Silbergleit, R., Palesch, Y. Y., Hertzberg, V. S., Frankel, M., Goldstein, F. C., Caveney, A. F., Howlett-Smith, H., Bengelink, E. M., Manley, G. T., Merck, L. H., Janis, L. S., Barsan, W. G. 2014; 371 (26): 2457-2466


    Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Progesterone has been shown to improve neurologic outcome in multiple experimental models and two early-phase trials involving patients with TBI.We conducted a double-blind, multicenter clinical trial in which patients with severe, moderate-to-severe, or moderate acute TBI (Glasgow Coma Scale score of 4 to 12, on a scale from 3 to 15, with lower scores indicating a lower level of consciousness) were randomly assigned to intravenous progesterone or placebo, with the study treatment initiated within 4 hours after injury and administered for a total of 96 hours. Efficacy was defined as an increase of 10 percentage points in the proportion of patients with a favorable outcome, as determined with the use of the stratified dichotomy of the Extended Glasgow Outcome Scale score at 6 months after injury. Secondary outcomes included mortality and the Disability Rating Scale score.A total of 882 of the planned sample of 1140 patients underwent randomization before the trial was stopped for futility with respect to the primary outcome. The study groups were similar with regard to baseline characteristics; the median age of the patients was 35 years, 73.7% were men, 15.2% were black, and the mean Injury Severity Score was 24.4 (on a scale from 0 to 75, with higher scores indicating greater severity). The most frequent mechanism of injury was a motor vehicle accident. There was no significant difference between the progesterone group and the placebo group in the proportion of patients with a favorable outcome (relative benefit of progesterone, 0.95; 95% confidence interval [CI], 0.85 to 1.06; P=0.35). Phlebitis or thrombophlebitis was more frequent in the progesterone group than in the placebo group (relative risk, 3.03; CI, 1.96 to 4.66). There were no significant differences in the other prespecified safety outcomes.This clinical trial did not show a benefit of progesterone over placebo in the improvement of outcomes in patients with acute TBI. (Funded by the National Institute of Neurological Disorders and Stroke and others; PROTECT III number, NCT00822900.).

    View details for DOI 10.1056/NEJMoa1404304

    View details for Web of Science ID 000346920300005

    View details for PubMedID 25493974

  • An Update on Neurocritical Care for the Patient With Kidney Disease ADVANCES IN CHRONIC KIDNEY DISEASE Hirsch, K. G., Josephson, S. A. 2013; 20 (1): 39-44


    Patients with kidney disease have increased rates of neurologic illness such as intracerebral hemorrhage and ischemic stroke. The acute care of patients with critical neurologic illness and concomitant kidney disease requires unique management considerations including attention to hyponatremia, renal replacement modalities in the setting of high intracranial pressure, reversal of coagulopathy, and seizure management to achieve good neurologic outcomes.

    View details for DOI 10.1053/j.ackd.2012.09.003

    View details for Web of Science ID 000313394500007

    View details for PubMedID 23265595

  • Treatment of Elevated Intracranial Pressure with Hyperosmolar Therapy in Patients with Renal Failure NEUROCRITICAL CARE Hirsch, K. G., Spock, T., Koenig, M. A., Geocadin, R. G. 2012; 17 (3): 388-394


    To evaluate the use of hyperosmolar therapy in the management of elevated intracranial pressure (ICP) and transtentorial herniation (TTH) in patients with renal failure and supratentorial lesions.Patients with renal failure undergoing renal replacement therapy treated with 23.4% saline (30-60 mL) and/or mannitol for high ICP or clinical evidence of TTH were analyzed in a retrospective cohort.The primary outcome measure was reversal of TTH or ICP crisis. Secondary outcome measures were modified Rankin scale on hospital discharge, survival to hospital discharge, and adverse effects. Of 254 subjects over 7 years, 6 patients with end-stage renal disease had 11 events. All patients received a 23.4% saline bolus, along with mannitol (91%), hypertonic saline (HS) maintenance fluids (82%), and surgical interventions (n = 2). Reversal occurred in 6/11 events (55%); 2 of 6 patients survived to discharge. ICP recording of 6 TTH events showed a reduction from ICP of 41 ± 3.8 mmHg (mean ± SEM) with TTH to 20.8 ± 3.9 mmHg (p = 0.05) 1 h after the 23.4% saline bolus. Serum sodium increased from 141.4 to 151.1 mmol/L 24 h after 23.4% saline bolus (p = 0.001). No patients were undergoing hemodialysis at the time of the event. There were no cases of pulmonary edema, clinical volume overload, or arrhythmia after HS.Treatment with hyperosmolar therapy, primarily 23.4% saline solution, was associated with clinical reversal of TTH and reduction in ICP and had few adverse effects in this cohort. Hyperosmolar therapy may be safe and effective in patients with renal failure and these initial findings should be validated in a prospective study.

    View details for DOI 10.1007/s12028-012-9676-2

    View details for Web of Science ID 000312069400012

    View details for PubMedID 22328033

  • Boomerang Sign on MRI NEUROCRITICAL CARE Hirsch, K. G., Hoesch, R. E. 2012; 16 (3): 450-451


    Altered mental status and more subtle cognitive and personality changes after traumatic brain injury (TBI) are pervasive problems in patients who survive initial injury. MRI is not necessarily part of the diagnostic evaluation of these patients.Case report with relevant image and review of the literature.Injury to the corpus callosum is commonly described in traumatic brain injury; however, extensive lesions in the splenium are not well described. This image shows an important pattern of brain injury and demonstrates a common clinical syndrome seen in patients with corpus callosum pathology.Injury to the splenium of the corpus callosum due to trauma may be extensive and can cause significant neurologic deficits. MRI is important in the diagnostic evaluation of patients with cognitive changes after TBI.

    View details for DOI 10.1007/s12028-012-9699-8

    View details for Web of Science ID 000304619000016

    View details for PubMedID 22565630

  • Cerebral blood flow and cerebrovascular autoregulation in a swine model of pediatric cardiac arrest and hypothermia CRITICAL CARE MEDICINE Lee, J. K., Brady, K. M., Mytar, J. O., Kibler, K. K., Carter, E. L., Hirsch, K. G., Hogue, C. W., Easley, R. B., Jordan, L. C., Smielewski, P., Czosnyka, M., Shaffner, D. H., Koehler, R. C. 2011; 39 (10): 2337-2345


    Knowledge remains limited regarding cerebral blood flow autoregulation after cardiac arrest and during postresuscitation hypothermia. We determined the relationship of cerebral blood flow to cerebral perfusion pressure in a swine model of pediatric hypoxic-asphyxic cardiac arrest during normothermia and hypothermia and tested novel measures of autoregulation derived from near-infrared spectroscopy.Prospective, balanced animal study.Basic physiology laboratory at an academic institution.Eighty-four neonatal swine.Piglets underwent hypoxic-asphyxic cardiac arrest or sham surgery and recovered for 2 hrs with normothermia followed by 4 hrs of either moderate hypothermia or normothermia. In half of the groups, blood pressure was slowly decreased through inflation of a balloon catheter in the inferior vena cava to identify the lower limit of cerebral autoregulation at 6 hrs postresuscitation. In the remaining groups, blood pressure was gradually increased by inflation of a balloon catheter in the aorta to determine the autoregulatory response to hypertension. Measures of autoregulation obtained from standard laser-Doppler flowmetry and indices derived from near-infrared spectroscopy were compared.Laser-Doppler flux was lower in postarrest animals compared to sham-operated controls during the 2-hr normothermic period after resuscitation. During the subsequent 4-hr recovery, hypothermia decreased laser-Doppler flux in both the sham surgery and postarrest groups. Autoregulation was intact during hypertension in all groups. With arterial hypotension, postarrest, hypothermic piglets had a significant decrease in the perfusion pressure lower limit of autoregulation compared to postarrest, normothermic piglets. The near-infrared spectroscopy-derived measures of autoregulation accurately detected loss of autoregulation during hypotension.In a pediatric model of cardiac arrest and resuscitation, delayed induction of hypothermia decreased cerebral perfusion and decreased the lower limit of autoregulation. Metrics derived from noninvasive near-infrared spectroscopy accurately identified the lower limit of autoregulation during normothermia and hypothermia in piglets resuscitated from arrest.

    View details for DOI 10.1097/CCM.0b013e318223b910

    View details for Web of Science ID 000294958500019

    View details for PubMedID 21705904

  • Clinical and Radiographic Natural History of Cervical Artery Dissections JOURNAL OF STROKE & CEREBROVASCULAR DISEASES Schwartz, N. E., Vertinsky, A. T., Hirsch, K. G., Albers, G. W. 2009; 18 (6): 416-423


    Cervical artery dissection (CADsx) is a common cause of stroke in young patients, but long-term clinical and radiographic follow-up from a large population is lacking.Epidemiologic data, treatment, recurrence, and other features were extracted from the records of all patients seen at our stroke center with confirmed CAD during a 15-year period. A subset of cases was examined to provide detailed information about vessel status.In all, 177 patients (mean age 44.0 +/- 11.1 years) were identified, with the male patients being older than the female patients. Almost 60% of dissections were spontaneous, whereas the remainder involved some degree of head and/or neck trauma. More than 70% of patients were treated with anticoagulation. During follow-up (mean 18.2 months; 0-220 months) there were 15 cases (8.5%) of recurrent ischemic events, and two cases (1.1%) of a recurrent dissection. About half of recurrent stroke/transient ischemic attack events occurred within 2 weeks of presentation. There was no clear association between the choice of antithrombotic agent and recurrent ischemic events. Detailed analysis of imaging findings was performed in 51 cases. Some degree of recanalization was seen in 58.8% of patients overall, and was more frequent in women. The average time to total or near-total recanalization was 4.7 +/- 2.5 months. Patients with complete occlusions at presentation tended not to recanalize.This large series from a single institution highlights many of the features of CAD. A relatively benign course with low recurrence rate is supported, independent of the type and duration of antithrombotic therapy.

    View details for DOI 10.1016/j.jstrokecerebrovasdis.2008.11.016

    View details for Web of Science ID 000272114400002

    View details for PubMedID 19900642

  • Occurrence of Perimesencephalic Subarachnoid Hemorrhage During Pregnancy NEUROCRITICAL CARE Hirsch, K. G., Froehler, M. T., Huang, J., Ziai, W. C. 2009; 10 (3): 339-343


    Perimesencephalic subarachnoid hemorrhage (P-SAH) is a benign subset of subarachnoid hemorrhage with a favorable prognosis and low rate of re-bleeding. Risk factors may include hypertension and tobacco use, but it has not previously been reported during pregnancy.We report two cases of P-SAH in pregnant women, a 40-year-old female, 8-weeks pregnant and a 37-year-old female at 35 weeks gestational age.CT scan confirmed P-SAH in both cases. CT angiography in one case and cerebral angiogram in the other did not reveal aneurysm or other potential bleeding source. The patients underwent transcranial Doppler ultrasound monitoring without evidence of vasospasm.P-SAH hemorrhage may occur during early or late pregnancy. We do not propose an increased risk of P-SAH during pregnancy. The clinical course appears favorable and CT angiography alone may be considered the preferred diagnostic test to assess for aneurysm in first trimester pregnancy.

    View details for DOI 10.1007/s12028-009-9189-9

    View details for Web of Science ID 000266328900013

    View details for PubMedID 19184552

  • Inhibition of PI-3 kinase sensitizes human leukemic cells to histone deacetylase inhibitor-mediated apoptosis through p44/42 MAP kinase inactivation and abrogation of p21(CIP1/WAF1) induction rather than AKT inhibition ONCOGENE Rahmani, M., Yu, C. R., Reese, E., Ahmed, W., Hirsch, K., Dent, P., Grant, S. 2003; 22 (40): 6231-6242


    Effects of the PI-3 kinase inhibitor LY294002 (LY) have been examined in relation to responses of human leukemia cells to histone deacetylase inhibitors (HDIs). Coexposure of U937 cells for 24 h to marginally toxic concentrations of LY294002 (e.g., 30 microM) and sodium butyrate (SB; 1 mM) resulted in a marked increase in mitochondrial damage (e.g., cytochrome c and Smac/DIABLO release, loss of DeltaPsi(m)), caspase activation, and apoptosis. Similar results were observed in Jurkat, HL-60, and K562 leukemic cells and with other HDIs (e.g., SAHA, MS-275). Exposure of cells to SB/LY was associated with Bcl-2 and Bid cleavage, XIAP and Mcl-1 downregulation, and diminished CD11b expression. While LY blocked SB-mediated Akt activation, enforced expression of a constitutively active (myristolated) Akt failed to attenuate SB/LY-mediated lethality. Unexpectedly, treatment of cells with SB+/-LY resulted in a marked reduction in phosphorylation (activation) of p44/42 mitogen-activated protein (MAP) kinase. Moreover, enforced expression of a constitutively active MEK1 construct partially but significantly attenuated SB/LY-induced apoptosis. Lastly, cotreatment with LY blocked SB-mediated induction of p21(CIP1/WAF1); moreover, enforced expression of p21(CIP1/WAF1) significantly reduced SB/LY-mediated apoptosis. Together, these findings indicate that LY promotes SB-mediated apoptosis through an AKT-independent process that involves MEK/MAP kinase inactivation and interference with p21(CIP1/WAF1) induction.

    View details for DOI 10.1038/sj.onc.1206646

    View details for Web of Science ID 000185506200013

    View details for PubMedID 13679862

  • The cyclin-dependent kinase inhibitor (CDKI) flavopiridol disrupts phorbol 12-myristate 13-acetate-induced differentiation and CDKI expression while enhancing apoptosis in human myeloid leukemia cells CANCER RESEARCH Cartee, L., Wang, Z. L., Decker, R. H., Chellappan, S. P., Fusaro, G., Hirsch, K. G., Sankala, H. M., Dent, P., Grant, S. 2001; 61 (6): 2583-2591


    Interactions between the cyclin-dependent kinase inhibitor (CDKI) flavopiridol (FP) and phorbol 12-myristate 13-acetate (PMA) were examined in U937 human leukemia cells in relation to differentiation and apoptosis. Simultaneous, but not sequential, exposure of U937 cells to 100 nM FP and 10 nM PMA significantly increased apoptosis manifested by characteristic morphological features, mitochondrial dysfunction, caspase activation, and poly(ADP-ribose) polymerase cleavage while markedly inhibiting cellular differentiation, as reflected by diminished plastic adherence and CD11b expression. Enhanced apoptosis in U937 cells was associated with an early caspase-independent increase in cytochrome c release and accompanied by a substantial decline in leukemic cell clonogenicity. Moreover, PMA/FP cotreatment significantly increased apoptosis in HL-60 promyelocytic leukemia cells and in U937 cells ectopically expressing the Bcl-2 protein. In U937 cells, coadministration of FP blocked PMA-induced expression and reporter activity of the CDKI p21WAF/CIP1 and triggered caspase-mediated cleavage of the CDKI p27KIP1. Coexposure to FP also resulted in a more pronounced and sustained activation of the mitogen-activated protein kinase kinase/extracellular signal-regulated protein kinase cascade after PMA treatment, although disruption of this pathway by the mitogen-activated protein kinase kinase 1 inhibitor U0126 did not prevent potentiation of apoptosis. FP accelerated PMA-mediated dephosphorylation of the retinoblastoma protein (pRb), an event followed by pRb cleavage culminating in the complete loss of underphosphorylated pRb (approximately Mr 110,000) by 24 h. Finally, gel shift analysis revealed that coadministration of FP with PMA for 8 h led to diminished E2F/pRb binding compared to the effects of PMA alone. Collectively, these findings indicate that FP modulates the expression/activity of multiple signaling and cell cycle regulatory proteins in PMA-treated leukemia cells and that such alterations are associated with mitochondrial damage and apoptosis rather than maturation. These observations also raise the possibility that combining CDKIs and differentiation-inducing agents may represent a novel antileukemic strategy.

    View details for Web of Science ID 000167697500042

    View details for PubMedID 11289135