Association of Early Beta-Blocker Exposure and Functional Outcomes in Critically Ill Patients With Moderate to Severe Traumatic Brain Injury: A Transforming Clinical Research and Knowledge in Traumatic Brain Injury Study.



We aimed to 1) describe patterns of beta-blocker utilization among critically ill patients following moderate-severe traumatic brain injury (TBI) and 2) examine the association of early beta-blocker exposure with functional and clinical outcomes following injury.


Retrospective cohort study.


ICUs at 18 level I, U.S. trauma centers in the Transforming Clinical Research and Knowledge in TBI (TRACK-TBI) study.


Greater than or equal to 17 years enrolled in the TRACK-TBI study with moderate-severe TBI (Glasgow Coma Scale of <13) were admitted to the ICU after a blunt TBI.




Primary exposure was a beta blocker during the first 7 days in the ICU, with a primary outcome of 6-month Glasgow Outcome Scale-Extended (GOSE). Secondary outcomes included: length of hospital stay, in-hospital mortality, 6-month and 12-month mortality, 12-month GOSE score, and 6-month and 12-month measures of disability, well-being, quality of life, and life satisfaction.

Main results

Of the 450 eligible participants, 57 (13%) received early beta blockers (BB+ group). The BB+ group was on average older, more likely to be on a preinjury beta blocker, and more likely to have a history of hypertension. In the BB+ group, 34 participants (60%) received metoprolol only, 19 participants (33%) received propranolol only, 3 participants (5%) received both, and 1 participant (2%) received atenolol only. In multivariable regression, there was no difference in the odds of a higher GOSE score at 6 months between the BB+ group and BB- group (odds ratio = 0.86; 95% CI, 0.48-1.53). There was no association between BB exposure and secondary outcomes.


About one-sixth of subjects in our study received early beta blockers, and within this group, dose, and timing of beta-blocker administration varied substantially. No significant differences in GOSE score at 6 months were demonstrated, although our ability to draw conclusions is limited by overall low total doses administered compared with prior studies.





Published Version (Please cite this version)


Publication Info

Kelly-Hedrick, Margot, Sunny Yang Liu, Nancy Temkin, Jason Barber, Jordan Komisarow, Geoffrey Manley, Tetsu Ohnuma, Katharine Colton, et al. (2023). Association of Early Beta-Blocker Exposure and Functional Outcomes in Critically Ill Patients With Moderate to Severe Traumatic Brain Injury: A Transforming Clinical Research and Knowledge in Traumatic Brain Injury Study. Critical care explorations, 5(9). p. e0958. 10.1097/cce.0000000000000958 Retrieved from

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Jordan Komisarow

Assistant Professor of Neurosurgery

Tetsu Ohnuma

Assistant Professor in Anesthesiology

Katharine Rose Colton

Assistant Professor of Neurology

Miriam Treggiari

Paul G. Barash Distinguished Professor of Anesthesiology

Daniel Todd Laskowitz

Professor of Neurology

Our laboratory uses molecular biology, cell culture, and animal modeling techniques to examine the CNS response to acute injury. In particular, our laboratory examines the role of microglial activation and the endogenous CNS inflammatory response in exacerbating secondary injury following acute brain insult. Much of the in vitro work in this laboratory is dedicated to elucidating cellular responses to injury with the ultimate goal of exploring new therapeutic interventions in the clinical setting of stroke, intracranial hemorrhage, and closed head injury.

In conjunction with the Multidisciplinary Neuroprotection Laboratories, we also focus on clinically relevant small animal models of acute CNS injury. For example, we have recently characterized murine models of closed head injury, subarachnoid hemorrhage, intracranial hemorrhage and perinatal hypoxia-ischemia, in addition to the standard rodent models of focal stroke and transient forebrain ischemia. Recently we have adapted several of these models from the rat to the mouse to take advantage of murine transgenic technology. The objective of these studies are two-fold: to gain better insight into the cellular responses and pathophysiology of acute brain injury, and to test novel therapeutic strategies for clinical translation. In both cell culture systems and animal models, our primary focus is on examining the role of oxidative stress and inflammatory mechanism in mediating brain injury following acute brain insult, and examining the neuroprotective effects of endogenous apolipoprotein E in the injured mammalian central nervous system.

Our laboratory is committed to translational research, and has several active clinical research protocols, which are designed to bring the research performed in the Multidisciplinary Research Laboratories to the clinical arena. These protocols are centered around patients following stroke and acute brain injury, and are primarily based out of the Emergency Room and Neurocritical Care Unit. For example, we are currently examining the role of inflammatory mediators for use as a point-of-care diagnostic marker following stroke, intracranial hemorrhage, and closed head injury. We have recently translated a novel apoE mimetic from the preclinical setting to a multi center Phase 2 trial evaluating efficacy in intracranial hemorrhage. We are also examining the functional role of different polymorphisms of of inflammatory cytokines in the setting of acute brain injury and neurological dysfunction following cardiopulmonary bypass.


Joseph P. Mathew

Jerry Reves, M.D. Distinguished Professor of Cardiac Anesthesiology

Current research interests include:
1. The relationship between white matter patency, functional connectivity (fMRI) and neurocognitive function following cardiac surgery.
2. The relationship between global and regional cortical beta-amyloid deposition and postoperative cognitive decline.
3. The effect of lidocaine infusion upon neurocognitive function following cardiac surgery.
4. The association between genotype and outcome after cardiac surgery.
5. Atrial fibrillation following cardiopulmonary bypass.


Adrian Felipe Hernandez

Duke Health Cardiology Professor

Michael Lucas James

Professor of Anesthesiology

With a clinical background in neuroanesthesia and neurointensive care, I have a special interest in translational research in intracerebral hemorrhage and traumatic brain injury. I am fortunate to be part of a unique team of highly motivated and productive individuals who allow me to propel ideas from bench to bedside and the ability to reverse translate ideas from the bedside back to the bench.


Karthik Raghunathan

Associate Professor of Anesthesiology

Dr. Karthik Raghunathan is an Associate Professor with Tenure in the Department of Anesthesiology, with a secondary appointment in the Department of Population Health Sciences, at the Duke University School of Medicine and is a Staff Physician at the Durham Veterans Affairs Healthcare System. He is co-director of the Critical care And Perioperative population hEalth Research (CAPER) Program. 

In addition to clinical practice as an anesthesiologist and intensive care physician, Dr. Raghunathan is an epidemiologist and health services researcher with over $2 Million in funding from Federal, Industry, and Non-Profit entities since 2015. He co-directs the Critical care and Perioperative Population Health Research (CAPER) program, generating and disseminating evidence to inform clinical practice guidelines.

His studies focus on: a) the comparative effectiveness and safety of procedures and medications used for acute postoperative pain management, fluid resuscitation during surgery and intensive care; b) the implementation and effectiveness of nonpharmacologic treatments, such as music medicine and peripheral neuromodulation, and c) reducing race, sex, and income-based inequities in treatments and outcomes.

Dr. Raghunathan collaborates with colleagues within Duke, as well as colleagues at Academically affiliated other VA Healthcare Systems. He welcomes collaboration and can be reached at 


Benjamin Alan Goldstein

Professor of Biostatistics & Bioinformatics

I study the meaningful use of Electronic Health Records data. My research interests sit at the intersection of biostatistics, biomedical informatics, machine learning and epidemiology. I collaborate with researchers both locally at Duke as well as nationally. I am interested in speaking with any students, methodologistis or collaborators interested in EHR data.

Please find more information at:

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