Early beta-blocker exposure and association with brain injury biomarkers following moderate to severe traumatic brain injury: A TRACK-TBI study

Pattrapun Wongsripuemtet; Tetsu Ohnuma; Nancy Temkin; Jason Barber; Jordan Komisarow; Geoffrey T Manley; Jordan Hatfield; Miriam Treggiari; Katharine Colton; Cina Sasannejad; Nophanan Chaikittisilpa; Ramesh Grandhi; Daniel T Laskowitz; Joseph P Mathew; Adrian Hernandez; Michael L James; Karthik Raghunathan; Joseph B Miller; Monica S Vavilala; Ben Goldstein; Vijay Krishnamoorthy; TRACK-TBI Investigators

doi:10.1177/17511437251349680

Early beta-blocker exposure and association with brain injury biomarkers following moderate to severe traumatic brain injury: A TRACK-TBI study

J Intensive Care Soc. 2025 Jun 29:17511437251349680. doi: 10.1177/17511437251349680. Online ahead of print.

Authors

Pattrapun Wongsripuemtet^{1

2}, Tetsu Ohnuma^{1

3}, Nancy Temkin^{4

5}, Jason Barber⁵, Jordan Komisarow⁶, Geoffrey T Manley⁷, Jordan Hatfield^{6

8}, Miriam Treggiari^{1

3}, Katharine Colton⁹, Cina Sasannejad⁹, Nophanan Chaikittisilpa², Ramesh Grandhi¹⁰, Daniel T Laskowitz^{3

6

9}, Joseph P Mathew³, Adrian Hernandez¹¹, Michael L James^{1

3

9}, Karthik Raghunathan^{1

3

12}, Joseph B Miller¹³, Monica S Vavilala¹⁴, Ben Goldstein¹⁵, Vijay Krishnamoorthy^{1

3

12}; TRACK-TBI Investigators

Affiliations

¹ Critical Care and Perioperative Population Health Research (CAPER) Program, Department of Anesthesiology, Duke University, Durham, NC, USA.
² Department of Anesthesiology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
³ Department of Anesthesiology, Duke University, Durham, NC, USA.
⁴ Department of Biostatistics, University of Washington, Seattle, WA, USA.
⁵ Department of Neurological Surgery, University of Washington, Seattle, WA, USA.
⁶ Department of Neurosurgery, Duke University, Durham, NC, USA.
⁷ Department of Neurosurgery, University of California, San Francisco, San Francisco, CA, USA.
⁸ Duke University School of Medicine, Durham, NC, USA.
⁹ Department of Neurology, Duke University, Durham, NC, USA.
¹⁰ Department of Neurosurgery, University of Utah, Salt Lake City, UT, USA.
¹¹ Department of Medicine, Duke University, Durham, NC, USA.
¹² Department of Population Health Sciences, Duke University, Durham, NC, USA.
¹³ Department of Emergency Medicine, Henry Ford Health System, Detroit, MI, USA.
¹⁴ Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA.
¹⁵ Department of Biostatistics, Duke University, Durham, NC, USA.

Abstract

Background: Beta-blockers have been studied for potential benefits in traumatic brain injury (TBI). This study aimed to investigate the association between early beta-blocker exposure and brain injury biomarkers following moderate-severe TBI.

Methods: We conducted a retrospective cohort study using data from the Transforming Clinical Research and Knowledge in TBI (TRACK-TBI) study. Patients ⩾ 17 years with moderate-severe TBI (Glasgow Coma Scale 3-12) admitted to an intensive care unit (ICU) were included. Early beta-blocker exposure was defined as administration within the first 72 h of admission. The primary outcome was blood-based brain injury biomarker levels on day 3 post-injury. Biomarkers included glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), neuron-specific enolase (NSE), S100 calcium-binding protein B (S100B), and the inflammatory biomarker C-reactive protein (CRP). Propensity-weighted models analyzed the association between beta-blocker exposure and biomarker levels.

Results: Among 450 patients, 31 (7%) received beta-blockers (BB+). The mean (SD) age of BB+ patients was 51.4 (16.2) years, compared to 39.5 (17.0) years for unexposed patients (BB-). BB+ group was associated with a decreased NSE level on day 3 (ratio = 0.71, 95% CI 0.52-0.96, p = 0.026), although this was not significant after adjusting for multiple comparisons (p = 0.13). For secondary outcomes, UCH-L1 levels increased on day 5 in the BB+ group (ratio = 1.62, 95% CI 1.12- 2.36, p = 0.011), but this was not significant after adjustment (p = 0.55). The NSE level on day 14 decreased in the BB+ group (ratio 0.45, 95% CI 0.30-0.66, p < 0.001) and remained significant after adjustment (p = 0.005).

Conclusions: There was no association between early beta-blocker exposure and the primary outcome which was blood-based brain injury biomarker levels on day 3. In exploratory analysis, we found that early beta-blocker may associated with decreased NSE level on day 14. Due to the retrospective nature of the study and the use of propensity-weighted analysis to identify associations, direct clinical practice changes cannot be recommended. However, the significant association with NSE level warrants further investigation through prospective studies or randomized controlled trials to confirm the potential neuroprotective effect of early beta-blocker exposure on neuronal cellular injury.

Keywords: Beta-blockers; biomarkers; critical care; traumatic brain injury.