Title : Remote ischemic conditioning as an adjunct intervention in ICU traumatic brain injury patients: Preliminary findings on injury biomarkers from a randomized controlled trial
Abstract:
Introduction: Management of Traumatic Brain Injury (TBI) is currently aimed at secondary brain injury prevention that results from brain ischemia. Remote ischemic conditioning (RIC) is a non-invasive intervention that has been shown to lessen ischemia/reperfusion injury and potentially reduce tissue/organ injury damage. RIC has also been shown to have neuroprotective effects via anti-inflammatory action, stabilization of mitochondria, and increased cerebral blood flow in experimental animal models. In a prior nonrandomized trial, TBI patients undergoing RIC showed amelioration of neuronal injury specific markers, neuron-specific enolase and S-100 calcium-binding protein B (S100B), compared to an untreated control group. We performed a randomized double-blinded control trial in TBI patients to test the hypothesis that RIC would exert beneficial effects on secondary injury as reflected by blood-based neurological injury biomarkers.
Methods: A randomized double-blinded controlled clinical trial with two arms (sham and RIC) is in progress in TBI ICU patients at St. Michael’s Hospital, Toronto, Canada. Thirteen plasma biomarkers measured at 0h (pre-intervention) and 4-6, 24, 48 and 72h (post-intervention) are primary outcome measures. Eligibility criteria include presence of intracranial hematoma on CT scan, Glasgow Coma Scale score ≤ 12. RIC involves 4 cycles of 5-min occlusion at 30mmHg>systolic blood pressure, followed by 5-min of deflation on an arm (using pneumatic torniquet) within 48h of injury. Secondary outcome measures will include clinical data and neurocognitive assessments. Currently, the trial has enrolled 43 out of 45 patients. Preliminary plasma biomarker measurements (pg/mL or copies/uL), performed by the immunoassay, commercial kits, or qPCR were conducted on 13/RIC and 15/Sham patients and levels were adjusted to baseline (0h).
Results: Five of the 13 biomarkers yielded significant and marginally significant differences between Sham and RIC groups at specific timepoints: RIC significantly lowered levels of neural injury marker S100B (-399 [95% CI: 64 to 734] pg/mL; ANCOVA P = 0.02164) and repair myokine Irisin (-1550 [95% CI: 740 to 2361] pg/mL; ANCOVA P = 0.00058) at 4-6h, and mitochondrial dysfunction marker lactate (-181 [95% CI: -310 to 671] pg/mL; ANCOVA P = 0.4517) at 72h. RIC significantly increased mitochondrial dysfunction marker ccf-mtDNA (12111 [95% CI: -23889 to -333] pg/mL; ANCOVA P = 0.044) at 24h while levels of inflammatory marker HMGB1 (-26569 [95% CI: -2887 to 56025] pg/mL; ANCOVA P = 0.074) were decreased with marginal significance (P ≤ 0.1) at 48h.
Conclusions: We report that RIC demonstrates promising preliminary effects in limiting post-injury elevations in S100B, Irisin, and lactate levels observed in TBI patients. Completed results of the ongoing trial will further elucidate the mechanisms and outcome of RIC treatment as a potential novel adjunctive therapy for moderate-to-severe TBI.
Audience Take Away
- Explain how the audience will be able to use what they learn?
- They will become more aware of current research in the field of TBI
- How will this help the audience in their job? Is this research that other faculty could use to expand their research or teaching? Does this provide a practical solution to a problem that could simplify or make a designer’s job more efficient? Will it improve the accuracy of a design, or provide new information to assist in a design problem? List of all other benefits.
- It will help individuals gain awareness of current research in the field of TBI
- Individuals will learn about a new therapeutic intervention
- Researchers can gain an understanding of our study protocol and implement it or enhance their own
- It provides new information in assessing the issue of secondary brain injury management
