Citation

Robertson CS, Salinas Martinez F, McQuillan L, Williamson JB, Lamb DG, Wang KKW, Rubenstein R, Wagner AKMD. J. Neurotrauma 2023; ePub(ePub): ePub.

Copyright

(Copyright © 2023, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2023.0111

PMID

37489296

Abstract

In patients with traumatic brain injury (TBI), serum biomarkers may have utility in assessing the evolution of secondary brain injury. A panel of nine brain-injury associated biomarkers were measured in archived serum samples over 10 days post-injury from 100 patients with moderate-severe TBI. Among the biomarkers evaluated, serum glial fibrillary acidic protein (GFAP) had the strongest associations with summary measures of acute pathophysiology, including intracranial pressure (ICP), cerebral perfusion pressure (CPP), and brain tissue pO2 (PbtO2). Group based trajectory (TRAJ) analysis was used to identify three distinct GFAP subgroups. The low TRAJ group (n=23) had peak levels of 9.4+1.2 ng/ml that declined rapidly. The middle TRAJ group (n=48) had higher peak values (31.5+5.0 ng/ml) and a slower decline over time. The high TRAJ group (n=26) had very high, sustained peak values (59.6+12.5 ng/ml) that even rose among some patients over 10 days. Patients in the high TRAJ group had significantly higher mortality rate than patients in low/middle TRAJ groups (26.9% vs. 7.0%, p=0.028). The frequency of poor neurological outcome (Glasgow Outcome Score Extended [GOS-E] 1-4) was 88.5% in the high TRAJ group, 54.2% in the middle TRAJ group, and 30.4% in the low TRAJ group (p<0.001). ICP was highest in the high TRAJ group (median 17.6 mmHg), compared to 14.4 mmHg in low and 15.9 mmHg in middle TRAJ groups (p=0.002). High TRAJ patients spent the longest time with ICP >25 mmHg, median 23 hrs compared to 2 and 6 hrs in low and middle TRAJ groups (p=0.006), and the longest time with ICP >30 mmHg, median 5 hrs, compared to 0 and 1 hr in low and middle TRAJ groups, respectively (p=0.013). High TRAJ group patients more commonly required tier 2 or 3 treatment to control ICP. The high TRAJ group had the longest duration where CPP was <50 mmHg (P=0.007), and where PbtO2 was <10 mmHg (p=0.002). Logistic regression was used to study the relationship between temporal serum GFAP patterns and 6-month GOS-E. Here, the low and middle TRAJ groups were combined to form a low-risk group, and the high TRAJ group was designated the high-risk group. High TRAJ group patients had a greater chance of a poor 6-month GOS-E (p<0.0001). When adjusting for baseline injury characteristics, GFAP TRAJ group membership remained associated with GOS-E (p=0.003). When an ICU injury burden score, developed to quantify physiological derangements, was added to the model, GFAP TRAJ group membership remained associated with GOS-E (p=0.014). Mediation analysis suggested that ICU burden scores were in the causal pathway between TRAJ group and 6-month mortality or GOS-E. Our results suggest that GFAP may be useful to monitor serially in moderate-severe TBI patients. Future studies in larger cohorts are needed to confirm these results.

Language: en

Keywords

HEAD TRAUMA; BIOMARKERS; INTRACRANIAL PRESSURE; SECONDARY INSULT