Effects of early adjunctive pharmacotherapy on serum levels of brain injury biomarkers in patients with traumatic brain injury: a systematic review of randomized controlled studies

Abstract

Objectives: Traumatic brain injury (TBI) is one of the top causes of morbidity and mortality worldwide. The review aimed to discuss and summarize the current evidence on the effectiveness of adjuvant neuroprotective treatments in terms of their effect on brain injury biomarkers in TBI patients.Methods: To identify relevant studies, four scholarly databases, including PubMed, Cochrane, Scopus, and Google Scholar, were systematically searched using predefined search terms. English-language randomized controlled clinical trials reporting changes in brain injury biomarkers, namely, neuron-specific enolase (NSE), glial fibrillary acid protein (GFAP), ubiquitin carboxyl-terminal esterase L1 (UCHL1) and/or S100 beta (S100 ß), were included. The methodological quality of the included studies was assessed using the Cochrane risk-of-bias tool.Results: A total of eleven studies with eight different therapeutic options were investigated; of them, tetracyclines, metformin, and memantine were discovered to be promising choices that could improve neurological outcomes in TBI patients. The most utilized serum biomarkers were NSE and S100 ß followed by GFAP, while none of the included studies quantified UCHL1. The heterogeneity in injury severity categories and measurement timing may affect the overall evaluation of the clinical efficacy of potential therapies. Therefore, unified measurement protocols are highly warranted to inform clinical decisions.Conclusion: Few therapeutic options showed promising results as an adjuvant to standard care in patients with TBI. Several considerations for future work must be directed towards standardizing monitoring biomarkers. Investigating the pharmacotherapy effectiveness using a multimodal biomarker panel is needed. Finally, employing stratified randomization in future clinical trials concerning potential confounders, including age, trauma severity levels, and type, is crucial to inform clinical decisions.Clinical Trial Registration: [https://www.crd.york.ac.uk/prospero/dis], identifier [CRD42022316327].

Effectiveness of biomedical interventions on the chronic stage of traumatic brain injury: a systematic review of randomized controlled trials

“…While this systematic review focuses on the effects of pharmacological, stimulation, and exercise-based interventions on the chronic phases of TBI, it remains imperative to compare and contrast their effectiveness between acute and chronic phases. This consideration is especially crucial in light of a recent systematic review pointing to the pharmacological efficacy in acute TBI ( 70 ).…”

Biomarkers associated with functional improvement after stroke rehabilitation: a systematic review and meta-analysis of randomized controlled trials

“…Over time, more data on biomarkers in stroke patients and the recovery of patients from different dysfunctions are needed to establish a timeline of biomarker changes and functional recovery progress, and determine the most sensitive and specific prognostic and diagnostic marker. In the future, brain injury biomarkers may also be normalized in brain-injured patients through therapies, such as adjunctive neuroprotective therapies, thereby improving neurological outcomes ( 65 ). The present study contained RCTs based on rigorous criteria, and the summarized evidence provided high quality data for this field.…”

The management of severe traumatic brain injury in the initial postinjury hours – current evidence and controversies

“…To decrease ICP, bedside manoeuvres such as sedation, cerebrospinal fluid (CSF) drainage, and, in refractory cases, barbiturate coma or DC can be used (Table 2) [15,31,32]. Of note, while several potentially neuroprotective agents that have been investigated in clinical trials, all failed to show benefit for sTBI [33,34 ▪ ].…”