Background Severe traumatic brain injury (sTBI) often results in prolonged coma and significant long-term disability. Evidence-based, widely accessible approaches to accelerate recovery of consciousness remain limited. This study evaluated whether adding a combined regimen of hyperbaric oxygen therapy (HBOT) and systematic auditory stimulation (SAS) to standard neurosurgical care improves recovery of consciousness and short-term outcomes in comatose patients with sTBI. Methods In this prospective randomized controlled trial, 89 comatose patients with sTBI Glasgow Coma Scale (GCS) 8 were randomized to standard neurosurgical care (control, n = 44) or standard care in addition to HBOT and SAS (HBOT+SAS, n = 45). HBOT was delivered at a pressure of 2.0 atmospheres absolute (ATA) for 60 min/session, five sessions per week for 4 weeks. SAS consisted of structured family-delivered storytelling and music sessions three times daily following a predefined schedule. The primary outcome was the change in the Full Outline of UnResponsiveness (FOUR) score from baseline to Day 28. Secondary outcomes included the GCS and Coma Recovery Scale-Revised (CRS-R) scores, the Glasgow Outcome Scale (GOS) score at 3 months, and serum biomarkers such as S100B, neuron-specific enolase (NSE), and brain-derived neurotrophic factor (BDNF); care-related satisfaction was analyzed as an exploratory outcome. Secondary endpoints were interpreted using a prespecified Bonferroni-adjusted threshold ( p 0.01). Results Compared to the control group, the HBOT+SAS group demonstrated greater improvement in measures of consciousness at Day 28 (FOUR: 12.1 ± 2.4 vs. 9.3 ± 2.1; GCS: 11.3 ± 2.2 vs. 9.1 ± 1.9; CRS-R: 11.8 ± 2.3 vs. 8.1 ± 2.0; all p 0.001). At 3 months, the functional outcome was higher in the HBOT+SAS group (GOS: 4.3 ± 0.5 vs. 3.6 ± 0.6, p 0.001). Biomarker patterns indicated a reduction in neuronal injury and an enhancement in neurotrophic activity. Specifically, levels of S100B and NSE were lower in the HBOT+SAS group (both p 0.001), and BDNF was higher ( p = 0.003) in this group. No serious adverse events related to the intervention were reported. Satisfaction outcomes favored HBOT+SAS (88.89% vs. 59.09%, p = 0.005) and were interpreted as exploratory due to the unblinded design of the study. Conclusion The addition of HBOT+SAS to standard care was associated with improved recovery of consciousness and better 3-month functional outcomes in comatose patients with sTBI, supported by consistent findings from clinical scales and serum biomarkers. However, since the trial did not include HBOT-only or SAS-only comparator arms, the findings support the effectiveness of the combined regimen compared to standard care but do not determine whether HBOT and SAS have a synergistic effect.
Rong et al. (Thu,) studied this question.