Effect of drug therapy on nerve repair of moderate-severe traumatic brain injury: A network meta-analysis

Objective: This network meta-analysis aimed to explore the effect of different drugs on mortality and neurological improvement in patients with traumatic brain injury (TBI), and to clarify which drug might be used as a more promising intervention for treating such patients by ranking. Methods: We conducted a comprehensive search from PubMed, Medline, Embase, and Cochrane Library databases from the establishment of the database to 31 January 2022. Data were extracted from the included studies, and the quality was assessed using the Cochrane risk-of-bias tool. The primary outcome measure was mortality in patients with TBI. The secondary outcome measures were the proportion of favorable outcomes and the occurrence of drug treatment–related side effects in patients with TBI in each drug treatment group. Statistical analyses were performed using Stata v16.0 and RevMan v5.3.0. Results: We included 30 randomized controlled trials that included 13 interventions (TXA, EPO, progesterone, progesterone + vitamin D, atorvastatin, beta-blocker therapy, Bradycor, Enoxaparin, Tracoprodi, dexanabinol, selenium, simvastatin, and placebo). The analysis revealed that these drugs significantly reduced mortality in patients with TBI and increased the proportion of patients with favorable outcomes after TBI compared with placebo. In terms of mortality after drug treatment, the order from the lowest to the highest was progesterone + vitamin D, beta-blocker therapy, EPO, simvastatin, Enoxaparin, Bradycor, Tracoprodi, selenium, atorvastatin, TXA, progesterone, dexanabinol, and placebo. In terms of the proportion of patients with favorable outcomes after drug treatment, the order from the highest to the lowest was as follows: Enoxaparin, progesterone + vitamin D, atorvastatin, simvastatin, Bradycor, EPO, beta-blocker therapy, progesterone, Tracoprodi, TXA, selenium, dexanabinol, and placebo. In addition, based on the classification of Glasgow Outcome Scale (GOS) scores after each drug treatment, this study also analyzed the three aspects of good recovery, moderate disability, and severe disability. It involved 10 interventions and revealed that compared with placebo treatment, a higher proportion of patients had a good recovery and moderate disability after treatment with progesterone + vitamin D, Bradycor, EPO, and progesterone. Meanwhile, the proportion of patients with a severe disability after treatment with progesterone + vitamin D and Bradycor was also low. Conclusion: The analysis of this study revealed that in patients with TBI, TXA, EPO, progesterone, progesterone + vitamin D, atorvastatin, beta-blocker therapy, Bradycor, Enoxaparin, Tracoprodi, dexanabinol, selenium, and simvastatin all reduced mortality and increased the proportion of patients with favorable outcomes in such patients compared with placebo. Among these, the progesterone + vitamin D had not only a higher proportion of patients with good recovery and moderate disability but also a lower proportion of patients with severe disability and mortality. However, whether this intervention can be used for clinical promotion still needs further exploration.