Repurposing of high-dose N-acetylcysteine as anti-inflammatory, antioxidant and neuroprotective agent in moderate to severe traumatic brain injury patients: a randomized controlled trial

Abstract

Introduction Traumatic brain injury (TBI) refers to an impact of the brain within the skull resulting in an altered mental state. The study aim is to determine the effect of a high dose of N -acetylcysteine (NAC) on biochemical and inflammatory markers of neuronal damage and clinical outcomes in patients with moderate to severe TBI. Methods A randomized open label-controlled trial was conducted on 40 patients with moderate to severe TBI patients presented to the emergency unit within < 24 h since the trauma occurred and randomized into NAC and control groups 20 patients each. Serum samples for evaluation of biomarkers: malondialdehyde (MDA), interleukin-6 (IL-6), neuron-specific enolase (NSE), and S100B were withdrawn at baseline and on day 7. The patients were followed for 7 days and evaluated clinically by the Glasgow Coma Scale (GCS). Results There was a significant decrease in NSE and MDA levels on day 7 from baseline in NAC group ( p < 0.001 and p < 0.001). Also, S100B and IL-6 decreased significantly in NAC group on day 7 from baseline ( p = 0.003 and p < 0.001 consequently) compared to control group. Moreover, patients in NAC group showed a significantly shorter length of stay at intensive care unit (ICU) ( p = 0.038). There was a significant increase in GCS in NAC group on day 7 from baseline ( p = 0.001). Conclusion Adjunctive early use of high-dose NAC significantly reduced inflammatory and oxidative markers and had neuroprotective effect which may be a novel treatment option for moderate to severe TBI patients. Trial registration Pactr.org identifier: (PACTR202209548995270) on 14 September 2022.

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