Amelioration of Acute Sequelae of Blast Induced Mild Traumatic Brain Injury by N-Acetyl Cysteine: A Double-Blind, Placebo Controlled Study
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BACKGROUND: Mild traumatic brain injury (mTBI) secondary to blast exposure is the most common battlefield injury in Southwest Asia. There has been little prospective work in the combat setting to test the efficacy of new countermeasures. The goal of this study was to compare the efficacy of N-acetyl cysteine (NAC) versus placebo on the symptoms associated with blast exposure mTBI in a combat setting. METHODS: This study was a randomized double blind, placebo-controlled study that was conducted on active duty service members at a forward deployed field hospital in Iraq. All symptomatic U.S. service members who were exposed to significant ordnance blast and who met the criteria for mTBI were offered participation in the study and 81 individuals agreed to participate. Individuals underwent a baseline evaluation and then were randomly assigned to receive either N-acetyl cysteine (NAC) or placebo for seven days. Each subject was re-evaluated at 3 and 7 days. Outcome measures were the presence of the following sequelae of mTBI: dizziness, hearing loss, headache, memory loss, sleep disturbances, and neurocognitive dysfunction. The resolution of these symptoms seven days after the blast exposure was the main outcome measure in this study. Logistic regression on the outcome of 'no day 7 symptoms' indicated that NAC treatment was significantly better than placebo (OR = 3.6, p = 0.006). Secondary analysis revealed subjects receiving NAC within 24 hours of blast had an 86% chance of symptom resolution with no reported side effects versus 42% for those seen early who received placebo. CONCLUSION: This study, conducted in an active theatre of war, demonstrates that NAC, a safe pharmaceutical countermeasure, has beneficial effects on the severity and resolution of sequelae of blast induced mTBI. This is the first demonstration of an effective short term countermeasure for mTBI. Further work on long term outcomes and the potential use of NAC in civilian mTBI is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT00822263.
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N-acetylcysteine administration after blast traumatic brain injury was associated with improved executive function compared with controls.
“NAC administration after blast traumatic brain injury was associated with improved executive function compared with that observed for controls [158].”
From Cognitive remission: a novel objective for the treatment of major depression? (2016) · cites this paper as [158]
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- Authors
- Hoffer, M. E., Balaban, C., Slade, M. D., Tsao, J. W., & Hoffer, B.
- Affiliations
- Naval Medical Center San Diego (US)
- University of Pittsburgh (US)
- Yale University (US)
- Bureau of Medicine and Surgery (US)
- Case Western Reserve University (US)
- Corresponding author
- Hoffer, Michael E.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-01-23
- Volume
- 8
- Issue
- 1
- Pages
- e54163
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3553161
- OpenAlex
- W2119701105
- Cited by
- 207
- References
- 42
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 12 · 2023: 8 · 2022: 15 · 2021: 12 · 2020: 19 · 2019: 16 · 2018: 14 · 2017: 24 · 2016: 25 · 2015: 16 · 2014: 14 · 2013: 10 · 2012: 1
- FWCI
- 15.79
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, public-domain)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- D-Scholarship@Pitt (University of Pittsburgh) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- U.S. Department of Defense
- U.S. Navy
- Topics
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Automotive and Human Injury Biomechanics
- Keywords
- mild traumatic brain injury, blast injury, N-acetylcysteine, combat casualty care, military personnel, neurocognitive impairment, symptom resolution, countermeasures, dizziness, headache, sleep disorders, memory loss, hearing loss
- MeSH terms
- Acetylcysteine, Adolescent, Adult, Blast Injuries, Brain Injuries, Cognition Disorders, Double-Blind Method, Female, Humans, Sleep Initiation and Maintenance Disorders, Male, Memory Disorders, Military Personnel, Neuropsychological Tests, Placebos, Severity of Illness Index, Free Radical Scavengers, Iraq War, 2003-2011
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