Therapeutic hypothermia preserves antioxidant defenses after severe traumatic brain injury in infants and children
Date
2009
Journal Title
Journal ISSN
Volume Title
Publisher
Critical care medicine
Abstract
Oxidative stress contributes to secondary damage after traumatic brain injury (TBI). Hypothermia decreases endogenous antioxidant consumption and lipid peroxidation after experimental cerebral injury. Our objective was to determine the effect of therapeutic hypothermia on oxidative damage after severe TBI in infants and children randomized to moderate hypothermia vs normothermia. Design: Prospective randomized controlled study. Setting: Pediatric ICU of Pittsburgh Children’s Hospital. Patients: The study included 28 patients. Measurements and main results: We compared the effects of hypothermia (32-33°C) vs normothermia in patients treated in a single center involved in a multi-center randomized controlled trial of hypothermia in severe pediatric TBI (GCS score ≤ 8). The patients randomized to hypothermia (n=13) were cooled to target temperature within ∼6h-24h for 48h and then re-warmed. Antioxidant status was assessed by measurements of total antioxidant reserve [AOR] and glutathione. Protein oxidation and lipid peroxidation were assessed by measurements of protein-thiols and F2-isoprostane, respectively in ventricular CSF samples (n=76) obtained on day1-3 after injury. The association between GCS score, age, gender, treatment, temperature, time after injury, and CSF AOR, glutathione, protein-thiol, F2-isoprostane levels were assessed by bivariate and multiple regression models. Demographic and clinical characteristics were similar between the two treatment groups. Mechanism of injury included both accidental injury and nonaccidental injury. Multiple regression models revealed preservation of CSF antioxidant reserve by hypothermia (p = 0.001). Similarly, a multiple regression model showed that glutathione levels were inversely associated with patient temperature at the time of sampling (p = 0.002). F2-isoprostane levels peaked on day 1 after injury and were progressively decreased thereafter. Although F2-isoprostane levels were ∼3-fold lower in patients randomized to hypothermia vs. normothermia, this difference was not statistically significant. Conclusion: To our knowledge this is the first study demonstrating that hypothermia attenuates oxidative stress after severe TBI in infants and children. Our data also support the concept that CSF represents a valuable tool for monitoring treatment effects on oxidative stress after TBI. (Author Abstract)
Description
item.page.type
Article
item.page.format
Keywords
child abuse, head injury, treatment, therapy, research
Citation
Bayir, H., Adelson, P. D., Wisniewski, S. R., Shore, P., Lai, Y., Brown, D., ... & Kochanek, P. M. (2009). Therapeutic hypothermia preserves antioxidant defenses after severe traumatic brain injury in infants and children. Critical care medicine, 37(2), 689.