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Randomized Controlled Trial
. 2009 Feb;37(2):689-95.
doi: 10.1097/CCM.0b013e318194abf2.

Therapeutic hypothermia preserves antioxidant defenses after severe traumatic brain injury in infants and children

Hülya Bayir  1 , P David Adelson, Stephen R Wisniewski, Paul Shore, YiChen Lai, Danielle Brown, Keri L Janesko-Feldman, Valerian E Kagan, Patrick M Kochanek
Affiliations
Randomized Controlled Trial

Therapeutic hypothermia preserves antioxidant defenses after severe traumatic brain injury in infants and children

Hülya Bayir et al. Crit Care Med. 2009 Feb.

Erratum in

  • Crit Care Med. 2009 Apr;37(4):1536

Abstract

Objective: 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 intensive care unit of Pittsburgh Children's Hospital.

Patients: The study included 28 patients.

Measurements and main results: We compared the effects of hypothermia (32 degrees C-33 degrees C) vs. normothermia in patients treated in a single center involved in a multicentered randomized controlled trial of hypothermia in severe pediatric TBI (Glasgow Coma Scale score <or=8). The patients randomized to hypothermia (n = 13) were cooled to target temperature within approximately 6 to 24 hours for 48 hours and then rewarmed. Antioxidant status was assessed by measurements of total antioxidant reserve and glutathione. Protein oxidation and lipid peroxidation were assessed by measurements of protein thiols and F2-isoprostane, respectively, in ventricular cerebrospinal fluid (CSF) samples (n = 76) obtained on day 1-3 after injury. The association between Glasgow Coma Scale score, age, gender, treatment, temperature, time after injury, and CSF antioxidant reserve, 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 approximately three-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.

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Figures

Figure 1
Figure 1
Effect hypothermia on CSF antioxidant reserves after TBI. Hypothermia preserved antioxidant reserves after TBI compared with normothermia.
Figure 2
Figure 2
Effect of hypothermia and time on CSF GSH levels after TBI.
Figure 3
Figure 3
Effect of hypothermia and time on CSF Protein sulfydryl levels after TBI.
Figure 4
Figure 4
Effect of hypothermia and time on CSF F2-isoprostane levels after TBI.
See this image and copyright information in PMC

Comment in

References

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