Controlled Mild Hypothermia Prolongs Survival in a Rat Model of Large Scald Burns

Abstract

Early surface cooling of burns reduces pain and depth of injury and improves healing. However, there are concerns that cooling of large burns may result in hypothermia and worsen outcomes. In contrast, controlled mild hypothermia improves outcomes after cardiac arrest and traumatic brain injury. The authors hypothesized that controlled mild hypothermia would prolong survival in a rat model of large scald burns. Thirty-six Sprague-Dawley rats (250-300 g) were anesthetized with 40 mg/kg intramuscular ketamine and 5 mg/kg xylazine, with supplemental inhalational isoflurane as needed. A single full-thickness scald burn covering 40% of total body surface area was created on each of the rats using a Mason-Walker template placed in boiling water (100 °C) for a period of 10 seconds. The rats were then randomized to hypothermia (n = 18) or no hypothermia (n = 18). Core body temperature was continuously monitored with a rectal temperature probe. In the experimental group, mild hypothermia was induced by applying ice packs over the prone rats until their rectal temperature was reduced by 2 °C for a period of 2 hours. After 2 hours of hypothermia, the rats were rewarmed back to their baseline temperature with a heating pad. The control rats were not cooled. The rats were monitored until death or for a period of 7 days, whichever was greater. The primary outcome was time to death. The difference in survival between the groups was determined using Kaplan-Meier analysis and the log-rank test. Hypothermia was induced in all experimental rats within a mean of 22 minutes (95% confidence interval [CI] = 17 to 27). The numbers of nonhypothermic and hypothermic rats that were dead at each time point were as follows: 2 hours, five versus none; 18 hours, 16 versus five; 24 hours, 18 versus eight; and 48 hours, 18 versus 13 (p = 0.05). There were no additional deaths after 48 hours. The mean time to survival of the hypothermic rats was significantly greater than that of the nonhypothermic rats (p < 0.001). Induction of brief, mild hypothermia prolongs survival and increases the survival rate in nonresuscitated rats with large scald burns.