Introduction: Many reports have shown benefit from hypothermia in traumatic brain injury (TBI); but its effect in the setting of TBI with secondary insult remains undefined. Clinical studies show an increase in morbidity and mortality after severe TBI with secondary brain insult.1 In experimental rat models, outcomes were worse in brain injury with secondary hypoxia.2 Recently, we characterized a model of TBI with secondary hypoxemia and reported prominent neuronal apoptosis after injury.3,4 We hypothesized that hypothermia would improve outcome after controlled-cortical impact (CCI) with secondary hypoxemic insult in rats. Methods: Rats were subjected to severe CCI injury followed by 30 min of hypoxemia (PaO2=35-45 mm Hg).3 Rats were then randomized to normothermia (NT=37°C, n=19), immediate hypothermia (IHT=32°C, after CCI, n=10), or delayed hypothermia (DHT=32°C, after hypoxemia, n=14) for 4 h. Motor (beam balance/ beam walking, d 1-5), cognitive (Morris Water Maze [MWM], d 14-21) and histologic outcome (lesion volume, hippocampal neuron counts, d21) were evaluated. Results: Motor and MWM performance were impaired, but did not differ between groups. Lesion volumes did not differ significantly between groups (NT=65.3 mm3 ±6.9, IHT=50.2±8.2, DHT=53.7±7.9). Hippocampal neuron counts (CA1,CA3) were decreased on the injured side, but did not differ between groups (NT-CAI = 19.8±4.2 cells/hpf, NT-CA3=19.8±4.6, IHT-CA1 = 13.2±8.7, IHT-CA3= 15.6±7.3, DHT-CA1 = 13.7±5.8, DHT-CA3=18.5±7.3). Mortality rate did not differ significantly between groups. Conclusions: Immediate or delayed hypothermia did not improve long-term outcome after severe CCl with secondary hypoxemia in rats. The severity of the combined insult may be outside of the therapeutic window of opportunity. Clinical studies5 have excluded patients with secondary insult, and have indicated that hypothermia is of limited efficacy in the subset of severely injured (GCS 3-4) patients. Novel therapeutic approaches or combination therapies may by necessary in this setting.
ASJC Scopus subject areas
- Critical Care and Intensive Care Medicine