Mild
hypothermia is effective in the prevention of
brain edema associated with
cerebral ischemia and
traumatic brain injury.
Brain edema is also a serious complication of
acute liver failure (ALF). To assess the effectiveness of
hypothermia in ALF, groups of rats were subjected to hepatic devascularization (
portacaval anastomosis, followed 48 hours later by hepatic artery
ligation), and body temperatures were maintained at either 35 degrees C (hypothermic) or 37 degrees C (normothermic). Mild
hypothermia resulted in a significant delay in the onset of severe
encephalopathy and in reduction of brain water content compared with normothermic ALF rats (control [n = 8] 80.22%; ALF-37 degrees C [n = 8] 81.74%; ALF-35 degrees C [n = 8] 80.48% [P <.01 compared with ALF-37 degrees C]). This protective effect was accompanied by a significant reduction of cerebrospinal fluid (CSF) (but not plasma)
ammonia concentrations (CSF
ammonia: control: 0.05 mg/dL; ALF-37 degrees C: 1.01 mg/dL; ALF-35 degrees C: 0.07 mg/dL, P <.01 compared with ALF-37 degrees C). In vivo cerebral microdialysis studies revealed that mild
hypothermia resulted in a significant reduction of extracellular
glutamate concentrations in the brains of rats with ALF (control: 1. 06 micromol/L; ALF-37 degrees C: 2.74 micromol/L; ALF-35 degrees C: 1.49 micromol/L [P <.01 compared with ALF-37 degrees C]). These findings suggest that: 1) mild
hypothermia is an effective approach to the prevention of the central nervous system consequences of experimental ALF; and that 2) the beneficial effect of
hypothermia is mediated via mechanisms involving reduced blood-brain transfer of
ammonia and/or reduction of extracellular brain
glutamate concentrations. Mild
hypothermia may be an effective approach to delay the onset of
brain edema in patients with ALF awaiting
liver transplantation.