Mild hypothermia delays the onset of coma and prevents brain edema and extracellular brain glutamate accumulation in rats with acute liver failure

Mild hypothermia is effective in the prevention of brain edema associated w ith cerebral ischemia and traumatic brain injury. Brain edema is also a ser ious complication of acute liver failure (ALF), To assess the effectiveness of hypothermia in ALF, groups of rats were subjected to hepatic devascular ization (portacaval anastomosis, followed 48 hours later by hepatic artery ligation), and body temperatures were maintained at either 35 degrees C (hy pothermic) or 37 degrees C (normothermic). Mild hypothermia resulted in a s ignificant 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 accompanie d 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 deg rees C). In vivo cerebral microdialysis studies revealed that mild hypother mia resulted in a significant reduction of extracellular glutamate concentr ations in the brains of rats with ALF (control: 1.06 mu mol/L; ALF37 degree s C: 2.74 mu mol/L; ALF-35 degrees C: 1.49 mu mol/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 conseque nces of experimental ALF; and that 2) the beneficial effect of hypothermia is mediated via mechanisms involving reduced blood-brain. transfer of ammon ia and/or reduction of extracellular brain glutamate concentrations. Mild h ypothermia may be an effective approach to delay the onset of brain edema i n patients with ALF awaiting liver transplantation.