Energy metabolism and pharmacodynamics in the human injured brain - a clinical microdialysis study

Nerv cell damage due to malperfusion is a main contributing factor to morbidity and mortality after subarachnoid hemorrhage (SAH). Malperfusion leads to a change in energy metabolism and as a consequence, concentrations of energy metabolites in the extracellular fluid of the brain vary. By the use of the microdialysis technique, continuous and reliable bed-side registration of the composition of the extracellular fluid is possible. The analysis of chemical substances in the outlet fluid of the microdialysis catheter allows conclusions on the metabolism of the studied organ. The aim of the study is to investigate the efficacy of certain therapy strategies which improve cerebral perfusion pressure and oxygenation after SAH and to obtain further knowledge on the question which level of perfusion pressure is necessary to prevent malperfusion in SAH. The concentrations of energy metabolites in the first days after SAH will be registered and compared to the course of clinical parameters (intracranial pressure, perfusion pressure, oxygen tissue pressure, electrical activity). Alterations due to routine therapies changing perfusion pressure will be registered and analysed. Antiepileptic prophylaxis is generally recommended in patients after SAH because the risk for epileptic seizures is high and may aggravate cerebral oxygenation critically. Phenytoin is the most widely used antiepileptic for this indication. Valproic acid is also a broad spectrum antiepileptic, the frequency of critical side effects is discussed to be lower. Knowledge on the time-profile of drug concentrations in brain tissue could offer the possibility of adjusting the drug dose directly to its tissue concentration. This will be important for the future management of centrally acting drugs like antiepileptics. The therapeutic effect could possibly be improved and adverse effects kept as low as possible. The aim of the second part of the study is to investigate the time-profile of cerebral tissue concentrations of both antiepileptics, to compare to the time-profile of blood concentrations, to compare the clinical efficacy of both drugs and to evaluate a possibly alternative therapy with fewer adverse effects.