Diuretic synergy in the treatment of acute experimental cerebral edema

Acute cerebral edema was created in dogs by the intracarotid injection of sodium lauryl sulfate, a method that produces no structural or vascular disruption in the brain. Cerebrospinal fluid (CSF) pressure elevations were measured through subdural balloons, and ranged from 300 to 1500 mm H2O. The nature of the cerebral edema produced was studied with intravital Trypan blue, electrocorticography, and visual observation of cerebral circulation, and by postmortem histological sections and determinations of brain water content. Two dissimilar diuretic agents were studied: the osmotic diuretic, mannitol; and the renal diuretic, ethacrynic acid. As expected, mannitol reduced CSF pressure effectively, with no significant rebound overshoot. Ethacrynic acid, despite favorable reports, proved to have only a slight effect on CSF pressure but did prove to be a potent diuretic. Unexpectedly, the two agents were found to act synergistically. When both agents were administered, significantly greater reductions in pressure were obtained and pressure reductions were maintained for longer periods.