Experimental dialysis disequilibrium syndrome: Prevention with glycerol

Abstract

Experimental dialysis disequilibrium syndrome: Prevention with glycerol. Patients with renal failure being treated with hemodialysis may develop a clinical syndrome characterized by headache, restlessness, nausea, and emesis, which may progress to seizures and coma. An experimental model of this syndrome, called dialysis disequilibrium syndrome (DDS), can be induced by rapid hemodialysis of uremic dogs (BUN, 200 mg/dl; creatinine, 11 mg/dl). In the experimental model, dogs treated with rapid dialysis developed a brain-to-plasma osmotic gradient which resulted in cerebral edema. There was also a fall in both pH of cerebrospinal fluid (CSF) and intracellular pH (pH i ) of cerebral cortex and an abnormal electroencephalogram (EEG). The cerebral edema was characterized by an increased osmole content in cerebral cortex tissue. The increased osmole content was not related to retention in brain of sodium, potassium, chloride, urea, or lactate, but was due to undetermined solute (idio-genic osmole s). When dialysis was modified by the addition of mannitol to the dialysate (plasma mannitol, 26 mM), brain edema did not occur, and the fall in brain pH i was prevented. The EEG, however, remained abnormal, and the pH of CSF fell. When dialysis was modified by adding glycerol to the dialysate (plasma glycerol, 26 mM), brain edema did not occur, brain pH i and the pH of CSF were normal, and the EEG improved towards normal. After dialysis with either mannitol or glycerol in the dialysate, idiogenic osmoles were not present in the brain. Eliminating the fall in brain pH i appeared to prevent the formation of idiogenic osmoles by cerebral cortex. Thus, DDS was partially prevented by mannitol added to the dialysate. Glycerol, however, not only prevented all the manifestation of DDS but also restored the EEG to a normal pattern. Glycerol may be a useful agent for prevention of dialysis disequilibrium in man.