Disequilibrium Syndrome

Disequilibrium Syndrome

The full blown syndrome is rarely seen now.  Disequilibrium syndrome most commonly occurs in:

  • First few dialysis sessions
  • Elderly and pediatric patients
  • Patients with pre-existing CNS lesions (recent stroke, head trauma) or conditions characterized by cerebral edema (malignant hypertension, hyponatremia, hepatic encephalopathy)
  • High pre-dialysis BUN
  • Severe metabolic acidosis


  • Cerebral edema resulting from urea removal from the blood more rapidly than from the CSF and brain tissue generating a urea osmotic gradient responsible for water moving into brain cells.
  • HD generates a CO2 gradient between plasma and CSF lowering the pH in the CSF and brain tissue.  This change will promote an increase in brain cell osmolality due to the rise in H+ concentration and the in-situ generation of osmols (acid radicals from protein metabolism) resulting in brain edema.


  • Usually self-limited.  However, for severe symptoms HD should be stopped.
  • If seizures occur, glucose, diazepam, phenytoin loading followed by infusion
  • Osmotically active agents in dialysate have been tried- albumin, glycerol, mannitol3)


  • Identify high risk patients
  • Reduce dialysis efficacy and limit urea reduction to 30% (smaller dialyzer, decreasing blood flow, sequential dialysis increasing dialysis time), however, a recent small series found tolerance to higher urea reduction4
  • Prophylactic administration of osmotically active agents (mannitol, glucose, fructose) and using high sodium dialysate
  • IV mannitol 20% at 50 ml/hr with intravenous diazepam- simplest way to prevent DDS in high risk patients5


  1. Port FK, Johnson WJ, Klass DW.  Prevention of dialysis disequilibrium syndrome by use of high sodium concentration in dialysis.  Kidney Int 3:327-333, 1973
  2. Arieff AI, Massry SG, Barrientos A, Kleman GR.  Brain water and electrolyte metabolism in uremia: Effects of slow and rapid HD.  Kidney Int 4:177-187, 1973
  3. Arieff AI. Dialysis disequilibrium syndrome: Current concepts on pathogenesis and prevention [editorial]. Kidney Int 45:629-635, 1994
  4. Macon EJ. Dialysis disequilibrium after acute dialysis: Must the urea reduction ratio be limited to 30%? J Am Soc Nephrol 9:259A 1998
  5. Anthony J Nicholls: Nervous System in  Daugirdas JT, Blake PG, Todd SI eds : Handbook of Hemodialysis. Third Edition. Philadelphia: Lippincott Williams & Wilikns. 2001:656-666