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

Etiology1,2

  • 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.

Treatment

  • 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)

Prevention

  • 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

  References:

  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