A Computer Simulation Study Relating to the Treatment of Fulminant Hepatic Failure by Hemoperfusion

Abstract

A lag period of 12-24 hr has frequently been observed to elapse between charcoal hemoperfusion therapy and arousal of patients in stage IV coma due to fulminant hepatic failure. This delay suggests that recovery of consciousness depends on depletion of an extravascular pool of a hypothetical toxin which requires 12-24 hr to equilibrate with plasma. No further definitive information about the nature of the toxin is available. Unconjugated biliru-bin is known to have an extrahepatic, extra-vascular pool which also equilibrates with plasma over a 12- to 24-hr period. Accordingly, a model of unconjugated bilirubin kinetics has been used to investigate the rate of depletion of slowly equilibrating extra-vascular metabolic compartments by hemoperfusion, employing computer simulation techniques. The results indicate that the rate of depletion of slowly equilibrating extravascular pools is critically dependent not merely on the intrinsic efficiency of the hemoperfusion device, but also on the schedule with which it is employed. The conventionally employed regimen of 4-hr of treatment per day is relatively inefficient in achieving depletion of such compartments. These data imply, by analogy, that alternative hemoperfusion regimens, employing longer initial perfusion or perfusions at intervals of approximately 12 hr, would be more effective than current schedules in awakening patients with acute hepatic coma.