Pharmacokinetics of Haemoperfusion for Drug Overdose

Abstract

Haemoperfusion has been used increasingly in treatment of patients with drug overdose. Blood is pumped from the patient through a column of adsorbent material and recirculated back to the patient. The adsorbent materials, activated charcoal and Amberlite XAD-4 resin, avidly bind particular drugs so that extraction from blood, including protein bound drug, is nearly complete. Activated charcoal removes both polar and nonpolar drugs and probably metabolites; Amberlite removes non-polar drugs better than charcoal but does not remove more polar drugs or polar metabolites. The haemoperfusion cartridge can be regarded as an extracorporeal clearance organ. Methodological issues in computing column clearance are discussed. The efficacy of haemoperfusion in removing a drug is determined by the relative magnitude of haemoperfusion and intrinsic body clearance, by volume of distribution, and by rate of movement of drug from peripheral tissues to the blood compartment. Haemoperfusion is most efficacious for drugs with low intrinsic clearance and a relatively small volume of distribution, such as phenobarbitone, theophylline, and tolbutamide. In contrast, haemoperfusion removes only a small fraction of drugs with high intrinsic clearance and large volumes of distribution, such as digoxin and amitriptyline. Drug overdose may influence pharmacokinetics of drugs such as salicylate, Phenytoin, and ethchlorvynol, making predictions and evaluation of haemoperfusion difficult. Clinical reports of haemoperfusion treatment for drug overdose indicate that haemoperfusion can effectively remove certain drugs and potentially significantly influence the clinical outcome, although the latter remains to be proven. Haemoperfusion is quite effective in removing phenobarbitone. Short and intermediate acting barbiturates are also removed in substantial quantity, but because of a larger volume of distribution they demonstrate rebound increase in blood concentrations with possible associated clinical deterioration, after haemoperfusion is completed. Haemoperfusion appears to be less effective for glulethimide because of the drug’s large volume of distribution, compared with barbiturates, and rebound appears to be an even more significant problem. Haemoperfusion may be useful in treating overdosage with ethchlorvynol or Phenytoin, particularly with high blood concentrations of drug, when the intrinsic clearance of the drug may be quite low due to non-linear metabolism. Salicylate can be removed by charcoal haemoperfusion, but no more effectively than can be effected with haemodialysis. The latter has the advantage of providing a means for fluid and electrolyte control and not requiring systemic heparinisation. Haemoperfusion does not substantially remove digoxin and tricyclic antidepressants compared with the total body burden because of the extremely large volumes of distribution. However, clinical responses during haemoperfusion for these types of overdose have been reported. Temporary reduction in the concentrations of these drugs in the brain or heart or removal of active metabolites might account for a discrepancy. Haemoperfusion is quite effective for removing theophylline, a drug with a small volume of distribution and moderate intrinsic clearance, and results in substantial clinical benefit. The major complication of haemoperfusion is thrombocytopenia with the potential risk of haemorrhage. Platelet counts are commonly halved during haemoperfusion and return to normal levels over 1 to 2 days.