Extracorporeal Therapies in Acute Intoxication and Poisoning

Criteria for Consideration of Extracorporeal Therapy

Discrete indications to recommend the use of dialysis exist for many specific intoxicants, including agents with delayed toxicity, such as mushrooms, paraquat, methanol, and ethylene glycol. Dialysis also should be considered when endogenous drug clearance is impaired or markedly slower (e.g., cardiac, renal, or hepatic failure) than with available extracorporeal therapy.

In most cases, the decision to use dialysis for drug clearance during intoxication is clinical. Symptoms to consider include abnormalities in vital signs suggesting hemodynamic instability; clinical deterioration despite adequate supportive treatment; and mental status deterioration (including confusion, lethargy, stupor, and coma). In addition to removing the offending agent, dialysis may improve electrolyte abnormalities and correct the metabolic acidosis that may accompany some types of poisoning. Dialytic therapies, involving dialysate and diffusion to lower potassium concentration or deliver alkali, should be considered when concomitant metabolic disorders are present. Hypotensive patients requiring hemodynamic support with an indication for dialysis should receive an infusion of adrenergic or vasopressin-agonist pressors distal to the dialysis or sorbent cartridge. Furthermore, careful monitoring of circulatory status is essential because pressor clearance will be increased by the modalities and requirements may change.

Hemodialysis

Hemodialysis is the most commonly used method of extracorporeal drug removal in the treatment of poisoning. Factors governing the efficiency of drug removal with hemodialysis are drug related and dialysis related. Drug factors that increase removal are small molecular size (molecular weight <500 Da), high water solubility, low degree of protein-binding, small volume of distribution (<1 L/kg), and rapid equilibration of plasma and tissue to maintain a concentration gradient. Limited drug clearances should be expected with drugs that are highly lipid soluble, tightly tissue bound, with large volumes of distribution, and slow plasma equilibration. Dialysis factors include access type, blood and dialysate flow rates, and dialyzer properties (material, surface area, and pore size). The use of low blood flow rates may prevent hemodynamic instability but necessitate longer or continuous treatments for adequate clearance. Although higher dialysate flow rates will increase diffusive clearance to some degree, there is limited benefit beyond flow rates greater than 1.5 times that of blood.

With the use of membranes having larger pore size, larger molecular weight drugs can be cleared. For example, vancomycin is cleared readily with large pore (high-flux) membranes despite a molecular weight of 1400 Da. As molecular weight increases, drug removal is less a function of diffusion than convection (the creation of an ultrafiltrate).

Efficient clearance of a large molecular weight intoxicant may be accomplished best by combining filtration and dialysis. Although modern dialysis employs convection for volume removal and accurately can be termed convection dialysis, a discrete and emerging modality, hemodiafiltration, uses ultrafiltration across a high-flux dialysis membrane and countercurrent flow of dialysate for combined diffusive and convective clearance. The principle of hemofiltration, which relies upon convective clearance alone, is discussed subsequently.

A list of readily dialyzable drugs is provided in Box 99.1 .