Poisoning by drugs and chemicals - methods to increase poison elimination - technical
Once a poison has been absorbed and providing there is no antidote, it is reasonable to consider the use of treatments that might speed its elimination from the body.
Multiple-dose activated charcoal (MDAC)
Use of MDAC involves repeated administration of oral activated charcoal to increase the elimination of a drug that has already been absorbed into the body. Elimination of drugs with a small volume of distribution (<1 litre/kg), low pK a (which maximizes transport across membranes), low binding affinity, and prolonged elimination half-life following overdose is particularly likely to be enhanced by MDAC. MDAC also improves total body clearance of the drug when endogenous processes are compromised by liver and/or renal failure.
Activated charcoal adsorbs material in the gut, which may be relevant in cases of poisoning with slow-release drug preparations. It also adsorbs drugs that are secreted in the bile, thereby preventing intestinal reabsorption, and binds any drug that diffuses from the circulation into the gut lumen. After absorption, drugs re-enter the gut by passive diffusion if the concentration in the gut is lower than that in the blood. The rate of passive diffusion depends on the concentration gradient and the intestinal surface area, permeability, and blood flow. Occasionally, drugs such as digoxin may be secreted actively by the intestinal mucosa, though the contribution of active secretion to the effect of MDAC on drug clearance is unlikely to be greater than that of passive diffusion.
Although many studies have demonstrated that MDAC significantly increases drug elimination, it has not been shown to reduce morbidity and mortality in controlled studies in poisoned patients. At present, use of MDAC should be considered only in patients who have ingested a life-threatening amount of carbamazepine, dapsone, phenobarbital, quinine, and theophylline.
Clinical experience in adults suggests that charcoal should be administered in an initial dose of 50 to 100 g and then at a rate of not less than 12.5 g/h, preferably via a nasogastric tube. Smaller initial doses (10–25 g) can be used in children because, generally, smaller overdoses have been ingested and the capacity of the gut lumen is smaller. If the patient has ingested a drug that induces protracted vomiting (e.g. theophylline), intravenous ondansetron is effective as an anti-emetic and thus enables administration of MDAC.
Increasing the urine pH enhances elimination of salicylate, phenobarbital, chlorpropamide, and chlorophenoxy herbicides (e.g. 2,4-dichlorophenoxyacetic acid, mecoprop). However, with the exception of salicylate poisoning, urine alkalinization cannot be recommended as first-line therapy for poisoning with these agents, as MDAC is superior for phenobarbital, and supportive care is invariably adequate for chlorpropamide. A substantial diuresis is required in addition to urine alkalinization to achieve clinically important elimination of chlorophenoxy herbicides.
Urine alkalinization is a metabolically invasive procedure requiring frequent biochemical monitoring and medical and nursing expertise. Before commencing urine alkalinization, it is important to correct plasma volume depletion, electrolytes (administration of sodium bicarbonate exacerbates pre-existing hypokalaemia), and metabolic abnormalities. Sodium bicarbonate is most conveniently administered intravenously as an 8.4% solution (1 mmol bicarbonate/ml). Sufficient bicarbonate is administered (225 mmol was the mean amount required in one study) to ensure that the pH of the urine, which is measured by narrow-range indicator paper or a pH meter, is more than 7.5 and preferably close to 8.5. As the administration of sodium bicarbonate forces potassium into cells, it is important that the patient has a normal serum potassium concentration before sodium bicarbonate is administered. Sodium bicarbonate 8.4% is highly irritant to veins and severe tissue damage can ensue if extravasation occurs. A secure, preferably wide-bore cannula (or control venous line), must therefore be used.
Dialysis, haemodialfiltration, haemofiltration, and haemoperfusion
Haemodialysis significantly increases elimination of ethanol, ethylene glycol, isopropanol, lithium, methanol, and salicylate, and is the treatment of choice in all cases of severe poisoning with these agents. Although haemofiltration and haemodialfiltration are widely available and increase elimination of poisons such as ethylene glycol and methanol, they are much less efficient than haemodialysis, and therefore should not be used unless haemodialysis is unavailable.
Haemodialysis, haemofiltration, and haemoperfusion are of no value in patients poisoned with drugs with large volumes of distribution (e.g. tricyclic antidepressants), because the plasma contains only a small proportion of the total amount of drug in the body. They are indicated in patients with both severe clinical features and high plasma toxin concentrations.
Charcoal haemoperfusion can significantly reduce the body burden of phenobarbital, carbamazepine, and theophylline, but MDAC is as effective and simpler to use.
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