Acceleration Of Elimination Of The Poison

Techniques for eliminating poisons have a role that is limited, but important when applicable.

Each method depends, directly or indirectly, on removing drug from the circulation and successful use requires that:

• The poison should be present in high concentration in the plasma relative to that in the rest of the body, i.e. it should have a small distribution volume

• The poison should dissociate readily from any plasma protein binding sites

• The effects of the poison should relate to its plasma concentration.

Methods used are:

Repeated doses of activated charcoal

Activated charcoal by mouth not only adsorbs ingested drug in the gut, preventing absorption into the body (see above), it also adsorbs drug that diffuses from the blood into the gut lumen when the concentration there is lower; because binding is irreversible the concentration gradient is maintained and drug is continuously removed; this has been called 'intestinal dialysis'. Charcoal may also adsorb drugs that are secreted into the bile, i.e. by interrupting an enterohepatic cycle. Evidence shows that activated charcoal in repeated doses effectively adsorbs (shortens tV2 of) phénobarbital (phenobarbitone), carbamazepine, theophylline, quinine, dapsone and salicylate.6 Repeated-dose activated charcoal is increasingly preferred to alkalinisation of urine (below) for phenobarbitone and salicylate poisoning. Activated charcoal in an initial dose of 50-100 g should be followed by not less than 12.5 g/h; the regular hourly administration is more effective than larger amounts less often.

Alteration of urine pH and diuresis

By manipulation of the pH of the glomerular filtrate, a drug can be made to ionise, become less lipid-soluble, remain in the renal tubular fluid, and so be eliminated in the urine (see p. 97). Maintenance of a good urine flow (e.g. 100ml/h) helps this process but it is the alteration of tubular fluid pH that is all important. The practice of forcing

6 Bradberry S M, Vale A] 1995 Journal of Toxicology: Clinical Toxicology 33(5): 407-416.

diuresis with frusemide (furosemide) and large volumes of i.v. fluid does not add significantly to drug clearance but may cause fluid overload; it is obsolete. Alkalinisation may be used for salicylate (>500mg/l + metabolic acidosis, or in any case > 750 mg/1), phenobarbital (75-150 mg/1) or phenoxy herbicides, e.g. 2,4-D, mecoprop, dichlorprop. The objective is to maintain a urine pH of 7.5-8.5 by an i.v. infusion of sodium bicarbonate. Available preparations of sodium bicarbonate vary between 1.2 and 8.4% (1 ml of the 8.4% preparation contains 1 mmol of sodium bicarbonate) and the concentration given will depend on the patient's fluid needs.

Acidification may be used for severe, acute amphetamine, dexfenfluramine or phencyclidine poisoning. The objective is to maintain a urine pH of 5.5-6.5 by giving i.v. infusion of arginine hydrochloride (10 g) over 30 min, followed by ammonium chloride (4 g) 2-hourly by mouth. It is rarely necessary. Phenoxybenzamine should be adequate for amphetamine-like drugs (a-adrenoceptor block).

Peritoneal dialysis

Peritoneal dialysis involves instilling appropriate fluid into the peritoneal cavity. Poison in the blood diffuses into the dialysis fluid down the concentration gradient. The fluid is then drained and replaced. The technique requires little equipment but is one-half to one-third as effective as haemo-dialysis; it may be worth using for lithium and methanol poisoning.

Haemodialysis and haemoperfusion

A temporary extracorporeal circulation is established, usually from an artery to a vein in the arm. In haemodialysis, a semipermeable membrane separates blood from dialysis fluid and the poison passes passively from the blood, where it is present in high concentration. The principle of haemoperfusion is that blood flows over activated charcoal or an appropriate ion-exchange resin which adsorbs the poison. Loss of blood cells and activation of the clotting mechanism are largely overcome by coating the charcoal with an acrylic hydrogel which does not reduce adsorbing capacity, though the patient must be anticoagulated with heparin.

Such artificial methods of removing poison from the body are invasive, demand skill and experience on the part of the operator and are expensive in manpower. Their use should therefore be confined to cases of severe, prolonged or progressive clinical intoxication, when high plasma concentration indicates a dangerous degree of poisoning, and when removal by haemoperfusion or dialysis constitutes a significant addition to natural methods of elimination.

• Haemodialysis is effective for: salicylate (> 750 mg/1 + renal failure, or in any case

> 900 mg/1), isopropanol (present in aftershave lotions and window-cleaning solutions), lithium and methanol.

• Haemoperfusion is effective for: phenobarbitone (> 100-150 mg/1, but repeat-dose activated charcoal by mouth appears to be as effective, see above) and other barbiturates, ethchlorvynol, glutethimide, meprobamate, methaqualone, theophylline, trichloroethanol derivatives.

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