A Textbook of Clinical Pharmacology and Therapeutics

446 DRUG OVERDOSE AND POISONING

appropriate resuscitation, repeated observations are neces-
sary, as drugs may continue to be absorbed with a subsequent
increase in plasma concentration. In the unconscious patient,
repeated measurements of cardiovascular function, including
blood pressure, urine output and (if possible) continuous elec-
trocardiographic (ECG) monitoring should be performed.
Plasma electrolytes and acid-base balance should be meas-
ured. Hypotension is the most common cardiovascular com-
plication of poisoning. This is usually due to peripheral
vasodilatation, but may be secondary to myocardial depres-
sion following, for example, α-blocker, tricyclic antidepressant
or dextropropoxyphine poisoning. Hypotension can usually be
managed with intravenous colloid. If this is inadequate, posi-
tive inotropic agents (e.g. dobutamine) may be considered. If
dysrhythmias occur any hypoxia or hypokalaemia should be
corrected, but anti-dysrhythmic drugs should only be adminis-
tered in life-threatening situations. Since the underlying cardiac
tissue is usually healthy (unlike cardiac arrests following
myocardial infarction), prolonged external cardiopulmonary
resuscitation whilst the toxic drug is excreted is indicated.
Respiratory function is best monitored using blood gas analysis –
aPaCO 2 of6.5 kPa is usually an indication for assisted venti-
lation. Serial minute volume measurements or continuous
measurement of oxygen saturation using a pulse oximeter are
also helpful for monitoring deterioration or improvement in
self-ventilation. Oxygen is not a substitute for inadequate ven-
tilation. Respiratory stimulants increase mortality.

ENHANCEMENT OF ELIMINATION

Methods of increasing poison elimination are appropriate in
less than 5% of overdose cases. Repeated oral doses of activated
charcoal may enhance the elimination of a drug by ‘gastro-
intestinal dialysis’. Several drugs are eliminated in the bile and
then reabsorbed in the small intestine. Activated charcoal can
interrupt this enterohepatic circulation by adsorbing drug in
the gut lumen, thereby preventing reabsorption and enhancing
faecal elimination. Cathartics, such as magnesium sulphate,
can accelerate the intestinal transit time, which facilitates the
process. Orally administered activated charcoal adsorbs drug in
the gut lumen and effectively leaches drug from the intestinal
circulation into the gut lumen down a diffusion gradient.
Although studies in volunteers have shown that this method
enhances the elimination of certain drugs, its effectiveness in
reducing morbidity in overdose is generally unproven.
However, it is extremely safe unless aspiration occurs. Forced
diuresis is hazardous, especially in the elderly, and is no longer
recommended. Adjustment of urinary pH is much more effec-
tive than causing massive urine output. Alkaline diuresis (uri-
nary alkalinization) should be considered in cases of salicylate,
chlorpropramide, phenoxyacetate herbicides and phenobarbital
poisoning, and may be combined with repeated doses of oral
activated charcoal. Acid diuresis may theoretically accelerate
drug elimination in phencyclidineandamfetamine/ ’ecstasy’
poisoning. However, it is not usually necessary, may be harmful
and is almost never recommended.

Haemodialysis and, much less commonly, charcoal haemo-

perfusion are sometimes used to enhance drug elimination.

Table 54.4 summarizes the most important indications and

methods for such elimination techniques. In addition, exchange

transfusion has been successfully used in the treatment of poi-

soning in young children and infants. The risk of an elimination

technique must be balanced against the possible benefit of

enhanced elimination.

SPECIFIC ANTIDOTES

Antidotes are available for a small number of poisons and the

most important of these, including chelating agents, are sum-

marized in Table 54.5.

NALOXONE

Naloxoneis a pure opioid antagonist with no intrinsic agonist

activity (Chapter 25). It rapidly reverses the effects of opioid

drugs, including morphine,diamorphine,pethidine,dextro-

propoxyphene and codeine. When injected intravenously,

naloxoneacts within two minutes and its elimination half-life is

approximately one hour. The plasma half-life of most opioid

drugs is longer (e.g. 12–24 hours) and repeated doses or infu-

sions of naloxone may be required. The usual dose is

0.8–1.2 mg, although much higher doses may be needed after

massive opioid overdoses, which are common in addicts and

especially after a partial agonist (e.g. buprenorphine) overdose,

because partial agonists must occupy a relatively large fraction

of the receptors compared to full agonists in order to produce

even modest effects. Naloxonecan precipitate withdrawal reac-

tions in narcotic addicts. This is not a contraindication, but it is

wise to ensure that patients are appropriately restrained if this

is a risk.

MANAGEMENT OF SPECIFIC OVERDOSES

PARACETAMOL

This over-the-counter mild analgesic is commonly taken in

overdose. Although remarkably safe in therapeutic doses,

Table 54.4: Methods and indications for enhancement of poison

elimination

Method Poison

Alkaline diuresis Salicylates, phenobarbital

Haemodialysis Salicylates, methanol, ethylene

glycol, lithium, phenobarbital

Charcoal haemoperfusion Barbiturates, theophylline,

disopyramide

‘Gastro-intestinal dialysis’ Salicylates, theophylline, quinine,

via multiple-dose most anticonvulsants, digoxin

activated charcoal