Clinical Pharmacology and Therapeutics

448 DRUG OVERDOSE AND POISONING
Table 54.6: Urinary alkalinization regimen for aspirin
Indicated in adults with a salicylate level in the range
600–800 mg/L and in elderly adults and children with levels in the
range 450–750 mg/L
Adults: 1 L of 1.26% sodium bicarbonate (isotonic) 40 mmol
KCl IV over 4 h, and/or 50-mL i.v. boluses of 8.5% sodium
bicarbonate (note: additional KCl will be required)
Children: 1 mL/kg of 8.4% sodium bicarbonate ( 1 mmol/kg)
20 mmol KCl diluted in 0.5 L of dextrose saline infused at
2–3 mL/kg/h
Source: National Poisons Information Service, Guy’s and St Thomas’ Trust
London Centre.
Poisons information Services: UK National Poisons Information Services,
Tel. 0844 892 0111, directs caller to relevant local centre.
Methionine is an effective oral antidote in paracetamol
poisoning. It may be useful in remote areas where there will be
a delay in reaching hospital or when acetylcysteine is contraindicated.
SALICYLATE
Patients poisoned with salicylate typically remain conscious,
but in contrast to paracetamol overdose usually look and feel ill,
The typical presentation includes nausea, tinnitus and hyperventilation
and the patient is hot and sweating. Immediate management
includes estimation of arterial blood gases, electrolytes,
renal function, blood glucose (hypoglycaemia is particularly
common in children) and plasma salicylate concentration. The
patient is usually dehydrated and requires intravenous fluids. A
stomach washout is performed, if within one hour of ingestion.
Activated charcoal should be administered. Multiple dose activated
charcoal is advised until the salicylate level has peaked.
Blood gases and arterial pH normally reveal a mixed metabolic
acidosis and respiratory alkalosis. Respiratory alkalosis frequently
predominates and is due to direct stimulation of the respiratory
centre. The metabolic acidosis is due to uncoupling of
oxidative phosphorylation and consequent lactic acidosis. If
acidosis predominates, the prognosis is poor. Absorption may
be delayed and the plasma salicylate concentration can increase
over many hours after ingestion. Depending on the salicylate
concentration (see Table 54.6) and the patient’s clinical condition,
an alkaline diuresis should be commenced using intravenous
sodium bicarbonate. However, this is potentially
hazardous, especially in the elderly. Children metabolize aspirin
less effectively than adults and are more likely to develop a
metabolic acidosis and consequently are at higher risk of death.
Plasma electrolytes, salicylate and arterial blood gases and pH
must be measured regularly. Sodium bicarbonate acutely lowers
plasma potassium, by shifting potassium ions into cells.
Supplemental intravenous potassium may cause dangerous
hyperkalaemia if renal function is impaired, so frequent monitoring
of serum electrolytes is essential. If the salicylate concentration
reaches 800–1000 mg/L, haemodialysis is likely to
be necessary. Haemodialysis may also be life-saving at lower
salicylate concentrations if the patient’s metabolic and clinical
condition deteriorates.
TRICYCLIC ANTIDEPRESSANTS
Tricyclic antidepressants cause death by dysrhythmias, myocardial
depression, convulsions or asphyxia. If the patient reaches
hospital alive they may be conscious, confused, aggressive or
in deep coma. Clinical signs include dilated pupils, hyperreflexia
and tachycardia. Following immediate assessment,
resuscitation and ECG monitoring as necessary, blood should
be taken for determination of arterial blood gases and electrolytes.
Gastric lavage may be performed up to one hour after
ingestion if the patient is fully conscious. ECG monitoring
should be continued during this procedure and for at least 12
hours after clinical recovery.
The most common dysrhythmia is sinus tachycardia, predominantly
due to anticholinergic effects and does not require
any intervention. Broadening of the QRS complex can result
from a quinidine-like (sodium ion blocking) effect and is associated
with a poor prognosis. Anti-dysrhythmic prophylaxis
should be limited to correction of any metabolic abnormalities,
especially hypokalaemia, hypoxia and acidosis. Intravenous
sodium bicarbonate (1–2 mmol/kg body weight) is the most
effective treatment for the severely ill patient and its mode
action may involve a redistribution of the drug within the tissues.
Some centres recommend prophylactic bicarbonate and
potassium to keep the pH in the range of 7.45–7.55 and
the potassium concentration at the upper end of the normal
range if the QRS duration is 100 ms or the patient is hypotensive
despite intravenous colloid. If resistant ventricular tachycardia
occurs, intravenous magnesium or overdrive pacing
have been advocated. If ventricular tachycardia results in
hypotension, DC shock is indicated. Convulsions should be
treated with intravenous benzodiazepines. Oral benzodiazepines
may be used to control agitation.
Occasionally, assisted ventilation is necessary.
SELECTIVE SEROTONIN REUPTAKE INHIBITORS
Substitution of selective serotonin reuptake inhibitors (SSRIs)
in place of tricyclic antidepressants has reduced the mortality
from antidepressant overdose. SSRIs do not have anticholinergic
actions and are much less cardiotoxic. Nausea and
diarrhoea are common. Seizures may occur and are associated
with venlafaxine (which blocks noradrenaline, as well as
serotonin reuptake, Chapter 20) overdose in particular.
Supportive and symptomatic measures are usually sufficient.
Oral activated charcoal is recommended following the
ingestion of more than ten tablets within one hour.
PARACETAMOL/DEXTROPROPOXYPHENE
(CO-PROXAMOL) – NOW DISCONTINUED
It is usually the dextropropoxyphene that causes death from
overdose with this mixture of dextropropoxyphene and paracetamol.
The patient may present with coma, hypoventilation
and pinpoint pupils. The cardiac toxicity includes a negative
inotropic effect and dysrhythmias. Immediate cardiopulmonary
resuscitation and intravenous naloxone are indicated. The
plasma paracetamol concentration should be measured and
acetylcysteine administered as shown in Figure 54.1. The