POISONOUS SUBSTANCES

2-agonists

Benzodiazepines

Allister Vale

D Nicholas Bateman

Poisoning with 2-agonists (e.g. fenoterol, pirbuterol, reproterol,

rimiterol, salbutamol (albuterol), terbutaline) may occur as a result
of deliberate or accidental ingestion or by therapeutic intravenous
infusion. Intoxication may also result from confusion about the
difference between oral and parenteral doses.

Many benzodiazepine compounds are available; the main differences between them relate to their duration of action. Benzodiazepines are often taken in overdose with CNS depressants
or ethanol, potentiating their respiratory depressant effects.
This may be particularly hazardous with opioids. However, coingestion of benzodiazepines may be beneficial if the other agent
causes convulsions. For this reason, routine use of benzodiazepine
antagonists as a diagnostic test in poisoning is absolutely
contraindicated.

Clinical features: patients who have taken an overdose of 2agonist have a feeling of excitement, often accompanied by tremor
and palpitations, which may be followed by agitation and convulsions. Electrolyte and acidbase disturbances are common in
severe poisoning. Hypokalaemia, caused by 2-receptor-mediated
activation of Na+/K+-ATPase, may precipitate supraventricular and
ventricular arrhythmias and must be corrected promptly. Hyperglycaemia and lactic acidosis may occur. Myocardial ischaemia,
with ST segment depression and T wave inversion, and pulmonary
oedema are also reported.

Clinical features: when taken alone in overdose, benzodiazepines

produce clinical features of drowsiness, dizziness, ataxia, dysarthria and nystagmus; less commonly, coma and hypotension
develop. Respiratory depression is a potential complication, particularly when opioids, ethanol and other CNS depressants have
also been ingested. It may require special attention in patients with
pre-existing chronic obstructive pulmonary disease.

Management: when a substantial dose of a 2-agonist has been

ingested less than 1 hour previously, gastric lavage may be considered or activated charcoal, 50100 g, may be administered,
though no clinical trial has been performed to confirm the efficacy
of these treatments. Symptomatic and supportive measures should
then be implemented.
Hypokalaemia should be corrected as soon as possible, by
administration of potassium, 4060 mmol/hour, diluted with 5%
dextrose or normal saline. Patients given potassium may develop
significant hyperkalaemia during recovery; potassium concentrations should be monitored closely. A non-selective -blocker (e.g.
propranolol, 15 mg) administered by slow intravenous injection
also reverses hypokalaemia, but may exacerbate pre-existing
obstructive airways disease.
If myocardial ischaemia occurs as a result of the tachyarrhythmia, propranolol, 15 mg i.v., should be administered. Convulsions
are usually single and short-lived but, if necessary, diazepam,
510 mg i.v., may be given.

Management: generally, only careful nursing and supportive care

are required. A specific benzodiazepine antagonist (flumazenil)
may be given in carefully selected patients, usually to avoid
ventilation. Its efficacy is determined clinically from the improvement in consciousness level and respiration. Flumazenil is used
more often than is justified by the severity of the poisoning and
should be reserved for patients with coma, hypotension or respiratory depression who are known not to be benzodiazepine
dependant, not to have epilepsy, and not to have ingested proconvulsants concurrently. It may precipitate convulsions and cardiac arrhythmias when tricyclic antidepressants have been taken,
and normal ECG is mandatory (i.e. no QRS or QT abnormality).
Flumazenil has a short half-life (about 1 hour), so patients
with severe poisoning may need repeated doses (0.5 mg i.v. over
1 minute, repeated if there is no or only partial response) or an
intravenous infusion (0.10.5 mg/hour). Most patients poisoned
with benzodiazepines respond to flumazenil, 1 mg. Many benzodiazepines have long half-lives (e.g. diazepam, 36 hours) or
active metabolites with long half-lives (e.g. nordiazepam, about
100 hours). Major functions return rapidly, but it may be several
days before the patient can perform skilled tasks safely.

FURTHER READING
Gaudreault P, Guay J, Thivierge R L et al. Benzodiazepine Poisoning.
Clinical and Pharmacological Considerations and Treatment. Drug Saf
1991; 6: 24765.
Kulka PJ, Lauven P M. Benzodiazepine Antagonists an Update of their
Role in the Emergency Care of Overdose Patients. Drug Saf 1992; 7:
3816.

FURTHER READING
Leikin J B, Linowiecki K A, Soglin D F et al. Hypokalaemia after Pediatric
Albuterol Overdose: A Case Series. Am J Emerg Med 1994; 12: 646.
Lewis L D, Essex E, Volans G N et al. A Study of Self-poisoning with Oral
Salbutamol Laboratory and Clinical Features. Hum Exp Toxicol 1993;
12: 397401.

MEDICINE

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2003 The Medicine Publishing Company Ltd