OVERDOSAGE
There has been limited experience with
overdosage of atracurium besylate. The possibility
of iatrogenic overdosage can be minimized by
carefully monitoring muscle twitch response to
peripheral nerve stimulation. Excessive doses of
atracurium can be expected to produce enhanced
pharmacological effects. Overdosage may increase
the risk of histamine release and cardiovascular
effects, especially hypotension. If cardiovascular
support is necessary, this should include proper
positioning, fluid administration, and the use of
vasopressor agents if necessary. The
patient’s airway should be assured, with
manual or mechanical ventilation maintained as
necessary. A longer duration of neuromuscular
block may result from overdosage and a peripheral
nerve stimulator should be used to monitor
recovery. Recovery may be facilitated by
administration of an anticholinesterase reversing
agent such as neostigmine, edrophonium, or
pyridostigmine, in conjunction with an
anticholinergic agent such as atropine or
glycopyrrolate. The appropriate package inserts
should be consulted for prescribing
information.
Three pediatric patients (3 weeks, 4
and 5 months of age) unintentionally received
doses of 0.8 mg/kg to 1 mg/kg of atracurium
besylate. The time to 25% recovery (50 to 55
minutes) following these doses, which were 5 to 6
times the ED95 dose, was moderately
longer than the corresponding time observed
following doses 2 to 2.5 times the atracurium
ED95 dose in infants (22 to 36
minutes). Cardiovascular changes were minimal.
Nonetheless the possibility of cardiovascular
changes must be considered in the case of
overdose.
An adult patient (17 years of age)
unintentionally received an initial dose of 1.3
mg/kg of atracurium besylate. The time from
injection to 25% recovery (83 minutes) was
approximately twice that observed following
maximum recommended doses in adults (35 to 45
minutes). The patient experienced moderate
hemodynamic changes (13% increase in mean
arterial pressure and 27% increase in heart
rate) which persisted for 40 minutes and did not
require treatment.
The intravenous LD50s
determined in non-ventilated male and female
albino mice and male Wistar rats were 1.9, 2.01
and 1.31 mg/kg, respectively. Deaths occurred
within 2 minutes and were caused by respiratory
paralysis. The subcutaneous LD50
determined in non-ventilated male Wistar rats was
282.8 mg/kg. Tremors, ptosis, loss of reflexes and
respiratory failure preceded death which occurred
45 to 120 minutes after injection.
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