Like all muscle relaxants, atracurium
has a quater-nary group; however, a benzylisoquinoline structure is responsible
for its unique method of degradation. The drug is a mixture of 10 stereoisomers.
Atracurium is so extensively metabolized
that its pharmacokinetics are independent of renal and hepatic function, and
less than 10% is excreted unchanged by renal and biliary routes. Two separate
processes are responsible for metabolism.
Th is action is catalyzed by nonspecific
esterases, not by acetylcholinesterase or pseudocholinesterase.
A spontaneous nonenzymatic chemical
breakdown occurs at physiological pH and temperature.
A dose of 0.5 mg/kg is administered
intravenously for intubation. After succinylcholine, intraoperative relaxation
is achieved with 0.25 mg/kg initially, then in incremental doses of 0.1 mg/kg
every 10–20 min. An infusion of 5–10 mcg/kg/min can effectively replace
Although dosage requirements do not
signifi-cantly vary with age, atracurium may be shorter act-ing in children and
infants than in adults.
Atracurium is available as a solution of
10 mg/ mL. It must be stored at 2–8°C,
as it loses 5% to 10% of its potency for each month it is exposed to room
temperature. At room temperature, it should be used within 14 days to preserve
Atracurium triggers dose-dependent
histamine release that becomes significant at doses above 0.5 mg/kg.
Cardiovascular side effects are unusual
unless doses in excess of 0.5 mg/kg are administered. Atracurium may also cause
a transient drop in systemic vascular resistance and an increase in cardiac
index indepen-dent of any histamine release. A slow rate of injec-tion
minimizes these effects.
Atracurium should be avoided in
asthmatic patients. Severe bronchospasm is occasionally seen in patients
without a history of asthma.
Laudanosine, a tertiary amine, is a
breakdown prod-uct of atracurium’s Hofmann elimination and has been associated
with central nervous system excita-tion, resulting in elevation of the minimum
alveolar concentration and even precipitation of seizures. Concerns about
laudanosine are probably irrelevant unless a patient has received an extremely
large total dose or has hepatic failure. Laudanosine is metabo-lized by the
liver and excreted in urine and bile.
Because of its unique metabolism,
atracurium’s duration of action can be markedly prolonged by hypothermia and to
a lesser extent by acidosis.
Atracurium will precipitate as a free
acid if it is introduced into an intravenous line containing an alkaline
solution such as thiopental.
Rare anaphylactoid reactions to
atracurium have been described. Proposed mechanisms include direct
immunogenicity and acrylate-mediated immune activation. IgE-mediated antibody
reac-tions directed against substituted ammonium com-pounds, including muscle
relaxants, have been described. Reactions to acrylate, a metabolite of
atracurium and a structural component of some dialysis membranes, have also
been reported in patients undergoing hemodialysis.