Nondepolarizing Muscle Relaxants: Atracurium

ATRACURIUM

Physical Structure

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.

Metabolism & Excretion

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.

A. Ester Hydrolysis

Th is action is catalyzed by nonspecific esterases, not by acetylcholinesterase or pseudocholinesterase.

B. Hofmann Elimination

A spontaneous nonenzymatic chemical breakdown occurs at physiological pH and temperature.

Dosage

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 intermittent boluses.

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 potency.

Side Effects & Clinical Considerations

Atracurium triggers dose-dependent histamine release that becomes significant at doses above 0.5 mg/kg.

A. Hypotension and Tachycardia

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.

B. Bronchospasm

Atracurium should be avoided in asthmatic patients. Severe bronchospasm is occasionally seen in patients without a history of asthma.

C. Laudanosine Toxicity

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.

D. Temperature and pH Sensitivity

Because of its unique metabolism, atracurium’s duration of action can be markedly prolonged by hypothermia and to a lesser extent by acidosis.

E. Chemical Incompatibility

Atracurium will precipitate as a free acid if it is introduced into an intravenous line containing an alkaline solution such as thiopental.

F. Allergic Reactions

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.