Elephant specific information, if available, is in blue.

Chemistry – A synthetic, non-depolarizing neuromuscular blocking agent, atracurium, is a bisquaternary, non-choline diester structurally similar to metocurine and tubocurarine. It occurs as white to pale yellow powder. 50 mg is soluble in 1 ml of water, 200 mg is soluble in 1 ml of alcohol, and 35 mg is soluble in 1 ml of normal saline.

The commercially available injection occurs as clear, colorless solution and is a sterile solution of the drug in sterile water for injection. The pH of this solution is 3.25 – 3.65. Atracurium besylate may also be known as: atracurium besilate .

Storage/Stability/Compatibility – Atracurium injection should be stored in the refrigerator and protected against freezing. At room temperature, approximately 5% potency loss occurs each month; when refrigerated, a 6% potency loss occurs over a years time.

Atracurium is compatible with the standard IV solutions, but while stable in lactated Ringer’s for 8 hours, degradation occurs more rapidly. It should not be mixed in the same IV bag or sy­ringe, or given through the same needle with alkaline drugs (e.g., barbiturates) or solutions (sodium bicarbonate) as precipitation may occur.

Pharmacology – Atracurium is a nondepolarizing neuromuscular blocking agent and acts by competitively binding at cholinergic receptor sites at the motor end-plate, thereby inhibiting the effects of acetylcholine. Atracurium is considered to be 1/4 to 1/3 as potent as pancuronium. In horses, atracurium is more potent than in other species tested and more potent than other nondepolarizing muscle relaxants studied.

At usual doses, atracurium exhibits minimal cardiovascular effects, unlike most other nondepolarizing neuromuscular blockers. While atracurium can stimulate histamine release, it is consid­ered to cause less histamine release than either tubocurarine or metocurine. In humans, less than one percent of patients receiving atracurium exhibit clinically significant adverse reactions or histamine release.

Uses/Indications – Atracurium is indicated as an adjunct to general anesthesia to produce muscle relaxation during surgical procedures or mechanical ventilation and also to facilitate endotracheal intubation. Atracurium can be used in patients with significant renal or hepatic disease.

Pharmacokinetics – After IV injection, maximal neuromuscular blockade generally occurs within 3-5 minutes. The duration of maximal blockade increases as the dosage increases. Systemic alkalosis may diminish the degree and duration of blockade; acidosis potentiates it. In conjunction with balanced anesthesia, the duration of blockade generally persists for 20-35 minutes. Recovery times do not change after maintenance doses are given, so predictable blocking effects can be attained when the drug is administered at regular intervals.

Atracurium is metabolized by ester hydrolysis and Hofmann elimination which occurs independently of renal or hepatic function.

Contraindications/Precautions – Atracurium is contraindicated in patients who are hypersensitive to it. Because it may rarely cause significant release of histamine it should be used with caution in patients where this would be hazardous (severe cardiovascular disease, asthma, etc.). Atracurium has minimal cardiac effects and will not counteract the bradycardia or vagal stimulation induced by other agents. Use of neuromuscular blocking agents must be done with extreme caution, or not at all, in patients suffering from myasthenia gravis. Atracurium has no analgesic or sedative/anesthetic actions.

Adverse Effects/Warnings – Clinically significant adverse effects are apparently quite rare in patients (<1% in humans) receiving recommended doses of atracurium and usually are secondary to histamine release.  They can include: allergic reactions, inadequate or prolonged block, hypotension vasodilatation, bradycardia, tachycardia, dyspnea, broncho-, laryngospasm, rash, urticaria, and a reaction at the injection site. Patients developing hypotension usually have preexisting severe cardiovascular disease.

Overdosage – Overdosage possibilities can be minimized by monitoring muscle twitch response to peripheral nerve stimulation. Increased risks of hypotension and histamine release occur with overdoses, as well as prolonged duration of muscle blockade.

Besides treating conservatively (mechanical ventilation, O2, fluids, etc.), reversal of blockade may be accomplished by administering an anticholinesterase agent (edrophomium, physostigmine, or neostigmine) with an anticholinergic (atropine or glycopyrrolate). Reversal is usually attempted (in humans) approximately 20-35 minutes after the initial dose, or 10-30 minutes after the last maintenance dose. Reversal is usually complete within 8-10 minutes.

Drug Interactions – The following agents may enhance the neuromuscular blocking activity of atracurium: procainamide, quinidine, verapamil, aminoglycoside antibiotics (gentamicin, etc), lincomycin, clindamycin, bacitracin, polymyxin B, lithium, magnesium sulfate, thiazide diuretics, enflurane, isoflurane, and halothane. Loop diuretics (e.g., furosemide) have been reported to both decrease and increase the effects of nondepolarizing neuromuscular blockers. Other muscle relaxant drugs may cause a synergistic or antagonistic effect. Succinylcholine may speed the onset of action and enhance the neuromuscular blocking actions of atracurium. Do not give atracurium until succinylcholine effects have diminished. Theophylline or phenytoin may inhibit or reverse the neuromuscular blocking action of atracurium.

Doses –

Horses:

a)   Intraoperative dose: 0.055 mg/kg IV (Mandsager 1988)

Monitoring Parameters –

1)   Level of neuromuscular blockade; cardiac rate

Client Information – This drug should only be used by professionals familiar with its use.

Dosage Forms/Preparations/FDA Approval Status/Withholding Times –

Veterinary-Approved Products: None

Human-Approved Products:

Atracurium Besylate Injection 10 mg/ml in 5 ml amps and 10 ml vials; Tracrium®  (Glaxo Wellcome); (Rx)