Atracurium (Monograph)

Drug class: Neuromuscular Blocking Agents
VA class: MS200
Chemical name: 2,2′- [1,5-Pentanediylbis [oxy(3-oxo-3,1-propanediyl)]]bis[1-[(3,4-dimethoxyphenyl)methyl] -1,2,3,4-tetrahydro-6,7-dimethoxy-2-methylisoquinolinium] dibenzenesulfonate
Molecular formula: C₆₅H₈₂N₂O₁₈S₂
CAS number: 64228-81-5

Medically reviewed by Drugs.com on Oct 12, 2023. Written by ASHP.

Introduction

Nondepolarizing neuromuscular blocking agent; benzylisoquinolone.

Uses for Atracurium

Skeletal Muscle Relaxation

Production of skeletal muscle relaxation during surgery after general anesthesia has been induced.

Facilitation of endotracheal intubation; however, a neuromuscular blocking agent with a rapid onset of action (e.g., succinylcholine, rocuronium) generally preferred in emergency situations when rapid intubation is required.

Also has been used to facilitate mechanical ventilation in the ICU. Has been given as a continuous IV infusion for up to 10 days in this setting. Whenever neuromuscular blocking agents are used in the ICU, consider benefits versus risks of such therapy and assess patients frequently to determine need for continued paralysis. (See Intensive Care Setting under Cautions.)

Compared with other neuromuscular blocking agents, atracurium has an intermediate onset and duration of action; exhibits minimal cardiovascular effects; and has minimal, if any, cumulative effects. Because elimination is not dependent on renal or hepatic pathways, may be particularly useful in patients with hepatic or renal dysfunction.

Atracurium Dosage and Administration

General

Dispensing and Administration Precautions

• Facilities and personnel necessary for intubation, administration of oxygen, and respiratory support should be immediately available. (See Boxed Warning.)

• Take special precautions (e.g., segregate storage, limit access, affix warning labels to storage containers and final administration containers) to ensure that the drug is not administered without adequate respiratory support. Institute for Safe Medication Practices (ISMP) recommends the following wording on auxiliary labels: “Warning: Paralyzing agent—causes respiratory arrest—patient must be ventilated.”

• Assess neuromuscular blockade and recovery with a peripheral nerve stimulator to accurately monitor the degree of muscle relaxation, determine need for additional doses, and minimize possibility of overdosage. (See Administration Precautions under Cautions.)

• To avoid patient distress, administer in conjunction with adequate analgesia and sedation, and only after unconsciousness has been induced.

• A reversal agent should be readily available in the event of a failed intubation or to accelerate neuromuscular recovery after surgery. (See Reversal of Neuromuscular Blockade under Dosage and Administration.)

Reversal of Neuromuscular Blockade

• To reverse neuromuscular blockade, administer a cholinesterase inhibitor (e.g., neostigmine, pyridostigmine, edrophonium) in conjunction with an anticholinergic agent such as atropine or glycopyrrolate to block adverse muscarinic effects of the cholinesterase inhibitor.

• To minimize risk of residual neuromuscular blockade, attempt reversal only after some degree of spontaneous recovery has occurred; monitor patients closely until adequate recovery of normal neuromuscular function is assured (i.e., ability to maintain satisfactory ventilation and a patent airway).

• Under balanced anesthesia, reversal generally can be attempted about 20–35 minutes after the initial dose or 10–30 minutes after the last maintenance dose, when recovery of muscle twitch has started.

• Complete reversal generally is achieved within 8–10 minutes after administration of the cholinesterase inhibitor.

Administration

Administer IV only; do not administer IM.

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer initial (intubating) dose by rapid IV injection; administer maintenance doses by intermittent IV injection or continuous IV infusion.

Use of a controlled-infusion device is recommended during continuous IV infusion of the drug.

Rate of spontaneous recovery after discontinuance of a maintenance infusion is comparable to that following administration of a single IV injection.

Repeated administration of maintenance doses does not have a cumulative effect on duration of neuromuscular blockade, provided recovery from blockade is allowed to begin prior to administering maintenance doses.

Consult specialized references for specific procedures and techniques of administration.

Do not mix in the same syringe or administer through the same needle as an alkaline solution.

Dilution

For continuous IV infusion, dilute atracurium besylate injection to the desired concentration (usually 0.2 or 0.5 mg/mL) in 5% dextrose, 5% dextrose and 0.9% sodium chloride, or 0.9% sodium chloride injection. Use within 24 hours.

Dosage

Available as atracurium besylate; dosage expressed in terms of the salt.

Adjust dosage carefully according to individual requirements and response.

Pediatric Patients

Skeletal Muscle Relaxation

Initial (Intubating) Dose

IV

Infants and children 1 month to 2 years of age: 0.3–0.4 mg/kg when used concomitantly with halothane anesthesia. (See Onset and also Duration under Pharmacokinetics.)

Children ≥2 years of age generally should receive same doses recommended for adults. (See Adults under Dosage and Administration.)

Insufficient data for recommendation of a specific initial dose of atracurium besylate in infants and children following administration of succinylcholine.

Maintenance Dosage During Prolonged Surgical Procedures

Intermittent IV Injection

Infants and children may require more frequent maintenance doses than adults.

Children ≥2 years of age generally should receive same doses recommended for adults. (See Adults under Dosage and Administration.)

Continuous IV Infusion

Children ≥2 years of age generally should receive same infusion rates as in adults. (See Adults under Dosage and Administration.)

Limited data suggest infusion rate requirements may be higher in pediatric ICU patients than in adults.

Adults

Skeletal Muscle Relaxation

Initial (Intubating) Dose

IV

0.4–0.5 mg/kg. Following administration of this initial dose, endotracheal intubation for nonemergency surgical procedures can be performed within 2–2.5 minutes in most patients. (See Onset and also Duration under Pharmacokinetics.)

Reduce initial dose by about 33% (i.e., to 0.25–0.35 mg/kg) if steady-state anesthesia has been induced with enflurane or isoflurane. (See Specific Drugs under Interactions.)

Consider reducing initial dose by about 20% if steady-state anesthesia has been induced with halothane. (See Specific Drugs under Interactions.)

If administering following succinylcholine, reduce dose to 0.3–0.4 mg/kg. Reduce dose further (e.g., to 0.2–0.3 mg/kg) when inhalation anesthetics are also administered concomitantly. (See Specific Drugs under Interactions.)

Maintenance Dosage During Prolonged Surgical Procedures

Intermittent IV Injection

0.08–0.1 mg/kg, administered as necessary.

Administer first maintenance dose generally 20–45 minutes after the initial dose in patients undergoing balanced anesthesia.

Administer repeat maintenance doses at relatively regular intervals (i.e., from 15–25 minutes in patients undergoing balanced anesthesia). Administration at longer intervals may be possible if higher maintenance doses (i.e., up to 0.2 mg/kg) are used or if used with enflurane or isoflurane.

Continuous IV Infusion

Individualize infusion rates based on patient response to peripheral nerve stimulation.

Initially, 9–10 mcg/kg per minute may be necessary to rapidly counteract spontaneous recovery from neuromuscular blockade. Maintenance infusion of 5–9 mcg/kg per minute generally maintains 89–99% neuromuscular blockade in patients receiving balanced anesthesia; however, adequate blockade may occur with infusion rates of 2–15 mcg/kg per minute.

Initiate continuous IV infusion only after early spontaneous recovery from initial intubating dose is evident.

Reduce infusion rate by about 33% if steady-state anesthesia has been induced with enflurane or isoflurane. (See Specific Drugs under Interactions.)

Consider a smaller reduction in the infusion rate if steady-state anesthesia has been induced with halothane. (See Specific Drugs under Interactions.)

Maintenance Dosage in ICU

To support mechanical ventilation in the ICU, average infusion rates of 11–13 mcg/kg per minute have been used; however, infusion rates may vary widely among patients and may increase or decrease with time. Following discontinuance of the infusion, spontaneous recovery to a train-of-four (TOF) >75% generally occurred within approximately 60 minutes.

Monitor degree of neuromuscular blockade with a peripheral nerve stimulator; do not administer additional doses before there is a definite response to nerve stimulation.

Following recovery from neuromuscular blockade, administration of a direct IV (“bolus”) dose may be necessary to reestablish neuromuscular blockade prior to reinstitution of the infusion.

Special Populations

Renal Impairment

Dosage adjustments not required.

Burn Patients

Substantially increased doses may be required due to development of resistance. (See Burn Patients under Cautions.)

Cardiopulmonary Bypass Patients with Induced Hypothermia

Infusion rate required to maintain adequate surgical relaxation during hypothermia (i.e., 25–28°C) is approximately 50% of the infusion rate necessary in normothermic patients.

Patients with Myasthenia Gravis

Administer at low initial doses and with careful monitoring in well-controlled patients whose usual therapy is continued up to the time of surgery.

Patients with Cardiovascular Disease

Initial dose of 0.3–0.4 mg/kg administered slowly or in fractional doses over 1 minute. (See Cardiovascular Effects under Cautions.)

Other Populations

Patients with an increased risk of histamine release (e.g., history of severe anaphylactoid reactions or asthma): Initial dose of 0.3–0.4 mg/kg administered slowly or in fractional doses over 1 minute.

Patients in whom potentiation of neuromuscular blockade or difficulties with reversal of blockade may occur (e.g., neuromuscular disease, severe electrolyte disturbances, carcinomatosis): Consider dosage reduction. However, no clinical experience to date in these patients, and no specific doses are recommended. (See Neuromuscular Diseases and also Electrolyte Disturbances under Cautions.)

Cautions for Atracurium

Contraindications

• Known hypersensitivity to atracurium.

• Multiple-dose vials in patients with known hypersensitivity to benzyl alcohol.

Warnings/Precautions

Warnings

Administration Precautions

Because of the potential for severely compromised respiratory function and other complications, take special precautions during administration. (See Boxed Warning and also see General under Dosage and Administration.)

Sensitivity Reactions

Hypersensitivity Reactions

Serious hypersensitivity reactions, including anaphylaxis, reported rarely. Potential for cross-sensitivity with other neuromuscular blocking agents (both depolarizing and nondepolarizing).

Take appropriate precautions; emergency treatment for anaphylaxis should be immediately available.

General Precautions

Neuromuscular Diseases

Possible exaggerated neuromuscular blockade in patients with neuromuscular diseases (e.g., myasthenia gravis, Eaton-Lambert syndrome).

Monitor degree of neuromuscular blockade with a peripheral nerve stimulator; consider dosage reduction.

Burn Patients

Resistance to therapy can develop in burn patients, particularly those with burns over 25–30% or more of body surface area.

Resistance generally becomes apparent ≥1 week after the burn, peaks ≥2 weeks after the burn, persists for several months or longer, and decreases gradually with healing.

Consider possible need for substantially increased doses. (See Distribution: Special Populations, under Pharmacokinetics.)

Histamine Release

Consider possibility of substantial histamine release in sensitive individuals.

Use with caution and at lower initial doses in patients in whom substantial histamine release would be particularly hazardous (e.g., those with clinically important cardiovascular disease) and in patients with any history suggesting a greater risk of histamine release (e.g., history of severe anaphylactoid reactions or asthma). Safety in patients with asthma not established.

Cardiovascular Effects

Exhibits minimal effects on heart rate; therefore, will not counteract the bradycardia induced by many anesthetic agents or by vagal stimulation. Bradycardia during anesthesia may be more common than with other neuromuscular blocking agents.

Intensive Care Setting

Possible prolonged paralysis and/or muscle weakness with long-term administration of neuromuscular blocking agents in the ICU.

Continuous monitoring of neuromuscular transmission recommended during neuromuscular blocking agent therapy in intensive care setting. Do not administer additional doses before there is a definite response to nerve stimulation tests. If no response is elicited, discontinue administration until a response returns.

Seizures reported rarely in patients with predisposing factors (e.g., head trauma, cerebral edema, hypoxic encephalopathy, viral encephalitis, uremia) receiving continuous IV infusions for facilitation of mechanical ventilation in intensive care settings.

Electrolyte Disturbances

Monitor the degree of neuromuscular blockade with a peripheral nerve stimulator and consider dosage reduction in patients with severe electrolyte disturbances (i.e., hypermagnesemia, hypokalemia, hypocalcemia).

Malignant Hyperthermia

Malignant hyperthermia is rarely associated with use of neuromuscular blocking agents and/or potent inhalation anesthetics. Be vigilant for its possible development and prepared for its management in any patient undergoing general anesthesia.

Carcinomatosis

Monitor the degree of neuromuscular blockade with a peripheral nerve stimulator and consider dosage reduction.

Specific Populations

Pregnancy

Category C.

Lactation

Not known whether atracurium is distributed into milk. Caution advised if used in nursing women.

Pediatric Use

Safety and efficacy not established in children <1 month of age.

Large amounts of benzyl alcohol (i.e., 100–400 mg/kg daily) have been associated with toxicity in neonates; each mL of atracurium besylate injection in multiple-dose vials contains 9 mg of benzyl alcohol.

Geriatric Use

No substantial differences in safety, efficacy, or dosage requirements relative to younger adults.

Common Adverse Effects

Skin flush.

Drug Interactions

Specific Drugs

Atracurium Pharmacokinetics

Absorption

Bioavailability

Poorly absorbed from the GI tract.

Onset

Time to maximum neuromuscular blockade decreases as the dose increases.

Following IV administration of 0.4–0.5 mg/kg, maximum neuromuscular blockade generally occurs within 3–5 minutes (range: 1.7–10 minutes).

Duration

Duration of maximum neuromuscular blockade increases as the dose increases.

Duration of neuromuscular blockade induced by 0.4–0.5 mg/kg under balanced anesthesia is about 20–35 minutes. Recovery generally is 25 and 95% complete approximately 35–45 and 60–70 minutes, respectively, after the injection.

Regardless of the dose, recovery from the maximum effect of neuromuscular blockade is 95% complete in approximately 30 minutes (range: 12–75.7 minutes) under balanced anesthesia and approximately 40 minutes (range: 6–104 minutes) under anesthesia with enflurane, isoflurane, or halothane.

Rate of recovery from neuromuscular blockade is more rapid in children than adults.

Alkalosis may enhance recovery.

Special Populations

Hepatic dysfunction does not substantially alter duration of and rate of recovery from neuromuscular blockade.

In patients with renal failure, onset may be slightly delayed; however, renal dysfunction does not substantially alter duration of and rate of recovery from neuromuscular blockade.

In patients undergoing cardiopulmonary bypass surgery under induced hypothermia, duration of blockade may be prolonged.

Distribution

Extent

Distributed into extracellular fluid; rapidly reaches site of action at motor end-plate of myoneural junction.

Crosses the placenta in small amounts.

Plasma Protein Binding

82%.

Special Populations

In burn patients, possible increased protein binding (possibly to α₁-acid glycoprotein) with subsequent decreases in the free fraction of circulating drug.

Elimination

Metabolism

Rapidly metabolized via Hofmann elimination and nonspecific enzymatic ester hydrolysis; the liver does not appear to play a major role.

Elimination Route

Excreted principally in urine and also in feces via biliary elimination.

Half-life

Biphasic; terminal elimination half-life is approximately 20 minutes.

Stability

Storage

Parenteral

Injection

2–8°C; do not freeze. Store in original carton until use; protect from light.

Use within 14 days once removed from refrigeration, regardless of whether injection was subsequently rerefrigerated.

Compatibility

Parenteral

Unstable in the presence of acids and bases. May be incompatible with alkaline solutions (e.g., barbiturate solutions).

Solution CompatibilityHID

Compatible for 24 hours at 5 or 30°C; use within 24 hours when diluted with dextrose 5%.

Compatible for 24 hours at 5 or 25°C; use within 24 hours when diluted with sodium chloride 0.9% injection.

Drug Compatibility

Actions

• Produces skeletal muscle relaxation by causing a decreased response to acetylcholine (ACh) at the myoneural (neuromuscular) junction of skeletal muscle.

• Exhibits high affinity for ACh receptor sites and competitively blocks access of ACh to motor end-plate of myoneural junction; may affect ACh release.

• Blocks the effects of both the small quantities of ACh that maintain muscle tone and the large quantities of ACh that produce voluntary skeletal muscle contraction; does not alter the resting electrical potential of the motor end-plate or cause muscular contractions.

• Exhibits minimal cardiovascular effects.

Advice to Patients

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., cardiovascular disease, neuromuscular disease).

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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