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Atracurium

Pronunciation

(a tra KYOO ree um)

Index Terms

  • Atracurium Besylate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous, as besylate:

Generic: 50 mg/5 mL (5 mL); 100 mg/10 mL (10 mL)

Solution, Intravenous, as besylate [preservative free]:

Generic: 50 mg/5 mL (5 mL)

Pharmacologic Category

  • Neuromuscular Blocker Agent, Nondepolarizing

Pharmacology

Blocks neural transmission at the myoneural junction by binding with cholinergic receptor sites

Distribution

Vd:

Infants: 0.21 L/kg

Children: 0.13 L/kg

Adults: 0.1 L/kg

Metabolism

Undergoes ester hydrolysis and Hofmann elimination (nonbiologic process independent of renal, hepatic, or enzymatic function); metabolites have no neuromuscular blocking properties; laudanosine, a product of Hofmann elimination, is a CNS stimulant and can accumulate with prolonged use. Laudanosine is hepatically metabolized.

Excretion

Urine (<5%)

Clearance:

Infants: 7.9 mL/kg/minute

Children: 6.8 mL/kg/minute

Adults: 5.3 mL/kg/minute

Onset of Action

Dose dependent: 2 to 3 minutes; Peak effect: 3 to 5 minutes

Duration of Action

Recovery begins in 20 to 35 minutes following initial dose of 0.4 to 0.5 mg/kg under balanced anesthesia; recovery to 95% of control takes 60 to 70 minutes

Half-Life Elimination

Infants: 20 minutes

Children: 17 minutes

Adults: Biphasic: Initial (distribution): 2 minutes; Terminal: 20 minutes

Use: Labeled Indications

Adjunct to surgical anesthesia (neuromuscular blockade): As an adjunct to general anesthesia, to facilitate endotracheal intubation and to provide skeletal muscle relaxation during surgery or mechanical ventilation.

Note: Atracurium does not relieve pain or produce sedation.

Contraindications

Hypersensitivity to atracurium besylate or any component of the formulation. Multiple-dose vials contain benzyl alcohol as a preservative; use is contraindicated in patients with a known hypersensitivity to benzyl alcohol.

Documentation of allergenic cross-reactivity for neuromuscular blockers is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosing: Adult

For IV administration only (not to be used IM): Dose to effect; doses must be individualized due to interpatient variability

Adjunct to surgical anesthesia (neuromuscular blockade):

IV (bolus): 0.4 to 0.5 mg/kg, then 0.08 to 0.1 mg/kg administered 20 to 45 minutes after initial dose to maintain neuromuscular block; repeat dose at 15- to 25-minute intervals as needed. Note: Initial dose may be reduced to 0.3 to 0.4 mg/kg in patients with significant cardiovascular disease or history of elevated risk of histamine release (eg, severe anaphylactoid reactions or asthma).

Initial dose after succinylcholine for intubation (balanced anesthesia): 0.3 to 0.4 mg/kg

Pretreatment/priming: 10% of intubating dose (eg, 0.04 to 0.05 mg/kg) given 2 to 4 minutes before the larger second dose (Mehta 1985; Miller 2010). Note: Although priming has been advocated by some, priming may either be uncomfortable for the patient, increase the risk of aspiration and difficulty swallowing, or intubating conditions after priming may not be as good as that seen with succinylcholine (Miller 2010).

Maintenance infusion for continued surgical relaxation during extended surgical procedures: At initial signs of recovery from bolus dose, a continuous infusion may be initiated at a rate of 9 to 10 mcg/kg/minute (0.54 to 0.6 mg/kg/hour); block usually maintained by a rate of 5 to 9 mcg/kg/minute (0.3 to 0.54 mg/kg/hour) under balanced anesthesia; range: 2 to 15 mcg/kg/minute (0.12 to 0.9 mg/kg/hour)

ICU paralysis (eg, facilitate mechanical ventilation) in selected adequately sedated patients (off-label dosing): IV: Initial bolus of 0.4 to 0.5 mg/kg, followed by 4 to 20 mcg/kg/minute (0.24 to 1.2 mg/kg/hour) (ACCM/SCCM/ASHP [Murray 2002]; Greenberg 2013)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Adjunct to surgical anesthesia (neuromuscular blockade): IV (not to be used IM): Dose to effect; doses must be individualized due to interpatient variability; use ideal body weight for obese patients

Infants and Children <2 years: Initial: 0.3 to 0.4 mg/kg followed by maintenance doses as needed to maintain neuromuscular blockade. Note: Maintenance doses in infants and children may need to be administered with slightly greater frequency compared to adults.

Children ≥2 years and Adolescents: 0.4 to 0.5 mg/kg, then 0.08 to 0.1 mg/kg administered 20 to 45 minutes after initial dose to maintain neuromuscular block; repeat dose at 15- to 25-minute intervals as needed. Note: Initial dose may be reduced to 0.3 to 0.4 mg/kg in patients with significant cardiovascular disease or history of elevated risk of histamine release (eg, severe anaphylactoid reactions or asthma).

Maintenance infusion for continued surgical relaxation during extended surgical procedures: Children ≥2 years and Adolescents: At initial signs of recovery from bolus dose, a continuous infusion may be initiated at a rate of 9 to 10 mcg/kg/minute (0.54 to 0.6 mg/kg/hour); block usually maintained by a rate of 5 to 9 mcg/kg/minute (0.3 to 0.54 mg/kg/hour) under balanced anesthesia; range: 2 to 15 mcg/kg/minute (0.12 to 0.9 mg/kg/hour)

Dosing: Renal Impairment

No dosage adjustment necessary.

Dosing: Hepatic Impairment

No dosage adjustment necessary.

Dosing: Obesity

Morbidly-obese patients should be dosed using ideal body weight or an adjusted body weight (ie, between IBW and total body weight [TBW]) (Erstad 2004). In a bariatric surgical population of morbidly-obese patients who were administered an induction dose of atracurium based on TBW as compared to IBW, time to recovery of twitch response was prolonged (Kralingen 2011).

Reconstitution

May prepare an infusion solution (final concentrations: 0.2 mg/mL or 0.5 mg/mL) by admixing with an appropriate diluent (eg, NS, D5W, D5NS). Do not mix with alkaline solutions.

Administration

May be given undiluted as a bolus injection; do not administer IM (excessive tissue irritation). May also administer via continuous infusion; requires the use of an infusion pump. Use infusion solutions within 24 hours of preparation.

Compatibility

See Trissel’s IV Compatibility Database

Storage

Store intact vials at 2°C to 8°C (36°F to 46°F). Do not freeze. Upon removal from refrigeration to room temperature storage conditions (25°C/77°F), use within 14 days even if re-refrigerated. Dilutions of 0.2 mg/mL or 0.5 mg/mL in 0.9% sodium chloride, dextrose 5% in water, or 5% dextrose in sodium chloride 0.9% are stable for up to 24 hours at room temperature or under refrigeration.

Drug Interactions

AbobotulinumtoxinA: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Acetylcholinesterase Inhibitors: May diminish the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Aminoglycosides: May enhance the respiratory depressant effect of Neuromuscular-Blocking Agents. Monitor therapy

Bacitracin (Systemic): May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Calcium Channel Blockers: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Capreomycin: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

CarBAMazepine: May decrease the serum concentration of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Cardiac Glycosides: Neuromuscular-Blocking Agents may enhance the arrhythmogenic effect of Cardiac Glycosides. Monitor therapy

Clindamycin (Topical): May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Colistimethate: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Consider therapy modification

Corticosteroids (Systemic): Neuromuscular-Blocking Agents (Nondepolarizing) may enhance the adverse neuromuscular effect of Corticosteroids (Systemic). Increased muscle weakness, possibly progressing to polyneuropathies and myopathies, may occur. Consider therapy modification

CycloSPORINE (Systemic): May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Fosphenytoin-Phenytoin: May diminish the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Fosphenytoin-Phenytoin may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Fosphenytoin-Phenytoin may decrease the serum concentration of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Inhalational Anesthetics: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Ketorolac (Nasal): May enhance the adverse/toxic effect of Neuromuscular-Blocking Agents (Nondepolarizing). Specifically, episodes of apnea have been reported in patients using this combination. Monitor therapy

Ketorolac (Systemic): May enhance the adverse/toxic effect of Neuromuscular-Blocking Agents (Nondepolarizing). Specifically, episodes of apnea have been reported in patients using this combination. Monitor therapy

Lincosamide Antibiotics: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Lithium: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Local Anesthetics: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Exceptions: Benzocaine; Benzydamine; Cocaine; Dibucaine; Dyclonine; Ethyl Chloride; Hexylresorcinol; Lidocaine (Ophthalmic); Lidocaine (Topical); Pramoxine; Proparacaine; Tetracaine (Ophthalmic); Tetracaine (Topical). Monitor therapy

Loop Diuretics: May diminish the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Loop Diuretics may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Magnesium Salts: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Minocycline: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

OnabotulinumtoxinA: Neuromuscular-Blocking Agents may enhance the neuromuscular-blocking effect of OnabotulinumtoxinA. Monitor therapy

Pholcodine: May enhance the adverse/toxic effect of Neuromuscular-Blocking Agents. Specifically, anaphylaxis has been reported. Monitor therapy

Polymyxin B: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Consider therapy modification

Procainamide: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

QuiNIDine: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

QuiNINE: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Avoid combination

RimabotulinumtoxinB: Neuromuscular-Blocking Agents may enhance the neuromuscular-blocking effect of RimabotulinumtoxinB. Monitor therapy

Spironolactone: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Tetracycline Derivatives: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Trimebutine: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Vancomycin: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Adverse Reactions

Frequency not defined. Adverse reactions are mild, rare, and generally suggestive of histamine release.

1% to 10%: Cardiovascular: Flushing

<1% (Limited to important or life-threatening): Bradycardia, bronchospasm, dyspnea, erythema, hypersensitivity reaction, hypotension, increased bronchial secretions, injection site reaction, laryngospasm, pruritus, seizure, tachycardia, urticaria, wheezing

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylaxis: Severe anaphylactic reactions have been reported with atracurium use; some life-threatening and fatal. Appropriate emergency treatment (including epinephrine 1 mg/mL) should be immediately available during use.

• Bradycardia: May be more common with atracurium than with other neuromuscular-blocking agents since it has no clinically-significant effects on heart rate to counteract the bradycardia produced by anesthetics.

• Neuromuscular cross-sensitivity: Cross-sensitivity with other neuromuscular-blocking agents may occur; use extreme caution in patients with previous anaphylactic reactions.

Disease-related concerns:

• Burn injury: Resistance may occur in burn patients (≥20% of total body surface area), usually several days after the injury, and may persist for several months after wound healing (Han 2009).

• Conditions which may antagonize neuromuscular blockade: Respiratory alkalosis, hypercalcemia, demyelinating lesions, peripheral neuropathies, denervation, and muscle trauma may result in antagonism of neuromuscular blockade (ACCM/SCCM/ASHP [Murray 2002]; Greenberg 2013; Miller 2010; Naguib 2002).

• Conditions which may potentiate neuromuscular blockade: Electrolyte abnormalities (eg, severe hypocalcemia, severe hypokalemia, hypermagnesemia), neuromuscular diseases, metabolic acidosis, metabolic alkalosis, respiratory acidosis, Eaton-Lambert syndrome and myasthenia gravis may result in potentiation of neuromuscular blockade (Greenberg 2013; Miller 2010; Naguib 2002).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Use with caution in the elderly, effects and duration are more variable.

• Immobilized patients: Resistance may occur in patients who are immobilized.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer’s labeling.

Other warnings/precautions:

• Appropriate use: Maintenance of an adequate airway and respiratory support is critical. Resistance may develop with chronic treatment.

• Experienced personnel: Should be administered by adequately trained individuals familiar with its use.

• Histamine release: Reduce initial dosage and inject slowly (over 1 to 2 minutes) in patients in whom substantial histamine release would be potentially hazardous (eg, patients with clinically-important cardiovascular disease).

Monitoring Parameters

Vital signs (heart rate, blood pressure, respiratory rate); degree of muscle relaxation (via peripheral nerve stimulator and presence of spontaneous movement)

In the ICU setting, prolonged paralysis and generalized myopathy, following discontinuation of agent, may be minimized by appropriately monitoring degree of blockade.

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events were observed in animal reproduction studies. Small amounts of atracurium have been shown to cross the placenta when given to women during cesarean section.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience flushing (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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