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Atracurium

Medically reviewed on September 10, 2018

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: 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; hypothermia may prolong the duration of action

Half-Life Elimination

Infants: 20 minutes

Children: 17 minutes

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

Use: Labeled Indications

Neuromuscular blockade for endotracheal intubation, surgery, or mechanical ventilation: As an adjunct to general anesthesia, to facilitate endotracheal intubation, and to provide skeletal muscle relaxation during surgery or mechanical ventilation in adequately sedated ICU patients

Note: Neuromuscular blockade does not provide pain control, sedation, or amnestic effects. Appropriate analgesic and sedative mediations should be used before and during administration of neuromuscular blockade to achieve deep sedation.

Off Label Uses

Acute respiratory distress syndrome

Based on the Society for Critical Care Medicine Clinical Practice Guidelines for Sustained Neuromuscular Blockade in the Adult Critically Ill Patient, a neuromuscular blocker may be considered for short-term use (up to 48 hours) during the early course of acute respiratory distress syndrome (ARDS) in adults with PaO2/FiO2 <150 mmHg [SCCM [Murray 2016]]. Some experts recommend that neuromuscular blockers be considered for short-term use (up to 48 hours) only in patients with ARDS and severe gas exchange abnormalities (PaO2/FiO2 ≤120 mmHg) [Siegel 2018]. Note: Only cisatracurium has been studied in patients with ARDS. Whether or not other neuromuscular blockers will yield similar results is unknown.

Shivering due to therapeutic hypothermia following cardiac arrest

Based on the Society for Critical Care Medicine Clinical Practice Guidelines for Sustained Neuromuscular Blockade in the Adult Critically Ill Patient, a neuromuscular blocker may be used to manage overt shivering in therapeutic hypothermia following cardiac arrest.

Contraindications

Hypersensitivity to atracurium or any component of the formulation; known hypersensitivity to benzyl alcohol (multiple dose vials)

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

Note: Dose to effect; doses must be individualized due to interpatient variability. Ensure adequate pain control and sedation prior to and during administration of neuromuscular blockade to achieve deep sedation (SCCM [Murray 2016]).

Intensive care unit paralysis (eg, use for up to 48 hours in patients with early ARDS with PaO2/FiO2 <150, to facilitate mechanical ventilation, or for shivering from therapeutic hypothermia) (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; SCCM [Murray 2016])

Neuromuscular blockade for endotracheal intubation, surgery, or mechanical ventilation (as adjunct to general anesthesia):

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 (increased incidence of hypotension) 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)

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

Obese and 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; SCCM [Murray 2016]). 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

IV: 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.

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

Amifampridine: Neuromuscular-Blocking Agents may diminish the therapeutic effect of Amifampridine. Amifampridine may diminish the therapeutic effect of Neuromuscular-Blocking Agents. 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

Bromperidol: 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 (Topical); 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

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

Thiazide and Thiazide-Like Diuretics: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). 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%, postmarketing, and/or case reports: 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. Use caution in patients with previous anaphylactic reactions to other neuromuscular blocking agents.

• 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.

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 that may antagonize neuromuscular blockade (decreased paralysis): 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 that may potentiate neuromuscular blockade (increased paralysis): Electrolyte abnormalities (eg, severe hypocalcemia, severe hypokalemia, hypermagnesemia), neuromuscular diseases, metabolic acidosis, 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. All patients should receive eye care including liberal use of lubricating drops, gel, or ointment, and eyelids should remain closed during continuous neuromuscular blockade to protect against damage to the cornea (ulceration and drying).

• 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).

• Risk of medication errors: Accidental administration may be fatal. Confirm proper selection of intended product, store vial so the cap and ferrule are intact and the possibility of selecting the wrong product is minimized, and ensure that the intended dose is clearly labeled and communicated, when applicable.

Monitoring Parameters

Vital signs (heart rate, blood pressure, respiratory rate); degree of muscle paralysis (eg, presence of spontaneous movement, ventilator asynchrony, shivering, and consider use of a peripheral nerve stimulator with train of four monitoring along with clinical assessments)

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.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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