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)
Pharmacology
Mechanism of Action
Blocks neural transmission at the myoneural junction by binding with cholinergic receptor sites
Pharmacokinetics/Pharmacodynamics
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.
Use: Off Label
Acute respiratory distress syndromeyes
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 arrestyes
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.
Dosage and Administration
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
Note: Dose to effect; doses must be individualized due to interpatient variability. Dosing in obese patients should be calculated using ideal body weight (Playfor 2007):
Adjunct to surgical anesthesia (neuromuscular blockade): Note: Maintenance doses in infants and children may need to be administered with slightly greater frequency compared to adults.
Initial:
Infants and Children <2 years: IV: 0.3 to 0.4 mg/kg, additional doses of 0.3 to 0.4 mg/kg may be repeated as needed to maintain neuromuscular blockade
Children ≥2 years and Adolescents: IV: 0.4 to 0.5 mg/kg once followed by 0.08 to 0.1 mg/kg 20 to 45 minutes after initial dose to maintain neuromuscular block; repeat dose at 15- to 25-minute intervals as needed
Maintenance infusion for continued surgical relaxation during extended surgical procedures:
Infants and Children <2 years: Continuous IV infusion: 6 to 14 mcg/kg/minute (0.4 to 0.8 mg/kg/hour) (Goudsouzian 1986; Goudsouzian 1988)
Children ≥2 years and Adolescents: Continuous IV infusion: Initial: 9 to 10 mcg/kg/minute (0.54 to 0.6 mg/kg/hour) at initial signs of recovery from bolus dose; block is usually maintained by a rate of 5 to 9 mcg/kg/minute (0.3 to 0.54 mg/kg/hour); range: 2 to 15 mcg/kg/minute (0.1 to 0.9 mg/kg/hour)
ICU paralysis (eg, facilitate mechanical ventilation) in selected adequately sedated patients: Infants, Children, and Adolescents: IV: Initial bolus: 0.3 to 0.6 mg/kg, followed by continuous IV infusion of 5 to 28 mcg/kg/minute (0.3 to 1.7 mg/kg/hour) (Martin 1999; Playfor 2007)
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
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
Botulinum Toxin-Containing Products: 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 (Systemic): May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. 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
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
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. Have patient report immediately to prescriber severe dizziness, passing out, fast heartbeat, or slow heartbeat (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 health care 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.
