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Cisatracurium

Medically reviewed on Nov 15, 2018

Pronunciation

(sis a tra KYOO ree um)

Index Terms

  • Cisatracurium Besylate

Dosage Forms

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

Solution, Intravenous:

Nimbex: 20 mg/10 mL (10 mL) [contains benzyl alcohol]

Generic: 20 mg/10 mL (10 mL)

Solution, Intravenous [preservative free]:

Nimbex: 10 mg/5 mL (5 mL); 200 mg/20 mL (20 mL)

Generic: 10 mg/5 mL (5 mL); 200 mg/20 mL (20 mL)

Brand Names: U.S.

  • Nimbex

Pharmacologic Category

  • Neuromuscular Blocker Agent, Nondepolarizing

Pharmacology

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

Distribution

Vdss: 145 mL/kg (21% larger Vdss when receiving inhalational anesthetics)

Metabolism

Undergoes rapid nonenzymatic degradation in the bloodstream (Hofmann elimination) to laudanosine and inactive metabolites; laudanosine may cause CNS stimulation (association not established in humans) and has less accumulation with prolonged use than atracurium due to lower requirements for clinical effect

Excretion

Urine (95%; <10% as unchanged drug); feces (4%)

Clearance: Children: 5.89 mL/kg/minute; Adults: 4.57 mL/kg/minute

Onset of Action

IV: 2 to 3 minutes; Peak effect: 3 to 5 minutes

Duration of Action

Dose dependent, 35 to 45 minutes after a single 0.1 mg/kg dose; recovery begins in 20 to 35 minutes when anesthesia is balanced; recovery is attained in 90% of patients in 25 to 93 minutes; hypothermia may prolong the duration of action (NCS [Madden 2017])

Half-Life Elimination

22 to 29 minutes

Protein Binding

Not studied due to rapid degradation at physiologic pH

Special Populations: Renal Function Impairment

The times to 90% block were approximately 1 minute slower in patients with ESRD. The half-life values of the metabolites are longer in patients with renal failure and concentrations may be higher after long-term administration.

Special Populations: Hepatic Function Impairment

The times to maximum block were approximately 1 minute faster in liver transplant patients compared with healthy adults. The half-life values of the metabolites are longer in patients with hepatic disease and concentrations may be higher after long-term administration.

Special Populations: Elderly

The times to maximum block were approximately 1 minute slower in elderly patients.

Special Populations: Children

Minor differences in pharmacokinetic/pharmacodynamic parameters in children resulted in a faster time to onset and a shorter duration of neuromuscular block.

Use: Labeled Indications

Neuromuscular blockade for endotracheal intubation, surgery, or mechanical ventilation: As an adjunct to general anesthesia, to facilitate endotracheal intubation, and to relax skeletal muscles 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

Data from a multicenter, placebo-controlled randomized trial in mechanically ventilated patients with moderate/severe acute respiratory distress syndrome (ARDS) and PaO2/FiO2 ≤150 mmHg for less than 48 hours supports the use of cisatracurium for a duration of 48 hours to improve 90-day survival in this population. However, subgroup analysis found the greatest benefit when PaO2/FiO2 ≤120 mmHg [Papazian 2010]. 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].

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) via continuous infusion during the early course of acute respiratory distress syndrome (ARDS) in adults with PaO2/FiO2 <150 mmHg [SCCM [Murray 2016]].

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 cisatracurium or any component of the formulation; use of the 10 mL multiple-dose vials in neonates <1 month of age and low birth-weight infants (formulation contains 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

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) (SCCM [Murray 2016]):

0.1 to 0.2 mg/kg loading dose followed immediately by an infusion of 1 to 3 mcg/kg/minute (0.06 to 0.18 mg/kg/hour); adjust rate accordingly (Greenberg 2013) or in patients with acute respiratory distress syndrome to prevent ventilator asynchrony (off-label use), may administer a non-weight based dosing regimen of 15 mg (loading dose) followed immediately by 37.5 mg/hour for 48 hours; may administer 20 mg rapid boluses during infusion based on clinical parameters (eg, end-inspiratory plateau pressure remains >32 cm H2O) (Papazian 2010; SCCM [Murray 2016]).

Manufacturer's labeling: Dosing in the prescribing information may not reflect current clinical practice. 0.15 to 0.2 mg/kg loading dose; at initial signs of recovery from bolus dose, begin the infusion at a dose of 3 mcg/kg/minute (0.18 mg/kg/hour) and adjust rate accordingly; dosage ranges of 0.5 to 10 mcg/kg/minute (0.03 to 0.6 mg/kg/hour) have been reported.

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

Operating room administration:

Intubating dose: 0.15 to 0.2 mg/kg bolus as components of propofol or thiopental/nitrous oxide/oxygen induction-intubation technique; doses up to 0.4 mg/kg have been administered. Note: May produce generally good or excellent conditions for tracheal intubation in 1.5 to 2 minutes with clinically effective duration of action during propofol anesthesia of 55 to 61 minutes. In patients with neuromuscular diseases (eg, myasthenia gravis, myasthenic syndrome, carcinomatosis), maximum initial bolus dose is 0.02 mg/kg. Initial dose after succinylcholine for intubation: 0.1 mg/kg

Maintenance dose:

Intermittent bolus dosing: 0.03 mg/kg 40 to 50 minutes (after initial dose of 0.15 mg/kg) or 50 to 60 minutes (after an initial dose of 0.2 mg/kg), then as needed based on clinical response.

Continuous infusion: After an initial bolus, a diluted solution can be given by continuous infusion for maintenance of neuromuscular blockade during extended surgery; adjust the rate of administration according to the patient's response as determined by peripheral nerve stimulation. An initial infusion rate of 3 mcg/kg/minute (0.18 mg/kg/hour) may be required to rapidly counteract the spontaneous recovery of neuromuscular function; thereafter, a rate of 1 to 2 mcg/kg/minute (0.06 to 0.12 mg/kg/hour) should provide 89% to 99% neuromuscular blockade in most patients. Consider reduction of the infusion rate by 30% to 40% when administering during stable isoflurane, enflurane, sevoflurane, or desflurane anesthesia. Spontaneous recovery from neuromuscular blockade following discontinuation of infusion of cisatracurium may be expected to proceed at a rate comparable to that following single bolus administration.

Dosing: Geriatric

Refer to adult dosing. Consider extending the interval between administration of cisatracurium and intubation attempt by at least 1 minute to achieve adequate intubation conditions (time to maximum neuromuscular blockade is ~1 minute slower in elderly patients).

Dosing: Pediatric

Neuromuscular blockade: IV (not to be used IM):

Intermittent dosing:

Infants and Children <2 years: 0.15 mg/kg over 5 to 10 seconds

Children ≥2 years and Adolescents: 0.1 to 0.15 mg/kg over 5 to 10 seconds (Martin 1999; Playfor 2007)

Continuous IV infusion: Infants, Children, and Adolescents: 1 to 4 mcg/kg/minute (0.06 to 0.24 mg/kg/hour); 3.9 ± 1.3 mcg/kg/minute (0.23 ± 0.08 mg/kg/hour) was the mean infusion rate needed to maintain neuromuscular blockade in 19 children (ages 3 months to 16 years) (Burmester 2005; Martin 1999; Playfor 2007); higher doses have been reported with prolonged infusions (Tobias 1997)

Dosing: Renal Impairment

Because slower times to onset of complete neuromuscular block were observed in renal dysfunction patients, extending the interval between the administration of cisatracurium and intubation attempt may be required to achieve adequate intubation conditions.

Dosing: Hepatic Impairment

No dosage adjustment provided in manufacturer’s labeling. The time to onset of action was ~1 minute faster in patients with end-stage liver disease, but was not associated with clinically significant changes in recovery time.

Dosing: Obesity

Infants, Children, and Adolescents: Dosing in obese patients should be calculated using ideal body weight (Playfor 2007).

Adults: Ideal body weight or an adjusted body weight (ie, between IBW and total body weight [TBW]) is recommended when calculating dose for obese patients (SCCM [Murray 2016]).

Administration

IV: Administer IV only; do not administer IM (excessive tissue irritation). Administer undiluted as bolus injection over 5 to 10 seconds. Continuous infusion requires the use of an infusion pump.

Storage

Refrigerate intact vials at 2°C to 8°C (36°F to 46°F). Use vials within 21 days upon removal from the refrigerator to room temperature of 25°C (77°F). Per the manufacturer, dilutions of 0.1 mg/mL in 0.9% sodium chloride (NS), dextrose 5% in water (D5W), or D5NS are stable for up to 24 hours at room temperature or under refrigeration; dilutions of 0.1-0.2 mg/mL in D5LR are stable for up to 24 hours in the refrigerator. Additional stability data: Dilutions of 0.1, 2, and 5 mg/mL in D5W or NS are stable in the refrigerator for up to 30 days; at room temperature (23°C), dilutions of 0.1 and 2 mg/mL began exhibiting substantial drug loss between 7-14 days; dilutions of 5 mg/mL in D5W or NS are stable for up to 30 days at room temperature (23°C) (Xu, 1998). Usual concentration: 0.1-0.4 mg/mL.

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

Effects are minimal and transient.

<1%, postmarketing, and/or case reports: Bradycardia, bronchospasm, flushing, hypotension, muscle calcification (prolonged use), myopathy (acute quadriplegic syndrome; prolonged use), pruritus, skin rash

Warnings/Precautions

Concern related to adverse effects:

• Anaphylaxis: Severe anaphylactic reactions have been reported (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 cisatracurium than with other neuromuscular-blocking agents since it has no clinically-significant effects on heart rate to counteract the bradycardia produced by anesthetics.

• Residual paralysis: Has been reported. Patients with neuromuscular diseases (eg, myasthenia gravis, myasthenic syndrome) and carcinomatosis may be at increased risk; a lower maximum initial bolus dose is recommended in these patients. Reversal agents may be considered, especially in cases where residual paralysis is more likely to occur. To prevent complications from residual paralysis, extubation is recommended only after the patient has sufficiently recovered from neuromuscular blockade.

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).

• Therapeutic hypothermia: Hypothermia may slow Hoffmann elimination thereby prolonging the duration of paralysis (Greenberg 2013).

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. 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.

• 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 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 Considerations

Adverse events have not been observed in animal reproduction studies.

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?)

• Have patient report immediately to prescriber seizures (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.

Further information

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

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