Cisatracurium (Monograph)

Brand name: Nimbex
Drug class: Neuromuscular Blocking Agents
VA class: MS300
Chemical name: [1R-[1α,2α(1′R*,2′R*)]]-2,2′-[1,5-pentanediyl-bis[oxy(3-oxo-3,1-propanediyl)]]bis[1-[(3,4-dimethoxyphenyl)methyl]-1,2,3,4-tetrahydro-6,7-dimethoxy-2-methyl-isoquinolinium dibenzenesulfonate
Molecular formula: C₆₅H₈₂N₂O₁₈S₂
CAS number: 96946-42-8

Medically reviewed by Drugs.com on Feb 21, 2024. Written by ASHP.

Introduction

Nondepolarizing neuromuscular blocking agent (benzylisoquinolone); isomer of atracurium.

Uses for Cisatracurium

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. Cisatracurium is not recommended for rapid sequence intubation because of its intermediate onset of action.

Also has been used to facilitate mechanical ventilation in the ICU. Has been given as a continuous IV infusion for up to 6 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, cisatracurium has an intermediate onset and duration of action; exhibits minimal, if any, cardiovascular effects; and causes less histamine release than atracurium. Because elimination is not dependent on renal or hepatic pathways, may be particularly useful in patients with hepatic or renal dysfunction.

Cisatracurium 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. Time to recovery of neuromuscular function is dependent upon strength of neuromuscular blockade at time of reversal.

• 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).

Administration

Administer IV only.

Commercially available 20-mL vial containing 10 mg/mL intended for ICU use only.

IV Administration

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

Consult specialized references for specific procedures and techniques of administration.

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

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

Continuous IV infusions have been administered for up to 3 hours without evidence of cumulative neuromuscular blocking effects; such administration has no effect on duration of blockade, provided partial recovery is allowed to occur between doses.

Dilution

For continuous IV infusion, dilute to desired concentration (e.g., 0.1–0.4 mg/mL) in a compatible IV solution. (See Storage and also Compatibility, under Stability.)

Rate of Administration

Direct IV injection: Usually administer over 5–10 seconds.

Continuous IV infusion: Individualize infusion rate based on patient requirements and response to peripheral nerve stimulation. (See Tables 1 and 2 for recommended rates of infusion.) Accurate dosage is best achieved using a precision infusion device.

Dosage

Available as cisatracurium besylate; dosage expressed in terms of cisatracurium.

Adjust dosage carefully according to individual requirements and response.

Pediatric Patients

Skeletal Muscle Relaxation

Initial (Intubating) Dose

IV

Infants 1–23 months of age: 0.15 mg/kg when used concomitantly with halothane or opiate anesthesia. Generally produces maximum neuromuscular blockade in about 2 minutes. (See Onset and also Duration under Pharmacokinetics.)

Children 2–12 years of age: 0.1–0.15 mg/kg when used concomitantly with halothane or opiate anesthesia. A dose of 0.1 or 0.15 mg/kg generally produces maximum neuromuscular blockade in about 2.8 or 3 minutes, respectively. (See Onset and also Duration under Pharmacokinetics.)

Adolescents ≥13 years of age: Manufacturer makes no specific dosage recommendations.

Maintenance Dosage During Prolonged Surgical Procedures

Continuous IV Infusion

After initial intubating dose is administered, children ≥2 years of age may receive continuous IV infusion of cisatracurium for maintenance of neuromuscular blockade; individualize infusion rate based on patient response to peripheral nerve stimulation.

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

Initially, 3 mcg/kg per minute may be necessary to rapidly counteract spontaneous recovery from neuromuscular blockade. Thereafter, 1–2 mcg/kg per minute generally sufficient to maintain 89–99% neuromuscular blockade in most pediatric patients receiving balanced anesthesia.

Consider reducing infusion rate by up to 30–40% if steady-state anesthesia has been induced with enflurane or isoflurane; greater reductions may be required with prolonged durations of enflurane or isoflurane administration. (See Specific Drugs under Interactions.)

Adults

Skeletal Muscle Relaxation

Initial (Intubating) Dose

IV

0.15 or 0.2 mg/kg depending on desired time to intubation and duration of procedure.

Following a dose of 0.15 or 0.2 mg/kg, good to excellent intubating conditions generally occur within 2 or 1.5 minutes, respectively. (See Onset and also Duration under Pharmacokinetics.)

Maintenance Dosage During Prolonged Surgical Procedures

Intermittent IV Injection

0.03 mg/kg as needed.

First maintenance dose generally required within 40–50 or 50–60 minutes following initial dose of 0.15 or 0.2 mg/kg, respectively.

Each 0.03-mg/kg dose provides approximately 20 minutes of additional neuromuscular blockade. For shorter or longer durations of action, administer smaller or larger doses.

Less frequent or lower doses of cisatracurium may be necessary when administered concomitantly with enflurane or isoflurane anesthesia during prolonged surgical procedures. No dosage adjustment appears to be necessary when cisatracurium is administered shortly (e.g., within 15–30 minutes) after initiation of the inhalation anesthetic. (See Specific Drugs under Interactions.)

Continuous IV Infusion

After initial intubating dose is administered, may initiate continuous IV infusion to maintain neuromuscular blockade during prolonged procedures; initiate infusion only after early spontaneous recovery from IV dose is evident.

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

Initially, 3 mcg/kg per minute may be necessary to rapidly counteract spontaneous recovery from neuromuscular blockade. Thereafter, 1–2 mcg/kg per minute generally sufficient to maintain 89–99% neuromuscular blockade in most patients receiving balanced anesthesia.

Consider reducing infusion rate by up to 30–40% if steady-state anesthesia has been induced with enflurane or isoflurane; greater reductions may be required with prolonged durations of enflurane or isoflurane administration. (See Specific Drugs under Interactions.)

Maintenance Dosage in ICU

Continuous IV Infusion

To support mechanical ventilation in the ICU, average infusion rates of approximately 3 mcg/kg per minute have been required. However, dosage requirements may vary widely among patients and may increase or decrease with time.

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 an IV (“bolus”) dose may be necessary to reestablish neuromuscular blockade prior to reinstitution of the infusion.

Use for >6 days during mechanical ventilation in the ICU has not been evaluated in clinical studies. (See Intensive Care Setting under Cautions.)

Special Populations

Renal Impairment

Onset of complete neuromuscular blockade may be slower; it may be necessary to extend the interval between administration of cisatracurium and the intubation attempt.

Geriatric Patients

Onset of complete neuromuscular blockade may be slower; it may be necessary to extend the interval between administration of cisatracurium and the intubation attempt.

Burn Patients

Substantially increased doses may be required due to development of resistance. However, no clinical studies to date in these patients, and no specific doses are recommended. (See Burn Patients under Cautions and also see Distribution: Special Populations, under Pharmacokinetics.)

Cardiopulmonary Bypass Patients with Induced Hypothermia

Infusion rate of atracurium required to maintain adequate surgical relaxation during hypothermia (i.e., 25–28°C) is approximately 50% of the infusion rate necessary in normothermic patients; a similar reduction in the infusion rate of cisatracurium may be expected.

Other Populations

Patients in whom potentiation of neuromuscular blockade or difficulties with reversal of blockade may occur (e.g., neuromuscular disease, carcinomatosis): A dose of ≤0.02 mg/kg is recommended along with monitoring of subsequent dosage adjustments. (See Neuromuscular Diseases and also see Carcinomatosis, under Cautions.)

Cautions for Cisatracurium

Contraindications

• Known hypersensitivity to cisatracurium or any of its components.

• Multiple-dose vials containing benzyl alcohol contraindicated in premature infants. (See Pediatric Use under Cautions.)

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; dosage reduction is recommended. (See Other Populations under Dosage and Administration.)

Burn Patients

Resistance to nondepolarizing neuromuscular blocking agents 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.

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 with atracurium 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 the ICU. Unclear whether laudanosine (metabolite of atracurium and cisatracurium) contributes to CNS excitation (see Metabolism under Pharmacokinetics).

Cardiovascular Effects

No clinically important effects on heart rate at recommended doses and exhibits minimal, if any, cardiovascular effects; therefore, will not counteract the bradycardia induced by many anesthetic agents or by vagal stimulation.

Electrolyte Disturbances

Acid-base and/or serum electrolyte abnormalities may potentiate or antagonize action of cisatracurium.

Hemiparesis and Paraparesis

Resistance to therapy may develop in the affected limbs of patients with hemiparesis or paraparesis.

Monitor neuromuscular transmission in a nonparetic limb to avoid inaccurate dosing.

Malignant Hyperthermia

Malignant hyperthermia is rarely associated with use of neuromuscular blocking agents and/or potent inhalation anesthetics. Cisatracurium has not been studied in patients with increased susceptibility to malignant hyperthermia. Be vigilant for its possible development and prepared for its management in any patient undergoing general anesthesia.

Carcinomatosis

Possible exaggerated neuromuscular blockade in patients with carcinomatosis. Carefully monitor the degree of neuromuscular blockade with a peripheral nerve stimulator; dosage reduction is recommended. (See Other Populations under Dosage and Administration.)

Specific Populations

Pregnancy

Category B.

Not known whether use during labor, delivery, or cesarean section has effects on the fetus.

Lactation

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

Pediatric Use

Safety and efficacy not established in neonates (<1 month of age).

Tracheal intubation was facilitated more reliably in children 1–4 years of age when used in conjunction with halothane than when used in conjunction with opiates and nitrous oxide.

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

Geriatric Use

No overall differences in safety and efficacy relative to younger adults, but increased sensitivity of some older patients cannot be ruled out.

Minor alterations in pharmacokinetics, but no substantial differences in recovery profile. (See Pharmacokinetics.)

Hepatic Impairment

Minor alterations in pharmacokinetics, but no substantial differences in recovery profile. Concentration of metabolites may be increased after prolonged administration in patients with hepatic disease. (See Pharmacokinetics.)

Renal Impairment

Pharmacokinetic/pharmacodynamic profile similar to that in healthy adults; concentration of metabolites may be increased after prolonged administration in patients with renal failure. (See Pharmacokinetics.)

Common Adverse Effects

Surgical patients: None with incidence >1% in clinical trials.

Intensive care patients: Prolonged recovery from neuromuscular blockade.

Drug Interactions

Specific Drugs

Cisatracurium Pharmacokinetics

Absorption

Bioavailability

Poorly absorbed from GI tract.

Onset

Intermediate onset of action. Generally, time to maximum neuromuscular blockade decreases as dose increases; time to maximum blockade is up to 2 minutes longer with cisatracurium than with equipotent doses of atracurium.

Good to excellent conditions for tracheal intubation occur within 1.5–2 or 1.5 minutes following IV dose of 0.15 or 0.2 mg/kg, respectively.

Onset is faster in pediatric patients than in adults; also faster in infants than in older children. Onset may be delayed in geriatric patients compared with younger adults.

In adults, doses of 0.15 or 0.2 mg/kg administered under balanced anesthesia produce maximum neuromuscular blockade in about 3.5 (range: 1.6–6.8) or 2.9 (range: 1.9–5.2) minutes, respectively. Maximum neuromuscular blockade after 0.1-mg/kg dose occurs about 1 minute later in geriatric patients than in younger adults.

In children, doses of 0.1 or 0.15 mg/kg administered under balanced anesthesia produce maximum neuromuscular blockade in about 2.8 (range: 1.8–6.7) or 3 (range: 1.5–8) minutes, respectively. In infants, doses of 0.15 mg/kg administered under balanced anesthesia produce maximum neuromuscular blockade in about 2 minutes (range: 1.3–4.3).

Duration

Intermediate duration of action. Duration of maximum neuromuscular blockade increases as the dose increases; when the cisatracurium dose is doubled, the clinically effective duration of blockade increases by approximately 25 minutes. Clinically effective duration of action and rate of spontaneous recovery with equipotent doses of cisatracurium and atracurium are similar.

Duration is longer in adults than in pediatric patients; also longer in infants than in older children. No substantial difference in recovery profiles between geriatric and younger adults. Recovery following reversal is faster in children than in adults.

In adults, clinically effective duration of neuromuscular blockade (i.e., time to 25% recovery) after dose of 0.15 or 0.2 mg/kg is 55 (range: 44–74) or 65 (range: 43–103) minutes, respectively.

In children 2–12 years of age, clinically effective duration of neuromuscular blockade after dose of 0.1 or 0.15 mg/kg is approximately 28 (range: 21–38) or 36 (range: 29–46) minutes, respectively. In infants, clinically effective duration of neuromuscular blockade after dose of 0.15 mg/kg is approximately 43 minutes (range: 34–58 minutes).

Duration of neuromuscular blockade induced by 0.03-mg/kg maintenance dose is approximately 20 minutes.

In studies in patients receiving long-term (i.e., up to 6 days) infusion during mechanical ventilation, recovery of neuromuscular function (train-of-four ratio ≥70%) occurred in approximately 50 (range: 20–175) or 55 (range: 20–270) minutes following infusion discontinuance.

Special Populations

In patients with end-stage liver disease, onset may be slightly faster; however, hepatic dysfunction does not substantially alter rate of recovery from neuromuscular blockade.

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

Gender and obesity not associated with substantial changes in predicted onset or rate of recovery.

Distribution

Extent

Neuromuscular blocking agents generally distribute into extracellular fluid and rapidly reach site of action at motor end-plate of myoneural junction.

Neuromuscular blocking agents may cross placenta.

Volume of distribution of cisatracurium may be limited by its large molecular size and increased polarity. Higher steady-state volume of distribution when nontraditional two-compartment model of elimination is used compared with a one-compartment model.

Plasma Protein Binding

Plasma protein binding cannot be determined because of rapid metabolism of cisatracurium. (See Elimination under Pharmacokinetics.)

Special Populations

Based on a one-compartment model, volume of distribution at steady-state may be increased in the elderly, ICU patients, and in patients with end-stage hepatic failure.

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

Elimination

Metabolism

Rapidly metabolized via Hofmann elimination (independent of liver) to form a monoquaternary acrylate metabolite (which undergoes nonspecific plasma esterase hydrolysis and subsequent Hofmann elimination) and laudanosine (which is demethylated and glucuronidated). Both metabolites lack neuromuscular blocking activity; laudanosine may have CNS excitatory activity when present in large amounts.

Rate of Hofmann elimination is dependent on temperature and pH.

Elimination Route

Eliminated principally by Hofmann elimination (77–80%) and to lesser extent by renal and hepatic elimination (20%). Metabolites are eliminated principally by renal and hepatic elimination. Following administration of radiolabeled dose of cisatracurium to healthy individuals, 95% of administered dose is recovered in urine and 4% in feces; <10% of the dose is recovered as unchanged drug.

Half-life

22–30 minutes.

Special Populations

Patients with renal or hepatic dysfunction may exhibit longer half-lives; concentrations of metabolites after prolonged administration may be higher.

Cisatracurium half-life may be slightly prolonged in geriatric patients.

Pediatric patients may exhibit faster clearance of cisatracurium than adults.

Stability

Storage

Parenteral

Injection

Original carton at 2–8°C; protect from light. Do not freeze.

Use within 21 days once removed from refrigeration, regardless of whether injection was subsequently returned to refrigeration.

Following dilution to final concentration of 0.1 mg/mL in 5% dextrose, 0.9% sodium chloride, or 5% dextrose and 0.9% sodium chloride injection, store at room temperature or refrigerate; use within 24 hours.

Compatibility

Parenteral

Solution CompatibilityHID

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.

• Neuromuscular blocking potency of cisatracurium is approximately threefold that of atracurium.

• Exhibits minimal, if any, cardiovascular effects.

• Exhibits little histamine-releasing activity at usual therapeutic doses.

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.

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