Cisatracurium

Usage

• Cisatracurium besylate is a non-depolarizing neuromuscular blocking agent indicated as an adjunct to general anesthesia, to facilitate tracheal intubation and to provide skeletal muscle relaxation during surgery or mechanical ventilation. It is also used in intensive care unit (ICU) settings for patients requiring prolonged muscle relaxation.
• Pharmacological Classification: Neuromuscular blocking agent, specifically a non-depolarizing agent.
• Mechanism of Action: Cisatracurium competitively binds to cholinergic receptors at the motor end-plate, antagonizing the action of acetylcholine. This prevents depolarization of the muscle fiber and subsequent muscle contraction, inducing paralysis.

Alternate Names

• (2S)-cis-2,2’-[1,5-Pentanediylbis[oxy(3-oxo-3,1-propanediyl)]]bis[1-[(3,4-dimethoxyphenyl)methyl]-1,2,3,4-tetrahydro-6,7-dimethoxy-2-methylisoquinolinium] dibenzenesulfonate
• Nimbex (brand name)

How It Works

• Pharmacodynamics: Cisatracurium produces skeletal muscle relaxation by competitively binding to nicotinic acetylcholine receptors at the neuromuscular junction. It does not have hormonal activity or effects on consciousness or the pain threshold. Neuromuscular monitoring with a peripheral nerve stimulator is essential.

• Pharmacokinetics:

  • Absorption: Administered intravenously; thus, absorption is immediate and complete.
  • Metabolism: Cisatracurium undergoes Hofmann elimination (a process dependent on pH and temperature) and ester hydrolysis in the body. These metabolic pathways are organ independent. Laudanosine is a major metabolite but its clinical significance at commonly used doses of cisatracurium is minimal.
  • Elimination: The elimination half-life is approximately 20 minutes. Elimination is not significantly affected by renal or hepatic impairment.

• Mode of Action: Competitive antagonism of nicotinic acetylcholine receptors at the motor end-plate.

• Receptor Binding: Binds to nicotinic acetylcholine receptors (nAChRs) at the neuromuscular junction.

• Elimination Pathways: Hofmann elimination (non-enzymatic) and ester hydrolysis.

Dosage

Standard Dosage

Adults:

• Intubation: 0.15 mg/kg IV bolus. Higher doses (up to 0.4 mg/kg) may be used for rapid sequence intubation.
• Maintenance: 0.03 mg/kg IV bolus every 20-40 minutes or by continuous infusion at 1-2 mcg/kg/min (after initial bolus of 3 mcg/kg/min).

Children (1 month to 12 years):

• Intubation: 0.15 mg/kg IV bolus over 5-10 seconds.
• Maintenance: 0.02 mg/kg IV bolus every 9-18 minutes or by continuous infusion (see adult dosing).

Special Cases:

• Elderly Patients: Similar pharmacodynamic profile to younger adults, but onset of action may be slightly slower. No dose adjustment needed except for potentially reducing the initial bolus dose to reduce risk of hypotension.
• Patients with Renal Impairment: No dose adjustment necessary.
• Patients with Hepatic Dysfunction: No dose adjustment necessary.
• Patients with Comorbid Conditions: Exercise caution in patients with neuromuscular diseases (e.g., myasthenia gravis), as they may be more sensitive to the effects of cisatracurium. Dose reduction is recommended in these patients (0.02 mg/kg). Electrolyte imbalances may potentiate the action of neuromuscular blocking agents.

Clinical Use Cases:

• Intubation: 0.15-0.2 mg/kg IV bolus.
• Surgical Procedures: Initial dose: 0.15 mg/kg IV bolus; maintenance: 0.03 mg/kg IV bolus or continuous infusion.
• Mechanical Ventilation: 3 mcg/kg/min initial infusion, then 1-2 mcg/kg/min.
• Intensive Care Unit (ICU) Use: Initial infusion rate: 3 mcg/kg/min, adjusted based on patient response and neuromuscular monitoring.

Side Effects

Common Side Effects:

• Bradycardia
• Hypotension
• Flushing

Rare but Serious Side Effects:

• Anaphylaxis (rash, hives, itching, swelling, difficulty breathing, bronchospasm, laryngospasm)
• Prolonged neuromuscular blockade

Adverse Drug Reactions (ADR):

• Anaphylaxis

Contraindications

• Hypersensitivity to cisatracurium, atracurium, or benzenesulfonic acid.

Drug Interactions

• Inhalational anesthetics: May prolong the duration of action of cisatracurium.
• Antibiotics (aminoglycosides, tetracyclines, others): May enhance neuromuscular blockade.
• Magnesium salts: May enhance neuromuscular blockade.
• Lithium: May enhance neuromuscular blockade.
• Phenytoin, Carbamazepine: May reduce the effectiveness of cisatracurium.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: Category B (US FDA). Animal studies have not shown fetal harm. Adequate and well-controlled studies in pregnant women have not been conducted. Use only if clearly needed and consider using benzyl alcohol-free formulations.

• Breastfeeding: The presence of cisatracurium in breast milk is unknown. Due to its short half-life and limited oral absorption, it is not expected to affect the breastfed infant if the mother restarts breastfeeding after the effects of the drug have worn off. Consider using benzyl alcohol-free formulations if needed during lactation. As a precaution, breastfeeding may be discontinued for 3 hours after administration.

Drug Profile Summary

• Mechanism of Action: Competitive inhibition of nicotinic acetylcholine receptors at the neuromuscular junction.
• Side Effects: Bradycardia, hypotension, flushing, anaphylaxis (rare).
• Contraindications: Hypersensitivity to cisatracurium, atracurium, or benzenesulfonic acid.
• Drug Interactions: Enhanced effect with inhalational anesthetics, aminoglycoside antibiotics, magnesium salts, lithium; reduced effect with phenytoin and carbamazepine.
• Pregnancy & Breastfeeding: Category B; unknown if excreted in breast milk. Use cautiously.
• Dosage: Adults: 0.15 mg/kg IV bolus initially; Children: 0.15 mg/kg IV bolus; Maintenance: 0.03 mg/kg (adults) or 0.02 mg/kg (children) IV bolus or continuous infusion.
• Monitoring Parameters: Heart rate, blood pressure, respiratory rate, peripheral nerve stimulator twitch response.

Popular Combinations

Cisatracurium is often combined with other anesthetic agents, such as propofol, fentanyl, and midazolam, for balanced anesthesia.

Precautions

• General Precautions: Monitor neuromuscular function with a peripheral nerve stimulator, ensure airway patency and adequate ventilation.
• Specific Populations: Use cautiously in elderly, patients with neuromuscular diseases, and pregnancy.

FAQs

Q1: What is the recommended dosage for Cisatracurium?

A: Adults: 0.15 mg/kg IV for intubation, 0.03 mg/kg for maintenance; Children: 0.15 mg/kg IV for intubation, 0.02 mg/kg for maintenance.

Q2: How is Cisatracurium metabolized?

A: Primarily by Hofmann elimination and ester hydrolysis, independent of organ function.

Q3: What are the common side effects of Cisatracurium?

A: Bradycardia, hypotension, and flushing.

Q4: Is Cisatracurium safe to use during pregnancy?

A: Category B. Use only if clearly needed. Consider using benzyl alcohol-free formulations.

Q5: Can Cisatracurium be used in patients with renal impairment?

A: Yes, no dose adjustment is necessary.

Q6: What are the signs of anaphylaxis with Cisatracurium?

A: Rash, hives, itching, swelling, bronchospasm, laryngospasm, and difficulty breathing.

Q7: What monitoring is essential during Cisatracurium administration?

A: Neuromuscular monitoring with a peripheral nerve stimulator.

Q8: How long should breastfeeding be withheld after Cisatracurium administration?

A: At least three hours, as a precaution.

Q9: Does Cisatracurium affect consciousness?

A: No, cisatracurium has no effect on consciousness or pain threshold.

Q10: What is the main contraindication for Cisatracurium?

A: Hypersensitivity to cisatracurium, atracurium, or benzenesulfonic acid.