CIS-CURON INJECTION

Indications

• Neuromuscular blockade during surgical procedures
• Facilitation of intubation
• Muscle relaxation in intensive care settings

Dosage

Children: Neonates: Initially 300–500 micrograms/kg, followed by 100–200 micrograms/kg as needed; for older children, refer to B

Adults: Initially by intravenous injection: 300–600 micrograms/kg; continuous intravenous infusion: usual dose 650–780 micrograms/kg/hour, adjusted as needed.

Mechanism of action

Cisatracurium binds competitively to cholinergic receptors at the motor end-plate, preventing acetylcholine from binding to these receptors. This blockade inhibits the development of end-plate potentials, keeping ion channels closed, and blocking the transmission of action potentials across neuromuscular junctions, which results in muscle paralysis.

Pharmacodynamics

The effective dose required to achieve 95% suppression of twitch response (ED95) is approximately 0.05 mg/kg in adults under opioid/nitrous oxide/oxygen anesthesia. The neuromuscular block produced by cisatracurium is dose-dependent, with a clear relationship between dosage and both the degree and duration of the blockade. Its onset and duration are intermediate compared to other neuromuscular blocking agents, and it can lead to residual paralysis and increased risk of seizures. Medication errors and certain drug interactions can enhance its neuromuscular blocking effects.

Pharmacokinetics

Cisatracurium is metabolized via a process of spontaneous degradation and by plasma esterases, which makes its pharmacokinetics less affected by organ function compared to other neuromuscular blockers. Its clearance is achieved through both non-specific plasma esterases and the Hofmann elimination pathway, resulting in a predictable and consistent duration of action regardless of patients’ renal or hepatic function.

Adverse effects

• Bradycardia
• Hypotension
• Skin flushing
• Bronchospasm
• Cardiac arrest
• Seizure

Interactions

• Acetylcholinesterase inhibitors such as neostigmine may antagonize the effects of cisatracurium
• Certain drugs may potentiate the neuromuscular blocking action of cisatracurium

Precautions

• Use with caution in patients with cardiovascular disease or sensitivity to hypotension
• Monitor for residual paralysis and seizures

Pregnancy

Cisatracurium should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether cisatracurium is excreted in human milk. Caution should be exercised when administering to nursing mothers.

Storage

Store below 25°C. Protect from light. Do not freeze.

Formulations

• Cisatracurium besilate 2 mg per 1 ml solution for injection (Nimbex®)
• Cisatracurium besilate 10 mg/5 ml solution for injection ampoules
• Cisatracurium besilate 20 mg/10 ml solution for injection ampoules

Mechanism of action

Like other non-depolarising neuromuscular blocking agents, cisatracurium binds competitively to cholinergic receptors in motor end-plate neurons, blocking acetylcholine from accessing the receptors. Therefore, in the presence of cisatracurium, an end-plate potential cannot be developed. Ion channels remain closed, the cell does not depolarize, and an action potential is not transmitted.

Pharmacodynamics

The dose required to produce 95% suppression of twitch response to nerve stimulation (ED₉₅) of cisatracurium is 0.05 mg/kg in adults receiving opioid/nitrous oxide/oxygen anesthesia. The degree and duration of the neuromuscular block produced by cisatracurium increases in a dose-dependent manner, while the time to maximum neuromuscular block decreases. Compared to other neuromuscular blocking agents, it is intermediate in its onset and duration of action. Cisatracurium acts on cholinergic receptors, blocking neuromuscular transmission. This action is antagonized by acetylcholinesterase inhibitors such as neostigmine. The use of cisatracurium may lead to residual paralysis, as well as a higher risk of seizure. Medication errors increase the risk of death, and the use of certain drugs may potentiate the neuromuscular blocking action of cisatracurium.