Cisatracurium

Cisatracurium besylate is an intermediate-acting, non-depolarizing neuromuscular blocking drug (NMBD). Cisatracurium has a benzylisoquinolinium structure and is the 1R cis-1’R cis isomer of atracurium. Metocurine and d-tubocurarine are also in the benzylisoquinolinium class.[1] As an NMBD, it has found use as an adjunct to general anesthesia facilitating tracheal intubation and providing skeletal muscle relaxation during surgery.  It may also function to provide skeletal muscle relaxation to facilitate mechanical ventilation in an intensive care unit setting, but its use requires sedation.[2][3]

Cisatracurium, like the other NMBDs, binds to the nicotinic cholinergic receptor at the muscle motor end-plate but is not capable of inducing the conformational change necessary for ion channel opening. Because acetylcholine cannot bind to its receptors, no end-plate potential can develop. Cisatracurium acts as a competitive antagonist to acetylcholine; acetylcholinesterase inhibitors such as neostigmine antagonize this action.

The neuromuscular blocking potency of cisatracurium is roughly three times that of atracurium.[4] The clinically beneficial duration of action and rate of spontaneous recovery from equipotent doses of the two drugs are similar. Continuous infusion or repeated administration of maintenance doses of cisatracurium for up to 3 hours does not correlate with the development of tachyphylaxis or cumulative neuromuscular blocking effects.

Cisatracurium undergoes organ-independent Hofmann elimination—a chemical process dependent on pH and temperature—to form the monoquaternary acrylate metabolite and laudanosine. Patients with hypothermia, which typically occurs in surgeries needing cardiopulmonary bypass and therapeutic hypothermia, may need a lower dose of cisatracurium. Alternatively, a persistently febrile patient in ARDS on cisatracurium drip may require higher doses of this medication.[5] Neither of these byproducts has any neuromuscular blocking activity.[6][7][8] The liver and kidney both play a minor role in the elimination of cisatracurium but are primary pathways for the elimination of metabolites. Therefore, the half-life of metabolites is longer in patients with kidney or liver dysfunction, and metabolite concentrations may be higher after long-term administration. More importantly, the values of laudanosine are significantly lower in healthy surgical patients who receive cisatracurium infusions than in patients receiving infusions of atracurium, making cisatracurium a better choice for long-term use in the ICU.

The following lists diseases that can lead to hypersensitivity to NMBDs:

• Amyotrophic lateral sclerosis
• Autoimmune disorders
  • Systemic lupus erythematosus
  • Polymyositis
  • Dermatomyositis
• Familial periodic paralysis hyperkalemia
• Guillain-Barre syndrome
• Muscular dystrophy (Duchenne type)
• Myasthenia gravis
• Myasthenic syndrome
• Myotonia
  • Dystrophic
  • Congenital
  • Paramyotonia

 The following lists diseases that can lead to a resistance to NMBDs:

• Burn injury
• Cerebral palsy
• Hemiplegia (on the affected side)
• Muscular denervation (peripheral nerve injury)
• Severe chronic infection
  • Tetanus
  • Botulism

Cisatracurium is administered intravenously. The typical dose for intubation is 0.15 to 0.2 mg/kg. After this typical dose, ideal intubating conditions are generally achievable in between 1.5 and 2 minutes. The clinically effective duration of an intubating dose lasts 55 to 65 minutes. Maintenance dosing by bolus is 0.02 mg/kg. Maintaining paralysis via infusion with cisatracurium is at 1 to 3 mcg/kg/min, although it is important to adjust the dosing based on peripheral nerve monitoring.[9]

Adverse effects are uncommon with the use of cisatracurium. Adverse reactions occurred at a rate of less than 1% and include bradycardia, hypotension, bronchospasm, rash, anaphylaxis, prolonged neuromuscular blockade, and myopathy.[10]

No clinically relevant alterations in the recovery profile were observed in patients with renal dysfunction or end-stage liver disease, making cisatracurium a good choice in a patient with either of these diseases.

Cisatracurium is contraindicated if there is a known hypersensitivity. Caution is advisable in patients with myasthenia gravis or myasthenic syndrome, as a profound effect may occur.

Severe anaphylactic reactions to NMBDs, including cisatracurium, have been reported. Precautions are also advisable in those patients with a history of prior anaphylactic reactions to neuromuscular blocking agents as there are reports of cross-reactivity in the neuromuscular blocking agent drug class, with both depolarizing and non-depolarizing agents.

Cisatracurium should be kept refrigerated at 2 to 8 degrees Celsius and protected from light to preserve potency. The rate of loss of potency is as high as 5% per month at 25 degrees Celsius. Once removed from refrigeration to room temperature storage, it should be used within 21 days.