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The Cisatracurium Besilate – a Short Review

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The Cisatracurium Besilate – a Short Review Review Article DOI: 10.18231/2394-2797.2017.0021 The cisatracurium besilate – A short review Akshaya N. Shetti1,*, Manju Jha Kashyap2, Pachipala Amaresh3, Rachita G. Mustilwar4 1Associate Professor, 2Professor, 3Post Graduate, 4Lecturer, 1,2,3Dept. of Anesthesiology and Critical Care, Rural Medical College 4Dept. of Periodontics and Implantology, Rural Dental College, Loni, Maharashtra, India *Corresponding Author: Email: [email protected] Abstract Various neuromuscular blocking agents are used in the routine anesthesia practice. Cisatracurium besilate is a nondepolarising neuromuscular blocking agent which has an intermediate duration of action. Due to the high molecular weight and high polarity the volume of distribution is low. Cisatracurium besilate undergoes Hofmann elimination which makes this as a drug of choice in organ failure patients. Keywords: Cisatracurium, Neuromuscular blocking agent, Nondepolarizing. Introduction blockers are available i.e., non-depolarizing and General anesthesia (GA) is commonly practiced depolarizing. Cisatracurium Iew benzylisoquinoline due to various disadvantages seen with regional which was introduced for clinical use since 1995. It is a techniques. With the newer research molecules of recently launched product in India with nondepolarising anesthetic drugs and the safety margins, the GA can be neuromuscular blocking property and has an conducted safely. GA has five components that are intermediate duration of action. analgesia, amnesia, paralysis, hypnosis, immobility. Chemical formulation: Cisatracurium is an Though achieving all the components are challenging, intermediate-acting bis-benzylisoquinolinium skeletal the use of muscle relaxant is very tricky and a thorough muscle relaxant. The chemical name is cisatracurium knowledge of the drugs before the use is very besylate and has the molecular weight of 1243.487 important. Muscle relaxants are used to facilitate g/mol. The molecular formula of cisatracurium is endotracheal intubation, ensure patient immobility and C65H82N2O18S2. It is one of the 10 isomer of the improve surgical exposure along with adequate atracurium which has the similar profile.(1) The hypnosis and analgesia. Two types of neuromuscular chemical structure is shown in Fig.1. Fig. 1: Chemical structure of Cistatracurium Pharmacodynamics: Cisatracurium is a new Dosage and formulation: Injection cisatracurium skeletal muscle relaxant which mainly acts on the besylate is available in solution formulation which is a cholinergic receptors leading to blocking of impulses sterile, non-pyrogenic solution provided in 5, 10 and 20 which are transmitted to skeletal muscle. The onset of ml vials. Each ml contains 2mg of cisatracurium. Many action and the duration of action are intermediate in manufacturers provide 20ml vial which is mainly for nature when compared to other skeletal muscle relaxant the ICU use, equivalent to 10mg/ml, intended for drugs. The action is mainly reversed by the acetyl infusion. The single use vials contain 0.9% benzyl cholinesterase inhibitors like neostigmine thus alcohol as a preservative. Initial dose for tracheal antagonizing the action of cisatracurium. intubation in adults is 0.15 or 0.2 mg/kg; then 0.03 mg/kg I.V every 40 to 50 minutes. Infusion dose of 3 Pharmacokinetics mcg/kg/minute can be considered for prolonged Route of administration: Intravenous surgery. In children 0.1mg/kg as a initial dose. International Journal of Pharmaceutical Chemistry and Analysis, 4(4):98-100 98 Akshaya N. Shetti et al. The cisatracurium besilate – A short review Onset, peak and duration: Onset of action is 1-3 junction monitoring while receiving.(4,5) The min and with the peak of 2-5 min and duration of action pharmacokinetics of cisatracurium differ marginally in is 25-45 minutes. elderly patients. Onset is also delayed in elderly due to Distribution: The volume of distribution is small slower biophase equilibration.(6,7) But certain studies due to relative large molecular weight and high have shown, clinically the onset time is not polarity. significantly different between the adults and elderly Metabolism & Elimination: The cisatracurium is population.(8,9) eliminated by both biliary and urinary route. The drug Pregnancy & lactation: The cisatracurium undergoes Hofmann elimination which is a pH and metabolite laudanosine crosses the placental barrier temperature dependent process. The metabolic products which is about 14% of maternal blood are laudanosine and monoquaternary acrylate. concentrations.(10) There are no specific studies exists Laudanosine is metabolized into desmethyl metabolites on usage of this drug in patient with lactation. and gets conjugated with glucuronic acid and excreted Drug interaction: Synergistic effects are seen with through urine. The later undergoes into hydrolysis to other muscle relaxants like, atracurium, vecuronium form monoquartenary alcohol which intern undergoes and rocuronium.(11) Hofmann elimination. Approximately 77% if the drug injected undergoes Hofmann elimination which is an Indications organ independent elimination process. The elimination This drug is used as a muscle relaxant for tracheal half-life of cisatracurium besilate in patients with intubation during general anesthesia. It is successfully normal organ function is 25 minutes. Raise in used in critical care where patient were put on temperature either body or room temperature will mechanical ventilation that were requiring complete reduce the potency of cisatracurium as its metabolism is skeletal muscle paralysis. The dosage requirement will temperature and pH dependent. The increased in be higher for the patients who are on mechanical metabolism of Cisatracurim seen in patients having ventilation for prolonged duration. This may be due to fever and prolonged action is seen in case of cardiac degradation of the receptors. Thus there is a need for surgeries where hypothermia was induced.(2,3) The drug neuromuscular monitoring in such patients.(12) should not be administered with the same line where Contraindications: Patients with known patient is receiving warm intravenous fluids. hypersensitivity to this drug, malignant hyperthermia Special population: There is no drug dosage and neuromuscular disorders. adjustment is required for renal failure patient receiving this drug. But it is recommended to have neuromuscular Table 1: Comparison with Atracurium and Vecuronium Feature Cisatracurium Artacurium Vecuronium Duration Intermediate Intermediate Intermediate Metabolite Laudanosine Laudanosine 3-desacetylvecuronium Elimination half life 22 minutes 20 minutes 65-75 minutes Metabolism Hofmann Hoffman By liver Cost effectiveness (In No - Yes comparison with Atracurium) Hypotension and bradycardia Insignificant Significant Insignificant due to histamine release Storage: The drug should be stored at 2-8oC to preserve the potency of the drug. Safety and tolerability: This drug has been of hemodynamic. Cisatracurium when compared with studied in patients with severer sepsis and receiving the vecuronium in coronary artery disease patients the prolonged mechanical ventilation and the results author found that there was a clinically insignificant showed that standard dosing of this drug may result in change in the hemodynamics.(15- 17) There is no systemic slower patient response with reduced effect. The author or cutaneous histamine release when the drug injected recommended to use larger dose to overcome the in either bolus or as continuous infusion method.(18) delayed effect.(13) The accumulation of metabolite laudanosine after prolonged infusion of cisatracurium Conclusion causes seizures in animals. This may not be true with Cisatracurium is a newer intermediate onset and the humans as reported earlier.(14) Various studies have duration skeletal muscle relaxant. This drug can be shown insignificant cardiovascular and cerebral safely be used in hepatorenal impairment. Like other parameter changes when given bolus and maintenance muscle relaxants it can be used in both elective surgical dose. This drug is preferred in patients with instability procedures under general anesthesia and in patients International Journal of Pharmaceutical Chemistry and Analysis, 4(4):98-100 99 Akshaya N. Shetti et al. The cisatracurium besilate – A short review who receive the prolonged controlled mechanical administration of cisatracurium. A comparison with ventilation. The only concern could be the cost vecuronium. Anaesthetist (1996), 45(11), 1024-9. effectiveness in comparison with available skeletal 17. Reich DL, Mulier J, Viby-Mogensen J, Konstadt SN, van Aken HK, Jensen FS, DePerio M, Buckley SG. muscle relaxants. Comparison of the cardiovascular effects of cisatracurium and vecuronium in patients with coronary artery disease. References Canadian Journal of Anaesthesia. (1998), 45(8), 794-7. 1. Correa, Claudia Maria Nogueira, Sudo, Gisele Zapata, 18. Selcuk M Celebioglu B Celiker V Basgul E Aypar U. and Sudo, Roberto Takashi.. Hemodynamic effects of Infusion and bolus administration of cisatracurium - atracurium and cisatracurium and the use of effects on histamine release. Middle East Journal of diphenhydramine and cimetidine. Revista Brasileira de Anaesthesiology. (2005), 18(2), 407-19. Anestesiologia, (2010),60(1),52-63. 2. Sharma V, Verma S, Biyani G, Bhatia PK. Temperature and cisatracurium degradation: So what is new? Indian Journal of Anaesthesia. (2015), 59(11):763. 3. Tewari P, Sikora R. Shortened duration of action of atracurium in a patient with pyrexia. Indian
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