COMPARATIVE EVALUATION OF CISATRACURIUM AND ATRACURIUM IN PATIENTS UNDERGOING ABDOMINAL LAPAROSCOPIC SURGERIES

Discovery of neuromuscular blocking agents was an important landmark for the advancement of anaesthesia. Use of these agents has contributed immensely to rapid developments and growth of different surgical specialties like cardiothoracic surgery, neurosurgery, cancer surgery and management of critical care patients.

Neuromuscular blocking drugs (NMBD) interrupt transmission of nerve impulses at the neuromuscular junction (NMJ), this provides excellent intubating conditions and prevent patient movement to facilitate surgery. Before the advent of muscle relaxants, anaesthesia was induced and maintained by intravenous or inhalation agents only. Tracheal intubation was uncommon, and muscle relaxation if needed was secured by deep inhalation anaesthesia with its attendant risks of respiratory or cardiac depression and recovery was awfully prolonged.

Griffith and Johnson were the first to use curare to provide muscle relaxation during general anaesthesia in 1942, which was a major milestone in the world of anaesthesia. It soon became popular and was used worldwide. Major side effects like histamine release, prolonged duration of action and re-curarization prompted researchers to look for better alternatives. The synthesis of the methonium compounds, and the demonstration of their clinical potential led to increased interest in this field. In 1949, the curariform action of Suxamethonium was described by three independent groups in Italy, Great Britain, and the United States . Suxamethonium had a faster onset of action and provided excellent intubating conditions within a minute which was clinically beneficial in comparison to curare. Since then the use of suxamethonium for securing airway became popular amongst anaesthesiologists. Being a depolarizing agent, suxamethonium produced fasciculations, malignant hyperthermia, rise in serum potassium, post-op myalgia, and repeated dosing posed serious concerns like the appearance of phase II block and arrhythmias. Gallamine (1949), a synthetic nondepolarizing agent became unpopular due to its vagolytic action and cumulative effect. Pancuronium was synthesized in 1964 by Savage and his co-workers, it is long acting and has better neuromuscular blocking properties than d-tubocurarine without any histamine release. Pancuronium slowly became popular in anaesthesia and forced practitioners to neglect curare. As time passed unfavorable cardiac side effects and cumulative effects of pancuronium were unraveled by clinical researchers worldwide. This provided an impetus to the clinical researchers to look for an ideal NMBD. Characteristics of an ‘ideal neuromuscular blocking drug’ are - 1. Non-depolarizing mechanism of action 2. Rapid onset of action 3. Short duration of action 4. Rapid recovery 5. Non-cumulative 6. No cardiovascular side effects 7. No histamine release 8. Reversible by cholinesterase inhibitors 9. High potency 10. Pharmacologically inactive metabolites 11.independent of renal or hepatic function for its elimination. Search for such an agent lead to the discovery of intermediate-acting neuromuscular blocking agents like vecuronium, atracurium, and cisatracurium.

Vecuronium discovered by Savarese and Kitz in 1975 was initially thought to an ideal NMBD. Vecuronium’s favourable cardiac profile, rapid onset of action, and predictable duration of action were soon overshadowed by the major drawbacks like organ dependent elimination and cumulative effect. In 1981 Stenlake and colleagues, in a collaborative Enterprise between the University of Strathclyde and Wellcome Laboratories, synthesized atracurium. It has the advantage over vecuronium as it is eliminated via organ independent Hofmann elimination and ester hydrolysis. Recovery following ED95 dose of atracurium is better than vecuronium. However, atracurium is associated with histamine release and a theoretical risk of acrylate derivatives and laudanosine -a compound which can cross the blood-brain barrier. Even though there is no clinical evidence of adverse effects of laudanosine in humans, in animal studies, it has shown to induce excitement and seizure activity via acetylcholine, glutamate, GABA and opioid receptors.

Cisatracurium, introduced in 1996, is the 1R cis–1′R cis isomer of atracurium comprising approximately 15% of atracurium by weight. It is approximately 3-4 times as potent as atracurium with an ED95 of 0.05 mg/kg during N2O/O2 anaesthesia . Like atracurium, cisatracurium undergoes Hofmann elimination and, therefore, does not depend upon renal or liver function for elimination.  There is no ester hydrolysis of the parent molecule. The principal advantage of cisatracurium is that there has been no evidence of histamine release at doses up to eight times the ED95 whereas atracurium causes histamine release in humans at doses greater than 2.5 times ED95, rendering its usage safe in patients with multiple allergies and bronchial asthma. The production of laudonosine in cisatracurium is negligible in comparison to atracurium.

Cisatracurium is relatively new to the Indian scenario and there is not much clinical data relating to its usage in the Indian population. Our study aims to fill in these gaps in our knowledge. The main objective of this study is to compare neuromuscular blockade and recovery characteristics between the two non-depolarizing neuromuscular blocking drugs; Cisatracurium besylate and atracurium besylate at equipotent doses (3xED95) in adult patients undergoing abdominal laparoscopic surgical procedures with general anaesthesia.