Cisatracurium - The Near Ideal NMB

Cisatracurium compared with Atracurium and Vecoronium
Non Depolarizing Neuromascular blocking agents/ drugs

1. Cisatracurium The Near Ideal NMB Dr. Shaikh Noorulhaque Secondary DNB Resident in Anaesthesiology Breach Candy Hospital, Mumbai PG Guide: Dr. Shilpa Bhojraj HOD: Dr. Alka Halbe

2. Introduction What are Neuromuscular Blocking (NMB) drugs ? These are agents that act peripherally at neuromuscular junction/muscle fibre itself to block neuromuscular transmission. Why do we need them ? In order to facilitate muscle relaxation for Intubation, Surgery & for Mechanical Ventilation during Surgery or in ICU

3. The Ideal NMB An ideal neuromuscular blocking agent needs to take the shortest time in endotracheal intubation The best intubating condition and have the shortest duration of muscle paralysis Non-depolarizing mechanism of action Rapid onset enabling quick intubation Rapid, complete and predictable recovery Short elimination half life No cumulative effect No histamine release High potency Should have pharmacologically inactive metabolites Reversible by cholinesterase inhibitors Elimination pathways less dependent on organ function Lack clinically important Cardiovascular side effects

4. Vecuronium Aminosteriod Onset of action-3-5min/Duration-20-35min Dosage: Intubation-0.08-0.12mg/kg Maintenance-0.04mg/kg Infusion-1-2 μ g/kg/min Depends primarily on biliary excretion and secondarily on renal excretion (no dose reduction required) Intermediate acting Active metabolites- 3 cis vecuronium responsible for prolonged effect Prolonged effect in Old Age, Obesity, Renal Failure, AIDS, Obesity…

5. Atracurium Benzoisoquinoline derivative Non-organ dependent elimination Non specific estererase :- 60% of elimination Hofmann elimination:- spontaneous nonenzymatic chemical breakdown occurs at physiologic pH and Temperature Histamine release at higher clinical dose in 30% of patients (Hypotension, tachycardia, Bronchospasm) Laudanosine toxicity:- Breakdown product from Hofmann elimination, assoc. with central nervous system excitation resulting in elevation of MAC and precipitation of seizures. Temperature and pH sensitivity:- action markedly prolonged in hypothermic or acidotic patients

6. Cisatracurium • It is a stereoisomer of atracurium. • Four times more potent than atracurium. • It undergoes Hoffmann elimination like atracurium but ester hydrolysis dose not occur. • It dose not produce the histamine and Laudanosine production is 5 times lesser than atracurium. • Metabolism and elimination are independent of hepatic and renal failure. • Does not alter heart rate or blood pressure, nor does it produce autonomic effects. • Cisatracurium shares with atracurium the… – production of Laudanosine, – pH and temperature sensitivity & chemical incompatibility.

7. Cisatracurium has Stable hemodynamics Cisatracurium has no important hemodynamic side effects

8. No dose-related effects on Mean Arterial Blood Pressure or Heart Rate in Patients without cardiovascular disease. Patients with serious cardiovascular disease Children NMB of choice for medium-to-long term surgeries on hemodynamically unstable patients

9. Cisatracurium has an Organ independent Hofmann elimination Responsible for 77% of the overall elimination of Cisatracurium. Minimally dependent on liver and kidneys Dependent on pH and Temperature Occurs in plasma and tissue

10. Cisatracurium results in Uniform Recovery • Shows spontaneous recovery rates of neuromuscular function • Number or size of doses minimally affect rate of recovery of neuromuscular function • Recovery is predictable irrespective of the age of the patient • Recovery is independent of renal and hepatic insufficiency

11. With Cisatracurium there is Lack of Histamine Release and Laudanosine toxicity Cisatracurium does not promote histamine release even at 8 times the ED95 Has no dose-related effects on blood pressure or heart rate 8 Laudanosine concentrations are lower following administration of Cisatracurium besilate than after administration of atracurium besilate

12. Dosage & Storage Intubating Dose:- 0.15 - 0.2 mg/Kg Onset of Action:- 3-4 minutes Results in blockades of intermediate duration i.e., 50 – 60 minutes Maintenance Infusion Dose:- 1 -2 mcg/Kg/min Storage: Refrigeration (2-8 C) Used within 21 days after removal from Refrigeration and exposure to room temperature

13. Cisatracurium compare with Vecuronium

14. Cisatracurium compare with Atracurium

15. Cisatracurium – Summarizing the benefits in the OT • Stable hemodynamics • Organ independent Hoffman elimination • Uniform recovery • Lack of clinically relevant histamine release • Better hemodynamic stability compared to atracurium and vecuronium

16. Cisatracurium S.O.U.L of the Operation Theatre.