A patient in ICU was started on atracurium infusion. He developed seizure on day 3. What is the most likely cause?
ANSWER: (B) Accumulation of laudanosine in the bodyREF: Longneckers anaesthesiology Ch 33, Stoelting's Pharmacology & Physiology in Anesthetic Practice 4th Ed Ch 8Atracurium undergoes elimination via 2 pathways- spontaneous Hoffman's elimination (chemical mechanism) & degradation by non-specific esterases (biologic mechanism). Both mechanisms lead to formation of Laudanosine. Laudanosine depends on liver for clearance (70% bile excretion). Laudanosine at high plasma levels can cause cerebral excitation and seizure activity in animals, (but this has not been a clinical problem in humans.)In animals receiving Laudanosine infusion who are anaesthetised: Plasma cone. > 6 mcg/ml causes hypotension, >10 mcg/ml cause EEG epileptic spike, >17 mcg/ml causes seizures (Chappie et al 1987).A full paralyzing dose of Atracurium (0.5mg/kg) causes Laudanosine levels of only 0.3 mcg/ml. Also, in presence of anaesthetic agents, CNS depression is present, & Atracurium induced muscle relaxation will prevent muscle movement due to seizure activity.However, in the ICU, where anaesthetic agents are not present, there is a theoretical possibility of laudanosine-induced CNS stimulation. (However, in spite of prolonged infusions, it has been shown that laudanosine level in plasma is still low to produce any effects)
Accumulation of atracurium in the body
Accumulation of Laudanosine in the body
Release of histamine
Hepatotoxicity of atracurium
Non-depolarising Neuromuscular Blocking Agents