A patient in ICU was started on atracurium infusion. He developed seizure on day 3. What is the most likely cause?
High-Yield Explanation
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)