Inflammatory liver disease shortens atracurium-induced neuromuscular blockade in rats

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Background and objectiveInflammatory liver dysfunction in rats leads to a prolonged vecuronium-induced neuromuscular blockade due to insufficient metabolism. A coexisting resistance against the drug partly counteracts this prolongation. The present study investigates the pharmacodynamics of atracurium whose metabolism does not depend on liver function.MethodsMale Sprague–Dawley rats (n =14; 290 ± 30 g) were randomly allocated to either a group in which liver inflammation was induced by intravenous injection of 60 mg kg−1 heat-killed Corynebacterium parvum or to a control group. On day 5 after injection, liver function was assessed using the aminopyrine breath test. Under propofol anaesthesia, duration of action of atracurium (4.8 mg kg−1) was measured by evoked mechanomyography (stimulation of the sciatic nerve; contraction of the gastrocnemius muscle). Nitric oxide concentrations, as variables for the severity of the inflammation, were assessed by measurement of nitrite/nitrate plasma concentrations.ResultsIn C. parvum-injected rats, nitrite/nitrate plasma concentrations were increased (972 ± 597 vs. 25 ± 7 μmol L−1), the aminopyrine turnover was depressed (1.7 ± 0.4% vs. 3.5 ± 0.5%), and the atracurium-induced neuromuscular blockade was shortened (372 ± 128 s vs. 1081 ± 234 s).ConclusionsA systemic inflammatory response syndrome with liver dysfunction results in decreased sensitivity to atracurium. Further investigations are needed regarding a possible up-regulation of acetylcholine receptors or an increased protein binding of atracurium during sepsis to clarify reasons behind this phenomenon.

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