Bin Yang1, Jin-Chao Song2, Ji-Hong Jiang1, Shi-Tong Li3. 1. Department of Anesthesiology, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P.R.China. 2. Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China. 3. Department of Anesthesiology, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P.R.China. Electronic address: shitongli.shh@gmail.com.
Abstract
BACKGROUND: Urgent tracheal intubation is common in intensive care units and the emergency room, and succinylcholine is a first-line neuromuscular blocker used in these situations. Paraplegic or critically ill patients may be at a high risk of receiving succinylcholine because the denervation stage changes nicotinic receptors, which affect the efficacy and safety of succinylcholine. The objective of this study was to determine the receptor subtypes associated with changes in the pharmacodynamics of succinylcholine and its time-line trend. METHODS: Denervated gastrocnemius was collected from tibial nerve transected rats. To determine the 50% effective dose of succinylcholine and rocuronium at 0 (control), 1, 3, 7, 14, and 28 d after denervation, action potential amplitude was monitored by an intracellular recording method. Subunits α1, α7, ε, and γ of the acetylcholine receptor (AChR) were quantified by real-time polymerase chain reaction. Receptor amount and pharmacodynamic changes were analyzed by correlation and regression analysis. RESULTS: The pharmacodynamic change in succinylcholine was a dynamic process, and at the same time α7, ε, and γ-nicotinic AChR genes in denervated muscle were significantly changed but only α7 was closely correlated with the action of succinylcholine. Subunit γ and α7 were related to pharmacodynamic change in the nondepolarizing neuromuscular agent, rocuronium. CONCLUSIONS: Nerve injury may alter nicotinic AChR subtypes in skeletal muscle at different stages, which probably affected the pharmacodynamics of neuromuscular blockers in different ways. Denervation time and stage and the type of neuromuscular blocker and dosage should be taken into consideration when using these drugs in patients with nerve injury.
BACKGROUND: Urgent tracheal intubation is common in intensive care units and the emergency room, and succinylcholine is a first-line neuromuscular blocker used in these situations. Paraplegic or critically illpatients may be at a high risk of receiving succinylcholine because the denervation stage changes nicotinic receptors, which affect the efficacy and safety of succinylcholine. The objective of this study was to determine the receptor subtypes associated with changes in the pharmacodynamics of succinylcholine and its time-line trend. METHODS: Denervated gastrocnemius was collected from tibial nerve transected rats. To determine the 50% effective dose of succinylcholine and rocuronium at 0 (control), 1, 3, 7, 14, and 28 d after denervation, action potential amplitude was monitored by an intracellular recording method. Subunits α1, α7, ε, and γ of the acetylcholine receptor (AChR) were quantified by real-time polymerase chain reaction. Receptor amount and pharmacodynamic changes were analyzed by correlation and regression analysis. RESULTS: The pharmacodynamic change in succinylcholine was a dynamic process, and at the same time α7, ε, and γ-nicotinic AChR genes in denervated muscle were significantly changed but only α7 was closely correlated with the action of succinylcholine. Subunit γ and α7 were related to pharmacodynamic change in the nondepolarizing neuromuscular agent, rocuronium. CONCLUSIONS:Nerve injury may alter nicotinic AChR subtypes in skeletal muscle at different stages, which probably affected the pharmacodynamics of neuromuscular blockers in different ways. Denervation time and stage and the type of neuromuscular blocker and dosage should be taken into consideration when using these drugs in patients with nerve injury.