Reversal of Neuromuscular Blockade

REVERSAL OF NEUROMUSCULAR BLOCKADE

Because succinylcholine is not metabolized by acetylcholinesterase, it unbinds the receptorand diffuses away from the neuromuscular junction to be hydrolyzed in the plasma and liver by another enzyme, pseudocholinesterase (nonspecific cholin-esterase, plasma cholinesterase, or butyrylcholin-esterase). Fortunately, this is a fairly rapid process, because no specific agent to reverse a depolarizing blockade is available.With the exception of the discontinued drug mivacurium, nondepolarizing agents are notmetabolized by either acetylcholinesterase or pseu-docholinesterase. Reversal of their blockade depends on unbinding the receptor, redistribution, metabolism, and excretion of the relaxant by the body, or administration of specific reversal agents (eg, cholinesterase inhibitors) that inhibit acetyl-cholinesterase enzyme activity. Because this inhibi-tion increases the amount of ACh that is available at the neuromuscular junction and can compete with the nondepolarizing agent, clearly, the reversal agents are of no benefit in reversing a depolarizing block. In fact, by increasing neuromuscular junc-tion ACh concentration and inhibiting pseudocho-linesterase-induced metabolism of succinylcholine, cholinesterase inhibitors can prolong neuromuscular blockade produced by succinylcholine. The ONLYtime neostigmine reverses neuromuscular block after succinylcholine is when there is a phase II block (fade of the train-of-four) AND sufficient time has passed for the circulating concentration of succinylcholine to be negligible.

Sugammadex, a cyclodextrin, is the first selec-tive relaxant-binding agent; it exerts its reversal effect by forming tight complexes in a 1:1 ratio with steroidal nondepolarizing agents (vecuronium, rocuronium,). This drug has been in use in the Euro-pean Union for the past few years, but is not yet commercially available in the United States.

The newer neuromuscular blocking agents, such as gantacurium, which are still under investiga-tion, show promise as ultrashort-acting nondepolar-izing agents; they undergo chemical degradation by rapid adduction with L-cysteine.