Phase II depolarizing blockade
Basic, Basic Sciences, Pharmacology
Succinylcholine is comprised of two acetylcholine molecules joined together and acts as a depolarizing neuromuscular blocker by binding acetylcholine receptors at the post-synaptic neuromuscular junction end plate. The resultant end plate depolarization initially stimulates muscle contraction; however, because succinylcholine is not degraded by acetylcholinesterase, it remains in the neuromuscular junction to cause continuous end plate depolarization and subsequent muscle relaxation. This is termed a phase I block.
Mechanism of Phase II Block
With increasing doses of succinylcholine (i.e., a large single dose, repeated doses, or a continuous infusion), a phase II block may occur. Continuous activation of acetylcholine receptors leads to ongoing shifts of sodium into the cell and potassium out of the cell. Despite this, the post-junctional membrane potential eventually moves in the direction of normal even in the continued presence of succinylcholine. This is due to increased activity of the sodium-potassium ATPase pump, which brings potassium into the cell in exchange for sodium. The receptor does not respond appropriately to acetylcholine, and neuromuscular blockade is prolonged. Phase II block may be seen clinically with doses of succinylcholine >4mg/kg, but some characteristics of this blockade have been reported at 0.3mg/kg.
The possibility of a phase II block should be suspected if succinylcholine is given as an infusion or if tachyphylaxis is noted with repeated doses. With regard to nerve stimulation, a phase II block has features of a non-depolarizing block (i.e., fade is seen with tetanic and train-of-four stimulation; there is post-tetanic potentiation). This is in contrast to a phase I block in which no fade is seen with tetanic or train-of-four stimulation and there is no post-tetanic potentiation.
Phase II block may be prevented by avoiding succinylcholine and its risk minimized by limiting the total dose. If phase II block occurs, it may be antagonized by acetylcholinesterase inhibitors; however, given the complexity of the pathophysiology and unpredictable response to antagonism, this practice is controversial. Some recommend simply waiting until the block resolves. Regardless, neuromuscular function should be monitored such that the development of phase II block and its management may be appropriately evaluated.