To the Editor:—
The excellent article by Jonsson et al. 1provides biophysical insight into the mechanism of action of succinylcholine on the muscle-type acetylcholine receptors. They conclude that succinylcholine activates these receptors followed by desensitization.
The initial phase of activation results in an endplate potential that opens the adjacent voltage-gated sodium channel, resulting in repetitive waves of action potentials that manifest as initial muscle fasciculations. Because succinylcholine is not metabolized by the specific cholinesterase at the endplate, the succinylcholine-induced depolarization is maintained, and the outer voltage-gated sodium channel remains open. However, the inner time-dependent sodium gate will close, resulting in an endplate-muscular block. Because the depolarizing block is beyond the endplate, it is not characterized by tetanic fade or posttetanic facilitation and is potentiated by neostigmine (fig. 1A).
Fig. 1. Tracings of the twitch response to ulnar nerve stimulation in three patients with homozygote atypical plasma cholinesterase. ( A ) Administration of succinylcholine 0.1 mg/kg resulted in a depolarizing block characterized by minimal tetanic fade (T) and no posttetanic facilitation (PTF). Neostigmine 0.05/mg potentiated block. ( B ) Twitch response in a second patient with atypical esterase showing recovery of the twitch response after succinylcholine 0.1 mg/kg, associated with moderate tetanic fade and posttetanic facilitation. Neostigmine 2.5 mg accelerated recovery. ( C ) The twitch response in a third patient with atypical esterase. Injection of succinylcholine 1 mg/kg resulted in a very prolonged neuromuscular block. After 90 min, recovery started and was associated with marked tetanic fade and posttetanic facilitation. Administration of neostigmine 0.05 mg/kg could completely reverse the block. Modified from Baraka .2
Fig. 1. Tracings of the twitch response to ulnar nerve stimulation in three patients with homozygote atypical plasma cholinesterase. ( A ) Administration of succinylcholine 0.1 mg/kg resulted in a depolarizing block characterized by minimal tetanic fade (T) and no posttetanic facilitation (PTF). Neostigmine 0.05/mg potentiated block. ( B ) Twitch response in a second patient with atypical esterase showing recovery of the twitch response after succinylcholine 0.1 mg/kg, associated with moderate tetanic fade and posttetanic facilitation. Neostigmine 2.5 mg accelerated recovery. ( C ) The twitch response in a third patient with atypical esterase. Injection of succinylcholine 1 mg/kg resulted in a very prolonged neuromuscular block. After 90 min, recovery started and was associated with marked tetanic fade and posttetanic facilitation. Administration of neostigmine 0.05 mg/kg could completely reverse the block. Modified from Baraka .2
Prolonged exposure of the endplate to succinylcholine will result in progressive desensitization to the depolarizing action of succinylcholine, as well as to the chemical transmitter acetylcholine; hence, the block will gradually change from a depolarizing endplate-muscular block (Phase I) into a desensitizing Phase II neuromuscular block, which is characterized by progressive tetanic fade and posttetanic facilitation. The neuromuscular block may be antagonized by neostigmine. The degree of reversal by neostigmine is proportional to the extent of fade and posttetanic facilitation (fig. 1, B and C).2
American University of Beirut, Beirut, Lebanon. abaraka@aub.edu.lb
