TOF: Cause of fade

Basic, Organ-Based and Clinical Sciences

Tetanic stimulation is most commonly considered to be electrical stimulation lasting for 5 seconds and at roughly 50Hz. This causes the release of significant amounts of acetylcholine at the NMJ. The result of this is a strong contraction of the muscle in people without any neuromuscular blockade. Succinylcholine administration, and subsequent phase one blockade will result in a significantly attenuated response to tetanus, but no fade will be observed. In patients treated with a non depolarizing neuromuscular blocking agent such as rocuroniuim or vecuronium, fade or progressive weakening in the response elicited by this 5 second long 50 Hz stimulus in patients is observed. 

Tetanic fade is generally thought to occur presynaptically.  The general thought is that during tetanic stimulation nerves initially dump large volumes of acetylcholine into the NMJ. The total amount that is put expelled from the presynaptic nerve into the NMJ decreases with time, and eventually equalizes with the amount of acetylcholine that is being produced in the nerve itself. When no neuromuscular blockade is present this is generally not detectable because the amount of acetylcholine being released is substantially greater than that which is needed to generate a response from a target muscle. 

When non-depolarizing neuromuscular blockade is present, the non depolarizing agent acts as a competitive inhibitor of acetylcholine, and results in decreased effect of acetylcholine concentrations in the NMJ that would typically result in a strong response.   It is also thought that neuromuscular blocking agents due work on the presynaptic nerve fiber as well by binding to presynaptic acetylcholine receptors, and decreasing acetylcholine mobilization.

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    Tetanic stimulation is most commonly considered to be electrical stimulation lasting for 5 seconds and at roughly 50Hz. This causes the release of significant amounts of acetylcholine at the NMJ. The result of this is a strong contraction of the muscle in people without any neuromuscular blockade. Succinylcholine administration, and subsequent phase one blockade will result in a significantly attenuated response to tetanus, but no fade will be observed. In patients treated with a non depolarizing neuromuscular blocking agent such as rocuroniuim or vecuronium, fade or progressive weakening in the response elicited by this 5 second long 50 Hz stimulus in patients is observed. Tetanic fade is generally thought to occur presynaptically. The general thought is that during tetanic stimulation nerves initially dump large volumes of acetylcholine into the NMJ. The total amount that is put expelled from the presynaptic nerve into the NMJ decreases with time, and eventually equalizes with the amount of acetylcholine that is being produced in the nerve itself. When no neuromuscular blockade is present this is generally not detectable because the amount of acetylcholine being released is substantially greater than that which is needed to generate a response from a target muscle. When non-depolarizing neuromuscular blockade is present, the non depolarizing agent acts as a competitive inhibitor of acetylcholine, and results in decreased effect of acetylcholine concentrations in the NMJ that would typically result in a strong response. It is also thought that neuromuscular blocking agents due work on the presynaptic nerve fiber as well by binding to presynaptic acetylcholine receptors, and decreasing acetylcholine mobilization.

39%

Answered correctly

2017

Year asked

35%

Answered correctly

2016

Year asked

Author
Russell Stuart, MD