Why does succinylcholine cause muscle fasciculations?

From the Guidelines

Succinylcholine causes muscle fasciculations because it initially stimulates nicotinic acetylcholine receptors at the neuromuscular junction before causing paralysis. When administered intravenously, succinylcholine first binds to these receptors and causes them to open, allowing sodium ions to enter the muscle cells. This creates widespread, uncoordinated depolarization of muscle fibers, visible as brief, involuntary muscle twitches or fasciculations. These fasciculations typically appear within seconds of administration and precede the subsequent phase of muscle paralysis. The paralysis occurs because succinylcholine, unlike acetylcholine, is not rapidly broken down by acetylcholinesterase, leading to persistent depolarization and preventing muscle contraction 1.

Key Points

• Succinylcholine is a depolarizing neuromuscular blocking agent (NMBA) that acts as an agonist at nicotinic receptors.
• The initial depolarization caused by succinylcholine is seen clinically as fasciculations and then as paralysis.
• The duration of effect of succinylcholine is only 3 to 5 minutes, making it suitable for short procedures such as tracheal intubation.
• To minimize fasciculations, a small dose of a non-depolarizing neuromuscular blocking agent like rocuronium or vecuronium can be administered as a "defasciculating" pretreatment 3-5 minutes before succinylcholine.

Mechanism of Action

The mechanism of action of succinylcholine involves the binding of succinylcholine to nicotinic acetylcholine receptors at the neuromuscular junction, causing the ion-gated channels to open and remain open 1. This leads to an influx of sodium ions into the muscle cells, resulting in depolarization and muscle contraction. However, because succinylcholine is not rapidly broken down by acetylcholinesterase, the depolarization persists, leading to muscle paralysis.

Clinical Implications

The fasciculations caused by succinylcholine can lead to post-operative myalgia, which can be reduced by administering a defasciculating dose of a non-depolarizing neuromuscular blocking agent before succinylcholine 1. Additionally, succinylcholine is contraindicated in patients with certain conditions, such as Duchenne muscular dystrophy, due to the risk of acute rhabdomyolysis, hyperkalemia, and cardiac arrest 1.

From the FDA Drug Label

As does acetylcholine, it combines with the cholinergic receptors of the motor end plate to produce depolarization. This depolarization may be observed as fasciculations. Succinylcholine causes muscle fasciculations because it produces depolarization of the motor end plate by combining with the cholinergic receptors, which can be observed as fasciculations.

• The depolarization caused by succinylcholine leads to muscle fasciculations before the onset of flaccid paralysis. 2

From the Research

Mechanism of Succinylcholine-Induced Muscle Fasciculations

• Succinylcholine binds to nicotinic acetylcholine receptors of the neuromuscular junction and produces prolonged depolarization during which activation of the muscle is blocked 3.
• Initial depolarization of the neuromuscular junction induces hectic fasciculation of the muscle fibers, which in turn may be responsible for the occurrence of post-operative myalgias (POM) 3.
• The depolarizing muscle relaxant succinylcholine (SCh) may cause several side effects including muscle fasciculations and postoperative myalgia 4.

Prevention of Succinylcholine-Induced Fasciculation and Myalgia

• Nondepolarizing muscle relaxants, lidocaine, or magnesium can prevent fasciculation 5.
• Best prevention of myalgia is with nonsteroidal antiinflammatory drugs and with rocuronium or lidocaine 5.
• Prior administration of a non-depolarizing muscle relaxant can attenuate or even prevent muscle fasciculations and postoperative myalgia 4.

Clinical Pharmacology of Neuromuscular Blocking Agents

• Succinylcholine attaches to receptors in the motor end plate and depolarizes the neuromuscular junction, making the end plate refractory to acetylcholine 6.
• The nondepolarizing relaxants have a structure similar to that of succinylcholine and bind to the same receptors, but instead of depolarizing the junction, they block acetylcholine from binding to the receptor and cause channel blockade 6.
• Neuromuscular blocking agents are essential to anesthesia, and their use can facilitate endotracheal intubation and provide skeletal muscle relaxation during surgery 7.