Succinylcholine (suxamethonium) is an ultra-short-acting skeletal muscle relaxant used primarily to achieve rapid muscle paralysis. It is frequently used to facilitate emergency procedures, such as tracheal intubation, which requires the quick and complete relaxation of the jaw and throat muscles to secure a breathing tube. Succinylcholine is classified as a depolarizing neuromuscular blocker due to its unique mechanism of action at the neuromuscular junction. Its powerful effect makes it invaluable for situations requiring muscle relaxation within seconds.
The Neuromuscular Junction: Normal Muscle Signaling
The fundamental site of communication between the nervous system and skeletal muscle is the neuromuscular junction (NMJ). This specialized synapse allows a motor nerve to transmit an electrical signal to a muscle fiber, triggering contraction. The process begins when the motor nerve releases the neurotransmitter acetylcholine (ACh) into the synaptic cleft.
ACh quickly diffuses across the gap and binds to nicotinic acetylcholine receptors on the muscle side. These receptors are ligand-gated ion channels; when ACh binds, the channel opens momentarily, allowing positively charged ions, primarily sodium, to rush into the muscle cell.
The influx of sodium ions generates a localized change in electrical charge known as depolarization. If this depolarization reaches a threshold, it propagates an action potential along the muscle fiber, leading to muscle contraction. The enzyme acetylcholinesterase rapidly breaks down the ACh, allowing the receptor to close and the muscle to repolarize, preparing it for the next signal.
Succinylcholine’s Initial Phase: Receptor Activation
Succinylcholine’s chemical structure mimics the natural neurotransmitter acetylcholine (ACh). When administered, succinylcholine binds to the nicotinic acetylcholine receptors at the muscle endplate. Because it is an agonist, this binding initially opens the ion channels, resulting in an uncontrolled influx of sodium ions and causing the muscle fiber membrane to depolarize.
This initial depolarization manifests clinically as visible, involuntary muscle twitching across the body, known as fasciculations. These fasciculations are brief and precede the onset of total muscle paralysis. Unlike ACh, succinylcholine is not readily broken down by acetylcholinesterase, meaning it remains bound to the receptor for an extended time.
The Mechanism of Relaxation: Sustained Depolarization Block
Muscle relaxation, or flaccid paralysis, occurs immediately after the initial fasciculations. This is a consequence of the sustained binding of succinylcholine, which keeps the ion channel open and holds the muscle cell membrane in a state of continuous depolarization, known as a Phase I or depolarization block.
The continuous depolarization prevents the muscle cell from repolarizing and resetting its electrical potential. This prolonged state forces the nearby voltage-gated sodium channels into an inactive or refractory state. Since these channels cannot reset, the muscle becomes unresponsive to any further nerve impulses. This sustained refractory state achieves the complete muscle paralysis required for procedures like intubation.
Breakdown and Recovery: Why the Effect is Short-Lived
The duration of succinylcholine’s action is short, typically lasting five to ten minutes following a single intravenous dose. This rapid termination is due to its metabolic pathway, which occurs away from the neuromuscular junction. Succinylcholine must first diffuse out of the synaptic cleft and into the bloodstream.
Once in the plasma, succinylcholine is rapidly broken down by the enzyme pseudocholinesterase (butyrylcholinesterase). This enzyme is synthesized in the liver and circulates throughout the body. Pseudocholinesterase hydrolyzes succinylcholine into inactive metabolites. This efficient breakdown by a circulating enzyme is why the drug is the only ultra-short-acting muscle relaxant used clinically.
Clinical Considerations and Specific Risks
Hyperkalemia and Malignant Hyperthermia
Succinylcholine is associated with several specific adverse effects that require careful consideration. One major concern is the risk of hyperkalemia, an abnormally high level of potassium in the blood. The prolonged opening of the ion channels during depolarization allows potassium ions to exit the muscle cell and enter the bloodstream.
While potassium efflux is usually minor in healthy patients, it can be dangerously exaggerated in those with severe burns, crush injuries, or spinal cord injuries. These conditions cause an increase in the number of acetylcholine receptors, leading to a massive, life-threatening release of potassium upon drug administration. Another serious risk is malignant hyperthermia (MH), a genetic hypermetabolic muscle disorder. Succinylcholine can trigger MH in susceptible individuals, causing severe muscle rigidity, a rapid increase in body temperature, and acidosis.
Prolonged Paralysis
A patient may also experience prolonged paralysis if they have atypical pseudocholinesterase. This genetic condition means the enzyme responsible for breaking down the drug does not function efficiently. In these cases, the metabolism of succinylcholine is significantly delayed, meaning the paralysis can persist for hours rather than minutes. Patients require mechanical ventilation until the drug is naturally cleared. Genetic variants of the enzyme can result in a prolonged block lasting anywhere from twenty minutes up to eight hours.