Suxamethonium chloride, also known as suxamethonium or succinylcholine, or simply sux by medical abbreviation, is a medication used to cause short-term

paralysis Paralysis (also known as plegia) is a loss of motor function in one or more muscles. Paralysis can also be accompanied by a loss of feeling (sensory loss) in the affected area if there is sensory damage. In the United States, roughly 1 in 5 ...

as part of

general anesthesia General anaesthesia (UK) or general anesthesia (US) is a medically induced loss of consciousness that renders the patient unarousable even with painful stimuli. This effect is achieved by administering either intravenous or inhalational general ...

. This is done to help with

tracheal intubation Tracheal intubation, usually simply referred to as intubation, is the placement of a flexible plastic tube into the trachea (windpipe) to maintain an open airway or to serve as a conduit through which to administer certain drugs. It is frequentl ...

electroconvulsive therapy Electroconvulsive therapy (ECT) is a psychiatric treatment where a generalized seizure (without muscular convulsions) is electrically induced to manage refractory mental disorders.Rudorfer, MV, Henry, ME, Sackeim, HA (2003)"Electroconvulsive th ...

. It is administered by injection, either into a vein or into a muscle. When used in a vein, onset of action is generally within one minute and effects last for up to 10 minutes. Common side effects include low blood pressure, increased

saliva Saliva (commonly referred to as spit) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which DNA can ...

production, muscle pain, and rash. Serious side effects include

malignant hyperthermia Malignant hyperthermia (MH) is a type of severe reaction that occurs in response to particular medications used during general anesthesia, among those who are susceptible. Symptoms include muscle rigidity, fever, and a fast heart rate. Complica ...

and

allergic reactions Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derm ...

. It is not recommended in people who are at risk of high blood potassium or a history of

myopathy In medicine, myopathy is a disease of the muscle in which the muscle fibers do not function properly. This results in muscular weakness. ''Myopathy'' means muscle disease ( Greek : myo- ''muscle'' + patheia '' -pathy'' : ''suffering''). This me ...

. Use during

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ...

appears to be safe for the baby. Suxamethonium is in the

neuromuscular blocker Neuromuscular-blocking drugs block neuromuscular transmission at the neuromuscular junction, causing paralysis of the affected skeletal muscles. This is accomplished via their action on the post-synaptic acetylcholine (Nm) receptors. In cli ...

family of medications and is of the depolarizing type. It works by blocking the action of

acetylcholine Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...

skeletal muscles Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscle ...

. Side effects of succinylcholine chloride injection include anaphylaxis, hyperkalemia, and malignant hyperthermia. Suxamethonium was described as early as 1906 and came into medical use in 1951. It is on the World Health Organization's List of Essential Medicines. Suxamethonium is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ...

. It may colloquially be referred to as "sux".

Medical uses

Succinylcholine chloride injection is

indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosi ...

, in addition to general anesthesia, to facilitate tracheal intubation and to provide skeletal muscle relaxation during surgery or mechanical ventilation. Its medical uses are limited to short-term muscle relaxation in

anesthesia Anesthesia is a state of controlled, temporary loss of sensation or awareness that is induced for medical or veterinary purposes. It may include some or all of analgesia (relief from or prevention of pain), paralysis (muscle relaxation), ...

and intensive care, usually for facilitation of

endotracheal intubation Tracheal intubation, usually simply referred to as intubation, is the placement of a flexible plastic tube into the trachea (windpipe) to maintain an open airway or to serve as a conduit through which to administer certain drugs. It is frequentl ...

. It is popular in emergency medicine due to its rapid onset and brief duration of action. The former is a major point of consideration in the context of trauma care, where endotracheal intubation may need to be completed very quickly. The latter means that, should attempts at endotracheal intubation fail and the person cannot be ventilated, there is a prospect for neuromuscular recovery and the onset of spontaneous breathing before low blood oxygen levels occurs. It may be better than

rocuronium Rocuronium bromide (brand names Zemuron, Esmeron) is an aminosteroid non-depolarizing neuromuscular blocker or muscle relaxant used in modern anaesthesia to facilitate tracheal intubation by providing skeletal muscle relaxation, most commonly r ...

in people without contraindications due to its faster onset of action and shorter duration of action. Suxamethonium is also commonly used as the sole

muscle relaxant A muscle relaxant is a drug that affects skeletal muscle function and decreases the muscle tone. It may be used to alleviate symptoms such as muscle spasms, pain, and hyperreflexia. The term "muscle relaxant" is used to refer to two major therap ...

during

, favoured for its short duration of action. Suxamethonium is quickly degraded by plasma

butyrylcholinesterase Butyrylcholinesterase ( HGNC symbol BCHE; EC 3.1.1.8), also known as BChE, BuChE, BuChase, pseudocholinesterase, or plasma (cholin)esterase, is a nonspecific cholinesterase enzyme that hydrolyses many different choline-based esters. In humans, it ...

and the duration of effect is usually in the range of a few minutes. When plasma levels of butyrylcholinesterase are greatly diminished or an atypical form is present (an otherwise harmless inherited disorder), paralysis may last much longer, as is the case in liver failure or in neonates. It is recommended that the vials be stored at a temperature between 2°-8 °C. The multi-dose vials are stable for up to 14 days at room temperature without significant loss of potency. Unless otherwise indicated in the prescribing information, room temperature for storage of medications is 15°-25 °C (59°-77 °F).

Side effects

Side effects In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

include

, muscle pains, acute rhabdomyolysis with high blood levels of potassium, transient

ocular hypertension Ocular hypertension is the presence of elevated fluid pressure inside the eye (intraocular pressure), usually with no optic nerve damage or visual field loss. For most individuals, the normal range of intraocular pressure is between 10 mmHg and 2 ...

constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement ...

and changes in cardiac rhythm, including

slow heart rate Bradycardia (also sinus bradycardia) is a slow resting heart rate, commonly under 60 beats per minute (BPM) as determined by an electrocardiogram. It is considered to be a normal heart rate during sleep, in young and healthy or elderly adults, a ...

, and

cardiac arrest Cardiac arrest is when the heart suddenly and unexpectedly stops beating. It is a medical emergency that, without immediate medical intervention, will result in sudden cardiac death within minutes. Cardiopulmonary resuscitation (CPR) and poss ...

. In people with neuromuscular disease or

burn A burn is an injury to skin, or other tissues, caused by heat, cold, electricity, chemicals, friction, or ultraviolet radiation (like sunburn). Most burns are due to heat from hot liquids (called scalding), solids, or fire. Burns occur ma ...

s, an injection of suxamethonium can lead to a large release of

potassium Potassium is the chemical element with the symbol K (from Neo-Latin ''kalium'') and atomic number19. Potassium is a silvery-white metal that is soft enough to be cut with a knife with little force. Potassium metal reacts rapidly with atmosph ...

from

, potentially resulting in cardiac arrest. Conditions having susceptibility to suxamethonium-induced high blood potassium are burns,

closed head injury Closed-head injury is a type of traumatic brain injury in which the skull and dura mater remain intact. Closed-head injuries are the leading cause of death in children under 4 years old and the most common cause of physical disability and cognitive ...

acidosis Acidosis is a process causing increased acidity in the blood and other body tissues (i.e., an increase in hydrogen ion concentration). If not further qualified, it usually refers to acidity of the blood plasma. The term ''acidemia'' describes ...

Guillain–Barré syndrome Guillain–Barré syndrome (GBS) is a rapid-onset muscle weakness caused by the immune system damaging the peripheral nervous system. Typically, both sides of the body are involved, and the initial symptoms are changes in sensation or pain oft ...

, cerebral stroke,

drowning Drowning is a type of suffocation induced by the submersion of the mouth and nose in a liquid. Most instances of fatal drowning occur alone or in situations where others present are either unaware of the victim's situation or unable to offer as ...

, severe intra-abdominal

sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...

, massive

trauma Trauma most often refers to: * Major trauma, in physical medicine, severe physical injury caused by an external source * Psychological trauma, a type of damage to the psyche that occurs as a result of a severely distressing event *Traumatic i ...

, and

tetanus Tetanus, also known as lockjaw, is a bacterial infection caused by ''Clostridium tetani'', and is characterized by muscle spasms. In the most common type, the spasms begin in the jaw and then progress to the rest of the body. Each spasm usually ...

. Suxamethonium does not produce

unconsciousness Unconsciousness is a state in which a living individual exhibits a complete, or near-complete, inability to maintain an awareness of self and environment or to respond to any human or environmental stimulus. Unconsciousness may occur as the re ...

, and its effects may cause considerable psychological distress while simultaneously making it impossible for a patient to communicate. Therefore, administration of the drug to a conscious patient is contraindicated.

Hyperkalemia

The side effect of high blood potassium may occur because the acetylcholine receptor is propped open, allowing continued flow of potassium ions into the

extracellular fluid In cell biology, extracellular fluid (ECF) denotes all body fluid outside the cells of any multicellular organism. Total body water in healthy adults is about 60% (range 45 to 75%) of total body weight; women and the obese typically have a low ...

. A typical increase of potassium ion serum concentration on administration of suxamethonium is 0.5 mmol per liter.The increase is transient in otherwise healthy patients. The normal range of potassium is 3.5 to 5 mEq per liter. High blood potassium does not generally result in adverse effects below a concentration of 6.5 to 7 mEq per liter. Therefore, the increase in serum potassium level is usually not catastrophic in otherwise healthy patients. Severely high blood levels of potassium can cause changes in

cardiac electrophysiology Cardiac electrophysiology is a branch of cardiology and basic science focusing on the electrical activities of the heart. The term is usually used in clinical context, to describe studies of such phenomena by invasive (intracardiac) catheter recor ...

, which, if severe, can result in arrhythmias and even

Malignant hyperthermia

Malignant hyperthermia Malignant hyperthermia (MH) is a type of severe reaction that occurs in response to particular medications used during general anesthesia, among those who are susceptible. Symptoms include muscle rigidity, fever, and a fast heart rate. Complica ...

(MH) from suxamethonium administration can result in a drastic and uncontrolled increase in skeletal muscle oxidative metabolism. This overwhelms the body's capacity to supply

oxygen Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as ...

, remove

carbon dioxide Carbon dioxide ( chemical formula ) is a chemical compound made up of molecules that each have one carbon atom covalently double bonded to two oxygen atoms. It is found in the gas state at room temperature. In the air, carbon dioxide is trans ...

, and regulate body temperature, eventually leading to circulatory collapse and death if not treated quickly. Susceptibility to malignant hyperthermia is often inherited as an autosomal dominant disorder, for which there are at least six genetic loci of interest, the most prominent being the

ryanodine Ryanodine is a poisonous diterpenoid found in the South American plant ''Ryania speciosa'' (Salicaceae). It was originally used as an insecticide. The compound has extremely high affinity to the open-form ryanodine receptor, a group of calcium cha ...

receptor gene (RYR1). MH susceptibility is

phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological pr ...

and genetically related to

central core disease Central core disease (CCD), also known as central core myopathy, is an autosomal dominantly inherited muscle disorder present from birth that negatively affects the skeletal muscles. It was first described by Shy and Magee in 1956. It is charact ...

(CCD), an autosomal dominant disorder characterized both by MH symptoms and by

. MH is usually unmasked by

, or when a family member develops the symptoms. There is no simple, straightforward test to diagnose the condition. When MH develops during a procedure, treatment with

dantrolene Dantrolene sodium, sold under the brand name Dantrium among others, is a postsynaptic muscle relaxant that lessens excitation-contraction coupling in muscle cells. It achieves this by inhibiting Ca2+ ions release from sarcoplasmic reticulum s ...

sodium is usually initiated; dantrolene and the avoidance of suxamethonium administration in susceptible people have markedly reduced the mortality from this condition.

Apnea

The normal short duration of action of suxamethonium is due to the rapid metabolism of the drug by non-specific plasma cholinesterases. However plasma cholinesterase activity is reduced in some people due to either genetic variation or acquired conditions, which results in a prolonged duration of neuromuscular block. Genetically, ninety six percent of the population have a normal (Eu:Eu) genotype and block duration; however, some people have atypical genes (Ea, Es, Ef) which can be found in varying combinations with the Eu gene, or other atypical genes (see Pseudocholinesterase deficiency). Such genes will result in a longer duration of action of the drug, ranging from 20 minutes up to several hours. Acquired factors that affect plasma cholinesterase activity include pregnancy, liver disease, kidney failure, heart failure,

thyrotoxicosis Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidism. ...

, and cancer, as well as a number of other drugs. If unrecognized by a clinician it could lead to awareness if anesthesia is discontinued whilst still paralyzed or hypoxemia (and potentially fatal consequences) if artificial ventilation is not maintained. Normal treatment is to maintain sedation and ventilate the patient on an intensive care unit until muscle function has returned. Blood testing for cholinesterase function can be performed. Mivacurium, a non-depolarizing neuromuscular blocking drug, is also metabolized via the same route with a similar clinical effect in patients deficient in plasma cholinesterase activity. Deliberate induction of conscious apnea using this drug led to its use as a form of

aversion therapy Aversion therapy is a form of psychological treatment in which the patient is exposed to a stimulus while simultaneously being subjected to some form of discomfort. This conditioning is intended to cause the patient to associate the stimulus wit ...

in the 1960s and 1970s in some prison and institutional settings. This use was discontinued after negative publicity concerning the terrifying effects on subjects of this treatment and ethical questions about the punitive use of painful aversion.

Mechanism of action

There are two phases to the blocking effect of suxamethonium.

Phase 1 block

Phase 1 blocking has the principal paralytic effect. Binding of suxamethonium to the nicotinic acetylcholine receptor results in opening of the receptor's monovalent cation channel; a disorganized

depolarization In biology, depolarization or hypopolarization is a change within a cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell compared to the outside. Depolarization is ess ...

of the

motor end-plate A neuromuscular junction (or myoneural junction) is a chemical synapse between a motor neuron and a muscle fiber. It allows the motor neuron to transmit a signal to the muscle fiber, causing muscle contraction. Muscles require innervation to ...

occurs and

calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar t ...

is released from the

sarcoplasmic reticulum The sarcoplasmic reticulum (SR) is a membrane-bound structure found within muscle cells that is similar to the smooth endoplasmic reticulum in other cells. The main function of the SR is to store calcium ions (Ca2+). Calcium ion levels are ke ...

. In normal skeletal muscle,

dissociates from the receptor following depolarization and is rapidly hydrolyzed by acetylcholinesterase. The muscle cell is then ready for the next signal. Suxamethonium has a longer duration of effect than acetylcholine, and is not hydrolyzed by acetylcholinesterase. By maintaining the membrane potential above threshold, it does not allow the muscle cell to repolarize. When acetylcholine binds to an already depolarized receptor, it cannot cause further depolarization. Calcium is removed from the muscle cell

cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...

independent of repolarization (depolarization signaling and muscle contraction are independent processes). As the calcium is taken up by the sarcoplasmic reticulum, the muscle relaxes. This explains muscle flaccidity rather than

tetany Tetany or tetanic seizure is a medical sign consisting of the involuntary contraction of muscles, which may be caused by disorders that increase the action potential frequency of muscle cells or the nerves that innervate them. Muscle cramps caus ...

following fasciculations. The results are membrane depolarization and transient fasciculations, followed by flaccid paralysis.

Phase 2 block

While this phase is not abnormal and is a part of its mechanism of action, it is undesirable during surgery, due to the inability to depolarize the cell again. Often, patients must be on a ventilator for hours if Phase 2 block occurs. It is caused by the blood concentration of suxamethonium exceeding the therapeutic window. Desensitization occurs at the nerve terminal, and the myocyte becomes less sensitive to acetylcholine; the membrane repolarizes and cannot be depolarized again.

Chemistry

Suxamethonium is an odorless, white

crystal A crystal or crystalline solid is a solid material whose constituents (such as atoms, molecules, or ions) are arranged in a highly ordered microscopic structure, forming a crystal lattice that extends in all directions. In addition, macro ...

line substance. Aqueous solutions have a pH of about 4. The

dihydrate In chemistry, a hydrate is a substance that contains water or its constituent elements. The chemical state of the water varies widely between different classes of hydrates, some of which were so labeled before their chemical structure was understo ...

melts at 160 °C, whereas the anhydrous melts at 190 °C. It is highly soluble in water (1 gram in about 1 mL), soluble in

ethyl alcohol Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an alcohol with the chemical formula . Its formula can be also written as or (an ethyl group linked to a hyd ...

(1 gram in about 350 mL), slightly soluble in chloroform, and practically insoluble in

ether In organic chemistry, ethers are a class of compounds that contain an ether group—an oxygen atom connected to two alkyl or aryl groups. They have the general formula , where R and R′ represent the alkyl or aryl groups. Ethers can again be ...

. Suxamethonium is a

hygroscopic Hygroscopy is the phenomenon of attracting and holding water molecules via either absorption or adsorption from the surrounding environment, which is usually at normal or room temperature. If water molecules become suspended among the substan ...

compound. The compound consists of two

molecules that are linked by their acetyl groups. It can also be viewed as a central moiety of

succinic acid Succinic acid () is a dicarboxylic acid with the chemical formula (CH2)2(CO2H)2. The name derives from Latin ''succinum'', meaning amber. In living organisms, succinic acid takes the form of an anion, succinate, which has multiple biological ro ...

with two

choline Choline is an essential nutrient for humans and many other animals. Choline occurs as a cation that forms various salts (X− in the depicted formula is an undefined counteranion). Humans are capable of some ''de novo synthesis'' of choline but r ...

moieties, one on each end.

History

Suxamethonium was first discovered in 1906 by Reid Hunt and René de M. Taveau. When studying the drug, animals were given

curare Curare ( /kʊˈrɑːri/ or /kjʊˈrɑːri/; ''koo-rah-ree'' or ''kyoo-rah-ree'') is a common name for various alkaloid arrow poisons originating from plant extracts. Used as a paralyzing agent by indigenous peoples in Central and South ...

and thus they missed the neuromuscular blocking properties of suxamethonium. Instead in 1949 an Italian group led by

Daniel Bovet Daniel Bovet (23 March 1907 – 8 April 1992) was a Swiss-born Italian pharmacologist who won the 1957 Nobel Prize in Physiology or Medicine for his discovery of drugs that block the actions of specific neurotransmitters. He is best known for hi ...

was first to describe succinylcholine induced paralysis. The clinical introduction of suxamethonium was described in 1951 by several groups. Papers published by Stephen Thesleff and Otto von Dardel in Sweden are important but also to be mentioned is work by Bruck, Mayrhofer and Hassfurther in Austria, Scurr and Bourne in UK, and Foldes in America.

Abuse

Dubai Dubai (, ; ar, دبي, translit=Dubayy, , ) is the most populous city in the United Arab Emirates (UAE) and the capital of the Emirate of Dubai, the most populated of the 7 emirates of the United Arab Emirates.The Government and Politics of ...

authorities deem that the murder of

Hamas Hamas (, ; , ; an acronym of , "Islamic Resistance Movement") is a Palestinian Sunni-Islamic fundamentalist, militant, and nationalist organization. It has a social service wing, Dawah, and a military wing, the Izz ad-Din al-Qassam ...

operative

Mahmoud al-Mabhouh Mahmoud Abdel Rauf al-Mabhouh ( ar, محمود عبد الرؤوف المبحوح; 14 February 1960 – 19 January 2010) was the chief of logistics and weapons procurement for Hamas's military wing, the Izz ad-Din al-Qassam Brigades. He is reme ...

was carried out on their soil by Mossad agents with the use of suxamethonium chloride injection. Entering Dubai under false passports in 2010, the Mossad agents found al-Mabhouh at a hotel, immobilized him with the drug, electrocuted him, then suffocated him by pillow in an assassination. A high concentration of suxamethonium chloride was found in al-Mabhouh's body post-mortem. The incident triggered significant diplomatic crises in the Middle East, Europe, and Australia. It was used by serial killer

Efren Saldivar Efren Saldivar (born September 30, 1969) is an American serial killer who murdered patients while working as a respiratory therapist at Adventist Health Glendale, named at that time Glendale Adventist Medical Center in Glendale, California. Ear ...

(1988-1998), and in the murder of Kathy Augustine (2006).

Brand names

It is available in German-speaking countries under the trade name Lysthenon among others.Compendium.ch: LYSTHENON 2% Inj Lös 100 mg/5ml

Other animals

It is sometimes used in combination with

pain medication An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...

s and sedatives for euthanasia and immobilization of horses.

References

External links

* {{DEFAULTSORT:Suxamethonium Chloride Chemical substances for emergency medicine Chlorides Choline esters Lethal injection components Muscle relaxants Neuromuscular blockers Nicotinic agonists Quaternary ammonium compounds Succinate esters World Health Organization essential medicines Wikipedia medicine articles ready to translate