Suxamethonium

Usage

• Suxamethonium is prescribed for the production of skeletal muscle relaxation during surgical procedures requiring only brief relaxation such as endotracheal intubation, endoscopic examinations, orthopedic manipulations, and electroconvulsive therapy. It’s also used to mitigate muscle contractions during pharmacologically or electrically induced convulsions.
• Pharmacological Classification: Neuromuscular blocking agent, depolarizing type.
• Mechanism of Action: Suxamethonium acts as a depolarizing neuromuscular blocking agent, mimicking the action of acetylcholine at the neuromuscular junction. It binds to nicotinic acetylcholine receptors on the motor end-plate, causing persistent depolarization. This initially leads to muscle fasciculations (twitching) followed by flaccid paralysis due to the inability of the muscle membrane to repolarize.

Alternate Names

• Succinylcholine Chloride
• Anectine (brand name)
• Quelicin (brand name)
• Scoline (brand name)
• Sucol (brand name)

How It Works

• Pharmacodynamics: Suxamethonium depolarizes the motor end-plate, initially causing muscle fasciculations followed by flaccid paralysis. It has no effect on consciousness, pain threshold, or cerebration.
• Pharmacokinetics:
  • Absorption: Primarily administered intravenously (IV) and less commonly intramuscularly (IM). IV administration leads to a rapid onset of action (30-60 seconds). IM administration has a slower onset (2-3 minutes).
  • Metabolism: Rapidly hydrolyzed by plasma pseudocholinesterase (butyrylcholinesterase) to succinylmonocholine and choline, with further metabolism of succinylmonocholine to succinic acid and choline.
  • Elimination: Primarily via renal excretion of the metabolites, with a small percentage of the drug excreted unchanged.
• Mode of Action: Binds to nicotinic acetylcholine receptors at the motor end-plate, causing persistent depolarization and preventing further activation by acetylcholine, leading to muscle paralysis.
• Receptor Binding: Nicotinic acetylcholine receptor agonist.
• Elimination Pathways: Renal excretion of metabolites.

Dosage

Standard Dosage

Adults:

• IV: 0.6 mg/kg (range 0.3-1.1 mg/kg) for intubation, administered over 10-30 seconds. For longer procedures, an IV infusion of 2.5-4.3 mg/minute (0.1-0.2% solution in 5% dextrose or normal saline) can be used. Maximum total dose for infusion: 500 mg/hour.
• IM: Up to 2.5 mg/kg (maximum 150 mg total) if IV access is unavailable.

Children:

• IV: 1-2 mg/kg. Continuous IV infusions are not recommended in children due to the risk of malignant hyperthermia. Pre-treatment with atropine may be necessary to reduce the risk of bradycardia.
• IM: Up to 4-5 mg/kg in infants, up to 4 mg/kg in older children (maximum 150 mg total).

Special Cases:

• Elderly Patients: Similar dosage to adults but may require close monitoring due to increased risk of cardiac arrhythmias, especially in patients taking digitalis.
• Patients with Renal Impairment: Use with caution as suxamethonium metabolites are renally excreted. Monitor for prolonged paralysis.
• Patients with Hepatic Dysfunction: May exhibit prolonged paralysis due to decreased pseudocholinesterase activity; avoid repeated doses.
• Patients with Comorbid Conditions: Use with caution in patients with cardiovascular, respiratory, or neuromuscular diseases, electrolyte imbalances, or suspected cardiac glycoside toxicity.

Clinical Use Cases

• Intubation: 0.6-1 mg/kg IV.
• Surgical Procedures (short duration): IV bolus or infusion as described above.
• Mechanical Ventilation: IV infusion, adjusting rate according to response.
• Intensive Care Unit (ICU) Use: Primarily for facilitating intubation or short procedures. Continuous use is generally avoided.
• Emergency Situations: IV administration for rapid sequence intubation.

Dosage Adjustments:

• Monitor renal and hepatic function and adjust the dose as needed.
• Individuals with genetic polymorphisms affecting pseudocholinesterase activity may experience prolonged paralysis and require lower doses.

Side Effects

Common Side Effects:

• Muscle fasciculations
• Post-operative muscle pain
• Increased salivation
• Transient rise in intraocular pressure

Rare but Serious Side Effects:

• Malignant hyperthermia
• Hyperkalemia
• Cardiac arrhythmias (bradycardia, tachycardia, cardiac arrest)
• Prolonged apnea
• Anaphylaxis
• Rhabdomyolysis

Long-Term Effects:

• Myoglobinuria (rare)
• Rarely, long-term effects may arise as consequences of prolonged apnea or severe side effects (e.g., renal failure from rhabdomyolysis).

Adverse Drug Reactions (ADR):

• Malignant hyperthermia
• Anaphylaxis
• Severe hyperkalemia
• Prolonged apnea

Contraindications

• Personal or family history of malignant hyperthermia
• Genetically determined disorders of pseudocholinesterase (butyrylcholinesterase deficiency)
• Myopathies associated with elevated creatinine kinase (CK)
• Duchenne muscular dystrophy
• Hypersensitivity to suxamethonium
• Severe hyperkalemia
• Acute narrow-angle glaucoma
• Penetrating eye injuries
• Conditions associated with acute major muscle wasting (burns, multiple trauma, extensive denervation, upper motor neuron lesions)

Drug Interactions

• Neuromuscular blocking agents: May enhance or prolong neuromuscular blockade.
• Cholinesterase inhibitors: Can intensify or prolong the depolarizing block.
• Certain antibiotics: Aminoglycosides, polymyxins can enhance the neuromuscular blocking action.
• Other Drugs: Several drugs including but not limited to promazine, oxytocin, aprotinin, quinidine, beta-blockers, magnesium salts, and lithium can potentiate the effects of suxamethonium.
• Halogenated anesthetic agents: May increase risk of malignant hyperthermia.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: There is no established pregnancy category for Suxamethonium according to the FDA, but some sources classify it as a Pregnancy Category Z, indicating there is evidence of fetal risk.
• Fetal risks: Prolonged neuromuscular blockade has been observed in neonates exposed to Suxamethonium during pregnancy.
• Breastfeeding: Drug crosses the placenta in small amounts. Consider potential neonatal risks.

Drug Profile Summary

• Mechanism of Action: Depolarizing neuromuscular blocking agent.
• Side Effects: Muscle fasciculations, post-operative pain, increased salivation, transient rise in intraocular pressure; rarely, malignant hyperthermia, hyperkalemia, cardiac arrhythmias.
• Contraindications: Malignant hyperthermia history, pseudocholinesterase deficiency, myopathies, severe hyperkalemia, acute narrow-angle glaucoma.
• Drug Interactions: Numerous, including other neuromuscular blockers, cholinesterase inhibitors, aminoglycosides, and drugs impacting potassium levels.
• Pregnancy & Breastfeeding: Potential risk to fetus/neonate.
• Dosage: Adults: 0.6-1.1 mg/kg IV; Children: 1-2 mg/kg IV. Dose adjustments needed for special populations.
• Monitoring Parameters: Respiratory rate, oxygen saturation, heart rate, blood pressure, potassium levels (with repeated dosing).

Popular Combinations

• Often used with sedatives and analgesics to facilitate intubation and provide anesthesia. Atropine may be co-administered to reduce the risk of bradycardia.

Precautions

• General Precautions: Thorough patient assessment, including history of allergies, metabolic disorders, and organ dysfunction, is essential before administering.
• Specific Populations: Assess potential risk in pregnant women, breastfeeding mothers, children, and the elderly.
• Lifestyle Considerations: No specific lifestyle considerations directly affect suxamethonium’s actions; however, patient underlying health conditions may require precaution.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Suxamethonium?

A: Adults: 0.6 mg/kg (range 0.3-1.1 mg/kg) IV. Children: 1-2 mg/kg IV. Infusion rates and IM doses also exist; refer to dosage section for details and special populations.

Q2: How does Suxamethonium differ from non-depolarizing neuromuscular blockers?

A: Suxamethonium causes initial depolarization (and fasciculations) before paralysis, while non-depolarizing agents compete with acetylcholine without causing depolarization.

Q3: What are the signs of malignant hyperthermia associated with Suxamethonium?

A: Hyperthermia, muscle rigidity, tachycardia, tachypnea, hypercarbia, and metabolic acidosis.

Q4: Can Suxamethonium be used in patients with renal impairment?

A: Use with caution; monitor for prolonged paralysis as metabolites are renally excreted.

Q5: How is Suxamethonium metabolized?

A: By plasma pseudocholinesterase (butyrylcholinesterase).

Q6: What is the antidote for Suxamethonium?

A: There is no direct antidote. Supportive care, including mechanical ventilation, is essential until the drug’s effects wear off.

Q7: Why are continuous infusions of Suxamethonium not recommended in children?

A: Increased risk of malignant hyperthermia and prolonged paralysis.

Q8: What precautions should be taken when administering Suxamethonium to elderly patients?

A: Careful monitoring for cardiac arrhythmias is important, especially if the patient is on digoxin.

Q9: Can Suxamethonium be used during pregnancy?

A: Use only if potential benefit outweighs risk. It may cause prolonged neuromuscular blockade in both mother and neonate.

Q10: Why should Suxamethonium not be mixed with barbiturates in the same syringe?

A: Barbiturates are alkaline and can inactivate suxamethonium. They are also incompatible.