Succinylcholine (Suxamethonium)

Mechanism

Mechanism of Action

Depolarizing neuromuscular blocking drug constituted by the union of two acetylcholine molecules. It competitively binds to muscle-type nicotinic cholinergic receptors (N_M) located in the motor end plate of the neuromuscular junction. Upon binding, it acts as an agonist and induces an initial generalized depolarization of the muscle cell membrane, which clinically translates into visible disorganized contractions known as fasciculations. Unlike acetylcholine, succinylcholine is not immediately hydrolyzed by acetylcholinesterase in the synaptic cleft, so it remains attached to the nicotinic receptor. This causes a continuous and prolonged depolarization of the muscle cell membrane, inactivating the voltage-gated sodium channels of the motor plate, which blocks the propagation of new action potentials and induces progressive flaccid paralysis (Phase I Block). After prolonged infusions or high doses, the plaque undergoes cellular desensitization and behaves similarly to a non-depolarizing competitive blockade (Phase II Blockade).

Pharmacokinetics

Key Pharmacokinetics

• Routes: Intravenous (rapid onset bolus), intramuscular (exceptional, if there is no venous access).
• Onset of effect: Exceptionally fast, between 30 to 60 seconds after your IV injection.
• Duration of paralysis: Short, approximately 4 to 10 minutes.
• Metabolism: Rapidly hydrolyzed in plasma by the enzyme **Butyrylcholinesterase** (plasma cholinesterase or pseudocholinesterase) to succinylmonocholine (minimum potency metabolite) and finally to succinic acid and choline. It is not metabolized by acetylcholinesterase.
• Elimination: Renal in the form of inactive metabolites.

Indicators and dose

Approved and Off-label Indications

Approved: Induction of rapid onset and short duration skeletal muscle paralysis to facilitate emergency endotracheal intubation (especially in the Rapid Sequence Intubation [RSI] in the emergency room or operating room); control of massive muscle spasms of traumatic origin or in electroconvulsive therapy (ECT).

Dosage and Adjustments

Rapid Sequence Intubation (Intravenous): 1.0 to 1.5 mg/kg IV real weight as a rapid bolus in adults.

Intubation (Pediatrics - IV): 1.5 to 2.0 mg/kg IV (children have a proportionally higher volume of distribution of extracellular water and require somewhat higher doses per kilo). Premedication with atropine is advised to avoid severe reflex bradycardia.

Renal adjustment: Absolutely contraindicated in chronic or acute anuric renal failure if hyperkalemia is suspected, regardless of the analytical eGFR.

Hepatic adjustment: Severe liver dysfunction (Child-Pugh B/C) decreases pseudocholinesterase synthesis, which can significantly prolong muscle paralysis.

Security

Contraindications

Absolute: Personal or family history of **Malignant Hyperthermia** (pharmacogenetic disease triggered by halogenates and succinylcholine); patients with recent or prolonged motor denervation (e.g., stroke, spinal cord injury of weeks' duration), major burn injuries or patients with severe crushing polytrauma, skeletal myopathies with known dystrophy (e.g., Duchenne); confirmed or suspected underlying hyperkalemia (massive muscle depolarization releases potassium into the bloodstream; an increase of >0.5 mEq/L is common, and can be catastrophic in these scenarios).

Relative: Congenital or acquired deficiency of active pseudocholinesterase, borderline serum potassium levels.

Adverse Effects (ADR)

Common: Transient post-injection fasciculations, intense diffuse generalized muscle myalgias post-operatively, reflex sialorrhea, moderate elevation of intraocular and transient intragastric pressure.

Serious: **Acute lethal hyperkalemia** with induction of ventricular fibrillation and asystole; **Malignant Hyperthermia** of hyperacute evolution (characterized by massive masseter rigidity, severe progressive hypercapnia, profound mixed acidosis, extreme tachycardia and massive thermal elevation of >1^ every 5 minutes); severe prolonged apnea (in patients with pseudocholinesterase mutation or deficiency); Sudden sinus bradycardia (common in pediatrics after a second successive dose due to direct nodal muscarinic stimulation).

Interactions

Acetylcholinesterase inhibitors (neostigmine, pyridostigmine): They significantly prolong the paralysis induced by phase I blockade, since they decrease the synthesis of plasmatic pseudocholinesterase.

Halogenated gases (halothane, isoflurane): High risk of triggering an acute crisis of malignant hyperthermia due to muscle cell mitochondrial synergy.

Pregnancy and Breastfeeding

FDA Classification: Category C. Due to its high polarity and ionization, it does not cross the placental barrier appreciably in conventional clinical doses, being considered the choice for emergency intubation in cesarean sections once the maternal risks have been assessed. It is not excreted in breast milk due to its rapid plasma metabolization.

Management of acute malignant hyperthermia

Malignant hyperthermia is a catastrophic medical emergency caused by a massive and uncontrolled influx of calcium through mutated ryanodine receptor (RYR1) channels in the sarcoplasmic reticulum of skeletal muscle. In case of clinical suspicion, the drug should be immediately suspended and the specific antidote **Dantrolene** administered intravenously, at an initial dose of 2.5 mg/kg as a rapid bolus, repeating the dose according to clinical evolution and monitoring core temperature and arterial blood gas.