Succinylcholine

BRAND NAMES: Anectine, succinylcholine, suxamethonium.

INDICATIONS:

	Muscle relaxant of choice for rapid sequence induction to facilitate endotracheal intubation.
	Skeletal muscle relaxation during surgery.
	Laryngospasm with inability to ventilate.
	Adjunct to general anesthesia.

CLASS: Bisquaternary ammonium compound with a chemical structure resembling two molecules of acetylcholine back to back. Ultrashort-acting depolarizing muscle relaxant.

MODE OF ACTION:

	Binds to the alpha subunit of the nicotinic post-junctional receptor. Produces depolarization of the postsynaptic membrane, which is similar but more persistent than that achieved by acetylcholine.
	Causes endplate depolarization and development of a surrounding zone of inexcitability through which a muscle action potential evoked by direct stimulation cannot propagate.
	Onset of neuromuscular block is characterized by fasciculations of muscle fibers thought to represent random repetitive neuronal firing.
	Fasciculations could also be due to the depolarization of prejunctional receptors.
	Binding to alpha units of the nicotinic cholinergic receptor on motor end plates, mimics acetylcholine, depolarizes the post-junctional membrane and is also known as phase I blockade.
	Both activation of presynaptic receptors and depolarization cause fasciculations.
	Acts at cardiac muscarinic cholinergic receptors, mimics acetylcholine and at autonomic nervous system ganglia increasing HR and BP.
	Increases lower esophageal sphincter pressure. Increase in intragastric pressure (up to 40 cm H2O) is related to the intensity of muscle fasciculations.
	Increases intraocular pressure transiently by 5-15 mmHg for 5 min.
	Transient increase in intracranial pressure, attenuated by precurarization.
	Transient increase in serum potassium 0.35–0.5 mmol/L
	Proliferation of extrajuctional cholinergic receptors occurs with denervation injury, giving rise to potassium loss, and causing severe hyperkalemia with succinylcholine.
	Histamine release occurs rarely.
	Increase in masseter muscle tone up to 500 g.
	Malignant hyperthermia may be triggered in susceptible patients.

ONSET:

	ED95 (dose producing 95% of maximum neuromuscular block at the adductor pollicis): 0.26 mg/kg.
	Onset time (to maximum effect): 1 min at 1 mg/kg IV. IM 1.5-3 min. May be administered IV, IM or intralingually (emergency route only).

DURATION:

	Clinical duration of action (to 25% recovery): 4-8 min.
	Total duration of action (to 90% recovery): 6-12 min. IM 10-30 min.
	Repeated doses or prolonged administration lead to a change in the nature of block to one resembling that of non-depolarizing block (phase II block). Neostigmine and edrophonium antagonize phase II block, after prolonged exposure to succinylcholine.

CLEARANCE: Rapid hydrolysis by pseudocholinesterase to succinylmonocholine, then further to succinic acid and choline. Urinary excretion 1-2%, unchanged

ADULT DOSE:

	Intubation: 1 mg/kg IV.
	Increase the initial dose of succinylcholine to 1.5 mg/kg IV when a non-depolarizing relaxant is given beforehand to prevent fasciculations (e.g. d-tubocurarine 0.05 mg/kg, rocuronium 0.06 mg/kg, atracurium 0.03 mg/kg). Pancuronium and vecuronium are less effective as defasciculants. Pretreatment with a non-depolarizing relaxant may prevent or reduce fasciculations, myalgia, myoglobinuria, increased intragastric and intracranial pressure. Pretreatment may cause diplopia or weakness - inform the patient.
	Supplementary doses should be given carefully using a nerve stimulator.
	Used very seldom for the maintenance of neuromuscular block.
	Maintenance: 0.04-0.07 mg/kg IV every 5-10 min.
	Continuous infusion: 10-100 µg/kg/min IV (dilute to 1-2 mg/mL).
	Carefully titrate with continuous infusion - phase II block may occur.
	Bradycardia may occur when a second dose is administered within 5 min.
	Where administered IM, use deep high deltoid muscle.

PEDIATRIC DOSE:

	Children are slightly more resistant than adults.
	IV 2 mg/kg for infants, 1 mg/kg IV for older children and adolescents.
	IM 4 mg/kg (maximum dose 150 mg).
	Precurarization is not necessary in patients < 10 yr.
	Maintenance: 0.3-0.6 mg/kg/dose every 5-10 min.
	Continuous maintenance infusion is not recommended.

WARNING:

	Use of succinycholine in children should be reserved for emergency intubation or conditions that require immediate securing of the airway. Rare reports of acute rhabdomyolysis with hyperkalemia, ventricular arrhythmias and cardiac arrest in apparently healthy children, who subsequently were found to have undiagnosed skeletal myopathy (frequently Duchenne muscular dystrophy). Often presents as peaked T waves and sudden cardiac arrest within minutes following its administration to healthy males (not exclusively), aged 8 yr or younger (has also been reported in adolescents).
	Immediate treatment for hyperkalemia must be instituted, consisting of IV calcium, glucose/insulin and hyperventilation. Additionally, in the presence of signs of malignant hyperthermia, appropriate treatment should be instituted concurrently.
	Bradycardia commonly occurs after a single IV dose in children. May be prevented by prior atropine administration (0.01-0.02 mg/kg IV).
	IM succinylcholine is associated with minimal heart rate and rhythm changes.
	Pretreat ambulatory children with a non-depolarizing relaxant in order to prevent postoperative muscle pains.
	Succinylcholine IV after halothane induction may cause masseter spasm (1:100 cases). Masseter spasm is rarely caused by succinylcholine after thiopental induction. If it occurs, it should be considered as an early warning sign of malignant hyperthermia trait.
	Myoglobinemia and myoglobinuria occur more commonly in pediatric patients.
	Increases intragastric pressure less in infants and young children.

NEONATAL DOSE:

	Intubation: 2-3 mg/kg IV, onset 20-30 s.
	Infants (< 6 months) require higher dose of succinylcholine despite lower plasma cholinesterase activity, due to distribution throughout extracellular fluid compartment. Cholinesterase activity is adequate for drug metabolism.
	Continuous maintenance infusion is not recommended.

CAUTION:

	Neuromusclular diseases: Myasthenia gravis: Slight resistance to succinylcholine, phase II block on recovery. Myasthenic syndrome (Eaton-Lambert): Very sensitive to depolarizing NMB. Myotonia: Sustained contractions with succinylcholine, ventilation difficult, avoid! Myotonic dystrophy: Avoid in succinylcholine all patients with Duchenne or Becker. Central core disease: Increased risk of MH susceptibility. Familial periodic paralysis: Contraindicated.
	Patients with decreased plasma cholinesterase activity: Severe liver disease, cirrhosis, last trimester pregnancy, malignancy, burns, uremia, malnutrition, hypothyroidism, plasmapheresis and oral contraceptives.
	Pre-existing hyperkalemia (e.g. renal failure).
	Hyperkalemia may occur following succinylcholine ministration in the presence of unrecognized muscular dystrophy, severe burns, severe skeletal muscle trauma, denervation injury with skeletal muscle atrophy, upper motor neuron lesions, paraplegia, spinal cord injury or transection, stroke, prolonged immobility, acidotic-hypovolemic states, Guillain-Barr?, amyotrophic lateral sclerosis, Friedreich's ataxia, tetanus, severe Parkinson's disease.
	Avoid succinylcholine in burned patients after the first 24 h, and for 2 yr from injury.
	Inhibition of plasma cholinesterase: Echothiophate eye-drops (should be discontinued 4 weeks before the use of succinylcholine), anticholinesterases, phenelzine (MAOI), organophosphates
	Other conditions: Electrolyte abnormalities. Patients with clinically significant cardiovascular disease. Patients with fractures or muscle spasms. Precipitates with barbiturates (thiopental); may occlude IV line. Some formulations contain benzyl alcohol. Dosage should be based on ideal body weight in obese patients. Requirements of succinylcholine may increase in obese patients (increased plasma cholinesterase).

	Hypersensitivity to succinylcholine or previous anaphylactic response.
	Pre-existing hyperkalemia.
	Personal or familial history of malignant hyperthermia susceptibility.
	Skeletal muscle myopathies (see Caution above).
	Acute narrow-angle glaucoma.
	Penetrating or open eye injury.
	Recent major trauma or burns.
	Spinal injury, upper motor neuron lesions.
	Atypical plasma cholinesterase gene (homozygous or heterozygous).
	Pseudocholinesterase activity (inherited or acquired).
	Myotonia congenita or dystrophica (sustained skeletal muscle contraction).
	Central core disease.
	Avoid in repeat strabismus surgery; increased incidence of malignant hyperthermia in patients with strabismus.

INTERACTIONS:

	Depolarizing and non-depolarizing relaxants are mutually antagonistic.
	Neostigmine causes a decrease in plasma cholinesterase activity.
	Duration of succinylcholine after 10 mg metoclopramide is prolonged.
	Increased arrhythmias with digoxin (due to potassium changes).
	Volatile anesthetics potentiate neuromuscular blockade.
	Drugs that enhance the neuromuscular-blocking action of succinylcholine include cholinesterase inhibitors (used in glaucoma, myasthenia gravis), cyclosphosphamide, promazine, oxytocin, quinidine, phenothiazines, beta-adrenergic blockers, procainamide, lithium, lidocaine, magnesium, chloroquine, amphotericin B, thiazides, furosemide, ester local anesthetics, MAOIs and aminoglycosides. Clindamycin, opioids may increase bradycardia.

ADVERSE REACTIONS:

	Malignant hyperthermia.
	CNS: increased intracranial pressure.
	CVS: sinus bradycardia with nodal rhythm or extraventricular beats, arrhythmias, asystole. Tachycardia (catecholamine release), hypertension, hypotension.
	Pulmonary: respiratory depression, apnea, bronchospasm.
	GIT: excessive salivation, increased intragastric and lower esophageal sphincter tone.
	Musculoskeletal: prolonged block, inadequate block, postoperative stiffness, myalgia, muscle fasciculations, increase in masseter muscle tone, jaw rigidity.
	Increased intraocular pressure.
	Hyperkalemia (serum K+ level increases by 0.35-0.5 mmol/L).
	Myoglobinemia, myoglobinuria, rhabdomyolysis.
	Anaphylactic reactions up to 0.06%, itching, erythema, rash.

PREGNANCY: Category C.

OBSTETRICS: General anesthesia for cesarean delivery: 1.5 mg/kg IV.

PROLONGED BLOCK:

	May occur with low plasma cholinesterase levels, drug-induced inhibition of cholinesterase activity, genetic atypical enzyme or phase II blockade.
	Presence of atypical plasma cholinesterase, often recognized only following administration of succinylcholine to a healthy patient.
	1:3200 patients homozygous for atypical plasma cholinesterase.
	1:480 patients heterozygous for atypical plasma cholinesterase.
	Homozygous - block will continue > 3 h; heterozygous - 30 min (following 1 mg/kg dose).
	Continue mechanical ventilation until recovery. Fresh frozen plasma (as an external source of pseudocholinesterase) is best avoided.
	Send blood for assessment of cholinesterase quality by dibucaine number.

COMMENTS: Anectine, isotonic solution, pH adjusted to 3.5 with hydrochloric acid, methylparaben (0.1%) is added as a preservative, keep refrigerated.