Succinylcholine

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Injection, as chloride:

Anectine: 20 mg/mL (10 mL) [contains methylparaben]

Quelicin: 20 mg/mL (10 mL) [contains methylparaben, propylparaben]

Generic: 20 mg/mL (10 mL)

Pharmacology

Mechanism of Action

Acts similar to acetylcholine, produces depolarization of the motor endplate at the myoneural junction which causes sustained flaccid skeletal muscle paralysis produced by state of accommodation that develops in adjacent excitable muscle membranes

Pharmacokinetics/Pharmacodynamics

Distribution

V_d higher in neonates and infants due to larger ECF volume; higher IV doses necessary

Metabolism

Rapidly hydrolyzed by plasma pseudocholinesterase to inactive metabolites

Excretion

Urine (~10% excreted unchanged)

Onset of Action

Dependent on route, age, and dose; data suggest faster onset with higher doses (Coté 2013):

IM: Infants and Children: 3 to 4 minutes (Liu 1981); Adults: 2 to 3 minutes

IV:

Neonates and Infants: ~30 seconds (range: 19 to 40 seconds [dose: 2 to 4 mg/kg]) (Meakin 1990)

Children and Adolescents: 35 to 55 seconds (Coté 2013); Dose-specific: 40 seconds (dose: 1.5 to 2 mg/kg); 50 seconds (dose: 1 mg/kg) (Coté 2013)

Adults: Flaccid paralysis rapid <60 seconds

Duration of Action

Dependent on route, age, and dose; hypothermia may prolong the duration of action:

IM: 10 to 30 minutes; observed to be shorter in infants than children

IV: ~4 to 6 minutes; faster recovery rate in infants and children compared to adults (Fisher 1975)

Use: Labeled Indications

Neuromuscular blockade for endotracheal intubation, surgery, or mechanical ventilation: As an adjunct to general anesthesia to facilitate tracheal intubation and to provide skeletal muscle relaxation during surgery or mechanical ventilation in adequately sedated patients

Note: Neuromuscular blockade does not provide pain control, sedation, or amnestic effects. Appropriate analgesic and sedative mediations should be used before and during administration of neuromuscular blockade to achieve deep sedation.

Use: Off Label

Electroconvulsive therapy, muscle relaxationc

Data from a limited number of patients studied suggest that succinylcholine may be beneficial to minimize muscle contractions during electroconvulsive therapy Mirzakhani 2016, Murali 1999.

Contraindications

Hypersensitivity to succinylcholine or any component of the formulation; personal or familial history of malignant hyperthermia; skeletal muscle myopathies; use after the acute phase of injury following major burns, multiple trauma, extensive denervation of skeletal muscle, or upper motor neuron injury.

Documentation of allergenic cross-reactivity for neuromuscular blockers is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosage and Administration

Dosing: Adult

Note: Dose to effect; doses will vary due to interpatient variability. Ensure adequate pain control and sedation prior to and during administration of neuromuscular blockade. Use carefully and/or consider dose reduction in patients with reduced plasma cholinesterase activity due to genetic abnormalities of plasma cholinesterase or when associated with other conditions (eg, electrolyte abnormalities, neuromuscular disease); prolonged neuromuscular blockade may occur.

Electroconvulsive therapy (ECT), muscle relaxation (off-label use): IV: 0.5 to 1.5 mg/kg (doses ≥0.75 mg/kg are more common in clinical practice); adjust dose higher or lower based on muscle mass, muscle relaxation with previous ECT, and patient-specific risks associated with suboptimal relaxation (eg, increase dose in patients with osteoporosis) (Ding 2002; Mirzakhani 2016; Murali 1999). Note: Most patients will recover respiratory function and muscle strength within 9 to 10 minutes (Mirzakhani 2016; Murali 1999).

Neuromuscular blockade for endotracheal intubation, surgery, or mechanical ventilation (as adjunct to general anesthesia):

IM: Up to 3 to 4 mg/kg, maximum total dose: 150 mg

IV:

Intubation: 0.6 mg/kg (range: 0.3 to 1.1 mg/kg)

Intubation (rapid sequence) (off-label dosing): 1 to 1.5 mg/kg (Sluga 2005; Weiss 1997)

Long surgical procedures (intermittent administration): Initial: 0.3 to 1.1 mg/kg; administer 0.04 to 0.07 mg/kg at appropriate intervals as needed.

Note: Pretreatment with atropine may reduce occurrence of bradycardia. Initial dose of succinylcholine must be increased when nondepolarizing agent pretreatment is used because of the antagonism between succinylcholine and nondepolarizing neuromuscular-blocking agents (Miller 2010). When the cumulative dose of succinylcholine exceeds 2 to 4 mg/kg under general anesthesia or succinylcholine is administered by continuous infusion, transition from a phase I to a phase II block may occur. If phase II block is suspected, diagnosis should be confirmed by peripheral nerve stimulation prior to administration of an anticholinesterase drug (Hilgenberg 1981).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Dose to effect; doses will vary due to interpatient variability. Use carefully and/or consider dose reduction in patients with reduced plasma cholinesterase activity due to genetic abnormalities of plasma cholinesterase or when associated with other conditions (eg, electrolyte abnormalities, neuromuscular disease); prolonged neuromuscular blockade may occur. Initial dose of succinylcholine must be increased when nondepolarizing agent pretreatment used because of the antagonism between succinylcholine and nondepolarizing neuromuscular-blocking agents (Miller 2010). Because of the risk of adverse effects including malignant hyperthermia and cardiac arrhythmias, surgical or long-term paralytic use (ie, continuous IV infusion) is not recommended (Coté 2013; Fisher 1999).

Endotracheal intubation; emergent (eg, rapid sequence intubation): Note: To reduce the risk of bradycardia or asystole, premedication with atropine recommended prior to IV succinylcholine doses (AAP [Hegenbarth 2008]; Coté 2013)

Infants, Children, and Adolescents: Note: In obese patients, pediatric patient data (age range: 9 to 15 years) suggest dosing based on use total body weight (Rose 2000).

IM:

Infants <6 months: Limited data available: 4 to 5 mg/kg; pharmacokinetic data suggests that young infants typically require doses on the higher end of this range (AAP [Hegenbarth 2008]; Coté 2013)

Infants ≥6 months and Children: 4 mg/kg; maximum dose: 150 mg/dose (AAP [Hegenbarth 2008]; Lui 1981)

Adolescents: 3 to 4 mg/kg; maximum dose: 150 mg/dose

IV:

Manufacturer's labeling:

Infants ≤6 months: 2 to 3 mg/kg/dose

Infants >6 months and Children ≤2 years: 1 to 2 mg/kg/dose

Children >2 years and Adolescents: 1 mg/kg/dose

Alternate dosing: Limited data available:

Infants: 2 to 3 mg/kg/dose (AAP [Hegenbarth 2008]; Coté 2013)

Children: 1 to 2 mg/kg/dose (AAP [Hegenbarth 2008]; Ballow 2012; Coté 2013)

Adolescents: 1 to 1.5 mg/kg/dose (Ballow 2012; Sluga 2005; Weiss 1997)

Dosing: Obesity

Use total body weight for obese patients (Bentley 1982; Brunette 2004; Rose 2000).

Administration

IM: Administer deep IM only when IV access is not available.

IV: May be administered undiluted by rapid IV injection.

Storage

Manufacturer recommends refrigeration at 2°C to 8°C (36°F to 46°F) and may be stored at room temperature for 14 days; however, additional testing has demonstrated stability for ≤6 months unrefrigerated (25°C) (Ross, 1988; Roy, 2008). Stability in polypropylene syringes (20 mg/mL) at room temperature (25°C) is 45 days (Storms, 2003).

Drug Interactions

Acetylcholinesterase Inhibitors: May increase the serum concentration of Succinylcholine. Management: Consider alternatives to this combination due to a risk of prolonged neuromuscular blockade. Consider therapy modification

Aminoglycosides: May enhance the respiratory depressant effect of Neuromuscular-Blocking Agents. Monitor therapy

Bacitracin (Systemic): May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Bambuterol: May enhance the therapeutic effect of Succinylcholine. Bambuterol may increase the serum concentration of Succinylcholine. Monitor therapy

Botulinum Toxin-Containing Products: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Bromperidol: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Capreomycin: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Cardiac Glycosides: Neuromuscular-Blocking Agents may enhance the arrhythmogenic effect of Cardiac Glycosides. Monitor therapy

Clindamycin (Topical): May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Colistimethate: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Consider therapy modification

Cyclophosphamide: May increase the serum concentration of Succinylcholine. Management: Consider alternatives to succinylcholine in patients who have received cyclophosphamide in the past 10 days, or reduced succinylcholine doses (a serum pseudocholinesterase assay may help inform this reduction) with close monitoring. Consider therapy modification

CycloSPORINE (Systemic): May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Echothiophate Iodide: May increase the serum concentration of Succinylcholine. Management: For patients receiving echothiophate iodide eye drops, consider using a neuromuscular-blocking agents other than succinylcholine. If succinylcholine is used, consider a reduced dose, and monitor for enhanced/prolonged effects. Consider therapy modification

Esmolol: May enhance the neuromuscular-blocking effect of Succinylcholine. Monitor therapy

Estrogen Derivatives: May increase the serum concentration of Succinylcholine. Monitor therapy

Lincosamide Antibiotics: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Lithium: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Local Anesthetics: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Exceptions: Benzocaine; Benzydamine; Cocaine (Topical); Dibucaine; Dyclonine; Ethyl Chloride; Hexylresorcinol; Lidocaine (Ophthalmic); Lidocaine (Topical); Pramoxine; Proparacaine; Tetracaine (Ophthalmic); Tetracaine (Topical). Monitor therapy

Loop Diuretics: May diminish the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Loop Diuretics may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Magnesium Salts: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Minocycline (Systemic): May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Opioid Agonists: Succinylcholine may enhance the bradycardic effect of Opioid Agonists. Monitor therapy

Phenelzine: May enhance the neuromuscular-blocking effect of Succinylcholine. Consider therapy modification

Pholcodine: May enhance the adverse/toxic effect of Neuromuscular-Blocking Agents. Specifically, anaphylaxis has been reported. Monitor therapy

Polymyxin B: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Consider therapy modification

Procainamide: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

QuiNIDine: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

QuiNINE: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Avoid combination

Sertraline: May increase the serum concentration of Succinylcholine. Monitor therapy

Tetracyclines: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Vancomycin: May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Adverse Reactions

Frequency not defined.

Cardiovascular: Bradycardia (higher with second dose; more frequent in children), cardiac arrhythmia, hypertension, hypotension, malignant hyperthermia, tachycardia

Dermatologic: Skin rash

Endocrine & metabolic: Hyperkalemia

Gastrointestinal: Sialorrhea

Hypersensitivity: Anaphylaxis

Neuromuscular & skeletal: Fasciculations, jaw tightness, myalgia (postoperative), rhabdomyolysis (with possible myoglobinuric acute renal failure)

Ophthalmic: Increased intraocular pressure

Respiratory: Apnea, respiratory depression (prolonged)

<1%, postmarketing, and/or case reports: Abnormal bone growth (myositis ossificans; prolonged use), myopathy (acute quadriplegic myopathy syndrome; prolonged use)

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylaxis: Severe anaphylactic reactions (some life-threatening and fatal) have been reported; immediate treatment (including epinephrine 1 mg/mL) for anaphylactoid and/or hypersensitivity reactions should be available during use. Use caution in patients with previous anaphylactic reactions to other neuromuscular blocking agents.
• Bradycardia: Risk of bradycardia may be increased with second dose and may occur more in children. Occurrence may be reduced by pretreating with anticholinergic agents (eg, atropine).
• Increased intraocular pressure (IOP): May increase IOP; avoid use in patients in which an increase in IOP is undesirable (eg, narrow-angle glaucoma, penetrating eye injuries).
• Intracranial pressure: May cause a transient increase in intracranial pressure (adequate anesthetic induction prior to administration of succinylcholine will minimize this effect).
• Intragastric pressure: May increase intragastric pressure, which could result in regurgitation and possible aspiration of stomach contents.
• Malignant hyperthermia: Use may be associated with acute onset of malignant hyperthermia; risk may be increased with concomitant administration of volatile anesthetics.
• Neuromuscular cross-sensitivity: Cross-sensitivity with other neuromuscular-blocking agents may occur; use extreme caution in patients with previous anaphylactic reactions to other neuromuscular-blocking agents.
• Vagal tone: May increase vagal tone.

Disease-related concerns:

• Burn injury: Use with caution in patients with extensive or severe burns; risk of hyperkalemia is increased following injury. Onset of time and duration of risk are variable, but risk is generally greatest 7 to 10 days after injury. Resistance may occur in burn patients (≥20% of total body surface area), usually several days after the injury, and may persist for several months after wound healing (Han 2009).
• Conditions that may antagonize neuromuscular blockade (decreased paralysis): Respiratory alkalosis, hypercalcemia, demyelinating lesions, peripheral neuropathies, denervation, muscle trauma, and diabetes mellitus may result in antagonism of neuromuscular blockade (ACCM/SCCM/ASHP [Murray 2002]; Greenberg 2013; Miller 2010; Naguib 2002).
• Conditions that may potentiate neuromuscular blockade (increased paralysis): Electrolyte abnormalities (eg, severe hypocalcemia, severe hypokalemia, hypermagnesemia), neuromuscular diseases, metabolic acidosis, respiratory acidosis, Eaton-Lambert syndrome, and myasthenia gravis may result in potentiation of neuromuscular blockade (Greenberg 2013; Miller 2010; Naguib 2002).
• Fractures/muscle spasm: Use with caution in patients with fractures or muscle spasm; initial muscle fasciculations may cause additional trauma.
• Hyperkalemia: Use with extreme caution in patients with pre-existing hyperkalemia. Severe hyperkalemia may develop in patients with chronic abdominal infections, burn injuries, multiple trauma/crush injuries, extensive denervation of skeletal muscle, upper motor neuron injury, subarachnoid hemorrhage, or conditions which cause degeneration of the central and peripheral nervous system.
• Plasma pseudocholinesterase disorders: Metabolized by plasma cholinesterase; use with caution (if at all) in patients suspected of being homozygous for the atypical plasma cholinesterase gene. Plasma cholinesterase activity may also be reduced by burns, anemia, decompensated heart disease, infections, malignant tumors, myxedema, pregnancy, severe hepatic or renal dysfunction, peptic ulcer, and certain medications and chemicals.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Use with caution in the elderly, effects and duration are more variable.
• Pediatric: [US Boxed Warning]: Use caution in children and adolescents. Acute rhabdomyolysis with hyperkalemia, ventricular arrhythmias and cardiac arrest have been reported (rarely) in children with undiagnosed skeletal muscle myopathy (eg, Duchenne muscular dystrophy); occurs soon after administration and requires immediate treatment of hyperkalemia. Prolonged resuscitation may be required. Use in children should be reserved for emergency intubation when immediate airway control is necessary (eg, laryngospasm, difficult airway, full stomach), or IM use when a suitable vein is inaccessible.

Other warnings/precautions:

• Appropriate use: Maintenance of an adequate airway and respiratory support is critical. All patients should receive eye care including liberal use of lubricating drops, gel, or ointment and eyelids should remain closed during continuous neuromuscular blockade to protect against damage to the cornea (ulceration and dryness).
• Experienced personnel: Should be administered by adequately trained individuals familiar with its use.
• Risk of medication errors: Accidental administration may be fatal. Confirm proper selection of intended product, store vial so the cap and ferrule are intact and the possibility of selecting the wrong product is minimized, and ensure that the intended dose is clearly labeled and communicated, when applicable.

Monitoring Parameters

Vital signs (heart rate, blood pressure, respiratory rate); degree of muscle paralysis (eg, presence of spontaneous movement, ventilator asynchrony, shivering, and consider use of a peripheral nerve stimulator with train of four monitoring along with clinical assessments); serum potassium and calcium

In the ICU setting, prolonged paralysis and generalized myopathy, following discontinuation of agent, may be minimized by appropriately monitoring degree of blockade.

Pregnancy

Pregnancy Considerations

Animal reproduction studies have not been conducted. Small amounts cross the placenta. Sensitivity to succinylcholine may be increased due to a ~24% decrease in plasma cholinesterase activity during pregnancy and several days postpartum.

Patient Education

What is this drug used for?

• It is used to calm muscles during surgery.
• It is used to calm muscles while on a breathing machine.

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Slow heartbeat
• Severe dizziness
• Passing out
• Severe headache
• Vision changes
• Muscle pain
• Muscle weakness
• Dark urine
• Twitching
• Unable to pass urine
• Eye pain
• Chest pain
• High potassium like abnormal heartbeat, confusion, dizziness, passing out, weakness, shortness of breath, or numbness or tingling feeling.
• Malignant hyperthermia like fast heartbeat, fast breathing, fever, spasm of jaw muscles, or stiffness of jaw muscles.
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.