VA Class:MS300

AHFS Class:

• Neuromuscular Blocking Agents 12:20.20

Generic Name(s):

• Succinylcholine Chloride

Succinylcholine chloride is a depolarizing neuromuscular blocking agent.

Skeletal Muscle Relaxation

Succinylcholine chloride is used to produce skeletal muscle relaxation during procedures of short duration such as endotracheal intubation after general anesthesia has been induced.

Because of its short duration of action, succinylcholine is generally considered the neuromuscular blocking agent of choice for procedures lasting less than 3 minutes. In addition, because of its rapid onset (less than 1 minute after IV administration) and short duration of action (approximately 4-6 minutes), succinylcholine traditionally has been considered the neuromuscular blocking agent of choice in emergency situations when rapid intubation (e.g., rapid sequence intubation) is required.100,110,424 However, the drug is associated with serious adverse effects (e.g., hyperkalemia, bradycardia, malignant hyperthermia), which can limit its use.100,110 Because of the risk of hyperkalemic rhabdomyolysis, cardiac arrest, and death, use of succinylcholine in pediatric patients should be restricted to those who require emergency intubation, those in whom an airway should be secured immediately (e.g., patients with laryngospasm, difficult airway, or full stomach), or those in whom a suitable vein is not accessible and IM administration is needed.100 (See Cautions: Pediatric Precautions.) If succinylcholine cannot be used, rocuronium (a nondepolarizing neuromuscular blocking agent with the most similar pharmacokinetic profile) generally is recommended as an acceptable alternative.110,420,421,424 Clinical studies have shown that rocuronium can produce similar intubating conditions to succinylcholine when given in sufficient doses (e.g., at least 1 mg/kg); however, succinylcholine is more likely to achieve excellent intubating conditions and remains clinically superior to rocuronium with respect to its shorter duration of action.110,421

Succinylcholine also is used to provide skeletal muscle relaxation during mechanical ventilation;100 however, the drug is not used for prolonged neuromuscular blockade in the intensive care unit (ICU).341,423

For additional information on uses and treatment principles of neuromuscular blocking agents, see Uses in the Neuromuscular Blocking Agents General Statement 12:20.20.

Reconstitution and Administration

Succinylcholine chloride usually is administered IV. For infants or older patients in whom a suitable vein is not accessible, the drug may be administered by IM injection. Because of a slower onset of effect (which can potentially compromise respiratory function), some clinicians recommend that IM administration be reserved for life-threatening situations.424

For prolonged procedures, the manufacturer states that succinylcholine may be given by continuous IV infusion or intermittent IV injection.100 Continuous IV infusion of the drug is preferable to administration of repeated fractional doses because the latter method of dosing may lead to tachyphylaxis and prolonged apnea which may be difficult to reverse. However, some clinicians state that continuous IV infusion of succinylcholine also is limited clinically because of tachyphylaxis, potential conversion from phase I to phase II block, and the uncertain nature and prolongation of the blockade.421

For continuous IV infusion, succinylcholine chloride usually is diluted to a concentration of 1-2 mg/mL (0.1-0.2%) with a compatible IV solution such as 5% dextrose injection or 0.9% sodium chloride injection.100 The 1-mg/mL concentration is usually used for optimum dosage control, but in patients in whom the amount of fluid should be limited, the 2-mg/mL concentration may be preferred. To provide a solution containing 1 or 2 mg/mL, 1 g of succinylcholine chloride injection may be added to 1 L or 500 mL of diluent, respectively.100 The infusion solution should be used within 24 hours of preparation.100 Use of a controlled-infusion device is recommended to ensure precise control of the flow rate during continuous IV infusion of the drug.359 Succinylcholine injections should not be admixed with alkaline (having a pH exceeding 8.5) solutions (e.g., barbiturates).

Dispensing and Administration Precautions

Neuromuscular blocking agents should be administered only by individuals who are adequately trained in their use and complications.100,359 For specific procedures and techniques of administration, specialized references should be consulted. Facilities and personnel necessary for intubation, administration of oxygen, and respiratory support should be immediately available whenever these drugs are used.100,359,424

Because neuromuscular blocking agents can cause respiratory arrest, precautions (e.g., storage segregation, warning labels, access limitations) should be taken to ensure that these drugs are not administered without adequate respiratory support.425 Affixing warning labels to storage containers and final administration containers is recommended to clearly communicate that respiratory paralysis can occur and ventilator support is required.425 The Institute for Safe Medication Practices (ISMP) recommends the following wording for these containers: “Warning: Paralyzing agent—causes respiratory arrest—patient must be ventilated”.425

Neuromuscular blocking agents have no known effect on consciousness, pain, or cerebration, and should therefore be used in conjunction with adequate levels of anesthesia and only after appropriate analgesics and sedatives are administered.100,359,421,423 To avoid distress to the patient, succinylcholine generally should be administered after unconsciousness has been induced; however, in emergency situations, the drug may be administered before a sedative has been given.100

Dosage

Dosage of succinylcholine must be carefully adjusted according to individual requirements and response.100 The use of a peripheral nerve stimulator is recommended during continuous IV infusion of the drug to accurately monitor the degree of neuromuscular blockade and recovery, detect the development of phase II block, and minimize the possibility of overdosage.100,421

Test Dose

To evaluate sensitivity to succinylcholine in patients with reduced plasma cholinesterase activity, a test dose of 5-10 mg of succinylcholine chloride is recommended; alternatively, a 1-mg/mL solution of the drug may be cautiously administered by slow IV infusion.100 In patients who metabolize succinylcholine normally, respiratory depression rarely occurs and, if it does, is transient and usually disappears in less than 5 minutes. Patients unable to metabolize the drug develop paralysis sufficient to permit endotracheal intubation; recovery generally occurs in 30-60 minutes. Apnea or prolonged muscle paralysis should be treated with controlled respiration.100

Adult Dosage

For short procedures, the manufacturer states that the usual adult IV dose of succinylcholine chloride is 0.6 mg/kg (range 0.3-1.1 mg/kg); following administration of this dose, neuromuscular blockade generally is attained in approximately 1 minute and persists for about 4-6 minutes.100 Because there is a wide variation in individual patient response, a test dose of succinylcholine chloride may be administered to determine the individual patient's sensitivity and recovery time. (See Test Dose under Dosage and Administration: Dosage.)

For rapid sequence intubation, the usual dose of succinylcholine chloride is 1.5 mg/kg; this dose generally produces an onset of effect within 45 seconds and a duration of paralysis of about 10 minutes.110,424

For maintenance of neuromuscular blockade during prolonged procedures, succinylcholine chloride may be administered by continuous IV infusion, generally at a rate of 2.5-4.3 mg/minute in adults; the rate may range from 0.5-10 mg/minute depending on the response and requirements of the patient.100 Succinylcholine also may be administered by intermittent IV injection for maintenance of neuromuscular blockade during prolonged procedures; a dose of 0.3-1.1 mg/kg may be given initially in adults, followed by additional doses of 0.04-0.07 mg/kg as necessary to maintain adequate relaxation.100

If IM administration is necessary, a succinylcholine chloride dose of up to 3-4 mg/kg may be given, but the total dose should not exceed 150 mg.100

Pediatric Dosage

The manufacturer states that the usual pediatric IV dose of succinylcholine chloride is 1-2 mg/kg (2 mg/kg for infants and small pediatric patients, and 1 mg/kg for older pediatric patients and adolescents).100 The possibility that succinylcholine may produce profound bradycardia or, rarely, asystole when administered by rapid IV injection in infants and children should be considered; as in adults, the risk of these effects increases with repeated doses, and pretreatment with atropine should be considered to reduce the risk of bradyarrhythmias.

Because of the risk of malignant hyperthermia, continuous IV infusions of succinylcholine are considered unsafe in neonates and children.

If IM administration is necessary, a succinylcholine chloride dose of up to 3-4 mg/kg may be given, but the total dose should not exceed 150 mg.100

Adverse Effects

Succinylcholine may produce initial muscle fasciculation which may result in postoperative pain; jaw rigidity also has been reported.

Patients with decreased concentrations and/or activity of plasma pseudocholinesterase are especially sensitive to the action of succinylcholine and may experience prolonged respiratory depression and apnea after receiving the drug. (See Cautions: Precautions and Contraindications.) About 1 individual in 2800 has a genetic abnormality that causes the production of an atypical pseudocholinesterase which is incapable of rapidly hydrolyzing succinylcholine. These individuals are homozygous for this trait and invariably respond to administration of succinylcholine by prolonged muscle relaxation. Several other genetic variants also exist, some producing enzymes that hydrolyze succinylcholine at slower than normal rates than others that hydrolyze succinylcholine more rapidly than normal. Plasma pseudocholinesterase concentrations may also be decreased in patients with hepatocellular disease, malnutrition, severe anemia, severe dehydration, burns, cancer, collagen diseases, myxedema, or abnormal body temperature and in pregnant women. (See also Drug Interactions.)

While succinylcholine does not have a direct effect on the myocardium, the drug stimulates autonomic ganglia and muscarinic receptors.100,420 Bradycardia accompanied by hypotension and cardiac arrhythmias ranging from nodal rhythms and extrasystoles to bigeminy, atrioventricular block, and cardiac arrest may occur after succinylcholine administration. Cardiac effects also may result from vagal stimulation or from hyperkalemia, and are most common during halothane anesthesia, with repeated administration of succinylcholine, in children, or in patients with pheochromocytoma. Prior administration of atropine may inhibit vagal stimulation. Succinylcholine has also been reported to cause sinus tachycardia with hypertension and sympathetic ganglion stimulation.

Succinylcholine causes an increase in intraocular pressure which may be hazardous in patients with glaucoma or in those undergoing eye surgery and in patients with penetrating wounds of the eye. Although administration of a small dose of a nondepolarizing neuromuscular blocking agent prior to succinylcholine can prevent the rise in intraocular pressure, it may be preferable to use a nondepolarizing blocking agent alone in patients with these conditions of the eye. An increase in intragastric pressure secondary to fasciculation of the abdominal muscles has been reported. An increase in intragastric pressure may be prevented by the administration of a small dose of a nondepolarizing agent prior to succinylcholine. Enlargement of the salivary glands, excessive salivation, rash, hypersensitivity reactions (e.g., anaphylaxis) and, rarely, bronchospasm have also been reported in patients receiving succinylcholine. Premedication with a parasympatholytic agent such as atropine or scopolamine may be used to prevent excessive salivation.

Rarely, myoglobinuria and myoglobinemia have been reported after succinylcholine administration, particularly in children. These symptoms have sometimes been reported in conjunction with malignant hyperthermia and muscle rigidity. Administration of succinylcholine has been associated with acute onset of malignant hyperthermia; the risk of developing such hyperthermia increases with concomitant administration of inhalation anesthetics. (See Cautions: Adverse Effects in the Neuromuscular Blocking Agents General Statement 12:20.20.) Manifestations associated with histamine release also can occur. Hyperkalemia has been reported in several catabolic patients who had either massive tissue destruction or CNS injury with muscle wasting (e.g., those with extensive or severe burns, severe abdominal infections, tetanus, massive trauma, spinal cord injury, neuromuscular disease) who received succinylcholine. The precise time of onset and duration of the risk period are not known. It has been reported that skeletal muscle denervation hypersensitivity usually develops over several weeks; however, it can occur as early as 1-2 days after injury. Results of an animal study indicate that hyperkalemia developed 7 days after denervation when receiving succinylcholine. In humans, succinylcholine-associated hyperkalemia can persist for over 6 months after neural injury. The risk of hyperkalemia depends on the extent and location of injury, increases over time, and usually peaks 7-10 days after the injury.

Serious hypersensitivity reactions, including anaphylaxis, have been reported rarely with all neuromuscular blocking agents; such reactions have been life-threatening or fatal in some cases.100 Although uncommon, succinylcholine has the potential to release histamine and cause histamine-related manifestations (e.g., bronchospasm, flushing, hypotension).100,420

Precautions and Contraindications

Succinylcholine chloride shares the toxic potentials of the depolarizing neuromuscular blocking agents, and the usual precautions of neuromuscular blocking agent administration should be observed. (See Cautions in the Neuromuscular Blocking Agents General Statement 12:20.20.)

When used inappropriately, neuromuscular blocking agents can severely compromise respiratory function and induce respiratory paralysis.100 Special precautions should be taken during and after administration of these drugs.100 (See Dispensing and Administration Precautions under Dosage and Administration: Reconstitution and Administration.)

Immediately after administration of succinylcholine and during the fasciculation phase, slight increases in intracranial pressure may occur.

Some clinicians suggest that plasma pseudocholinesterase activity should be determined prior to administration of succinylcholine. The drug should be administered with extreme caution and in reduced doses, if at all, to patients with abnormally low pseudocholinesterase concentrations including those who are homozygous for the genetic trait that causes the production of an atypical pseudocholinesterase. If low pseudocholinesterase activity is suspected, a small test dose (5-10 mg) may be administered or relaxation may be produced by cautious IV infusion of a 0.1% solution of the drug. Apnea or prolonged muscle paralysis should be treated with controlled respiration. Administration of fresh whole blood or plasma has been reported to be of benefit in restoring pseudocholinesterase concentrations.

Succinylcholine should be used with extreme caution in patients with electrolyte imbalance, those receiving quinidine or cardiac glycosides, or those with suspected cardiac glycoside toxicity, since succinylcholine may induce serious cardiac arrhythmias or cardiac arrest in such patients. Succinylcholine should be used with extreme caution, if at all, during ocular surgery or in patients with glaucoma. The drug also should be used with extreme caution in patients with preexisting hyperkalemia or paraplegia and those with chronic abdominal infection, subarachnoid hemorrhage, degenerative or dystrophic neuromuscular disease, or conditions that may cause degeneration of central and peripheral nervous systems, since the potential of developing severe hyperkalemia is increased in such patients. Succinylcholine is contraindicated in patients with upper motor neuron injury, multiple trauma, extensive or severe burns, extensive denervation of skeletal muscle because of disease or injury to the CNS, since such patients tend to become severely hyperkalemic following succinylcholine administration which may result in cardiac arrest. (See Cautions: Adverse Effects.)

Since neuromuscular blocking agents have been reported to cause severe anaphylactic reactions, appropriate emergency treatment should be readily available whenever these drugs are administered.100 Because of potential cross-sensitivity, succinylcholine should be used with caution in patients who have experienced previous anaphylactic reactions to other neuromuscular blocking agents (depolarizing or nondepolarizing).100

Succinylcholine is contraindicated in patients with known hypersensitivity to the drug, personal or familial history of malignant hyperthermia, or skeletal muscle myopathies.100

Pediatric Precautions

Acute rhabdomyolysis with hyperkalemia followed by ventricular dysrhythmias, cardiac arrest, and death has been reported rarely in apparently healthy children and adolescents receiving succinylcholine; subsequently it was observed that these children had undiagnosed skeletal muscle myopathy, most frequently Duchenne type muscular dystrophy.100 Peaked T-waves and sudden cardiac arrest within minutes of administration of succinylcholine may occur in apparently healthy children, usually males 8 years of age or younger, although this syndrome has been reported in some adolescents. Therefore, when an apparently healthy infant or child develops cardiac arrest shortly after administration of succinylcholine (supposedly not associated with inadequate ventilation, oxygenation, or overdosage of an anesthetic), treatment for hyperkalemia should be initiated immediately.100 Emergency measures for the treatment of hyperkalemia should include hyperventilation and IV administration of calcium, sodium bicarbonate, glucose, and insulin.100 Since this syndrome is characterized by an abrupt onset, standard resuscitative measures may be unsuccessful.100 Prolonged or unusual resuscitative measures have been successful in some patients. If signs of malignant hyperthermia are present, appropriate therapy should be instituted concurrently.100 Since it is difficult to identify which children and adolescents may be at risk of developing such a syndrome, it is recommended that a nondepolarizing neuromuscular blocking agent be used in these patients and succinylcholine be reserved for children and adolescents undergoing emergency intubation, for those in whom an airway should be secured immediately (e.g., those with laryngospasm, difficult airway, full stomach), or for those in whom a suitable vein is not accessible and IM administration is needed.100

The possibility that succinylcholine may produce profound bradycardia or, rarely, asystole when administered by rapid IV injection in infants and children should be considered; as in adults, the risk of these effects increases with repeated doses, and pretreatment with atropine should be considered to reduce the risk of bradyarrhythmias.100

Geriatric Precautions

Clinical studies of succinylcholine did not include sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently than younger patients. While other clinical experience has not revealed age-related differences in response or tolerance, drug dosage generally should be titrated carefully in geriatric patients, usually initiating therapy at the low end of the dosage range. The greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly also should be considered.

Pregnancy and Lactation

Pregnancy

Animal reproduction studies have not been performed to date with succinylcholine chloride. It is also not known whether the drug can cause fetal harm when administered to pregnant women. Pseudocholinesterase concentrations are decreased during pregnancy and for several days postpartum, and a higher proportion of patients may be expected to show sensitivity to succinylcholine when pregnant. Succinylcholine may be used to provide muscle relaxation during delivery by cesarean section. Although succinylcholine generally crosses the placenta in small amounts, residual neuromuscular blockade (apnea, flaccidity) may occur in the neonate after repeated administration of high doses to the mother or in the presence of atypical pseudocholinesterase in the mother. Succinylcholine should be used during pregnancy only when clearly needed.

Lactation

It is not known whether succinylcholine is distributed into human milk, and the manufacturers recommend that the drug be used with caution in nursing women.

Cholinesterase inhibitors, particularly the irreversible organophosphate type, can substantially reduce the activity of plasma pseudocholinesterase. Prolonged apnea and death have occurred following administration of succinylcholine to patients who had received prolonged therapy with echothiophate iodide ophthalmic drops (no longer commercially available in the US). The possibility of reactions should be considered in patients receiving isofluorophate or demecarium bromide and in those who have recently been exposed to organophosphate insecticides. In high blood concentrations, procaine competes with succinylcholine for hydrolysis by pseudocholinesterase, and procaine should not be given IV concurrently with succinylcholine because prolonged apnea may result. In addition, promazine, oxytocin, certain anti-infective agents (excluding penicillins), chloroquine, quinine, terbutaline, β-adrenergic blocking agents, lidocaine, procainamide, quinidine, lithium carbonate, magnesium salts, metoclopramide, and inhalation anesthetics (e.g., isoflurane) may potentiate the neuromuscular blocking effect of succinylcholine. Several other drugs, including cyclophosphamide, oral contraceptives, corticosteroids, some monoamine oxidase inhibitors (e.g., phenelzine), pancuronium, neostigmine, phenothiazines, and thiotepa, have been reported to reduce plasma pseudocholinesterase concentrations and possibly enhance the neuromuscular blocking effects of succinylcholine. Although most of these reports are poorly documented and the clinical importance of their interaction with succinylcholine is unknown, caution should be used when administering these drugs simultaneously with succinylcholine.

Acute Toxicity

Manifestations

The duration of neuromuscular blockade produced by an overdose of succinylcholine may be longer than that following usual doses, and skeletal muscle weakness, decreased respiratory reserve, low tidal volume, or apnea beyond the period of surgery and anesthesia may occur.

Treatment

In succinylcholine overdosage, supportive and symptomatic treatment should be initiated. Maintenance of an adequate, patent airway and respiratory support are necessary until recovery of normal respiration is assured. Depending on the dose and duration of succinylcholine administration, the characteristic phase I depolarizing neuromuscular block may change to a superficially resembling, phase II nondepolarizing neuromuscular block.

Pharmacology

Succinylcholine produces pharmacologic effects similar to those of other depolarizing neuromuscular blocking agents. The drug possesses histamine-releasing properties. It has been reported that succinylcholine stimulates the cardiac vagus and subsequently sympathetic ganglia.

Succinylcholine causes a slight, transient increase in intraocular pressure immediately after injection and during the fasciculation phase, and the increase may persist after the onset of complete paralysis.

Pharmacokinetics

Absorption

Succinylcholine has a rapid onset and a short duration of action. Following IV administration of 10-30 mg of succinylcholine chloride in healthy adults, complete muscle relaxation occurs within 0.5-1 minute, persists for about 2-3 minutes, and gradually dissipates within 10 minutes. The duration of action following a single IV dose appears to be determined by the rate of diffusion of the drug away from the motor end-plate rather than the elimination of the drug by enzymatic hydrolysis. After relatively stable blood concentrations are achieved, however, as with continuous infusion or multiple injections, the short duration of action of succinylcholine results from its rapid hydrolysis. Following IM administration the onset of action occurs in about 2-3 minutes and the duration of action ranges from 10-30 minutes. The duration of action is prolonged in patients with low plasma pseudocholinesterase concentrations.

Distribution

Succinylcholine crosses the placenta, generally in small amounts.

Elimination

Succinylcholine (succinyldicholine) is metabolized rapidly, mainly by plasma pseudocholinesterase, to succinylmonocholine and choline. Succinylmonocholine has only about one-twentieth the activity of succinylcholine and produces a nondepolarizing rather than a depolarizing block.

Succinylmonocholine is excreted partly in urine; the remainder of the metabolite is further broken down in the plasma, principally by alkaline hydrolysis to succinate and choline, which are inactive. Since hydrolysis of succinylmonocholine occurs relatively slowly, succinylmonocholine may occasionally accumulate and cause prolonged apnea, especially in patients with impaired renal function. Up to 10% of a dose of succinylcholine is excreted unchanged in urine.

Chemistry and Stability

Chemistry

Succinylcholine chloride is a depolarizing neuromuscular blocking agent. The drug occurs as a white, odorless, crystalline powder and has solubilities of approximately 1 g/mL in water and 2.9 mg/mL in alcohol at 25°C. Succinylcholine chloride usually contains about 2 molecules of water of hydration, but its potency is labeled in terms of its anhydrous equivalent. Commercially available succinylcholine chloride injections are adjusted to pH 3-4.5 with hydrochloric acid or sodium hydroxide and may contain methylparaben and propylparaben as preservatives.100

Stability

Succinylcholine decomposes in solutions with pH greater than 4.5. Succinylcholine chloride injection is incompatible with alkaline solutions such as barbiturates; decomposition of succinylcholine chloride and precipitation of the barbiturate may occur if the drugs are mixed.

Succinylcholine chloride undergoes hydrolysis in aqueous solutions and the commercially available injections should be stored at 2-8°C to retard loss of potency. Multiple-dose vials of the injection are stable for up to 14 days at room temperature without substantial loss of potency.

Additional Information

For further information on chemistry, pharmacology, pharmacokinetics, uses, cautions, drug interactions, and dosage and administration of succinylcholine chloride, see the Neuromuscular Blocking Agents General Statement 12:20.20.

Only references cited for selected revisions after 1984 are available electronically.

100. Hospira. Quelicin^® (succinylcholine chloride injection) prescribing information. Lake Forest, IL; 2010 Sept.

110. Tran DT, Newton EK, Mount VA et al. Rocuronium versus succinylcholine for rapid sequence induction intubation. Cochrane Database Syst Rev . 2015; :CD002788. [PubMed 26512948]

341. Society of Critical Care Medicine and American Society of Health-System Pharmacists. Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient. Am J Health-Syst Pharm . 2002; 59:179-95. [PubMed 11826571]

359. Institute for Safe Medication Practices. Paralyzed by mistakes: reassess the safety of neuromuscular blockers in your facility. ISMP Medication Safety Alert! Acute Care edition. Horsham, PA; 2016 June. From ISMP website [Web]

420. McManus MC. Neuromuscular blockers in surgery and intensive care, part 1. Am J Health-Syst Pharm . 2001; 58:2287-99. [PubMed 11763807]

421. McManus MC. Neuromuscular blockers in surgery and intensive care, part 2. Am J Health-Syst Pharm . 2001; 58: 2381-99. [PubMed 11794954]

423. Murray MJ, DeBlock H, Erstad B et al. Clinical Practice Guidelines for Sustained Neuromuscular Blockade in the Adult Critically Ill Patient. Crit Care Med . 2016; 44:2079-2103. [PubMed 27755068]

424. Hampton JP. Rapid-sequence intubation and the role of the emergency department pharmacist. Am J Health Syst Pharm . 2011; 68:1320-30. [PubMed 21719592]

425. Institute for Safe Medication Practices. 2018-2019 Targeted medication safety best practices for hospitals. Horsham, PA; 2017 Dec. From ISMP website [Web]