c



(succinylcholine chloride) Injection, USP

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 The mechanism of action of Anectine involves what appears to be a "persistent"
depolarization of the neuromuscular junction. This depolarization is caused by Anectine mimicking the
effect of acetylcholine but without being rapidly hydrolysed by acetylcholinesterase. This depolarization
leads to desensitization.

 c c

Succinylcholine is contraindicated in persons with personal or familial history of malignant hyperthermia,

skeletal muscle myopathies, and known hypersensitivity to the drug. It is also contraindicated in patients
after the acute phase of injury following major burns, multiple trauma, extensive denervation of skeletal
muscle, or upper motor neuron injury, because succinylcholine administered to such individuals may
result in severe hyperkalemia which may result in cardiac arrest (see c   ). The risk of
hyperkalemia in these patients increases over time and usually peaks at 7 to 10 days after the injury. The
risk is dependent on the extent and location of the injury. The precise time of onset and the duration of
the risk period are not known.

 c

Succinylcholine chloride is indicated as an adjunct to general anesthesia, to facilitate tracheal intubation,

and to provide skeletal muscle relaxation during surgery or mechanical ventilation.

 c

c 
c   c

The dosage of succinylcholine should be individualized and should always be determined by the clinician
after careful assessment of the patient (see c   ).

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to
administration whenever solution and container permit. Solutions which are not clear and colorless should
not be used.

c
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 The average dose required to produce neuromuscular
blockade and to facilitate tracheal intubation is 0.6 mg/kg ANECTINE Injection given intravenously. The
optimum dose will vary among individuals and may be from 0.3 to 1.1 mg/kg for adults. Following
administration of doses in this range, neuromuscular blockade develops in about 1 minute; maximum
blockade may persist for about 2 minutes, after which recovery takes place within 4 to 6 minutes.
However, very large doses may result in more prolonged blockade. A 5- to 10-mg test dose may be used
to determine the sensitivity of the patient and the individual recovery time (see

c ).

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The dose of succinylcholine administered by infusion depends upon the
duration of the surgical procedure and the need for muscle relaxation. The average rate for an adult
ranges between 2.5 and 4.3 mg per minute.

Solutions containing from 1 to 2 mg per mL succinylcholine have commonly been used for continuous
infusion. The more dilute solution (1 mg per mL) is probably preferable from the standpoint of ease of
control of the rate of administration of the drug and, hence, of relaxation. This IV solution containing 1 mg
per mL may be administered at a rate of 0.5 mg (0.5 mL) to 10 mg (10 mL) per minute to obtain the
required amount of relaxation. The amount required per minute will depend upon the individual response
as well as the degree of relaxation required. Avoid overburdening the circulation with a large volume of
fluid. It is recommended that neuromuscular function be carefully monitored with a peripheral nerve
stimulator when using succinylcholine by infusion in order to avoid overdose, detect development of
Phase II block, follow its rate of recovery, and assess the effects of reversing agents (see


c ).

Intermittent IV injections of succinylcholine may also be used to provide muscle relaxation for long
procedures. An IV injection of 0.3 to 1.1 mg/kg may be given initially, followed, at appropriate intervals, by
further injections of 0.04 to 0.07 mg/kg to maintain the degree of relaxation required.

 For emergency tracheal intubation or in instances where immediate securing of the airway is
necessary, the IV dose of succinylcholine is 2 mg/kg for infants and small children; for older children and
adolescents the dose is 1 mg/kg (see 
c   and

c : Pediatric Use).

Intravenous bolus administration of succinylcholine in infants or children may result in profound

bradycardia or, rarely, asystole. As in adults, the incidence of bradycardia in children is higher following a
second dose of succinylcholine. The occurrence of bradyarrhythmias may be reduced by pretreatment
with atropine (see

c : Pediatric Use).


  If necessary, succinylcholine may be given intramuscularly to infants, older children,
or adults when a suitable vein is inaccessible. A dose of up to 3 to 4 mg/kg may be given, but not more
than 150 mg total dose should be administered by this route. The onset of effect of succinylcholine given
intramuscularly is usually observed in about 2 to 3 minutes.







For immediate injection of single doses for short procedures: ANECTINE (succinylcholine chloride)
Injection, 20 mg in each mL.

Multiple-dose vials of 10 mL, box of 12 vials







Adverse reactions to succinylcholine consist primarily of an extension of its pharmacological actions.

Succinylcholine causes profound muscle relaxation resulting in respiratory depression to the point of
apnea; this effect may be prolonged. Hypersensitivity reactions, including anaphylaxis, may occur in rare
instances. The following additional adverse reactions have been reported: cardiac arrest, malignant
hyperthermia, arrhythmias, bradycardia, tachycardia, hypertension, hypotension, hyperkalemia,
prolonged respiratory depression or apnea, increased intraocular pressure, muscle fasciculation, jaw
rigidity, postoperative muscle pain, rhabdomyolysis with possible myoglobinuric acute renal failure,
excessive salivation, and rash.

c  

SUCCINYLCHOLINE SHOULD BE USED ONLY BY THOSE SKILLED IN THE MANAGEMENT OF

ARTIFICIAL RESPIRATION AND ONLY WHEN FACILITIES ARE INSTANTLY AVAILABLE FOR
TRACHEAL INTUBATION AND FOR PROVIDING ADEQUATE VENTILATION OF THE PATIENT,
INCLUDING THE ADMINISTRATION OF OXYGEN UNDER POSITIVE PRESSURE AND THE
ELIMINATION OF CARBON DIOXIDE. THE CLINICIAN MUST BE PREPARED TO ASSIST OR
CONTROL RESPIRATION.

TO AVOID DISTRESS TO THE PATIENT, SUCCINYLCHOLINE SHOULD NOT BE ADMINISTERED

BEFORE UNCONSCIOUSNESS HAS BEEN INDUCED. IN EMERGENCY SITUATIONS, HOWEVER, IT
MAY BE NECESSARY TO ADMINISTER SUCCINYLCHOLINE BEFORE UNCONSCIOUSNESS IS
INDUCED.

SUCCINYLCHOLINE IS METABOLIZED BY PLASMA CHOLINESTERASE AND SHOULD BE USED

WITH CAUTION, IF AT ALL, IN PATIENTS KNOWN TO BE OR SUSPECTED OF BEING
HOMOZYGOUS FOR THE ATYPICAL PLASMA CHOLINESTERASE GENE.

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c  #$
Succinylcholine should be administered with 
c
c
to patients suffering from electrolyte abnormalities and those who may have massive digitalis toxicity,
because in these circumstances succinylcholine may induce serious cardiac arrhythmias or cardiac arrest
due to hyperkalemia.


c
c should be observed if succinylcholine is administered to patients during the acute
phase of injury following major burns, multiple trauma, extensive denervation of skeletal muscle, or upper
motor neuron injury (see  c c ). The risk of hyperkalemia in these patients increases
over time and usually peaks at 7 to 10 days after the injury. The risk is dependent on the extent and
location of the injury. The precise time of onset and the duration of the risk period are undetermined.
Patients with chronic abdominal infection, subarachnoid hemorrhage, or conditions causing degeneration
of central and peripheral nervous systems should receive succinylcholine with 
c
c
because of the potential for developing severe hyperkalemia.

%
 &  Succinylcholine administration has been associated with acute onset of
malignant hyperthermia, a potentially fatal hypermetabolic state of skeletal muscle. The risk of developing
malignant hyperthermia following succinylcholine administration increases with the concomitant
administration of volatile anesthetics. Malignant hyperthermia frequently presents as intractable spasm of
the jaw muscles (masseter spasm) which may progress to generalized rigidity, increased oxygen
demand, tachycardia, tachypnea, and profound hyperpyrexia. Successful outcome depends on
recognition of early signs, such as jaw muscle spasm, acidosis, or generalized rigidity to initial
administration of succinylcholine for tracheal intubation, or failure of tachycardia to respond to deepening
anesthesia. Skin mottling, rising temperature, and coagulopathies may occur later in the course of the
hypermetabolic process. Recognition of the syndrome is a signal for discontinuance of anesthesia,
attention to increased oxygen consumption, correction of acidosis, support of circulation, assurance of
adequate urinary output, and institution of measures to control rising temperature. Intravenous dantrolene
sodium is recommended as an adjunct to supportive measures in the management of this problem.
Consult literature references and the dantrolene prescribing information for additional information about
the management of malignant hyperthermic crisis. Continuous monitoring of temperature and expired
CO2 is recommended as an aid to early recognition of malignant hyperthermia.

&  In both adults and children, the incidence of bradycardia, which may progress to asystole, is
higher following a second dose of succinylcholine. The incidence and severity of bradycardia is higher in
children than in adults. Pretreatment with anticholinergic agents (e.g., atropine) may reduce the
occurrence of bradyarrhythmias.

Succinylcholine causes an increase in intraocular pressure. It should not be used in instances in which an
increase in intraocular pressure is undesirable (e.g., narrow angle glaucoma, penetrating eye injury)
unless the potential benefit of its use outweighs the potential risk.

Succinylcholine is acidic (pH = 3.5) and should not be mixed with alkaline solutions having a pH greater
than 8.5 (e.g., barbiturate solutions).


c

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c  #$

  When succinylcholine is given over a prolonged period of time, the characteristic depolarization
block of the myoneural junction (Phase I block) may change to a block with characteristics superficially
resembling a nondepolarizing block (Phase II block). Prolonged respiratory muscle paralysis or weakness
may be observed in patients manifesting this transition to Phase II block. The transition from Phase I to
Phase II block has been reported in seven of seven patients studied under halothane anesthesia after an
accumulated dose of 2 to 4 mg/kg succinylcholine (administered in repeated, divided doses). The onset of
Phase II block coincided with the onset of tachyphylaxis and prolongation of spontaneous recovery. In
another study, using balanced anesthesia (N2O/O2/narcotic-thiopental) and succinylcholine infusion, the
transition was less abrupt, with great individual variability in the dose of succinylcholine required to
produce Phase II block. Of 32 patients studied, 24 developed Phase II block. Tachyphylaxis was not
associated with the transition to Phase II block, and 50% of the patients who developed Phase II block
experienced prolonged recovery.

When Phase II block is suspected in cases of prolonged neuromuscular blockade, positive diagnosis
should be made by peripheral nerve stimulation prior to administration of any anticholinesterase drug.
Reversal of Phase II block is a medical decision which must be made upon the basis of the individual,
clinical pharmacology, and the experience and judgment of the physician. The presence of Phase II block
is indicated by fade of responses to successive stimuli (preferably ³train-of-four´). The use of an
anticholinesterase drug to reverse Phase II block should be accompanied by appropriate doses of an
anticholinergic drug to prevent disturbances of cardiac rhythm. After adequate reversal of Phase II block
with an anticholinesterase agent, the patient should be continually observed for at least 1 hour for signs of
return of muscle relaxation. Reversal should not be attempted unless: (1) a peripheral nerve stimulator is
used to determine the presence of Phase II block (since anticholinesterase agents will potentiate
succinylcholine-induced Phase I block), and (2) spontaneous recovery of muscle twitch has been
observed for at least 20 minutes and has reached a plateau with further recovery proceeding slowly; this
delay is to ensure complete hydrolysis of succinylcholine by plasma cholinesterase prior to administration
of the anticholinesterase agent. Should the type of block be misdiagnosed, depolarization of the type
initially induced by succinylcholine (i.e., Phase I block) will be prolonged by an anticholinesterase agent.

Succinylcholine should be employed with caution in patients with fractures or muscle spasm because the
initial muscle fasciculations may cause additional trauma.

Succinylcholine may cause a transient increase in intracranial pressure; however, adequate anesthetic
induction prior to administration of succinylcholine will minimize this effect.

Succinylcholine may increase intragastric pressure, which could result in regurgitation and possible
aspiration of stomach contents.

Neuromuscular blockade may be prolonged in patients with hypokalemia or hypocalcemia.

  


&'  
c( Succinylcholine should be used carefully in patients with
reduced plasma cholinesterase (pseudocholinesterase) activity. The likelihood of prolonged
neuromuscular block following administration of succinylcholine must be considered in such patients (see
 c

c 
c   c ).
Plasma cholinesterase activity may be diminished in the presence of genetic abnormalities of plasma
cholinesterase (e.g., patients heterozygous or homozygous for atypical plasma cholinesterase gene),
pregnancy, severe liver or kidney disease, malignant tumors, infections, burns, anemia, decompensated
heart disease, peptic ulcer, or myxedema. Plasma cholinesterase activity may also be diminished by
chronic administration of oral contraceptives, glucocorticoids, or certain monoamine oxidase inhibitors,
and by irreversible inhibitors of plasma cholinesterase (e.g., organophosphate insecticides,
echothiophate, and certain antineoplastic drugs).

Patients homozygous for atypical plasma cholinesterase gene (1 in 2500 patients) are extremely sensitive
to the neuromuscular blocking effect of succinylcholine. In these patients, a 5- to 10-mg test dose of
succinylcholine may be administered to evaluate sensitivity to succinylcholine, or neuromuscular
blockade may be produced by the cautious administration of a 1-mg/mL solution of succinylcholine by
slow IV infusion. Apnea or prolonged muscle paralysis should be treated with controlled respiration.

'%  )
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  There have been no long-term studies
performed in animals to evaluate carcinogenic potential.

 % 

     Pregnancy Category C. Animal reproduction studies have not been
conducted with succinylcholine chloride. It is also not known whether succinylcholine can cause fetal
harm when administered to a pregnant woman or can affect reproduction capacity. Succinylcholine
should be given to a pregnant woman only if clearly needed.

‘ 

     Plasma cholinesterase levels are decreased by approximately 24% during
pregnancy and for several days postpartum. Therefore, a higher proportion of patients may be expected
to show increased sensitivity (prolonged apnea) to succinylcholine when pregnant than when
nonpregnant.

+'

 ( Succinylcholine is commonly used to provide muscle relaxation during delivery by
cesarean section. While small amounts of succinylcholine are known to cross the placental barrier, under
normal conditions the quantity of drug that enters fetal circulation after a single dose of 1 mg/kg to the
mother should not endanger the fetus. However, since the amount of drug that crosses the placental
barrier is dependent on the concentration gradient between the maternal and fetal circulations, residual
neuromuscular blockade (apnea and flaccidity) may occur in the neonate after repeated high doses to, or
in the presence of atypical plasma cholinesterase in, the mother.

%
'&  It is not known whether succinylcholine is excreted in human milk. Because many
drugs are excreted in human milk, caution should be exercised following succinylcholine administration to
a nursing woman.


  There are rare reports of ventricular dysrhythmias and cardiac arrest secondary to acute
rhabdomyolysis with hyperkalemia in apparently healthy children who receive succinylcholine (see 

c  ). Many of these children were subsequently found to have a skeletal muscle myopathy such
as Duchenne's muscular dystrophy whose clinical signs were not obvious. The syndrome often presents
as sudden cardiac arrest within minutes after the administration of succinylcholine. These children are
usually, but not exclusively, males, and most frequently 8 years of age or younger. There have also been
reports in adolescents. There may be no signs or symptoms to alert the practitioner to which patients are
at risk. A careful history and physical may identify developmental delays suggestive of a myopathy. A
preoperative creatine kinase could identify some but not all patients at risk. Due to the abrupt onset of this
syndrome, routine resuscitative measures are likely to be unsuccessful. Careful monitoring of the
electrocardiogram may alert the practitioner to peaked T-waves (an early sign). Administration of IV
calcium, bicarbonate, and glucose with insulin, with hyperventilation have resulted in successful
resuscitation in some of the reported cases. Extraordinary and prolonged resuscitative efforts have been
effective in some cases. In addition, in the presence of signs of malignant hyperthermia, appropriate
treatment should be initiated concurrently (see c   ). Since it is difficult to identify which patients
are at risk, it is recommended that the use of succinylcholine in children should be reserved for
emergency intubation or instances where immediate securing of the airway is necessary, e.g.,
laryngospasm, difficult airway, full stomach, or for intramuscular use when a suitable vein is inaccessible.

As in adults, the incidence of bradycardia in children is higher following the second dose of
succinylcholine. The incidence and severity of bradycardia is higher in children than in adults.
Pretreatment with anticholinergic agents, e.g., atropine, may reduce the occurrence of bradyarrhythmias.

,


Overdosage with succinylcholine may result in neuromuscular block beyond the time needed for surgery
and anesthesia. This may be manifested by skeletal muscle weakness, decreased respiratory reserve,
low tidal volume, or apnea. The primary treatment is maintenance of a patent airway and respiratory
support until recovery of normal respiration is assured. Depending on the dose and duration of
succinylcholine administration, the characteristic depolarizing neuromuscular block (Phase I) may change
to a block with characteristics superficially resembling a nondepolarizing block (Phase II) (see


c ).

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