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Succinylcholine is a diquaternary base consisting of the dichloride salt of the dicholine ester
of succinic acid. It is a white, odorless, slightly bitter powder, very soluble in water. The drug
is incompatible with alkaline solutions but relatively stable in acid solutions. Solutions of the
drug lose potency unless refrigerated.
Solution intended for multiple-dose administration contains 0.18% methylparaben and 0.02%
propylparaben as preservatives (List No. 6629). Solution intended for single-dose
administration contains no preservatives. Unused solution should be discarded. Product not
requiring dilution (multiple-dose fliptop vial) contains sodium chloride to render isotonic. May
contain sodium hydroxide and/or hydrochloric acid for pH adjustment. pH is 3.6 (3.0 to 4.5).
See table in HOW SUPPLIED for characteristics.
Sodium Chloride, USP, chemically designated NaCl, is a white crystalline compound freely
soluble in water.
WARNING
RISK OF CARDIAC ARREST FROM HYPERKALEMIC RHABDOMYOLYSIS
There have been rare reports of acute rhabdomyolysis with hyperkalemia followed by
ventricular dysrhythmias, cardiac arrest and death after the administration of succinylcholine
to apparently healthy pediatric patients who were subsequently found to have undiagnosed
skeletal muscle myopathy, most frequently Duchenne's muscular dystrophy.
This syndrome often presents as peaked T-waves and sudden cardiac arrest within minutes
after the administration of the drug in healthy appearing pediatric patients (usually, but not
exclusively, males, and most frequently 8 years of age or younger). There have also been
reports in adolescents.
Therefore, when a healthy appearing infant or child develops cardiac arrest soon after
administration of succinylcholine, not felt to be due to inadequate ventilation, oxygenation or
anesthetic overdose, immediate treatment for hyperkalemia should be instituted. This should
include administration of intravenous calcium, bicarbonate, and glucose with insulin, with
hyperventilation. Due to the abrupt onset of this syndrome, routine resuscitative measures
are likely to be unsuccessful. However, extraordinary and prolonged resuscitative efforts
have resulted in successful resuscitation in some reported cases. In addition, in the presence
of signs of malignant hyperthermia, appropriate treatment should be instituted concurrently.
Since there may be no signs or symptoms to alert the practitioner to which patients are at
risk, it is recommended that the use of succinylcholine in pediatric patients 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
INDICATION
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.
DOSAGE
The dosage of succinylcholine should be individualized and should always be determined by
the clinician after careful assessment of the patient (seeWARNINGS).
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.
Adults
For Short Surgical Procedures
The average dose required to produce neuromuscular blockade and to facilitate tracheal
intubation is 0.6 mg/kg Quelicin (succinylcholine chloride) 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 (seePRECAUTIONS).
and
cardiac
arrest
secondary
to
adults only after repeated exposure. The occurrence of bradyarrhythmias may be reduced by
pretreatment with atropine (see PRECAUTIONS: Pediatric Use).
Intramuscular Use
If necessary, succinylcholine may be given intramuscularly to infants, older pediatric patients
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.
Compatibility and Admixtures
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). Admixtures containing 1 to 2 mg/mL may be
prepared by adding 1 g Quelicin to 1000 or 500 mL sterile solution, such as
5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP. Admixtures of Quelicin
must be used within 24 hours after preparation. Aseptic techniques should be used to
prepare the diluted product. Admixtures of Quelicin should be prepared for single patient use
only. The unused portion of diluted Quelicin should be discarded.
To prevent needle-stick injuries, needles should not be recapped, purposely bent, or broken
by hand.
SIDE EFFECT
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,
prolonged
INTERACTIONS
Drugs which may enhance the neuromuscular blocking action of succinylcholine include:
promazine, oxytocin, aprotinin, certain non-penicillinantibiotics, quinidine, -adrenergic
blockers,
procainamide,
lidocaine,
trimethaphan, lithium
carbonate,
magnesium
WARNINGS
SUCCINYLCHOLINE SHOULD BE
FOR
TRACHEAL
INTUBATION
AND
FOR
PROVIDING
HOWEVER,
IT
MAY
BE
NECESSARY
TO
ADMINISTER
rigidity,
increased
oxygen
profound
Other
In both adults and pediatric patients 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 pediatric patients than adults. Whereas bradycardia is common in
pediatric patients after an initial dose of 1.5 mg/kg, bradycardia is seen in adults only after
repeated exposure. 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).
OVERDOSE
Overdosage with succinylcholine may result in neuromuscular block beyond the time needed
for surgery and anesthesia. This may be manifested byskeletal 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 non-depolarizing block (Phase II) (see PRECAUTIONS).
CONTRAINDICATIONS
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, extensivedenervation of skeletal muscle, or upper motor neuron injury,
because
succinylcholine
administered
to
such
individuals
may
result
in
severehyperkalemia which may result in cardiac arrest (see WARNINGS). 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.
CLINICAL PHARMACOLOGY
Succinylcholine is a depolarizing skeletal muscle relaxant. As does acetylcholine, it combines
with the cholinergic receptors of the motor end plate to produce depolarization. This
depolarization may be observed as fasciculations. Subsequent neuromuscular transmission
is inhibited so long as adequate concentration of succinylcholine remains at the receptor site.
Onset of flaccid paralysis is rapid (less than one minute after intravenous administration),
and with single administration lasts approximately 4 to 6 minutes.
Succinylcholine is rapidly hydrolyzed by plasma cholinesterase to succinylmonocholine
(which possesses clinically insignificant depolarizingmuscle relaxant properties) and then
more slowly to succinic acid and choline (see PRECAUTIONS). About 10% of the drug is
excreted unchanged in the urine. Succinylcholine levels were reported to be below the
detection limit of 2 g/mL after 2.5 minutes of an IV bolus dose of 1 or 2 mg/kg in fourteen
(14) anesthetized patients. The paralysis following administration of succinylcholine is
progressive, with differing sensitivities of different muscles. This initially involves
consecutively the levator muscles of the face, muscles of the glottis and finally the
intercostals and the diaphragm and all other skeletal muscles.
Succinylcholine has no direct action on the uterus or other smooth musclestructures.
Because it is highly ionized and has low fat solubility, it does not readily cross the placenta.
Tachyphylaxis occurs with repeated administration (see PRECAUTIONS).
Depending on the dose and duration of succinylcholine administration, the characteristic
depolarizing neuromuscular block (Phase I block) may change to a block with characteristics
superficially resembling a non-depolarizing block (Phase II block). This may be associated
with prolonged respiratory muscle paralysis or weakness in patients who manifest the
transition to Phase II block. When this diagnosis is confirmed by peripheral nerve stimulation,
it may sometimes be reversed with anticholinesterase drugs such as neostigmine
(see PRECAUTIONS). Anticholinesterase drugs may not always be effective. If given before
succinylcholine is metabolized by cholinesterase, anticholinesterase drugs may prolong
rather than shorten paralysis.
Succinylcholine has no direct effect on the myocardium. Succinylcholine stimulates both
autonomic ganglia and muscarinic receptors which may cause changes in cardiac rhythm,
including cardiac arrest. Changes in rhythm, including cardiac arrest, may also result from
vagal stimulation, which may occur during surgical procedures, or from hyperkalemia,
particularly in pediatric patients (see PRECAUTIONS: Pediatric Use). These effects are
enhanced by halogenated anesthetics.
Succinylcholine causes an increase in intraocular pressure immediately after its injection and
during the fasciculation phase, and slight increases which may persist after onset of
complete paralysis (see WARNINGS).
Succinylcholine may cause slight increases in intracranial pressure immediately after its
injection and during the fasciculation phase (seePRECAUTIONS).
As with other neuromuscular blocking agents, the potential for releasinghistamine is present
following succinylcholine administration. Signs and symptoms of histamine mediated release
such as flushing, hypotension and bronchoconstriction are, however, uncommon in normal
clinical usage.
Succinylcholine has no effect on consciousness, pain threshold or cerebration. It should be
used only with adequate anesthesia (seeWARNINGS).
HALOTHANE
halothane, USP is supplied as a liquid and is vaporized for use as an inhalation anesthetic. It is 2bromo-2-chloro-1, 1, 1-trifluoro-ethane. C2 HBrClF 3
The molecular weight is 197.38. The drug substance halothane moleculehas an asymmetric
carbon atom; the commercial product is a racemic mixture. Resolution of the mixture has not
been reported.*
* Klaus Florey, editor, Analytical Profiles of Drug Substances, Vol. 1, page 127, (1972).
Halothane is miscible with alcohol, chloroform, ether, and other fat solvents.
The specific gravity is 1.872-1.877 at 20C, and the boiling point (range) is 49C-51C at 760 mm
Hg. The vapor pressure is 243 mm Hg at 20C. The blood/gas coefficient is 2.5 at 37C, and
the olive oil/water coefficient is 220 at 37C. Vapor concentrations within anesthetic range are
nonirritating and have a pleasant odor.
Fluothane (halothane) is nonflammable, and its vapors mixed with oxygen in proportions from 0.5
to 50% (v/v) are not explosive.
Fluothane (halothane) does not decompose in contact with warm soda lime. When moisture is
present, the vapor attacks aluminum, brass, and lead, but not copper. Rubber, some plastics, and
similar materials are soluble in Fluothane (halothane) ; such materials will deteriorate rapidly in
contact with Fluothane (halothane) vapor or liquid. Stability of Fluothane (halothane) is
maintained by the addition of 0.01% thymol (w/w), up to 0.00025% ammonia(w/w).
INDICATIONS
Fluothane (halothane, USP) is indicated for the induction and maintenance of general anesthesia.
Fluothane (halothane) may be administered with either oxygen or a mixture of oxygen and nitrous
oxide.
Fluothane (halothane) should not be kept indefinitely in vaporizer bottles not specifically designed
for its use. Thymol does not volatilize along with Fluothane (halothane) and, therefore,
accumulates in the vaporizer and may, in time, impart a yellow color to the remaining liquid or to
wicks in vaporizers. The development of such discoloration may be used as an indicator that the
vaporizer should be drained and cleaned, and the discolored Fluothane (halothane, USP)
discarded. Accumulation of thymol may be removed by washing with diethyl ether. After cleaning
a wick or vaporizer, make certain all the diethyl ether has been removed before reusing the
equipment to avoid introducing ether into the system.
Because
of
the
more
rapid
uptake
required
for
of
Fluothane
anesthesia
in
(halothane)
younger
and
the
patients,
the
minimum alveolar concentration (MAC) 1 values will decrease with age as follows:
Age
MAC %
Infants
1.08
3 yrs
0.91
10 yrs.
0.87
15 yrs.
0.92
24 yrs.
0.84
42 yrs.
0.76
81 yrs.
0.64
SIDE EFFECTS
As with other agents of this type, halothane anaesthesia has been shown totrigger a skeletal
muscle hypermetabolic
state
leading
to
high oxygendemand
and
the
clinical syndrome known as malignant hyperthermia (MH). The syndrome includes non
DRUG INTERACTIONS
FLUOTHANE (halothane) augments the action of non-depolarising muscle relaxants and
the muscle relaxant effects of aminoglycosides.
FLUOTHANE (halothane) may augment the hypotension caused by the ganglionic-blocking
effect of tubocurarine.
Caution
should
be
exercised
during
the
administration
of adrenaline to
patients
WARNINGS
When
previous
exposure
to
Fluothane
(halothane)
was
followed
by
unexplained hepatic dysfunction and/or jaundice, consideration should be given to the use of
other agents.
PRECAUTIONS
GENERAL
Fluothane (halothane) should be used in vaporizers that permit a reasonable approximation
of output, and preferably of the calibrated type. The vaporizer should be placed out of circuit
in closed-circuit rebreathing systems; otherwise, overdosage is difficult to avoid. The patient
should
be
closely
observed
for
signs
of
overdosage,
susceptible
individuals,
skeletal-muscle
hypermetabolic state leading to a high oxygen demand and the clinical syndrome known
as malignant hyperthermia.
The
syndrome
includes
nonspecific
features
arrhythmias,
such
and
unstable blood pressure. (It should also be noted that many of these nonspecific signs may
appear with light anesthesia, acutehypoxia, etc.) An increase in overall metabolism may be
reflected in an elevated temperature (which may rise rapidly, early or late in the case, but
usually is not the first sign of augmented metabolism) and an increased usage of the
CO 2 absorption system (hot canister). PaO 2 and pH may decrease, and hyperkalemia and a
base deficit may appear. Treatment includes discontinuance of triggering agents (e.g.,
halothane), administration of intravenous dantrolene, and application of supportive therapy.
Such
therapy
includes
vigorous
efforts
to
restore
body
temperature
to
normal,respiratory and circulatory support as indicated, and management of electrolyte-fluidacid-base derangements. Renal failure may appear later, and urine flow should be sustained
if possible. It should be noted that the syndrome of malignant hyperthermia secondary to
halothane appears to be rare.
INFORMATION FOR PATIENTS
When appropriate, as in some cases where discharge is anticipated soon after general
anesthesia, patients should be cautioned not to drive automobiles, operate hazardous
machinery, or engage in hazardous sports for 24 hours or more (depending on the total dose
of Fluothane (halothane) ,condition of the patient, and consideration given to other drugs
administered after anesthesia).
DRUG INTERACTIONS
Epinephrine or norepinephrine should be employed cautiously, if at all, during Fluothane
(halothane, USP) anesthesia, since their simultaneous use may induce ventricular
tachycardia or fibrillation.
Nondepolarizing relaxants and ganglionic-blocking agents should be administered cautiously,
since their actions are augmented by Fluothane (halothane, USP).
Clinical experience and animal experiments suggest that pancuronium should be given with
caution to patients receiving chronic tricyclic antidepressant therapy who are anesthetized
with halothane, because severe ventricular arrhythmias may result from such usage.
CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY
An 18-month inhalational carcinogenicity study of halothane at 0.05% in the mouse revealed
no evidence of anesthetic-related carcinogenicity. This concentration is equivalent to 24
hours of 1% halothane.
Mutagenesis testing of halothane revealed both positive and negative results. In the rat, oneyear exposure to trace concentrations of halothane (1 and 10 ppm) and nitrous
oxide produced chromosomal damage to spermatogonia cells and bone marrow cells.
Negative
mutagenesis
tests
included:
Chinese
hamster
lung fibroblast assay, sister chromatid exchange in Chinese hamster ovary cells, and human
leukocyte culture assay.
Reproduction studies of halothane (10 ppm) and nitrous oxide in the rat caused decreased
fertility. This trace concentration corresponds to 1/1000 the human maintenance dose.
PREGNANCY
Teratogenic Effects: Pregnancy Category C. Some studies have shown Fluothane
(halothane) to be teratogenic, embryotoxic, and fetotoxic in the mouse, rat, hamster, and
rabbit at subanesthetic and/or anestheticconcentrations. There are no adequate and wellcontrolled studies inpregnant women. Fluothane (halothane) should be used during
pregnancy only if the potential benefit justifies the potential risk to the fetus.
OVERDOSE
In the event of overdosage, or what may appear to be overdosage, drug administration
should be stopped, and assisted or controlled ventilation with pure oxygen initiated.
There is no specific antidote. Treatment should be aimed at maintainingrespiratory function
(by moving the patient to fresh air or inserting an emergency airway with respiratory support)
and cardiovascular function.
Cases of internal ingestion must be treated symptomatically.
CONTRAINDICATIONS
Fluothane (halothane) is not recommended for obstetrical anesthesia except when uterine
relaxation is required.
CLINICAL PHARMACOLOGY
Fluothane (halothane) is an inhalation anesthetic. Induction and recovery are rapid, and
depth
of anesthesia can
depresses respiration.
be
There
rapidly
may
altered.
Fluothane
be tachypnea with
(halothane)
reduced
progressively
tidal
volume
and alveolar ventilation. Fluothane (halothane) is not an irritant to the respiratory tract, and
no
increase
in
salivary
or
bronchial
are
secretions
rapidly obtunded.
ordinarily
It
causes
greater
the
concentration
of
the
drug,
the
more
evident
these
changes
become. Atropine may reverse the bradycardia. Fluothane (halothane) does not cause the
release
of
catecholamines
from
adrenergic
stores.
Fluothane
(halothane)
also
the
myocardial
conduction
system
to
the
action
of epinephrine and
norepinephrine, and the combination may cause serious cardiac arrhythmias. Fluothane
(halothane) increases cerebrospinal-fluid pressure. Fluothane (halothane) produces
moderatemuscular relaxation. Muscle relaxants are used as adjuncts in order to maintain
lighter levels of anesthesia. Fluothane (halothane) augments the action of nondepolarizing
relaxants and ganglionic-blocking agents. Fluothane (halothane) is a potent uterine relaxant.
The mechanism(s) whereby Fluothane (halothane) and other substances induce general
anesthesia is unknown. Fluothane (halothane) is a very potent anesthetic in humans, with a
minimum alveolar concentration (MAC) determined to be 0.64%. The MAC has been found to
decrease with age (see MAC table in "Dosage and Administration").
Malignant hyperthermia
*Malignant hyperthermia facts medical author: Melissa Conrad Stppler, MD
Malignant hyperthermia is a severe reaction to particular drugs that are often used
during general anesthesia for surgery.
essential role in activating the RYR1 channel to release calcium ions into muscle cells.
Although this gene is thought to be related to malignant hyperthermia in a few families, no
causative mutations have been identified.
Hyperpyrexia, Malignant
Hyperthermia, Malignant
Malignant Hyperpyrexia