PRECAUTIONS
(SEE BOX WARNING.)
General
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 “train-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.
Since allergic cross-reactivity has been reported in this
class, request information from your patients about previous anaphylactic
reactions to other neuromuscular blocking agents. In addition, inform your
patients that severe anaphylactic reactions to neuromuscular blocking agents,
including ANECTINE (succinylcholine chloride) have been reported.
Reduced Plasma Cholinesterase Activity
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 DOSAGE AND ADMINISTRATION).
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.
Carcinogenesis, Mutagenesis, Impairment of Fertility
There have been no long-term studies performed in animals to
evaluate carcinogenic potential.
Pregnancy
Teratogenic Effects - 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.
Nonteratogenic Effects
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.
Labor and Delivery
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.
Nursing Mothers
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.
Pediatric Use
There are rare reports of ventricular dysrhythmias and
cardiac arrest secondary to acute rhabdomyolysis with hyperkalemia in
apparently healthy children who receive succinylcholine (see BOX WARNING).
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 WARNINGS).
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.