(SEE BOX WARNING)
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
non-depolarizing 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 7 of
7 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
succinylcholine 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 intravenous 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 of succinylcholine. Genetic toxicology
studies have not been completed to evaluate the genotoxic potential of
succinylcholine. There are no studies to evaluate the potential impact of
succinylcholine on fertility.
It is also not known whether succinylcholine can cause
fetal harm when administered to a pregnant woman or can affect reproduction
capacity. Animal reproduction studies have not been conducted with succinylcholine
chloride. Succinylcholine should be given to a pregnant woman only if clearly
needed. The estimated background risk of major birth defects and miscarriage
for the indicated population is unknown. All pregnancies have a background risk
of birth defect, loss, or other adverse outcomes. In the U.S. general population,
the estimated background risk of major birth defects and miscarriage in clinically
recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
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 caesarean 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 newborn 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.
Safety and effectiveness of succinylcholine chloride have
been established in pediatric patient age groups, neonate to adolescent. There
are rare reports of ventricular dysrhythmias and cardiac arrest secondary to
acute rhabdomyolysis with hyperkalemia in apparently healthy pediatric patients
who receive succinylcholine (see BOX WARNING). Many of these pediatric
patients 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 pediatric patients 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 intravenous
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 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.
As in adults, the incidence of bradycardia in pediatric
patients is higher following the second dose of succinylcholine. The incidence
and severity of bradycardia is higher in pediatric patients than adults. Pre-treatment
with anticholinergic agents, e.g., atropine, may reduce the occurrence of bradyarrhythmias.
Clinical studies of QUELICIN did not include sufficient
numbers of subjects aged 65 and over to determine whether they respond differently
from younger subjects. Other reported clinical experience has not identified
differences in responses between the elderly and younger patients.
In general, dose selection for an elderly patient should
be cautious, usually starting at the low end of the dosing range, reflecting
the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant
disease or other drug therapy.