The safety and effectiveness of local anesthetics depend
on proper dosage, correct technique, adequate precautions, and readiness for
emergencies. Resuscitative equipment, oxygen, and other resuscitative drugs
should be available for immediate use (see WARNINGS, ADVERSE
REACTIONS, and OVERDOSAGE). During major regional nerve blocks, the
patient should have IV fluids running via an indwelling catheter to assure a
functioning intravenous pathway. The lowest dosage of local anesthetic that results
in effective anesthesia should be used to avoid high plasma levels and serious
adverse effects. The rapid injection of a large volume of local anesthetic solution
should be avoided and fractional (incremental) doses should be used when feasible.
During epidural administration of Sensorcaine
(bupivacaine HCl), 0.5% and 0.75% solutions should be administered in
incremental doses of 3 mL to 5 mL with sufficient time between doses to detect
toxic manifestations of unintentional intravascular or intrathecal injection.
Injections should be made slowly, with frequent aspirations before and during
the injection to avoid intravascular injection. Syringe aspirations should also
be performed before and during each supplemental injection in continuous
(intermittent) catheter techniques. An intravascular injection is still
possible even if aspirations for blood are negative.
During the administration of epidural anesthesia, it is
recommended that a test dose be administered initially and the effects
monitored before the full dose is given. When using a “continuous” catheter
technique, test doses should be given prior to both the original and all
reinforcing doses, because plastic tubing in the epidural space can migrate
into a blood vessel or through the dura. When clinical conditions permit, the
test dose should contain epinephrine (10 mcg to 15 mcg has been suggested) to
serve as a warning of unintended intravascular injection. If injected into a blood
vessel, this amount of epinephrine is likely to produce a transient
“epinephrine response” within 45 seconds, consisting of an increase in heart
rate and/or systolic blood pressure, circumoral pallor, palpitations, and
nervousness in the unsedated patient. The sedated patient may exhibit only a
pulse rate increase of 20 or more beats per minute for 15 or more seconds.
Therefore, following the test dose, the heart rate should
be monitored for a heart rate increase. Patients on beta-blockers may not manifest
changes in heart rate, but blood pressure monitoring can detect a transient
rise in systolic blood pressure. The test dose should also contain 10 mg to 15
mg of Sensorcaine or an equivalent amount of another local anesthetic to detect
an unintended intrathecal administration. This will be evidenced within a few
minutes by signs of spinal block (e.g., decreased sensation of the buttocks,
paresis of the legs, or, in the sedated patient, absent knee jerk). An intravascular
or subarachnoid injection is still possible even if results of the test dose
are negative. The test dose itself may produce a systemic toxic reaction, high
spinal or epinephrine-induced cardiovascular effects.
Injection of repeated doses of local anesthetics may
cause significant increases in plasma levels with each repeated dose due to
slow accumulation of the drug or its metabolites, or to slow metabolic
degradation. Tolerance to elevated blood levels varies with the status of the
patient. Debilitated, elderly patients and acutely ill patients should be given
reduced doses commensurate with their age and physical status. Local anesthetics
should also be used with caution in patients with hypotension or heartblock.
Careful and constant monitoring of cardiovascular and
respiratory (adequacy of ventilation) vital signs and the patient's state of
consciousness should be performed after each local anesthetic injection. It
should be kept in mind at such times that restlessness, anxiety, incoherent
speech, lightheadedness, numbness and tingling of the mouth and lips, metallic
taste, tinnitus, dizziness, blurred vision, tremors, twitching, depression, or drowsiness
may be early warning signs of central nervous system toxicity.
Local anesthetic solutions containing a vasoconstrictor
should be used cautiously and in carefully restricted quantities in areas of
the body supplied by end arteries or having otherwise compromised blood supply
such as digits, nose, external ear, or penis. Patients with hypertensive
vascular disease may exhibit exaggerated vasoconstrictor response. Ischemic
injury or necrosis may result.
Because amide-local anesthetics such as bupivacaine are
metabolized by the liver, these drugs, especially repeat doses, should be used
cautiously in patients with hepatic disease. Patients with severe hepatic
disease, because of their inability to metabolize local anesthetics normally,
are at a greater risk of developing toxic plasma concentrations. Local
anesthetics should also be used with caution in patients with impaired
cardiovascular function because they may be less able to compensate for functional
changes associated with the prolongation of AV conduction produced by these drugs.
Serious dose-related cardiac arrhythmias may occur if
preparations containing a vasoconstrictor such as epinephrine are employed in
patients during or following the administration of potent inhalation
anesthetics. In deciding whether to use these products concurrently in the same
patient, the combined action of both agents upon the myocardium, the
concentration and volume of vasoconstrictor used, and the time since injection,
when applicable, should be taken into account.
Many drugs used during the conduct of anesthesia are
considered potential triggering agents for familial malignant hyperthermia.
Because it is not known whether amide-type local anesthetics may trigger this
reaction and because the need for supplemental general anesthesia cannot be
predicted in advance, it is suggested that a standard protocol for management
should be available. Early unexplained signs of tachycardia, tachypnea, labile
blood pressure, and metabolic acidosis may precede temperature elevation.
Successful outcome is dependent on early diagnosis, prompt discontinuance of
the suspect triggering agent(s) and prompt institution of treatment, including
oxygen therapy, indicated supportive measures and dantrolene (consult dantrolene
sodium intravenous package insert before using).
Use In Head And Neck Area
Small doses of local anesthetics injected into the head
and neck area, including retrobulbar, dental and stellate ganglion blocks, may
produce adverse reactions similar to systemic toxicity seen with unintentional
intravascular injections of larger doses. The injection procedures require the
utmost care. Confusion, convulsions, respiratory depression, and/or respiratory
arrest, and cardiovascular stimulation or depression have been reported. These
reactions may be due to intra-arterial injection of the local anesthetic with
retrograde flow to the cerebral circulation. They may also be due to puncture
of the dural sheath of the optic nerve during retrobulbar block with diffusion
of any local anesthetic along the subdural space to the midbrain. Patients
receiving these blocks should have their circulation and respiration monitored
and be constantly observed. Resuscitative equipment and personnel for treating
adverse reactions should be immediately available. Dosage recommendations
should not be exceeded (see DOSAGE AND ADMINISTRATION).
Use In Ophthalmic Surgery
Clinicians who perform retrobulbar blocks should be aware
that there have been reports of respiratory arrest following local anesthetic
injection. Prior to retrobulbar block, as with all other regional procedures,
the immediate availability of equipment, drugs, and personnel to manage
respiratory arrest or depression, convulsions, and cardiac stimulation or
depression should be assured (see also WARNINGS and Use in Head and Neck
Area, above). As with other anesthetic procedures, patients should be
constantly monitored following ophthalmic blocks for signs of these adverse
reactions, which may occur following relatively low total doses.
A concentration of 0.75% bupivacaine is indicated for
retrobulbar block; however, this concentration is not indicated for any other
peripheral nerve block, including the facial nerve, and not indicated for local
infiltration, including the conjunctiva (see INDICATIONS and PRECAUTIONS,
General). Mixing Sensorcaine (bupivacaine HCl) with other local
anesthetics is not recommended because of insufficient data on the clinical use
of such mixtures.
When Sensorcaine (bupivacaine HCl) 0.75% is used for
retrobulbar block, complete corneal anesthesia usually precedes onset of
clinically acceptable external ocular muscle akinesia. Therefore, presence of
akinesia rather than anesthesia alone should determine readiness of the patient
Use In Dentistry
Because of the long duration of anesthesia, when
Sensorcaine 0.5% with epinephrine is used for dental injections, patients
should be cautioned about the possibility of inadvertent trauma to the tongue,
lips, and buccal mucosa and advised not to chew solid foods or test the
anesthetized area by biting or probing.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Long-term studies in animals to evaluate the carcinogenic
potential of bupivacaine hydrochloride have not been conducted. The mutagenic
potential and the effect on fertility have not been determined.
Pregnancy Category C
There are no adequate and well-controlled studies in
pregnant women. Sensorcaine should be used during pregnancy only if the
potential benefit justifies the potential risk to the fetus. Bupivacaine
hydrochloride produced developmental toxicity when administered subcutaneously
to pregnant rats and rabbits at clinically relevant doses. This does not
exclude the use of Sensorcaine at term for obstetrical anesthesia or analgesia
(see Labor and Delivery).
Bupivacaine hydrochloride was administered subcutaneously
to rats at doses of 4.4, 13.3, & 40 mg/kg and to rabbits at doses of 1.3,
5.8, & 22.2 mg/kg during the period of organogenesis (implantation to
closure of the hard palate). The high doses are comparable to the daily maximum
recommended human dose (MRHD) of 400 mg/day on a mg/m body surface area (BSA)
basis. No embryo-fetal effects were observed in rats at the high dose which
caused increased maternal lethality. An increase in embryo-fetal deaths was
observed in rabbits at the high dose in the absence of maternal toxicity with
the fetal No Observed Adverse Effect Level representing approximately 1/5th the
MRHD on a BSA basis.
In a rat pre- and post-natal development study (dosing
from implantation through weaning) conducted at subcutaneous doses of 4.4,
13.3, & 40 mg/kg mg/kg/day, decreased pup survival was observed at the high
dose. The high dose is comparable to the daily MRHD of 400 mg/day on a BSA
Labor And Delivery
SEE BOX WARNING REGARDING OBSTETRICAL USE of 0.75%
Sensorcaine is contraindicated for obstetrical
paracervical block anesthesia.
Local anesthetics rapidly cross the placenta, and when
used for epidural, caudal, or pudendal block anesthesia, can cause varying
degrees of maternal, fetal, and neonatal toxicity (see CLINICAL PHARMACOLOGY,
Pharmacokinetics ). The incidence and degree of toxicity depend upon the
procedure performed, the type, and amount of drug used, and the technique of
drug administration. Adverse reactions in the parturient, fetus, and neonate
involve alterations of the central nervous system, peripheral vascular tone, and
Maternal hypotension has resulted from regional
anesthesia. Local anesthetics produce vasodilation by blocking sympathetic
nerves. Elevating the patient's legs and positioning her on her left side will
help prevent decreases in blood pressure. The fetal heart rate also should be
monitored continuously and electronic fetal monitoring is highly advisable.
Epidural, caudal, or pudendal anesthesia may alter the
forces of parturition through changes in uterine contractility or maternal
expulsive efforts. Epidural anesthesia has been reported to prolong the second
stage of labor by removing the parturient's reflex urge to bear down or by
interfering with motor function. The use of obstetrical anesthesia may increase
the need for forceps assistance.
The use of some local anesthetic drug products during
labor and delivery may be followed by diminished muscle strength and tone for
the first day or two of life. This has not been reported with bupivacaine.
It is extremely important to avoid aortocaval compression
by the gravid uterus during administration of regional block to parturients. To
do this, the patient must be maintained in the left lateral decubitus position
or a blanket roll or sandbag may be placed beneath the right hip and gravid
uterus displaced to the left.
Bupivacaine has been reported to be excreted in human
milk suggesting that the nursing infant could be theoretically exposed to a
dose of the drug. Because of the potential for serious adverse reactions in
nursing infants from bupivacaine, a decision should be made whether to
discontinue nursing or not administer bupivacaine, taking into account the importance
of the drug to the mother.
Until further experience is gained in pediatric patients
younger than 12 years, administration of Sensorcaine (bupivacaine HCl)
Injection in this age group is not recommended. Continuous infusions of
bupivacaine in children have been reported to result in high systemic levels of
bupivacaine and seizures; high plasma levels may also be associated with
cardiovascular abnormalities (see WARNINGS, PRECAUTIONS, and OVERDOSAGE).
Patients over 65 years, particularly those with
hypertension, may be at increased risk for developing hypotension while
undergoing anesthesia with bupivacaine (see ADVERSE REACTIONS).
Elderly patients may require lower doses of bupivacaine
(see PRECAUTIONS, Epidural Anesthesia and DOSAGE AND
In clinical studies, differences in various
pharmacokinetic parameters have been observed between elderly and younger
patients (see CLINICAL PHARMACOLOGY).
This product is known to be substantially excreted by the
kidney, and the risk of toxic reactions to this drug may be greater in patients
with impaired renal function. Because elderly patients are more likely to have
decreased renal function, care should be taken in dose selection, and it may be
useful to monitor renal function (see CLINICAL PHARMACOLOGY).