WARNINGS
LOCAL ANESTHETICS SHOULD ONLY BE EMPLOYED BY CLINICIANS WHO ARE WELL VERSED IN DIAGNOSIS AND MANAGEMENT OF DOSE-RELATED TOXICITY AND OTHER ACUTE EMERGENCIES WHICH MIGHT ARISE FROM THE BLOCK TO BE EMPLOYED, AND THEN ONLY AFTER INSURING THE IMMEDIATE AVAILABILITY OF OXYGEN, OTHER RESUSCITATIVE DRUGS, CARDIOPULMONARY RESUSCITATIVE EQUIPMENT, AND THE PERSONNEL RESOURCES NEEDED FOR PROPER MANAGEMENT OF TOXIC REACTIONS AND RELATED EMERGENCIES. (See also ADVERSE REACTIONS, PRECAUTIONS and OVERDOSAGE.) DELAY IN PROPER MANAGEMENT OF DOSE-RELATED TOXICITY, UNDERVENTILATION FROM ANY CAUSE AND/OR ALTERED SENSITIVITY MAY LEAD TO THE DEVELOPMENT OF ACIDOSIS, CARDIAC ARREST, AND, POSSIBLY, DEATH.
Spinal anesthetics should not be injected during uterine contractions, because spinal fluid current may carry the drug further cephalad than desired.
A free flow of cerebrospinal fluid during the performance of spinal anesthesia is indicative of entry into the subarachnoid space. However, aspiration should be performed before the anesthetic solution is injected to confirm entry into the subarachnoid space and to avoid intravascular injection.
Bupivacaine solutions containing epinephrine or other vasopressors should not be used concomitantly with ergot-type oxytocic drugs, because a severe persistent hypertension may occur. Likewise, solutions of bupivacaine containing a vasoconstrictor, such as epinephrine, should be used with extreme caution in patients receiving monoamine oxidase inhibitors (MAOI) or antidepressants of the triptyline or imipramine types, because severe prolonged hypertension may result.
Until further experience is gained in patients younger than 18 years, administration of bupivacaine in this age group is not recommended.
Mixing or the prior or intercurrent use of any other local anesthetic with bupivacaine cannot be recommended because of insufficient data on the clinical use of such mixtures.
PRECAUTIONS
General:
The safety and effectiveness of spinal 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.) The patient should have I.V. 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. Aspiration for blood should be performed before injection and injection should be made slowly. Tolerance varies with the status of the patient. Debilitated, elderly patients and acutely ill patients may require reduced doses. Reduced doses may also be indicated in patients with increased intra-abdominal pressure (including obstetrical patients), if otherwise suitable for spinal anesthesia.
There should be careful and constant monitoring of cardiovascular and respiratory (adequacy of ventilation) vital signs and the patient’s state of consciousness after local anesthetic injection. Restlessness, anxiety, incoherent speech, lightheadedness, numbness and tingling of the mouth and lips, metallic taste, tinnitus, dizziness, blurred vision, tremors, depression or drowsiness may be early warning signs of central nervous system toxicity.
Spinal anesthetics should be used with caution in patients with severe disturbances of cardiac rhythm, shock, or heart block.
Sympathetic blockade occurring during spinal anesthesia may result in peripheral vasodilation and hypotension, the extent depending on the number of dermatomes blocked. Blood pressure should, therefore, be carefully monitored especially in the early phases of anesthesia. Hypotension may be controlled by vasoconstrictors in dosages depending on the severity of hypotension and response of treatment. The level of anesthesia should be carefully monitored because it is not always controllable in spinal techniques.
Because amide-type 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. However, dosage recommendations for spinal anesthesia are much lower than dosage recommendations for other major blocks and most experience regarding hepatic and cardiovascular disease dose-related toxicity is derived from these other major blocks.
Serious dose-related cardiac arrhythmias may occur if preparations containing a vasoconstrictor such as epinephrine are employed in patients during or following the administrationof potent inhalation agents. 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.)
The following conditions may preclude the use of spinal anesthesia, depending upon the physician’s evaluation of the situation and ability to deal with the complications or complaints which may occur:
-
Pre-existing diseases of the central nervous system, such as those attributable to pernicious anemia, poliomyelitis, syphilis, or tumor.
-
Hematological disorders predisposing to coagulopathies or patients on anticoagulant therapy. Trauma to a blood vessel during the conduct of spinal anesthesia may, in some instances, result in uncontrollable central nervous system hemorrhage or soft tissue hemorrhage.
-
Chronic backache and preoperative headache.
-
Hypotension and hypertension.
-
Technical problems (persistent paresthesias, persistent bloody tap).
-
Arthritis or spinal deformity.
-
Extremes of age.
-
Psychosis or other causes of poor cooperation by the patient.
Information for Patients:
When appropriate, patients should be informed in advance that they may experience temporary loss of sensation and motor activity, usually in the lower half of the body, following proper administration of spinal anesthesia. Also, when appropriate, the physician should discuss other information including adverse reactions in the Bupivacaine Spinal (Bupivacaine in Dextrose Injection, USP) package insert.
Clinically Significant Drug Interactions:
The administration of local anesthetic solutions containing epinephrine or norepinephrine to patients receiving monoamine oxidase inhibitors or tricyclic antidepressants may produce severe, prolonged hypertension. Concurrent use of these agents should generally be avoided. In situations when concurrent therapy is necessary, careful patient monitoring is essential.
Concurrent administration of vasopressor drugs and of ergot-type oxytocic drugs may cause severe persistent hypertension or cerebrovascular accidents.
Phenothiazines and butyrophenones may reduce or reverse the pressor effect of epinephrine.
Carcinogenesis, Mutagenesis and Impairment of Fertility:
Long-term studies in animals of most local anesthetics including bupivacaine to evaluate the carcinogenic potential have not been conducted. Mutagenic potential or the effect on fertility have not been determined. There is no evidence from human data that Bupivacaine Spinal (Bupivacaine in Dextrose Injection, USP) may be carcinogenic or mutagenic or that it impairs fertility.
Pregnancy Category C:
Decreased pup survival in rats and an embryocidal effect in rabbits have been observed when bupivacaine hydrochloride was administered to these species in doses comparable to 230 and 130 times respectively the maximum recommended human spinal dose. There are no adequate and well-controlled studies in pregnant women of the effect of bupivacaine on the developing fetus. Bupivacaine hydrochloride should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. This does not exclude the use of Bupivacaine Spinal at term for obstetrical anesthesia. (See Labor and Delivery.)
Labor and Delivery:
Spinal anesthesia has a recognized use during labor and delivery. Bupivacaine hydrochloride, when administered properly, via the epidural route in doses 10 to 12 times the amount used in spinal anesthesia has been used for obstetrical analgesia and anesthesia without evidence of adverse effects on the fetus.
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.
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 the gravid uterus displaced to the left.
Spinal anesthesia may alter the forces of parturition through changes in uterine contractility or maternal expulsive efforts. Spinal anesthesia has also 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.
There have been reports of cardiac arrest during use of bupivacaine hydrochloride 0.75% solution for epidural anesthesia in obstetrical patients. The package insert for bupivacaine hydrochloride for epidural, nerve block, etc. has a more complete discussion of preparation for, and management of, this problem. These cases are compatible with systemic toxicity following unintended intravascular injection of the much larger dose recommended for epidural anesthesia and have not occurred within the dose range of bupivacaine hydrochloride 0.75% recommended for spinal anesthesia in obstetrics. The 0.75% concentration of bupivacaine hydrochloride is therefore not recommended for obstetrical epidural anesthesia. Bupivacaine Spinal (bupivacaine in dextrose injection, USP) is recommended for spinal anesthesia in obstetrics.
Nursing Mothers:
It is not known whether local anesthetic drugs are excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when local anesthetic drugs are administered to a nursing woman.
Pediatric Use:
Until further experience is gained in patients younger than 18 years, administration of Bupivacaine Spinal in this age group is not recommended.
|
