1986 ACEP Call for Abstracts

• Publisher: Elsevier Science
• Year: 1985
• Tongue: English
• Weight: 192 KB
• Volume: 14
• Category: Article
• ISSN: 1097-6760
• DOI: 10.1016/s0196-0644(85)80231-6

✦ Synopsis

~arcailll~ HCl (bupivacaine HCI injection, USP) ;' o' , ~e~;~:i ~2Vl ~oo. ooo Carcinogenesis, Mutagenesis, and Impairment of Fertility: Long-term studies in animals of most local anesthetics including bupivecaine have not been conducted. There is no evidence from human data that MARCAINE 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 was administered to either in doses comparable to 5 to 9 times the maximum recommended daily human dose (400 mg). There are no adequate and well-controlled studies in pregnant women of the drug's effect on fetal development, and potential fetal risk must be justified by potential benefit. This does not exclude use of MARCAINE at term for obstetric anesthesia or analgesia. (See Labor and Delivery.) Labor and Delivery: SEE BOXED WARNING REGARDING OBSTETRIC USE OF 0.75% MARCAINE, and its contraindication in obstetric paracervical block. Local anesthetics cross the placenta rapidly and, when used for epidural, caudal, or pudendal block, can cause varying degrees of maternal, fetal, and neonatal toxicity. (See Pharmacokinetics in CLINICAL PHARMACOLOGY) The incidence and degree of toxicity depend upon the procedure performed, and drug type, amount, and technique of administration. Adverse reactions in the parturient, fetus, and neonate involve alterations of the CNS, peripheral vascular tone, and cardiac function.

Maternal hypotenslon has resulted from regional anesthesia. Local anesthetics produce vasodilation by blocking sympathetic nerves. Elevating the patient's legs and leff-side positioning will help prevent decrease in blood pressure. Fetal heart rate should be monitored continuously, preferably electronically. Epidural, caudal, or pudendal anesthesia may alter parturition through changes in uterine contractility or maternal expulsive efforts. Epidural anesthesia has been reported to prolong second-stage labor by removing the parturient's reflex urge to bear down, or by interference with motor function. Use of obstetric anesthesia may increase need for forceps assistance, Some local anesthetic drugs may diminish muscle strength and tone for the first day or two of life. It is unreported with bupiveceine.

Of extreme importance: Avoid aortocaval compression of the gravid uterus during administration of regional block.To do this, maintain the parturient in the left lateral decu bitus position, or place a blanket roll or sandbag beneath the right hip to displace the gravid uterus away from the great vessels. Nursing Mothers: It is not known whether local anesthetics are excreted in human milk; because many drugs are, administer with caution. Pediatric Use: Without further experience in children under 12, MARCAINE is not recommended for this group. ADVERSE REACTIONS: A major cause of adverse reactions to amide-typa local anesthetics is excessive plasma levels, possibly due to overdosage, unintentional intravescular injection, or slow metabolic degradation. Systemic: The most common acute experiences, demanding immediate countermeasures, involve the CNS and cardiovascular systems. Adverse events are generally dose-related and due to high plasma levels which may result from overdossge, rapid absorption from the injection site, diminished tolerance, or unintentional intravascular injection of the solution. In addition to systemic dose-relsted toxicity, unintentional subarachnoid injection during performance of caudal or lumbar epidural block or nerve blocks near the vertebral column (especially in the head and neck region) may result in underventilation or apnea. Also, hypotension due to loss of sympathetic tone, and respiratory paralysis or underventilation due to cephaled extension of the motor level of anesthesia, may occur, leading to secondary cardiac arrest if untreated. Factors influencing plasma protein binding such as acidosis, systemic diseases which alter protein production or competition of other drugs for protein binding sites, may diminish individual tolerance. Central Nervous System: Excitation and/or depression, restlessness, anxiety, dizziness, tinnitus, blurred vision, or tremors may occur, possibly convulsions. Excitement may be transient, depression being the first manifestation of an adverse reaction. Drowsiness merging into unconsciousness and respiratory arrest may quickly follow. Other CNS effects may be nausea, vomiting, chills, pupillary constriction. Incidence of convulsions vedes with the procedure used and total dose administered, in studies of epidural anesthesia, overt toxicity progressing to convulsions occurred in approximately 0.1% of procedures. Cardiovascular: High doses of unintentional intravescular injection may lead to high plasma levels and related myocardial depression, decreased cardiac output, heart block, hypotenslon, bradycardia, ventricular arrhythmia including ventricular tachycardia and ventricular fibrillation, and cardiac arrest. (See WARNINGS, PRECAUTIONS, OVERDOSAGE.) Allergic: Rare, and may occur as a result of sensitivity to the local anesthetic or to other formulation ingredients such as the antimicrobial preservative methylparaben contained in multiple-dose vials or sulfites in epinephrine-containing solutions. Possible reactions: urticaria, pruritus, erytheme, angioneurotic edema (including laryngeal), tachycardia, sneezing, nausea, vomiting, dizziness, syncope, excessive sweating, elevated temperature, perhaps anephylactoid symptoms (including severe hypotension). Cross-sensitivity among members of the amide-typa anesthetic group reported; value of sensitivity screening is unestablished, Neurologte: Incidence of adverse reactions associated with use of such drugs may be related to the total dose administered, and dependent upon the particular drug used, route of administration, and the patient's physical status. Many effects may be related to technique, with or without the drug being contributory.

In performing caudal or lumbar epidural block, occasional unintentional penetration of the subarachnoid space by catheter or needle may occun Subsequent adverse effects may depend partially on the amount of drug administered intrathecally and physiologic and physical effects of dural puncture. High spinals are characterized by leg paralysis, loss of consciousness, respiratory paralysis, and bradycardia. Effects following epidural or caudal anesthesia may include: spinal block of varying magnitude (including high or total spinal block); hypotension secondary to spinal block; urinary retention; fecal and urinary incontinence; loss of perineal sensation and sexual function; persistent anesthesia, parasthesia, weakness, paralysis of the lower extremities, and loss of sphincter control-all of which may show slow, incomplete, or no recovery; headache; backache; septic meningitis; meningismus; slowing of labor; increased incidence of forceps delivery; cranial nerve palsies due to traction on nerves from loss of cerebrospinal fluid, OVERDOSAGE: Acute emergency during therapeutic local anesthesia is generally related to high plasma levels or unintended subarachnoid injection of the solution. (See ADVERSE REACTIONS, WARNINGS, PRECAUTIONS.)

The first consideration in management is prevention, best accomplished by careful, constant monitoring of cardiovascular and respiratory vital signs and the patient's state of consciousness after each injection~ At the first sign of change, administer oxygen. The first step in the management of systemic toxic reactions, as well as undetventilation or apnea due to unintentional subarachnoid injection of drug solution, consists of immediate attention to the establishment and maintenance of a patent airway and effective assisted or controlled ventilation with 100O/o oxygen with a delivery system capable of permitting immediate positive airwayprassura by mask, Endotracheal intubation may be indicated to meet the need for prolonged ventilator'/ support or if difficulty is encountered in the maintenance of e patent airway.

If necessary, use drugs to control convulsions. A 50-100 mg bolus LV. injection of succinylcholine will paralyze the patient (without CNS or cardiovascular depression) and facilitate ventilation. A 5-10 mg I,V, bolus of diazepam, or 50-100 mg of thiopantal, will permit ventilation and counteract CNS stimulation, but these drugs also depress CNS, respirstory and cardiac function, add to postictal depression, and may cause apnea. Intravenous barbiturates, anticonvulsent agents, or muscle relaxants should be administered only by those familiar with use. Immediately after institution of venitlatory measures, circulatory adequecy should be evaluated; supportive treatment may require administration of I.V. fluids and, when appropriate, a veseprsssor dictated by the clinical situation (eg, ephedrine or epinephrine to enhance myocardial contractile force).

Recent clinical data from patients experiencing convulsions induced by local anesthetics demonstrated rapid development of hypoxia, hyperoarbia, and acidosis; with bupivaceine, within a minute of onset. These observations suggest that O~ consumption and CO= production are greatly increased during the convulsions and emphasize the importance of immediate ventilation with oxygen; if not treated effectively, convulsions and their complications plus myocardial depression from direct effects of the local anesthetic may result in cardiac arrhythmiss, bradycardia, ssystole, ventricular fibrillation, or cardiac arrest. Respiratory abnormalities including apnee may occur; underventilation or apnea due to unintentional subarachnoid injection of the solution may also lead to these signs and cardiac arrest if ventilatory support is not instituted. If cardiac arrest occurs, prolonged resuscitative effort may determine a successful outcome.

In treating systemic toxicity, maternal hypotension, or fetal bradycerdia following regional block, avoid ecrtocavsl compression by the gravid uterus. The supine position is dangerous in pregnant women. The parturient should be maintained in the left lateral decubitus position if possible, or manual displacement of the uterus off the great vessels be aecomplished. (See Labor and Delivery in PRECAUTIONS.) Composition of Marcaine Solutions: 0.25%-each mL contains 2.5 mg bupivacaine; 0.5%-each mL contains 5 mg bupivacaine; O.75%-eech mL contains 7.5 mg bupivecaine. All concentrations contain NaCI for isotonicity in Water for Injection.

In multiple-dose vials, each mL also contains 1 mg methylparaben. With epinephrine, each mL also contains 0.0091 mg epinephrine bitartrate, 0.5 mg sodium bisulfite, 0.001 mL monothioglycerol, 2 mg ascorbic acid, 0.0017 mL 60% sodium lactate, and 0.1 mg edetate calcium disodium.