Risk Factor: BM
Class: Cardiovascular drugs/ Cardiac drugs
Fetal Risk Summary
Lidocaine is a local anesthetic that is also used for the treatment of cardiac ventricular arrhythmias. The majority of the information on the drug in pregnancy derives from its use as a local anesthetic during labor and delivery. Reproduction studies have revealed no evidence of fetal harm in pregnant rats at doses up to 6.6 times the human dose (1).
The drug rapidly crosses the placenta to the fetus, appearing in the fetal circulation within a few minutes after administration to the mother. Cord:maternal serum ratios range between 0.50 and 0.70 after IV and epidural anesthesia (2,3,4,5,6,7,8,9,10,11 and 12). In 25 women just before delivery, a dose of 23 mg/kg was given by IV infusion at a rate of 100 mg/minute (2). The mean cord:maternal serum ratio in 9 patients who received 3 mg/kg was 0.55. A mean ratio of 1.32 was observed in nonacidotic newborns following local infiltration of the perineum for episiotomy (13). A similarly elevated ratio was measured in an acidotic newborn (14). The infant had umbilical venous/arterial pH values of 7.23/7.08 and a lidocaine cord:maternal serum ratio of 1.32 following epidural anesthesia. Because lidocaine is a weak base, the high ratio may have been caused by ion trapping (14).
Both the fetus and the newborn are capable of metabolizing lidocaine (8,9). The elimination half-life of lidocaine in the newborn following maternal epidural anesthesia averaged 3 hours (8). After local perineal infiltration for episiotomy, lidocaine was found in neonatal urine for at least 48 hours after delivery (13).
A number of studies have examined the effect of lidocaine on the newborn. In one report, offspring of mothers receiving continuous lumbar epidural blocks had significantly lower scores on tests of muscle strength and tone than did controls (15). Results of other tests of neurobehavior did not differ from those of controls. In contrast, four other studies failed to find adverse effects on neonatal neurobehavior following lidocaine epidural administration (10,11 and 12,16). Continuous infusion epidural analgesia with lidocaine has been used without effect on the fetus or newborn (17).
Lidocaine may produce central nervous system depression in the newborn with high serum levels. Of eight infants with lidocaine levels greater than 2.5 g/mL, four had Apgar scores of 6 or less (3). Three infants with levels above 3.0 g/mL were mildly depressed at birth (3). A 1973 study observed fetal tachycardia (3 cases) and bradycardia (3 cases) after paracervical block with lidocaine in 12 laboring women (18). The authors were unable to determine whether these effects were a direct effect of the drug. Accidental direct injection into the fetal scalp during local infiltration for episiotomy led to apnea, hypotonia, and fixed, dilated pupils 15 minutes after birth in one infant (19). Lidocaine-induced seizures occurred at 1 hour. The lidocaine concentration in the infant’s serum at 2 hours was 14 g/mL. The heart rate was 180 bpm. Following successful treatment, physical and neurologic examinations at 3 days and again at 7 months were normal.
Lidocaine is the treatment of choice for ventricular arrhythmias (20,21). A 1984 report described the use of therapeutic lidocaine doses (100 mg IV injection followed by 4 mg/minute infusion) in a woman who was successfully resuscitated after a cardiac arrest at 18 weeks’ gestation (22). A normal infant was delivered at 38 weeks’ gestation. Neurologic development was normal at 17 months of age, but growth was below the 10th percentile.
The Collaborative Perinatal Project monitored 50,282 mother-child pairs, 293 of which had exposure to lidocaine during the 1st trimester (23, pp. 358363). No evidence of an association with large classes of malformations was found. Greater than expected risks were found for anomalies of the respiratory tract (3 cases), tumors (2 cases), and inguinal hernias (8 cases), but the statistical significance is unknown and independent confirmation is required (23, pp. 358363, 477). For use anytime during pregnancy, 947 exposures were recorded (23, pp. 440, 493). From these data, no evidence of an association with large categories of major or minor malformations or to individual defects was found.
Breast Feeding Summary
Small amounts of lidocaine are excreted into breast milk (24). A 37-year-old, lactating woman was treated with intravenous lidocaine for acute onset ventricular arrhythmia secondary to chronic mitral valve prolapse. The woman had been nursing her 10-month-old infant up to the time of treatment. She was treated with lidocaine, 75 mg over 1 minute, followed by a continuous infusion of 2 mg/minute (23 g/kg/minute). A second 50-mg dose was given 5 minutes after the first bolus dose. The woman’s serum lidocaine level 5 hours after initiation of therapy was 2 g/mL. The drug concentration in a milk sample, obtained 2 hours later when therapy was stopped, was 0.8 g/mL (40% of maternal serum). Although the infant was not allowed to nurse during and immediately following the mother’s therapy, the potential for harm of the infant from exposure to lidocaine in breast milk is probably very low. The American Academy of Pediatrics considers lidocaine to be compatible with breast feeding (25).
- Product information. Xylocaine. Astrazeneca, 2000.
- Shnider SM, Way EL. The kinetics of transfer of lidocaine (Xylocaine) across the human placenta. Anesthesiology 1968;29:94450.
- Shnider SM, Way EL. Plasma levels of lidocaine (Xylocaine) in mother and newborn following obstetrical conduction anesthesia: clinical applications. Anesthesiology 1968;29:9518.
- Lurie AO, Weiss JB. Blood concentrations of mepivacaine and lidocaine in mother and baby after epidural anesthesia. Am J Obstet Gynecol 1970;106:8506.
- Petrie RH, Paul WL, Miller FC, Arce JJ, Paul RH, Nakamura RM, Hon EH. Placental transfer of lidocaine following paracervical block. Am J Obstet Gynecol 1974;120:791801.
- Zador G, Lindmark G, Nilsson BA. Pudendal block in normal vaginal deliveries. Acta Obstet Gynecol Scand 1974;Suppl 34:5164.
- Blankenbaker WL, DiFazio CA, Berry FA Jr. Lidocaine and its metabolites in the newborn. Anesthesiology 1975;42:32530.
- Brown WU Jr, Bell GC, Lurie AO, Weiss JB, Scanlon JW, Alper MH. Newborn blood levels of lidocaine and mepivacaine in the first postnatal day following maternal epidural anesthesia. Anesthesiology 1975;42:698707.
- Kuhnert BR, Knapp DR, Kuhnert PM, Prochaska AL. Maternal, fetal, and neonatal metabolism of lidocaine. Clin Pharmacol Ther 1979;26:21320.
- Abboud TK, Sarkis F, Blikian A, Varakian L. Lack of adverse neurobehavioral effects of lidocaine. Anesthesiology 1982;57(Suppl):A404.
- Kileff M, James FM III, Dewan D, Floyd H, DiFazio C. Neonatal neurobehavioral responses after epidural anesthesia for cesarean section with lidocaine and bupivacaine. Anesthesiology 1982;57(Suppl):A403.
- Abboud TK, David S, Costandi J, Nagappala S, Haroutunian S, Yeh SY. Comparative maternal, fetal and neonatal effects of lidocaine versus lidocaine with epinephrine in the parturient. Anesthesiology 1984;61(Suppl):A405.
- Philipson EH, Kuhnert BR, Syracuse CD. Maternal, fetal, and neonatal lidocaine levels following local perineal infiltration. Am J Obstet Gynecol 1984;149:4037.
- Brown WU Jr, Bell GC, Alper MH. Acidosis, local anesthetics, and the newborn. Obstet Gynecol 1976;48:2730.
- Scanlon JW, Brown WU Jr, Weiss JB, Alper MH. Neurobehavioral responses of newborn infants after maternal epidural anesthesia. Anesthesiology 1974;40:1218.
- Abboud TK, Williams V, Miller F, Henriksen EH, Doan T, Van Dorsen JP, Earl S. Comparative fetal, maternal, and neonatal responses following epidural analgesia with bupivacaine, chloroprocaine, and lidocaine. Anesthesiology 1981;55(Suppl):A315.
- Chestnut DH, Bates JN, Choi WW. Continuous infusion epidural analgesia with lidocaine: efficacy and influence during the second stage of labor. Obstet Gynecol 1987;69:3237.
- Liston WA, Adjepon-Yamoah KK, Scott DB. Foetal and maternal lignocaine levels after paracervical block. Br J Anaesth 1973;45:7504.
- Kim WY, Pomerance JJ, Miller AA. Lidocaine intoxication in a newborn following local anesthesia for episiotomy. Pediatrics 1979;64:6435.
- Tamari I, Eldar M, Rabinowitz B, Neufeld HN. Medical treatment of cardiovascular disorders during pregnancy. Am Heart J 1982;104:135763.
- Rotmensch HH, Elkayam U, Frishman W. Antiarrhythmic drug therapy during pregnancy. Ann Intern Med 1983;98:48797.
- Stokes IM, Evans J, Stone M. Myocardial infarction and cardiac arrest in the second trimester followed by assisted vaginal delivery under epidural analgesia at 38 weeks gestation. Case report. Br J Obstet Gynaecol 1984;91:1978.
- Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA:Publishing Sciences Group, 1977.
- Zeisler JA, Gaarder TD, De Mesquita SA. Lidocaine excretion in breast milk. Drug Intell Clin Pharm 1986;20:6913.
- Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:13750.