Acta Aiiaesthesiol Scand 1992: 36: 722-727

Lidocaine hydrocarbonate and lidocaine hydrochloride for cesarean section: transplacental passage and neonatal effects J. GUAY'", P. GAUDREAULTZg3, A.

BOULANGER',

A. TANG', L.

LORTIE'

and c . DUPUI~"

Departments of 'Anesthesiology, 'Pediatrics and 'Biochemistry, 'Clinical Pharmacology and Toxicology Section, Ste-Justine Hospital, and 'Department of Anesthesiology, Hotcl-Dieu Hospital of Montreal and the University of Montreal, Canada

Twenty-six patients, ASA physical status I , scheduled for elective cesarean section, were divided at random into two groups and received via an epidural catheter 20 rnl of 2.2% lidocaine hydrocarbonate (1 7.3 mg . ml- I lidocaine base) with 5 pg. rnl-' epinephrine freshly added (Group CO,= 13 patients) or 20 ml of 2% lidocaine hydrochloride (17.3 mg. ml- lidocaine base) also with 5 pg . ml-' epinephrine freshly added. Following clampage of the umbilical cord (at 40.1 4.9 min after the injection of lidocaine for the CO, group and at 41 .Of 5.4 rnin for the HCI group), serum concentrations of lidocaine were measured both in the mother and in the umbilical vein. All newborns were examined by the same blinded pediatrician with Apgar scores at I , 5 and 10 min and with Neurobchavioral Adaptive Capacity Scores (NACS) at 15 min, 2 h and 24 h. The concentrations of lidocaine in the serum were comparable in both groups: in the mothers 8.6 I f I .48 p o l . I I for the CO, group vs 8.04 f 2.36 pmol. I - ' for the HCI group and in the newborns 3.86 f 0.84 pmol . 1.' for the CO, group vs 3.92 f 0.95 p o l . I-' for the HCI group. The ratio of umbilical vein to maternal vein concentrations of lidocaine was also similar in both groups: 0.45 f 0.07 for the CO, group vs 0.54 f 0.24 for the HCI group. The percentage of newborns with a normal NACS (score2 35/40) was cqual in both groups, i.e. 91% at 15 min and 2 h of life and 100% at 24 h of life. We conclude that both lidocaine solutions are similar with respect to their transplacental passage and their effects on the neonatal neurobehavioral performance, and that both are safe when used for cesarean section in normal term pregnancy since the majority of newborns (91%) had a normal NACS (score>35/40), even at the first evaluation at 15 min of life.

'

Receiued 27 September 1991, accepted f o r publication 4 March 1992

Kcy words: Anesthesia: obstetrics; anesthctic techniques: epidural; anesthetics, local: lidocaine hydrocarbonate, lidocaine hydrochloride; measurement techniques: Apgar, NACS.

Lidocaine is one of the most popular agents used for epidural anesthesia during cesarean section. Two solutions are presently available: lidocaine hydrocarbonate (lidocaine COP)and lidocaine hydrochloride (lidocaine HCI). The carbonated solution is more costly but has been said to have a more rapid onset (1). However, not all authors agree on this advantage (2, 3). Furthermore, the serum levels of lidocaine measured after an epidural injection of carbonated lidocaine seem to be higher than those found after an injection of lidocaine hydrochloride (4).Since lidocaine concentrations in the umbilical vein of the newborns arc directly proportional to the maternal concentrations, it is possible that with equal doses the serum concentrations in the umbilical vein obtained after an epidural injection of carbonated lidocaine might be higher than those obtained with lidocaine hydrochloride ( 5 ) . U p to now, no study has compared the

transplacental transfer of the two solutions of lidocaine when administered by epidural route at equivalent doses. The auditory evoked potentials study shows that neonates born by cesarean section under lidocaine epidural anesthesia have a prolongation of the wave (IV) interpeak interval compared to neonates born by normal vaginal delivery without local anesthesia (6). The prolongation of the wave (IV) interpeak interval found at 4 h of life is proportional to the ratio of umbilical cord arterial : venous blood lidocaine concentrations, and therefore to the body tissue concentration, but this effect disappears at 24 h of life (7). The impact of this auditory compromise on postnatal adaptation has not yet been clearly defined since to date the literature has reported conflicting results on the effects of lidocaine on the neurobehavioral asscssment (8-1 1). The Neurobehavioral Adaptive Capacity

LIDOCAINE HYDROCARBONATE VS LIDOCAINE HYDROCHLORIDE

Score (NACS score) has been specifically designed as a screening test to detect central nervous system depression caused by drugs and to distinguish it from that caused by perinatal asphyxia or birth trauma (12). To date, no study has compared the effects of lidocaine carbonated vs lidocaine hydrochloride on neonates using the NACS test. The aim of this study was to compare the two solutions of lidocaine during cesarean sections with respect to their passage through the placenta and their effects on the newborn using the NACS test. PATIENTS AND METHODS After obtaining approval from the hospital ethics committee and informed written consent from all patients, 26 patients, ASA physical status I, scheduled for elective cesarean section under epidural anesthesia, were divided at random into two groups. One group received 20 ml of a solution of 2.2% lidocaine CO, (17.3 mg. ml-' lidocaine base) with 5 pg.ml-' epinephrine freshly added (CO, group) and the other group received 20 ml of a solution of 2% lidocaine hydrochloride (17.3 mg.ml-' lidocaine base) also with 5 p g ' m l - ' epinephrine freshly added (HCI group). The patients were monitored with a cardioscope, a pulse oximeter and an automated oscillometric blood pressure device, and received an intravenous preload of 1 to 2 I of Ringer's lactate. All mothers received oxygen via a face mask before delivery of the infant. The fetal heart rate was measured before and after the epidural injection of lidocaine and during any hypotensive episode until the beginning of surgery. With the patients in the left lateral decubitus position, an epidural catheter was inserted at the L,, or L3.4 interspace. A 17-gauge Tuohy needle was used, employing 1 ml 0.25% bupivacaine for skin anesthesia, and a loss of resistance technique using normal saline to identify the epidural space. The patients were placed in the dorsal decubitus position with left uterine displacement, and the lidocaine was injected at the following rate: 3 ml of the solution administered at time zero as a test dose. Three minutes later, a dose of 5 ml was administered, which was repeated at 4 and at 5 min, and the last dose of 2 ml was injected at 6 min after time zero to complete the total dose of 20 ml. Every second minute after time zero a nurse, who was unaware of the solution used, determined the sensory level using an ice cube and a dented wheel. The intensity of motor block was assessed according to the Bromage scale from 1 to 4, the score I being given to patients unable to move their feet and the score 4 to patients able to move both hips and knees (13). In an effort to maintain an equal quantity of lidocaine in all patients, those in whom the T, level was not attained within 20 min were withdrawn from the study. Any hypotensive episode with a systolic blood pressure lower than 100 mmHg (13.3 kPa) was treated with a bolus of 500 ml of Ringer's lactate and ephedrine 5 to 10 mg iv. The times of cutaneous incision, uterine incision and delivery (clamping of the umbilical cord) were noted as well as the number of patients who needed intravenous narcotic supplementation. After clamping the umbilical cord, a 10-ml blood sample was taken from the maternal antecubital vein contralateral to the iv infusion and from the umbilical vein to determine lidocaine blood concentrations. These samples were sent to the laboratory on ice, centrifuged immediately and frozen at - 40°C.Plasma concentrations of lidocaine were measured by the fluorescence polarization immunoassay technique using the TDx system from AbbotP. Four specimens were measured in duplicate with the following results: 9.73 vs 9.76pmol~1~',5.05vs5.07pmol~1~', 3.65vs3.64pmol.l~'and3.97

723

vs 4.01 pmol.1-l. Interassay coefficients of variation were 5.3% at 6.4 pmol.Ikl (n=7), 2.0% at 12.8 pmol.l-' ( n = 5 ) and 2.8% at 32.0 pmol . I-' (n = 3). Blood gases from the umbilical vein were also measured. All the neonates were examined by the same pediatrician, who was blinded to the solution used, with Apgar scores at 1, 5 and 10 min and Neurobehavioural Adaptive Capacity Scores (NACS score) as described by Amiel-Tison at 15 min, 2 and 24 h (12). Data were analysed for statistical significance using an unpaired t-test (twotailed), the Mann-Whitney rank sum test (two-tailed) and Fisher's exact test (two-tailed), where appropriate. P < 0.05 was considered significant.

RESULTS Of the 26 patients studied, four were withdrawn from the study since the T, level was not attained within 20 min and they therefore required an extra dose of lidocaine: two patients from the COP group and two patients from the HCl group. The two groups of mothers were comparable as to age, weight and height. Also comparable were the intervals of lidocaine injection-cutaneous incision, incision-birth, latency of spread to bilateral S2-S, and T, sensory block and level of motor blockade (Table 1). Three patients in each group received ephedrine before the delivery and two patients in each group were given iv fentanyl after the umbilical cord was clamped because of insufficient analgesia. No fetal heart rate lower than 120 or higher than 180 beats per min was detected before the beginning of surgery in either group. When the umbilical cord was clamped, i.e. at 40.1 k 4.9 min after zero time for the COz group and at 41 .O f 5.4 rnin for the HCl group, there was no significant difference between the two groups in terms of lidocaine concentrations either in the mother (8.61 f 1.48 pmol * l - ' for the COz group Table 1 Comparison of general data for mothers. ~

CO, (n=ll) Age (years) Height (cm) Weight (kg) Time intervals (min) Injection-cutaneous incision Injection-delivery Bilateral block of S,-S, Bilateral block of T, Level of motor blockade (Bromage scale) Number of patients who needed narcotic supplementation (given after delivery) Iv fluids given before lidocaine injection (I) Number of patients with hypotension < 100 mmHg ( 1 3.3 kPa)

HCI (n=ll)

29.3 5 4.9 29.4 & 3.2 161.857.4 164.1 k6.9 74.82 12.0 71.62 17.2 28.9 f 4.3 40.1 k 4 . 9 7.7 5 1.8 12.2 f 5.2 2.2 f 0.8

30.1 f 5.2 41.025.4 8.5 2 2.7 15.5 f 2.2 1.9 t 0.9

2

2

1.9fO.2 3

1.750.4

3

Mean ( 5 s.d.). There was no significant statistical difference between the two groups for all values.

724

J. GUAY ET AL

Table 2 Comparison of newborns

co, Sex Gestational age (weeks) Weight (kg) Hysterotomy-birth (min) Umbilical venous pH Apgar scores > 7 (Yo) 1 min 5 min 10 rnin NACS >35 (%) 15 rnin

(n=ll)

HCI (n=ll)

3 F:8 M 38.2 ( k 0.8) 3.4 ( f 0.6) 2.27 (k 1 . 7 ) 7.35 ( k 0 . 0 3 )

5 F:6 M 38.4 ( f 0.8) 3.3 ( f 0.4) 2.18 (f1 . 1 ) 7.33 ( k 0 . 0 6 )

100 100 100

100

I00

91 91

I00

91 91 I00

8.61 ( k 1.48) 3.86 ( f 0.84) 0.45 (kO.07)

8.04 ( f 2.36) 3.92 ( f 0.95) 0.54 ( k 0 . 2 4 )

2h 24 h Iidocaine (pnol . I - ' ) Mother Umbilical vein Ratio UV/MV

91

Mean ( f s.d.).There was no significant statistical difference between the two groups for all values.

vs 8.04_+2.36 pmol.1-' for the HCI group), or in the

newborn: (3.86 _+ 0.84 pmol * 1-' for the CO, group vs 3.92k0.95 pmol.l-' for the HCl group), or in the ratio umbilical vein :maternal vein blood concentrations (0.45k 0.07 for the CO, group vs 0.54 f 0.24 for the HCl group) (Table 2 ) . The newborns were similar in the two groups for gestational age, weight, umbilical vein pH, Apgar score at 1, 5 and 10 min, and the NACS score at 15 min, 2 h and 24 h (Tables 2 and 3). Only one newborn scored less than 7 at 1 rnin of life (HCI Group) and received 100% oxygen with positive pressure by mask for 2 min. Each group had one newborn with a NACS score lower than 35 at 15 rnin and at 2 h of life. These two newborns had lidocaine concentrations of 3.05 (CO, group) and 1.89

pmol.1-' (HCl group), and their umbilical cord pH was 7.39 (CO, group) and 7.17 (HCl group). The number of newborns with an abnormal response to sound (score 1/2) was comparable in the two groups: i.e. two patients (19%) for the COY group vs four patients (37%) for the HC1 group at 15 rnin of life, one patient (loo/,) for the CO, group vs two patients (19Y0) for the HC1 group at 2 h of life and no patients for the CO, group vs one patient (10%) for the HCl group at 24 h of life. No patients in either group had a score of 012 for the response to sound at any of the studied times. DISCUSSION Lidocaine blood concentration3 In this study the maternal concentrations of lidocaine were comparable in the two groups, that is 8.61 f 1.48 pmol 1-' for the CO, group vs 8.04 k 2.36 pmol .1-' for the HCl group. These results are similar to the maternal blood concentrations of lidocaine obtained by Cole et al. in patients receiving lidocaine by the epidural route for cesarean sections, that is 9.8 + 2.5 pmol*l-' for the CO, group vs 10.3 1.7 pmo1.l-' for the HCl group (3). However, in their study the total doses of lidocaine were not maintained perfectly equal in the two groups. In the present study, we have maintained strictly equal injected doses of lidocaine in the two groups. It was impossible to reproduce the results of Martin et al., who reported with multiple samplings that the serum concentrations of lidocaine obtained after an epidural injection of 15 ml of a 2% solution of lidocaine CO, were higher than those obtained with an injection of the same amount of an equivalent concentration of a solution of lidocaine HCI. For example, in their study, the serum concentrations measured 5 rnin after the injection were 10.9 k 1 . 1 pmol. 1- I

Table 3 Comparison of newborns for neurobehavioral adaptive capacity scores at 15 min. 2 h and 24 h. 15 rnin

co2

NACS test Adaptive capacity Response to sound Habituation to sound Response to light Habituation to light Consolability Passive tone Active tone Primary reflexes General assessment Total score

9 2 2 2 2 2 8 9 6 6 37

(7-10) (1-2) (1-2)

(1-2) (1-2) (2-2) (8-8) (7-10) (54) (64)

(34-40)

2h

24 h

HCI 9 (7-10) 2 (1-2) 2 (1-2) 2 (2-2) 2 (1-2) 2 (2-2) 8 (5-8) 9 (7-10) 6 (5-6) 6 (6-6) 38 (32-39)

HCl 10 2 2 2 2

2 8 9 6 6 39

(8-10) (1-2) (1-2) (2-2) (1-2) (2-2) (8-8) (7-10) (5-6) (6-6) (34-40)

9 2 2 2 2 2 8 9 6 6 38

(8-10) (1-2) (1-2) (2-2) (1-2) (1-2) (6-8) (7-10) (5-6) (6-6) (32-40)

Median (range). There was no significant statistical difference between the two groups for all values.

CO, 10 (9-10) 2 (2-2) 2 (2-2) 2 (2-2) 2 (1-2) 2 (2-2) 8 (8-8) 9 (8-10) 6 (4-6) 6 (6-6) 39 (36-40)

HCI 10 (9-10) 2 (1-2) 2 (2-2) 2 (2-2) 2 (2-2) 2 (2-2) 8 (8-8) 10 (9-10) 6 (5-6) 6 (6-6) 39 ( 3 8 4 0 )

LIDOCAINE HYDROCARBONATE VS LIDOCAINE HYDROCHLORIDE

for lidocaine CO, and 8.4 f 1.1 pmol-l-' for lidocaine HCl (2). Several factors might explain the discrepancy between our results and those of Martin et al. First Martin et al. sampled from the arteries while we sampled from veins. Secondly, the differences in serum concentrations observed by Martin et al. were more important during the first 30 min following the injection, while we studied the serum concentrations at the moment of birth which was approximately 40 min after time zero. Finally the populations studied were different, ours being pregnant women. It is possible that the physiological changes caused by the pregnancy modified the absorption of lidocaine in the epidural space. No significant differences were found between the two groups either in the concentrations of lidocaine in the umbilical vein (3.86 f 0.84 pmol 1-' for the CO, group vs 3.92 f 0.95 pmol .1-' for the HCl group), or in the ratio umbilical vein : maternal vein (0.45 0.07 for the C 0 2 group vs 0.54 f 0.24 for the HCl group). Therefore, there is no evidence that the addition of C 0 2 increases the concentrations of lidocaine in the fetal body tissues, at least not at the moment of birth which in this study occurred approximately 40 min after the onset of the lidocaine injection.

Neurobehavioral examination There is no proof that a change in the neurobehavioral performance of the newborn caused by the secondary effects ofmedication taken by the mother will have longterm consequences. Nevertheless, the Committee on drugs of the American Academy of pediatrics recommends the choice of an anesthetic or analgesic agent that, while equal in efficacy will have the least effect on the neonate as determined by neurobehavioral testing (14). Many authors believe the mother-child interaction during the first minutes is crucial for the future development of maternal-infant bonding (1 5). Indeed, inconsolability or excessive sleepiness may impair successful establishment of breast-feeding or might induce negative feelings in the mother toward her child (15). The effects of lidocaine on the neurobehavioral response are controversial. In a study published in 1974, Scanlon et al. reported, using the Early Neonatal Neurobehavioral Scale (ENNS), that neonates born to mothers receiving lidocaine or mepivacaine by the epidural route during labor had diminished muscular strength and tone during the 8 h following their birth (8).Nevertheless, in that study approximately one third ofthe patients had received not only a local anesthetic but also a narcotic or barbiturate. Kuhnert et al. reported that an assessment done with the Brazelton Neonatal Behavioral Assessment Scale (BNBAS) within 5 h of life shows that newborns of mothers who received lidocaine for vaginal delivery or cesarean section had diminished muscular

725

tone compared to those born of mothers receiving chloroprocaine (1 1). In that study, an inverse correlation existed between the lidocaine concentration and the performance of the BNBAS. These authors nevertheless concluded that the correlation between the lidocaine concentration and BNBAS was very subtle and more feeble compared to the correlation of the BNBAS and the other aspects surrounding birth, such as the route of delivery, with cesarean section infants receiving either drug performing significantly better than their vaginally delivered counterparts. O n the contrary, Abboud et al. reported that the assessments done with the ENNS at 2 h and 4 h of life on neonates whose mothers had received lidocaine 1.5% by the epidural route during labor were comparable to children born to mothers receiving no analgesic (9). Unfortunately, that study did not include an assessment immediately after birth, that is within 2 h of life, thus possibly missing transitory effects. The Neurobehavioral Adaptive Capacity Score (NACS) was specifically designed as a screening test to detect central nervous system depression caused by drugs and to distinguish it from that caused by perinatal asphyxia or birth trauma (12). By insisting more on the active muscular tone, its discriminating power might be more valuable than that of ENNS (1 5). The system of points in the NACS allows for a total score, which in turn facilitates statistical comparisons ( 15). Twenty criteria are tested and scored as 0, 1 or 2, encompassing five general areas: adaptive capacity, passive tone, active tone, primary reflexes and alertness. Tests of adaptive capacity include the response to sound, habituation to sound, response to light, habituation to light and consolability (Table 3). The NACS test is highly reproducible, as shown by an interobserver reliability of 92.8% (12). To date, very few authors have used the NACS test to examine the effects of lidocaine on infants born by cesarean section (16, 17). Abboud et al. reported that 93% of neonates born to mothers who received epidural anesthesia had a normal NACS score (>35/40) (16). However, their group was made up of mothers receiving either lidocaine or chloroprocaine (16). Brose & Cohen reported that neonates born to mothers who received epidural lidocaine with varying concentrations of epinephrine had mean NACS scores from 33 1 to 35 f 1 and normal active and passive tone (17). The exact number of patients with normal NACS score ( 2 35/40) in their study was not specified ( 1 7). In this study, the two groups of newborns were comparable for the NACS scores at each studied time and 91 Yo of newborns had a normal score ( > 35/40),even at 15 min after birth (Tables 2 and 3). Thus, we conclude that both solutions are similar with respect to their effects on the adaptive capacity of the newborn. Furthermore, we

726

J. GUAY ET AL.

believe that the effects of lidocaine on the neurobehavioral assessment are probably minimal and do not impair the newborn’s adaptive capacity. I n this study, which involved solely patients in good health, undergoing an elective cesarean section, without any detectable signs of fetal distress prior to surgery and who received no other substances prior to delivery except for the local anesthetic, the majority of neonates, i.e. 91% (20/22) had a perfectly normal score ( 2 35/40), even at the first evaluation at 15 min of life. The percentage of newborns with a normal score (235/40) found in this study appears relatively high when compared to a simultaneously conducted study in patients in good health undergoing elective cesarean section under general anesthesia, In this study where the newborns were examined by the same blinded pediatrician, the percentage of newborns with a normal score ( >, 35/40) at 15 min of life was only 83% (l5/18) in a group of mothers rcceiving d-tubocurarine 0.3 mg . kg-’ and 55% (1 1/ 20) in a group receiving atracurium 0.3 mg kg-’ (18). I n a similar study, Daily et al. reported that the percentage of newborns with a normal score (235/40) at 15 min oflife was 73% (8/11)and 29% (2/7) for newborns whose mothers had received either vecuronium 0.04 mg. kg-’ or pancuronium 0.04 mg. kg-’, respectively (19). Furthermore, a study published by Stefani et al. shows that the percentage of newborns with a normal score ( 2 3 5 / 4 0 ) at 15 rnin of life varied from 75.5 to 78.4% for neonates born by vaginal delivery to mothers who had been given iv narcotics and/or nitrous oxide or enflurane plus a local anesthetic for local infiltration or pudendal block (20). Finally, in their study, Abboud et al. reported that the percentage of newborns with a normal score ( 235/40) at 15 rnin of life was 78% for newborns from mothers who received spinal tetracaine and 93% for those whose mothers received epidural lidocaine or chloroprocaine during a cesarean section ( 1 6). Our present study did not include a control group without lidocaine but according to our results, neonates born to mothers receiving lidocaine have a perccntage of normal score ( 2 35/40) at 15 rnin of life greater than or cqual to those previously described with other forms of analgesic or anesthetic agents, that is 91% (20/22) compared to 29% to 93% ( 16, 18-20). According to some authors, lidocaine interferes with the neuronal transmission of sound (21, 22). Recently Diaz et al. and Bozynski et al. were able to demonstrate that newborns whose mothers had received lidocaine by the epidural route had an alteration of auditory brain-stem evoked potentials (prolonged IV interpeak) in proportion to the estimated body tissue concentration of lidocaine in the newborn (ratio of umbilical cord blood arterial : venous lidocaine) (6, 7). These authors nevertheless concluded that the effect of these

auditory changes on the post-natal adaptation was yet to be determined. In our study no patient was found with an absence of response to sound and the percentage of patients showing a partially abnormal response (score 1/2) was low even during the first evaluation at 15 min of life, and similar in the two groups, that is 37% for Group C 0 2 and 19% for Group HCI. We conclude that both solutions of lidocainc are similar with respect to their clinically apparent effects on hearing. Furthermore, these effects do not seem to disturb the post-natal adaptive capacity nor the mother-infant interaction capacity, since not one child prcsented an absence of response to sound and the majority of newborns (91%) had a total score in the normal range ( 2 35/40), even at the first evaluation at 15 rnin of life. The lack of adverse effects of lidocaine on the neonates that we have found is in agreement with the results of Loftus et al. who reported no changes in fetal heart rate after epidural lidocaine administercd for elective cesarean section (23). Howcver, as these results were obtained from normal term pregnancy, it would be wise not to extend our conclusions to the asphyxiated fetus. Animal data suggest that the transplacental passage of lidocaine is increascd in the acidotic fetus and that the asphyxiated preterm fetus loses its cardiovascular adaptation to asphyxia when exposed to clinically acceptable plasma concentrations of lidocaine (24, 25). The effects of lidocaine in the human asphyxiated fetus are still unknown and therefore its use cannot be recommcnded in such circumstances. This study demonstrates that there is no difference between lidocaine carbonated and lidocaine hydrochloride with respect to their transplacental passagc and their effects on the neurobehavioral assessment. Furthermore, both solutions arc safe when used for a cesarean section in a normal-term pregnancy, since the majority of newborns (91%) have a normal NACS (score 235/40), even at the first evaluation at 15 min of life.

ACKNOWLEDGEMENTS The authors wish to thank Mrs Rachelle Mayrand for help i n rollecting data, Dr Victor Faria Blanc for his help in statistical analysis, Dr Margaret Haig for her editorial assistance and all the members of the Department of Anaesthesia at Ste-Justine Hospital for their collaboration and support. Presented at the Annual Meeting of the Canadian Anaesthetist’s Society in Quebec, June 1991.

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LIDOCAINE HYDROCARBONATE VS LIDOCAINE HYDROCHLORIDE

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15. Cohen S E. Evaluation of the neonate. In: Shnider S M, Levinson G L eds. Anesthesia for obstetrics, 2nd ed. Baltimore: Williams and Wilkins, 1987: 48%507. 16. Abboud T K, Nagappala S, Murakawa K, et al. Comparison of the effects of general and regional anesthesia for cesarean section on neonatal neurologic and adaptive capacity scores. Ancsth Analg 1985: 64: 9961000. 17. Brose W G, Cohen S. Epidural lidocaine for cesarean section: effect of varying epinephrine concentration. Anesthesiology 1988: 69: 936-940. 18. Perrault C, Guay J, Gaudreault P, Cyrenne L, Varin F. Residual curarisation after caesarean section. Can J Anacsth 1991: 38: 587-59 1. 19. Dailey P A, Fisher D M, Shnider S M, et al. Pharmacokinetics, placental transfer, and neonatal effects of vecuronium and pancuronium administered during cesarean section. Anesthesiology 1984: 60: 569-574. 20. Stefani S J, Hughes S C, Shnider S M, et al. Neonatal neurobehavioral effects of inhalation analgesia for vaginal delivery. Anesthesiology 1982: 56: 351-355. 21. Javel E, Mouney D F, McGee J, Walsh E J. Auditory brainstem responses during systemic infusion of lidocaine. Arch Otolaryngol 1982: 108 71-76. 22. Ruth R, Gral T J, DiFazio C Z, Mosicki J C. Brain-stem auditory-evoked potentials during lidocaine infusion in humans. Arch Otolaryngol 1985: 111: 799-802. 23. Loftus JR, Holbrook R H, Cohen S E. Fetal heart rate after epidural lidocaine and bupivacaine for elective cesarean section. Anesthesiology 1991: 75: 406-412. 24. Biehl D, Shnider S M, Levinson G, Callender K. Placental transfer of lidocaine: effects of acidosis. Anesthesiology 1978: 48: 409-41 2. 25. Morishima H 0, Pederson H, Santos A C, et al. Adverse effects of maternally administered lidocaine on the asphyxiated preterm fetal lamb. Anesthesiology 1989: 71: 110-1 15. Address: Dr. Joanne Guny Department of Anesthesia Ste-Justine Hospital 3175 Cote Ste-Catherine Road Montreal, Que. Canada H3T 1C5