Gas 32#2 200

Journal of Pediatric Gastroenterology and Nutrition
32:142–144 February 2001 Lippincott Williams & Wilkins, Inc., Philadelphia
Could Local Anesthesia While Breast-Feeding Be *Michele Giuliani, †Giovanni Battista Grossi, ‡Mauro Pileri, *Carlo Lajolo, and *School of Dentistry, Catholic University of Rome; and the Departments of †Dental and ‡Clinical Chemistry, IRCCS “Casa Sollievo della Sofferenza,” San Giovanni Rotondo (FG), Italy. ABSTRACT
concentration in maternal milk ranged from 120.5 ± 54.1 ␮g/L Background: Few studies have been carried out on the levels
(3 hours after injection) to 58.3 ± 22.8 ␮g/L (6 hours after and possible toxicity of local anesthetics in breast milk after injection), the MEGX concentration in maternal plasma 2 hours parenteral administration. The purpose of this study is to de- after injection was 58.9 ± 30.3 ␮g/L, and the MEGX concen- termine the amount of lidocaine and its metabolite monoethyl- tration in maternal milk ranged from 97.5 ± 39.6 ␮g/L (3 hours glycinexylidide (MEGX) in breast milk after local anesthesia after injection) to 52.7 ± 23.8 ␮g/L (6 hours after injection).
According to these data and considering an intake of 90 mL Methods: The study population consisted of seven nursing
breast milk every 3 hours, the daily infant dosages of lidocaine mothers (age, 23–39 years) who received 3.6 to 7.2 mL 2% and MEGX were 73.41± 38.94 ␮g/L/day and 66.1 ± 28.5 ␮g/ lidocaine without adrenaline. Blood and milk concentrations of lidocaine and its metabolite MEGX were assayed using high- Conclusions: This study suggests that even if a nursing mother
performance liquid chromatography. The milk-to-plasma ratio undergoes dental treatment with local anesthesia using lido- and the possible daily doses in infants for both lidocaine and caine without adrenaline, she can safely continue breast- feeding. JPGN 32:142–144, 2001. Key Words: Lidocaine—
Results: The lidocaine concentration in maternal plasma 2
Monoethylglycinexylidide—Breast-feeding—Local anesthe- hours after injection was 347.6 ± 221.8 ␮g/L, the lidocaine sia. 2001 Lippincott Williams & Wilkins, Inc.
In recent years, many investigators have been inter- MATERIALS AND METHODS
ested in the risk–benefit ratios for administrating drugsduring puerperium (1–4). Breast-feeding is strongly rec- Patients
ommended by pediatricians, and the age for weaning The study population consisted of seven healthy, nursing usually varies from 4 to 8 months but may be 18 to 24 mothers (age range, 23–39 years) who needed local anesthetic months or even more in less developed countries. Even for dental treatment. Written informed consent was obtained though several studies have shown that many antibiotic from each woman before she underwent the procedure. Six and analgesic drugs are not contraindicated for women women received 3.6 mL of an injection of 2% lidocaine without who are breast-feeding, the literature provides little in- adrenaline, and one woman received 4.5 mL 2% lidocaine formation on the levels of local anesthetics in breast milk without adrenaline on the first occasion and, 3 months later, 7.2 after parenteral administration (5–10). Local anesthetics mL 2% lidocaine without adrenaline. The patients were advised used in dentistry have not been studied sufficiently re- to discard their milk for 36 hours after the injection of lidocaine garding either their concentration in breast milk or their to allow complete elimination of the drug in the maternal sys-tem.
possible toxicity for the newborn (11). The aim of thisstudy was to determine the amount of lidocaine and its Assay Procedures
metabolite monoethylglycinexylidide (MEGX) in breastmilk after dental anesthesia.
Two-milliliter blood samples were drawn into heparinized syringes from a maternal vein 2 hours after the injection oflidocaine, and two milk samples were collected 3 and 6 hours Received March 17, 2000; accepted October 18, 2000.
after the injection. The concentrations of lidocaine and its pri- Address correspondence and reprint requests to Dr. Michele mary metabolite MEGX were assayed using high-performance Giuliani, School of Dentistry, Largo A. Gemelli, 8, 00168 Rome, Italy.
LOCAL ANESTHESIA IN DENTISTRY WHILE BREAST-FEEDING The high-performance liquid chromatographic system con- injection was 120.5 ± 54.1 ␮g/L (LDM1), the lidocaine sisted of a Cromath 3 CDM (Biorad, Segrate, Milan, Italy) and concentration in maternal milk 6 hours after injection a column (300 × 4-mm internal diameter; ␮-Bondapak Phenyl, was 58.3 ± 22.8 ␮g/L (LDM2), the MEGX concentration Waters Associates, Australia). Lidocaine and MEGX were sup- in maternal plasma 2 hours after injection was 58.9 ± plied by Astra Pharmaceuticals (Rydalmere B.C., Sodertalje, 30.3 ␮g/L (MEGXP), the MEGX concentration in ma- Sweden). Stock drug standards were dissolved in absolute etha- ternal milk 3 hours after injection was 97.5 ± 39.6 ␮g/L nol to give concentrations of MEGX at 2 g/L and of lidocaineat 5g/L. A working solution was prepared by diluting these (MEGXM1), the MEGX concentration in maternal milk 6 standards as follows: MEGX, 0.250 mL, and lidocaine, 0.250 hours after injection was 52.7 ± 23.8 ␮g/L (MEGXM2), mL to 100 mL, with distilled water. The internal standard was the lidocaine milk-to-plasma ratio was 0.38 ± 0.09 ␮g/L, a 1:200 solution of mexiletine (Mexitil; Boeringher, Milan, and the MEGX milk-to-plasma ratio was 1.61 ± 0.48 Italy) in distilled water. The extracting solvent was hexane:eth- ␮g/L. All measures were calculated using plasma and ylacetate:methanol (60:40:0.4) (11).
milk samples taken 2 and 3 hours respectively after in- Standard calibration samples were prepared by adding 10 ␮L lidocaine working solution and 20 ␮L MEGX working solution Assuming an infant intake of 90 mL breast milk every to 1.0 mL blank plasma or milk. To 1.0 mL plasma or milk 3 hours, the daily infant dosages of lidocaine and MEGX were added 1) 20 ␮L mexiletine (1:200) internal standard, 2) were 73.41 ± 38.94 ␮g/L/day and 66.1 ± 28.5 ␮g/L/day 100 ␮L 1 mol NaOH, and 3) 10.0 mL extracting solvent. Themixture was shaken vigorously for 5 minutes and then centri- respectively (10). The mean ± standard deviation and fuged at 1,300 g for 10 minutes. A 9.0-mL aliquot of the range of all parameters are shown in Table 1. The dif- organic phase was transferred to a second glass tube, reex- ferences between LDM1 versus LDM2, and MEGXM1 ver- tracted into 0.2 mL 0.1 mol HCl by gentle shaking, and then sus MEGXM2 were significant (P ס 0.008) and not sig- centrifuged. The organic phase was aspirated, and the acid nificant (P ס 0.0078) respectively. The differences be- extract was placed in a water bath at 50°C for 5 minutes to tween LDM1 versus LDP, and MEGXM1 versus MEGXP remove the last traces of solvent. Aliquots were then injected were significant (P ס 0.002 and P ס 0.046 respec- onto the high-performance lipid chromatographic column.
• Lidocaine concentrations in maternal plasma 2 hours DISCUSSION
• Lidocaine concentrations in maternal milk 3 hours af- As our data show, the amount of lidocaine seems to be very small, given the poor systemic bioavailability of the • Lidocaine concentrations in maternal milk 6 hours af- drug along with its short half-life, and considering that an infant can tolerate much higher doses of lidocaine (16).
• MEGX concentrations in maternal plasma 2 hours af- In addition, a clinically important aspect must be con- • MEGX concentrations in maternal milk 3 hours after TABLE 1. Maternal and neonatal data
• MEGX concentrations in maternal milk 6 hours after • Milk-to-plasma ratio for lidocaine and MEGX (using the milk sample taken 3 hours after injection) • Possible daily doses of lidocaine and MEGX that an infant might assume consuming 90 mL breast milk Statistical Analysis
The mean ± standard deviation and range of all parameters were measured. The Shapiro Wilk’s normality test was per- formed to verify distributions. Nonparametric rank signed and rank tests for paired and unmatched data were performed whenappropriate.
Data are mean ± SD.
LDP, lidocaine concentrations in maternal plasma 2 hr after injec- tion; LDM1, lidocaine concentrations in maternal milk 3 hr after injec- tion; LDM2, lidocaine concentrations in maternal milk 6 hr after injec-tion; MEGXP, MEGX concentrations in maternal plasma 2 hr after The lidocaine concentration in maternal plasma 2 injection; MEGXM1, MEGX concentrations in maternal milk 3 hr afterinjection; MEGXM2, MEGX concentrations in maternal milk 6 hr after hours after injection was 347.6 ± 221.8 ␮g/L (LDP), the injection; M/P, milk/plasma ratio for lidocaine and MEGX calculated lidocaine concentration in maternal milk 3 hours after using the milk sample taken 3 hr after injection.
J Pediatr Gastroenterol Nutr, Vol. 32, No. 2, February 2001 sidered: these anesthetic agents are used on a single-dose 6. Bond GM, Holloway AM. Anaesthesia and breast-feeding: the basis, thus preventing their accumulation in maternal effect on mother and infant. Anaesth Intensive Care 1992;20: 7. Kanto J. Risk–benefit assessment of anaesthetic agents in the pu- The current study suggests that an infant may safely erperium. Drug Saf 1991;6:285–301.
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additives (e.g., methylparaben or sulfite) often used with 10. Zeisler JA, Gaarder TD, De Mesquita SA. Lidocaine excretion in local anesthetics (17,18), it may be advisable to use local breast milk. Drug Intell Clin Pharm 1986;20:691–3.
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12. Chen Y, Potter JM. Fluorescence polarization immunoassay and Acknowledgment: The authors thank Prof Carlo Mario Mi-
HPLC assays compared for measuring monoethylglycinexylidide ani, Dean of the School of Dentistry of Catholic University of in liver-transplant patients. Clin Chem 1992;38:2426–30.
Rome, for his useful suggestions, and Astra Pharmaceuticals 13. Chen Y, Potter JM, Ravenscroft PJ. A quick, sensitive high- for supplying the pure lidocaine and MEGX.
performance liquid chromatography assay for monoethylglycinex-ylidide and lignocaine in serum/plasma using solid-phase extrac-tion. Ther Drug Monit 1992;14:317–21.
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J Pediatr Gastroenterol Nutr, Vol. 32, No. 2, February 2001

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