2-Chloroprocaine for local perineal infiltration

Elliot H. Philipson, M.D., Betty R. Kuhnert, Ph.D., and Carol D. Syracuse, B.S.

Cleveland, Ohio

Lidocaine was recently found to rapidly cross the placenta and result in considerable fetal exposure after local infiltration of the perineum for episiotomy. For this reason, a more appropriate agent for local perineal infiltration might be a drug with rapid metabolism and inactive metabolites. 2-Chloroprocaine, an ester-linked local anesthetic agent, is available but is not commonly used for this procedure. The purpose of this study was to evaluate the placental transfer of 2-chloroprocaine after local perineal infiltration. The drug was administered to 17 normal term pregnant women for episiotomy. After local perineal infiltration, the levels of 2-chloroprocaine and/or its metabolite, chloroaminobenzoic acid, were quantitated in maternal and neonatal plasma or urine. The pharmacologic data indicated that 2-chloroprocaine was nondetectable at delivery in maternal and umbilical cord vein; one patient had trace levels in the cord. Chloroprocaine was not detectable in neonatal plasma, but chloroaminobenzoic acid was detectable in both maternal and cord vein plasma. Mean levels of chloroaminobenzoic acid in maternal plasma at delivery were 1.04 ± 0.32 J-Lg/ml, and mean levels in cord vein were 0.35 ± 0.54 J-Lg/ml. Clinically, 2-chloroprocaine provided good analgesia. These results indicate that very little, if any pharmacologically active drug, reaches the fetus after local perineal infiltration with 2-chloroprocaine. Therefore 2-chloroprocaine appears to be preferable to lidocaine when used for local perineal infiltration. (AM J OssTET GYNECOL

1987;157:1275-8.)

Key words: 2-Chloroprocaine, perineal infiltration, chloroaminobenzoic acid

Local infiltration of the perineum is a commonly per­formed procedure used to provide analgesia for episi­otomy. The most commonly used local anesthetic agent for this purpose has been lidocaine. Since small quan­tities of lidocaine were used and administration oc­curred very close to delivery, it was assumed that very little drug would reach the fetus. However, in a recent study, lidocaine was found to rapidly cross the placenta with considerable drug levels in the umbilical cord vein at delivery.' Furthermore, the rapid placental transfer of lidocaine resulted in a mean fetal-maternal ratio sig­nificantly higher than that found with much larger doses of lidocaine for lumbar epidural anesthesia.

Thus lidocaine crosses the placenta in considerable amounts after local perineal infiltration. Further­more, lidocaine is metabolized slowly in the liver into two pharmacologically active metabolites. Therefore other local anesthetic agents may be more appropri­ate for local perineal infiltration. One possibility is 2-chloroprocaine, an ester-linked local anesthetic agent that is rapidly metabolized by plasma enzymes into in­active metabolites.

From the Perinatal Clinical Research Center, Cleveland Metropolitan General Hospital, and Case Western Reserve University.

Supported in part by U.S. Public Health Service Perinatal Clinical Research Center Grant No. M01-RR00210.

Received for publication January 8, 1987; revised May 4, 1987; accepted june 3, 1987.

Reprint requests: Elliot H. Philipson, M.D., Department of Obstetrics and Gynecology, Cleveland Metropolitan General Hospital, 3395 Scranton Road, Cleveland, Ohio 44109.

The purpose of this study was to determine (1) the disposition of 2-chloroprocaine and its metabo­lite, 2-chloroaminobenzoic acid, in mother, fetus, and neonate after local perineal infiltration and (2) if 2-chloroprocaine provides adequate pain relief.

Material and methods

Patients. Seventeen normal gravida at term from the obstetric service at Cleveland Metropolitan Gen­eral/Highland View Hospital were studied. Informed consent for sample collection was obtained in early labor. Local infiltration of the perineum with 1% 2-chloroprocaine was administered as needed for epi­siotomy. No patients had a history of liver or kidney disease or of known drug abuse.

Procedure. Local perineal infiltration was performed with a 22-gauge needle. 2-Chloroprocaine without epi­nephrine was injected superficially into the area of the posterior fourchette during the crowning phase of the second stage of labor. The drug was injected as needed, and the amount injected was determined by the physician. The total dose of 2-chloroprocaine (mil­ligrams) and the time (minutes) from administration to delivery (the drug-to-delivery interval) were recorded.

Sample collection. Maternal blood samples (3 ml) were collected from an indwelling cannula in a periph­eral arm vein. After a premedication blood sample was obtained, blood samples were collected after local perineal infiltration at 1, 3, 5, 7, 10, 20, and 30 minutes or until delivery, at which time the final sample was drawn. Postpartum maternal blood samples were

1275

1276 Philipson, Kuhnert, and Syracuse

4.0

2.0 ...... ~ E ..... Cl

1.0 :I .... c .8 0 :;::

.6 CIS .. -c Q) () .4 c 0 0

.2

2 6 10 14 Time (min)

Fig. I. Maternal plasma concentration of chloroaminoben­zoic acid after local perineal infiltration with 8 ml of 1% 2-chloroprocaine (80 mg). (C. V. = Cord vein; DEL = de­livery.)

obtained at 24, 48, and 72 hours after delivery. All samples were immediately put into heparinized Vacu­tainers and placed on ice. Samples to be analyzed for 2-chloroprocaine and chloroaminobenzoic acid levels were collected in Vacutainers containing 0.3 ml of a cho­linesterase inhibitor, echothiophate iodide, 0.2 gm/ml (Ayerst Laboratories, New York, New York); samples analyzed for cholinesterase activity were obtained in Vacutainers without the inhibitor. The plasma was re­moved after centrifugation and frozen until assayed.

Neonatal blood samples were obtained at birth from a doubly clamped section of umbilical cord and at 24, 48, and 72 hours of age by either heel stick or venipuncture. Neonatal urine samples were collected in plastic urine collection bags (Hollister Newborn U-Bag, Libertyville, Illinois). Collection of six consec­utive 6-hour samples was attempted, but collections were stopped if signs of skin irritation occurred. All urine samples were frozen until analyzed.

Specimen analysis. Plasma levels of 2-chloropro­caine were analyzed by single ion-monitoring gas chro­matography and mass spectrometry.2 The sensitivity of this method is 1 ng/ml of plasma. Plasma and urine levels of chloroaminobenzoic acid were analyzed by gas chromatography with a modification of a previously reported method." The modifications included use of an electron capture detector for increased specificity and use of diiodoaminobenzoic acid as an internal stan­dard. The sensitivity of this method is 50 ng/ml. Total

November 1987 Am J Obstet Gynecol

Table I. Maternal, neonatal, and intrapartum anesthesia of the study group (N = 17)

Mothers Age (yr)* 20.0 ± 4.5 (16-27) Parity

Nulliparous 15 Multiparous 2

Neonates Gestational age (wk) 39.6 ± 1.2 (38-42) Birth weight (gm) 3312 ± 411 (2660-4190) Apgar score < 7

1 min 4 5 min 0

Sex Male 11 Female 6

Intrapartum anesthesia Total dose (mg) 81.8 ± 27.0 (20-100) Drug-to-delivery interval 6.7 ± 4.3 (2-17)

(min)

*Mean ± standard deviation with range in parentheses.

chloroaminobenzoic acid in neonatal urine was ana­lyzed. No attempt was made to distinguish between free and bound chloroaminobenzoic acid since only trace levels of conjugated chloroaminobenzoic acid have been reported in neonates. 1 Urinary chloroprocaine levels were not determined. Plasma cholinesterase ac­tivity and the dibucaine number were determined by spectrophotometry for documentation of normal cho­linesterase levels.5

Pharmacokinetic analysis. Fetal-maternal ratios were calculated by dividing the amount of chloroami­nobenzoic acid in the cord vein at birth by the amount in the maternal vein at birth. Disappearance of chlo­roaminobenzoic acid from urine was monitored by re­cording drug concentration in micrograms of drug ex­creted per milliliter against hours after delivery for the neonate.

Clinical evaluation. The quality and duration of pain relief were evaluated subjectively by each patient. If additional pain relief was required because of an ex­tension of the episiotomy or a laceration of the vaginal mucosa, 1% lidocaine was administered.

Newborn evaluation consisted of 1- and 5-minute Apgar scores and fetal acid-base status from the um­bilical cord vein. Each infant was weighed postpartum and underwent a complete physical examination, and gestational age was determined by the Ballard modi­fication of the Dubowitz examination.6

Results

Patient population. The maternal, neonatal, and in­trapartum anesthesia characteristics of the 17 study pa­tients are shown in Table I. The mothers were at term and without any underlying obstetric problems. All neonates had Apgar scores of >7 at 5 minutes. Four

Volume 157 Number 5

neonates had 1-minute Apgar scores <7. Three of these neonates had thick meconium at delivery and required endotracheal suctioning immediately. The other neonate had a shoulder dystocia. The mean pH of the umbilical cord blood at delivery was 7.32 ± 0.05. There were no signs of anesthetic toxicity in any of the neonates.

Plasma drug levels. 2-Chloroprocaine was not de­tectable in maternql plasma after local perineal infil­tration or at delivery. Detectable levels of 2-chloropro­caine were found at delivery in only one umbilical cord vein sample. The concentration in this one umbilical cord was 4.84 ng/ml. 2-Chloroprocaine was not de­tectable postpartum in neonatal plasma.

The appearance of chloroaminobenzoic acid was rapid and detectable in all patients before delivery. An example of a maternal plasma concentration time pro­file is shown in Fig. 1. As seen in this figure, the highest maternal plasma level of chloroaminobenzoic acid (2 .13 1-lg/ml) occurred 8 minutes after receiving 8 ml of 1% 2-chloroprocaine (80 mg).

The mean, standard deviation, and range of chlo­roaminobenzoic acid concentration at delivery in the maternal plasma and umbilical cord vein are shown in Table II. The means were 0.62 and 0.28 1-lg/ml, re­spectively. The fetal-maternal ratio of chloroamino­benzoic acid at delivery ranged from 0.32 to 1.39, with a mean of 0.80.

Urine drug levels. Thirty-one samples were collected from nine neonates. Seven of the nine neonates had measurable levels of chloroaminobenzoic acid in their urine. Half of the samples had levels of chloroamino­benzoic acid below the detection limit (50 ng). The con­centrations ranged from 0 to 2.4 1-lg/ml. Urinary chlo­roaminobenzoic acid was detectable in some neonates 36 hours post partum.

Clinical evaluation. The quality and duration of pain relief as judged by each patient were adequate. There were no adverse effects. The quality and du­ration of analgesia as evaluated by the obstetrician were sufficient except in two patients in whom additional local anesthetic was necessary for fourth-degree epi­siorrhaphies.

Comment

The purpose of this study was to describe the dis­position of 2-chloroprocaine and its metabolite, chlo­roaminobenzoic acid, in mother and neonate after local perineal infiltration. The key finding of this study in­dicates that very little, if any, unchanged 2-chloropro­caine reaches the fetus after local infiltration of the perineum with 2-chloroprocaine.

These results are similar to those from previous stud­ies of 2-chloroprocaine administered by other routes. 2-Chloroprocaine has been shown to reach the fetus in

2-Chloroprocaine for local perineal infiltration 1277

Table II. Chloroaminobenzoic acid concentration (micrograms per milliliter) at delivery in maternal plasma and umbilical cord vein after local perineal infiltration

Sample I Concentrations

Maternal plasma (at delivery)* Umbilical cord vein Fetal/maternal ratiot

0.62 ± 0.38 (0.36-1.31) 0.28 ± 0.42 (0-1.43) 0.80 ± 0.4 7 (0.32-1.39)

*Mean ± standard deviation with range in parentheses. tRatio of level in cord vein to level in maternal vein at

delivery (mean of individual ratios and not ratio of means).

only small amounts after paracervical block and lumbar epidural anesthesia.'· 7 This apparent lack of placental transfer occurs because 2-chloroprocaine is rapidly me­tabolized by maternal plasma cholinesterases. This rapid metabolism was evidenced immediately by de­tectable chloroaminobenzoic acid levels and nonde­tectable levels of 2-chloroprocaine. In the present study, trace levels of 2-chloroprocaine were found in only one umbilical cord vein sample at delivery. Any unchanged 2-chloroprocaine that crossed the placenta was probably metabolized by fetal plasma cholinester­ases. 8·

9 Although fetal levels in utero were not mea­sured, these data suggest that very little active drug reaches the fetus after local perineal infiltration with 2 -chloroprocaine.

The neonatal excretion of chloroaminobenzoic acid has been reported after administration of 2-chloropro­caine for paracervical block and lumbar epid,ual an­esthesia.'·'· 7 These reports consistently indicate that the neonate excretes less than 0.25% of Ltie total maternal dose as chloroaminobenzoic acid. These find­ings support the premise that very little active drug reaches the fetus after local perineal infiltration with 2-chloroprocaine.

The fetal-maternal ratio of chloroaminobenzoic acid (0.80) is similar to the fetal-maternal ratio reported for lumbar epidural anesthesia for cesarean section and for paracervical block. 3•

4•

7 The clinical data revealed no adverse effects of 2-chloroprocaine or chloroamino­benzoic acid on the mother, fetus, or neonate. More important, 2-chloroprocaine provided adequate anal­gesia for the episiorrhaphy except in two patients who required additional local anesthetic for a fourth-degree episiorrhaphy.

What clinical significance, if any, do the results of this study have? A previous study indicated that a common, obstetric procedure traditionally performed with li­docaine can result in considerable neonatal drug ex­posure.' In fact, neonatal lidocaine toxicity with con­vulsions has been reported after accidental scalp injec­tion with lidocaine at the time of episiotomy.]() This study suggests that this exposure can be minimized

Philipson, Kuhnert, and Syracuse

with the use of an equally effective, alternative, pharmacologic agent that is metabolized differently. Hence 2-chloroprocaine, an este;·.Jinked local anes­thetic agent, may be preferable to lidocaine for local perineal infiltration.

REFERENCES

1. Philipson EH, Kuhnert BR, Syracuse CD. Maternal, fetal and neonatal lidocaine levels following local perineal in­filtration. AM j 0BSTET GYNECOL 1984; 149:403-7.

2. Kuhnert BR, Kuhnert PM, Reese ALP. Measurement of 2-chloroprocaine in plasma by selected ion monitoring. J Chromatogr 1981;224:488-91.

3. Kuhnert BR, Kuhnert PM, Prochaska ALP, et al. Plasma levels of 2-chloroprocaine in obstetric patients and their neonates after epidural anesthesia. Anesthesiology 1980; 53:21-5.

4. Kuhnert BR, Kuhnert PM, Reese ALP, et al. Maternal and neonatal elimination of CABA after epidural anes-

November 1987 Am J Obstet Gynecol

thesia with 2-chloroprocaine during parturition. Anesth Analg 1983;62:1089-94.

5. Kalow W, Genest K. A method for the detection of atypical forms of human serum cholinesterase. Determination of dibucaine numbers. Can J Biochem Physiol 1957;35: 339-46.

6. Ballard JL, Novak K, Driver M. A simplified score for assessment of fetal maturation of newly born infants. J Pediatr 1979;95:769-74.

7. Philipson EH, Kuhnert BR, Syracuse CD, et al. Intrapar­tum paracervical block anesthesia with 2-chloroprocaine. AM j 0BSTET GYNECOL 1983;146:16-22.

8. O'Brien JE, Abbey V, Hinsvark 0, et al. Metabolism and measurement of chloroprocaine, an ester-type local an­esthetic. J Pharm Sci 1979;68:75-8.

9. Finster M, Perel JM, Hinsvark 0, et al. Pharmacody­namics of 2-chloroprocaine (Nesacaine), an ester-type lo­cal anesthetic [Abstract 330]. Proceedings of Fourth Eu­ropean Congress of Anesthesia. Amsterdam: Excerpta Medica, 1974:189.

I 0. Kim WY, Pomerance JJ, Miller AA. Lidocaine intoxication in a newborn following local anesthesia for episiotomy. Pediatrics 1979;64:643-5.

Breast galactography in the treatment of infected cysts

Dennis P. Tihansky, M.D., Ph.D., and Joseph A. DiBlasio, M.D.

Valhalla, New York, and Clarksburg, West Virginia

Galactography is a valuable procedure to localize the cause of nipple duct secretions or hemorrhage. A unique variant is illustrated by cannulating a periareolar sinus tract, which drains from an infected epidermoid cyst communicating with several ducts. (AM J OssTET GYNECOL 1987;157:1278-80.)

Key words: Galactography, mammography, breast, cyst, fistula

Among examinations for the evaluation of abnor­mal breast discharge, routine mammography is gen­erally ordered for initial screening. However, its false­negative rate is high, such that only half of malignant tumors are typically identified on routine films.' Gal­actography yields a more detailed image of ductal dis­ease on injection of contrast medium into the affected nipple duct. We report for the first time a galactogram variant in which a draining fistula is cannulated outside the areolar zone to demonstrate an inflamed epidermal cyst.

Method

After a scout mammogram is taken, the breast drain­age site is cleaned, and the draining duct or sinus tract

From the Department of Radiology, New York Medical College, and the Department of Surgery, United Hospital Center.

Received for publication May 26, 1987; accepted june 18, 1987. Reprint requests: Dennis P. Tihansky, M.D., Department of Radi­

ology, New York Medical College, Valhalla, NY 10595.

1278

is gently cannulated with a 27-gauge blunt needle. Ra­diopaque contrast medium is slowly injected until the patient complains of discomfort or until it leaks around the needle. If the gynecologist anticipates interven­tional therapy, methylene blue dye can also be injected to delineate the extent of the inflammatory or neo­plastic process. Mammography films are then taken at the end of the procedure.

Case report A 24-year-old white woman with fibrocystic disease

had pain and swelling in her upper right breast, in addition to purulent drainage from a nipple duct. Six months earlier, she had an infected cyst lanced and drained within this area, but soon afterward the nipple discharge recurred and a sinus tract formed and drained along the supraareolar ridge.

Mammograms revealed extensive dysplasia but no dominant mass or skin thickening. A galactogram was performed next, but no fluid could be expressed from the nipple, so the draining sinus tract rather than the occluded duct was cannulated (Fig. 1). The contrast