LTHE TRANS~SSXON OF ~EPERI~XNE ACROSS THE

        HUMAN PLACENTA3
VIRGINIA~GAR, &ED., J. J. &URNS, PH.D., BERNARD €3, ~IE, PH.D., AND

       E. M.~APPER, M.D., NEW YORK, N. Y.
(From the ~e~ar~~en~ of A~esth€~o~ogy, College of Phy~~~ and Szlrgeons, Colzlmb&
iJniver&y, and the Besearch Service, Third New Pork University Medical Divisim, Gold-
water Memorial Hospital, New Pork, and the Section on Chemical Pharmacology, National

Heart I~~ti~u~e~ Nat~o~a~ ~~~it~~es of Health, Pddic Health Service,
      Federal Security Agency, Bethesda, Ma.)

  UA~TITATI~~ data on the transmission of certain anesthetic and anal-
Q gesic drugs from the maternal to the fetal circulation have been cited.'-s
Such information is of value to the obstetrician and anesthesiolo~st for a bet-
ter understanding of the effects upon the the newborn baby of drugs adminis-
tered to the mother during labor.
  Hitherto, such knowledge was unavailable with regard to meperidine (Dem-
erol).  This drug has been used with increasing frequency for the relief of
labor pain because it is said to produce little or no effect upon the respiration
of the newborn baby when employed in this manner.' Because of the important
place meperidine has in the management of labor, the current studies of the
pattern of its placental transfer from mother to fetus were undertaken.

~et~o~

  Nine healthy pregnant women at term were used for this study. TWO
patients were delivered by cesarean section, the remainder spontaneo~y, mth
episiotomy. Meperidine in doses of 50 to 100 mg. was administered intramuscu-
larly or intravenously during labor.  The average total quantity of drug Per
patient during labor was 175 mg. and ranged from 50 to 300 mg.  The last
dose of meperidine varied from 40 minutes to 3 hours and 38 minutes Prior
to delivery. The first dose varied from 1 hour and 40 minutes to 15 hours before
delivery. The method of drug ad~inistration was adjusted to the need of the
patient for satisfactory analgesia.

  Five patients were anesthetized for delivery with nitrous oxide-oxygen
(a minimum concentration of 25 per cent oxygen was given) ; two with CYclO-
propane, and one each with low spinal anesthesia and caudal block.
At delivery, samples of blood were drawn simultaneously from the mothe*
and the umbilical cord. The latter was considered representative of the fetal
blood. Meperidine in plasma was determined according to a method to be Pub-
lished el~ewhere.~ This method has been shown to be specific in that it included
none of the metabolites of meperidine in the measurement.

Results

Plasma levels of meperidine indicate clearly that the drug crossed the Pia-
                  These varied from 45 to 106

centa in significant concentrations (Table I).

*Supported in part by the Squibb Institute for Medical Research.

1368

TABLE I

        TIME PRIOR                                     MATERNAL      CORD
ROUTE OF TO DELIVERY ANALGESIC DEPRESSANT                 PLASMA      BLOOD
        ~    LEVEL ~ LEVEL

TYPE OF MEPERIDINE ADMINIS- IN RR. AND EFFECT ON EFFECT ON

PATIENT 1 DELIVERY 1 (IN Ma.) 1 TRATION ~ ( MfN.)

MOTXER

INFANT ~ ANESTHESIA (IN biG./I..\ (IN biG./I..\

He Vaginal 100 IM 2:OO Good 0 Cyclopropane 0.40 0.22

Zi Cesarean 50 IM 1 :43 Good 0 CvcloDroDane 0.38 0.24

PO Vaginal 50
                 50
Fr Vaginal 100

Ni Vaginal 75
                 75
                 50

St Vaginal 100
                100
                100
Pa Cesarean 100
                100
                50

Bu Vaginal loo
                100
A1 Vaginal 100

50
50
50

IM
IM
IM

IM
IM
IV
IM
IM
IV
IM
TM
IV
IM
IM
IM
IM
IM
IM

2:40
1:15
1:40

4:OR
2:oo
0:43
7:00
4:OO
2:45

15:OO
9:oo
0:40
4:52
3:38
15:00
11 :oo
6:40
3:15

Good 0

Good Moderate

Poor 0

depression

Good 0

Good 01

Good Of

Good 0

Nitrob oxide      0.29 0.13

Nitrous oxide      0.45 0.35

Nitrous oxide      0.50 0.39

Nitrous oxide 0.76 0.55

Low spinal 0.73 0.76

Nitrous oxide 0.23 0.26

Caudal 1.02 0.72

*Spontaneous breathing early. Aspirated meconium. No sequelae.
tDifffcult to evaluate.

De!ivery wa? complicated by impaction of the shouIders of the fetus in the bfrth canal.

A difl'fcult delivery was

followed by fetal anoxia requiring 20 minutes of fntratracheal oxygen ~nsufflation.

Fetat recovery was satrsfactory.

1370

APGAR ET AL.

Am. J. Obst. k Gpnec.
   December, 1952

per cent (average 77 per cent) of the levels measured simultaneously in the
maternal blood.
  Satisfactory analgesia for the mother was achieved in all but one patient.
In only one instance was there a clearly demonstrable depression of fetal respi-
ration, presumably due to meperidine.  Even so, the fetal plasma level of 0.38
mg. per liter was not the highest encountered.  There were two other eompli.
cations in the newborn.  One was attributable to early intrauterine respiration
and aspiration of meconium ; the other to a difficult delivery caused by shoulder
impaction of the fetus.  Neither complication was harmful to the baby.

Comment

  With the aid of a sensitive method for its estimation, it was demonstrat~d
that meperidine enters the fetal circulation relatively freely after parenteral
administration to the mother.  It also appears that doses of the drug which
can produce satisfactory analgesia in the mother do not necessarily cause signifi-
cant depression of respiration in the newborn baby.  The rate of trans~lacental
movement of the drug is unknown.

Summary

1. Meperidine crosses the human placenta in significant concentrations.
2. In therapeutic doses administered to the mother, meperidine appears

to cause little or no depression of respiration of the newborn child.

1.

3.
4.
5.

0

I.

Beferences

Dille, J. M.:
Lell, W. A., Liher, K. E., and Snyder, F. F.:
Falkiner, N. M.:  Proc. Roy. Soc. Med. 37: 417-475, 1943-44.
Shumann, W. R.:  AM. J. OBST. & GYNEC. 47: 93,1944.
Brodie, B. B., Levy, B. B., and Burns, J. J.:

AM. J. OBST. & GYNKC. 32: 328, 1936.

Am. J. Physiol. 100: 21-31, 1932.

To be ~ublishe~.