FETUS, PLACENTA, AND NEWBORN
Naloxone and its possible relationship endorphin levels and fetal distress
to fetal
This case report of fetal asphyxia and related studies suggest that fetal endorphins play a role in fetal pain tolerance and cardiovascular asphyctic responses. Elevated fetal endorphin levels may, like narcotics, produce abnormally “flat” fetal heart rate patterns intrapartum and fetal tolerance to pain. Although naloxone hydrochloride was used with some success to return flat fetal heart rate patterns to “normal,” the unopposed antagonism of fetal endorphins by naloxone in times of fetal distress may be detrimental. (AM. J. OBSTET. GYNECOL. 139:16, 1981.)
IIYDR~~HI.o~I~E
NAI.ox~NE
is considered
to hc 2
tfie actions of‘ morphine-like drugs. Nor does it produce respiratory deprt5siori, f~sychotornimeti~ elThus, nalosone h;is f’ecth, or pupillary c-onstric-tion. been considereti to have no l~harmacologi~ activirv iti the absence of narcotics. Reported here are I xes in which intrapartiim nalokonc had 2 f~rofx~bfe ef’t’ec I upon human fetal hart rate responses in the alxerw of’ f,riol- narcotic adminisrr~ltion, presumably IxcausC naloxone inhibits fetal endorfdlins.
pure
narcotic.
agonistic
Studies
16
antagonist
its
it
does
not
possess
Naloxone
11lllllllilll
!
Fig. 1. Four the
riort
remainetl
at
lower
(i cm
tin
of a fetal
recording,
2 hours.
the
Ari
heart
rate
recording
paper
speed
oxycocin
int
was
Ii-
sion up to 16 mU/niin \v;ib begun and the membranes ~\‘erc ruptured. Meconium staining of the amniotic fluid was noted, and the fetal heart rate patterns (XV. 40677, I;&. 1) dcmonstr-atcd ;I loss ot’ beat-to-beat variability. An attelrlpl to obtain a f’etal scalp pH was unwctesstid. Kccailse of’ the heart rate pattern and meconirmi staining of‘ the fluid, preparations were made f<)r :I possible (esarean section and oxygen administralicui was kgiin. i\\ indicatctl in Fig. I. attempts JVCI’Ctlwn niactc (0 “arouse” the t’cbtus (,\‘.io. JfSOl to h’o. -#0006) by tactile stimulation of the fetal \‘ertex and hp an external sound kmulus over the ycwex ( 100 dB, 2,000 HI f’or 30 seconds). LVhen these efforts to increase the fetal heart beat-to-heat variabilit) tiled, and 23 rltinutes af’ter the os!.tocin intilsio~l \\‘a> begun, the patient was given nalosont
Ii\ cti.ochIoritle,
0.4
nig
intramuscularly,
to
and purpose of the dru‘g I~ad be?11 explained to the patient. Ten minutes later. the letal Iwart rate pattern was considered to show “t~oi~riial” beat-to-beat variabilitv (h’o. BJt34). Fift? minutes alter the oxyl&iti inf’kiion was begun, the tcr\.is was full) dilated, and the vertex was at station + I; thr patient began to push. For the first time “cnushoots”.~ were noted in tlw fetal heat-t rate pattwn (.Vo. 8-M) 01‘ Fig. 2). A fetal scalp pH obtained at this time \vas 6.97 and maternal “arterialized” venous blood pH was 7.X). Hecause the fetal heart rate pattern soon it \vas assumed that the scalp pH re\,erted to “normal.”
;trotw
hrr
Irtus.
The
n;ituTe
to fetal endorphins
and fetal distress
17
I Ib!rliLi:,;yU
sections right
related
demonstraring changed
from
bss 3 to
of beat-to-beat 1 cmimin
variability. in
ol-dvr
In
to better
was in error; nesertheless, the deliver)- was expedited. Frame iV0. K&&I9 01’ Fig. :! ~cas obtained in the deliver\ room immediately prior to application of the fin-ceps. An easy midforceps deliver! was accomplished, and the 3,Y.W gm female infant hat1 a I-minute Apgar score of 2. Attcr resuscitation, the infant’s .‘,-minute Plpgal score was 3. In the nursery, the infant appeared to be somewhat depressed and had signs and symptoms of mc(.onium aspiration, although no meconium had bee11 seen below the vocal co1 ds at the time of delivery. -Thv infant ~vas maintained on a respirator with high settings, but at 2” hours of age, she began to ha\,e generalired seizures. J‘hese could not be controlled and she died at 37 hours of age of apparent respirator) failure. Postmortem examination showed minimal meconium aspiration ;II~CI no gross abnormalities of the brain. Death was presumed to be secondarv LO asphyxia in utero. The use of n&sow under these cir&stances was discontinued after this case. Comment Hyperactive intrapartum fetal heal-t rate patterns may reflect increased arousal caused bv fetal suffering or pain. Swh fetal heart rate patterns. or even ominous patterns, may revert to normal with significant maternal systemic pain relief and/or anesthesia.‘, 5 ‘I‘imorTritsch and associates” considered this apparent improvement in fetal heart rate patterns foilowing
18 Goodlln
SCALP
_.-
PH = 6,%’
i I
DELIVERY
ROCWl
LOA
+
3
STATION
general anesthesia to rcprewnt decreased intensity 01’ uterine contractions. Howe\-er, another- interpretation is that the well-being otthr intraparturn fetws subjected to srvere pain. jrlst 35 itr lllc sufttring adult. is impi-ovrd 1,~ analgesia. ‘. ’ Narcotics of‘ler a sn~all degree of f’etal protection from asph~xia.‘~ ’ and cnclogenous endorphins or other self~produccd opiates may serve a like function
FORCEPS '
for the stressed f&is. (;autrav and associates’ lound increased endorphins in amniotic fluid during labor. especially in the case of f’etal distress. Wardlaw and associatesX observed increased plasma heta endot-phin levels in fttal sheep after hqmxid and, in hunian letuses. described a negative correlation betwrcn urnhiliral artery pH and fetal beta endorphin-like irnnnnoactivity. They concluded that hypoxia and scconclar!
Naloxone
;icidosia
ma)-
tlorphin~. n;do\;oi~~~ cotic
hc a stimulus
Despite is lvithout
lagoiiism
” the
ot entlorl~liins has
.ldllll\.~‘-
release
possibility
of fetal
exists
b! naloxone
distressed
nalosoirc
the
en-
n~~merous studies suggesting effect in the absence of prior
~ltln~iniatl.atio~~,‘.
1~1 to vmit’
f’or
fetuses.
been
Inay single
In
associated
with
that nar-
that
an-
h~droc~hloride
~iitlorphins
ah well
is considered
as narc-otics.
in
humans,
it has
prior baseline
ciated
with
acideniia,
heart
rate
lf one
this
fetus
at
and
blockage
sho\\n that l~l;iceho-ilidticed tolerance to chronic ia retlucccl by naloxone injection.” This increased
both
enhanced
ante
of’ “normal”
pairi
wll\itivity
given
Ilisnl
of
c Iironic
the
cndorphins
pain.
Human
reflects
nalosone
produced
in
fetuses
their
and
vai-y ing ‘miotints of’enclorphin activity.x. explain their ditfcr-cnt intraparluni I-C;IC tivitirs.
oiic’.
The
\vhich intrapartrim
treat-to-l,eat t’etal
may
fetal
wriability
entlorphin
during
l;il~w.
c.i;itt~(l
u ith
(~oii( em the fetus
fttal
\vhich
are
fetal
l’etal
levels
heart
01 the
heat-to-beat
initial variability.
discoI-cry Kane
lo\\
a high to “sleep”
when of‘
rate the
asso-
medical
patterns
after
hypothesis
that
contribute
rate pattcriis of‘ loss of‘ beat-to-beat In the case of’% N., no scalp pH time
with
to attempt to arouse This modest success
wpports
endorphin
fetus
sometimes
and
“~iorinal”
nalos-
reflect
patterns
it seems rcasoiiable to confirm its IveIl-hcing.
b\
pattern
the
rate
have
I” which could fetal heart rate
rate
allows
to
placentas
could
heart
;Idmirlistr~ttion
clw,lted
heart
decelerations
response
be increased
(reactivity)
level. Such
of‘ obtaitling naloxow
likwise
antago-
of
decreased
of‘ the
to fetal
\ariahilit> was obtained other
heart
of
cannot
be l~ovecl
tetus
tar,
nalosone ical
experielice
provat
of the
the
that Academy
that clin-
lTnretatetl (with
has
( IWO)
that
nalosone
process
stress.
The
concept
at the
the
fetal
heart
like
fetuses
with
REFERENCES
9. 10.
11. 12.
13.
1-t 15. 16
the
is not
purpose
fetus
‘Ii and
this
repori
of
that
fetuses
mav
endorphins
or
similar
tetus
endure
reu~mn~eritled
may
counteracting
such be
that
mat
is to pain
stress,
detrimental their
birth
is a
be a source support
ot the
during
self~produced
in withstanding
nalosone
through
for
the
.just prior to dvtiver~ eff’ccta of’ matcwiall~-
administered narcotic analgesics.‘” The psychiatric literature suggests pinfiil
and
G>ncc.ologists)
antI
to the mother fetal and neonatal
Lo the ap-
ot Pediatrics
of Obstetrician5
stated
to this
although
on Drugs
(:ollege
it
repoH,
fi)r- cvrtaiti
it does.”
r\merican
li)r administration to ruerse the
Obviously.
detrimental
known
IXIVC
;II~XI]F
ast
the placenta.
Committee
ill
111;1\
the
pattern\. R;IS
American
IIO ac.id(,iiiia
caused
nalosone even
l’etal
Ivit II fytal
n;dosol~c
particular
cusses
li~~ntl
0thc.r
~itiriiiilisti-atioii
and rate
asso-
wemed li;i\~
tv;is
of’this
suggests
ronccpts,
ialosone
it is not
cf‘f’ectivelv
these
thew
the
heart
that
indeed,
that
asphvxi;~
fetal
deliwry
assoc.i;ltetl
cndorphins.
fetal
the uncertainties
that
I. Shnitler, S. M., and Levinson. G.: Anesthesia for Ohstetrics, Baltimore. 1979. The Williams & Wilkins Co.. p. X9. 2. (:hang, A.. Gilbert, M.. Wood. C.. and Humphrey, M.: ‘I’he eif‘ects ot nalorphine and naloxone on maternal and letal blood gas and pH. Med. J. Aust. 1:26X. 1976. 3. Gootllin, R. C.. and Lowe, E. W.: A functional umbilical cord occlusion overshoot, Ohstet. Gynecol. 43:225, 1974. R. C.: Fetal medication in high risk pregnancies, -4. (;oodlin. Ohstet. Gvnecol. 34: 109. 1Q6Q. .i. (;oodlin. k. C.: Care of the Fetus, ed. I, New York. lQ79. 411sson c 8; Cie. 6 ‘r‘irnor-Tritsth. I., Gergely. Z., Ahramovici, H.. and Branties, J. hl.: Electronic monitoring of’ the fetal heart rate and uterine contractions during cesarean section rtndcl halanrad anesthesia. Ohstet. Gynecol. 48:23?, I976. 7 (;autl ay. J. P.. Jolivet, A., Vielh, J. P.. and Guillemin, R.: I’rr~ence ot immunoassayable P-endorphin in human amniotic fluid: Elevation in cases of fetal distress. AM. J. ()BSTET. GYNECOL. 129:21 1, 1977. S. L., Stark, R. J., Baxi. L.. and Frantl. A. G.: x U’artllaw.
time
of fetal
Iweii paili
l~resiin~al~l~
~SSUIIICS
the
a flat fttal
without
is seldom
and
\vas Ilot
siniilartv
variahilit~
abnormalities
acidcmia.
that
fin- vaginal
@iltigan”’
loss of‘ hea-to-beat
19
pHs.
decelerations
plans and
abnormal
suggested
\vithout
Zator
and fetal distress
had
esperierice
rate
that
to antagonize
In adult
our
variabilit)-
heart
reasonable.
“l
N;~losoile
because
be dctrimeil-
hypertension
to fetal endorphins
loss of’ beat-to-beat
case
reports,
related
lalx~r.
opiates aud to
that t’et;~l
aid qents
\\elfarc
endorphins.
Plasma p-endorphin and P-lipotropin in the human tetuh at delivery: correlation with arterial pH and p0?. J. Clin. Endocrinol. Metah. 49:X%, 1979. Tanake, G. Y .: Hvpertensive reaction to nalosone. .JAMA 228:25, IQ74 Azar. I., and Turndorf. H.: Severe hypet-Lension and multiple atria1 premature contractions following nalosone a’dministration. Anesth. Analg. 58:524, 1079. Levine. J. D.. Gordon, N. C., and Field, H. I..: The merhanisms of placebo analgesia, Lancet 2:6X, 1978. Houck, J. C.. Kimball. C., Chang. C., Pedigo. N. \V.. and Yamamura. H. 1.: Placental U-endorphin-like t,ct>tid,s. . . Science 207:78. ?QRO. ’ %alor, R., and Quilligan, E. J.: The inHucnce of scalp sampling on the cesarean section rate for fetal distress. AM. J. OBSTET. GYNECOI.. 135:2X1, 1979. Payne, J. I’.: Narcotic antagonists and their ure in ohstetrics. Br. J. Anaesth. 45:794, 1973. Segal, S., Anyan, W., Hill, R. M., Kauffman, R. E.. et al.: Naloxone use in newborns. Pediatrics 65:665. 10X0. Grow’, S.: Realms of the Human Unconscious. New York. 1976. Dutton.