Naloxone and its possible relationship to fetal endorphin levels and fetal distress

Naloxone and its possible relationship to fetal endorphin levels and fetal distress

FETUS, PLACENTA, AND NEWBORN Naloxone and its possible relationship endorphin levels and fetal distress to fetal This case report of fetal asphyxia...

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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.