Sydney Segal, Walter R. Anyan, Jr, Reba M. Hill, Ralph... Albert W. Pruitt, Henry R. Shinefield, Harvey S. Singer and... Naloxone Use in Newborns

Sydney Segal, Walter R. Anyan, Jr, Reba M. Hill, Ralph... Albert W. Pruitt, Henry R. Shinefield, Harvey S. Singer and... Naloxone Use in Newborns

Naloxone Use in Newborns
Sydney Segal, Walter R. Anyan, Jr, Reba M. Hill, Ralph E. Kauffman, Howard Mofenson,
Albert W. Pruitt, Henry R. Shinefield, Harvey S. Singer and Miles M. Weinberger
Pediatrics 1980;65;667
The online version of this article, along with updated information and services, is located on
the World Wide Web at:
http://pediatrics.aappublications.org/content/65/3/667
PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication,
it has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked
by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village,
Illinois, 60007. Copyright © 1980 by the American Academy of Pediatrics. All rights reserved. Print
ISSN: 0031-4005. Online ISSN: 1098-4275.
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Committee
on Drugs
Naloxone
Use in Newborns*
Naloxone
hydrochloride
(Narcan)
is a pure
narcotic
antagonist
that
is the drug
of choice
in the
treatment
of central
nervous
system
and cardiorespiratory
It has
depression
virtually
no
produces
in greater
the
when
doses,
administered
in contrast
to
approved
a dosage
form
of 0.02 mg/ml
use in newborns
that
scription
of
pressed
naloxone
in
newborn
merits
information
endogenous
long-term
the
management
of
clarification.
regarding
In
opiate
of
was
whose
the
de-
addition,
receptors
and
opioids
raises
questions
concerning
the
safety
of naloxone
in neonates.
A review
available
published
and
taming
to naloxone
the Committee
on
following
commentary
unpublished
data
per-
use in the newborn
infant
Drugs
forms
the basis
for
and recommendations.
by
the
The potent
narcotic
antagonist
activity
of naloxone is well documented
in infants
and children
as
well as in adults.
Naloxone
has been effectively
used
to reverse
respiratory
depression
in
infants
and
children
analgesia.’2
Additional
which
naloxone
was
who
received
narcotics
for
cases
have
been reported
in
successfully
and safely
used to
treat
were
*
children
This
tee
who
statement
Ofl
Fetus
Maternal
tricians
and
PEI)IATRICS
American
and
has
and
been
Newborn
Fetal
Gynecologists.
(ISSN
Academy
poisoned
approved
and
Medicine,
the
0031
4005).
of Pediatrics.
by the
the
with
American
Copyright
narcotic
Academy’s
Committee
on
College
0
CommitObstetrics:
of Obste-
1980
by
as
methadone
the
diphenoxylate
hydrochloride,57
hydrochloride
and
pro-
hydrochloride
(Darvon)?
Most
of the controlled
clinical
trials
to study
the
safety
and efficacy
of naloxone
in treating
respirapoxyphene
tory
have
depression
been
carried
overt
clinical
pression
at
narcotic
in
evidence
birth.
The
effect
include
the
assessment
of respiratory
the
narcotic-exposed
out on full-term,
healthy
received
morphine
during
labor,
but
vary
or
who
of respiratory
parameters
from
study
newborn
infants
meperidine
showed
or
used
to
Apgar
score,
various
scales,
and
physiologic
function.
Not only
no
CNS
deto detect
study.
These
neurobehavioral
measurements
do the methods
of
assessment
vary from study
to study,
but naloxone
dose and route
of administration
are different.
This
makes
comparison
of the studies
difficult
and,
not
surprisingly,
results
Several
significant
fants
who
with
and
are
controlled
differences
received
respect
ventilatory
to
inconsistent.
trials
have
shown
statistically
between
narcotic-exposed
innaloxone
and those
who did not
alveolar
response
CO2 tension.”
The
onstrated
significantly
EFFICACY
postoperatively
such
whose
mothers
hydrochloride
receive
narcotic
analgesics
during
labor
are born with narcotic-induced
respiratory
this drug was marketed
for general
preuse. Three
years
after its introduction,
the
depression;
of
FDA
in a concentration
designed
for
mothers
and who
recent
even
agonist
drugs.
and therefore
hydrochloride
and levallorphan
tartrate,
mixed
agonist-antagonist
activity.
1975
naloxone
specifically
role
narcotic
activity
no narcotic
effect
than
recommended
nalorphine
which
have
In
due to
agonist
agonists
(Lomotil),’4
Pco2,”
tidal
volume,9”
to breathing
an increased
infants
in one
improved
study”
sucking
and
shortened
time
for habituation
stimuli
after
receiving
naloxone,
200
times
the usual
recommended
dose).
of 43
higher
newborns,
“alertness
sound”
than
the naloxone-treated
scores”
and greater
the
studies
was there
or central
nervous
control
infants.’2
evidence
system
also dembehavior
to auditory
gig/kg
IM (20
In one series
infants
“response
In none
of significant
depression
had
to
of these
respiratory
as reflected
by Apgar
scores.
With
the possible
exception
of one
study,”
capillary
pH and Pco2
also did not differ
significantly
between
naloxone-treated
and control
group
infants.
Several
uncontrolled
studies
have
claimed
beneficial
effects
due to naloxone
based
on
subjective,
nonquantitative
observations
such
as
increase
increased
Only
in
depth
of
activity,
and
one controlled
respiration,
increased
clinical
improved
crying.2”
trial
(P. Lynd,
AMERICAN
ACADEMY
OF PEDIATRICS
Downloaded from pediatrics.aappublications.org by guest on August 29, 2014
tone,
J. J.
667
Piecoro,
and
R. A. Beargie,
unpublished
data)
has
tion
of sensory
information
attempted
to look
at the efficacy
of naloxone
in
treating
newborns
with
overt
clinical
evidence
of
respiratory
and/or
central
nervous
system
depression at delivery.
Eleven
infants
with presumed
nar-
tuitary
function.
There
that naloxone
is capable
cotic-induced
dents
to thermal
endorphin-mediated
depression
were
compared
mothers
received
group
cotics
(Apgar
score
less
greater
appeared
intralingually.
than
7).
The
activity,
in all
infants
who
10 to 15 tg naloxone
heart
rate, respiratory
and
infants
capillary
during
other
parameters.
poorly
or not
causes
pneumonia,
of
depression
undefined
pression,
ending
The other
at all and
infants
reto have
including
central
and
asphyxia
with
emergency
three
appeared
system
prolonged
section.
de-
labor
Two
of
the
principal
parameters
used
in this
study,
ie,
Apgar
score
and respiratory
rate,
have been
shown
by other
investigators
to be crude
and nondiscriminating
measures
of respiratory
depression.’5
No
data
are
available
regarding
use of naloxone
in
premature
infants.
The single
published
administered
study
to the
reverse
potential
pression
of the
of the
mother
just
prior
narcotic-induced
neonate
is difficult
to the poorly
controlled
conditions
Naloxone
is not recommended
for
to the parturient
for this indication.
use
of naloxone
to delivery
to
respiratory
de-
to interpret
due
of the study.’6
administration
immediate
short-term
to be negligible.
Even
does
not
detectable
safety
have
narcotic
adverse
effects.
of naloxone
The
administration
a narcotic-dependent
has
not
toxicity
of
in excessive
agonist
activity
However,
the
been
naloxone
doses
it
or other
long-term
investigated.
of naloxone
to the infant
mother
may
precipitate
acute
withdrawal
syndrome
in the
infant.
It
therefore,
important
for the physician
to ascertain
whether
the
mother
may
be narcotic-dependent
prior
to using
naloxone
in her infant.
668
PEDIATRICS
may
function
as
Endogenous
opioids
functions
involving
stimuli’8
and may
interfere
clinical
analgesia.’9’#{176}
increases
plasma
corticosteroid
not known,
the observations
must
be answered
before
narcotic-exposed
neonates
with
Naloxof proluteinizin
male
that nal-
concentra-
tion
and theoretically
might
influence
or endorphin-mediated
stress
responses.2’
the relationships
of these
observations
naloxone
in the depressed
and stressed
Central
nervous
sion in the newborn
many
factors
tion of narcotic
enkephalin
Although
to the use of
newborn
are
do raise questions
routine
use of naloxone
can be recommended.
system
infant
other
than
analgesics
it is imperative
be immediately
that
in
depression
are present
ation.
Naloxone
should
resuscitative
measures
adjunctive
onstrate
and respiratory
depresmay be attributable
to
intrapartum
to the mother.
administraTherefore,
that customary
resuscitation
efforts
initiated
when
signs
of neonatal
therapy
significant
to ensure
adequate
oxygennot be used
in lieu of such
but should
be reserved
for
in selected
depression,
infants
who
demwho have
been ex-
posed
to intrapartum
narcotics,
and
who are receiving
or have
received
assisted
ventilation
and
are
not
able
to maintain
effective
spontaneous
sponse
likely
after
2 to 3 doses,
the
not due to narcotic
effect.
response
to
repeated
narcotic
in 30 to
and
dose
naloxone,
of
an
newborn
action
is,
should
preferably
either
through
peripheral
vein
Recent
information
regarding
opiate
receptors
and endogenous
opioid
substances
(endorphins
and
enkephalins)
suggests
that
opiate
receptors
probably have
physiologic
roles
and enkephalin
and endorphin
polypeptides
neurotransmitters.’7
important
regulatory
For example,
response
of ro-
ventilation
despite
other
resuscitative
efforts.
The
recommended
dose of naloxone
is 0.01 mg/kg.
This
dose
may
be repeated
in three
to five minutes
if
there
is no immediate
response.
If there
is no re-
SAFETY
The
appears
and endorphins.
nociceptive
evidence
physiologic
COMMENT
aspiration
nervous
following
cesarean
inand
in the
the
hypothalamic-pi-
one reduces
enkephalin-mediated
secretion
lactin
and growth
hormones
and increases
ing
and
follicle-stimulating
hormone
rats.21’22 Preliminary
data
in mice indicate
oxone
blood
gases
the first six
hours
of life. Eight
of the 1 1 naloxone-treated
fants
seemed
to respond
rapidly
to naloxone
showed
no difference
from the control
infants
monitored
sponded
6)
whose
and a
received
narbirth
(Apgar
eleven
depressed
received
Temperature,
color,
cry,
monitored
than
a group
of seven
infants
no narcotics
during
labor
of seven
infants
whose
mothers
but who
appeared
normal
at
scores
rate,
were
to
effects
of enkephalins
naloxone
increases
and
is experimental
of blocking
the
important
may play
integra-
dose
may
exposed,
since
is relatively
be administered
an umbilical
venous
in order
to obtain
Although
the drug
or subcutaneously,
is most
is an initial
need
90 minutes,
depending
of the
narcotic
to
has been
of naloxone
response.
muscularly
delayed
stricted
support
the
depression
If there
the
short.
to
on
which
be
the
the
duration
Naloxone
intravenously,
catheter
or
an immediate
of
a
may
be given
intraabsorption
may
be
and
erratic
in the stressed
and
vasoconinfant.
There
is not clear-cut
evidence
to
the routine
administration
of naloxone
to
infants
who
during
central
labor
nervous
have
but
been
show
system
exposed
to narcotic
no overt
or respiratory
Vol. 65 No. 3 March
1980
Downloaded from pediatrics.aappublications.org by guest on August 29, 2014
analgesia
clinical
signs
depression.
of
CONCLUSIONS
AND
RECOMMENDATIONS
Naloxone
should
be
therapy
in selected
infants
reserved
for adjunctive
who have
not initiated
1.
or established
ventilation,
high
independent
significantly
are
probability
2. When
respirations
depressed,
of being
naloxone
the 0.02 mg/mi
recommended
3. Rumack
4.
following
and have
5.
a
narcotized.
6.
is administered
preparation
dose
is 0.01
to the
neonate,
should
be used.
mg/kg.
The
initial
The
dose
may be repeated
in three
to five minutes
if there
is
no response.
The dose
may need
to be repeated
in
30 to 90 minutes,
depending
on the degree
of depression
of the
infant,
because
of the relatively
short
duration
of action
of naloxone.
Naloxone
should
be given
tion
to the
mother
just
prior
to delivery
fants
of
precipitate
infant.
narcotic-dependent
withdrawal
5. Naloxone
mothers
in the physically
should
newborns.
cotic-exposed
not
be used
COMMITTEE
Sydney
Walter
Reba
Ralph
Howard
Albert
Henry
Harvey
Miles
in-
as
this
may
dependent
routinely
in nar-
ON
DRUGS
Segal,
MD, Chairman
R. Anyan,
Jr, MD
M. Hill, MD
E. Kauffman,
MD
Mofenson,
MD
W. Pruitt,
MD
R. Shinefield,
MD
S. Singer,
MD
M.
Weinberger,
MD
REFERENCES
1.
Fisher
nistic
CG, Cook
effects
of
DR: The
naloxone
respiratory
in infants.
and
Anesth
narcotic
Analg
Data
Welfare,
file,
Food
US
and
Department
I)rug
of
Health,
Administration,
Education
Bureau
MIJ,
Rosen
Gerhardt
neonatal
J 2:228,
T, Bancalari
narcotic
J Pediatr
M: Reversal
of narcotic
Br Med J 2:1098,
by naloxone.
Rosen
M:
1977
E, Cohen
respiratory
Effects
depression:
of
H, et al: Use
depression
naloxone
1. Intravenous
in the
de1976
on
nat-
of naloxone
to
newborn
in-
fant.
90:1009,
1977
Bonta
BW, Gagliardi
JV, Williams
V, et al: Naloxone
reversal of mild
neurobehavioral
depression
in normal
newborn
infants
after
routine
obstetric
analgesia.
J Pediatr
94:102,
1979
13. Wolochowicz-J#{243}zwick
Z, Norek
W: Evaluation
of antidepressive
effect
of naloxone
in newborns
(Polish).
Anesth
Reanim
Inten
Tenap
9:269,
1977
14. Clark
RB, Beard
AG, Barclay
DI: Naloxone
in the newborn
15.
and
of Drugs
infant. Anesth
Rev 2:9, 1975
Gerhardt
T, Bancalari
E, Cohen
H, et al: Respiratory
de-
pression
at birth:
Value
of Apgar
score
and
ventilatory
measurements
in its detection.
J Pediatr
90:971,
1977
16. Clark RB, Beard
AG, Greifenstein
FE, et al: Naloxone
in the
parturient
and her infant.
South
Med
J 69:570,
1976
17. Snyder
SH: Opiate
receptors
in the brain.
N Engi J Med
296:266, 1977
18. Kosterlitz
HW, Hughes
J: Possible
physiological
significance
of enkephalin,
an endogenous
ligand
of opiate
receptors,
Bonica
ii,
Albe-Fessard
D (eds):
in Advances
in Pain
Research
and Therapy,
Vol 1. New York,
Raven
Press,
1976,
p 641
19.
Levine
JD,
Gordon
NC,
Fields
HL:
The
mechanism
of
placebo
analgesia.
Lancet
2:654,
1978
20. Stephenson
JBP:
Reversal
of hypnosis-induced
analgesia
by
naloxone.
Lancet
2:991, 1978
21. Bruni
JF, Van Vugt D, Marshall
S, et al: Effects
of naloxone,
morphine,
and methionine
enkephalin
on serum
prolactin,
luteinizing
hormone,
follicle
stimulating
hormone,
thyroid
stimulating
hormone,
and growth
hormone.
Life Sci 21:461,
1977
22. Shaar
CJ, Frederickson
RCA,
Dininger
NB, et al: EnkephaIm analogues
and naloxone
modulate
the release
of growth
hormone
23.
on
Hogg
in the neonate
PC, Hogg
MIJ,
pethidine-induced
oxone.
Br Med
antago53:849,
1974
2.
10.
JM,
pression
Wiener
12.
adminto
9. Evans
reverse
to reverse
the fetal and neonatal
effects
of maternally
istered
narcotic
analgesics.
4. Naloxone
should
not be administered
8.
I 1.
intravenously
if possible.
is not recommended
for administra-
3. Naloxone
7.
BH, Temple
AR: Lomotil
poisoning.
Pediatrics
53:
495, 1974
Snyder
R, Mofenson
HC, Greensher
J: Toxicity
from
Lomotil: Accidental
ingestion
by a 22-month-old
child.
Clin
Pediatr
12:47,
1973
Buchner
LH, Cimino
JA, Raybin
HW,
et al: Naloxone
versal
of methadone
poisoning.
NY
State
J Med
72:2305,
1972
Sesso
AM, Rodzvilla
JP: Naloxone
therapy
in a seven
month
old with
methadone
poisoning.
Clin Pediatr
14:388, 1975
Simons
PS: The
treatment
of methadone
poisoning
with
naloxone
(Narcan)
J Pediatn
83:846,
1973
Lovejoy
FH, Mitchell
AA, Goldman
P: The
management
of
propoxyphene
poisoning.
J Pediatn
85:98,
1974
and
prolactin:
Evidence
for regulation
Sci 21:853,
dogenous
opioid
peptide
in brain.
Life
Gibson
A, Ginsburg
M, Hall
M, et
naloxone
and
normorphine
on plasma
in normal
and stressed
mice.
J Physiol
AMERICAN
ACADEMY
OF
al: The
influence
of
corticosteroid
leveLs
270:28,
1977
PEDIATRICS
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by an en1977
669
Naloxone Use in Newborns
Sydney Segal, Walter R. Anyan, Jr, Reba M. Hill, Ralph E. Kauffman, Howard Mofenson,
Albert W. Pruitt, Henry R. Shinefield, Harvey S. Singer and Miles M. Weinberger
Pediatrics 1980;65;667
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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication, it
has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked by the
American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007.
Copyright © 1980 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0031-4005.
Online ISSN: 1098-4275.
Downloaded from pediatrics.aappublications.org by guest on August 29, 2014