The Route, Dose, and Interval of

Epinephrine for Neonatal

Resuscitation: A Systematic Review
Tetsuya Isayama, MD, MSc, PhD,a Lindsay Mildenhall, MBChB, FRACP,b Georg M. Schmölzer, MD, PhD,c,d Han-Suk Kim, MD, PhD,e
Yacov Rabi, MD,f Carolyn Ziegler, MA, MIS,g Helen G. Liley, MBChB, FRACP,h INTERNATIONAL LIAISON COMMITTEE ON RESUSCITATION
NEWBORN LIFE SUPPORT TASK FORCE

Current International Liaison Committee on Resuscitation recommendations on

CONTEXT: abstract
epinephrine administration during neonatal resuscitation were derived in 2010 from indirect
evidence in animal or pediatric studies.
Systematic review of human infant and relevant animal studies comparing other
OBJECTIVE:
doses, routes, and intervals of epinephrine administration in neonatal resuscitation with
(currently recommended) administration of 0.01 to 0.03 mg/kg doses given intravenously
(IV) every 3 to 5 minutes.

Medline, Embase, Cumulative Index to Nursing and Allied Health Literature,

DATA SOURCES:
Cochrane Database of Systematic Reviews, and trial registry databases.
STUDY SELECTION: Predefined criteria were used for selection.
DATA EXTRACTION: Risk of bias was assessed by using published tools appropriate for the study
type. Certainty of evidence was assessed by using Grading of Recommendations Assessment,
Development and Evaluation.
RESULTS: Only 2 of 4 eligible cohort studies among 593 unique retrieved records yielded data
allowing comparisons. There were no differences between IV and endotracheal epinephrine
for the primary outcome of death at hospital discharge (risk ratio = 1.03 [95% confidence
interval 0.62 to 1.71]) or for failure to achieve return of spontaneous circulation, time to
return of spontaneous circulation (1 study; 50 infants), or proportion receiving additional
epinephrine (2 studies; 97 infants). There were no differences in outcomes between 2
endotracheal doses (1 study). No human infant studies were found in which authors
addressed IV dose or dosing interval.
The search yielded sparse human evidence of very low certainty (downgraded for
LIMITATIONS:
serious risk of bias and imprecision).
CONCLUSIONS: Administration
of epinephrine by endotracheal versus IV routes resulted in similar
survival and other outcomes. However, in animal studies, researchers continue to suggest
benefit of IV administration using currently recommended doses.

a
National Center for Child Health and Development, Tokyo, Japan; bMiddlemore Hospital, Otahuhu, Auckland, New Zealand; cCentre for the Studies of Asphyxia and Resuscitation, Neonatal
Research Unit, Royal Alexandra Hospital, Edmonton, Alberta, Canada; dUniversity of Alberta, Edmonton, Alberta, Canada; eDepartment of Pediatrics, Seoul National University College of
Medicine, Seoul, Korea; fUniversity of Calgary, Calgary, Alberta, Canada; gSt Michael’s Hospital, Toronto, Ontario, Canada; and hMater Research Institute and Mater Clinical School, Faculty of
Medicine, The University of Queensland, Brisbane, Queensland, Australia

To cite: Isayama T, Mildenhall L, Schmölzer GM, et al. The Route, Dose, and Interval of Epinephrine for Neonatal Resuscitation: A Systematic Review. Pediatrics. 2020;
146(4):e20200586

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PEDIATRICS Volume 146, number 4, October 2020:e20200586 REVIEW ARTICLE
Asphyxia is a leading cause of
neonatal death and disability
worldwide, and some of these deaths
may be preventable by
improvements in neonatal
resuscitation.1 Epinephrine
(adrenaline) is recommended as
a key medication in neonates who
have not responded to previous
resuscitation measures, including
lung ventilation and chest
compressions2; however, the
evidence for its use is limited. The
International Liaison Committee on
Resuscitation (ILCOR) evaluates and
promotes the best available evidence
on resuscitation in all age groups
using rigorous review processes to
generate an international consensus
on science with treatment
recommendations (CoSTR), which
can be used to develop national and
multinational resuscitation
guidelines and algorithms.3 The most
recent ILCOR treatment
recommendations on epinephrine for
neonatal resuscitation were derived
largely from indirect evidence from
pediatric studies of uncertain
relevance to neonates or from animal
studies.2 These recommendations
are for epinephrine at a dose of 0.01
to 0.03 mg/kg intravenously (IV)
(with repeated doses each
3–5 minutes if needed) if adequate
assisted ventilation of the lungs and
chest compressions have failed to
increase the heart rate .60 beats
per minute. Endotracheal
epinephrine administration at
a higher dose (0.05–0.1 mg/kg) is
suggested but only if IV access is
unavailable. These 2010
recommendations still stand because
for the 2015 CoSTR, ILCOR did not
rereview epinephrine for neonatal
resuscitation.4
Since 2015, ILCOR has used the
Grading of Recommendations
Assessment, Development and
Evaluation (GRADE) process to
appraise evidence.5 The need to
assess evidence for epinephrine use
during neonatal resuscitation by
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2 ISAYAMA et al
using GRADE, together with the
possibility that relevant human or
animal evidence had been published
since the 2010 ILCOR review, led to
a decision to conduct a new
systematic review. Polling of the
ILCOR Neonatal Life Support Task
Force prioritized 3 areas of focus. In
collaboration with the ILCOR
Neonatal Life Support Task Force,
we use this systematic review and
meta-analysis to assess the
following areas: the doses, routes,
and intervals of epinephrine
administration in neonatal
resuscitation.
METHODS
The systematic review protocol was
registered in the International
Prospective Register of Systematic
Reviews (CRD42019132219).
Review Question
With this systematic review, we
assessed the question, “Among
neonates (of any gestation) at
#28 days of age who have no
detectable cardiac output, have
asystole, or have a heart rate ,60
beats per minute despite ventilation
and chest compressions, does any
nonstandard dose, interval, or route
of epinephrine (adrenaline) improve
the primary outcome (death at
discharge) or any secondary
outcomes compared to standard-
dose IV epinephrine
(0.01–0.03 mg/kg at intervals of
every 3–5 minutes)?”
Criteria for Study and Participant
Inclusion
Eligible participants were neonates of
any gestational age within 28 days of
birth who had either no detected
cardiac output or asystole or heart
rate ,60 beats per minute despite
ventilation and chest compressions
and had received epinephrine for
resuscitation. In eligible studies,
authors either compared predefined
outcomes between infants receiving
epinephrine by using standard or
nonstandard routes, doses, or
intervals of administration or they
reported predefined outcomes of
infants receiving nonstandard
administration of epinephrine. For
this review (reflecting the ILCOR
2010 CoSTR), the standard
administration of epinephrine was
defined as IV administration of
0.01 to 0.03 mg/kg per dose, and if
return of spontaneous circulation
(ROSC) did not occur in response,
it was defined as repeated
administration at 3- to 5-minute
intervals.2
Randomized controlled trials (RCTs)
and nonrandomized studies (non-RCTs,
interrupted time series, controlled
before-and-after studies, and cohort
studies) were eligible for inclusion.
Unpublished studies (eg, conference
abstracts, trial protocols), case series in
which authors could not provide an
estimate of incidence of outcomes, and
animal studies were excluded. In
cohort studies, authors may compare
different interventions or report
outcomes for a single arm receiving
one intervention. For this review,
observational studies were considered
to be cohort studies eligible for
inclusion if the authors used
a defined strategy to ensure that the
participants were either all of those
who received an exposure of interest
in a defined population (eg, infants
born at a hospital between specified
dates) or were sampled in such
a way as to be representative of
such a population.6 Otherwise, the
study was considered to be an
ineligible case series. All languages
were eligible if there was an English
abstract.
Outcomes
The prespecified primary outcome
was death at hospital discharge, and
secondary outcomes were rate of
failure to achieve ROSC (defined as
a sustained audible heart rate .60
beats per minute),7,8 time until ROSC,
moderate or severe hypoxic ischemic
encephalopathy (only for term
infants), intraventricular hemorrhage
grade III or IV, other morbidities in
early infancy (eg, necrotizing
enterocolitis, retinopathy of
prematurity, bronchopulmonary
dysplasia, periventricular
leukomalacia [only for preterm
infants]), and neurodevelopmental
outcomes. The need for repeat doses
of epinephrine was evaluated as
a post hoc secondary outcome.
Literature Searches
An information specialist (C.Z.)
conducted database searches on March
6, 2019, from Ovid Medline, Embase,
the Cochrane Central Register of
Controlled Trials, the Cochrane
Database of Systematic Reviews, and
Cumulative Index to Nursing and Allied
Health Literature. The search strategies,
adapted for each database, used
a comprehensive combination of
subject headings and keywords for
neonates, cardiac arrest, and
epinephrine, combined by using the
Boolean operator “AND.” The Medline
search strategy is found in the
Supplemental Information. The
databases were searched from
inception, and no language limits were
applied. The Medline search strategy
was peer reviewed by another
information specialist using the Peer
Review of Electronic Search Strategies
checklist.9 References from included
studies and review articles were also
hand searched, and ILCOR Neonatal
Life Support Task Force and Working
Group members were consulted. Trial
registries in the United States, Europe,
and Australia and/or New Zealand
were searched.10–12
Study Selection and Data Extraction
Titles and abstracts were
independently screened by two authors
(T.I. and H.G.L.) who then screened full-
text articles selected by either reviewer.
Discrepancies were resolved by
consensus of all investigators. Cohen’s
k statistic for agreement was
calculated. The same two authors
independently extracted the data on
study designs, study population,
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PEDIATRICS Volume 146, number 4, October 2020
interventions, and outcomes. Study
authors were contacted to obtain
missing data or for clarification.
Risk-of-Bias Assessment and Data
Synthesis
Two authors (T.I. and L.M.) assessed
the risk of bias of each included study
as low, moderate, serious, or
critical using the Risk of Bias in
Nonrandomized Studies - of
Interventions (ROBINS-I) tool for
comparative cohort studies.13 For
single-arm (uncontrolled) cohort
studies, a modification of a tool
proposed by Murad et al14 was used.
For studies in which authors
compared either primary or
secondary outcomes between two
interventions, meta-analyses were
performed with random-effect
models because heterogeneity was
anticipated. Review Manager version
5.3 (Nordic Cochrane Centre,
Copenhagen, Denmark) was used for
the analyses.15 The results are shown
with risk ratio (RR) for binary
outcomes and mean differences
(MDs) for continuous variables along
with their 95% confidence intervals
(CIs). For studies in which authors
assessed one intervention (single
arm), the proportions of outcomes
were calculated. Statistical
significance was determined by using
two-sided P values ,.05. No
adjustment was conducted for
multiple outcomes, which is typical of
systematic reviews. Heterogeneity
was evaluated among included
studies by examining forest plots, the
I2 statistic, and x2 tests for
heterogeneity.16
The GRADEpro Guideline Development
Tool (software) was used to assess the
certainty of evidence as high, moderate,
low, or very low for each outcome.5,17
For nonrandomized studies assessed
by using ROBINS-I, in accord with
recent recommendations of GRADE
methodologists, an initial assumption
of high certainty of evidence was
applied.18 Ratings were downgraded
on the basis of the assessment of risk of
bias, inconsistency, indirectness,
imprecision, and other considerations
where applicable.18
Narrative Summary of Noneligible
Human Studies
Because there were so few eligible
studies during screening, articles in
which outcomes for nonstandard
doses, routes, or dosing intervals were
reported but did not meet inclusion
criteria for the systematic review were
set aside to include in a table and
narrative summary.
Narrative Summary of Animal
Studies
Because there were few eligible
human studies, the searches were
subsequently rerun to include animal
studies. They were expected to
contribute information regarding
mechanisms, pharmacokinetics or
pharmacodynamics, or toxicity and
adverse effects. Animal studies were
not submitted to GRADE analysis,
combined with human studies, or
used for estimates of magnitude of
effect.
RESULTS
Study Selection
Among 593 unique articles retrieved,
98 articles were selected for full-text
screening, and 4 studies were
considered eligible (Supplemental
Fig 2, Table 1).7,8,19,20 Initial agreement
between the two reviewers was fair (k
= 0.34), but differences were resolved
by discussion. All 4 included studies
were single-center, retrospective cohort
studies and included only newly born
infants. Three studies were from the
same institution, although the study
populations did not overlap.7,8,20 In two
sequential studies from one institution,
authors reported outcomes of infants
receiving chest compressions for
resuscitation, some of whom received
epinephrine initially via endotracheal
and some via IV administration
(referred to hereafter as two-arm
studies).7,8 Of note, the endotracheal
epinephrine doses used in both
3
TABLE 1 Included Studies
Halling et al7 2017 Barber and Wyckoff8 2006 Jankov et al19 2000 Perlman and Risser20 1995
Study design Cohort study (2 arms) Cohort study (2 arms) Cohort study (1 arm) Cohort study (1 arm)
Setting Single center (level 3 NICU), Texas, Single center (level 3 NICU),
Single center (level 3 Single center (level 3 NICU), Texas,
United States Texas, United States NICU), Ontario, Canada United States
Years of recruitment 2006‒2014 1999‒2004 1990‒1996 1991‒1993
Infants included in Newborns who received Newborns who received Newborns with birth Preterm infants who received
this review epinephrine in DR epinephrine in DR wt #750 g who epinephrine in DR
received epinephrine
in DR
Authors’ exclusion Lethal anomalies (n = 5); infants Lethal congenital anomalies Major congenital Not specified
criteria born outside of the hospital (n = 1) (n = 3); infants born outside the anomalies; infants not
hospital (n = 1); missing charts intubated in DR
(n = 1)
No. infants receiving 50 47 12 8
epinephrine
included in this
reviewa
Proportion of infants 0.05 (56 of 114 367) 0.06 (52 of 93 656) 6.06 (12 of 198) 0.13 (39 of 30 839) for all term and
receiving preterm infantsa
epinephrine among
all infants in the
cohort, % (n of N)
Interventions Initial endotracheal epinephrine Initial endotracheal epinephrine Endotracheal Endotracheal epinephrine
(0.03–0.05 mg/kg) (0.01 mg/kg) epinephrine (median (0.01–0.03 mg/kg)
total dose of 0.1 mg)
without IV epinephrine
Controls Initial IV epinephrine (0.01 mg/kg) Initial IV epinephrine None None
(0.01 mg/kg)
Indication for NRP guidelines (ie, HR ,60 beats NRP guidelines (ie, HR ,60 HR ,100 beats per HR ,80 beats per minute after 30 s of
epinephrine per minute) beats per minute) minute after intubation CPR
and chest
compressions
Intervals between 3–5 min 3–5 min Not applicable 3–5 min
epinephrine doses
Outcomes reported Death in DR, death at discharge, Apgar 10 min, death at
Death in DR, death Death, neurodevelopmental
time of first epinephrine-dose discharge, ROSC, and time to
before discharge, and impairment, IVH, PVL, and seizure
ROSC, and time to ROSC ROSC neurologic impairment
at median 24 mo of age
Notes Initial endotracheal epinephrine The original study was focused The authors provided Of 16 epinephrine-treated infants, 5
dose changed from 0.03 to on 37 infants who received additional data for this term infants received epinephrine, (4
0.05 mg/kg from 2006–2008 (June) initial endotracheal epinephrine systematic review. endotracheal and 1 IV), but their
to 2008 (July)–2014. The authors and responded (n = 14) or results were not presented by route of
provided additional data for this responded to subsequent IV administration and 4 additional
systematic review. epinephrine (n = 23). preterm infants received epinephrine
without chest compressions. Only the
8 preterm infants who received
epinephrine by a known route
(endotracheal) are included in
subsequent tables.
CPR, cardiopulmonary resuscitation; DR, delivery room (birth location as used by authors; may have included operating theater); HR, heart rate; IVH, intraventricular hemorrhage; NRP,
Neonatal Resuscitation Program; PVL, periventricular leukomalacia.
a Proportion of preterm infants who received epinephrine not reported.

studies (0.01 mg/kg per dose7 and
0.03–0.05 mg/kg per dose8)
were lower than those currently
recommended (0.05–0.1 mg/kg per
dose).2 Furthermore, the proportion of
infants receiving initial endotracheal
epinephrine decreased from 44 of 47
infants in the first to 30 of 50 infants in
the second study, indicating a practice
shift. In both studies, some infants who
initially received endotracheal
epinephrine subsequently received $1
doses of IV epinephrine. In the other
two studies, authors reported the
outcomes of preterm infants receiving
endotracheal epinephrine for
resuscitation (single-arm studies).19,20
Jankov et al19 included only infants
#750 g birth weight. Although
Perlman et al20 included preterm and
term infants, the subgroup of term

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4 ISAYAMA et al
 a Stated in the article that, “As might be expected, for infants who received the first dose of epinephrine IV, there was sufficient time to anticipate that IV access would be needed (early recognized abruption, maternal motor vehicle crash, and

b The mean gestational age and time of initial endotracheal epinephrine of infants included in this review from Barber and Wyckoff8 (2006) was derived for 37 infants who responded to endotracheal or IV epinephrine. The gestational age and time
infants (with one group receiving IV

Median (range): 672 (575–750) Median (range): 1186 (626–1785)

Median (range): 7.22 (6.60–7.33)

Median (range): 29 (25–33)
Endotracheal (0.01–0.03) epinephrine) were excluded from this

Median (range:) 1 (0–6)

review because their outcomes were
Risser20 1995
Perlman and

3 of 8 (38)

2 of 8 (25)
not reported by route of

NA

NA
administration. Therefore, gestation
8

and birth weight characteristics were

lower for included infants from these
two studies than for the two-arm
studies (Table 2). None of the included
studies were specifically designed to
Endotracheal (0.01) IV (0.01) Endotracheal (median dose 0.1)

Median (range): 25 (24–28)

Median (range): 3 (1–15)

address the question for this

Median (range): 1 (1–5)
Jankov et al19 2000

systematic review, so we extracted

0 of 12 (0)

such data that did allow any

NA

NA
NA
12

comparison of review outcomes

(Table 2). Reasons for exclusion of
other studies are summarized in
Supplemental Table 5.

Risk-of-Bias Assessment
Barber and Wyckoff8 2006a

NA
NA
NA
NA
NA
NA
NA
NA
3a

On the basis of the ROBINS-I, both

two-arm studies had very serious risk
Mean: 4.2–5.2b

of bias because of the risk of

Mean: 36b

confounding (Supplemental Table

NA
NA
NA

NA
NA
NA
44

6).7,8 On the basis of the modified

Murad’s tool,14 both single-arm
studies had serious risk of bias (or
Mean 6 SD: 2559 6 1073 Mean 6 SD: 2868 6 1487

Mean 6 SD: 6.98 6 0.2 Mean 6 SD: 6.97 6 0.17

indirectness) because the thresholds

Mean 6 SD: 220 6 8
Mean 6 SD: 5.4 6 2.2
Mean 6 SD: 35 6 5

Median 0 (IQR 0–0)

for administering epinephrine

13 of 20 (65)

16 of 20 (80)

appeared to be lower than those of

IV (0.01)

prolonged shoulder dystocia). In each case, there was time to mobilize appropriate personnel and equipment.”8
20

current ILCOR recommendations

(Supplemental Table 7).19,20
Halling et al7 2017

of initial endotracheal epinephrine for 7 infants who failed to respond epinephrine were not reported.

Initial Endotracheal Versus Initial IV

Epinephrine
Route (dose of initial epinephrine treatment), mg/kg Endotracheal (0.03–0.05)

Mean 6 SD: 219 6 9

Mean 6 SD: 5.1 6 2.7
Mean 6 SD: 36 6 6

Median 0 (IQR 0–1)

In only one study did authors provided

17 of 30 (57)

21 of 30 (70)

data used to address the primary

outcome of the systematic review. This
30

study (reporting 50 infants treated

TABLE 2 Infants’ Baseline Characteristics in Included Studies

with epinephrine) revealed no

difference in death at hospital
discharge between initial endotracheal
and IV epinephrine (RR = 1.03 [95% CI
0.62 to 1.71]; absolute risk difference
[ARD] = 17 more [209 fewer, 391
Emergency cesarean delivery, n of N (%)

more] per 1000 infants; very low

IQR, interquartile range; NA, not available.

certainty of evidence, downgraded for

Time to first epinephrine, min

very serious risk of bias and very

serious imprecision) (Table 3, Fig 1).7
Cord blood base excess

For the secondary outcome of failure to

Asystole, n of N (%)

achieve ROSC, meta-analysis of two

studies (97 infants treated with
Gestation, wks

Apgar 1 min
Birth wt, g
No. infants

epinephrine) revealed no difference

Cord pH

between initial endotracheal and initial

IV administration (RR = 0.97 [95% CI
0.38 to 2.48]; ARD = 7 fewer [135

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PEDIATRICS Volume 146, number 4, October 2020 5
6
TABLE 3 GRADE Evidence Profile Table Comparing the Outcomes After Initial Endotracheal Versus Initial IV Epinephrine Administration
No. Studies Certainty Assessment No. Patients Effect Certainty Importancea
Study Design Risk of Inconsistency Indirectness Imprecision Other Initial Initial IV Relative RR Absolute RR (95%
Bias Considerations Endotracheal Epinephrine (95% CI) CI)
Epinephrine
Death at hospital discharge
N = 17 Observational Very Not serious Not serious Very None 17 of 30 (57%) 11 of 20 1.03 (0.62 17 more per 1000 Very low Critical
studies seriousb seriousc (55%) to 1.71) (from 209 fewer to
391 more) infants
Failure to achieve ROSC
N = 27,8 Observational Very Not serious Not serious Very None 14 of 74 (19%) 5 of 23 (22%) 0.97 (0.38 7 fewer per 1000 Very low Critical
studies seriousb seriousc to 2.48) (from 135 fewer to
322 more) infants
Time to ROSC (in min)
N = 17 Observational Very Not serious Not serious Seriousd None 11 9 — MD 2 more (0.6 Very low Important
studies seriousb fewer to 4.6 more)
min
Receiving additional doses
after initial epinephrine
administration (post hoc)
N = 27,8 Observational Very Not serious Not serious Very None 58 of 74 (78%) 16 of 23 1.94 (0.18 654 more per 1000 Very low Important
studies seriousb seriousc (70%) to 20.96) (from 570 fewer to
1000 more) infants
On the basis of GRADE,18 serious risk of bias in ROBINS-I corresponds to very serious risk-of-bias GRADE (downgrade 2 levels). —, not applicable.
a Importance was assigned by the consensus of the ILCOR Neonatal Life Support Task Force.
b In the included studies, no adjustment for potential confounders (gestational age, Apgar score, asystole, cord blood pH, or base excess, etc) was conducted. Furthermore, there was a high risk of indication bias.
c The relative risk included both the benefit (RR = 0.75) and harm (RR = 1.25) as well as the null effect (RR = 1.00).
d The relative risk included the null effect (RR = 1.00).

Hoc Analysis)

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died or had severe

Supplemental Fig 3).7

administration (RR = 1.94

Endotracheal Epinephrine
endotracheal versus initial IV
received subsequent doses of
very low certainty of evidence,

with very serious risk of bias;

of the proportion of infants who

revealed no difference after initial

a mean gestation of 25 weeks).19

Infants Who Received Only Initial

for infants only exposed to initial

was 0.58 (7 of 12 infants born at

fewer, 322 more] per 1000 infants;

to hospital discharge among these

[95% CI 0.18 to 20.96]; ARD = 654

downgraded for very serious risk of

downgraded for very serious risk of

two doses (30 infants in one study

0.03 vs 0.05 mg/kg per Dose (Post
neurodevelopmental impairment at
Outcomes in Single-Arm Studies of

The rates of death at discharge and

bias and very serious imprecision).7,8
bias and very serious imprecision).7,8

epinephrine (two studies; 97 infants)

for very serious risk of bias and very

a median assessment age of 2 years

and initial IV epinephrine (MD = 2.00

Doses of Endotracheal Epinephrine:

failure to achieve ROSC were similar

treated with epinephrine) revealed no

[95% CI 20.60 to 4.60] minutes; very

infants was 0.38 (3 of 8 infants born

endotracheal epinephrine.19,20 In one
difference between initial endotracheal

low certainty of evidence, downgraded

for infants treated with each of these

more [570 fewer, 1000 more] per 1000
For time to ROSC, one study (50 infants

ISAYAMA et al
the second study, the proportion who
study, authors reported that mortality
serious imprecision).7 Post hoc analysis

In two studies, authors provided data

at a mean gestation of 30 weeks)20 In

infants; very low certainty of evidence,
FIGURE 1
Forest plots comparing the primary and secondary outcomes between initial endotracheal epinephrine and IV epinephrine. Meta-analyses were
performed with random-effect models by using Review Manager version 5.3. A, Death at hospital discharge. B, Failure to achieve ROSC. C, Time to ROSC (in
minutes). D, Receiving additional epinephrine after initial dose (post hoc). df, degree of freedom; I2, I2 statistic; M-H, Mantel-Haenszel.

Narrative Summary of Additional
Human Studies
No studies eligible for this systematic
review evaluated alternative doses of
IV epinephrine, routes other than IV
and endotracheal (eg, intraosseous,
intramuscular [IM]) administration, or
dosing intervals. We summarized
results of ineligible studies assessing
these points in Table 4. Data on the use
of high-dose IV epinephrine for
neonatal resuscitation are meager
(Table 4). In adults and children,
a systematic review of 15 RCTs in
which authors compared high-dose
versus standard-dose epinephrine for
cardiac arrest (typical starting dose for
children of 0.1 mg/kg vs 0.01 mg/kg)
reported a slight reduction in survival
to admission and time until ROSC with
high-dose epinephrine; however, the
quality of evidence was very low, the
subgroup of pediatric studies revealed
no difference, and the applicability to
newborn infants is uncertain.21
Although authors of a few case series
reported high-dose IV or endotracheal
epinephrine in preterm infants, the
safety and effectiveness of high

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PEDIATRICS Volume 146, number 4, October 2020 7
TABLE 4 Additional Referenced Studies
Study Study Design Population and Interventionsa
High dose of
epinephrine
Finn et al21 2019 SR of RCTs Fifteen RCTs were included comparing High-dose epinephrine slightly
a high dose versus standard dose
of epinephrine (mostly
administered IV) for cardiac arrest
in adults (12 RCTs; n = 6697) or
children (3 RCTs; n = 317).
Standard dose in children was
mostly 0.01 mg/kg per dose, and
the high dose was 0.1 mg/kg per
dose.
Schwab and von Case series Preterm infants (median gestation 29 Free plasma epinephrine was
Stockhausen23 (N = 9) wk; birth wt 1225 g) received
1994 a high dose of endotracheal
epinephrine (0.25 mg/kg per dose).
Goetting and Case series Consecutive children in cardiac arrest All 3 preterm infants responded to the In these 3 infants given epinephrine
Oaradis22 1989 (N = 7) (3 given a high dose of epinephrine
preterm (0.2 mg/kg) after failure to respond
infants) to 2 doses of 0.01 mg/kg. A high
dose of epinephrine (0.2 mg/kg per
dose) was given via umbilical
arterial catheter in 3 preterm
infants (28, 29, and 34 wk’
gestation) on day 2–3 after birth.
Epinephrine intervals
Hoyme et al24 2017 Cohort study Children #18 y old with in-hospital
(N = 1133) cardiac arrest who received .2
epinephrine doses at intervals of
1–5, .5–,8, and 8–,10 min
(1630 events) (the average interval
was calculated by dividing the time
between the first dose and end of
resuscitation by the total No.
doses)
Intraosseous route
Ellemunter et al25 Cohort study Preterm and term infants of median All intraosseous line insertion was
1999 with 1 arm (range) gestation = 31 (25–41) wk
(N = 27) and birth wt = 1560 (515–4050) g
received intraosseous line for
resuscitation after birth. (Not all
infants received intraosseous
epinephrine.)
Suominen26 2015 Case report A 24-day-old infant received
(N = 1) continuous epinephrine and
norepinephrine infusion via
intraosseous line after
cardiopulmonary resuscitation and
hypothermia treatment of 24 h.
Oesterlie et al27 Case report A neonate received volume and
2014 (N = 1) ionized calcium infusion via
intraosseous line to manage septic
shock.
IM route
Doglioni et al28 2015 Case report Case report of a term infant who
received IM epinephrine
(0.02 mg/kg; concentration 1:
10 000) in the right thigh
Resultsa Conclusionsa
There is uncertainty about the effect
increased survival to admission of high-dose epinephrine versus
(n = 5764; RR 1.13 [95% CI 1.03 to standard dose because of very
1.24]) and ROSC in adults (n = 7014; low quality of evidence and
RR 1.15 [95% CI 1.02 to 1.29]) (very uncertain applicability to
low quality of evidence). No neonates because they were
significant differences in survival at excluded from most studies.
discharge were noted. No significant
difference in ROSC in children was
noted.
Free epinephrine is degraded over
increased to 28.6 (7.4–1283) nmol/L 1–2 h in preterm infants after
in ∼30 min and reduced to 5.07 high-dose endotracheal
(1.2–44.4) nmol/L at ∼100 min after epinephrine.
endotracheal epinephrine.
high dose of epinephrine and had via umbilical arterial catheter,
an ROSC within 2–3 min after the adverse effects were not
dose. All survived. reported. All 3 were also given
atropine before high-dose
epinephrine.
The survival to discharge was lower The study raises the possibility that
for longer intervals (crude OR 0.62 more frequent exposure to
[95% CI 0.49 to 0.79], 0.56 [0.39 to epinephrine impairs survival. The
0.81]) but higher after adjusting for change in direction of effect after
several variables. (adjusted OR 1.71 adjustment and uncertainty
[1.27 to 2.31] and 1.93 [95% CI 1.23 about applicability to newborns
to 3.03]) comparing 1–5 min to limit the conclusions that can be
between 5–8 and 8–10 min, drawn.
respectively.
The authors concluded that
successful with a procedure time of intraosseous line is quick, safe,
#2 min with no major and effective in neonatal
complications. Complications resuscitation even for extremely
included 1 hematoma, 1 preterm or low birth wt infants.
subcutaneous necrosis, and 3
dislocations of intraosseous lines.
The neonate had dislodgement of —
intraosseous line twice and
developed compartment syndrome
24 h after intraosseous line
insertion that resulted in the below-
knee amputation of lower limb.
The neonate developed white —
demarcation likely because of
extravasation of calcium that
progressed to tissue necrosis
resulting in transtibial amputation.
The infant developed a “circumscribed, —
irregular, edematous, red-violet,
3 cm 3 2 cm plaque surrounded by
an ischemic line” at the injection
site.

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8 ISAYAMA et al
TABLE 4 Continued
Study Study Design Population and Interventionsa
Time for securing
epinephrine routes
Heathcote et al29 Cohort study Infants with 1-min Apgar score of
2018 with 1 arm 0 received full resuscitation
(N = 27) (median [range] gestation 36 wk
[27–41 wk]; birth wt 2774 g
[980–4778 g]).
McKinsey and Simulation Time for intubation, UVC placement, Mean postnatal age of intubation, UVC
Perlamn30 2016 cohort study and IV epinephrine administration
with 1 arm were measured in simulation of
neonatal resuscitation of simulated
asystole neonates performed by 10
neonatal fellows.
Rajani et al31 2011 Simulation A total of 40 health care personnel (16 Mean procedure time (from time that
crossover residents, 6 fellows, 5 hospitalists,
RCT 5 neonatal nurse practitioners, and
8 neonatologists) performed
intraosseous and UVC placement
on neonatal manikins in simulated
neonatal resuscitation scenarios
after practice of intraosseous and
UVC procedures.
Abe et al32 2000 Simulation First- and second-year medical
students (n = 42) without previous
experience with intraosseous and
UVC performed intraosseous and
UVC procedures on task training
models (twice for each procedure).
OR, odds ratio; SR, systematic review; —, not applicable.
a Information most pertinent to our systematic review is summarized in this table.
Resultsa Conclusionsa
Median postnatal age of intubation, The real-life times for UVC
central IV access, and IV placement and IV epinephrine
epinephrine were 3.8 (95% CI 2.0 to were longer than those reported
7.5), 9.0 (95% CI 7.0 to 14.0), and 10.0 in previous simulated studies.
(95% CI 8.0 to 14.0) min after birth.
Applicability to infants is uncertain.
placement, and IV epinephrine
injection were ∼2, 6, and 6.5 min
after birth, respectively.
Applicability to infants is uncertain.
the relevant vascular access kit was
opened to time that lines were
inserted and flushed) was
significantly shorter for
intraosseous than UVC by a mean of
46 s (59 vs 105 s; P , .001). The
time difference was larger for
residents than for other groups. No
differences were found in the No.
errors or ease of use between
intraosseous and UVC, although
residents considered UVC
significantly more difficult than
intraosseous.
The mean procedure time was Applicability to infants is uncertain.
significantly shorter for
intraosseous than for UVC (52 and
134 s in the first attempt and 45 and
95 s in the second attempt for
intraosseous and UVC, respectively).
The intraosseous procedure was
considered to be less difficult than
the UVC procedure.

doses remain unknown.22,23 Longer
latency between doses was examined
in an observational cohort study of
children with cardiac arrest and was
associated with improved survival.
However, the direction of effect had
reversed after adjustment for
confounders, suggesting a high risk
of bias.24
In a few studies, authors described
routes for epinephrine administration
other than via endotracheal or IV
during neonatal resuscitation. In
a cohort study of 27 neonates within
5 hours of birth (median gestation of
31 weeks [range 25–41 weeks]), the
authors commented that intraosseous
access was always accomplished within
2 minutes (although data were not
shown) and incurred few major
complications.25 Nevertheless, in a few
case reports, authors have described
severe complications including
amputation of an extremity due to
extravasation and compartment
syndrome attributable to intraosseous
lines in infants.26,27 In one case report,
authors described severe skin lesions
at the site of an IM epinephrine
injection.28
In several studies, authors addressed
the time to obtain access suitable for
administering epinephrine (Table 4).
In a cohort of neonates who had a
1-minute Apgar score of 0 (median
gestation of 36 weeks [range 27–41
weeks]), among 23 for whom the time
was documented, umbilical venous
catheter (UVC) placement was
accomplished at a median time of 9
(95% CI 7 to 14) minutes after birth,
probably longer than ideal for
asystolic neonates, whereas
endotracheal tubes were placed much
earlier at a median time of 3.8 (95%
CI 2.0 to 7.5) minutes after birth.29
Simulation studies in which authors
used neonatal manikins suggest
shorter times to intraosseous than

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PEDIATRICS Volume 146, number 4, October 2020 9
UVC placement, but variation in study
design, participants, and models
makes it difficult to know whether
these results would correspond to
clinically meaningful time differences
in practice.31,32 Furthermore,
selection of participants in some
of these studies may have been
weighted to those who had greater
previous familiarity with
intraosseous insertion than UVC
placement.
Narrative Summary of Relevant
Animal Studies
Several animal studies provided
relevant information, although there
were variations in animal models and
interventions (Supplemental Table 8).
This systematic review was based on
the presumption that epinephrine is
efficacious, but this is based on expert
opinion because there are no adequate
human newborn infant trials.2 Animal
studies are used to address this
question. In near-term lambs
undergoing perinatal transition with
asphyxia-induced cardiac arrest,
administration of IV epinephrine
(0.01–0.015 mg/kg) was critical for
increasing carotid arterial pressure and
carotid blood flow and thereby
achieving ROSC.33 However, authors of
other animal models after the perinatal
transition (porcine asphyxial cardiac
arrest) found no benefit of
epinephrine.34,35 Wagner et al35
reported that 50% of animals achieving
ROSC did so without epinephrine,
whereas Linner et al34 revealed that
80% of saline controls achieved ROSC.
Both reported that epinephrine did not
improve the rate of ROSC.34,35
Furthermore, early epinephrine
(0.01 mg/kg administered before
closed-chest cardiac massage) did
not reduce the time to achieve
ROSC, improve the rate of ROSC,
or improve postresuscitation
survival compared with saline
controls.34
A neonatal lamb study (asphyxial
cardiac arrest) revealed that
epinephrine doses administered
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10
into the right atrium at 0.05 or
0.1 mg/kg resulted in a greater
increase in heart rate and systemic
vascular resistance than lower
doses (0.001 and 0.01 mg/kg).36
However, the higher dose
(0.1 mg/kg) blunted the rise in
cardiac output and stroke volume,
probably because of a dose-
dependent rise in peripheral
vascular resistance.36 Vali et al37
examined asphyxiated term lambs
in cardiac arrest with transitioning
fetal circulation and fluid-filled
lungs to compare IV versus
endotracheal epinephrine. In this
study, epinephrine administered via
the right atrium or UVC (0.03 mg/kg
every 3 minutes; maximum 4 doses)
achieved higher and faster peak
plasma concentrations than
epinephrine administered via
endotracheal (0.1 mg/kg) and
resulted in a shorter time to ROSC
with fewer doses.37
DISCUSSION
The human infant data on which to
base guidelines for epinephrine
treatment during neonatal
resuscitation are sparse. In this
systematic review, we included 4
retrospective cohort studies in which
authors reported outcomes for 117
eligible neonates. Only two studies
reporting 97 neonates allowed
comparison of endotracheal and IV
epinephrine administration, and only
one of these allowed analysis of the
primary outcome for this systematic
review: death at hospital discharge.7,8
The combined results revealed no
difference in the primary outcome or
the other critical and important
outcomes that were reported: failure to
achieve ROSC, time to ROSC, or the
proportion of infants receiving
additional epinephrine doses (post
hoc analysis). The very low certainty of
the evidence indicates that the findings
of “no difference” should be
interpreted cautiously; the wide CIs
mean that the data could still be
consistent with large, clinically
meaningful differences between IV
and endotracheal epinephrine for
neonatal resuscitation.
The 2010 ILCOR recommendations
were informed by indirect evidence
from animal or pediatric studies of
uncertain applicability to newborns.2
The human studies provided evidence
against using doses .0.03 mg/kg IV. A
pediatric case series suggested some
improvement in ROSC if a higher dose
was used after two lower doses had
failed to achieve ROSC,22 authors of
another study that included children
found no associated benefit,38 and the
only pediatric RCT suggested harm.39
Of note, the “high” epinephrine doses
of these pediatric studies
(0.1–0.2 mg/kg per dose) were 3 to
6 times higher than the maximum
dose currently recommended for
newborns (0.03 mg/kg per dose).
Taken together, the evidence at that
time was assessed as suggesting that
endotracheal might be less effective
than IV epinephrine, with the
possibility that lower response rates
could be mitigated by using a higher
endotracheal dose.2 The evidence from
the current systematic review is
insufficient to confirm or refute these
recommendations, and the available
studies highlight the difficulties of
studying, in vulnerable patients, rare
events (eg, 0.05%–0.06% of all births)
that are difficult to predict.7,8 Even if
multihospital databases were used to
increase the sample size, the high risk
of bias seems inescapable in
retrospective studies of routine
practice for rare events. The reasons
for choice of route of epinephrine
administration were not predefined in
either of the two studies that allowed
comparison of routes. The choice was
likely to have been influenced by
factors such as the extent of
forewarning and the characteristics of
the resuscitation team available at the
time.7,8 Because the use of epinephrine
in newborn resuscitation is rare and
unpredictable and the decision to use
it must be made rapidly, it is difficult
to design and perform adequate,
ethical randomized trials in human
ISAYAMA et al
infants, especially if previous
parental informed consent is required.
Prospective, multicenter cluster-
randomized trials could offer a way
forward.
We justified the decision to include
single-arm cohort studies that did not
allow any comparison between our
predefined “intervention” and “control”
by the extreme paucity of any evidence
from comparative studies, but these
studies did not alter the direction or
strength of evidence. They provided
data on preterm infants, but no robust
conclusion about the efficacy or safety
of endotracheal epinephrine in preterm
infants can be drawn.19,20 In the cohort
studied by Jankov et al,19 as many as
6% of all infants #750 g received
epinephrine, raising the possibility that
not all the infants were asphyxiated. A
proportion of those receiving chest
compressions and epinephrine might
have responded to better lung
ventilation alone, leading to
overestimation of survival and quality
of survival after epinephrine.
The lack of studies in which authors
evaluated high doses, administration
routes other than endotracheal or IV,
and nonstandard intervals of
administration of epinephrine
precluded any conclusions about
efficacy and risks. The narrative
summary of human studies that did not
meet the inclusion criteria of this
systematic review yielded little more.
The applicability of very low certainty
evidence from a recent systematic
review of adults and children in cardiac
arrest to newborns is uncertain.21
There are major differences in the
conditions that necessitate chest
compressions and epinephrine in
adults (predominance of asystole due
to cardiac causes), in children (mixed
causes), and in neonates (mostly
intrapartum hypoxia or asphyxia
related, against the background of the
perinatal cardiorespiratory transition).
Therefore, the extrapolation of study
findings from adults and children to
neonates requires caution. In the study
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PEDIATRICS Volume 146, number 4, October 2020
by Halling et al,7 most of the infants (11
of 15 [73%]) who achieved ROSC after
IV epinephrine required a cumulative
dose of 0.03 mg/kg or more (median
of $2 doses). This raises the
possibility that the initial IV dose of
0.01 mg/kg per dose was too low for
most infants. However, considering
all the evidence, the balance of
benefits and harms of higher doses
epinephrine for neonates remains
unresolved.
The best route of administration for
epinephrine is also uncertain. Although
in their study, Halling et al7 reported
similar median time for first
epinephrine administration via
endotracheal and IV (median 5.1 and
5.4 minutes after birth, respectively),
further research is needed to
determine if this is achievable in other
institutions. It is suggested in other
evidence that there may be potential
for endotracheal administration to be
achieved faster, but the impact on
efficacy is unknown.29,30 Although
simulation studies (also of uncertain
external validity with respect to
resuscitation of newborn infants)
indicated faster time for insertion of
intraosseous than umbilical venous
lines,31,32 caution is needed because
severe complications of intraosseous
lines in neonates have been
reported.26,27 There is a need for
future research to investigate any
advantages and the safety of
intraosseous lines in neonatal
resuscitation.
For the key questions of this
systematic review, animal studies
reveal mixed results, which might be
because of the variation in models.
These include term or near-term
lambs or piglets either during the
perinatal transition or at a few days
of age. The studies reflecting
transitional physiology, that is,
before closure of fetal shunts and
before establishment of sustained
lung aeration,34,38 might provide
more valid evidence for newly
born infants than studies in
which authors use older animals.
These transitional model studies
revealed benefit of IV epinephrine
treatment compared to no
epinephrine or endotracheal
epinephrine.33,37
Strengths of our study include
rigorous literature searching and
systematic review by using
a preregistered protocol, assessment
of certainty of evidence by using
GRADE,18 and input from experts
from the ILCOR Neonatal Life Support
Task Force. Limitations include the
absence of RCTs and the small
number of eligible studies and
infants. Because all eligible studies
included only newly born infants,
the findings may not be applicable
later in the neonatal period.
Furthermore, no eligible studies
examined alternative doses of IV
epinephrine, nonstandard intervals
of repeated epinephrine, and
routes other than IV and
endotracheal.
CONCLUSIONS
We found evidence that administration
of epinephrine by endotracheal versus
IV routes was associated with similar
rates of death at discharge, failure to
achieve ROSC, time to ROSC, and the
proportion of patients receiving
additional doses of epinephrine, but the
evidence is of very low certainty.
However, indirect evidence from
animal studies supports IV
administration over endotracheal
administration at the 0.01 to
0.03 mg/kg dose that has been
recommended by ILCOR. Although
epinephrine can be administered
via intraosseous instead of IV
routes, further human infant data
are needed.
ACKNOWLEDGMENTS
Several of the authors of this study
were ILCOR Neonatal Life Support
Task Force members (T.I., L.M., G.M.S.,
H.-S.K., Y.R., and H.G.L.). The following
11
additional task force members
provided input to the review protocol,
interpretation of the results, and on
the article as experts in neonatal
resuscitation: Dr Myra Wyckoff (The
University of Texas Southwestern
Medical Center, Dallas, TX); Dr
Jonathan Wyllie (James Cook
University Hospital, Middlesbrough,
Cleveland, United Kingdom); Dr
Khalid Aziz (Royal Alexandra
Hospital, Edmonton, Alberta,
Canada); Dr Maria Fernanda de
Almeida (Federal University of Sao
Paulo, Sao Paulo, Brazil); Dr Ruth
Guinsburg (Federal University of Sao
Paulo, Sao Paulo, Brazil); Dr
Shigeharu Hosono (Jichi Medical
University Saitama Medical Center,
Saitama, Japan); Dr Vishal Kapadia
(The University of Texas
Southwestern Medical Center, Dallas,
TX); Dr Jeffrey Perlman (Weill
Medical College, Weill Cornell
Medicine, New York, NY); Dr Charles
Roehr (University of Oxford and John
Radcliffe Hospital, Oxford, United
ABBREVIATIONS
Kingdom); Dr Edgardo Szyld ARD: absolute risk difference
(University of Oklahoma, Oklahoma CI: confidence interval
City, OK); Dr Daniele Trevisanuto CoSTR: consensus on science with
(University of Padua, Padua, treatment
Veneto, Italy); and Dr Sithembiso recommendations
Velaphi (Chris Hani Baragwanath GRADE: Grading of Recommendations
Academic Hospital, Johannesburg, Assessment, Development
South Africa). and Evaluation
ILCOR: International Liaison
We thank the authors of two included Committee on Resuscitation
studies (Dr Cecilie Halling, The IM: intramuscular
University of Texas Southwestern IV: intravenous(ly)
Medical Center, Dallas, TX; Dr Robert MD: mean difference
P. Jankov, Children’s Hospital of RCT: randomized controlled trial
Eastern Ontario and the Ottawa ROBINS-I: Risk of Bias in Non-
Hospital, Ontario, Canada) for randomized Studies - of
providing additional data for this Interventions
systematic review. We also thank Dr ROSC: return of spontaneous
Monica Kleinman (Boston Children’s circulation
Hospital, Boston, MA) for overseeing RR: risk ratio
and monitoring the progress of UVC: umbilical venous
our review as an ILCOR domain catheter
lead.

Dr Isayama drafted the protocol, screened studies, abstracted data, completed risk-of-bias evaluations and the Grading of Recommendations Assessment,
Development and Evaluation, completed the analysis, and prepared the first draft of the manuscript; Dr Mildenhall applied risk-of-bias assessment tools to articles
regarding human infants and drafted sections of the manuscript; Prof Schmölzer screened animal studies, extracted data, and drafted the section of the
manuscript in which the results of animal studies are reported; Dr Kim screened animal studies; Dr Rabi monitored the progress of this systematic review and
provided editorial and methodologic feedback at each step as a representative of the Scientific Advisory Committee of the International Liaison Committee of
Resuscitation; Ms Zeigler constructed the literature search strategies, obtained additional expert review of the search strategies and performed the database
searches, and drafted the part of the Methods section in which these processes are described; Prof Liley screened the human infant studies, extracted data, and
oversaw manuscript development; two reviewers provided suggestions to the manuscript; and all authors conceptualized and designed the study, including
preparing the protocol and critically reviewing and revising the manuscript for important intellectual content, approved the final manuscript as submitted, and
agree to be accountable for all aspects of the work.
DOI: https://doi.org/10.1542/peds.2020-0586
Accepted for publication Jun 16, 2020
Address correspondence to Tetsuya Isayama, MD, MSc, PhD, Division of Neonatology, Center for Maternal-Fetal Neonatal and Reproductive Medicine, National Center
for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan. E-mail: isayama-t@ncchd.go.jp
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright © 2020 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.
FUNDING: Funded by the American Heart Association, on behalf of the International Liaison Committee on Resuscitation for article submission to the editor. Dr
Isayama received payment from this funding source to complete this systematic review as expert systematic reviewer. The St Michael’s Hospital Health Sciences
Library received payment from this funding source for performing a literature search in this systematic review. Our information specialist, Ms Ziegler, did not
personally receive compensation. Dr Schmölzer is a recipient of the Heart and Stroke Foundation and University of Alberta Professorship in Neonatal Resuscitation,
is a National New Investigator of the Heart and Stroke Foundation Canada, and is an Alberta New Investigator of the Heart and Stroke Foundation Alberta; the other
authors have indicated they have no financial relationships relevant to this article to disclose.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

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12 ISAYAMA et al
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14 ISAYAMA et al
 The Route, Dose, and Interval of Epinephrine for Neonatal Resuscitation: A
Systematic Review
Tetsuya Isayama, Lindsay Mildenhall, Georg M. Schmölzer, Han-Suk Kim, Yacov
Rabi, Carolyn Ziegler, Helen G. Liley and INTERNATIONAL LIAISON
COMMITTEE ON RESUSCITATION NEWBORN LIFE SUPPORT TASK FORCE
Pediatrics originally published online September 9, 2020;

Updated Information & including high resolution figures, can be found at:
Services http://pediatrics.aappublications.org/content/early/2020/09/07/peds.2
020-0586
References This article cites 32 articles, 12 of which you can access for free at:
http://pediatrics.aappublications.org/content/early/2020/09/07/peds.2
020-0586#BIBL
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 The Route, Dose, and Interval of Epinephrine for Neonatal Resuscitation: A
Systematic Review
Tetsuya Isayama, Lindsay Mildenhall, Georg M. Schmölzer, Han-Suk Kim, Yacov
Rabi, Carolyn Ziegler, Helen G. Liley and INTERNATIONAL LIAISON
COMMITTEE ON RESUSCITATION NEWBORN LIFE SUPPORT TASK FORCE
Pediatrics originally published online September 9, 2020;

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/early/2020/09/07/peds.2020-0586

Data Supplement at:

http://pediatrics.aappublications.org/content/suppl/2020/09/07/peds.2020-0586.DCSupplemental

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