Problem
Criteria
Is there a problem
priority?
Benefits & harms of the options
What is the overall
certainty of this evidence?
Judgements
○ No
○ Probably no
○ Uncertain
○ Probably yes
○ Yes
○ Varies
Prolonged resuscitation of the neonate and guidelines for interruption
are critically necessary. However the frequency of asystole in term
and/or late preterm neonates at 10 minutes of life (Apgar 10 min.
=0) or absence of detectable HR after 10 minutes of adequate
resuscitation is low.
○ No included studies
○ Very low
○ Low
○ Moderate
○ High
In infants ≥36 weeks GA with an Apgar score of 0 for ≥ 10 minutes,
in spite of ongoing resuscitation, the
- Survival to NICU admission occurred in 41/78 (52%) infants
(3 studies – very low quality evidence)
- Death up to 24 months occurred in 123/183 (67%) infants that
survived DR resuscitation (9 studies – moderate quality evidence)
- Neurocognitive impairment at 18-24months occurred in 33/60
(55%) infants that survived up to 24 months (7 studies – low
quality)
- Survival without moderate or severe disability occurred in 24/160
(15%) infants that survived DR resuscitation and were evaluated for
neurologic outcomes (7 studies – low quality)
- Modern studies (≥ 2009) that included nested observational series
in RCTs of therapeutic hypothermia and series of infants that
received therapeutic hypothermia (3 articles encompassing 5
original studies) included 90 patients with Apgar at 10 minutes of
zero and successfully resuscitated at birth of whom: 45 (50%) died;
68 (76%) died or have major/moderate disability at 18-24 months,
and 22 (24%) survived without major/moderate disability at 18-24
months. Nelson’s study was discarded because it included preterm
infants and hypothermia was not available.
- Modern studies (≥ 2009) that included nested observational series
in RCTs of therapeutic whole body hypothermia and series of infants
that received whole body or selective head cooling (3 articles
encompassing 5 original studies) included 90 patients with Apgar at
10 minutes of zero and successfully resuscitated at birth of whom:
56 (62%) received hypothermia and 34 (38%) did not. Among the
56 cooled infants, 15 (27%) survived without major/moderate
disability at 18-24 months. Among the 34 non-cooled infants, 7
(21%) survived without major/moderate disability at 18-24 months.
○ Important
uncertainty or
variability
○ Possibly important
Is there important
uncertainty about how
much people value the
main outcomes?
Research evidence
uncertainty or
variability
○ Probably no
important uncertainty
of variability
○ No important
uncertainty of
variability
○ No known
undesirable
Additional considerations
Death or survival with
major/moderate disability after
birth is a highly valuable outcome
for families, health professionals
and society.
Criteria
Are the desirable
anticipated effects large?
Are the undesirable
anticipated effects small?
Are the desirable effects
large relative to
undesirable effects?
Judgements
○ No
○ Probably no
○ Uncertain
○ Probably yes
○ Yes
○ Varies
○ No
○ Probably no
○ Uncertain
○ Probably yes
○ Yes
○ Varies
○ No
○ Probably no
○ Uncertain
○ Probably yes
○ Yes
○ Varies
Research evidence
The desirable effects are intact neurologic survival after prolonged
resuscitation of newly born infants. Even though good quality care at
delivery room and NICU associated to therapeutic hypothermia and
potential new neuroprotective strategies may enhance this desirable
effect, it is not probable that a large number of infants will need this
care (the frequency of the event is relatively rare – around 5-10% of
severely asphyxiated infants by extrapolating from RCTs trials) nor a
large number of infants will be successfully resuscitated in the DR
after prolonged bradycardia or asystole.
The undesirable effect is mainly more survival but with a high
frequency of moderate/major disability. With improvements in the
neonatal care, continued resuscitation of term/late preterm infants
without detectable HR after 10 minutes of adequate resuscitation, it is
possible that death prior to hospital discharge will be avoided in a
majority of neonates, but CNS lesions would not be avoided.
Additional considerations
Criteria
Resource use
Are the resources required
small?
Is the incremental cost
small relative to the net
benefits?
Judgements
○ No
○ Probably no
○ Uncertain
○ Probably yes
○ Yes
○ Varies
increased
Equity
The resources needed to take good quality neonatal intensive care
and to offer neuroprotective strategies to newly born infants that
required prolonged resuscitation and did not have detectable HR at 10
minutes after resuscitation are extensive and expensive. They
include: equipped NICUs with technological devises to provide life
support and neuroprotection and skilled health professionals.
○ No
○ Probably no
○ Uncertain
○ Probably yes
○ Yes
○ Varies
○ Increased
○ Probably
What would be the impact
on health inequities?
Research evidence
○ Uncertain
○ Probably reduced
○ Reduced
○ Varies
The gap between poor/rich or well developed/less developed
countries (regions/cities/counties/neighborhoods) would probably
increase. The low resource placed would have more deaths and more
survival with major/moderate disabilities (no research on this item).
Additional considerations
Criteria
Judgements
Research evidence
The situation is very slippery:
Acceptability
1st. The patient is a newly born non-autonomous human being
Is the option acceptable to
key stakeholders?
○ No
○ Probably no
○ Uncertain
○ Probably yes
○ Yes
○ Varies
2nd. The family is, in general, in an emergency situation with
difficulties to make a decision, but this decision will have a huge
impact on them: death or life with a chance of important disabilities.
3rd. The health professionals have to act in the best interest of the
newly-born and its family, but their own principles will play a major
role in deciding for or against interrupting the resuscitation of the
newly born infants that required prolonged resuscitation and did not
have detectable HR at 10 minutes after resuscitation.
(no research on this item)
Feasibility
It is possible to continue to resuscitate newly born that do not have
detectable HR at 10 minutes after adequate resuscitation
Is the option feasible to
implement?
○ No
○ Probably no
○ Uncertain
○ Probably yes
○ Yes
○ Varies
Additional considerations
Recommendation
Balance of
consequences
Type of
recommendation
Recommendation
Justification
Undesirable consequences
clearly outweigh desirable
consequences in most
settings
Undesirable consequences
probably outweigh desirable
consequences in most
settings
The balance between desirable
and undesirable consequences
is closely balanced or
uncertain
Desirable consequences
probably outweigh
undesirable consequences in
most settings
Desirable consequences
clearly outweigh undesirable
consequences in most
settings
○
○
○X
○
○
We recommend against offering this
option
We suggest not offering this
option
We suggest offering this
option
We recommend offering this option
○
○
○X
○
We suggest that the decision to continue or withdraw resuscitative efforts after 10 minutes of adequate resuscitation with effective ventilation, CC
and IV epinephrine if heart rate remains undetectable should be individualized. Variables to be taken into consideration may include availability of
neonatal care and therapeutic hypothermia, and wishes expressed by the family (Quality of evidence is low)
In infants ≥ 35 weeks with an Apgar score of 0 for ≥10 minutes, the likelihood of dying or having severe or moderate developmental disabilities at
18-24 months is very high. Studies that included 69 infants with an Apgar score of zero at 10 minutes after birth who were successfully resuscitated
and randomized to hypothermia or normothermia, and case series of 21 additional infants who were managed with therapeutic hypothermia, suggest
improvement in outcome compared to previously reported cohorts. Among these 90 infants, 45 (50%) died and 22 (24%) survived without major or
moderate disability at 18-24 months. However, the number of infants with no HR at 10 minutes who died in the delivery room is unknown
[Low quality of evidence (selection bias & imprecision)]
Subgroup
considerations
Implementation
considerations
Monitoring and
evaluation
Research
possibilities