Neonatal Life Support
Octubre - 2020
VII .- PROGNOSTICATION DURING CPR
1.-
Impact of Duration of Intensive
Resuscitation (NLS 896: SysRev)
It can be difficult for clinicians to decide how long resuscitative
efforts should continue in a newborn infant
with no heart rate and/or absent respirations with a very
low heart rate after sustained resuscitative efforts.12–14 This critical decision involves knowing when to redirect
the care of the newborn infant from resuscitation to
the provision of comfort and contact with the parents.
If such a decision is made too early, some infants with
potential to survive with good neurodevelopmental
outcome may die. If the decision is made too late, there
is likely to be a diminishing potential for survival, especially
without severe neurological injury.
In recent years, long-term outcomes for survivors requiring
prolonged resuscitation have improved somewhat.
In 2015, the CoSTR focused on the following question:
“In infants with a gestational age of 36 weeks or
greater and an Apgar score of 0 for 10 minutes or longer,
despite ongoing resuscitation, what is the rate of survival
to NICU admission and death or neurocognitive impairment
at 18 to 22 months?” In 2019, the NLS Task Force
revised the question slightly to better reflect the questions
clinicians and families ask in such a crisis situation.
The current PICOST attempts to reduce the emphasis
on the Apgar score at 10 minutes and puts more focus
on the incremental time of resuscitation exposure from
birth as related to outcome.
Population, Intervention, Comparator, Outcome,
Study Design, and Time Frame
Population: Newborn infants presenting with at least 10 minutes of asystole, bradycardia (heart rate less than 60/min), or pulseless electric activity after birth for which CPR is indicated
Intervention: Ongoing CPR for incremental time intervals beyond 10 minutes after birth
Comparator: CPR discontinued at 10 minutes after birth
Outcome21 :
Survival (to any age) (critical)
Neurodevelopmental outcomes (critical)
Composite of survival to any age without moderate or severe neurodisability (critical)
Study design: Cross-sectional or cohort studies were eligible for inclusion. Ancillary analyses of RCTs and nonrandomized studies (non-RCTs, interrupted time series, controlled before-and-after studies, cohort studies, case series) were eligible for inclusion. All years and languages were included if there was an English abstract. Conference abstracts and trial protocols were excluded.
Time frame: All years were included from inception of the searched databases to October 17, 2019.
A Priori Subgroups to Be Examined
Hypothermia postresuscitative care among newborn infants
36 weeks’ or greater gestational age; 36 weeks’
or greater gestational age versus less than 36 weeks’;
birthweight 2500 g or greater; infants enrolled in population-level cohort studies
PROSPERO Registration: CRD42020157370
Consensus on Science
The SysRev102a identified 15 studies that included 470
infants (see Figure 2). For the critical outcome of survival until last follow up,
we identified very low-certainty evidence (downgraded
for risk of bias and inconsistency) from 15 studies103–117 reporting
outcomes of 470 newborns to last known followup
(range: 4 months–8 years of age). The number of enrolled
newborns ranged from 3 to 177 per study. Across
studies, reported survival rates to last follow up ranged
from 1.7% to 100%.
Figure 2. Modified flow diagram of
number of studies and infants included for each specified outcome for
infants experiencing resuscitation that
exceeded 10 minutes. Moderate to severe NDI was defined by
each study.
Among all 470 newborns reported in the literature, including studies that required survival to NICU admission or enrollment in a cooling protocol for inclusion, 187 (39.8%) survived to last follow-up. The decision was made not to calculate confidence intervals as a result of heterogeneity across included studies. For the critical outcome of neurodevelopmental outcomes among survivors, we identified very low-certainty evidence (downgraded for risk of bias and inconsistency) from 13 studies including 277 infants.103,104,106–112,114–117 Neurodevelopmental outcomes were assessed in 80 survivors. Thirty infants among 80 survivors (37.5%) did not have moderate or severe NDI (range: 0% to 100%). There was important heterogeneity across studies (and in some cases within studies) about the timing and tools used to assess neurodevelopmental outcomes that precluded calculation of confidence intervals.
For the composite critical outcome of survival without
NDI, we identified very low-certainty evidence (downgraded
for risk of bias and inconsistency) from 13 studies
of 277 infants103,104,106–112,114–117 reporting neurodevelopmental
outcomes. Among all 277 infants reported in
these studies, 69% died before last follow up, 18% survived
with moderate to severe impairment, and 11% survived
without moderate to severe impairment (2% lost
to follow up).
There was important heterogeneity across studies (and in some cases, within studies) about the timing and tools used to assess neurodevelopmental outcomes that precluded calculation of confidence intervals. Note: Neurodevelopmental outcomes in postdischarge follow-up were reported in 13 studies using structured exams. 103,104,106–112,114–117 In 11 studies, these assessments used validated developmental assessment tools.106–112,114–117
These tools included developmental assessment tools such as the Bayley Scales of Infant and Toddler Development (any version) or a Japanese version of the Bayley Scales (Kyoto Scale of Psychological Development); motor assessment tools such as Gross Motor Function Classification System or Peabody Developmental Motor Scales; and cognitive evaluation tools such as Stanford-Binet Test, Griffiths Scales of Child Development (any version), or Wechsler Preschool and Primary Scale of Intelligence (any version).
Two studies103,104 reported only a formal neurological evaluation of the survivors. Auditory and visual assessment varied among studies. Of note, children assessed only by screening tools (such as Denver Developmental Screening Test) in any study were analyzed as lost to followup. Time of follow-up for the 80 survivors assessed for NDI was 12 months or greater in 83% (66/80) of the infants (range: 12 months–8 years) and less than 12 months in 6% (5/80) of the infants. Time of assessment was not reported in 1 study114 with 11% (9/80) survivors. Moderate and severe NDI were defined by each study.
Subgroup Considerations
Prespecified subgroup analyses for the specified critical
outcomes of survival to last follow-up, survival without
NDI, and the composite of survival without moderate
to severe NDI are depicted in Table 4. Insufficient details
about birthweight precluded the planned subgroup
analysis based on birthweight.
Given the small sample sizes and heterogeneity of
study characteristics, there is no strong evidence on
which to base recommendations for specific subgroups
of infants.
Table 4. Subgroup Analyses for Specified Outcomes for Infants Who Had Resuscitation That Exceeded 10 Minutes.
Treatment Recommendations
Failure to achieve return of spontaneous circulation in newborn infants despite 10 to 20 minutes of intensive resuscitation is associated with a high risk of mortality and a high risk of moderate-to-severe neurodevelopmental impairment among survivors. However, there is no evidence that any specific duration of resuscitation consistently predicts mortality or moderate-to-severe neurodevelopmental impairment. If, despite provision of all the recommended steps of resuscitation and excluding reversible causes, a newborn infant requires ongoing cardiopulmonary resuscitation (CPR) after birth, we suggest discussion of discontinuing resuscitative efforts with the clinical team and family. A reasonable time frame to consider this change in goals of care is around 20 minutes after birth. (Weak recommendation, very low-certainty evidence).
Justification and Evidence-to-Decision Framework Highlights
In making this recommendation, we recognize the
need to balance the risk of ceasing resuscitation too
early, when ROSC and long-term survival may still be
achievable, and continuing resuscitation for too long,
when ROSC may occur but survival is associated with a
high risk of severe neurological injury. The appreciable
number of survivors without moderate or severe NDI after 10 minutes or greater of resuscitation suggests that
early cessation of resuscitation may preclude survival of
some infants who may have a good outcome.
While an Apgar score of 0 or 1 at 10 minutes is a
strong predictor of mortality and morbidity, recent case
reports and series have reported favorable outcomes
among newborn infants with Apgar scores of 0 or 1 at
10 minutes after birth who achieved ROSC and received
therapeutic hypothermia. In this subgroup of newborns
with severe depression at birth, both survival and survival
without moderate-to-severe impairment have been reported.
Among 105 such infants reported in the literature
with Apgar scores 0 or 1 who were successfully resuscitated,
were treated with therapeutic hypothermia, and
were assessed after discharge, 20% of all infants survived
without moderate-to-severe NDI, and 37% of the survivors
did not have moderate or severe NDI.107,109–112,116,117 The evidence supporting this recommendation is of
very low certainty.
However, we value the possibility of survival and intact survival after ongoing resuscitation. In a large multisite cohort of 659 newborn infants who survived to discharge after more than 1 minute of chest compressions in the delivery room, 25% of survivors received 10 minutes or more of resuscitation.118 This study did not specifically report on infants with 10-minute Apgar scores of 0 or 1. While these data indicate that survival to discharge is possible after a lengthy duration of CPR, neurodevelopmental outcomes among survivors in this study were not reported.
Extremely limited data are available about outcomes
of newborn infants who received 20 or more minutes
of CPR after birth. Five studies included in this systematic
review110–112,116,117 reported results for 39 newborn
infants in whom first detectable heart rate or heart rate
100/min or greater occurred at or beyond 20 minutes
after birth. Of these, 38% (15/39) survived until last follow
up and 40% (6/15) of survivors did not have moderate
or severe neuroimpairment.
The task force agreed that in addition to considering
duration of resuscitation, it was important to consider
whether all recommended resuscitation interventions
were provided. Studies suggest that the time taken to
accomplish steps of a resuscitation up to the point of
administration of 1 or more doses of epinephrine varies
widely across studies but may take as long as 20
minutes.7,93,111,119 The variation in the interval from birth
to completion of these steps may depend on the characteristics
and time to attendance of the resuscitation
team. Thus, using a single time interval after birth to
discontinue intensive resuscitation for all newborns
might mean in some cases that the full repertoire of recommended resuscitation
interventions were not provided
before cessation of resuscitation.
Another issue considered by the task force was the
potential impact on infants and their families. Among
the included studies, most deaths occurred either in
the delivery room/birth suite or during the initial hospitalization.
In this systematic review, rates of survival
to discharge were similar to rates of survival to last
follow up (see Figure 2). For those infants who ultimately
die in early infancy, achieving even this shortterm
survival may provide the family the time and opportunity
to participate in decision-making and care
of their infant. Moreover, intact survival is possible
among surviving infants. In this systematic review,
38% of surviving infants did not have moderate or
severe impairment.
Given these considerations, we do not recommend
a specific duration of resuscitation after which point resuscitative
efforts should cease. Instead, we suggest that
providers consider changing the goals of care if a newborn
infant has not responded to all recommended steps
of resuscitation that are appropriate to the given setting.
We acknowledge that cultural and religious differences,
including different perceptions of the value of extending
life, the quality of life, and the acceptance of comfort
care as an option, may influence the decision.120–122 Ultimately, the decision to initiate and continue
resuscitative efforts should be individualized and informed by factors such as gestational age, the presence
of congenital anomalies, the timing of perinatal insult
(if known), the perceived adequacy of resuscitative interventions,
the family’s stated preferences and values,
and the availability of postresuscitative resources, such
as neonatal intensive care, and neuroprotective strategies,
such as therapeutic hypothermia. Finally, in lowresource
settings, where emphasis is given to face-mask
ventilation with 21% oxygen for nonbreathing neonates,
123 advanced resuscitation procedures and prolonging
resuscitation may not be an option. Therefore,
caution must be taken in the global adoption of this
treatment recommendation as local/regional discussion
and customization are necessary.
Implementation Considerations
Acceptability of the intervention should be thoroughly discussed in the different settings according to cultural, ethical, and moral standards that prevail in each country or region. High-quality resuscitation should be available for infants in need, and training of skills and team performance are critical to achieve it. Communication with families should be optimized, and whenever possible, parents’ wishes and values must be considered, even in urgent and stressful situations. Availability of neonatal intensive care and neuroprotective strategies for postresuscitation care is another aspect that may be considered in the decision-making process.
Monitoring and Implementation
It is important to monitor both short- and long-term
outcomes for infants who had a prolonged interval
between birth and ROSC. In addition, although health
equity was not objectively reported for prolonged neonatal
resuscitation, it is possible that prolonged resuscitation
may be offered to a higher proportion of infants
in higher-resource settings; outcomes may also be better
in settings with full availability of intensive care and
neuroprotective strategies.
Prolonged CPR after birth is relatively rare, so an international
registry of events, with detailed description
of procedures and their timing in the delivery room,
postresuscitation care, and neurological outcomes assessed
in follow-up, would provide essential evidence
to inform the discussion f how long is too long. Such a
registry would also provide valuable information about
variability in practice regarding duration of resuscitation
in different settings.
For more information, refer to the evidence-to-decision table in Supplement Appendix A-5.
Knowledge Gaps
Many studies reported only outcomes of infants who survived
resuscitation and met a specific study eligibility criterion,
such as NICU admission or initiation of therapeutic
hypothermia. Therefore, estimates of mortality after prolonged
resuscitation are likely to underestimate the true
rate of death after prolonged resuscitation because this
would need to also include infants for whom resuscitation
had failed. Studies that account for the full population of
newborn infants who receive CPR after birth by using consistent
definitions of stillbirths and resuscitation failures
are needed to identify the incidence of death and NDI after
prolonged resuscitation of term and preterm infants.
In addition, the extent and timing of resuscitation interventions
were not reported in most studies; therefore,
prognosis of newborn infants after prolonged resuscitation
at birth is inferred from the available data.
Further, most available studies characterized the infant’s response to resuscitation using the Apgar score at 10 minutes, which is prone to subjective assessment and does not provide information about ongoing assessments or responses to resuscitation beyond 10 minutes. More granular information about the interval from birth to detectable heart rate that uses objective measures such as ECG and time to ROSC is needed to inform more precise recommendations about the duration of intensive resuscitation after birth.
Additionally, as the ECG is used more frequently in the delivery
room environment, additional information about the
presenting rhythm (bradycardia, asystole, pulseless electric
activity) preceding chest compressions will be helpful to
identify outcomes after these varied presentations.
Therefore, studies that report outcomes on the full
population of infants who present without signs of life
and receive intensive resuscitation are needed with the
following :
A priori definitions of stillbirths and completeness of resuscitation attempts
Complete description of cointerventions (resuscitation procedures), timing of procedures at birth, and interventions in postresuscitative care
Description of methods to assess the heart rate during resuscitation by using objective measures, such as ECG, and report of timing for detection of heart rate and heart rate 60/min or greater and 100/min or greater
Complete follow-up of survivors with accurate and consistent methods of assessment of neurodevelopment, comparable across studies and population