Neonatal Life Support
Octubre - 2020
IV.- Ventilación y
Oxigenación
1.- Sustained Inflation (NRP 809: SysRev)
When a newborn does not breathe spontaneously, establishing
functional residual capacity requires clearing
the lung fluid and replacing it with air. Debate continues
about the most effective method to achieve this. Animal
studies suggest that a longer sustained inflation may be
beneficial for short term respiratory outcomes, but most
such studies were performed in intubated animal models. 51 It is unknown whether the same is true in newborn
infants.52,53 In 2015, the NLS Task Force evaluated the evidence
supporting use of sustained inflation for initiation
of PPV in the delivery room and suggested against its routine
use.1,9,10 Multiple clinical trials of sustained inflation
have been published after that 2015 recommendation,
prompting the NLS Task Force to request a 2020 SysRev.53a
Population, Intervention, Comparator, Outcome, Study Design, and Time Frame
Population: Newborn infants who receive PPV due to bradycardia or ineffective respirations at birth
Intervention: Initiation of PPV with sustained inflation(s) more than 1 second
Comparator: Initiation of PPV with intermittent inflations, lasting 1 second or less per breath
Outcome21:
Primary: Death before discharge (critical)
Secondary:
Death in the delivery room (critical)
Death within first 48 hours (critical)
Need for mechanical ventilation during hospitalization (critical)
Air leaks (pneumothorax, pneumomediastinum, pneumopericardium, pulmonary interstitial emphysema) reported individually or as a composite outcome at any time during initial hospitalization and also within first 48 hours (critical)
Bronchopulmonary dysplasia, any grade,54 defined as need for supplemental oxygen at 28 days of life; need for supplemental oxygen at 36 weeks’ gestational age for infants born at or before 32 weeks of gestation (critical)
Intraventricular hemorrhage: Of any grade55 and Grade 3 or above (critical)
Retinopathy of prematurity: Of any stage56 and Stage 3 or above (critical)
Death by time of latest follow-up (critical)
Long-term neurodevelopmental or behavioral or education outcomes (greater than18 months of corrected age; test used to assess neurodevelopmental outcome should be of adequate quality and validated) (critical)
Study design: RCTs and nonrandomized studies (non- RCTs, interrupted time series, controlled before-andafter studies, cohort studies) were eligible for inclusion.
Time frame: All years and languages were included if there was an English abstract; unpublished studies (eg, conference abstracts, trial protocols) were excluded. Literature search was updated to October 25, 2019. PROSPERO Registration: CRD 42020155639
A Priori Subgroup Analyses
Preterm infants at 28+0 weeks or less, 28 weeks and 1 day to 31 weeks and 6 days, 32 weeks to 36 weeks and 6 days, 37 weeks or more (term)
Duration of first sustained inflation:
1 to 5 seconds, 6 to 15 seconds, greater than 15 seconds
Inflation pressure used during first sustained inflation :
20 cm H2O or less, greater than 20 cm H2O
Interface or device used to generate sustained inflation :
Nasopharyngeal tube, endotracheal tube, face mask, or T-piece device versus other device
A Priori Sensitivity Analyses
Effects of whether or not studies allowed multiple sustained inflations
Effects of the methodological quality of trials (to ascertain whether studies with high risk of bias overestimated treatment effects)
Consensus on Science
The SysRev identified 10 eligible RCTs including 1502
newborn infants. From analysis of this evidence, the NLS
Task Force developed a draft CoSTR that was posted
on the ILCOR website for a 2-week public commenting
period beginning February 17, 2020. The Justification
section was revised to address the public comments.
For the primary outcome of death before discharge, evidence of low certainty (downgraded for risk of bias and inconsistency) from 10 RCTs57–66 enrolling 1502 preterm newborns who received PPV for bradycardia or ineffective respirations at birth showed no significant benefit or harm from initiating PPV with sustained inflation greater than 1 second compared with initiating PPV with intermittent inflations lasting 1 second or less. See Table 2.
For the secondary critical long-term neurodevelopmental
outcomes and death at latest follow-up, no
studies were identified. The remainder of the secondary
outcomes are reported in Table 2.
Table 2. Meta-analysis of RCTs Comparing Initiation of PPV With Sustained Inflation(s) Greater Than 1 Second Versus Initiation of PPV With Intermittent Inflations, Last 1 Second or Less per Breath.
Subgroup Analysis for Primary Outcome
Subgroup Newborns Less Than 28+0 Weeks.
For the critical outcome of death before discharge, low-certainty evidence (downgraded for risk of bias and imprecision) from 5 RCTs57,58,61,62,65 enrolling 862 preterm newborns who received PPV for bradycardia or ineffective respirations at birth showed evidence of potential harm from initiating PPV with sustained inflation(s) greater than 1 second compared with initiating PPV with intermittent inflations lasting 1 second or less per breath (RR, 1.38; 95% CI, 1.00–1.91; I2, 0%; 46 more patients/1000 died before hospital discharge with sustained inflation(s) [0 fewer to 110 more per 1000]). The number needed to harm is 22 (95% CI, 9–1000 or greater).
Subgroup Newborns 28+1 Weeks to 31+6 Weeks
of Age.
For the critical outcome of death before discharge, very low-certainty
evidence (downgraded for risk of bias and very serious imprecision) from
4 RCTs 57,61,62,66 enrolling 175 preterm newborns who received PPV for
bradycardia or ineffective respirations at birth showed no significant
benefit or harm from initiating PPV with sustained inflation(s) greater
than 1 second when compared with initiating PPV with intermittent
inflations lasting 1 second or less per breath (RR, 1.33; 95% CI,
0.22–8.20; I2, 5%; 4 more patients/1000 died before hospital discharge
with sustained inflation(s) [9 fewer to 86 more per 1000]).
Subgroup Newborns 32+0 to 36+6 Weeks. No published data for this
gestational age group were available. Subgroup Newborns 37+0 Weeks or
More (Term).
No published data for this gestational age group were available.
Subgroup Analyses: by Duration of First Sustained Inflation or Inflation
Pressure of the Sustained Inflation.
For the critical outcome of death before discharge, subgroup analyses were conducted for the duration of the first sustained inflation (6–15 seconds versus greater than 15 seconds) and for the inspiratory pressure of the first sustained inflation with inspiratory pressure greater than 20 mm Hg versus 20 mm Hg or less). For each of these subgroup analyses, the evidence was of very low certainty (downgraded for risk of bias in all cases and variously for imprecision, very serious imprecision, and inconsistency). None of the subgroup analyses showed any significant benefit or harm of sustained inflation when compared with initiating PPV with intermittent inflations lasting 1 second or less per breath.
These conclusions were based on 9 RCTs57–61,63–66 enrolling 1300 preterm
newborns (sustained inflation 6–15 seconds), 2 RCTs 62,64 enrolling 222
preterm newborns (sustained inflation of greater than 15 seconds), 6
RCTs58–62,66 enrolling 803 preterm newborns (inspiratory pressure
greater than 20 mm Hg), and 4 RCTs57,63–65 enrolling 699 preterm
newborns (inspiratory pressure 20 mm Hg or less).
Sensitivity Analysis for Primary Outcome
Excluding Studies With High Risk of Bias. For the critical outcome of
death before discharge, lowcertainty evidence (downgraded for risk of
bias and
imprecision) from 9 RCTs 57–62,64–66 enrolling 1390 preterm newborns who
received PPV for bradycardia or ineffective respirations at birth showed
no significant
benefit or harm from initiating PPV with sustained inflation(s) greater
than 1 second compared with initiating PPV with intermittent inflations
lasting 1 second
or less per breath. (RR, 1.24; 95% CI, 0.92–1.68; I2, 24%; 21 more
patients/1000 died before hospital discharge with sustained inflation(s)
[95% CI, 7 fewer to
61 more per 1000]).
Excluding Studies That Allowed Only a Single Sustained Inflation During Resuscitation.
For the critical outcome of death before discharge, lowcertainty evidence (downgraded for risk of bias and imprecision) from 9 RCTs57–63,65,66 enrolling 1402 preterm newborns who received PPV for bradycardia or ineffective respirations at birth showed no significant benefit or harm from initiating PPV with sustained inflation greater than 1 second compared with initiating PPV with intermittent inflations lasting 1 second or less per breath (RR, 1.17; 95% CI, 0.88–1.55; I2, 22%; 18 more patients/1000 died before hospital discharge with sustained inflation(s) [95% CI, 13 fewer to 58 more per 1000]).
Sustained Inflation With Mask Only. When considering only studies where
a face mask was used to deliver initial sustained inflation, for the
critical outcome of death before discharge, low-certainty evidence (downgraded
for risk of bias and imprecision from 9 RCTs58–66 enrolling 1441 preterm
newborns who received PPV for bradycardia or ineffective respirations at
birth showed no significant benefit or harm from initiating PPV with
sustained inflation(s) greater than 1 second compared with initiating
PPV with intermittent inflations lasting 1 second or less per breath
(RR, 1.06; 95% CI, 0.61–1.39; I2, 42%; 7 more patients/1000 died before}
hospital discharge with sustained inflations [95% CI, 44 fewer to 44
more per 1000]).
Treatment Recommendations
For preterm newborn infants who receive PPV for bradycardia or ineffective respirations at birth, we suggest against the routine use of initial sustained inflation(s) greater than 5 seconds (weak recommendation, lowcertainty evidence).
A sustained inflation may be considered in research settings. For term or late preterm infants who receive PPV for bradycardia or ineffective respirations at birth, it is not possible to recommend any specific duration for initial inflations due to the very low confidence in effect estimates.
Justification and Evidence-to-Decision
Framework Highlights
This topic was prioritized by the NLS Task Force after
completion of a large RCT65 published after the 2015
CoSTR.1,9,10 In making these recommendations, the
NLS Task Force considered the potential for increased
death within 48 hours in preterm infants and increased
death before discharge in preterm infants less than
28+0 weeks, a predefined subgroup of the systematic
review.53a The task force recognizes that the outcome
of death within 48 hours was influenced primarily by
1 study for which death within 48 hours was one of
multiple secondary outcomes.65 The NLS Task Force also
considered the absence of evidence for either benefit
or harm after sustained inflation at birth for all other critical and
important outcomes.
The study comparisons were compromised by methodological heterogeneity
across studies, including indication, duration, the use of different
inspiratory pressures during sustained inflation and different inflation
durations. No study was identified comparing short duration sustained
inflation (less than 5 seconds) with intermittent inflations by using
inspiratory time of 1 second or less. There is no new evidence to
support or refute the practice of inflations less than 5 seconds
immediately after birth.
Hunt et al67 was excluded from
this systematic review because the control group received short duration
sustained
inflations (5 inflations of 2–3 seconds each) and the intervention
group received sustained inflations of 15 seconds
duration (and thus did not meet predefined inflation duration
criteria for the comparator group).
A patent airway is necessary for effective lung inflation or ventilation.
A recent study demonstrated that preterm rabbit pups are prone to
closure of the larynx
(ie, it opens only briefly during a spontaneous breath); this impedes
noninvasive PPV after birth.53 Studies in preterm infants have shown
that very little gas enters
the lungs in the absence of spontaneous breathing, suggesting that the
same phenomenon occurs in preterm infants.68,69
This SysRev53a (and most studies it identified) focused on use of sustained inflation in newborns who are not breathing effectively, so inadequate laryngeal patency could explain the absence of benefit from sustained inflation immediately after birth in preterm infants. In addition, the NLS Task Force noted that the trials included in the systematic review were pragmatic in design and did not include respiratory function monitors to assess actual pressure and volume delivered or the actual duration of the sustained inflation. It remains unknown if mask leak or airway obstruction influenced the effectiveness of the sustained inflations. This further decreases the confidence in the effect estimates, especially for the subgroup analyses. See Supplement Appendix A-2 for the evidence-todecision table for this SysRev.
Knowledge Gaps
How much of a role does glottis closure play in determining the effectiveness of sustained inflation in newborn of different gestational ages ?
What is the optimal duration, optimal inspiratory pressure, and number of sustained inflation maneuvers that allow establishment of functional
residual capacity without barotrauma ?The NLS Task Force recognizes that the total number of infants studied thus far is insufficient to have confidence in the estimate of effect. Larger
multicenter trials are needed in both term and preterm newborns to determine whether there are benefits or harms from sustained inflations.Studies comparing short duration sustained inflation (less than 5 seconds) with intermittent inflations (inspiratory time 1 second or less) are needed. This is an important knowledge gap as the European Resuscitation Council currently recommends using inflations of a 2- to 3-second
duration for the first 5 breaths in infants who are gasping or not breathing.Is there a role for sustained inflation for other situations in resuscitation, such as during cardiac compressions ?
(For more detail, see EvUp for NLS 895 CPR Ratios)
2.-
PEEP Versus No PEEP (NLS 897: EvUp)
During resuscitation after birth, PPV is provided to inflate
and ventilate the lungs. The lungs of sick or preterm
newborns tend to collapse as they are not supported
by a stiff chest wall and the infant’s breathing efforts
may be weak; the lungs may also be immature and surfactant-
deficient.70 PEEP provides low positive pressure
to the airway, which helps prevent lung collapse at the
end of expiration. PEEP maintains lung volume during
PPV in animal studies and improves lung function and
oxygenation.71,72 PEEP may be beneficial during neonatal
resuscitation, but the evidence from human studies is
limited. The previously reported evidence for use of PEEP
was evaluated as part of the 2015 CoSTR for NLS.1,9,10
In 2020, The NLS Task Force undertook an EvUp to
determine whether additional evidence published after
2015 warranted consideration of a new SysRev.
The evidence update (see Supplement Appendix C-4)
identified no evidence that would suggest the need for
a new SysRev or a change in the 2015 treatment recommendation. 1,9,10 Most of the new studies identified confirm the 2015
recommendation for use of PEEP during PPV in the delivery room.
Population, Intervention, Comparator, Outcome, Study Design, and Time Frame
Population: Preterm/term newborn infants who do not establish spontaneous respiration at birth
Intervention: Use of PEEP as part of the initial ventilation strategy
Comparator: No PEEP
Outcome21:
Survival to discharge (critical)
5-minute Apgar scores (important)
Time for heart rate to rise above 100/min (important)
Intubation rate in the delivery room (important)
Chest compressions in the delivery room (important)
Incidence of air leaks (important)
Oxygen saturation/oxygenation (important)
Fio2 exposure in the delivery room (important)
Mechanical ventilation in the first 72 hours (important)
Bronchopulmonary dysplasia (any) (important)
Treatment Recommendation
This treatment recommendation has not changed from 2015.1,9,10
We suggest using PEEP for the initial ventilation of premature newborn infants during delivery room resuscitation (weak recommendation, low-quality evidence).
We cannot make any recommendation for term infants because of insufficient data.
3.- CPAP Versus Intermittent
Positive Pressure Ventilation (NLS 590: EvUp)
Newborn infants who breathe spontaneously need to
establish a functional residual capacity after birth.73
Some newborn infants experience respiratory distress,
which manifests as labored breathing or persistent cyanosis.
Continuous positive airway pressure (CPAP), a
form of respiratory support, helps prevent atelectasis
in newborns. CPAP is especially helpful for preterm
newborn infants with breathing difficulty after birth
or after resuscitation.74 CPAP may also reduce the risk
of death or bronchopulmonary dysplasia in very preterm
infants when compared with endotracheal intubation
and PPV.75–79 For the newborn infant, CPAP is a
less- invasive form of respiratory support than intubation
and PPV.
Population, Intervention, Comparator, Outcome, Study Design, and Time Frame
Population: Spontaneously breathing preterm newborn infants with respiratory distress requiring respiratory support in the delivery room
Intervention: CPAP
Comparator: Intubation and intermittent PPV
Outcome21:
Death or bronchopulmonary dysplasia (critical)
Death (critical)
Bronchopulmonary dysplasia54 (important)
Air leak (important)
Necrotizing enterocolitis (important)
Severe intraventricular hemorrhage55 (critical)
Severe retinopathy of prematurity56 (critical)
This topic was last reviewed in
the 2015 CoSTR.1,9,10 The NLS Task Force sought an EvUp to identify any
studies published after the 2015 CoSTR. The EvUp did not identify any
new studies that would potentially change the current recommendation.
The 2015 CoSTR treatment recommendation remains in effect.1,9,10
The entire EvUp can be reviewed in Supplement Appendix C-5.
Treatment Recommendations
This treatment recommendation (below) is unchanged from 2010.1,9,10
For spontaneously breathing preterm newborn infants with respiratory distress requiring respiratory support in the delivery room, we suggest initial use of CPAP rather than intubation and intermittent PPV (weak recommendation, moderate certainly of evidence).
4.- T-Piece Resuscitator Versus Self-Inflating Bag for Ventilation (NLS 870: ScopRev)
Rationale for Review
In 2015, the ILCOR Neonatal Task Force published a
CoSTR summarizing the evidence comparing the use
of a T-piece resuscitator with the use of a self-inflating
bag for newborns receiving ventilation during resuscitation. 1,9,10 The studies reviewed for the 2015 CoSTR
noted that the use of T-piece resuscitators demonstrated
marginal but not statistically significant benefits
for the clinical outcome of achieving spontaneous
breathing.
The NLS Task Force decided to reevaluate this topic
through a ScopRev79a to determine whether sufficient
new evidence had been published after the 2015
CoSTR1,9,10 to justify a new SysRev.
Population, Intervention, Comparator, Outcome, Study Design, and Time Frame
Population: Newborn infants receiving ventilation (PPV) during resuscitation
Intervention: T-piece resuscitator
Comparator: Self-inflating bag
Outcome21:
Survival to hospital discharge (critical)
Air leak (important)
Development of stable spontaneous breathing (no need for intubation in delivery room) (important)
Bronchopulmonary dysplasia (any) (important)
Study design: RCTs and nonrandomized studies (non-RCTs, interrupted time series, controlled before-and-after studies, cohort studies) are eligible for inclusion.
Time frame: All years and languages were included if there was an English abstract; unpublished studies (eg, conference abstracts, trial protocols) were excluded. Literature search was updated to January 3, 2020.
Summary of Evidence
Using the 2015 search strategy, this ScopRev79a identified 2 additional studies: 1 RCT80 and 1 observational study81 published after the review for the 2015 CoSTR was completed. When these 2 studies were added to the 2 studies identified in the 2015 CoSTR for NLS,1,9,10 a total of 4 clinical studies could be included in the data analysis, representing a total of 2889 newborns (927 in 3 RCTs and 1962 in 1 observational study).80–83
The 4 studies investigated different populations; 2 studies included
term and preterm infants,80,83 and 2 studies enrolled preterm infants
only.81,82 The studies also differed in reported outcomes and were from
diverse geographical areas. The large observational study found that use
of a
T-piece resuscitator increased survival and decreased bronchopulmonary
dysplasia and intubation in the delivery room.81 The latest RCT
also found decreased intubation in the delivery room when T-piece
resuscitators were used.80 The ScopRev can be reviewed in its entirety
in Supplement Appendix B-3.
Task Force Insights
Data from a substantial number of additional patients reported in 1 RCT and 1 large observational study suggest improved survival, less need for intubation, and a lower incidence of bronchopulmonary dysplasia when a T-piece resuscitator is used (compared with a self-inflating resuscitator bag) during PPV at birth, particularly in preterm infants.
The NLS Task Force concludes that these findings justify a new SysRev of the use of a T-piece resuscitator versus self-inflating bag for administering PPV at birth. The task force anticipates that not only the strength, but the direction of evidence may be changing toward support for using T-piece devices. Until a new SysRev is completed and results are analyzed by the NLS Task Force, the 2015 treatment recommendation remains in effect.1,9,10
Treatment Recommendation
This treatment recommendation (below) is unchanged from 2010.1,9,10
There is insufficient evidence regarding the use of T-piece resuscitator or self-inflating bag for initial PPV at birth, so the recommendation of one device over another would be purely speculative because the confidence in effect estimates is so low.
5.- Oxygen for Preterm Resuscitation (NLS
864: 2019 CoSTR)
Preterm newborn infants are
vulnerable to oxidative stress as a result of reduced antioxidant
defenses and frequent exposure to oxygen during stabilization in
the
delivery room.84 Many common preterm morbidities, such as
bronchopulmonary dysplasia, retinopathy of prematurity and
intraventricular hemorrhage are directly
associated with oxygen toxicity. In the delivery room, it is imperative
that clinicians prevent hypoxia while limiting hyperoxia. In 2019, the
NLS Task Force published a SysRev with meta-analysis of the relevant
available evidence on this topic,85 and published an ILCOR CoSTR
statement.86,87
Population, Intervention, Comparator, Outcome, Study Design, and Time Frame
Population: Preterm newborn infants (less than 35 weeks’ estimated gestational age) who receive respiratory support at birth
Intervention: Lower initial oxygen concentration (50% or less O2)
Comparator: Higher initial oxygen concentration (more than 50% O2)
Outcome21 :
Primary: All-cause short-term mortality (in hospital or 30 days) (critical)
Secondary:
All-cause long-term mortality (1–3 years) (critical)
Long-term NDI (1–3 years) (critical)
Retinopathy of prematurity (Stages III–V)56 (critical)
Necrotizing enterocolitis Stage II (pneumatosis) or III (surgical)88 (important)
Bronchopulmonary dysplasia (moderate to severe)54 (critical)
Major intraventricular hemorrhage (Grade III–IV)55 (critical)
Time to heart rate more than 100/min (important)
Study design: RCTs, quasi-RCTs and nonrandomized studies included; animal studies, unpublished studies, and published abstracts (eg, conference abstracts) excluded
Time frame: Literature search was from 1980 to August 10, 2018.
PROSPERO Registration: CRD42018084902
Treatment Recommendations
This treatment recommendation (below) is unchanged from 2019.86,87
For preterm newborn infants (less than 35 weeks’ gestation) who receive respiratory support at birth, we suggest starting with a lower oxygen concentration (21% to 30%) rather than higher initial oxygen concentration (60% to 100%) (weak recommendation, very low-certainty evidence).
We suggest the range of 21% to 30% oxygen because all trials used this for the low oxygen concentration group.
Subsequent titration of oxygen concentration using pulse oximetry is advised (weak recommendation, very low-certainty evidence).
6.-
Oxygen for Term Resuscitation (NLS 1554: 2019 CoSTR)
Administration of high oxygen concentrations leads to
free radical formation and may be toxic to many tissues
and organs of the newborn. Questions persist about the
risks of hypoxia versus risks of exposure to excess oxygen
for late preterm and term newborn infants who receive
respiratory support in the delivery room. In 2019, the
NLS Task Force published a SysRev with meta-analysis of
the relevant available evidence on this topic89 and also
published an NLS CoSTR.86,87 For complete review of the
consensus on science for the secondary outcomes and
subgroup analyses, please see the NLS Task Force section
of the recently published 2019 CoSTR summary.86,87
Population, Intervention,
Comparator, Outcome, Study Design, and Time Frame
Population: Newborn infants (35 weeks’ or greater gestation) who receive respiratory support at birth
Intervention: Lower initial oxygen concentration (50% O2 or less)
Comparator: Higher initial oxygen concentration (greater than 50% O2)
Outcome21:
Primary: All-cause short-term mortality (in hospital or 30 days) (critical)
Secondary: All-cause long-term mortality (1–3 years) (critical)
Long-term NDI (1–3 years) (critical)
HIE (Sarnat Stage 2–3)90 (critical)
Study design: RCTs, quasi-RCTs, and nonrandomized studies included; animal studies, unpublished studies, and published abstracts (eg, conference abstracts) excluded
Time frame: Literature search was from 1980 to August 10, 2018.
PROSPERO Registration: CRD42018084902
Treatment Recommendations
This treatment recommendation (below) is unchanged from 2019.86,87
For newborn infants at 35 weeks’ or greater gestation receiving respiratory support at birth, we suggest starting with 21% oxygen (air) (weak recommendation, low certainty of evidence).
We recommend against starting with 100% oxygen (strong recommendation, low certainty of evidence).