Resuscitation in High-Risk

Infants: What Can We Do

Better?
Rinawati Rohsiswatmo
Who is Considered as High Risk Infant?

Extreme preterm infants

Term infants with comorbidities, such as

• Congenital Hernia Diaphragm

• Meconium Aspiration Syndrome
• Congenital Heart Disease
• Etc.
 Premature :
(WHO)

All babies born within gestational age of <37 weeks

 Thermoregulation
In the delivery room and during transportation, interventions
can be practiced to prevent hypothermia:

Plastic wrap or bag,

Radiant warmer Thermal mattress
plastic caps, cling wrap

Pre-warmed
Warm humidified VAPOTHERM TRANSFER UNIT
single/double walled Skin to skin contact
gases
incubators

Hosono S, et al. Summary of Japanese Neonatal Cardiopulmonary Resuscitation Guidelines 2015. Pediatrics International (2020) 62,128–139
Meyer MP, Owen LS, te Pas AB. Use of Heated Humidified Gases for Early Stabilization of Preterm Infants: A Meta-Analysis. Front Pediatr. 2018 Oct 25;6:319.
 Humidification
Heating and humidification was achieved
by adding 30-50 ml of water and turning
on the device prior to expected delivery.
The median humidifier temperature was
36.5 oC
• Two studies (476 preterm infants <32 weeks gestation) were enrolled
• The number of infants with more severe hypothermia (<35.5◦C) was significantly reduced
• Preterm infants <28 weeks had significantly less admission hypothermia
• Mortality and measures of respiratory outcome were not significantly different, though there
was a trend to improvement in all respiratory measures assessed.
• There were no significant adverse events and no increase in admission hyperthermia (>37.5◦C)

Meyer MP, Owen LS, te Pas AB. Use of Heated Humidified Gases for Early Stabilization of Preterm Infants: A Meta-Analysis. Front Pediatr. 2018 Oct 25;6:319.
 Humidification
• Heating and humidification of inspired gases immediately after birth
and during transport 🡪 improves admission temperature in preterm
infants
• Consideration should be given to incorporating this technique into other strategies (e.g., use of
plastic wrap) designed to keep preterm infants warm on admission to the neonatal unit

With the use of heated humidified gases in delivery room, hypothermia was
significantly reduced, especially in ELBW infants

Meyer MP, Owen LS, te Pas AB. Use of Heated Humidified Gases for Early Stabilization of Preterm Infants: A Meta-Analysis. Front Pediatr. 2018 Oct 25;6:319.
 Humidification
• Short periods of exposure to cold dry respiratory gases 🡪 destructive effects
• ↓ lung compliance, ↑ work of breathing, release of proinflammatory cytokines
and damage to the mucociliary layer
• Humidity enhances mucociliary clearance

Meyer MP, Owen LS, te Pas AB. Use of Heated Humidified Gases for Early Stabilization of Preterm Infants: A Meta-Analysis. Front Pediatr. 2018 Oct 25;6:319.
Bustamante-Marin XM, Ostrowski LE. Cilia and Mucociliary Clearance. Cold Spring Harb Perspect Biol. 2017;9(4).
 RCT to compare nasal high-flow
therapy with standard care (no
nasal high-flow therapy or
supplemental oxygen) in neonates
undergoing oral endotracheal
intubation
Primary outcome 🡪 successful
intubation on the first attempt
without physiological instability*
in the infant.
Nasal high-flow therapy during
the procedure improved the
likelihood of successful
intubation on the first attempt
without physiological instability in
the infant.

*defined as an absolute decrease in the

peripheral oxygen saturation of >20% from the
pre-intubation baseline level or bradycardia
with a heart rate of <100 beats per minute

N Engl J Med 2022; 386:1627-1637

DOI: 10.1056/NEJMoa2116735
SHINE Procedure

Courtesy of Peter Davis

The use of high-flow nasal cannulae is
After extubation, 303 very preterm Infants in whom treatment with
an increasingly popular alternative to
infants is either using: high-flow nasal cannulae failed could
nasal continuous positive airway
pressure (CPAP) for noninvasive high-flow nasal cannulae (5-6Lpm) be treated with nasal CPAP
respiratory support of very preterm VS Infants in whom nasal CPAP failed
infants (gestational age, <32 weeks) were reintubated.
nasal CPAP (7 cmH2O)
after extubation.

The primary outcome was

treatment failure within 7 days.

Manley BJ, Owen LS, Doyle LW, Andersen CC, Cartwright DW, Pritchard MA, Donath SM, Davis PG. High-flow nasal
cannulae in very preterm infants after extubation. N Engl J Med. 2013 Oct 10;369(15):1425-33. doi:
10.1056/NEJMoa1300071. PMID: 24106935.
High-flow nasal cannulae was noninferior to the use of nasal CPAP, with treatment failure
occurring in 52 of 152 infants (34.2%) in the nasal-cannulae group and in 39 of 151 infants
(25.8%) in the CPAP group

Almost half the infants in whom treatment with high-flow nasal cannulae failed were
successfully treated with CPAP without reintubation.

The incidence of nasal trauma was significantly lower in the nasal-cannulae group than in the
CPAP group (P=0.01), but there were no significant differences in rates of serious adverse
events or other complications.

Although the result for the primary outcome was close to the margin of noninferiority, the
efficacy of high-flow nasal cannulae was similar to that of CPAP as respiratory support for very
preterm infants after extubation.

Manley BJ, Owen LS, Doyle LW, Andersen CC, Cartwright DW, Pritchard MA, Donath SM, Davis PG. High-flow nasal
cannulae in very preterm infants after extubation. N Engl J Med. 2013 Oct 10;369(15):1425-33. doi:
10.1056/NEJMoa1300071. PMID: 24106935.
Surfactant Therapy

12
 Clinical Indications
Surfactant replacement therapy should be Surfactant replacement therapy may be
considered in: considered in:

Severe meconium aspiration syndrome with

Neonates with clinical and radiographic evidence severe respiratory failure – may improve
of RDS oxygenation and reduce the need for
extracorporeal membrane oxygenation (ECMO)

Neonates at risk of developing RDS (e.g. <32 Pulmonary haemorrhage with clinical
weeks or low birth weight <1300g) deterioration

Severe respiratory syncytial virus-induced

Neonates who are intubated, regardless of respiratory failure - may improve gas exchange
gestation, and requiring FiO2 >40% and respiratory mechanics and shorten the
duration of invasive mechanical ventilation

The Royal Children's Hospital Melbourne

1. If a preterm baby <30 weeks of gestation requires intubation for stabilisation, they should be given surfactant (A2).

2. Babies with RDS needing treatment should be given an animal-derived surfactant preparation (A1).

3. LISA is the preferred method of surfactant administration for spontaneously breathing babies on CPAP (A1).

4. Laryngeal mask surfactant may be used for more mature infants >1.0 kg (B2).

5. An initial dose of 200 mg/kg of poractant alfa is better than 100 mg/kg of poractant alfa or 100 mg/kg beractant for
rescue therapy (A1).
6. Rescue surfactant should be given early in the course of the disease (A1). Suggested protocol would be to treat worsening
babies with RDS when FiO2 > 0.30 on CPAP pressure ≥6 cm H2O or if lung ultrasound suggests surfactant need (B2).
7. A second and occasionally a third dose of surfactant should be given if there is ongoing evidence of RDS such as persistent
high oxygen requirement and other problems have been excluded (A1).
Sweet DG, Carnielli VP, Greisen G, Hallman M, Klebermass-Schrehof K, Ozek E, Te Pas A, Plavka R, Roehr CC, Saugstad OD, Simeoni U, Speer CP, Vento M, Visser GHA, Halliday HL. European Consensus Guidelines on the Management of
Respiratory Distress Syndrome: 2022 Update. Neonatology. 2023;120(1):3-23. doi: 10.1159/000528914. Epub 2023 Feb 15. PMID: 36863329; PMCID: PMC10064400.
 Surfactant Indications
Prophylactic Rescue
Preterm infants with established RDS (within 12
hours after birth) 🡪 intubated preterm neonates
Infants at high risk of developing RDS 🡪 preventing
who needs FiO2 > 40% & PIP up to 20cmH2O to
worsening RDS, NOT treatment of established RDS
maintain SpO2 of 88-92% (or Oxygen Index > 15),
and given twice with 4 hours apart

Preterm neonates with CPAP failure 🡪 apnea,

Administration in delivery room before initial Downe score > 6 (severe retraction), PEEP
resuscitation efforts or onset of respiratory distress 8cmH2O and FiO2 > 40% still with respiratory
(within 10-30 minutes after birth) distress, Blood Gas Analysis of ph <7.25, po2
<50mmHg, pCO2 >60mmHg, BE > -10

Administer to all neonate less than 28 weeks

Primary HFO use is not routinely done, instead used
gestation before they develop respiratory distress
as a rescue therapy when conventional ventilation
syndrome
fails.

“Recommendations for neonatal surfactant therapy”  Paediatrics & child healthvol. 10,2 (2005): 109-16.
 Surfactant Administration
• Invasive
• Intubate and mechanical ventilator
• INSURE Method
• Intubation may cause adverse effects and PPV
after intubation may increase acute lung injury
in preterm infants
• Minimally invasive (MIST)
• Using inhalation, LMA
• Using thin endotracheal catheter (Cologne and
Hobart method) 🡪 recommended method but
rarely done, lack of suitable catheter for
insertion

“Recommendations for neonatal surfactant therapy” Paediatrics & child healthvol. 10,2 (2005): 109-16.
Shim, Gyu-Hong. "Update of minimally invasive surfactant therapy." Korean journal of pediatrics 60.9 (2017): 273
Congenital Diaphragmatic Hernia (CDH)
 Congenital Diaphragmatic Hernia (CDH)
• Physiological adaptation after birth is a critical transition for infants
with CDH
• They struggle to independently achieve lung aeration due to pulmonary
hypoplasia and space-occupying effects of herniated abdominal organs
• The risks of developing severe respiratory distress and pulmonary
hypertension are very high and the majority of infants are symptomatic at
birth

The key principles of successful delivery room resuscitation are to establish

adequate preductal arterial saturation and to avoid progressive hypercapnia

Foglia EE, Ades A, Hedrick HL, Rintoul N, Munson DA, Moldenhauer J, et al. Initiating resuscitation before umbilical cord clamping in infants with congenital diaphragmatic hernia: a pilot feasibility trial. Arch Dis Child Fetal Neonatal Ed. 2020 May;105(3):322–6.
O’Rourke-Potocki A, Ali K, Murthy V, Milner A, Greenough A. Resuscitation of infants with congenital diaphragmatic hernia. Arch Dis Child Fetal Neonatal Ed. 2017 Jul 1;102(4):F320.
 Delivery Management of CDH

Immediate intubation in the delivery room

Bag-mask ventilation should be avoided

Pre-ductal pulse oximeter is placed on the

right upper extremity as soon as possible
• Oxygen saturation targets are based on NRP (Neonatal
Resuscitation Program) guidelines

Orogastric/nasogastric tube with suction to

attain bowel decompression
Chandrasekharan PK, Rawat M, Madappa R, Rothstein DH, Lakshminrusimha S. Congenital Diaphragmatic hernia – a review. Matern Health Neonatol Perinatol. 2017;3
 Oxygen Concentration
for The Resuscitation of Infants with CDH

• Retrospective cohort study comparing 68 patients resuscitated with starting FiO2 0.5 versus 45
historical controls resuscitated with starting FiO2 1.0
• Reduced starting FiO2 had no adverse effect upon survival, duration of intubation, need for ECMO,
duration of ECMO, or time to surgery
• No increase in complications, adverse neurological events, or neurodevelopmental delay
• Conclusion:
• Starting FiO2 0.5 may be safe for the resuscitation of CDH infants
• The need to increase FiO2 to 1.0 during resuscitation is associated with worse outcomes
Riley, J.S., Antiel, R.M., Rintoul, N.E. et al. Reduced oxygen concentration for the resuscitation of infants with congenital diaphragmatic hernia. J Perinatol. 2018; 38, 834–843
 Conventional Mechanical Ventilation (CMV) Versus
High-frequency Oscillatory Ventilation (HFO) for CDH

• CDH infants diagnosed prenatally (n = 171) born between Nov 2008 - Dec 2013 🡪 randomized for
initial ventilation strategy
• There is no difference in effect between CMV and HFO as a primary mode of ventilation in infants
with antenatally diagnosed CDH
• No statistically significant difference in the combined outcome of mortality or BPD
• Infants with CDH initially ventilated by CMV compared with those who received HFO required a
shorter duration of ventilation and vasoactive medication and were less likely to require other
medication to treat pulmonary hypertension or ECMO
Snoek KG, Capolupo I, van Rosmalen J, Hout L de J den, Vijfhuize S, Greenough A, et al. Conventional Mechanical Ventilation Versus High-frequency Oscillatory Ventilation for Congenital Diaphragmatic Hernia: A Randomized Clinical Trial (The VICI-trial). Annals
of Surgery. 2016 May;263(5):867–74.
 Ventilation Management of CDH
CMV is the optimal initial ventilation strategy

HFO can be used as rescue therapy if conventional mechanical ventilation fails

Adapt ventilation settings to reach a preductal saturation between 80-95% and a

postductal saturation > 70%

The target PaCO2 should be between 50-70 mmHg

Pressure-controlled ventilation:
• Initial settings: PIP <25 cm H2O, PEEP of 3–5 cm H2O, rate 40–60/min
After stabilization, reduce FiO2 if the preductal saturation > 95%
Snoek KG, Reiss IKM, Greenough A, Capolupo I, Urlesberger B, Wessel L, et al. Standardized Postnatal Management of Infants with Congenital Diaphragmatic Hernia in Europe: The CDH EURO Consortium Consensus - 2015 Update. Neonatology. 2016;110(1):66–74
 Ventilation Management of CDH
• If a PIP of >28 cm H2O is necessary to achieve pCO2 and saturation levels within
the target range, other treatment modalities (such as HFO or ECMO) should be
considered
• The settings on HFO are not well defined
• Mean Airway Pressure (MAP) of 13-17 cmH2O, a frequency of 10 Hz, an
amplitude (Δp, cm H2O) of 30-50 obtaining chest vibrations, and an
inspiration/expiration rate (I:E) of 1:1

Chandrasekharan PK, Rawat M, Madappa R, Rothstein DH, Lakshminrusimha S. Congenital Diaphragmatic hernia – a review. Matern Health Neonatol Perinatol. 2017;3
Van den Hout L, Tibboel D, Vijfhuize S, te Beest H, Hop W, Reiss I. The VICI-trial: high frequency oscillation versus conventional mechanical ventilation in newborns with congenital diaphragmatic hernia: an international multicentre randomized controlled trial. BMC Pediatr. 2011
Nov 2;11:98.
 Congenital Diaphragmatic Hernia

⇒ Infants with congenital diaphragmatic hernia (CDH) often

experience cardiorespiratory instability immediately after birth.

⇒ Resuscitation with an intact cord is feasible, is without adverse

events for mothers and infants with CDH, and may result in
short-term physiological benefit.

⇒ Ex utero intrapartum therapy (EXIT) may improve the outcome for

infants born with airway compromise.

Bence CM, Wagner AJ. Ex utero intrapartum treatment (EXIT) procedures. Semin Pediatr Surg. 2019 Aug;28(4):150820. doi:
10.1053/j.sempedsurg.2019.07.003. Epub 2019 Jul 22. PMID: 31451172.
Meconium Aspiration Syndrome (MAS)
 Lung Lavage
• Lung Lavage : any procedure where fluid is instilled into lung
followed by an attempt to remove it by suctioning and/or postural
drainage
• MAS result from relatively acute influx of a noxious substance into a
previously healthy and normally developed lung

Removal of Improve gas

Inhaled meconium Deleterious effect meconium may exchange and
migrated distally need time interrupt the pulmonary
pathogenesis mechanic

Paschen C. Therapeutic lung lavages in children and adults. Respir Res. 2005;6:138
Dargaville. Innovation in surfactant therapy. Neonatology. 2012;101:320-6.
 Surfactant lavage
• Animal model :
• Improved oxygenation and lung mechanics in post lavage period, superior to
those with bolus surfactant therapy
• Relatively well tolerated, transient hypoxemia

Lavage can remove inhibitor that

reside within meconium

Paranka MS. Surfactant lavage in a piglet model of meconium

aspiration syndrome. Pediat Res. 1992;31:625-8.
Ebgert H, Surfactant for meconium aspiration syndrome
 How much?
• Experimental setting
• 5-80 ml /kg
• Optimal volume 20-30 ml/kg
• Experimental studies
• 2 ml to 15 ml/kg
• Optimum aliqout 15 ml/kg (maximum aliqout)

15 ml/kg 30 ml/kg 45 ml/kg 60 ml/kg

Optimal Dargaville PA. Therapeutic lung lavage in the piglet model of meconium
aspiration syndrome. Am J Respir Crit Care Med. 2003;168:456-63.
Balance between recovery Dargaville PA. Mills JF. Therapeutic lung lavage in meconium
of meconium and aspiration syndrome: a prelimiary report. J Pediatr Child Helath.
2007;43:539-45.
retention of lavage
 How to deliver?
• Disconnect from ventilation during suctioning
• CPAP used to be applied throughout procedure
• Gentle manual squeezing of chest
• Dilute surfactant
• 5 mg/ml is optimal for lavage
• When to give ?
• Average time 3-23 h
• Criteria for selection for infant to receive lavage are widely variable
and arbitrary, the reported outcomes are somewhat inconsistent

Cochrane CG, Revak SD. Bronchoalveolar lavage with surfactant. Peditr Res. 1998;44:705-15.
Dargaville. Innovation in surfactant therapy. Neonatology. 2012;101:320-6.
Procedure
Video

Courtesy of Prof. Peter Dargaville, MD

Lavage Return Fluid
• Average return fluid :
• 50% in Wiswell
• 46% in Dargaville

Wiswell TE, Knight GR, Finner NN, Donn SM. Desai H, et al. A multicenter randomized controlled
trial comparing surfaxin (lucinactant) lavage with standard care for treatment of meconium
aspiration syndrome. Pediatrics. 2002;109:1081-7.
Dargaville PA, Copnell B, Mills JF, Haron I, Lee JK, et al. Randomized controlled trial of lung lavage
with dilute surfactant for meconium aspiration syndrome. J Pediatr. 2011;158:383-89.
Thank You