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The Golden Hour

Physiologic Considerations of Neonatal Resuscitation
by

K H

on 22 June 2016

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Transcript of The Golden Hour

The Golden Hour
Quarter
Preterm lungs
Susceptible to injury...
Structurally immature
Surfactant deficient
Fluid-filled
Compliant chest wall
The Classic Studies
Lung injury mainly due to high VT ventilation - not by high pressure.
Injury occurs in the first two minutes of ventilation.
When VT is controlled to avoid over-distention, little or no injury occurred.
Am Rev Respir Dis 1985;132:880-4
J Appl Physiol 1989;66:2364-8
Neonatology 2008;94:190–196
Just 6 manual breaths...
Poor compliance
Atelectasis
Widespread lung injury
Both treated with surfactant
Control
Ped Res 1997;42:348-355
Months
15 minutes
9 months
Nutrition
Postnatal Care
Steroids
Nutrition
Preecclampsia
chorioamnionitis
pregnancy
Flow
Rate
Delivery Room Management
O2
VT
Cold and
dry gas
PEEP
Surfactant
Temp.
Control
PDA
Others
Sepsis
Ventilation
Oxygen
Outcomes
Years
Prolonged Inflation?
Inflammation
How to avoid injury?
Fluid-filled lungs are difficult to ventilate
Normal use of PEEP, oxygen, flow rate, and tidal volume
Hyperoxia
Hypocarbia
Immature airway
Surfactant deficiency
Compliant chest wall
Term lung 50 ml/kg
Preterm lung 30 ml/kg
or smaller
"The net effect is that the pressures and tidal volumes needed to maintain FRC and to achieve gas exchange may encroach on the TLC, and these volumes can stretch the preterm lung and cause injury."
Neonatology 2008;94:190–196
Lung
Liver
Epithelial disruption & Protein leak
Crit Care 2010, 14:R1
Pediatr Res 67:630-635, 2010
J Appl Physiol 112:481-489, 2012
PLoS One 7(6): e39535, 2012
Am J Physiol Lung Cell Mol Physiol 2011 Feb; 300(2): L232-L241
Brain
Am J Respir Crit Care Med vol 176. pp 575-581, 2007
Induction of mRNA for serum amyloid and TLR 2 and TLR4 receptors in both lung and liver.
TLC
Time to introduce the measurement of V in the delivery room?
T
High V
Low V
T
Monitor Chest Rise?
High V
T
Even experienced hands and eyes cannot accurately judge chest rise.
... or face mask air leak.
Resuscitation 82 (2011) 175-79
Arch Dis Child Fetal Neonatal Ed
2010;95:F393-F397
J Pediatr 2008;153:741-5
What about Oxygen?
"Doctors are men that prescribe medicine of which they know little, to cure disease of which they know less, to human beings of which they know nothing."

Voltaire
DO2 = CO [(Hb)(%sat)(1.36) + (PaO2)(0.0031)]
If the PaO is 60 mmHg, how much oxygen is being delivered at the tissue level?
Pediatrics vol. 85 No. 1 Jan 1990
Oxygenation after birth
Healthy term infants - no oxygen
Infants <37 weeks - no oxygen
Infants <28 weeks
S O 90% by 2 to 10 minutes
p
2
p
2
S O 75% by 4.2 minutes
Roughly 2 minute delay
S O 91% by 3 minutes
and 97% by 5 minutes
p
2
Neonatology 2011;99:342-348

I have no actual or potential conflict of interest in relation to this CME activity.
I have not received anything of value from any commercial support of this activity.
My presentation will not include a discussion of an unlabeled use or an investigational use of a product or device that has not been approved by the FDA for the use I plan to discuss.
The Genome is Damaged
Oxygen Toxicity
Oxygen Toxicity
Superoxide radical anions
H O
2
2
OH
-
O
2
-
ROS
NF-kB
AP-1
membrane permeability transition pores
release of cytochrome c
Apoptosis
Alter signal transduction
Enzyme activation
Protein synthesis
DNA and RNA synthesis
Acta Paediatrica 2007;96:801-812
Exp Biol Med 2002;227:671-682
Exp Biol Med 2002;227:671-682
Base damage
DNA strand breaks
Cellular growth arrest
Cell death, apoptosis, or necrosis
BAD
Worse
Inheritable disease
Cancer
Aging
Superoxide dismutase and catalase systems are deficient in neonates.
100% oxygen exposure at birth
Epidemiologic association with childhood leukemia and cancer
Nearly 15% of cancers might be prevented if oxygen had not been used at birth
Act Paediatr 2002;91:1328-33
J Pediatr 2005;147:27-31
J Pediatr 2005;147:4-6
(greater than 3 minutes)
Third to 97th Spo2 percentiles for preterm infants at <32 weeks of gestation with no medical intervention after birth.
Pediatrics 2010;125;e1340-e1347
50th percentile crosses 90% at ~6 minutes
Not to mention...
ROP
Risk of severe ROP is increased with pO above 80 mmHg in the first week of life.
2
BPD
Sats 85-93%
Oxygen induced inflammation related to NF-kB
Increased numbers of mast cells and eosinophils
Increased septal thickness with decreased alveolar surface area.
Arrest of alveolarization due to TGF-beta/BMP signaling
Upregulation of gene expression of p53 "Guardian of the Genome"
Inducing transcription of p21 mRNA
Cell cycle arrest and decreased lung growth
Angiogenesis (2007) 10:133–140
Phase 1
Bevacizumab
Phase 2
Proc Natl Acad Sci USA. 2001 May 8; 98(10): 5804–5808
Respiration 2010;79:425–436
Oxygen toxicity in the lung
Protein oxidation
Lipid peroxidation
Surfactant inactivation
Decreased alveolar surface area
Increased septal thickness
Apoptosis
Seminars in Neonatology 2003;8:39-49
Act Paediatr 2007;96:801-812
But to summarize...
Hypothermia
Admission hypothermia is common.
31-78% for infants <1500 g
J Perinatology 2007;27:S45-S47
California
CPQCC
Israel
Nepal
Hypothermia more common in the warm season.
BMC Medicine 2010,8:43
India
54% reduction in neonatal mortality by avoiding hypothermia
Increased Risk of Mortality
Lancet 2008;372(9644):1151-1162
Increased risk of mortality
Increased risk of IVH
Neonatology 2011;100:373-379
J Perinatology 2011;31:S49-S56
Increased risk of mortality
No increased risk of IVH
Pediatr 1957;20:477-486
Pediatr 1958;22:876-886
Pathophysiology
Hypothermia defined
Normal - 36.5 to 37.5
Cold stress - 36 to 36.5
Moderate hypothermia 32 to 36
Severe hypothermia <32
o
C
o
C
o
C
o
C
Possible mechanisms include...
Decreased perfusion
Decreased oxygen delivery
Increased ROS
Protein and enzyme alterations
Inflammation
Apoptosis
Recommendations
Delivery room temperature 75 2
Pre-heat overhead warmer
Cap
Polyethylene bag for infants <28 weeks
o
F
+
-
J Perinatology 2007;27:S45-S47
2
Fluid filled lungs are difficult to ventilate
Non-uniform
Aeration
FRC = 11 mL/kg
TLC = 19 mL/kg
Preterm lung volumes
Tidal volumes of >8 mL/kg can distend the lung above TLC
J Pediatr 2008;153:741-5
V 5 mL/kg
PEEP of 5 cm H O
How might gas enter the lungs of a 1 kg infant?
T
2
20 breaths
Large airway FRC = 3 mL
Parenchyma essentially fluid-filled
5 mL/kg tidal volume distends small airways resulting in wall stretch and high fluid-mechanical shear forces
By ~2 minutes of age, 20% of saccules opened
5 mL /kg tidal volume is distributed between the open saccules = 5 times the volume expected if all saccules were aerated.
That's 25 mL/kg
Neonatology 2008;94:190-196
Arjan B. Pas, et al. Pediatr Res 2009;66:295-300
TE
Rabbit lungs exposed to 1, 5, 10 or 20 second inflation
Mean time to full inflation was 14 seconds
10 and 20 s inflation increased inspiratory volume and produced a greater FRC
20 second inflation uniformly aerated the lung before ventilation started.
Regionalization
Golden Hour
NICU
Management

Improved Outcomes
Quarter
(and prenatal care too)
http://prezi.com/97lk2yyynpnu/nutrition-for-the-neonate/?kw=view-97lk2yyynpnu&rc=ref-952879
Full transcript