Complete definition of Hypoxic Ischemic Encephalopathy, clinical manifestations according to Sarnat staging system, risk factor, pathophysiology and details of management and approaches to be used.

1. Perinatal Asphyxia
&
Hypoxic Ischemic Encephalopathy
Zeinab Noormonavar
Pharm D candidate
24/4/2022
1

2. Outline
At the end of presentation you will be able to:
• Recall definition, pathophysiology, symptoms of HIE.
• Recommend appropriate treatment plan.
• Discuss management of HIE.
• Identify future prospect medications.
2

3. Background
• Despite major advances in monitoring technology and knowledge of
fetal and neonatal pathologies, perinatal asphyxia or, more
appropriately, hypoxic-ischemic encephalopathy (HIE), remains a
serious condition that causes significant mortality and long-term
morbidity.
• HIE is characterized by clinical and laboratory evidence of acute or
subacute brain injury due to asphyxia (i.e., hypoxia, acidosis). Most
often, the exact timing and underlying cause remain unknown.
3
Neonatal hypoxic ischemic encephalopathy. ucsfbenioffchildrens.org. (n.d.). Retrieved April 28, 2022, from https://www.ucsfbenioffchildrens.org/conditions/neonatal-
hypoxic-ischemic-encephalopathy#:~:text=Hypoxic%20ischemic%20encephalopathy%20(HIE)%20is,and%20encephalopathy%20means%20brain%20disorder.

4. Definition
4
Ohio hie lawyers pursue brain damage claims on behalf of newborns. Ohio HIE Lawyers | Infant Hypoxic Ischemic Encephalopathy. (n.d.). Retrieved April 28, 2022, from
https://www.birthinjuryohio.com/brain-injuries/hie/

5. Assessment
Apgar score of <5 at 5 minutes and 10 minutes
Fetal umbilical artery pH <7.0, or base deficit ≥12
mmol/L, or both
Acute brain injury seen on brain MRI
Presence of multisystem organ failure (kidney, lung,
liver, heart,…)
5
Assessment of Hypoxic ischemic Encephalopathy. Retrieved April 28, 2022, from https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(18)30051-
8/fulltext

6. Clinical Feature
Abnormal state of consciousness (hyper-alert, irritable, lethargic, or obtunded)
Diminished spontaneous movements
Weak or absent cry
Respiratory or feeding difficulty
Poor tone
Abnormal posturing
Abnormal primitive reflexes
Seizures
6
Allen, K. A., &amp; Brandon, D. H. (2011, September 1). Hypoxic ischemic encephalopathy: Pathophysiology and experimental treatments. Newborn and
infant nursing reviews : NAINR. Retrieved April 28, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3171747/

7. 7
Clinical Feature – Sarnat Staging System
Severity of hypoxic ischemic encephalopathy ... - researchgate. (n.d.). Retrieved April 28, 2022, from
https://www.researchgate.net/publication/334575225_Severity_of_hypoxic_ischemic_encephalopathy_and_heart_rate_variability_in_neonates_A_systematic_review/fulltext/5d31fed5a6fdcc370
a4e8f7c/334575225_Severity_of_hypoxic_ischemic_encephalopathy_and_heart_rate_variability_in_neonates_A_systematic_review.pdf

8. Risk factors
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Preconceptual
• IDDM
• Thyroid disease
• Fertility treatments
• Nulliparity
• Advanced maternal age
Antepartum
• Severe pre-eclampsia
• Placental abruption
• IUGR
• Hemorrhage
Intrapartum
• Breech
• Cord prolapse
• C-section
• Induction
• Maternal pyrexia
Neonatal hypoxic ischemic encephalopathy. ucsfbenioffchildrens.org. (n.d.). Retrieved April 28, 2022, from https://www.ucsfbenioffchildrens.org/conditions/neonatal-
hypoxic-ischemic-encephalopathy#:~:text=Hypoxic%20ischemic%20encephalopathy%20(HIE)%20is,and%20encephalopathy%20means%20brain%20disorder.
IDDM: Insulin Dependent Diabetes Mellitus
IUGR: Intra Uterine Growth Retardation

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Risk factors (Con’t)
Nuchal cord Prolapsed cord Knotted cord
Neonatal hypoxic ischemic encephalopathy. ucsfbenioffchildrens.org. (n.d.). Retrieved April 28, 2022, from https://www.ucsfbenioffchildrens.org/conditions/neonatal-
hypoxic-ischemic-encephalopathy#:~:text=Hypoxic%20ischemic%20encephalopathy%20(HIE)%20is,and%20encephalopathy%20means%20brain%20disorder.

10. Pathophysiology
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• Birth Injury: an injury that occurred
during the process of birth
• Birth Asphyxia: asphyxia that occurred
during 2nd and 3rd stages of labor
• Perinatal Asphyxia: asphyxia that
occurred anytime between
conception to first month of life.

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Pathophysiology (Con’t)
Santina A Zanelli, M. D. (2021, April 3). Hypoxic-ischemic encephalopathy. Practice Essentials, Background, Pathophysiology. Retrieved April 28, 2022, from
https://emedicine.medscape.com/article/973501-overview

12. Intervention and Therapies
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Criteria
• Gestational age ≥36 weeks and ≤6 hours of age
And one of the following:
1. Metabolic or mixed acidosis with a pH of ≤7.0 or a base
deficit of ≥16 mmol/L in a sample of umbilical cord blood or
any blood obtained within the first hour after birth
2. A 10-minute Apgar score of ≤5
3. Ongoing resuscitation (eg, assisted ventilation, chest
compressions, or cardiac medications) initiated at birth and
continued for at least 10 minutes
• Moderate to severe encephalopathy on clinical examination
Guideline: Hypoxic ischaemic ... - queensland health. (n.d.). Retrieved April 28, 2022, from https://www.health.qld.gov.au/__data/assets/pdf_file/0014/140162/g-hie.pdf

13. Therapeutic Hypothermia
• Must be initiated within 6 hours of birth
• All external head sources off
• Desired temperature: 33.5 ± 0.1 Centigrade
• Monitor temperature every 15 minutes
• Maintain for 72 hours
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Intervention and Therapies
Guideline: Hypoxic ischaemic ... - queensland health. (n.d.). Retrieved April 28, 2022, from https://www.health.qld.gov.au/__data/assets/pdf_file/0014/140162/g-hie.pdf

14. Whole Body Head Only
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Intervention and Therapies
Therapeutic Hypothermia
Guideline: Hypoxic ischaemic ... - queensland health. (n.d.). Retrieved April 28, 2022, from https://www.health.qld.gov.au/__data/assets/pdf_file/0014/140162/g-hie.pdf

15. 1. Reduce metabolic rate and energy depletion.
2. Decrease excitatory transmission release.
3. Reduce alteration in ion flux.
4. Reduce apoptosis due to Hypoxic-Ischemic Encephalopathy
5. Reduce vascular permeability, edema, and disruption of BBB function.
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Intervention and Therapies
Therapeutic Hypothermia
Abate, B. B., Bimerew, M., Gebremichael, B., Mengesha Kassie, A., Kassaw, M. W., Gebremeskel, T., &amp; Bayih, W. A. (2021). Effects of therapeutic hypothermia
on death among asphyxiated neonates with hypoxic-ischemic encephalopathy: A systematic review and meta-analysis of Randomized Control Trials. PLOS ONE,
16(2). https://doi.org/10.1371/journal.pone.0247229

16. Recommended lab
Glucose
CBC
Blood
culture
PT, PTT,
Fibrinog
en
ABG
LFTs
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Intervention and Therapies
Therapeutic Hypothermia
Douglas-Escobar, M., &amp; Weiss, M. D. (2012, November 2). Biomarkers of hypoxic-ischemic encephalopathy in newborns. Frontiers in neurology. Retrieved April
28, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3486976/

17. Arrhythmia
• Bradycardia
• Ventricular tachycardia
Thrombocytopenia
Persistent acidosis Bleeding
Subcutaneous fat
necrosis ±
hypercalcemia
Death
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Intervention and Therapies
Therapeutic Hypothermia’s Complication
Texaschildrens.org ▷ Texas Children's Hospital. Webrate. (n.d.). Retrieved April 28, 2022, from https://webrate.org/index.php/site/texaschildrens.org/

18. • Warm slowly after 72 hours
Monitor very closely
• Increase temperature by 0.5 degree every hour
Until reach 36.5
• Once temperature reaches 36.5 for 1 hour
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Intervention and Therapies
Rewarming
Texaschildrens.org ▷ Texas Children's Hospital. Webrate. (n.d.). Retrieved April 28, 2022, from https://webrate.org/index.php/site/texaschildrens.org/

19. Supportive Management
• Aside from treatment with therapeutic hypothermia, suggested
management of neonatal encephalopathy includes the following
recommendations:
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Treat Seizure
Phenobarbital
Phosphenytoin
Lorazepam
Levetiracetam
Ventilation
Inhaled NO
Extracorporeal
membrane
oxygenation
Replace volume
Use of inotropes
Metabolic
disorder
Stop feeding
Correct acidosis
Vitamin
supplementation if
needed
Maintain
Euglycemia
Guideline: Hypoxic ischaemic ... - queensland health. (n.d.). Retrieved April 28, 2022, from https://www.health.qld.gov.au/__data/assets/pdf_file/0014/140162/g-hie.pdf

20. Follow – Up
Developmental
pediatric consult &
evaluation prior to
discharge
Neurology clinic
post discharge
Brain MRI at 1 year
of age
Developmental
clinic at 6 months, 1
year, and 18 months
(Bayley exam)
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Texaschildrens.org ▷ Texas Children's Hospital. Webrate. (n.d.). Retrieved April 28, 2022, from https://webrate.org/index.php/site/texaschildrens.org/

21. Promising Drugs
• Reduces apoptotic, inflammatory and oxidative brain
injury.
Erythropoietin
• Antioxidant, antiapoptotic, cross BBB,
neuroprotective
Melatonin
• Precursor of glutathione which is act as antioxidant
N-Acetylcycteine
(NAC)
• Antioxidant, inhibitor of superoxide and hydrogen
peroxide production
Allopurinol
21
Nair, J., &amp; Kumar, V. H. S. (2018, July 19). Current and emerging therapies in the management of hypoxic ischemic encephalopathy in neonates. Children (Basel,
Switzerland). Retrieved April 28, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6069156/

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