1. Neonatal Hypoxic Ischemic Brain Injury Management in the First Hours
Dongli Song, MD, PhD
Santa Clara Valley Medical Center
Neonatology

2. History
Baby girl F, born to a 35 year old G5P4 mother with good antenatal care. This pregnancy complicated by GDM, diet control.
Blood group O positive; Hep B neg: HIV neg: RPR neg: Rubella immune: GBS negative
Mom admitted at 37+2 weeks with active vaginal bleeding. US showed placenta abruption.

3. Pediatric team get called to the DR stat
Infant was delivered via stat c/s.
At delivery, she was floppy with no respiratory effort and no heart rate.
Bag and mask ventilation started immediately, HR > 100 bpm at 3 min, and some respiration effort noted at 5 min. She was intubated at 7 min for poor sustained respiration. Color improved but remained floppy at 10 min. Apgar score min; 5 min; 10 min.
What should you ask OB/L&D staff in the DR?

4. Get cord blood gas Answer: ask OB/L&D staff to send cord blood gas.
Cord arterial gas: pH 6.8, PCO2 103, Bicarb 15 and BD19.7
Cord blood gas provides critical information regarding the severity and/or duration of hypoxic ischemic insults prior to delivery.
Cord arterial gas (from UA) is a part of the criteria for hypothermia treatment.
If cord blood gas is not available, get infant ABG within first hour of life.

5. Physical examination
Weight 3720gms (>90%), OFC 35.5 cm (90%), Length 54.4 (>90%)
Temperature 36.5oC
HR 190bpm, BP 37/23 mmHg.
Pale and poor perfused
On ventilator with periodic respiration effort
No significant dysmorphic features

6. Neurological examination
Does this infant display encephalopathy?
How could the neurological examination have been done/documented to show this?

7. Neurological examination
A systemic detailed neuro exam were performed and documented:
Level of Consciousness: poor eye opening to stimulation, no sustained alertness
Movements and Tone: minimal spontaneous activity, hypotonia
Brainstem/Autonomic Functions: pupils constricted but reactive, no suck, no gag
Reflexes: incomplete Moro, no DTR

8. NICHD Exam Criteria for Hypothermia
Moderate
Encephalopathy
Severe
1. Consciousness
Lethargic
Stupor/coma
2. Activity
Decreased
No Activity
3. Posture
Distal Flexion
Decerebrate
4. Tone
Hypotonia (focal or general)
Flaccid
5. Primitive Reflexes
Suck
Moro
Weak
Incomplete
Absent
6. Autonomic
Pupils
Heart Rate
Respirations
Constricted
Bradycardia
Periodic
Fixed; Unequal
Variable HR
Apnea 8

9. Lab tests Your initial lab work should include following:
Check blood glucose
CBC
BCx
Chem 7
LFTs
Coagulation tests

10. Lab tests Answer: All above.
Correcting hypoglycemia is critical for brain protection.
Mom had placenta abruption, HCT and platelet count will help to determine if blood product transfusion is indicated.
Increase in creatinine indicates kidney injury, and elevation of LFTs and coagulopathy indicates liver damage.

11. Lab results
Cord arterial gas: pH 6.8, PCO2 103, Bicarb 15 and BD 19.7.
Blood glucose 15
CBC: WBC 17.7k, HCT 30%, platelet count 141K
Creatinine 1.3
AST 945, ALT 220
PT/PTT/INR significant prolonged

12. Antepartum Risk Factors
Socioeconomic Status
Family History
Infertility treatment
Maternal thyroid disease
Severe pre-eclampsia
Bleeding in pregnancy
Viral illness
Abnormal placenta
IUGR
Postmaturity 12

13. Intrapartum Risk Factors
Operative vaginal delivery or emergency C-section
Maternal fever
Occipito-posterior presentation
Acute intrapartum events: cord prolapse, abruptio placentae… 13

14. Heterogeneous cause
Badawi N. et al. BMJ.1998 14

15. Hypothermia treatment
One hour later, fluid boluses were given, hypoglycemia was corrected and FFP transfusion was started. Infant started to have spontaneous respiration effort and movements and her tone improved.
Your next treatment plan include:
Start hypothermia treatment ASAP
Obtain brain imagine to confirm hypoxic-ischemic brain injury before start hypothermia treatment
Continue monitoring. Hypothermia will not be indicated if infant’s condition significantly improved at 6hr of life.

16. Hypothermia treatment
Answer: A and B 16

17. Diagnosis of Neonatal Encephalopathy is Clinical
Careful history and neurological exam
Laboratory studies to exclude “mimics” of hypoxia-ischemia
Metabolic abnormalities
including inborn errors of metabolism
Infection
Acute bilirubin encephalopathy
Stroke 17

18. Diagnosis – Neuro imaging
HUS - may detect basal ganglia and thalamic injury, not sensitive to cortical injury. Most useful in detecting and following intracranial bleeding.
CT - can detect diffuse cortical neuronal injury, most useful to r/o intracranial hemorrhage that requiring immediate surgical intervention. Concerns for radiation.
MRI - is the study choice of assessing HI brain injury. It provides specific information regarding the injury pattern, severity and evolution.
Neuro imaging is not an absolute requirement for initiating hypothermia treatment for HIE. 18

19. Cortical Injury Basal Ganglia Injury 19
Chao, C. P. et al. Radiographics 2006;26:S159-S172
Copyright ©Radiological Society of North America, 2006
Basal Ganglia Injury 19

20. Parent’s questions
You talked to infant’s father and explained to him that the his baby is critically ill and may have suffered serious brain injury.
He asked:
What causes her brain injury?
Is my baby going to die?
If she survived, will she be normal?
What can you do to save my baby? 20

21. Significance Incidence of HIE: 1-2/1000 live births
*California: 4.5/1000 live births
HIE is a major cause of infant mortality and morbidity with significant long term neurological deficits:
% die in infancy and % survived with some neurological abnormalities including cerebral palsy, cortical visual impairment, seizures, developmental delay and mental retardation. 21

22. Hypothermia treatment
Neonatal encephalopathy is a neurological emergency.
Brain injury evolves over time.
Biphasic nature of cell death (Gluckman PD, et al 1992): Primary neuronal death (cell hypoxia/primary energy failure). Latent period – at least 6 hours. Secondary phase - delayed neuronal death begins. 22

23. Mechanisms of ischemic brain injury
Delayed
neuronal
death
Hypoxia-ischemia
Primary
neuronal death
Cytotoxic
mechanisms
1 hour
6 hours
Days
Modified from Gunn and Thoresen, 2006
Hypothermia

24. Mechanisms of ischemic brain injury
Ferriero D. NEJM 2004 24

25. No “Lethal” chromosomal or congenital anomalies Cooling
INCLUSION
≥36wks GA and ≥ 1800gms
Meet both Physiologic and Neurological Criteria
No “Lethal” chromosomal or congenital anomalies
PHYSIOLOGIC CRITERIA
NEUROLOGIC EXAM CRITERIA
Cord or Baby’s ABG < 1 hour
Moderate Encephalopathy
3 of 6 findings below
1. Lethargic
2. Inactive/decreased activity
3. Distal flexion
4. Hypotonia- focal or general
5. Weak suck/incomplete moro
6. Pupil constricted/ Bradycardia /
periodic breathing
No gas <1hr OR
pH and BD
pH ≤7.0 OR
BD ≥ 16
Plus OR
Severe Encephalopathy
3 of 6 findings below
1. Stupor/coma
2. No activity
3. Decerebrate
4. Flaccid tone
5. Absent suck/moro
6. Pupils dilated /unreactive /skew,
variable HR, apnea
A MAJOR PERINATAL EVENT
nonreassuring FHR
cord prolapse/rupture,
uterine rupture,
maternal trauma, abruption, hemorrhage, CPR,
AND
Apgar ≤ 5 at 10 min,
or PPV ≥ 10 min
MEET
PHYSIOLOGIC CRITERIA
MEET
NEUROLOGIC CRITERIA
AND OR
Seizure
Clinical or Electrical
Cooling
Based on NICHD total body cooling protocol

26. Hypothermia treatment
Whole Body Cooling
cooling blanket > esophageal temp 33.5oC
for 72hrs
Select Head Cooling
Cooling Cap >
rectal temp oC
for 72hrs 26

27. Hypothermia Trials: 50% Cooled Babies had Poor Outcomes
Controls
Died or severe disability
44-55%
62-66%
Died
24-33%
38%
Bayley MDI < 70
25-30%
39%
Bayley PDI < 70
27-30%
35-41%
NICHD and CoolCap trials, Lancet and NEJM 2005

28. Hypothermia treatment improves outcome28

29. Hypothermia treatment Potential adverse effects
Hypotension
Cardiac arrhythmia (mainly sinus bradycardia )
Persistent acidosis
Increased oxygen consumption
Increased blood viscosity
Reduction in platelet count
Pulmonary hemorrhage
Sepsis
Necrotizing enterocolitis
no severe side effects have been reported so far 29

30. Best patient care depends on
Close communication with family
Multidisciplinary care
Neurology– neurological examination (structured /routine), diagnosis, prognosis, follow up
Radiology – timing and interpretation
Physical and occupational therapy – evaluation, pre-discharge examination

31. “The world belongs to the enthusiast who keeps cool”
Thank you!
“The world belongs to the enthusiast who keeps cool”