lecture of 30 slide

1. Neonatal Hypoxic Ischemic
encephalopathy
Management in the First Hours
By
Dr Magdy Shafik
Pediatric Consultant

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 0@1 min; 4@ 5 min; 5@ 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
Encephalopathy
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
Absent
6. Autonomic
Pupils
Heart Rate
Respirations
Constricted
Bradycardia
Periodic
Fixed; Unequal
Variable HR
Apnea

9. Lab tests
Your initial lab work should include following:
A. Check blood glucose
B. CBC
C.BCx
D.Chem 7
E. LFTs
F. 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

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

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

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:
A. Start hypothermia treatment ASAP
B. Obtain brain imagine to confirm hypoxic-ischemic brain
injury before start hypothermia treatment
C. Continue monitoring. Hypothermia will not be indicated if
infant’s condition significantly improved at 6hr of life.

16. Hypothermia treatment
Answer: A and B

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

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.

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

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?

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:
• 15 - 20% die in infancy and 20 -25% survived with
some neurological abnormalities including cerebral
palsy, cortical visual impairment, seizures,
developmental delay and mental retardation.

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.

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. 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
No gas <1hr
OR
pH 7.01-7.15 and BD 10-15.9
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
pH ≤7.0
OR
BD ≥ 16
Seizure
Clinical or Electrical
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
OR
MEET
PHYSIOLOGI
C CRITERIA
MEET
NEUROLOGIC
CRITERIA
AND
Plus
Cooling
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
Based on NICHD total body cooling protocol

25. Hypothermia treatment
Whole Body Cooling
cooling blanket >
esophageal temp 33.5oC
for 72hrs
Select Head Cooling
Cooling Cap >
rectal temp 34-35 oC
for 72hrs

26. NICHD and CoolCap trials, Lancet
and NEJM 2005
Hypothermia Trials:
50% Cooled Babies had Poor
Outcomes
Cooled 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%

27. Hypothermia treatment improves
outcome

28. 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. 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