Neonatal Hypoxic Ischemic Brain Injury

Management in the First Hours

Dongli Song, MD, PhD

Santa Clara Valley Medical Center

Neonatology

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.

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?

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.

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

Neurological examination

• Does this infant display encephalopathy?

• How could the neurological examination have been done/documented to show this?

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

NICHD Exam Criteria for HypothermiaModerate

EncephalopathySevere

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 ReflexesSuckMoro

WeakIncomplete

AbsentAbsent

6. AutonomicPupilsHeart RateRespirations

ConstrictedBradycardia

Periodic

Fixed; UnequalVariable HR

Apnea

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

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.

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

Antepartum Risk Factors

• Socioeconomic Status

• Family History • Infertility treatment• Maternal thyroid

disease

• Severe pre-eclampsia• Bleeding in pregnancy• Viral illness• Abnormal placenta• IUGR• Postmaturity

Intrapartum Risk Factors

• Operative vaginal delivery or emergency C-section

• Maternal fever• Occipito-posterior presentation• Acute intrapartum events: cord prolapse,

abruptio placentae…

Heterogeneous cause

Badawi N. et al. BMJ.1998

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.

Hypothermia treatment

Answer: A and B

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

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.

Copyright ©Radiological Society of North America, 2006

Chao, C. P. et al. Radiographics 2006;26:S159-S172

Cortical InjuryCortical Injury

Basal Ganglia Injury

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?

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.

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.

Mechanisms of ischemic brain injury

Delayed neuronal death

Hypoxia-ischemia

Primaryneuronal death

Cytotoxic mechanisms

1 hour

6 hours Days

Modified from Gunn and Thoresen, 2006

HypothermiaHypothermia

Mechanisms of ischemic brain injury

Ferriero D. NEJM 2004

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 <1hrOR

pH 7.01-7.15 and BD 10-15.9

Moderate Encephalopathy3 of 6 findings below

1. Lethargic2. Inactive/decreased activity3. Distal flexion4. Hypotonia- focal or general5. Weak suck/incomplete moro6. Pupil constricted/ Bradycardia /periodic breathing

pH ≤7.0OR

BD ≥ 16

SeizureClinical or Electrical

OR

Severe Encephalopathy3 of 6 findings below

1. Stupor/coma2. No activity3. Decerebrate4. Flaccid tone5. Absent suck/moro6. Pupils dilated /unreactive /skew, variable HR, apnea

OR

MEETPHYSIOLOGIC CRITERIA

MEETNEUROLOGIC

CRITERIAAND

Plus

Cooling

A MAJOR PERINATAL EVENTnonreassuring FHR cord prolapse/rupture,uterine rupture, maternal trauma, abruption, hemorrhage, CPR, ANDApgar ≤ 5 at 10 min, or PPV ≥ 10 min

Based on NICHD total body cooling protocol

Hypothermia treatment

Whole Body Coolingcooling blanket > esophageal temp 33.5oC for 72hrs

Select Head Cooling Cooling Cap >rectal temp 34-35 oC for 72hrs

NICHD and CoolCap trials, Lancet and NEJM 2005

Hypothermia Trials: 50% Cooled Babies had Poor

OutcomesCooledCooled ControlsControls

Died or severe Died or severe disabilitydisability

44-55%44-55% 62-66%62-66%

DiedDied 24-33%24-33% 38%38%

Bayley MDI < 70Bayley MDI < 70 25-30%25-30% 39%39%

Bayley PDI < 70Bayley PDI < 70 27-30%27-30% 35-41%35-41%

Hypothermia treatment improves outcome

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

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

“The world

belongs to the

enthusiast who

keeps cool”

Thank you!