Download Asphyxia and Hypoxic Ischemic Encephalopathy (HIE)

Lisa Jorgenson, MSN, NNP-BC
Angela Riley, MSN, NNP-BC
Avera McKennan Hospital NICU
Objectives
 Review incidence, timing, risk factors, and
pathophysiology for HIE
 Review Sarnet Staging for Encephalopathy
 Briefly review Whole Body Cooling
 Discuss HIE case studies
Definition of HIE
 Hypoxic= not enough oxygen to the tissues
 Ischemic= a restriction in blood supply to tissues,
causing a shortage of oxygen and glucose needed for
cellular metabolism (to keep tissues alive)
 Encephalopathy= disturbed neurological function
Hypoxic Ischemic Encephalopathy (HIE)
 Incidence
- Affects 2-3/1000 full term live births,
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With annual birth rate of 4 million it is expected 800012,000 will be diagnosed with this disorder each year in the
USA.
The SD birth rate in 2013 was 11,894 so that would be about
24-36 babies each year in SD.
- Accounts for 15-25% neonatal mortality
- Accounts for 15-28% of children with cerebral
palsy and 25% of all cases of developmental
delay
HIE – Timing
 Timing of insult occurrence
 Antepartum: 20%
 Intrapartum:
30%
 Antepartum-intrapartum: 35%
 Postpartum: 10%
HIE - Etiology
 Antepartum
 Socioeconomic status (SES)
 Maternal thyroid disease
 Fetal Growth Restriction
 Post-dates
 Faulty placental gas exchange
 Diabetes
 Preeclampsia or severe PIH
 Acute
 Acute hypotension
 Placental separation with uterine hemorrhage
HIE - Etiology
 Intrapartum risk factors
 Cord strangulation (i.e. Nuchal Cord, Knot in Cord,
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Prolapsed Cord)
Placental problems
Difficult delivery
Maternal fever
Persistent occiput posterior (OP) fetal position
Uterine abruption or rupture
Abnormal fetal heart rate pattern
Fresh meconium
HIE Pathophysiology
 Impaired cerebral blood flow is the principal
pathogenetic mechanism underlying neuropathology
of hypoxia-ischemia
 Brain injury occurs in phases
 Acute – During the initial insult
 Recovery-After restoration of circulation (reperfusion
injury)
 Infant evolves from primary energy failure→ reperfusion
period→latent phase→secondary energy failure
Primary Energy Failure
 Initial increased cerebral
 Activation of cell death
vasodilation (secondary to
hypercapnia and
hypoxemia)
 Loss of cerebral
autoregulation
 Redistribution of organ
blood flow
 ↑CBF is quickly followed by
impairment (bradycardia
and hypotension)
 Neuronal death vs.
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necrosis
Cell lysis
Excitotoxins
Calcium entry
↓ATP & PCr
↑ anaerobic glycolysis
Occurs in the first 30
minutes after insult
Reperfusion Period
 Return of CBF
 Normal BP and pH
 Transient improvement in cytotoxic edema
 Absence of seizures (EEG depressed)
 Rapidly transitions into the latent phase
Latent Phase of Cerebral Injury
 Occurs during hours 6 – 15.
 Recovery of oxidative metabolism
 Apoptotic cascade (ATP and PCr again ↓)
 Secondary inflammation
 Receptor hyperactivity
 Unlike primary phase, intracellular pH and
cardiorespiratory status are usually stable
Secondary Phase of Cellular Injury
 Occurs from 3 – 10 days
 Failing oxidative metabolism
 Seizures (↑ CBF)
 Cytotoxic edema
 Excitotoxins
 Final cell death
Sarnat Stage for HIE
 Sarnat Stage 1 (mild encephalopathy)
 Hyper alertness
 Normal muscle tone, active suck, strong Moro reflex,
normal/strong grasp, normal doll’s-eye reflex
 Increased tendon reflexes
 Myoclonus present
 Hyper-responsiveness to stimulation
 Tachycardia possible
 Dilation of pupils, reactive
 No convulsions (unless by other cause, i.e. hypoglycemia)
 EEG within normal limits
 Usually lasts <24 hours
Sarnat Stage for HIE
 Sarnat Stage 2 (moderate encephalopathy)
 Hypotonia and lethargy
 Increased tendon reflexes
 Diminished brainstem reflexes - weak suck or gag,
incomplete Moro reflex, sluggish pupil reaction, varying
respiration
 Possible clinical seizures
 At this stage, the condition will either improve & the infant
will get better or it will worsen & the infant will deteriorate
 Results in ~40-70% death or disability with more cases of
disability than death (cerebral palsy, cognitive deficits and
seizures)
Sarnat Stage for HIE
 Sarnat Stage 2 (moderate encephalopathy)
 Recovery
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No further seizure activity
EEG returns to normal
Transient jitteriness
Improvement in level of consciousness
Sarnat Stage for HIE
 Sarnat Stage 3 (severe encephalopathy)
 Clinical Features
 Apnea/bradycardia
 Mechanical ventilation required to sustain life
 Level of consciousness deteriorates from obtunded to stuporous
or coma
 Seizures within the first 12 postnatal hours, usually multifocal
clonic seizures; all display subtle seizures
 Severe hypotonia & flaccidity; reflexes depressed or absent
 Pupils often unequal; variable reactivity & poor light reflex
Sarnat Stage for HIE
 Sarnat Stage 3 (severe encephalopathy)
 Deterioration
 Occurs within 24 to 72 hours
 Severely affected infants often worsen, sinking into deep stupor
or coma
 Death may ensue
 Survivors
 Often improve in the next several days to months
 Feeding difficulties often develop
 Generalized hypotonia is common; hypertonia is uncommon
 Almost always result in death or disability with death > disability
Category
Moderate Encephalopathy
Severe Encephalopathy
1. Level of Consciousness
Lethargic
Stupor/coma
2. Spontaneous Activity
Decreased activity
No activity
3. Posture
Distal flexion, full
extension
Decerebrate
4. Tone
Hypotonia (focal,
general)
Flaccid
Primitive Reflexes
Suck
Moro
Weak
Incomplete
Absent
Absent
Autonomic System
Pupils
Constriction
Skew deviated,
dilated, non-reactive to
light
Variable HR
Apnea
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6.
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Heart Rate
Respirations
Bradycardia
Periodic Breathing
HIE - Outcomes
 Factors associated with poor outcome:
 Apgar score
 If score is 0-3 for 20 minutes or more, approximately 60% die
 If score is less than 3 at 1 minute & less than 5 at 5 minutes, with
abnormal neurologic signs
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About 20% die
About 40% are normal
About 40% suffer neurologic sequelae
 Encephalopathy
 Mild: No subsequent deficits
 Severe: 75% die; 25% have sequelae
 Disappearance of abnormal neurologic signs by 1 to 2 weeks:
good chance of being normal
HIE - Outcomes
 Seizures early and/or difficult to control
associated with poorer prognosis
 Hyperactivity & attention difficulties seen in
infants with less severe encephalopathy
 Rapid initial improvement indicative of better
outcomes
 Long-term sequelae based on
 Site
 Extent of cerebral injury
 Duration of abnormal clinical presentation
Neuroimaging in HIE
 MRI is the primary and most sensitive method for
brain injury patterns, timing of injury, and diagnosis of
HIE.
 Injury to basal ganglia and thalamus is most strongly
associated with poorest outcomes.
Mechanism of Action for
Hypothermia Therapy
 Better maintenance of the cerebral energy state
 Attenuation of the release of exicitatory
neurotransmitters
 Decreased caspase -3 activation and morphologic
evidence of apoptosis
 Reduction in oxygen free radicals
 Blockage of inflammatory mediators and inhibition of
apoptotic pathways
Whole Body Cooling
 Actively works by cooling the head and body together
by a water blanket composed of coils
 Maintain an esophageal and skin temperature of
32.5°C – 34.5°C
Outcomes in Hypothermia Therapy
 Severe HIE – outcomes remain bleak despite cooling
 One in 6 babies will garner some benefit
 Studies have shown decrease in mortality from 39 -
25% and reducing occurrence of cognitive
impairments from 28 - 11%
 More effective in milder encephalopathy
 Either whole body cooling or selective head cooling
protocols may be adopted to cool infants with HIE
Avera Childrens’ Hypothermia Program
 Established November 2010
 Infants undergo whole body cooling utilizing
Blanketrol III system
 Undergo 72 hours of active cooling with close
monitoring of lab studies and esophageal temperature
 Evaluation and follow up with pediatric neurologist
and developmental follow up group
Therapeutic Hypothermia –
Inclusion Criteria
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Before 6 hours of age (mandatory)
≥35 weeks gestation (mandatory)
History of an acute perinatal event
Apgar score ≤ 5 at 10 minutes
Cord pH ≤ 7.0 or first postnatal blood gas pH ≤ 7.0
within 1 hour
Base deficit on cord gas ≥ 16 mEq/L or first
postnatal blood gas ≥16 mEq/L within 1 hour
Continued need for ventilation initiated at birth
and continued for at least 10 minutes
Therapeutic Hypothermia –
Inclusion Criteria
 The attending physician or designee will perform a
neurologic exam for infants who did not receive a ABG
within one hour of delivery and does not have seizure
activity. The infant must show signs of moderate or severe
HIE in at least 3 of the 6 categories to be eligible for
Therapeutic Hypothermia.
 Infants who present with clinical seizures and meet the
requirement of an acute perinatal event or have seizure
activity with a qualifying blood gas will qualify for
therapeutic hypothermia.
Therapeutic Hypothermia –
Exclusion Criteria
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Inability to enroll within 6 hours
Gestational age <35 weeks
Presence of known chromosomal anomaly
Presence of major congenital anomalies
Severe intrauterine growth restriction (weight ≤
1800g)
Infants in extremis; no additional intensive therapy
planned
Case Study #1
 Risk Factors: variable and prolonged decels, category 2
FHTs, induction at 40.6 weeks for post dates,
meconium
 Apgars 1 (for present HR) and 8 (-1 color and -1 tone)
 Baby born with meconium stained fluid with no
tone/resp effort, brought to warmer and immediately
intubated for meconium. No meconium noted below
cords. PPV initiated and baby improved so changed to
CPAP. Blowby continued until 7 mins of age for sats.
 Brought to NICU for further care
Initial Lab Results
 Cord blood gas: 7.26/40/24/18/-9 arterial and
7.30/35/26/17/-9 venous
 Started on oxygen at 2 hours of age for desats. Blood
gas 7.37/39/53/23/-2 on NC 1L 30%
Case Study #1
 At 7 hours of age, baby presented with seizure activity.
He was loaded with phenobarbital. EEG showed
several persistent subclinical seizures that would last
up to 5 min. with short interval resolution between
episodes.
 Baby then loaded with Keppra. Seizures persisted so
baby started on a versed drip. Intubated for his heavy
sedation/seizure management.
Healthcare Maintenance
 Infection: Amp/Gent x 48 hour rule out, Acyclovir, BC
negative, LP negative
 Neurologic:
 CT was essentially normal, no acute intracranial process
 MRI- extensive cortical and subcortical signal
hyperintensity and diffusion restriction in the left
cerebral hemisphere, etiology uncertain.
 Peds Neurologist consulted/following patient
Healthcare Maintenance
 Fluids, Electrolytes, Nutrition: Initially presented with
hypoglycemia and was placed NPO. Started on gavage
feedings at 3 days of life. Started feeding by mouth by
7 days of life and feeding ad lib by 11 days of life.
 Respiratory: Extubated at 4 days of life. Attempts
made to wean NC but still required it for discharge.
 Discharge: Home at 14 days of age and 43 weeks
gestation
Case #2
 Risk Factors: decreased fetal movement for prior 24
hours, fetal heart tones nonreactive, occasional late
decelerations during induction, vacuum assisted
delivery
 Apgars: 1(heart rate noted),4(2-HR, 1-RR, 1-color),5(2HR, 1-tone, 1-reflex, 1-color), 6(2-HR, 1-RR, 1-tone, 1reflex, 1-color)
 Baby gave initial gasp, followed by no respiratory
effort, infant noted to poor tone and very pale in color
Case #2
 Baby was given PPV with good HR response but still
minimal respiratory effort noted, so was electively
intubated
 No spontaneous movement noted until around 9 min.
of age when she opened her eyes
 Baby brought to NICU for further care
Initial lab results
 Cord arterial gas: 7.17/49/35/17/-10
 Cord venous gas: 7.17/75/39/18/-12
 Capillary gas upon immediate admission to NICU:
6.81/72/42/11.4/-23
 Follow-up arterial blood gas: 7.14/13.5/70/4.7/-24
 WBC-37.7, Hgb-3.2, Hct-11.4, Plt-142, Segs-30, Bands19
Healthcare Maintenance
 Neurologic: Baby was electively cooled per policy
 EEG obtained showing no seizure activity
 MRI obtained after rewarming DOL 4 showing acute focal infarct
on the right with no mass effect or associated hemorrhage
 Hematologic: She received 3 rounds of PRBC that day
 Respiratory: Extubated by 2 days of life. ENT consult done
on day 5 of life for stridor and noted moderate bilateral
vocal cord paresis
 FEN: Gavage feeds started on day 6 of life and baby began
orally feeding by day 10 of life
 Discharge: home after spending 17 days in the NICU eating
all feeds and thriving
Case Study #3
 3.5 kg 39 5/7 weeks CGA, G3 P23, vag delivery,
nuchal cord x2, meconium stained fluid
 Delivery: no respiratory effort, no heart rate, and pale
so PPV and chest compressions required. Electively
intubated with slow improvement.
 Initial blood gas pH 6.9, pCO2 90, HCO3 -15
Healthcare Maintenance
 Neurologic: Whole body cooling initiated per
protocol
 EEG was normal
 Head US normal
 MRI showed left periatrial white matter ischemic changes
 Respiratory: Severe pulmonary hypertension,
intubated x 16 days, HFOV x 7 days
 Cardiovascular: PPHN, hypotension upon
rewarming requiring dopamine and dobutamine
along with hydrocortisone
Healthcare Maintenance
 Infectious: Amp/Gent x 5 days for clinical sepsis
and Acyclovir x 48 hours until HSV culture came
back negative
 Hematologic: Developed DIC, thrombocytopenia,
anemia
 Renal: mild renal failure with decreased urine
output
 Discharged at 33 days and 44 3/7 weeks feeding ad lib
on demand
Case study #4
 Risk factors: Unplanned pregnancy with no prenatal care,
mother admitted to drinking alcohol, delivered at home,
 Apgars: Unable to obtain due to delivery at home without
medical supervision.
 It was noted that infant was delivered into the toilet and
had a loose nuchal cord. Nearby person delivered a finger
sweep and gave two rescue breaths prior to calling EMS.
 He was delivered resuscitation in the ambulance back to
the hospital.
Initial lab results
 Venous gas at 0920: 7.05/32.5/134/8.8/-20.6
 Extubated to NC and received NS bolus
 Follow up gas upon arrival of transport team:
7.14/62/36/22/-7
 WBC 16.9, Hgb 19.7, Hct 56.5, plt 135,000, segs 36,
bands 24
Healthcare Maintenance
 Neurologic: Baby was electively cooled per policy
 Baby was noted to have seizure-like activity - lip
smacking, apnea, intermittent tonic posturing of
UE>LE, lateral eye deviation, periodic breathing so baby
was loaded with phenobarbital
 Skull x-ray, Head US and MRI all obtained with all
reported within normal limits
 Cardiac: Pulmonary hypertension suspected and
started on INO 20ppm with good response noted upon
initiation
Healthcare Maintenance
 Infectious: Treated for with ampicillin/claforan until a
positive culture was reported from outlying facility as
coag neg staph. Antibiotics were switched to
vancomycin and a blood culture was redrawn.
Antibiotics were stopped after repeat culture was
negative.
 FEN: Baby was kept NPO initially with IV fluids of
60ml/kg/day. Gavage feeds started on DOL 5, began
oral feeds on DOL 7 and ad lib by 10 days
 Discharged home on DOL 12
Avera McKennan’s
Summary of TBC infants
 Total of 14 patients have received total body cooling since the start in
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2011
5 Had EEG confirmed seizures
 6 were placed on anti-seizure medications
MRI findings- 4 Showed evidence of HIE
 7 had no signs of HIE
Neurologic assessment upon discharge
 8 had normal exams
 4 had abnormal exams
***2 infants were electively taken off life support, given the grim
outcome**
References
 Department of Health, NSW. Whole Body Cooling – Neonates
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Suspected Moderate or Severe Hypoxic Ischaemic
Encephalopathy. Policy Directive, 28-July 2009.
Fatemi, A., Wilson, M., and Johnston, M. Hypoxic-Ischemic
encephalopathy in the term infant. Clinics in Perinatology,
2009; 36: 835-858.
Rajadurai, VS. Therapeutic hypothermia for neonatal hypoxicischaemic encephalopathy. Annals Academy of Medicine. 2006;
v35, 1: 3-5.
Sahni, R., and Sanocka, U. Hypothermia for hypoxic-ischemic
encephalopathy. Clinics in Perinatology; 2008; 35: 717-734.
Schulzke, S., Rao, S., and Patole, SK. A systematic review of
cooling for neuroprotection in neonates with hypoxic ischemic
encephalopathy-are we there yet? BMC Pediatrics. 2007; 1-10.
Wachtel, E., and Hendricks-Munoz, K. Current Management of
the Infant Who presents with Neonatal Encephalopathy. Current
Problems in Pediatric Adolescent Health Care. 2011; 41: 132-153.