Lisa Jorgenson, MSN, NNP-BC

Angela Riley, MSN, NNP-BC

Avera McKennan Hospital NICU

ObjectivesReview incidence, timing, risk

factors, and pathophysiology for HIEReview Sarnet Staging for

EncephalopathyBriefly review Whole Body CoolingDiscuss HIE case studies

Definition of HIEHypoxic= not enough oxygen to the tissuesIschemic= 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, - With annual birth rate of 4 million it is expected

8000-12,000 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 occurrenceAntepartum: 20%Intrapartum: 30%Antepartum-intrapartum: 35%Postpartum: 10%

HIE - EtiologyAntepartum

Socioeconomic status (SES)Maternal thyroid diseaseFetal Growth RestrictionPost-datesFaulty placental gas exchange

Diabetes Preeclampsia or severe PIH

Acute Acute hypotension Placental separation with uterine hemorrhage

HIE - EtiologyIntrapartum risk factors

Cord strangulation (i.e. Nuchal Cord, Knot in Cord, Prolapsed Cord)

Placental problemsDifficult deliveryMaternal feverPersistent occiput posterior (OP) fetal positionUterine abruption or ruptureAbnormal fetal heart rate patternFresh meconium

HIE PathophysiologyImpaired cerebral blood flow is the principal

pathogenetic mechanism underlying neuropathology of hypoxia-ischemia

Brain injury occurs in phasesAcute – During the initial insultRecovery-After restoration of circulation

(reperfusion injury)Infant evolves from primary energy failure→

reperfusion period→latent phase→secondary energy failure

Primary Energy FailureInitial increased cerebral

vasodilation (secondary to hypercapnia and hypoxemia)

Loss of cerebral autoregulation

Redistribution of organ blood flow

↑CBF is quickly followed by impairment (bradycardia and hypotension)

Activation of cell deathNeuronal death vs.

necrosisCell lysis ExcitotoxinsCalcium entry ↓ATP & PCr↑ anaerobic glycolysisOccurs in the first 30

minutes after insult

Reperfusion PeriodReturn of CBFNormal BP and pHTransient improvement in cytotoxic edemaAbsence of seizures (EEG depressed)Rapidly transitions into the latent phase

Latent Phase of Cerebral InjuryOccurs during hours 6 – 15.Recovery of oxidative metabolismApoptotic cascade (ATP and PCr again ↓)Secondary inflammationReceptor hyperactivityUnlike primary phase, intracellular pH and

cardiorespiratory status are usually stable

Secondary Phase of Cellular InjuryOccurs from 3 – 10 daysFailing oxidative metabolismSeizures (↑ CBF)Cytotoxic edema ExcitotoxinsFinal cell death

Sarnat Stage for HIESarnat Stage 1 (mild encephalopathy)

Hyper alertnessNormal muscle tone, active suck, strong Moro

reflex, normal/strong grasp, normal doll’s-eye reflexIncreased tendon reflexesMyoclonus presentHyper-responsiveness to stimulationTachycardia possibleDilation of pupils, reactiveNo convulsions (unless by other cause, i.e.

hypoglycemia)EEG within normal limitsUsually lasts <24 hours

Sarnat Stage for HIESarnat 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 seizuresAt 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 HIESarnat Stage 2 (moderate encephalopathy)

Recovery No further seizure activity EEG returns to normal Transient jitteriness Improvement in level of consciousness

Sarnat Stage for HIESarnat 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 HIESarnat 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

5. Primitive Reflexes Suck Moro

Weak

Incomplete

Absent

Absent

6. Autonomic System Pupils

Heart Rate Respirations

Constriction

Bradycardia

Periodic Breathing

Skew deviated, dilated, non-reactive to light

Variable HR

Apnea

HIE - OutcomesFactors 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 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 - OutcomesSeizures early and/or difficult to control

associated with poorer prognosisHyperactivity & attention difficulties seen

in infants with less severe encephalopathyRapid initial improvement indicative of

better outcomesLong-term sequelae based on

SiteExtent of cerebral injuryDuration of abnormal clinical presentation

Neuroimaging in HIEMRI 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 forHypothermia 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 radicalsBlockage of inflammatory mediators and

inhibition of apoptotic pathways

Whole Body CoolingActively works by cooling the head and body

together by a water blanket composed of coilsMaintain an esophageal and skin

temperature of 32.5°C – 34.5°C

Outcomes in Hypothermia TherapySevere HIE – outcomes remain bleak despite

coolingOne in 6 babies will garner some benefitStudies have shown decrease in mortality

from 39 -25% and reducing occurrence of cognitive impairments from 28 - 11%

More effective in milder encephalopathyEither whole body cooling or selective head

cooling protocols may be adopted to cool infants with HIE

Avera Childrens’ Hypothermia ProgramEstablished November 2010Infants undergo whole body cooling utilizing

Blanketrol III systemUndergo 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 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 CriteriaThe 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 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 #1Risk 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 ResultsCord blood gas: 7.26/40/24/18/-9 arterial and

7.30/35/26/17/-9 venousStarted on oxygen at 2 hours of age for

desats. Blood gas 7.37/39/53/23/-2 on NC 1L 30%

Case Study #1At 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 MaintenanceInfection: Amp/Gent x 48 hour rule out,

Acyclovir, BC negative, LP negativeNeurologic:

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 MaintenanceFluids, 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 #2Risk 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(2-HR, 1-tone, 1-reflex, 1-color), 6(2-HR, 1-RR, 1-tone, 1-reflex, 1-color)

Baby gave initial gasp, followed by no respiratory effort, infant noted to poor tone and very pale in color

Case #2Baby 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 resultsCord arterial gas: 7.17/49/35/17/-10Cord venous gas: 7.17/75/39/18/-12Capillary gas upon immediate admission to

NICU: 6.81/72/42/11.4/-23Follow-up arterial blood gas:

7.14/13.5/70/4.7/-24WBC-37.7, Hgb-3.2, Hct-11.4, Plt-142, Segs-

30, Bands-19

Healthcare MaintenanceNeurologic: Baby was electively cooled per policy

EEG obtained showing no seizure activityMRI 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 dayRespiratory: 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 #33.5 kg 39 5/7 weeks CGA, G3 P23, 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 MaintenanceNeurologic: Whole body cooling initiated per

protocolEEG was normalHead 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 MaintenanceInfectious: 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 #4Risk 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 resultsVenous gas at 0920: 7.05/32.5/134/8.8/-20.6Extubated to NC and received NS bolusFollow up gas upon arrival of transport team:

7.14/62/36/22/-7WBC 16.9, Hgb 19.7, Hct 56.5, plt 135,000,

segs 36, bands 24

Healthcare MaintenanceNeurologic: Baby was electively cooled per

policyBaby 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 MaintenanceInfectious: 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’sSummary of TBC infantsTotal of 14 patients have received total body cooling since

the start in 20115 Had EEG confirmed seizures

6 were placed on anti-seizure medicationsMRI findings- 4 Showed evidence of HIE

7 had no signs of HIE Neurologic assessment upon discharge

8 had normal exams4 had abnormal exams

***2 infants were electively taken off life support, given the grim outcome**

ReferencesDepartment of Health, NSW. Whole Body Cooling –

Neonates-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 hypoxic-ischaemic 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.