SHIVANJAN Hypoxic ischemic encephalopathy

All concepts compiled in an easy way including recent advances in the treatment of hie. For pediatricians, residents working in nicu i hope it will help you both in practical aspect as well as your academic needs.

1. HYPOXIC ISCHEMIC ENCEPHALOPATHY(HIE) BY- Dr. SHIVANJAN GOYAL(JR3) GUIDE- Dr. SUVIDHA SARDAR

2. HIE is characterized by clinical & laboratory evidence of acute or subacute brain injury due to hypoxia / ischemia Birth Asphyxia causes 8,40,000 or 23% neonatal deaths worldwide .

3. ETIOLOGY OF HIE ASPHYXIA ANTEPARTUM INTRAPARTUM POSTPARTUM PLACENTAL FACTORS MATERNAL FACTORS NEONATAL FACTORS FETAL FACTORS ABRUPTION HYPERTENSION/ HYPOTENSION CYANOTIC CHD FETOMATERNAL HAEMORRAGE INFARCTION INFECTIONS PPHN HYDROPS UMBLICAL CORD PROLAPSE CARDIAC /PULMONARY DISORDERS MAS CARDIOMYOPATHY ENTANGALMENT MATERNAL VASCULAR DISEASES SEPTIC SHOCK INFECTIONS CORD COMPRESSION EXPOSURE TO DRUGS LIKE COCAINE CONGENITAL PNEUMONIA CIRCULATORY INSUFFICIENCY PNEUMOTHORAX

4. American Academy of Paediatrics (AAP) and the American College of Obstetrics and Gynaecology (ACOG) for HIE indicate that all of the following must be present for the designation of perinatal asphyxia severe enough to result in acute neurologic injury: Profound metabolic or mixed acidemia (pH < 7) in an umbilical artery blood sample. Persistence of an Apgar score of 0-3 for longer than 5 minutes Neonatal neurologic sequelae ( eg :- seizures, coma, hypotonia) Multiple organ involvement ( eg :- kidney, lungs, liver, heart, intestines) DIAGNOSIS

5. Laboratory studies include: Serum electrolyte levels Renal function studies Cardiac and liver enzymes: Assess the degree of hypoxic-ischemic injury to the heart and liver Coagulation system: Includes prothrombin time, partial thromboplastin time, and fibrinogen levels Arterial blood gas: Blood gas monitoring is used to assess acid-base status and to avoid hyperoxia and hypoxia, as well as hypercapnia and hypocapnia

6. BRAIN IMAGING MODALITIES:- CRANIAL SONOGRAPHY :- can demonstrate edema as loss of gray-white differentiation and small ventricles when severe but is generally insensitive for detection of HI injury. CT :- used to detect cerebral edema , hemorrhage and eventually HI brain injury. MRI :- Best imaging modality for determining the presence , severity & distribution of irreversible HI brain injury. Diffusion – weighted imaging (DWI) – Early DWI –usually show restricted diffusion in areas affected by hypoxic- ischemia At 7 to 10 days – pseudonormalisation of diffusion After 7 to 10 days - diffusion usually increased in areas of affected areas 2. Proton Magnetic Resonance spectroscopy(MRS) 3. Susceptibility – weighted imaging 4.Magnetic Resonance Angiography or Venography

7. MRI - useful tool in the determination of prognosis. I njuries to the basal ganglia or thalamus have an unfavourable neurologic outcome when compared with infants with a white matter predominant pattern of injury. Abnormal signals in the PLIC have also been associated with poor neurologic outcome at 2 years of age. Echocardiography A n echocardiogram to evaluate the cardiac contractility and ejection fraction. N eonates with HIE receiving therapeutic hypothermia may experience a reduction in cardiac output and descending aorta blood flow.   

8. Additional studies may include: EEG: Standard and amplitude-integrated EEG Hearing test: An increased incidence of deafness has been found among infants with hypoxic-ischemic encephalopathy who require assisted ventilation Retinal and ophthalmic examination

9. There is a profound injury to the whole corpus callosum that shows diffusion restriction on DWI. S paring of the cortical and deep grey matter and the basal nuclei.  Bilateral hyperintense signals are seen in watershed area.

10. EVOLUTION OF INJURY ON MRI

11. ELECTROENCEPHALOGRAM

12. Burst Suppression in EEG

13. ELECTROENCEPHALOGRAPHIC PATTERNS OF PROGNOSTIC SIGNIFICANCE IN ASPHYXIATED TERM INFANTS ASSOCIATED WITH FAVORABLE OUTCOME Mild depression (or less) on day 1 Normal background by day 7 ASSOCIATED WITH UNFAVORABLE OUTCOME Predominant inter burst interval 20 sec on any day Burst-suppression pattern on any day Isoelectric tracing on any day

14. CLINICAL SPECTRUM OF HIE NEUROLOGICAL SIGNS AND SYMPTOMS ENCEPHALOPATHY BRAIN STEM AND CRANIAL NERVE ABNORMALITIES MOTOR ABNORMALITIES SEIZURES RAISED ICP Hyper alert Abnormal pupillary , corneal, gag reflex. Hypotonia and weakness Start within 12-24 hours Vomiting Decreased activity Abnormal eye movements , ocular bobbing, abnormal eye movements Hypertonia , spasticity, hyperreflexia Subclinical Hypertension Stupor Facial weakness Diminished primitive reflexes 24 Hr video EEG is gold standard to diagnose. Bradycardia Coma Poor or absent suck reflex with poor feeding Bulging AF

15. MULTIORGAN DYSFUCTION KIDNEY CARDIAC PULMONARY HEMATOLOGICAL LIVER DYSFUNCTION GI Acute tubular necrosis ST depression and T wave inversion PPHN DIC Raised liver enzymes Necrotizing Enterocolitis Raised creatinine and urea Cardiogenic shock Pulmonary hemorrhage Platelet dysfunction Hypoglycemia Oliguria Fixed Heart Rate Pulmonary edema Raised PT/INR Drug toxicity

16. Clinical Features of Severe HIE and Time Frame Time Frame Clinical Features Birth to 12 hours Decreased alertness & tone Convulsions Periodic breathing or respiratory failure Intact pupillary & oculomotor responses 12 to 24 hours Change in alertness level Apneic spells Increase convulsions Jitteriness Weakness in proximal limbs In Term Neonates UL more involved than LL ,In Preterm LL more involved 24 to 72 hours Further Decreased alertness pupillary & oculomotor disturbances Respiratory arrest In Preterm, IVH or Periventricular hemorrhagic infarction also seen >72hours Persistent & diminished stupor Abnormal Sucking, Swallowing, gag & tongue movements Hypotonia more common than hypertonia Weakness in Proximal limbs

17. MANAGEMENT OF NEONATE WITH PERINATAL ASPHYXIA Delivery room care   For neonates born at term and near term (≥35 weeks) gestation, resuscitation should start with 21% oxygen.   For preterm neonates born at less than 35 weeks of gestation, resuscitation should start with 21% to 30% oxygen; further oxygen concentration should be titrated to achieve target saturations.   Obtain arterial cord blood for analysis after cutting the cord, apply additional clamp on umbilical cord on placental side keeping a cord segment of 10 to 15 cm between two clamps. Take a heparinized syringe and puncture the cord (in the clamped segment, once placenta is out and resuscitation is over) to take blood sample from umbilical artery.

18. Transfer the neonate to NICU, if   Apgar score at 1 minutes ≤3   Required prolonged bag and mask ventilation (60 seconds or more)   Required chest compressions M onitor frequently in the first 48-72 hours for development of features suggestive of HIE. CARE IN NICU 1. Maintain normal temperature After drying, place the baby under the radiant warmer   Maintain normal body temperature 2. Maintain normal oxygenation and ventilation   Assess the infant for adequacy of oxygenation and ventilation and provide support as needed   Keep under oxygen hood   Assisted ventilation is required if there is apnoea, or spontaneous respiration is inadequate or there is continuing hypoxia or hypercarbia   Measure arterial blood gas, if any respiratory or perfusion abnormalities are present

19. 3) Maintain normal tissue perfusion 4) Maintain hematocrit and metabolic milieu Target hematocrit – 45% to 55% Target glucose 75mg/dl to 100mg/dl 5) Treat seizures 6) Nutrition 7) Early intervention strategies includes promoting KMC, 1 hour noise free period, passive exercise of joints and gentle massage.

20. CAN YOU GUESS THE PICTURE?

21. Therapeutic hypothermia D efined as core body temperature less than 35°C within six hours of hospitalization Therapeutic Hypothermia has proven neuroprotective effects in global cerebral ischemia. Hypothermia should be induced as early as possible to achieve maximum neuroprotection and edema blocking effect. 

22. Selection Criteria of neonates for Therapeutic Hypothermia Sr No 1 Gestation/Birth weight >35 weeks/2Kg >2Kg(gestation not known) 2 Age of Presentation <6hours since birth <6hours since birth 3 Evidence of Birth Asphyxia Any of the following:- APGAR at 5 minutes <5 Need of IPPV 5 minutes of birth Cord arterial blood or blood obtained within 1hr of birth with pH <7.0 Cord arterial blood or blood obtained within 1hr of birth with base deficit >16.0 Any of the following:- Absence of cry at 5 Minutes of age Need of IPPV till 5 minutes of birth 4 Staging Of Encephalopathy Any of the following:- Clinical Seizures Altered state of consciousness(lethargy , stupor or Coma) and Any of the following Hypotonia Abnormal reflexes including oculomotor or pupillary reflexes Absent or weak cry Any of the following:- Clinical Seizures Altered state of consciousness(lethargy , stupor or Coma) and Any of the following Hypotonia Abnormal reflexes including oculomotor or pupillary reflexes Absent or weak cry Criteria Inborn Neonates Out born Neonates

23. Phases of Therapeutic Hypothermia Induction Maintenance Phase Rewarming Phase

24. Phase Change Materials have been incorporated in a polymer matrix to ensure that when changing phase from solid to liquid PCMs retain its shape and form avoiding any risk of the PCM leaking from its encapsulation, thus making it completely safe for the user as well as the patient. MIRACRADLE NEONATAL COOLER

25. CONTRAINDICATIONS OF THERAPEUTIC HYPOTHERMIA Major congenital malformations Suspected/known chromosomal disorder PPHN Active bleeding Catecholamine resistant shock

26. Other ongoing treatment modalities in HIE

27. Preventive Measures Prenatal Testing Prenatal and Neonatal Testing especially high risk pregnancies Fetal Heart Monitoring Preventing Premature Birth Corticosteroid's Magnesium Sulphate Proper Neonatal Resuscitation Measures

28. THANK YOU .!!!!