Hypoxic-ischemic encephalopathy (HIE) is a significant cause of central nervous system damage leading to neonatal death or long-term conditions such as cerebral palsy, with 15-20% of affected infants dying shortly after birth. The document outlines causes, physiological effects, clinical manifestations, and treatment options for HIE, emphasizing the necessity of supportive care and monitoring for seizures. Prognosis varies widely depending on factors like gestational age, severity of the condition, and management of metabolic complications.

1. Hypoxic Ischemic Encephalopathy Prof. Saad S Al-Ani Senior Pediatric Consultant Head of Pediatric Department Khorfakkan Hospital . Sharjah [email_address]

2. Ischemia refers to blood flow to cells or organs that is insufficient to maintain their normal function Definitions Anoxia is a term used to indicate the consequences of complete lack of oxygen as a result of a number of primary causes Hypoxia refers to an arterial concentration of oxygen that is less than normal Biagioni E, Mercuri E, Rutherford M, et al: Combined use of electroencephalogram and magnetic resonance imaging in full-term neonates with acute encephalopathy. Pediatrics 2001;107:461

3. Hypoxic-ischemic encephalopathy Is an important cause of permanent damage to CNS cells that may result in neonatal death or be manifested later as cerebral palsy or mental deficiency Nelson Textbook of Pediatrics 19 th ed.2010 . pages 566 - 568

4. 25-30% of survivors are left with permanent neurodevelopmental abnormalities (cerebral palsy, mental retardation). Dixon G, Badawi N, Kurinczuk JJ, et al: Early developmental outcomes after newborn encephalopathy. Pediatrics 2002;109:26-33 Fifteen to 20% of infants with hypoxic-ischemic encephalopathy die in the neonatal period

5. Effects of Asphyxia System Effect I. Central nervous system 1.Hypoxic-ischemic encephalopathy 2.Infarction 3. Intracranial hemorrhage 4.Seizures 5. Cerebral edema 6. Hypotonia 7. Hypertonia II.Cardiovascular 1. Myocardial ischemia 2. Poor contractility 3. Cardiac stun 4. Tricuspid insufficiency 5. Hypotension Cowan F, Rutherford M, Groenendaal F, et al: Origin and timing of brain lesions in term infants with neonatal encephalopathy. Lancet 2003;361:736-42.

6. Effects of Asphyxia System Effect (cont.) III. Pulmonary 1. Pulmonary hypertension 2. Pulmonary hemorrhage 3. Respiratory distress syndrome IV. Renal Acute tubular or cortical necrosis V. Adrenal Adrenal hemorrhage VI. Gastrointestinal 1. Perforation 2. Ulceration with hemorrhage 3. Necrosis Cowan F, Rutherford M, Groenendaal F, et al: Origin and timing of brain lesions in term infants with neonatal encephalopathy. Lancet 2003;361:736-42.

7. Effects of Asphyxia System Effect (cont.) VII. Metabolic 1. Inappropriate secretion of antidiuretic hormone 2. Hyponatremia 3. Hypoglycemia 4. Hypocalcemia 5. Myoglobinuria VIII. Integument Subcutaneous fat necrosis IX. Hematology Disseminated intravascular coagulation Cowan F, Rutherford M, Groenendaal F, et al: Origin and timing of brain lesions in term infants with neonatal encephalopathy. Lancet 2003;361:736-42.

8. Asphyxia is considered in infants with : Fetal acidosis (pH <7.0) A 5-min Apgar score of 0-3 Hypoxic-ischemic encephalopathy: i. Altered tone ii. Depressed level of consciousness iii. Seizures And 4. Other multiorgan system signs Battin MR, Dezoete A, Gunn TR, et al: Neurodevelopmental outcome of infants treated with head cooling and mild hypothermia after perinatal asphyxia. Pediatrics 2001;107:480

9. Causes Of Fetal Hypoxia Inadequate oxygenation of maternal blood as a result of: I. Hypoventilation during anesthesia II. Cyanotic heart disease III. Respiratory failure IV. Carbon monoxide poisoning (2) low maternal blood pressure as a result of the hypotension that may: I. Complicate spinal anesthesia II. Result from compression of the vena cava and aorta by the gravid uterus

10. Causes Of Fetal Hypoxia (cont.) (4) Premature separation of the placenta Johnson MV: MRI for neonatal encephalopathy in full-term infants. Lancet 2003;361:713-4 (3) Inadequate relaxation of the uterus to permit placental filling as a result of uterine tetany caused by the administration of excessive oxytocin

11. Causes Of Fetal Hypoxia (cont.) (6) Uterine vessel vasoconstriction by cocaine (7) placental insufficiency from numerous causes including toxemia and postmaturity. Johnson MV: MRI for neonatal encephalopathy in full-term infants. Lancet 2003;361:713-4 (5) Impedance to the circulation of blood through the umbilical cord as a result of compression or knotting of the cord

12. Fetal hypoxia Nelson Textbook of Pediatrics (on 20 November 2003) 2003 Elsevier Abnormal Doppler velocimetry . On an umbilical artery Doppler flow velocity waveform The umbilical placental impedance is so high that the diastolic component shows flow in a reverse direction. This finding is an indication of severe intrauterine hypoxia and intrauterine growth restriction .

13. Causes of after birth hypoxia Anemia severe enough to lower the oxygen content of the blood to a critical level, as after severe hemorrhage or hemolytic disease (2) Shock severe enough to interfere with the transport of oxygen to vital organs as a result of i. Overwhelming infection ii. Massive blood loss iii. Intracranial or adrenal hemorrhage Crowley P: Prophylactic corticosteroids for preterm birth. Cochrane Database Syst Rev 2002;Issue 1. De Felice C, Toti P, Laurini RN, et al: Early neonatal brain injury in histologic chorioamnionitis. J Pediatr 2001;138:101

14. Causes of after birth hypoxia (cont.) (4) Failure of oxygenation of an adequate amount of blood as a result of severe forms of cyanotic congenital heart disease or pulmonary disease (3) Deficit in arterial oxygen saturation from failure to breathe adequately postnatally because of i. Cerebral defect ii. Narcosis iii. Injury Crowley P: Prophylactic corticosteroids for preterm birth. Cochrane Database Syst Rev 2002;Issue 1. De Felice C, Toti P, Laurini RN, et al: Early neonatal brain injury in histologic chorioamnionitis. J Pediatr 2001;138:101

15. The initial circulatory response of the fetus * is increased shunting through the ductus venosus, ductus arteriosus, and foramen ovale * with transient maintenance of perfusion of the brain, heart, and adrenals in preference to the lungs (because of pulmonary vasoconstriction), liver, kidneys, and intestine. Pathophysiology Within minutes of the onset of total fetal hypoxia : 1.Bradycardia 2. Hypotension 3. decreased cardiac output 4. severe metabolic as well as respiratory acidosis occur

16. . Hon EH: An Atlas of Fetal Heart Rate Patterns . New Haven, CT, Harty Press, 1968.) Patterns of periodic fetal heart rate (FHR) deceleration A shows early deceleration occurring during the peak of uterine contractions as a result of pressure on the fetal head

17. . Hon EH: An Atlas of Fetal Heart Rate Patterns . New Haven, CT, Harty Press, 1968.) Patterns of periodic fetal heart rate (FHR) deceleration (cont . ) B , Late deceleration caused by uteroplacental insufficiency

18. . Hon EH: An Atlas of Fetal Heart Rate Patterns . New Haven, CT, Harty Press, 1968.) Patterns of periodic fetal heart rate (FHR) deceleration (cont.) C , Variable deceleration as a result of umbilical cord compression

19. Clinical Manifestations Hypoxic-Ischemic Encephalopathy in Term Infants Signs: Stage 1 Stage 2 Stage 3 I. Level of consciousness Hyperalert , Lethargic Stuporous coma II. Muscle tone Normal Hypotonic Flaccid III. Posture Normal Flexion Decerebrate Biagioni E, Mercuri E, Rutherford M, et al: Combined use of electroencephalogram and magnetic resonance imaging in full-term neonates with acute encephalopathy. Pediatrics 2001;107:461

20. Clinical Manifestations Hypoxic-Ischemic Encephalopathy in Term Infants (cont.) Signs: Stage 1 Stage 2 Stage 3 IV. Tendon reflexes Clonus ,Hyperactive Hyperactive Absent V. Myoclonus Present Present Absent VI. Moro reflex Strong Weak Absent Biagioni E, Mercuri E, Rutherford M, et al: Combined use of electroencephalogram and magnetic resonance imaging in full-term neonates with acute encephalopathy. Pediatrics 2001;107:461

21. Clinical Manifestations Hypoxic-Ischemic Encephalopathy in Term Infants (cont.) Signs: Stage 1 Stage 2 Stage 3 VII. Pupils Mydriasis Miosis Unequal Poor light reflex VIII. Seizures None Common Decerebration IX. Electroencephalographic Normal Low voltage changing Burst suppression to seizure activity to isoelectric Biagioni E, Mercuri E, Rutherford M, et al: Combined use of electroencephalogram and magnetic resonance imaging in full-term neonates with acute encephalopathy. Pediatrics 2001;107:461

22. Clinical Manifestations Hypoxic-Ischemic Encephalopathy in Term Infants (cont.) Signs: Stage 1 Stage 2 Stage 3 X. Duration <24 hr if progresses; otherwise, Days to weeks may remain normal24 hr to 14 days XI. Outcome Good Variable Death, severe deficits Biagioni E, Mercuri E, Rutherford M, et al: Combined use of electroencephalogram and magnetic resonance imaging in full-term neonates with acute encephalopathy. Pediatrics 2001;107:461

23. Treatment Therapy is supportive and directed at the organ system manifestations Careful attention to : Ventilatory status and adequate oxygenation Blood volume, Hemodynamic status Acid-base balance Possible infection is important Dixon G, Badawi N, Kurinczuk JJ, et al: Early developmental outcomes after newborn encephalopathy. Pediatrics 2002;109:26-33.

24. Treatment (cont.) No established effective treatment is available for the brain tissue injury, although many drugs (phenobarbital, allopurinol, calcium channel blockers) and procedures (total body or local cranial hypothermia) are under study Aggressive treatment of seizures is critical and may necessitate continuous electroencephalographic monitoring. Dixon G, Badawi N, Kurinczuk JJ, et al: Early developmental outcomes after newborn encephalopathy. Pediatrics 2002;109:26-33.

25. Phenytoin (20 mg/kg loading dose) or lorazepam (0.1 mg/kg) may be needed for refractory seizures. Treatment (cont.) Seizure activity may be severe and refractory to the usual doses of anticonvulsants Phenobarbita l, the drug of choice, is given with an intravenous loading dose (20 mg/kg); additional doses of 10 mg/kg (up to 40-50 mg/kg total) may be needed. Phenobarbital levels should be monitored 24 hr after the loading dose and maintenance therapy (5 mg/kg/24 hr) are begun Dixon G, Badawi N, Kurinczuk JJ, et al: Early developmental outcomes after newborn encephalopathy. Pediatrics 2002;109:26-33.

26. Prognosis The outcome of hypoxic-ischemic encephalopathy ranges from complete recovery to death The prognosis depending on : 1.Whether the metabolic and cardiopulmonary complications (hypoxia, hypoglycemia, shock) can be treated 2. Infant's gestational age (outcome is poorest if the infant is preterm) 3. Severity of the encephalopathy Battin MR, Dezoete A, Gunn TR, et al: Neurodevelopmental outcome of infants treated with head cooling and mild hypothermia after perinatal asphyxia. Pediatrics 2001;107:480.

27. Severe encephalopathy characterized by : 1.Flaccid coma 2.Apnea 3.Absence oculocephalic reflexes 4. Refractory seizures Is associated with a poor prognosis Prognosis (Cont.) Battin MR, Dezoete A, Gunn TR, et al: Neurodevelopmental outcome of infants treated with head cooling and mild hypothermia after perinatal asphyxia. Pediatrics 2001;107:480.

28. 1. A low Apgar score at 20 min 2. Absence of spontaneous respirations at 20 min of age 3. Persistence of abnormal neurologic signs at 2 wk of age predict death or severe cognitive and motor deficits Prognosis (Cont.) Battin MR, Dezoete A, Gunn TR, et al: Neurodevelopmental outcome of infants treated with head cooling and mild hypothermia after perinatal asphyxia. Pediatrics 2001;107:480.

29. Brain death after neonatal hypoxic-ischemic encephalopathy is diagnosed by: 1. Clinical findings of coma unresponsive to pain, auditory, or visual stimulation 2. Apnea with Pco2 rising from 40 to over 60 mm Hg 3. Absent brainstem reflexes (pupil, oculocephalic, oculovestibular, corneal, gag, sucking) Prognosis (Cont.) Battin MR, Dezoete A, Gunn TR, et al: Neurodevelopmental outcome of infants treated with head cooling and mild hypothermia after perinatal asphyxia. Pediatrics 2001;107:480.

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