1. Hypoxic-IschemicEncephalopathy DR. MAHMOUD MOHAMED OSMAN MBBCH, MSc (Pedia), MRCPCH (UK), FRCP (Edinburgh) Consultant Pediatrician & Neonatologist Al Yammamah Hospital, MOH 1

2. 2 Learning Objectives of Hypoxic-ischemic Encephalopathy :  Introduction  Definition  Risk factors  Causes  Pathophysiology  Clinical features  Diagnosis  Managament  Prognosis

3. INTRODUCTION:  Anoxia is a term used to indicate the consequences of complete lack of oxygen as a result of a number of primary causes.  Hypoxemia refers to decreased arterial concentration of oxygen.  Hypoxia refers to a decreased oxygenation to cells or organs.  Ischemia refers to blood flow to cells or organs that is insufficient to maintain their normal function.  Hypoxic-ischemic encephalopathy Is an abnormal neurobehavioral state in which the predominant pathogenic mechanism is impaired cerebral blood flow that may result in neonatal death or be manifested later as cerebral palsy or developmental delay. 3 Hypoxic-Ischemic Encephalopathy…………..

4. Despite major advances in fetal monitoring technology and knowledge of fetal and neonatal pathologies; hypoxic-ischemic encephalopathy (HIE), remains a serious condition that causes significant mortality and long-term morbidity. Hypoxic-Ischemic Encephalopathy…………..

5. ETIOLOGY. Asphyxia can occur in the antepartum or intrapartum period as a result of impaired gas exchange across the placenta. That leads to the inadequate provision of oxygen and removal of carbon dioxide and hydrogen from the fetus. Asphyxia can also occur in the postpartum period, usually secondary to pulmonary, cardiovascular, or neurologic abnormalities. Hypoxic-ischemic encephalopathy is characterized by clinical and laboratory evidence of acute or subacute brain injury due to asphyxia (hypoxia, ischemia, and acidosis). Most often, the exact timing and underlying cause remain unknown

6. RISK FACTORS Preconceptual IDDM Thyroid disease Fertility treatments Nulliparity Advanced maternal age. Antepartum Severe pre- eclampsia Placental abruption IUGR Antepartum haemorrhage Intrapartum Breech Cord prolapse Emergency C-section Induction Maternal pyrexia Hypoxic-Ischemic Encephalopathy…………..

7. 7 CAUSES OF FETAL HYPOXIC-ISCHEMIC INSULT

8.  After an episode of hypoxia and ischemia, anaerobic metabolism occurs and generates amounts of lactate, inorganic phosphates, glutamate, free radicals and nitric oxide.  The initial circulatory response of the fetus is transient maintenance of perfusion of the brain, heart, and adrenals in preference to the lungs, liver, kidneys, and intestine. 8 Hypoxic-Ischemic Encephalopathy………….. Pathophysiology

9. Cardiovascular Response to Asphyxia

10. The pathology of hypoxia-ischemia depends on the affected organ and the severity of the injury; these lead to signs of coagulation necrosis and cell death. If fetal distress produces gasping, the amniotic fluid contents (meconium, squames, lanugo) are aspirated into the trachea or lungs. Hypoxic-Ischemic Encephalopathy…………..

11.  Term infants demonstrate neuronal necrosis of the cortex (later, cortical atrophy) and parasagittal ischemic injury.  Preterm infants demonstrate Periventricular leukomalacia (later, spastic diplegia), basal ganglia injury, and IVH.  Term more often than preterm infants have focal or multifocal cortical infarcts that manifest clinically as focal seizures and hemiplegia. 11 Hypoxic-Ischemic Encephalopathy…………..

12. Patterns of brain injury in mild to moderate hypoperfusion. The premature neonatal brain (left) has a hypoperfusion results in a periventricular border zone (red shaded area) of white matter injury. In the term infant (right), as the brain matures; the border zone during hypoperfusion is more peripheral (red shaded area) with subcortical white matter injury. LR

13. Definition of parasagittal distribution. Cerebral parenchyma between major vascular territories (ie, between the anterior cerebral arteries [ACA] and middle cerebral arteries [MCA] and between the middle and posterior cerebral arteries [PCA]) is called the watershed zone. In combination with the previously defined border zone (refer to Fig 2),the parasagittal parenchyma (areas shaded red on axial MR image) is at risk for ischemic injury from hypoperfusion.

15.  Continuous fetal heart rate recording may reveal a slow heart rate; or variable or late deceleration.  These signs should lead to giving high oxygen to the mother and consideration of immediate delivery to avoid fetal death and CNS damage.  The presence of meconium-stained amniotic fluid is evidence that fetal distress has occurred.  At birth, affected infants may be depressed and may fail to breathe spontaneously; with pallor, cyanosis, a slow heart rate, and unresponsiveness to stimulation. 15 Hypoxic-Ischemic Encephalopathy………….. Clinical Manifestations:

16.  During the next hours, they may remain hypotonic, change to a hypertonic state, or to a normal tone.  Cerebral edema may develop and result in profound brainstem depression.  During this time, seizure activity may occur; it may be severe and refractory to the usual doses of anticonvulsants.  Seizures in asphyxiated newborns may also be due to hypocalcemia, hypoglycemia, or infection. 16 Hypoxic-Ischemic Encephalopathy…………..

17. Clinical Staging of Hypoxic-Ischemic Encephalopathy 17 Hypoxic-Ischemic Encephalopathy…………..

18.  Heart failure and cardiogenic shock, respiratory distress syndrome, gastrointestinal perforation,, and acute tubular necrosis may occur.  The severity of neonatal encephalopathy depends on the duration and timing of injury. Symptoms develop over a series of days. 18 Hypoxic-Ischemic Encephalopathy…………..

19. Consequences of Hypoxic- Ischemic Encephalopath y

20. Criteria for diagnosis of Hypoxic-ischemic encephalopathy : Profound metabolic or mixed acidemia (pH < 7) in an umbilical artery blood sample, if obtained Persistence of an Apgar score of 0-3 for longer than 5 minutes Neonatal neurologic sequelae (seizures, coma, hypotonia) Multiple organ involvement (kidney, lungs, liver, heart, intestines) Hypoxic-Ischemic Encephalopathy………….. Diagnosis

21. THE APGAR SCORE

22. There are no specific tests to confirm or exclude a diagnosis of hypoxic-ischemic encephalopathy (HIE). The diagnosis is made based on the history, physical and neurological examinations, and laboratory evidence.

23. Serum electrolyteMarkedly low serum sodium, potassium, and chloride levels in the presence of reduced urine flow and excessive weight gain may indicate acute tubular damage or (SIADH) secretion, particularly during the initial 2-3 days of life. Renal functionSerum creatinine levels, creatinine clearance, and BUN levels Cardiac & liver enzymes Assess the degree of hypoxic-ischemic injury to other organs Coagulation systemProthrombin time, partial thromboplastin time, and fibrinogen levels. ABGAssess acid-base status and to avoid hyperoxia and hypoxia as well as hypercapnia and hypocapnia LABORATORY EVALUATION OF ASPHYXIA :

24.  MRI is the preferred imaging modality in neonates with HIE because of its increased sensitivity and specificity early in the process and its ability to outline the topography of the lesion.  CT scans are helpful in identifying focal hemorrhagic lesions, diffuse cortical injury, and damage to the basal ganglia.  Ultrasonography has limited utility in evaluation of hypoxic injury in the term infant; it is the preferred modality in evaluation of the preterm infant.  Amplitude-integrated electroencephalography (aEEG); or EEG. 24 Hypoxic-Ischemic Encephalopathy………….. NEUROIMAGING INCLUDE:

25. Neuroprotective Strategies:  Therapeutic hypothermia(Selective head or whole body) reduces mortality or major neurodevelopmental impairment in term and near-term infants with HIE.  Hypothermia decreases the rate of apoptosis and suppresses production of mediators known to be neurotoxic, including extracellular glutamate, free radicals, nitric oxide, and lactate.  The neuroprotective effects are thought to be secondary to down regulation of the secondary mediators of injury resulting from cerebral edema, accumulation of cytokines, and seizures. 25 Hypoxic-Ischemic Encephalopathy………….. MANAGAMENT

26.  Several clinical trials and a meta-analysis demonstrate that a core temperature of 33.5 C within the 1st 6 hr after birth reduces mortality and major neurodevelopmental impairment.  Aggressive treatment of seizures is critical and may necessitate continuous EEG monitoring.  Phenobarbital, the drug of choice for seizures, is given as IV loading dose (20 mg/kg); additional doses of 5-10 mg/kg (up to 40-50 mg/kg total). And maintenance therapy (5 mg/kg/24hr)  Phenytoin (20 mg/kg loading dose) or lorazepam (0.1 mg/kg) may be needed for refractory seizures.  There is some clinical evidence that high-dose prophylactic phenobarbital may decrease neurodevelopmental impairment. 26 Hypoxic-Ischemic Encephalopathy…………..

27.  Hyperthermia has been found to be associated with impaired neurodevelopment, so it is important to prevent hyperthermia before initiation of hypothermia.  Careful attention to ventilatory status and, hemodynamic status (adequate oxygenation, blood pressure, acid-base balance).  Careful attention to possible infection is important.  Secondary hypoxia or hypotension due to complications of HIE must be prevented. 27 Hypoxic-Ischemic Encephalopathy…………..

28. Olympic Cool Cap System

30. 1.In severe hypoxic-ischemic encephalopathy, the mortality rate is reported as 25-50%. 2.As many as 80% of infants who survive severe HIE develop serious complications, 10% develop moderately serious disabilities, and as many as 10% are healthy. 3.The infants who survive moderately severe HIE 30-50% may have serious long-term complications, and 10-20% have minor neurological morbidities. 4.Infants with mild hypoxic-ischemic encephalopathy tend to be free from serious CNS complications. Prognosis:

31. Predictors of Mortality and Neurologic Morbidity after Perinatal Hypoxic-Ischemic Insult 31 Hypoxic-Ischemic Encephalopathy…………..

32. 32 Hypoxic-Ischemic Encephalopathy…………..