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

OF HYPOXIC-ISCHEMIC ENCEPHALOPATHY LEARNING OBJECTIVES: Introduction Definition Risk factors Causes Pathophysiology Clinical features Diagnosis Managament Prognosis OF HYPOXIC-ISCHEMIC ENCEPHALOPATHY

Hypoxic-Ischemic Encephalopathy………….. 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 is insufficient blood flow to cells or organs that 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.

Hypoxic-Ischemic Encephalopathy………….. 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.

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

RISK FACTORS Preconceptual IDDM Thyroid disease Fertility treatments Hypoxic-Ischemic Encephalopathy………….. 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

CAUSES OF FETAL HYPOXIC-ISCHEMIC INSULT:

Pathophysiology 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.

Cardiovascular Response to Asphyxia Pathophysiology………. Cardiovascular Response to Asphyxia

Pathophysiology………. 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. Term infants demonstrate neuronal necrosis of the cortex and parasagittal ischemic injury, that manifest clinically as cortical atrophy, focal seizures and hemiplegia. Preterm infants demonstrate Periventricular leukomalacia (later, spastic diplegia), basal ganglia injury, and IVH. If fetal distress produces gasping, the amniotic fluid contents (meconium, squames, lanugo) are aspirated into the trachea or lungs.

Patterns of brain injury in hypoperfusion: Pathophysiology………. Patterns of brain injury in hypoperfusion: The premature neonatal brain has a ventriculopetal vascular pattern, and hypoperfusion results in a periventricular border zone of white matter injury. The term infant, develops a ventriculofugal vascular pattern as the brain matures, and the border zone during hypoperfusion is more peripheral with subcortical white matter and parasagittal cortical injury. Term Premature

Parasagittal Watershed Area (Mature baby) The parasagittal parenchyma (the watershed zone) is at risk for ischemic injury from hypoperfusion

Clinical Manifestations: 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.

Clinical Manifestations…………

Clinical Manifestations……….. 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.

Clinical Manifestations……….. Heart failure and cardiogenic shock, respiratory distress syndrome, gastrointestinal perforation, and acute tubular necrosis may occur (multiorgan failures). The severity of neonatal encephalopathy depends on the duration and timing of injury. Symptoms develop over a series of days.

Clinical Staging of Hypoxic-Ischemic Encephalopathy: Clinical Manifestations……….. Clinical Staging of Hypoxic-Ischemic Encephalopathy:

Multi-organ injuries as consequences of hypoxic-ischemic encephalopathy

Diagnosis Criteria for diagnosis of HIE: 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)

Diagnosis……… THE APGAR SCORE:

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

LABORATORY EVALUATION OF ASPHYXIA: Serum electrolyte Diagnosis……… LABORATORY EVALUATION OF ASPHYXIA: Serum electrolyte Markedly 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 function Serum creatinine levels, creatinine clearance, and BUN levels Cardiac & liver enzymes Assess the degree of hypoxic-ischemic injury to other organs Coagulation system Prothrombin time, partial thromboplastin time, and fibrinogen levels. ABG Assess acid-base status and to avoid hyperoxia and hypoxia as well as hypercapnia and hypocapnia

NEUROIMAGING INCLUDES: Diagnosis……… NEUROIMAGING INCLUDES: 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.

MANAGAMENT 1. Hypothermia Therapy Selective head or whole body hypothermia of a core temperature of 33.5 C applied within 6 hours of birth for 48-72 hours is neuroprotective. Possible mechanisms include: Reduced metabolic rate and energy depletion. Decreased excitatory transmitter release. Reduced alterations in ion flux. Reduced apoptosis due to hypoxic-ischemic encephalopathy. Reduced vascular permeability, edema, and disruptions of blood-brain barrier functions. Several clinical trials demonstrate that therapeutic hypothermia is a promising therapy for mild-to-moderate cases of HIE. It reduces mortality and major neurodevelopmental impairment.

2. Aggressive treatment of seizures: MANAGAMENT………. 2. Aggressive treatment of seizures: It 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.

3. General supportive measures: MANAGAMENT…….. 3. General supportive measures: 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); to prevent secondary hypoxia or hypotension due to complications of HIE. Careful attention to possible infection is important.

Olympic Cool Cap System

Prognosis: In severe hypoxic-ischemic encephalopathy, the mortality rate is reported as 25-50%. 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. The infants who survive moderately severe HIE 30-50% may have serious long-term complications, and 10-20% have minor neurological morbidities. Infants with mild hypoxic-ischemic encephalopathy tend to be free from serious CNS complications.

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

Hypoxic-Ischemic Encephalopathy………….. BEST WISHES