课件新生儿缺氧缺血脑病（hie） 七年制2010

HYPOXIC-ISCHEMIC ENCEPHALOPATHY,Prof. Huimin Yu M.D. (俞惠民) Department of Pediatrics Zhejiang University School of Medicine,DEFINITION,HIE: Hypoxic-ischemic damage of the brain resulting from perinatal asphyxia; Brain dysfunction：encephalopathy Primary cause of permanent damage to CNS.,ETIOLOGY,Fetal asphyxia (80%-90%) Any process that Impairs maternal oxygenation Decreases blood flow from the mother to the placenta or from paecenta to the fetus Impairs gas exchange across the placenta or at the fetal tissure Increases fetal O2 requirement will exacerbate perinatal asphyxia,ETIOLOGY,Fetal asphyxia (80%-90%) Maternal Hypertension; Vascular disease; Diabetes; Drug use; Hypotension; Infection; Hypoxia from pulmonary, cardiac, or neurologic disease Placental or cordal Placental infarction or fibrosis; abruption; premature separation; insuficiency Cordal prolapse; entanglement; true knot; compression; abnormal vessels Fetal Hydrops; Infection; IUGR; Postterm,ETIOLOGY,Diseases after birth (10%) Severe anemia Severe CHD Shock Respiratory failure (central or peripheral),The problem,Severe asphyxia: 2-4 per 1000 full-term births 2050% mortality 25% of the survivors will exhibit permanent neuropsychological handicaps: Mental retardation Cerebral palsy Epilepsy Learning disability,PATHOPHYSIOLOGY,CBF changes due to cardiac dysfunction & impairs of cerebrovascular autoregulation Abnormal metabolism of brain tissue Failure of energy metabolism Neurologic toxity of the excitory amino acid Ca+ influx Reperfution Oxygen free radicals,Asphyxia increase in lactate ( pH ) hypoxia decreased ATP & GS depletion cardiac output cerebrovascular autoregulation CBF faliure of ATP production impairs ion pumps (Na+-K+ ATPase) excitoxic amino acid (glutamate, NMDA) Ca+ influx open ion channels Na+, Cl- and H2O influx delayed neuronal death immediate neuronal death,NMDA activate phosphoinosotol 2nd messenger system open voltage-dependent Ca+ channel Ca+ influx activation of undesirable enzyme (lipases and proteases) pertubation of mitochondrial respiratory electron chain transport generation of free radicals and leukotrienes depletion of energy stores delayed neuronal death (apoptosis),after CPR, reperfution,Severe asphyxia,Cell injury,Primary Insult,Necrosis,Apoptosis,Hours to days,Hypothermia SOD/ Allopurinol EPO,Neurological disability,Energy failure Na+ overload Excitotoxicity,Ca+ overload Reperfusion Reactive Oxygen Species (ROS),Minutes,cerebral metabolism transiently recovers,Mitochondrial dysfunction,Secondary Insult,ATP failure and the brain cell,Glutamate release from presynatic receptor Na influx Na/K ATPase AMPA/KA cytotoxic edema Ca+ influx via NMDA Voltage-Dependent ATP failure Na+/Ca+ Brain damage,选择易损性(selective vulnerability） 慢性、部分性窒息常导致大脑弥漫性坏死，尤以皮层为甚 而急性、完全性窒息主要累及脑干、丘脑以及基底神经节。 早产儿的易损区位于脑室周围的白质区 足月儿的易损区在大脑矢状旁皮质区,PATHOLOGY,Edema Hemorrhage Subarachnoid Periventricular (subependymal germinal matrix) Intraventricular Necrosis & apoptosis Focal or multifocal cortical necrosis Cystic encephalomalacia, ulegyria (attenuation of depth of sulci) Watershed infarcts PVL, in pretem infant Parasagittal cortical and subcortical white matter , in term infant Selective neuronal necrosis （brainstem nuclei, thalamic nuclei and basal ganglia，CA1 region of the hippocampus),HIE病理类型(选择易损性),损害类型 孕周 解剖部位 足月儿 早产儿 1 选择性神经原的坏死 大脑或小脑皮质、丘脑 脑干、海马 局灶和多灶坏死 一侧或双侧大脑皮质 2 矢状旁区损害 矢状旁区的皮质、皮质 下白质 脑梗死 大脑皮质、白质 3 基底核和丘脑损害 丘脑、基底核 4 脑室周围白质软化 脑室周围白质 5 室管膜下-脑室内出血 室管膜下、脑室,4440,Germinal matrix,4441,IVH,2213,Severe IVH,4442,Post hemorrhagic hydrocephalus,Acute histological changes,2573,Severe case: ulegyria,4447,Periventricular leukomalacia, PVL,CLINICAL MANIFESTATIONS,A. Hx of fetal distress or asphyxia: Slow fetal heart rate (100/min5min) Scalp blood analysis: pH bellow 7.20 Yellow, meconium-stained amniotic fluid Low Apgar score 1 min 3 5 min 5 Umbilical ABG pH7.00,CLINICAL MANIFESTATIONS,B. Syndrome of cerebral dysfunction Abnormal consciousness Change of muscle tone Change of primary reflex Seizures Brainstem dysfunction,CLINICAL MANIFESTATIONS,C. Symptoms of other organ or systems: Kidneys: tubular (proximal) necrosis oliguria GI: NEC Lungs: ARDS, MAS Heart: CHF Blood: DIC Metabolic:hypoglycemia, hyperbilirubinemia,Hypoxic-Ischemic Encephalopathy in Term Infants Signs Stage 1 Stage 2 Stage 3 Level of consciousnes Hyperalert Lethargic Stuporous,coma Muscle tone Normal Hypotonic Flaccid Posture Normal Flexion Decerebrate Tendon reflexes/clonus Hyperactive Hyperactive Absent Myoclonus Present Present Absent Moro reflex Strong Weak Absent Pupils Mydriasis Miosis Unequal, poor light reflex Seizures None Common Decerebration EEG Normal Low voltage Burst suppression Duration 24hr 24hr to 14 days days to weeks Outcome Good Variabl Ds Modified from Sarnat H, Sarnat M: Arch Neurol 1976; 3:696. Copyright 1976, American Medical Association.,HIE临床分度,Neurologic Sequelae,Cerebral palsy Mental retardation Auditory dysfunction Visual dysfunction Language difficulties Epilepsy Hydroencephalus,Ultrasonic Examination,Edema (diffused uniform increased echo, midline shift, ventricular compression) Hemorrhage: increased echo (useful in preterm infants) Infarct and necrosis: focal or multifocal echo Nuclei and basal ganglia injury: symetric hyper-echo PVL: symetric irregular periventricular hyper-echo,Cranial Computed Tomography Scan,Edema: diffused hypodensity (2-4days after the insult) Hemorrhage: focal hyperdensity Infarct and necrosis: focal or multifocal hypodensity Nuclei and basal ganglia injury: symetric hyperdensity PVL in preterm: symetric periventricular hypodensity,Magnetic Resonance Imaging (MRI) normal signals in brain,GM WM CSF Bone Fat T1WI high low low low high T2WI low high high low high,T1WI T2WI,Magnetic Resonance Imaging (MRI) abnormal signals in brain,Hemo Infar Edema Cyst T1WI 高 低 低 低 T2WI 低 高 高 高,T2WI,T1WI,MRI 、CT 及B超比较,神经病理类型 MRI CT B超 选择性神经元坏死 脑皮质 + + 基底节和丘脑 + + + 脑干 + 矢状旁区脑损害 + + 脑室周围白质软化 + + + 局灶和多灶缺血脑损害 + + + Volpe JJ. Neurology of the Newborn. 4ed,2001.338.,Early Stage 5d,Cerebral edema,图1 生后24h,图2 生后7d,图1 示脑实质弥漫性点状强回声，基底节回声增强更为显著，侧脑室 显示不清脑水肿 图2 脑实质和基底节回声基本恢复正常，侧脑室显示清晰 脑水肿消失,头颅B超,4439 Hemorrhage,Convalescent Stage （neuron death） 710d later,infarct,cortex and subcortical leukomalacia（CT值6Hu),Nuclei and basal ganglia injury,7d CT scan,Sequelae Stage： 34Wks later，cystic change,or preterm PVL,1W,PVL（Ultrasound）,3W,PVL（Ultrasound）,5W,14M,PVL（CT）,18M, MRI,T1,T2,PVL诊断（MRI影象）,MRI,Mild HIE,左顶叶局灶性水肿，T2WI信号增高，皮层变薄，灰白质分界欠清，而正常灰白质的高低相间的柱状影消失。,MRI,Severe HIE（3d）,T1WI,T2WI,双侧大脑皮层深部呈线条状高信号,双侧弥漫性脑水肿,白质信号增高,灰质变薄,灰白质分界消失,丘脑异常高信号，示大理石样基底 节（箭头）；脑萎缩；硬脑膜下积液（箭头）,Severe HIE（3 M）,MRI,MRI,Severe HIE: infarct,T2WI,DWI,左侧顶枕叶大面积脑梗死（箭头），呈楔形高信号,DIAGNOSIS & DIFFERENT Dx,Fetal distress or birth asphyxia CNS symptoms (24 hs) RO: other diseases manifested by seizures,MANAGEMENT,CPR Intensive Care (monitor vital signs) Oxygen supply PaO2 50-70mmHg (6.65-9.31kPa) PaCO240 mmHg (5.32 kPa) keep adequate brain perfusion (systolic P above 50 mmHg) Dopamine 3-5 ug/kg/min i.v. gtt. dobutamine 2.5-10 ug/kg/min i.v. gtt.,MANAGEMENT,Anti-convulsion 1. Phenobarbital (1st line) Lording dose 10-20 mg/kg iv Maintain dose (after 12 hr.) 5 mg/kg/d b.i.d. for 7 days 2. Dilantin (2nd line) Lording dose: 15-20 mg/kg i.v. slowly 1 mg/kg/Min Maintain dose (after 6-12 hr.) 3-4 mg/kg/d b.i.d. or t.i.d. 3. Valium (1st choice for seizures status) 0.1-0.3 mg/kg i.v. 4. Chloral hydrate 0.5 ml/kg,MANAGEMENT,Control of brain edema 1. Controle fluid intake: 60-80 ml/kg/d 2. Furosemide (Lasix) 0.5-1.0 mg/kg b.i.d. 3. Albumin: 0.51g/kg, i.v. q.db.