Lecture III Neonatal Asphyxia & Its Complications ( 新生儿窒息及其并发症 ) Department of Pediatrics Soochow University Affiliated Children’s Hospital

Part I Neonatal Asphyxia 新生儿窒息

Aim & Claim Understand the assessment & care of normal birth Familiar with the pathogenesis of birth asphyxia Hold of Apgar score & ABCDE resuscitation Familiar with the complication of severe asphyxia

Definition Birth asphyxia is defined as a reduction of oxygen delivery and an accumulation of carbon dioxide owing to cessation of blood supply to the fetus around the time of birth.

This is pathologic condition referred to neonate who have no spontaneous breathing or represented irregular breathing movement after birth. Usually caused by perinatal hypoxia. It is emergency condition and need quickly treatment (resuscitation ，复苏 ).

Etiology Pathologically, any factors which interfere with the circulation between maternal and fetal blood exchange could result in the happens of perinatal asphyxia. These factors can be maternal factor, delivery factor and fetal factor.

Etiology—High Risk Factors Maternal factor: hypoxia, anemia, diabetes, hypertension, smoking, nephritis, heart disease, too old or too young,etc Delivery condition: Abruption of placenta, placenta previa, prolapsed cord, premature rupture of membranes,etc Fetal factor: Multiple birth, congenital or malformed fetus,etc

Pathophysiology When fetal asphyxia happens, the body will show a self-defended mechanism which redistribute blood flow to different organs called “inter-organs shunt” in order to prevent some important organs including brain, heart and adrenal from hypoxic damage.

Pathophysiology(I) Hypoxic cellular damages: a.Reversible damage(early stage): Hypoxia may decrease the production of ATP, and result in the cellular functions. But these change can be reversible if hypoxia is reversed in short time.

b. Unreversible damage: If hypoxia exist in long time enough, the cellular damage will become unreversible that means even if hypoxia disappear but the cellular damages are not recovers. In other words, the complications will happen.

Pathophysiology(II) Asphyxia development: a.Primary apnea breathing stop but normal muscular tone or hypertonia （肌 张力增高）, tachycardia (quick heart rate), and hypertension Happens early and shortly, self-defended mechanism ， could not be damage to organ functions if corrected quickly

b. Secondary apnea Features of severe asphyxia or unsuccessful resuscitation, usually result in damage of organs function.

Pathophysiology(III ) Other damages: a.Persistent pulmonary hypertension (PPHN) b.Hyper/hypoglycemia c.Hyperbilirubinemia

Clinic manifestations Fetal asphyxia fetal heart rate: tachycardia bradycardia fetal movement: increase decrease amniotic fluid: meconium-stained

Clinic manifestations Apgar score: A: appearance(skin color) P: pulse(heart rate) G: grimace(reactive ability) A: activity(muscular tension) R: respiration

APGAR score Score H eart rate none 100 Respiration none irregular regular Muscle tone limp reduced normal Response to none grimaced cough stimulation Color of trunk white blue pink

Degree of asphyxia: Apgar score 8~10: no asphyxia Apgar score 4~8: mild/cyanosis asphyxia Apgar score 0~3: severe/pale asphyxia

Clinic manifestations Complications: CNS: HIE, ICH RS: MAS, RDS, pulmonary hemorrhage CVS: heart failure, cardiac shock GIS: NEC, stress gastric ulcer Others: hypoglycemia, hypocalcemia （低钙血 症）, hyponatremia （低钠血症）

Diagnosis 1/ Evidence of fetal distress 2/ Fetal metabolic acidosis 3/ Abnormal neurological state 4/ Multiorgan involvement

Management ABCDE resuscitation A (air way) B (breathing) C (circulation) D (drug) E (evaluation)

Airway 1/ open by placing the head in the neutral position 2/ clean up completely amniotic fluid from the airway by suction with syringe （ 注射器） as soon as possible 3/ if meconium-stained, tracheal catheter （气管插管） should be placed to ensure meconium to be removed

Breathing 1 / ensure face mask covers nose & mouth connect to oxygen bag 2/ establish respiration of 30-40/min with chest wall movement 3/ if no response, intubation & mechanic ventilation （通气） is necessary

Circulation 1/ if heart rate <60/bpm, start external cardiac compression with fingers 2/ ratio 3:1 ( 90 compressions to 30 bpm )

Drugs 1/ if profound bradycardia （心动过缓）, give adrenaline （肾 上腺素） (1:10000, ml/kg) by endotracheal （气管 内） tube or umbilical vein 2/ if no response, intravenous fluid (saline, albumin, plasma, blood) with 10ml/kg 3/ if acidosis, give 5% sodium bicarbonate (SB) with 3- 5ml/kg 4/ if bradypnea, consider using naloxone （纳洛酮） (0.1mg/kg)

Evaluation Evaluate the result of resuscitation to determine if more rescue necessary: –If not good, repeat the resuscitation –If good, transmit baby to NICU

Remember In the whole resuscitation, the most important step is A --- clean up completely the airway

Part II Hypoxic Ischemic Encephalopathy (HIE) ( 新生儿缺氧缺血性脑病 )

Aim & Claim Familiar with the severity of HIE Familiar with the management of HIE

Definition The brain damage after perinatal asphyxia and the most severe condition showed high mortality or remain cerebral complications such as mental retardation & cerebral palsy.

Clinically, more term babies suffered from this disease than premature babies. Pathologically, more premature babies suffered from this disease than term babies.

Etiology & Pathology Etiology The most and direct cause of HIE is perinatal asphyxia. Pathology

Pathophysiology Cerebral blood flow early stage: normal (intraorgans shunt) then slow down (selective vulnerability) finally ischemia Cerebral metabolism

Clinic Manifestation The clinic features of HIE are mainly symptoms of consciousness which usually represent in tow types:

Excitation: hyperalert （激惹）, irritable, hypertonia, tachycardia, tachypnea, seizure, etc Depressing: coma, hypotonia, bradycardia, bradypnea, unresponsibility, etc

Classification—Clinic Mild(stage I): hyperalert, irritable, normal muscular tone & reflex, no seizure, normal EEG Moderate(stage II): lethargy, hypotonia, weak sucking & Moro response, often seizure, EEG+ Severe(stage III): coma, absent muscular tone & reflex, persistent seizure, EEG++

Classification—CT Stage I(normal): no hypodensity （低密度） Stage II(mild): local or patchy hypodensity Stage III(moderate): hypodensity in tow area of brain or more, usually no hemorrhage Stage IV(severe): extensive & generalized hypodensity, usually combined with brain hemorrhage

轻度：散在或局限性低密度改变，在 2 个脑叶以内

中度 ： 低密度改变超过 2 个脑叶，灰白质对比模糊 中度不伴出血 中度伴出血

重度 ： 弥漫性低密度改变， 灰白质界限消失， 脑室受压。 中、重度 HIE 常伴 ICH 。 颅内出血

Management(I) Generalized treatment: –Ventilation: CPAP, CMV, HFOV –Circulation: Dopamine( 多巴胺） /Dobutamine （多巴酚丁胺） –Energy: normal glucose –Fluid: restriction < 60-80ml/kg/d

Management(II) Control of seizures: –Phenobarbital( 苯巴比妥 ): loading dose 15-20mg/kg, iv maintenance dose 3-5mg/kg, iv –Diazepam( 安定 ): mg/kg, iv –Chloralhydrate( 水合氯醛 ): 50mg/kg, E

Management(III) Cerebral edema & high pressure –Furosemide( 速尿 ): 1mg/kg, iv, q4-12h –Mannitol( 甘露醇 ): 0.5g/kg, iv, q8-12h –Albumin( 白蛋白 ): g/kg, iv

Prognosis Depend on the severity of brain damage & medical treatment, usually: Mild or moderate cases could be cured completely, but severe cases represent poor prognosis with high mortality or cerebral complications such as mental retardation & cerebral palsy.

Prevention Perinatal healthy care Prevention of asphyxia

Part III Intracranial Hemorrhage (ICH) ( 颅内出血 )

Aim & Claim Familiar with the etiology of ICH Familiar with the characterastic of all types of ICH

Introduction The intracranial hemorrhage (ICH) is one of the most common and dangerous disease with very high mortality & disability rate in alive cases.

The morbidity is higher in premature infants than in term ones. There are differing etiology and varying prognosis. With improvement in perinatal care, there have be considerable improvement in survival recently.

Etiology & Pathology Vessels factor Pressure factor ICH Injury factor Other factors (Vit K deficiency, maternal medication, thrombopenia, etc)

Etiology & Pathology Vessels factors Premature vessels of neonate especially in preterm babies is vulnerable to damage

Etiology & Pathology Pressure factor Any change of blood pressure could interfere with the cerebral circulation and break the blood vessels

Etiology & Pathology Injury factor Any injury during the delivery may break the blood vessels

Etiology & Pathology Other factors Deficiency of vitamin K Maternal bleeding or thrombocytopenia （血小板减少 症） Maternal medications

Classification of ICH Periventricular-intraventricular hemorrhage(PVH-IVH) Primary subarachoid hemorrhage (SAH) Intraperenchymal hemorrhage (IPH) Subdural hemorrhage (SDH) intracerebellar hemorrhage (ICH)

PVH-IVH Premature infant, especially VLBW Onset early, <72 h Depressing symptoms: apnea, hypotonia, lethargy, no crying, coma

SAH Usually have history of birth injury Excitation symptom Seizure appear in 2 nd day Bloody cerebral spinal fluid Hydrocephalus （脑积水）

IPH Usually term baby Caused by hypertension Poor prognosis

SDH Usually huge baby Often have injury history Onset early: <24h

ICH Premature below 32 weeks GA Nonspecific features Affected vital signs Frequent apnea & bradycardia Poor prognosis

Diagnosis History: asphyxia birth injury premature, etc

Symptoms & signs: excitation or depressing

Radiological evidence : hyperdencity （高密度） (white) on CT or MRI

Management General management: keep quiet, keep normal glucose (5mmol/L) maintain normal blood-gas analysis maintain the balance of vital signs & fluid/energy

Management Hemostasis( 止血 ) – vitamin K, plasma or blood transfusion, – hemostatic (bleeding stopping medications)

Management Control seizure Phenobarbital Diazepam Chloralhydrate

Management Decreasing intracranial pressure Furosemide( 速尿 ): 0.5-1mg/kg, iv, q8-12h Dexmethasone( 地塞米松 ): mg/kg, iv, q8- 12h Albumin( 白蛋白 ): g/kg, iv Mannitol( 甘露醇 ): 0.5g/kg, iv, q8-12h

Management Treatment of hydrocephalus serial lumbar punctures surgery operation

Prognosis Related to the severity of bleeding and locations. High mortality and instabilities.

Prevention Prenatal care Prevention of asphyxia & birth injury

Summery Neonatal asphyxia and its complication (HIE, ICH) are the most dangerous conditions clinically with high mortality and incidence of poor neurological outcome

Questions What is APGAR score ? What is the composition of ABCDE resuscitation ?

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