Neonatal hypoxia and hypoxic-hemorrhagic encephalopathy (HIE)
Changsha Revision (2004)
Neonatology Group of China Medical Branch
A concept:
Hypoxia and cerebral blood flow reduction caused by various perinatal factors and fetal and neonatal brain injuries are called hypoxic-ischemic encephalopathy. Hypoxic ischemic encephalopathy plays an important role in perinatal nervous system diseases. The annual incidence of asphyxia in China is180,000-20 million dollars, and the disability rate of live births is 13.6%. Every year, about 300,000 children are disabled and seriously threatened, which damages the quality of life of our children.
Any number of factors: yes
The oxygen concentration in the blood of fetus or newborn decreases HIE, which is closely related to the intrauterine environment during delivery.
(1) Maternal factors: ① Mother's systemic diseases: diabetes, heart and kidney diseases, severe anemia and acute infectious diseases.
② Obstetric diseases: pregnancy-induced hypertension syndrome, placenta previa, placental abruption and placental dysfunction.
③ Mother taking drugs, smoking and passive smoking.
④ Mother's age >; 35 years old or 16 years old, multiple pregnancy.
(2) Labor factors: (1) umbilical cord compression, knotting around the neck, and attraction (2) surgical delivery such as high forceps, breech position, and fetal head failure; ③ Narcotic analgesics and oxytocin should not be used during delivery.
(3) Fetal factors: (1) small gestational age infants, macrosomia; 2 deformities: such as webbed throat, atelectasis and congenital heart disease; ③ Nasal atresia after amniotic fluid or meconium inhalation leads to airway obstruction; ④ Damage of uterine infection to nervous system.
Postpartum factors: infection, pneumonia, Gay syndrome, polycythemia, etc.
Pathogenesis Pathogenesis is very complicated and unknown in many fields, but it is mainly related to the changes of cerebral blood flow in the following aspects:
(1) Redistribute the blood flow of body organs with incomplete asphyxia to ensure the blood flow of heart, brain, adrenal cortex and other tissues. If hypoxia persists, the compensation mechanism is that cerebral blood flow perfusion is reduced, and secondary flow redistribution reduces cerebral blood flow to ensure blood flow perfusion in thalamus, brain stem and cerebellum. In this case, the sagittal white matter of cerebral cortex (the marginal area of posterior cerebral artery perfusion) is the most vulnerable, such as the compensation mechanism of acute asphyxia is invalid, and the metabolic cerebral cortex (thalamus and brain stem nucleus) of brain injury is the most, which will not be affected.
(2) The main mechanism of energy metabolism is brain energy = glucose and lactic acid oxidation, and the consumption of anoxic sugar increases during anaerobic glycolysis, leading to hypoglycemia and metabolic acidosis; The sodium pump ATP↓ in cell membrane is not enough to play the role of calcium pump. Sodium and calcium ions enter cells, leading to immunogenic brain edema of cells. Calcium can also activate enzymes and their regulation, which leads to the decomposition of phospholipid components in plasma membrane to produce a large amount of arachidonic acid and thromboxane. Prostacyclin ATP camp ① affects the structure and function of neurotransmitters through synapses; (2) The brain that affects nerve cells →→→→ ③ The function of many vasoactive substances that depend on cAMP decreases → vasospasm → brain tissue damage.
(3) Neurotoxic substances: brain hypoxia →AA excitement, increased oxygen free radical phosphorylation → blocking mitochondrial oxidation, destroying cell structure and enzymes.
(d) One form of cell death caused by neuronal apoptosis is that if excessive apoptosis occurs, a separate physiological process of maturation and maintenance is necessary, that is, a pathological state. Recent studies have confirmed that HIE-induced neuronal apoptosis is the result of the interaction between pathological mechanism and apoptosis of various nerve cells in acute necrotizing pancreatitis. 1 hour in advance until after hypoxia and ischemia 1? Two weeks.
Fourth, the clinical manifestations are
After the neurological symptoms of HIE are gradually born, in some cases, inhibition or even coma is the most serious, lasting 72 hours. After 72 hours, the excitement gradually improved and recovered. Symptoms and reactions of nervous system 3 days after birth, clinicians carefully observed and gave indicators.
The clinical grading items of neonatal hypoxic-ischemic encephalopathy can be divided into mild and severe.
Overconsciousness, overexcitation, lethargy and slow coma
Muscle tension decreased normally and the original reflex disappeared.
The front of the hug weakened slightly and disappeared.
Nothing is more common or lasting than before.
Central respiratory failure is often without lights.
The pupil changes or shrinks, and the asymmetric or enlarged light reflection weakens and disappears.
Convulsive sucking is normal BR/> Normal tension, normal or slightly swollen, full of tension.
The most obvious process and result: the symptoms of excitement gradually disappeared within 24 hours and after 3 days. Most of the symptoms with good prognosis are in 1 weekend, and the anti-inflammatory and 10 day sequelae have not disappeared. The mortality rate is high, and most of them die within 1 week. The symptoms and sequelae of survivors may be several weeks.
diagnose
Historical and nonspecific clinical manifestations are often confused and easily associated with other diseases in the neonatal period, mainly based on the following points:
(1) clinical basis
1。 Clear the abnormal obstetric history of fetal hypoxia, such as severe fetal distress such as fetal movement and obvious decrease of fetal heart rate.
2。 Birth asphyxia, severe asphyxia, if more than two minutes, Apgar score ≤3, 5 minutes ≤6' rescue exceeds 10 minutes, tracheal intubation is needed for positive pressure breathing.
3。 Within 65,438+02 hours after birth, there are conscious obstacles, such as excessive excitement (trembling limbs, eyes wide open for a long time, staring, etc. ), lethargy, lethargy, even coma, changes in muscle tone of limbs (weak and soft), abnormal primitive reflex, hyperactivity, weakening or disappearance of Moro reflex, hyperactive sucking reflex and weakening or disappearance of sucking reflex.
4。 In severe cases, convulsions or frequent convulsions may occur, and muscle tension may increase.
5。 Severe cases may be brainstem symptoms, such as respiratory rhythm arrhythmia, respiratory depression and central respiratory failure. When the pupil shrinks or expands, it is slow to respond to light or even disappears, and some children have nystagmus.
6。 HIE should be differentiated from obstetric intracranial hemorrhage, intrauterine encephalitis and congenital malformation.
Laboratory examination
1。 Laboratory examination: blood gas analysis to understand hypoxia and acidosis; Blood sugar, blood electrolyte, myocardial zymogram, liver and kidney dysfunction and multiple organ dysfunction, creatine kinase brain isoenzyme (CK-BB) and nerve-specific enolase (NSE) can determine the severity of brain injury.
2。
The purpose of imaging research is to further clarify the lesion and scope of HIE, determine whether it is complicated with intracranial hemorrhage and the type of hemorrhage, and conduct a series of dynamic examinations to evaluate the prognosis. Intracranial hemorrhage, mainly brain edema, can usually be detected within 3 days after birth; Appropriate, check after 3-4 weeks, if you want to check the brain material and intraventricular hemorrhage of hypoxic-ischemic brain damage after birth? 10 day, the lesion still exists, which is closely related to the prognosis.
See 2. 1 CT:
(1) Diffuse low-density ventricles in both hemispheres shrink or even disappear, suggesting brain edema.
(2) The symmetrical density of bilateral basal ganglia and thalamus increased, suggesting that there are lesions in basal ganglia and thalamus and brain edema is needed.
(3) Reduce the density of brain tissue, distribute infarcts in cerebral arteries, and point out the main arteries and their branches.
(4) Symmetrical low-density areas around the ventricles, especially outside the anterior horn of the lateral ventricles, indicate periventricular leukomalacia, often accompanied by intraventricular hemorrhage, which is more common in premature infants.
(5) According to CT examination, the low density distribution range of white matter can be divided into light, medium and 3 degrees. CT grading is not completely consistent with clinical grading. ① Mild: scattered in the brain with low-density brain lobes. ② Moderate: The contrast between white matter and gray matter in low-density brain lobes is blurred for more than two years. ③ Severe: diffuse low-density shadow, the boundary between gray matter and white matter disappears, the density of basal ganglia and cerebellum is normal, and cerebral hemorrhage is often accompanied by severe subarachnoid hemorrhage and ventricular hemorrhage.
2.2 B-ultrasound examination shows that
(1) Slightly and widely distributed echoes in brain parenchyma, accompanied by shrinkage or disappearance of ventricles, sulcus and hemispheric fissure, and weakened pulse of cerebral arteries, suggesting the existence of brain edema.
(2) Symmetrical strong echo reflex of bilateral basal ganglia and thalamus, that is, N ganglion and hypothalamus were damaged.
(3) The localized strong echo reflex is distributed in the middle cerebral artery, suggesting that there is myocardial infarction in the brain, main arteries and their branches.
(4) Coronal region, please refer to the inverted triangle bilateral symmetric strong echo region above the anterior corner of the lateral ventricle; The sagittal section above the lateral ventricle is an irregularly distributed strong echo area, indicating that there is white matter softening in the ventricle.
2.3 Examination of brain functional status
2.3. 1 EEG
Electroencephalogram (EEG) can reflect the changes of brain dysfunction, which has certain effect on early diagnosis and prognosis of hypoxic-ischemic encephalopathy.
(1) The manifestations of hypoxic-ischemic encephalopathy, abnormal EEG background activity, low voltage, equipotential and sudden inhibition are common.
(2) After birth 1 week, the clinical classification of EEG abnormalities is basically the same. After 2-3 weeks, the prognosis of EEG has not improved significantly.
(3) If 24-hour ambulatory EEG can be realized, the clinical application value can be improved.
2.3.2 The application of color Doppler ultrasound in cerebral hemodynamics can effectively measure the blood flow velocity of anterior cerebral artery, artery and artery, and evaluate the changes of vascular cerebral hemodynamics.
2.3.3 Magnetic Resonance Spectroscopy (MRS) is a noninvasive method to detect chemical components (ATP, creatine phosphate, lactate) in the brain. In recent years, a non-invasive diagnostic method-Near Infrared Spectrometer (NIRS) has attracted much attention. Using oxygenated hemoglobin, deoxyhemoglobin and other substances, the brain oxygenation and cell metabolism can be monitored in real time according to different principles of near-infrared absorption of specific light.
Principles of treatment of VI
Handling of ...
(1) 1. Strive for early treatment: For nervous system symptoms, resuscitation treatment should be started, preferably within 24 hours, not more than 48 hours.
2。 Comprehensive measures should be taken to ensure the stability of internal environment and organ function during normal operation, followed by symptomatic treatment and recovery of energy metabolism and nerve cells, so as to promote the repair and regeneration of damaged nerve cells.
3。 Treatment should be careful within the specified time, and every treatment measure should be carefully operated.
4。 The effect is full treatment, mild HIE needs 10 to 14 days, and severe hypoxic-ischemic encephalopathy needs 20? 28 days, even extended to the neonatal period, the course of treatment is too short, and there is not much intervention for mild HIE.
5。 Medical staff will actively strive for the trust and cooperation of parents who have confidence in treatment. It is believed that treatment will improve the prognosis, and even severe hypoxic-ischemic encephalopathy will reduce or avoid the occurrence of nervous system sequelae after active treatment.
(two) within 3 days after birth, treatment.
This stage treats multiple organ dysfunction caused by asphyxia and hypoxia, ensures the stability of internal environment, and actively controls various nervous system symptoms. Treatment focuses on three diseases.
1。 Three brackets
(1) Maintain good ventilation, ventilation function, blood gas and pH value? Keep it within the normal range. After 6 hours of low-flow oxygen inhalation, he recovered, and his face was blue and he had difficulty breathing. Increase the oxygen concentration and prolong the oxygen inhalation time. Use small dose, sodium bicarbonate metabolic acidosis, mild respiratory acidosis PaCO2.
(2) the perfusion of the whole body and organs, heart rate, and keep enough blood and blood pressure within the normal range. The sound of the heart is dull, and the heart rate is
(3) Keep the blood sugar at a normal high value (5.0 mmol/L) and ensure the required nerve cell metabolism. Second place in school? Blood sugar was monitored for 3 days, and glucose input was adjusted, such as increased intracranial pressure, vomiting, frequent convulsions, and early oral or nasal feeding of sugar, water or milk to prevent hyperglycemia during the day and hypoglycemia at night. The appropriate speed is 6? 8 mg/(kg min).
Students should strengthen monitoring within 3 days, such as vital signs, blood gas, electrolytes, blood sugar, etc.
Symptomatic treatment
(1) Convulsion control: Hypoxic-ischemic encephalopathy often occurs within 12 hours. For 12 hours, phenobarbital load, 30mg/kg 20mg/kg slow intravenous injection or 5 mg/(kg d) intravenous injection or intramuscular injection under trickle load of side tube are preferred. The general clinical symptoms are obviously improved, and the drug is stopped. If the convulsion lasts for a long time, use a short-acting sedative, such as anal injection of chloral hydrate 50mg/kg or 0.3? 0.5 mg/kg stability. Stimulate children's irritability, do not participate in convulsions, and can also apply benzene sticks at an early stage. 20mg/kg group.
(2) Reduce intracranial pressure: increased intracranial pressure occurs at 4 hours after birth, usually 24 hours, and the fontanel tension increases more obviously before the first day. After intravenous injection of furosemide 1 mg/kg, the anterior fontanel is still tense or swollen after 6 hours, and mannitol 0.25-0.5g/kg can be used repeatedly for 4, 4-6 hours. After three days, efforts to reduce intracranial pressure can obviously stop taking drugs. After three days, the limit of fluid production was 60-80 ml/(kg d), and the tax rate was about 3 ml/(kg h), so renal insufficiency was obvious. Mannitol should be used with caution. Intracranial enlargement and PaCO 2↑(& gt；; 9.33 kPa), brain edema caused by mechanical ventilation.
(3) Eliminating brain stem symptoms: when severe HIE→ deep coma, shallow and slow breathing, irregular rhythm or apnea, pupil narrowing or expanding, light reaction disappearing, eyeball fixation or tremor, pale complexion, cold limbs, dull heart sounds, time for skin capillary refilling, frequent seizures and uncontrollable drugs, naloxone should be used as much as possible, with a dose of 0.05-0.600000.
3。 Others: free radical scavenging and vitamin C (0.5g /e intravenous drip) or vite 10-50-50m g/ day IM or oral vitamin K 15 to 10mg/ day or IM×2-3 days can promote the early application of N-cell metabolic drugs after 24 hours.
(3) 4- 10 days after birth.
Apply and popularize N- cell metabolism drugs or drugs to improve cerebral blood flow, eliminate the energy metabolism disorder caused by hypoxic-ischemic brain damage, and gradually restore the function of nerve cells. The following drugs.
1。 CDPC: Is it 100- 125mg/d or Livzon (2? 5ml/ day +50 ml liquid×10? 14 days), both drugs are.
2。 Compound Danshen injection: this will be suitable for 24 hours after delivery, 6? Intravenous drip10ml/e×10-14 days.
3。 In the treatment of moderate HIE, the condition of severe hypoxic-ischemic encephalopathy ranges from 4? It can start to improve in 5 days, such as crying, sucking, restoring muscle tension and ending seizures. It lasts for 9 days and obviously improves in 7 days. Such children can be discharged from the hospital after continuous treatment for 10 to 14 days, and often there are no sequelae.
4。 After the treatment of severe HIE 10, there is still no obvious improvement, such as sudden entry or coma, hypotonia, disappearance of primitive reflex, non-smoking, seizure and intracranial ↑, which indicates that the condition is serious and the prognosis is poor, so it is necessary to extend the treatment time and strengthen the treatment.
5。 At this stage, during the treatment, it is best to monitor the symptoms and signs of the nervous system with NBNA score and EEG.
(4) Born after treatment 10 days.
These treatments are not ideal for severe hypoxic-ischemic encephalopathy to prevent nervous system sequelae. Key points:
1。 Livzon Saile ◎ Danshen injection can be repeated for two or three courses of treatment.
2。 Conditional peptides that may promote the growth of brain cells.
3。 Strengthen neonatal intervention, such as touching and passive physical activity.
4。 Keep the balance of water and electrolyte, warm milk and adequate supply.
5。 Neonatal intervention. (1) visual stimulation: hanging red balls on the bedside every day to tease or look at people's faces (2) auditory stimulation: deep and melodious music, three times a day, each time 15 minutes; (3) tactile stimulation: passive limb flexion, touching and massage; (4) vestibular movement stimulation: shaking and shaking.
During neonatal treatment
1。 The following conditions require continued treatment
(1), after 28 days of treatment, neurological symptoms did not disappear, NBNA score.
(2)2 months and 3 months, CT scan, B-ultrasound or MRI brain softening, ventricular enlargement, brain atrophy, periventricular white matter softening, or basal ganglia lesions.
(3)2 months, 3 months can not look up, hands are not flexible, do not pick objects, tiptoe landing, muscle dystonia, knee flexion.
2。 Treat Livzon Celeron 5ml or Brain Cell Growth Factor 1600? 4000U or compound Danshen 6- 10ML infusion: 1× 10 times, ***2 to 3 to 6 months, and early intervention, physical and mental, behavioral, emotional, feeding and comprehensive treatment were carried out according to age and functional pronunciation defect training. about
7 forecast
When the prognosis of children with long-term hypoxic-ischemic encephalopathy is evaluated timely and objectively, the rescue decision should be comprehensive evaluation.
1, time and content of evaluation: the evaluation content is different at different stages of the disease.
Healthy 24 hours: the occurrence of HIE;
72 hours: severity of brain injury, preliminary prognosis estimation;
10? 14 days: possibility and severity assessment of nervous system sequelae; /& gt； 28 days: Full recovery, intervention plan. reference value
Phase 2 clinical and laboratory examination:
(1)NBNA score: within 14 days after birth, the score was ≤35, the estimated sensitivity was 96.3%, and the prognosis was poor.
(2) Shadow examination: the abnormal changes of light and moderate HIE images returned to normal within 1 week. In the case of moderate and severe imaging, if the image changes have not recovered, brain edema will not appear again from 18 to 14 days after regression, but pathological changes of nerve cell degeneration and necrosis will appear. Atrophic changes appear after 4 weeks, which indicates that the prognosis is poor and there will be clinical nervous system sequelae.
(3) Electrophysiological examination: HIE was accompanied by EEG changes and completely returned to normal. Within two weeks, the prognosis was good. However, serious changes, such as burst suppression, low voltage and electric rest, appear in EEG, especially for a long time, which indicates a dangerous prognosis and serious sequelae.