Introduction
Neonatal respiratory distress syndrome(Neonatal respiratory distress syndrome, NRDS) indicates progressive dyspnea, cyanosis, expiratory sputum, inspiratory tri-concavity, and respiratory failure shortly after birth. Mainly found in premature infants, especially gestational age less than 32 to 33 weeks. Its basic characteristics are progressive immature lung, pulmonary alveolar dysplasia caused by lack of pulmonary surfactant, pulmonary fluid transport disorder, pulmonary capillary-alveolar high permeability exudative lesions. Its pathological feature is that a clear membrane of eosin is attached to the wall of the alveolar wall to the terminal bronchioles. Also known as hyaline mimbrane disease (HMD).
Cause
(1) Causes of the disease
Neonatal respiratory distress syndrome is caused by the lack of pulmonary surfactant (PS). Because of the surface tension between the alveolar and air interface, if there is no surfactant, the alveoli are compressed and gradually form atelectasis. Gradually increase. The blood flow passes through the atelectasis area, and the gas returns to the heart without exchange, forming a short circuit in the lung. Therefore, the blood PaO2 is decreased, the oxygenation is lowered, and the metabolism in the body can only be carried out under the condition of hypoxia to cause acidosis. In the case of acidosis, pulmonary vasospasm, pulmonary blood flow resistance increases, the right heart pressure increases, and sometimes the arterial catheter can be opened again, forming a right-to-left shunt. In severe cases, 80% of the heart beat volume becomes a partial flow, resulting in baby cyanosis. Obviously, after the blood flow into the lungs is reduced, the amount of lung perfusion is insufficient, and the blood vessel wall is increased due to hypoxia permeability, so that the plasma contents are extravasated, including proteins, in which fibrin is deposited, so that the exudate forms a transparent membrane of the lung.
Inducing factors of NRDS:
a premature baby
When the fetus is 22 to 24 weeks old, the lung type II cells can produce PS, but the amount is small, and rarely metastasize to the alveolar surface. As the gestational age increases, the synthesis of PS gradually increases, so the baby is born in the lungs earlier. The smaller the amount of PS, the higher the incidence of RDS. At the age of 24 to 30 weeks, various hormones have the greatest effect on promoting lung maturation. At this time, it is the best stage for prenatal prevention. After 32 to 34 weeks, the effect of hormone on lung maturation is not very important. After 35 weeks of gestational age, PS quickly enters the stage of the alveolar surface. The lungs of premature infants continue to develop after birth, and the PS produced within 72 to 96 hours after birth can generally maintain normal breathing. Therefore, as long as the premature infants survive the difficulties in the PS deficiency stage, the survival rate can be improved.
Two pregnant women with diabetes
The blood sugar of pregnant women with diabetes is high, and the blood sugar of the fetus is also increased. At this time, the secretion of fetal insulin must be increased to meet the needs of glucose metabolism, and the glucose is converted into glycogen. In this case, the fetus grows fat, but the lungs are not necessarily mature, and insulin has an antagonistic effect on adrenocortical hormones, which affects lung development.
Distress in the Three Palaces and suffocation at birth
The distress in the palace occurs mostly in the fetus with insufficiency of the placenta. Due to long-term hypoxia, the development of fetal lungs is low, and the secretion of PS is low. The suffocation at birth is caused by dystocia, which is one of the causes of RDS in newborns.
The appearance of the lung is normal. Due to the high degree of stagnation, it is dark red, with a tough texture such as the liver. It sinks into the water. The cut surface is dark red. The lung tissue shows a wide resorption of atelectasis under the microscope. The alveolar walls are close to each other. There is only a small amount of dilated alveoli in the lung, and the wall is covered with a layer of eosinophilic homogeneous and unstructured substance, that is, a transparent membrane. Sometimes the transparent membrane is partially freed from the alveoli, the alveolar duct and bronchioles are dilated, and the wall is also Comes with a transparent film. There is edema in the lung tissue, and sometimes the process of concentrating the edema fluid into a transparent membrane can be seen, and large mononuclear and multinucleated cells can be seen to exude. Those who survive for more than 32 hours often have pneumonia, and the transparent membrane has been absorbed or loosely granulated. Fragmentation.
(two) pathogenesis
PS can reduce the surface tension at the junction of the alveolar wall and the air in the alveoli, making the alveoli open, and its half-life is short and needs to be continuously replenished. When PS is absent, the alveolar surface tension is increased, the alveolar collapses, the functional residual volume decreases, the lung compliance curve moves down, the compliance decreases, the ineffective cavity ventilation, the respiratory work increases significantly, and the energy is depleted, leading to systemic organ failure. According to the formula:
P (alveolar retraction rate) = 2T (surface tension) / r (alveolar radius).
The alveoli with the smallest radius during exhalation was the first to collapse, so progressive atelectasis occurred. The number of alveoli and ventilation area of the immature lung was too small, the alveolar space was wide, and the gas dispersion and exchange were seriously insufficient. End-expiratory alveolar collapse, difficulty in ventilation, hypoxemia, and decreased ability of alveolar epithelial cells to synthesize surfactant. It causes clinical symptoms such as difficulty in breathing and cyanosis to progress progressively. Continuous hypoxia leads to pulmonary vasospasm, pulmonary hypertension, pulmonary blood flow reduction, right-to-left shunt outside the lung, and arteriovenous shunt in the lung, which makes the ventilation-perfusion ratio imbalance, affecting blood and blood exchange. Continuous hypoxia and acidosis can cause myocardial damage, decreased cardiac output, systemic hypotension, low perfusion, and finally multiple organ failure with respiratory failure. The process is as follows: insufficient alveolar surfactant → increased alveolar wall surface tension (increased alveolar retraction force) → minimum radius of alveoli first collapse → progressive atelectasis → hypoxia, acidosis → pulmonary arteriolar spasm → pulmonary artery pressure Increase → foramen ovale and arterial catheter opening → right to left shunt (continuous fetal circulation) → lung perfusion flow decreased → lung tissue hypoxia more heavy → capillary permeability increased → fibrin deposition → transparent membrane formation → hypoxia, Acidosis is more serious, causing a vicious circle.
Due to the decreased secretion synthesis of lung PS, the blockage of the PS recirculation pathway, or due to excessive fluid in the alveolar space (transportation barrier, hyperosmotic), PS can be insufficient. Pathological exudates contain large amounts of plasma proteins that interfere with and inhibit PS function in the alveolar space. Early birth conditions such as inhalation, pneumonia, pulmonary dysplasia, pulmonary hemorrhage, and hypoxic suffocation at birth can be related to the above pathophysiology. The total amount of phospholipids in the lungs of premature infants is only 10% to 30% of the full-term children, or lower, and lacks major pulmonary surfactant proteins such as SP-A, B, C, etc., thus the quantity and quality The above is inferior to full-term children, which is the main reason for the occurrence of RDSN. The application of exogenous pulmonary surfactant preparations can rapidly increase the amount of pulmonary surfactant in the lungs. After pulmonary surfactant is instilled into the lungs of children with RDSN through the airway, pulmonary surfactant phospholipids are immediately taken up by alveolar epithelial cells and gradually enhance the functional activity of endogenous pulmonary surfactants, especially SP-A. , B, C synthetic secretion. This process is closely related to the clinical response and outcome after administration.
symptom
Most of the infants are premature infants. The crying sound can be normal at birth, and breathing difficulties occur within 6 to 12 hours, gradually increasing with convulsions. Irregular breathing, with apnea. The complexion becomes grayish or grayish due to lack of oxygen, and the cyanosis is obvious after the right-to-left shunt, and oxygen supply cannot be alleviated. People with severe hypoxia have low muscle tone in their limbs. The signs are nose flaps, and the thorax starts to bulge. After the lungs are incarcerated, the thorax is subsided and the underarm is more obvious. The thoracic soft tissue depression during inhalation is most obvious under the costal margin and the lower end of the sternum. The lungs have a reduced breath sound and a fine wet rales can be heard when inhaling. The disease is a self-limiting disease. The survival of the lungs can be increased for more than three days, and the hope for recovery is greater. However, many babies have pneumonia, which continues to worsen the condition and improves after infection control. Infants with severe illnesses mostly died within three days, with the highest mortality rate on the second day after birth.
The disease is also light, may be due to lack of surface active substances, the onset is late, can be as late as 24 to 48 hours, breathing difficulties are light, no sputum, bruising is not obvious, after three or four days, it will improve.
PaO2 increased due to poor ventilation and PaO2. Due to the decreased pH of metabolic acidosis, these three tests can be monitored percutaneously. Although it is very simple, it does not represent the actual situation in the blood. It is necessary to take direct examination of arterial blood. In the case of metabolic acidosis, the residual base (BE) is reduced and the carbon dioxide binding force is decreased. During the course of the disease, blood is prone to low Na+, K+, and high Cl-, so blood electrolytes need to be measured.
diagnosis
In the early lungs of the lung hyaline membrane, the general transparency of the lung fields is reduced, and there are evenly distributed fine particles and a-shaped shadows. The small particles represent the ateloids of the alveoli, and the reticular shadows represent small blood vessels that are congested. The bronchus has a sign of aeration, but is easily covered by the heart and thymus shadows, and is clearly visible to the segment and the distal bronchus. If the atelectasis expands to the entire lung, the lung field is frosted glass, which makes the inflated bronchi show clearer, like a branch with a bald leaf, the entire thorax is well dilated, and the transverse position is normal.
Identification
a B-group β-hemolytic streptococcus infection
Group B hemolytic streptococcus pneumonia or sepsis infected during intrauterine or delivery, very similar to hyaline membrane disease, difficult to distinguish, such as pregnant women with a history of premature rupture of amnion or late pregnancy infection needs to consider the occurrence of B group β hemolysis in infants The possibility of streptococcal infection, timely blood collection for culture to identify, before the diagnosis is not clear, should be treated as an infectious disease, given penicillin.
Second wet lung
Wet lungs are more common in term infants. The symptoms are mild and the course of disease is short. It is not easy to distinguish from light hyaline membrane disease. However, the X-ray performance of the wet lung is different and can be identified.
Three intracranial hemorrhage
Intracranial hemorrhage caused by hypoxia is more common in premature infants, showing respiratory depression and irregularities, with apnea. On the other hand, intracranial hemorrhage can also be caused by hypoxia after NRDS. Intracranial B-ultrasound can make a diagnosis of intracranial hemorrhage.
Four transverse nerve injury
Difficulties in dyspnea can occur in the injury of the diaphragmatic nerve (or the dysfunction of the diaphragmatic movement) and sputum, but the cardiopulmonary signs and X-ray findings can be identified.
complication
After mechanical respiration and oxygen supply treatment, the patent ductus arteriosus was established in 30% of cases during the recovery period. The tissue of the arterial catheter in premature infants was immature and could not be spontaneously closed, but the pulmonary vascular resistance increased in the early stage of hyaline membrane disease. Not only does the left-to-right shunt not occur, but sometimes the right-to-left shunt occurs. When the pulmonary vascular resistance decreases during the recovery period, the left-to-right shunt can occur. At this time, pulmonary edema is caused by increased pulmonary blood flow, and intermittent Apnea and congestive heart failure, even life-threatening. The systolic murmur can be heard in the left sternal border of the anterior region of the anterior region. The second to third ribs are the loudest, such as the decrease in pulmonary vascular resistance, and even continuous murmurs may occur. Chest X-ray shows enlargement of the heart shadow, lung field congestion, B-mode echocardiography can directly detect the patent ductus arteriosus.
Complications of hyaline membrane disease occur mostly during oxygen therapy or during the recovery period after treatment. Severe cases often have pulmonary hypertension, respiratory and heart failure.
1. Air leakage due to damage of the alveolar wall, gas spills into the pulmonary interstitial, or due to excessive peak inspiratory pressure or mean airway pressure (MAP) caused by mechanical ventilation, interstitial emphysema, gas along the blood vessels to the mediastinum, Causes mediastinal emphysema. Interstitial emphysema can also cause pneumothorax, breathing is more difficult when air leaks.
2. Oxygen poisoning When the inhaled oxygen concentration (FiO2) is too high, or the oxygen supply time is too long, oxygen poisoning may occur, and bronchopulmonary dysplasia (BPD) and intraocular lens fibrosis are most common. The former is the lung itself. The lesions make the ventilator difficult to remove, and the latter manifests as retinal hyperplasia or retinal detachment after the lens, which causes vision loss and even blindness.
3. In the recovery period, the arterial catheter is open. After mechanical respiration and oxygen supply treatment, the patent ductus arteriosus occurs in about 30% of the cases during the recovery period. The tissue of the arterial catheter in premature infants is immature and cannot be spontaneously closed, but in the transparent membrane of the lung. In the early stage of the disease, the pulmonary vascular resistance increases, not only does the left-to-right shunt occur, but sometimes the right-to-left shunt occurs. When the pulmonary vascular resistance decreases during the recovery period, the left-to-right shunt can occur, which is caused by the increase of pulmonary blood flow. Pulmonary edema, intermittent apnea and congestive heart failure, and even life-threatening. The systolic murmur can be heard in the left sternal border of the anterior region of the anterior region. The second to third ribs are the loudest, such as the decrease in pulmonary vascular resistance, and even continuous murmurs may occur. Chest X-ray showed enlarged heart shadow and lung congestion. B-mode echocardiography can directly detect the patent ductus arteriosus.
treatment
Western medicine treatment
General treatment
(1) Nursing: Care should be given to premature infants. Place the baby in a warm box at a moderate temperature or on a radiant infrared warm bed, monitor the body temperature, respiration, heart rate, and TcO2 and TcCO2 with a monitor. The average airway pressure also needs to be monitored. The ambient temperature needs to maintain the abdominal skin temperature at 36.5 ° C or the rectal temperature (core or deep temperature) at 37 ° C, so that the body's oxygen consumption is at the lowest level. The relative humidity is preferably about 50%. Frequently remove pharyngeal mucus and keep the airway open. Pay attention to the amount of fluid intake and nutrition, using intravenous high nutrient droplets, to breastfeeding when sucking and swallowing.
(2) Supportive treatment: to ensure the nutrition and liquid intake, 1/5 sodium containing liquid can not be used for breast-feeding, 60-80ml/(kg·d), after the second day, 100-120ml/(kg·d), intravenous drip Note. If a respirator is used, if the water vapor in the inhalation is saturated, the amount of rehydration should be reduced to 50-60 ml/(kg·d).
(3) Oxygen supply and mechanical respiration: In order to improve hypoxia and reduce anaerobic metabolism, sufficient oxygen must be supplied, and nasal congestion, mask or continuous positive airway pressure (CPAP) can be used for mild cases. If FiO2 has reached 0.8, and PaO2 is still below 6.65kP (50mmHg), an endotracheal intubation is required and a ventilator is used. Inspiratory peak pressure does not exceed 2.9kPa (30cmH2O), average airway pressure <0.98kPa (<10cmH2O), respiratory rate 25-30 times/min, inspiratory time (I): (E)=1:1~2FiO2 When the time is high, it will gradually decrease to 0.4. When the ventilator is removed, the first step is to strengthen the breathing (IMV) and strengthen it every 10 breaths. High-frequency breathing can also be used. Ventilation with a small tidal volume and a higher ventilation frequency. For some reason, the inspiratory time is short, so the inspiratory peak pressure and the average airway pressure are low, and the intrathoracic pressure is also low. It is conducive to venous return. The commonly used method is high-frequency jet ventilation (HFJV), which is inserted into the neonatal nasal cavity by 1.5 to 2 cm, the oxygen pressure (working pressure) is 0.125 kg/cm2, and the ejection frequency is 150-300 beats/min. According to the condition, after 1 to 3 hours, it is treated with oxygen in the normal nasal congestion method. When the blood PaO2 can maintain 7.98 kPa (60 mmHg) or more, but does not exceed 11.97 to 13.3 kPa (90-100 mmHg), the nasal congestion method can be used instead. .
2. Surfactant (PS) replacement therapy: PS has become the routine treatment of NRDSP, the first dose of natural PS (including pig lung, bovine lung PS) 120 ~ 200mg / kg, the second and third dose can be Reduced to 100 ~ 120mg / kg, each interval of about 8 ~ 12 hours, each time the calculated dose is placed in 3 ~ 5mg / kg of normal saline for use, the trachea temporarily removed from the ventilator, and then from the tracheal intubation with PS Directly drip into the lungs, turning the baby's position when dripping, from the supine position to the right side to the left side, so that the drug enters the lobes more evenly. If there is a small bypass channel in the tracheal intubation, the PS can be dripped from the small channel so as not to affect the fluctuation of blood oxygen saturation. The symptoms of respiratory distress can be alleviated after 1 to 2 hours of use. For example, the synthetic Exosurf is used at a dose of 5 ml/kg, and the DPPC is contained at 67 mg/kg. The effective time is later, and the symptoms are improved after about 12 to 18 hours. Regardless of whether the natural or synthetic PS treatment effect is used earlier, the better. Natural PS does not increase the incidence of allergic diseases in the future.
A small number of infants have poor response to PS because of the multifaceted nature. The 1 very low birth weight lung is not only immature, structurally immature, with lung dysplasia, 2 severe asphyxia, poor response, 3 pulmonary edema (For example, the PDA has a large left-to-right flow rate), and there are many proteins in the exudate, which antagonize PS. 4 with other diseases such as severe pneumonia, it is necessary to find the cause, plus treatment.
3. Symptomatic treatment
(1) Correction of water, electrolyte and acid-base balance disorders: 5% sodium bicarbonate is preferred for acid poisoning at 3 to 5 ml/kg each time, or calculated according to the measured BE and CO2-CP: BE × body weight (kg) × 0.3 = Na+HCO 3 mmol/L, but the amount per day does not exceed 6-8 mmol/kg. High blood sodium was administered intravenously with 3.64% Sam (tromethamine, THAM) 2 to 3 ml/time. In the case of hyperkalemia, 25% glucose 50 mg/kg is used, and 1 U of insulin is added every 3 to 4 g of glucose, and intravenously instilled.
(2) control of heart failure: rapid preparation with digitalis, such as ouabain K (Polygonum sinensis K) 0.01mg / (kg · times), or gerberin C (Westland) each time 0.015mg /kg, slow intravenous injection. Patients with reopening of the arterial catheter may try indomethacin (indomethacin) at 0.02 mg/kg each time, sharing 3 times, with each dose being 12 hours apart; for less than 2 days, the dose of the latter 2 doses is halved.
(3) Severe hypoxia: When convulsions occur in severe hypoxia, intravenous injection is given with 20% mannitol at 5 ml/kg each time.
(4) Respiratory failure: In case of respiratory failure, use Lobelin (Hawthorn) or Nicocam (Kolamin) in time.
(5) convulsions: irritability and convulsions of Xiqiao (Dingding) 0.2 ~ 0.3mg / kg each time, intravenous injection; or phenobarbital 5 ~ 7mg / kg each time, intramuscular injection.
(6) Treatment of patent ductus arteriosus during recovery: Inflammatory pain can be used, sharing 3 doses, each dose is 12 hours, the first dose is 0.2mg/kg, and the doses of the second and third doses are gradually increased according to the age, less than 2 days. Each time 0.1mg/kg, day age 2 ~ 70.2mg / kg, > 8 days each is 0.25mg / kg. The entry route can be intravenously instilled, and if it is directly dripped through the cardiac catheter to the arterial catheter port, the effect is better, or oral, but the curative effect is poor. Side effects of indomethacin have reduced renal function, decreased urine output, decreased blood sodium, elevated blood potassium, and recovery after discontinuation. If the drug does not close the arterial catheter, it can be surgically ligated.
4. Prevention and control of infections Strict disinfection and isolation system, use effective antibiotics. Because the hyaline membrane disease is not easy to distinguish from the B group β-hemolytic streptococcus infection, it is recommended to use penicillin for the treatment of common pain, the dose is 20 ~ 250,000 μ / kg · d, divided into 3 ~ 4 intravenous infusion or intramuscular injection.
prevention
Prenatal prevention
Pregnant women with preterm birth may be given adrenal-cortical hormone (ACH) at the end of pregnancy to prevent RDS or reduce RDS symptoms in preterm infants. In 1969, Liggins first discovered that intravenous infusion of dexamethasone promoted the maturation of premature sheep lungs. The same results can be obtained for other heterogeneous lungs, and gradually applied to pregnant women to promote the maturation of lungs in premature infants. The most commonly used hormones are betame-thasone and dexamethasone because they are more ACH than others. Easy to enter the fetus through the placenta.
The effect of ACH is to stimulate the production of phospholipids and small molecular proteins in fetal lung type II cells, reduce the permeability of capillaries in the lungs, and reduce pulmonary edema, thus reducing the incidence of RDS. Even if the disease occurs, the symptoms are milder, which can reduce the mortality rate. The oxygen concentration during treatment is not necessarily too high, and complications such as bronchopulmonary dysplasia (BPD) and post-crystal fibrosis (ROP) can be prevented. Due to the reduction of hypoxia, it is reasonable to reduce the incidence of neonatal necrotizing enterocolitis and hypoxic ischemic intracranial hemorrhage.
The preventive dose of ACH for pregnant women; 24 mg of betamethasone or dexamethasone, divided into 2 intramuscular injections, 24 hours apart, the commonly used dose in China is 5-10 mg, intramuscular or intravenous drip, once a day for 3 days. Prevention should be given 7 to 24 hours before the delivery of the pregnant woman, so that the drug has enough time to play its due role. ACH prevention does not increase the risk of infection for pregnant women and fetuses, even if the amnion is broken, it will not increase the infection rate on the basis of the original. Intrauterine growth retardation is not a contraindication. In the very low birth weight infants delivered, the effect of preventing RDS is still inconsistent. It is generally considered that the incidence of RDS cannot be reduced, but the incidence of subventricular epidural hemorrhage may be reduced in the infants who have survived. ACH is less effective in infants with diabetes mellitus, Rh hemolytic disease and multiple pediatric children.
Although ACH prevention has a positive effect, there are still 10% of premature infants with RDS, so consider adding other hormones to improve the effect. Thyroxine has the effect of promoting lung maturation, but it is not clinically applicable because it is not easy to pass through the placental barrier. Later, it was found that the thyrotropin releasing hormone (TRH) structure in animal brain tissue is similar to thyroxine and can pass through the placenta. Can be used as a prophylactic agent. The dose is 0.4 mg each time, once every 8 hours for a total of 4 times. Some pregnant women may have side effects, including nausea, vomiting and high blood pressure, which can be reduced to half. After the addition of TRH, the incidence and mortality of RDS are even lower.
Second postpartum prevention
It is pointed out that the lung surface activity and substances are given to the baby within half an hour after birth to prevent or reduce the symptoms of RDS, and are often used in infants whose prenatal mothers are not prevented. The better the prevention, the better the effect. It is best to instill into the tracheal intubation before the baby begins to breathe or before the ventilator positive pressure breathing begins. The PS can be evenly distributed in the lung. The preventive effect is reflected in the incidence of RDS and The mortality rate is lower, and the disease is milder. Because PS can improve the oxygenation function in the body early, some babies can use the ventilator, the oxygen concentration and the average airway pressure can be lower, so the air leak and oxygen The incidence of poisoning is significantly reduced, and the occurrence of oxygen-ischemic intracranial hemorrhage can also be reduced. Chronic lung diseases (CLD) are rare. CLD refers to diseases requiring oxygen supply within 28 days after birth. Although the advantages of prevention are many, RDS does not necessarily occur in premature infants and asphyxia, and the prevention of non-occurring infants will increase costs and unnecessary endotracheal intubation, and suffocation and premature infants often require more urgent resuscitation, PS Prevention will temporarily interrupt the continuous process of recovery. Therefore, in preterm infants with a birth rate of <28 weeks or a birth weight <1000g in the delivery room, if the antenatal mother does not receive ACH prevention, PS can be prevented under the treatment of experienced and skilled resuscitation personnel, and other infants are in RDS. Immediately after use, the ventilator and the tracheal intubation were used to drip the PS and treated according to the treatment.
PS prevention and PS treatment are not easily separated. Many newborns who have just recovered have irregular breathing or distress and need PS to continue treatment. The amount of prevention is similar to the amount of treatment, such as 100-150 mg/kg with natural PS (whether pig lung or bovine lung PS), such as 5 ml/kg with synthetic Exosurf (containing DPPC 67 mg/kg). See the treatment of respiratory distress syndrome and Chapter 3, Section 3, Introduction to Pulmonary Surfactant and its clinical application.
Triple joint prevention
Refers to the pre-natal use of ACH for pregnant women, postpartum for the joint prevention of neonatal PS, for 1 prenatal prevention started late, pregnant women have not delivered to 24 hours, 2 neonates with severe distress, RDS after birth It is also often serious, and this combination prevention is appropriate. Animal experiments prove that joint prevention is better than prevention alone.
简体中文