Respiratory distress syndrome in newborns

Respiratory distress syndrome in newborns (RDS) is a respiratory failure of varying severity, predominantly in premature infants in the first 2 days of life, caused by immaturity of the lungs and primary surfactant deficiency.

In foreign literature, the terms "respiratory distress syndrome in newborns" (RDS) and "hyaline membrane disease" (HMD) are synonyms. This condition is also called respiratory distress syndrome (RDS).

Epidemiology

This pathology occurs in 1% of all live births and in 14% of newborns with a birth weight of less than 2500 g. Respiratory distress syndrome in newborns and its consequences are the cause of 30-50% of neonatal deaths in the United States.

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What causes respiratory distress syndrome?

The etiological factors for the development of SDR are considered to be:

• deficiency in the formation and release of surfactant;
• surfactant quality defect;
• inhibition and destruction of surfactant;
• immaturity of the lung tissue structure.

These processes are facilitated by:

• prematurity;
• congenital infections;
• chronic intrauterine and acute hypoxia of the fetus and newborn;
• diabetes mellitus in the mother;
• acute blood loss during childbirth;
• intra- and periventricular hemorrhages;
• transient hypofunction of the thyroid gland and adrenal glands;
• hypovolemia;
• hyperoxia;
• cooling (general or inhalation of unheated oxygen-air mixture);
• born second of twins.

Acute perinatal stress, namely an increase in the duration of labor, can reduce the frequency and severity of respiratory distress syndrome in newborns. Therefore, planned cesarean section can also be considered a risk factor. An increase in the duration of the anhydrous interval reduces the risk of RDS.

Pathogenesis

In the development of respiratory distress syndrome in newborns, the main role is played by immature lung tissue and surfactant deficiency. Surfactant is a surface-active substance synthesized by type II pneumocytes, consisting mainly of lipids (90%, of which 80% are phospholipids) and proteins (10%).

Surfactant performs the following functions:

• reduces surface tension in the alveoli and allows them to straighten;
• prevents the collapse of the alveoli during exhalation;
• has bactericidal activity against gram-positive bacteria and stimulates the macrophage reaction in the lungs;
• participates in the regulation of microcirculation in the lungs and the permeability of the alveolar walls;
• prevents the development of pulmonary edema.

Synthesis of surfactant in the alveoli begins at 20-24 weeks of gestation through ethanolcholinemethylation reactions. During this period, the rate of synthesis is low. From 34-36 weeks, the choline pathway begins to function and surfactant accumulates in large quantities. Surfactant production is stimulated by glucocorticoids, thyroid hormones, estrogens, adrenaline and noradrenaline.

With surfactant deficiency, after the first breath, some of the alveoli collapse again, and disseminated atelectasis occurs. The ventilation capacity of the lungs decreases. Hypoxemia, hypercapnia, and respiratory acidosis increase. On the other hand, the lack of formation of residual air causes an increase in intrapulmonary pressure. High resistance of the pulmonary vessels leads to shunting of blood from right to left along collaterals, bypassing the pulmonary blood flow. A decrease in intrapulmonary pressure after the first breath leads to the fact that the blood that has already entered the capillary bed is “fenced off” from the active blood flow of the pulmonary circulation by a reflex spasm of the arteries and a tendency to spasm of the venules. In conditions of blood stasis, “royal columns” (sludge) appear. In response to this, the coagulation potential of the blood increases, fibrin threads are formed, microthrombi are formed in intact vessels, and a hypocoagulation zone is formed around them. DIC syndrome develops. Microthrombi impede capillary blood flow, and blood through the intact vascular wall enters the tissues, leading to hemorrhagic pulmonary edema. Exudate and transudate accumulate in the alveoli (stage of edematous-hemorrhagic syndrome). Hyaline is formed in the plasma entering the alveoli. It lines the surface of the alveoli and disrupts gas exchange, since it is impermeable to oxygen and carbon dioxide. These changes are called hyaline membrane disease. The lungs are airy, the child breathes intensively, and gas exchange does not occur. Proteolytic enzymes destroy hyaline and fibrin within 5-7 days. Under conditions of severe hypoxia and increasing acidosis, surfactant synthesis practically ceases.

Thus, all three forms of respiratory distress syndrome in newborns (disseminated atelectasis, edematous-hemorrhagic syndrome and hyaline membrane disease) are phases of one pathological process, which results in severe hypoxemia and hypoxia, hypercapnia, mixed (respiratory-metabolic) acidosis and other metabolic disorders (tendency to hypoglycemia, hypocalcemia, etc.), pulmonary hypertension and systemic hypotension, hypovolemia, microcirculation disorders, peripheral edema, muscle hypotension, disorders of the functional state of the brain, heart failure (mainly of the right ventricular type with right-left shunts), temperature instability with a tendency to hypothermia, functional intestinal obstruction.

Symptoms of Respiratory Distress Syndrome in Newborns

Symptoms of respiratory distress syndrome in newborn premature babies are detected from the first day of life, less often - from the second. The Apgar score at birth can be any. Intense dyspnea (up to 80-120 breaths per minute) with the participation of accessory muscles, retraction of the sternum, bulging of the abdomen on inhalation (the "swing" symptom), as well as a noisy, groaning, "grunting" exhalation and general cyanosis are noted. Disseminated atelectasis is characterized by shallow weakened breathing and crepitant wheezing. With edematous-hemorrhagic syndrome, foamy discharge from the mouth is noted, sometimes pink in color, multiple crepitant fine-bubble wheezing are heard over the entire surface of the lungs. With hyaline membrane disease, breathing in the lungs is harsh, wheezing is usually absent.

In SDR, a tendency to hypothermia and suppression of central nervous system (CNS) functions due to hypoxia are also observed. Cerebral edema progresses rapidly, and a comatose state develops. Intraventricular hemorrhages (IVH) are often detected, and subsequently - ultrasound signs of periventricular leukomalacia (PVL). In addition, patients rapidly develop acute heart failure of the right and left ventricular type with an enlarged liver and edema syndrome. Preservation of fetal shunts and right-to-left blood flow through the arterial duct and oval window are due to pulmonary hypertension. With the progression of respiratory distress syndrome in newborns, the severity of the condition is determined by the time of shock and DIC syndrome development (bleeding from injection sites, pulmonary hemorrhages, etc.).

The Silverman scale is used to assess the severity of respiratory distress in newborns. Each symptom in the "Stage I" column is assessed at 1 point, in the "Stage II" column - at 2 points. With a total score of 10 points, the newborn has extremely severe RDS, 6-9 points - severe, 5 points - moderate, below 5 - incipient respiratory distress syndrome in newborns.

Silverman Andersen scale

Stage I	Stage II	Stage III
The upper part of the chest (in the supine position) and the anterior abdominal wall participate synchronously in the act of breathing. No retraction of the intercostal spaces on inhalation. No retraction of the xiphoid process of the sternum on inhalation. No movement of the chin during breathing. No noise on exhalation.	Lack of synchrony or minimal lowering of the upper chest when the anterior abdominal wall rises on inspiration. Mild retraction of the intercostal spaces on inspiration. Slight retraction of the xiphoid process of the sternum on inspiration. Lowering of the chin on inspiration, mouth closed. Expiratory sounds ("expiratory grunting") are heard on auscultation of the chest	Noticeable retraction of the upper chest during the rise of the anterior abdominal wall on inspiration. Noticeable retraction of the intercostal spaces on inspiration. Noticeable retraction of the xiphoid process of the sternum on inspiration. Lowering of the chin on inspiration, mouth open. Expiratory noises ("expiratory grunting") are heard when a phonendoscope is brought to the mouth or even without a phonendoscope.

In the uncomplicated course of the moderate form of RDS, clinical manifestations are most pronounced on the 1st-3rd day of life, then the condition gradually improves. In children with a birth weight of less than 1500 g, respiratory distress syndrome in newborns, as a rule, occurs with complications, in these cases, mechanical ventilation continues for several weeks.

Typical complications of respiratory distress syndrome in newborns are air leak syndromes, bronchopulmonary dysplasia, pneumonia, pulmonary hemorrhage, pulmonary edema, retinopathy of prematurity, renal failure, DIC syndrome, patent ductus arteriosus and patent foramen ovale, and IVH.

Diagnosis of respiratory distress syndrome in newborns

The diagnosis of SDR is considered confirmed when three main groups of criteria are combined.

1. Clinical signs of respiratory distress syndrome in newborns.
2. X-ray changes. In children with diffuse atelectasis, small dark areas are detected in the root zones. Edematous-hemorrhagic syndrome is characterized by a decrease in the size of the lung fields, an unclear, "blurred" pulmonary pattern up to a "white" lung. With BGM, an "air bronchogram" and a reticular-nadose network are observed.
3. Tests that detect immaturity of lung tissue.
4. Absence of surfactant in biological fluids obtained from the lungs: amniotic fluid, gastric aspirate at birth, nasopharyngeal and tracheal fluids. The "foam test" ("shake test") is also used to assess lung maturity. When alcohol (ethanol) is added to the analyzed fluid and then shaken, bubbles or foam are formed on its surface in the presence of surfactant.
5. Surfactant maturity indices.
6. The lecithin/sphingomyelin ratio is the most informative indicator of surfactant maturity. SDR develops in 50% of cases when this ratio is less than 2, and in 75% of cases when it is less than 1.
7. Phosphatidylglycerol level.

In the case of RDS, to detect apnea and bradycardia in newborns, it is necessary to continuously monitor the heart rate and respiration. It is necessary to determine the gas composition of the blood from the peripheral arteries. It is recommended to maintain the partial pressure of oxygen in arterial blood within 50-80 mm Hg, carbon dioxide - 45-55 mm Hg, arterial blood oxygen saturation - 88-95%, the pH value should be no lower than 7.25. The use of transcutaneous monitors to determine p02 and pCO2 and pulse oximeters allows for continuous monitoring of oxygenation and ventilation indicators.

At the height of severity of respiratory distress syndrome in newborns, clinical blood analysis (hemoglobin, hematocrit), blood culture and tracheal contents, coagulogram (as indicated), ECG are prescribed in dynamics. Levels of urea, potassium, sodium, calcium, magnesium, total protein, albumin in the blood serum are determined.

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Differential diagnostics

Choanal agenesis is characterized by abundant mucous discharge from the nose, and it is not possible to insert a catheter or probe into the nasopharynx.

Tracheoesophageal fistula is clinically manifested by choking, cyanosis, coughing, wheezing in the lungs during feeding. The diagnosis is confirmed by contrast examination of the esophagus and bronchoscopy.

At birth, diaphragmatic hernia is characterized by a small scaphoid abdomen and a retracted anterior abdominal wall. Asynchronous movements of the right and left halves of the chest and displacement of the apical impulse of the heart (usually to the right, left-sided diaphragmatic hernia occurs 5-10 times more often than right-sided), shortening of the percussion sound and the absence of respiratory sounds in the lower part of the lung are also detected. X-ray examination of the chest reveals the intestines, liver, etc.

In children with birth trauma of the brain and spinal cord, along with respiratory disorders, signs of damage to the central nervous system are also noted. Neurosonography, lumbar puncture, etc. help in diagnosis.

In case of congenital heart defects of the blue type, the skin of newborns retains a cyanotic tint even with inhalation of 100% oxygen. To clarify the diagnosis, data from a clinical examination, auscultation, chest X-ray, ECG, and echocardiography are used.

Massive aspiration is typical for post-term and full-term infants. The newborn is born with a low Apgar score. SDR is often detected from birth. During tracheal intubation, amniotic fluid (AF) can be obtained. Chest X-ray reveals flattening of the diaphragm, displacement of mediastinal organs to the affected side, coarse, irregularly contoured darkening or polysegmental atelectasis.

Pneumonia caused by group B streptococci and other anaerobes is characterized by symptoms of infectious toxicosis. Clinical blood tests, chest X-rays, and bacteriological tests help differentiate the diseases.

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Treatment of respiratory distress syndrome in newborns

Treatment of respiratory distress syndrome in newborns is aimed primarily at eliminating hypoxia and metabolic disorders, as well as normalizing cardiac activity and hemodynamic parameters. The measures must be carried out under the control of the respiratory rate and its conductivity to the lower parts of the lungs, as well as the heart rate, arterial pressure, blood gas composition, and hematocrit.

Temperature conditions

It is important to remember that cooling the child leads to a significant decrease in surfactant synthesis, the development of hemorrhagic syndrome and pulmonary hemorrhages. That is why the child is placed in an incubator with a temperature of 34-35 °C to maintain skin temperature at 36.5 °C. It is important to ensure maximum rest, since any touch to the child in a serious condition can provoke apnea, a drop in PaO2 or blood pressure. It is necessary to monitor the patency of the airways, therefore, the tracheobronchial tree is periodically sanitized.

Respiratory therapy

Respiratory therapy begins with inhalation of heated, humidified 40% oxygen through an oxygen tent, mask, and nasal catheters. If this does not normalize PaO2 (< 50 mm Hg with a Silverman scale score of 5 or more), spontaneous breathing under increased positive pressure (SPPP) is performed using nasal cannulas or an intubation tube. The manipulation begins with a pressure of 4-6 cm H2O at an O2 concentration of 50-60%. Improved oxygenation can be achieved, on the one hand, by increasing the pressure to 8-10 cm H2O, and on the other hand, by increasing the concentration of inhaled O2 to 70-80%. For premature infants weighing less than 1500 g, the initial positive pressure in the airways is 2-3 cm H2O. Increasing the pressure is done very carefully, since this increases the resistance in the airways, which can lead to a decrease in CO2 elimination and an increase in hypercarbia.

If the effect of SDPPD is favorable, they first try to reduce the concentration of O2 to non-toxic values (40%). Then, also slowly (by 1-2 cm H2O) under the control of the gas composition of the blood, the pressure in the respiratory tract is reduced to 2-3 cm H2O with subsequent transfer to oxygenation through a nasal catheter or oxygen tent.

Artificial ventilation of the lungs (AVL) is indicated if, against the background of SDPPD, the following persists for an hour:

• increasing cyanosis;
• shortness of breath up to 80 per minute;
• bradypnea less than 30 per minute;
• Silverman scale score greater than 5 points;
• PaCO2 more than 60 mm Hg;
• PaO2 less than 50 mmHg;
• pH less than 7.2.

When transferring to mechanical ventilation, the following initial parameters are recommended:

• maximum pressure at the end of inhalation is 20-25 cm H2O;
• inhalation to exhalation ratio 1:1;
• respiratory rate 30-50 per minute;
• oxygen concentration 50-60%;
• end-expiratory pressure 4 cm H2O;
• gas flow 2 l/(min x kg).

20-30 minutes after transfer to artificial ventilation, the child's condition and blood gas parameters are assessed. If PaO2 remains low (less than 60 mm Hg), it is necessary to change the ventilation parameters:

• inhalation to exhalation ratio 1.5:1 or 2:1;
• increase the pressure at the end of exhalation by 1-2 cm H2O;
• increase oxygen concentration by 10%;
• increase the gas flow in the breathing circuit by 2 l/min.

After normalization of the condition and blood gas parameters, the child is prepared for extubation and transferred to the SDPDP. At the same time, sputum is aspirated from the mouth and nasal passages every hour, the child is turned over, using the drainage position, vibration and percussion massage of the chest.

Infusion therapy and nutrition

Enteral feeding is impossible in newborns with RDS during the acute period of the disease, so partial or total parenteral nutrition is necessary, especially with extremely low body weight. Already 40-60 minutes after birth, infusion therapy with a 10% glucose solution is started at a rate of 60 ml/kg, with a subsequent increase in volume to 150 ml/kg by the end of the first week. Fluid administration should be limited in case of oliguria, since increased water load complicates the closure of the arterial duct. The balance of sodium and chlorine [2-3 mmol/kg x day)], as well as potassium and calcium [2 mmol/kg x day)] is usually achieved by intravenous administration with a 10% glucose solution from the second day of life.

Breastfeeding or adapted formula is started when the condition improves and dyspnea decreases to 60 per minute, there is no prolonged apnea, regurgitation, after a control dose of distilled water. If enteral feeding is not possible by the 3rd day, the child is transferred to parenteral nutrition with the inclusion of amino acids and fats.

Correction of hypovolemia and hypotension

In the acute phase of the disease, it is necessary to maintain the hematocrit at a level of 0.4-0.5. For this purpose, 5 and 10% albumin solutions are used, less often - transfusions of fresh frozen plasma and red blood cell mass. In recent years, Infucol has been widely used - a 6% isotonic solution obtained from potato starch, a synthetic colloid of hydroxyethyl starch. Prescribed 10-15 ml / kg for the prevention and treatment of hypovolemia, shock, microcirculation disorders. Hypotension is relieved by the introduction of dopamine (a vasopressor agent) 5-15 mcg / kg x min), starting with small doses.

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Antibacterial therapy

The question of prescribing antibiotics for respiratory distress syndrome in newborns is decided individually, taking into account the risk factors for the development of pneumonia. In practice, they are not prescribed only for mild forms. The following are recommended as starting regimens:

• 2nd generation cephalosporins:
• cefuroxime 30 mg/kg/day) in 2-3 administrations for 7-10 days;
• 3rd generation cephalosporins:
• cefotaxime 50 mg/kg/day) up to 7 days of life 2 times a day, from the 1st to the 4th week - 3 times;
• ceftazidime 30 mg/kg/day) in 2 doses;
• ceftriaxone 20-50 mg/kg/day) in 1-2 administrations;
• aminoglycosides:
• amikacin 15 mg/kg/day) in 2 doses;
• netilmicin 5 mg/kg/day) in one administration up to 7 days of life and in 2 administrations - from the 1st to the 4th week;
• gentamicin 7 mg/kg/day) once for newborns up to 7 days of life and in 2 doses from the 1st to the 4th week;
• Ampicillin can be prescribed at 100-200 mg/kg/day).

All of the above antibacterial drugs are administered intramuscularly or intravenously.

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Vitamin therapy

The use of vitamin E for the prevention of bronchopulmonary dysplasia has not been proven, but it can be used to prevent retinopathy of prematurity at 10 mg/kg for 7-10 days. Vitamin A, administered parenterally at 2000 IU every other day, is indicated for all children before the start of enteral feeding to reduce the incidence of necrotizing enterocolitis and bronchopulmonary dysplasia.

Diuretics

From the 2nd day of life, furosemide is used at 2-4 mg/kg x day). Dopamine at a dose of 1.5-7 mcg/kg x min also has a diuretic effect due to improved renal blood flow.

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Glucocorticoid therapy

Currently, glucocorticoid therapy is used in cases of acute adrenal insufficiency and shock in children.

Surfactant replacement therapy

Surfactant replacement therapy is used to prevent and treat respiratory distress syndrome in newborns. There are biological and synthetic surfactants. For prophylactic purposes, the drug is administered in the first 15 minutes after birth, for therapeutic purposes - at the age of 24-48 hours, provided that artificial ventilation is carried out. The administered dose is 100 mg / kg (about 4 ml / kg) - infused endotracheally through an intubation tube in 4 doses with an interval of about 1 minute and with a change in the position of the child with the introduction of each subsequent dose. If necessary, infusions are repeated after 6-12 hours. In total, no more than 4 infusions are carried out in 48 hours.

Outpatient observation

A child who has suffered from respiratory distress syndrome should, in addition to the local pediatrician, be observed by a neurologist and ophthalmologist once every 3 months.

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Prevention

Respiratory distress syndrome in newborns can be prevented by combating hypoxia and miscarriage. In addition, the method of using surfactant for prophylactic purposes was described above. Also, the content of surfactant in the lungs of the fetus increases with the introduction of betamethasone (to women with a risk of miscarriage at 28-34 weeks) or dexamethasone (48-72 hours before delivery).