Pediatric pulmonary edema

　　1. Etiology

　　Obstruction in the exchange and circulation of interstitial fluid between the pulmonary vessels and tissues leads to the leakage of fluid and proteins from the blood vessels, exceeding the clearance capacity of the lymphatic tissues. Excessive fluid then accumulates in the pulmonary tissue, forming pulmonary edema.

　　1. Increased hydrostatic pressure in pulmonary capillaries

　　It is hemodynamic pulmonary edema, which is the most important cause of pulmonary edema and can be seen in the following situations:

　　(1) Excessive blood volume: Such as excessive and rapid blood transfusion, fluid infusion, especially in children with pre-existing heart or lung dysfunction or severe anemia, as well as excessive secretion of antidiuretic hormone (such as severe pneumonia and asthma) and the result of drug action.

　　(2) Left ventricular dysfunction: Insufficient ejection leads to increased diastolic pressure in the left atrium, seen in any type of left heart failure, including arrhythmias, myocardial disease, severe aortic stenosis, mitral valve lesions, acute glomerulonephritis, and other conditions.

　　(3) Excessive negative pressure in the pleural cavity: An increase in the transmural pressure gradient of the pulmonary capillaries is seen during the 'negative phase' of intermittent positive pressure ventilation, that is, when the airway pressure is lower than atmospheric pressure. Abnormally increased negative pressure in the pulmonary interstitium is often seen when a large amount of pleural effusion or pleural cavity gas is rapidly aspirated, causing the lung to expand too quickly, resulting in an excessively negative pressure in the pleural cavity, causing fluid to flow from the pulmonary capillaries to the interstitium. Some people call it reactive pulmonary edema. Some studies have confirmed that there is a reduction in mitochondrial superoxide dismutase and cytochrome oxidase in the collapsed lung tissue, and when the lung is reexpanded, it leads to an increase in the production of oxygen free radicals, causing damage to the pulmonary epithelial and endothelial cells and leading to pulmonary edema.

　　(4) Other: Excessive pulmonary blood flow can lead to a sharp increase in pulmonary capillary pressure, seen in left-to-right cardiac shunts, anemia, and other conditions.

　　2. Decreased plasma protein osmotic pressure

　　It occurs in severe liver disease, kidney disease, and severe hypoproteinemia. Pulmonary edema occurring in renal failure is also related to changes in capillary permeability.

　　3. Increased permeability of pulmonary capillaries

　　Also known as toxic pulmonary edema or non-cardiogenic pulmonary edema. Capillary endothelial damage can be caused by many reasons. Common outbreaks of pulmonary edema include endotoxins, inhaled gastric acid or other acids, inhaled nitrogen dioxide, chlorine, phosgene, high concentrations of oxygen, or other toxic gases, or shock lung. The characteristic is that due to increased permeability, proteins enter the interstitium and alveoli, leaving a layer of protein lining the alveoli, which is histologically similar to the hyaline membrane of neonatal respiratory distress syndrome. The clinical characteristics are decreased lung compliance and gas exchange disorders.

　　4. Lymphatic obstruction

　　Lymphatic drainage disorder is also one of the causes of pulmonary edema, but it is actually not very common. Neonatal wet lung is often considered to be due to a delay in the clearance of fetal alveolar fluid in the pulmonary lymphatic system.

　　5. Increased surface tension at the air-liquid interface of the alveolar capillary membrane

　　When there is a lack of pulmonary surfactant, the surface tension of the alveolar surface increases, promoting the movement of fluid from the blood vessels to the interstitium and then into the alveoli. The occurrence of pulmonary edema can also lead to a decrease in the synthesis of surfactant, resulting in increased surface tension, exacerbating pulmonary edema, and forming a vicious cycle.

　　6. Other causes

　　There are other causes for the formation of pulmonary edema.

　　(1) Neurogenic pulmonary edema: It occurs in head trauma or other brain lesions, the mechanism is unclear. It may be due to increased permeability of alveolar capillaries, or due to dysfunction of the hypothalamus, central sympathetic nervous system activation, peripheral vascular constriction, increased pulmonary blood volume, and increased pulmonary capillary pressure.

　　(2) High-altitude pulmonary edema: It may be due to pulmonary hypertension, or due to mechanical stretching of the vascular endothelium, causing increased permeability and leakage of plasma proteins, or due to hypoxia causing increased permeability of the pulmonary capillaries. High molecular weight proteins, red blood cells, and white blood cells can be seen in the lung lavage fluid of the patients.

　　(3) Gram-negative septicemia: Pulmonary edema may be caused by endotoxin-induced damage to alveolar epithelial cells, vasoconstriction of the pulmonary vessels, and increased capillary hydrostatic pressure, but it is mainly due to increased capillary permeability, as seen in shock lung.

　　(4) Respiratory obstruction: Conditions such as bronchiolitis and asthma may cause pulmonary edema due to increased pleural cavity pressure, negative alveolar pressure, and negative interstitial pressure, increased pulmonary capillary pressure and increased permeability, and excessive water intake can further promote its occurrence.

　　The pathogenesis

　　The basic cause is the destruction of the balance between the hydrostatic pressure difference across the pulmonary capillary wall (transmural pressure difference) and the colloidal osmotic pressure difference; in recent years, research has also considered the permeability of the alveolar capillary membrane to be very important. The force for fluid filtration through capillaries (transcapillary filtration of fluid, abbreviated as FF) can be expressed by the following formula: FF = K[(Pcap - Pis) - δ(πcap - πis)] where K is the filtration coefficient, including the surface area and permeability of the pulmonary capillary membrane. Pcap is the hydrostatic pressure inside the pulmonary capillary [normally about 1.3 kPa (10 mmHg)], Pis is the hydrostatic pressure of the interstitial fluid [the normal value is not known, generally considered to be about -1.3 kPa (-10 mmHg)], δ is the reflection coefficient, representing the transcapillary colloidal pressure difference, reflecting the resistance of the membrane to protein flow, usually 0.8. πcap is the colloidal osmotic pressure inside the pulmonary capillary [normally about 25 mmHg], and πis is the colloidal osmotic pressure of the interstitial fluid [the normal value is not known, generally considered to be half of the plasma osmotic pressure]. The hydrostatic pressure and colloidal osmotic pressure of the interstitial fluid are not easy to measure. Some believe that the hydrostatic pressure of the interstitial fluid is negative, so fluid moves from the capillaries to the interstitium; the colloidal osmotic pressure of the interstitial fluid is about half of the plasma osmotic pressure, causing fluid to flow from the interstitium into the blood vessels. The combined effect of these two pressure differences results in fluid moving from the capillaries to the interstitium. In addition, the movement of fluid is also affected by the surface tension at the air-liquid interface of the alveolar capillary membrane, the alveolar surface tension promotes fluid from the capillaries to the alveoli, but it is generally offset by the alveolar pressure, so the final force vector causes fluid to flow from the capillaries to the interstitium, and then to be drained away by the lymphatic system. This is because the hydrostatic pressure of the capillary lymphatic vessels is similar to that of the interstitium, and the colloidal osmotic pressure is higher than that of the interstitium, so fluid moves from the interstitium to the lymphatic vessels. Also, due to the presence of smooth muscle in the lymphatic vessels and the funicular valves, as well as the pumping effect, all of which are conducive to the drainage of interstitial fluid into the lymphatic vessels, preventing the occurrence of pulmonary edema. Although when the hydrostatic pressure of the pulmonary capillaries increases or the plasma colloidal osmotic pressure decreases, the filtration of water into the interstitium increases, but only when it exceeds the lymphatic drainage volume, does the fluid begin to accumulate in the interstitium.

　　Severe hypoxia can lead to respiratory failure, which can cause metabolic and respiratory acidosis, alveolar collapse, and even asphyxial death. Respiratory failure is a clinical syndrome characterized by severe respiratory impairment, resulting in inability to breathe normally at rest, leading to hypoxia or carbon dioxide retention, and causing a series of physiological and metabolic disorders. In the early stages of mild disease, there is only a feeling of effortful breathing, and in severe cases, it is difficult to breathe, with profuse sweating, significant cyanosis of the lips and nails, changes in intellectual function, disorientation, headache, insomnia, confusion, irritability, and restlessness. It may progress to drowsiness and even coma, seizures, increased heart rate, elevated blood pressure, and skin vascular dilation. Some severe patients may have oliguria, lower limb edema, or liver dysfunction and gastrointestinal bleeding.

　　The onset of the disease may be acute or chronic, with chest discomfort, local pain, difficulty breathing, and cough as the main symptoms. Common signs include pallor, cyanosis, and a look of fear. Coughing often results in frothy sputum, and a small amount of blood may be present. Initially, chest signs are mainly seen in the lower posterior part of the chest, such as mild dullness and numerous vesicular sounds, gradually developing to the entire lung. The heart sound is generally weak, the pulse rapid and weak. As the disease progresses, symptoms such as reverse breathing, apnea, peripheral vasoconstriction, bradycardia, and liver enlargement may occur. Interstitial pulmonary edema usually has no clinical symptoms or signs. When alveolar edema occurs, lung compliance decreases, and the first symptom is increased breathing. At the peak of alveolar edema, the above symptoms and signs worsen, hypoxia intensifies, and if not treated promptly, death may occur due to respiratory and circulatory failure. Typical clinical manifestations include increased breathing in infants, indentation of the chest wall, flaring of the nostrils, groaning, tachycardia, liver enlargement, and in severe cases, cyanosis, prolonged expiration, progressive respiratory insufficiency, such as intermittent apnea, peripheral vasoconstriction, and tachycardia. Due to the presence of fluid in the alveoli, rales can be heard at the base of the lung. When respiratory failure occurs, tissue oxygen supply is insufficient, leading to metabolic and respiratory acidosis. Older children often complain of difficulty breathing, or chest pain and oppression, coughing with red frothy sputum, sometimes resembling an asthma attack, pale or cyanotic complexion, rapid and weak pulse, crackles or vesicular sounds at the base of the lung, liver enlargement, and blood pressure drop.

　　Pulmonary edema often occurs at the end stage of various serious diseases, so it is necessary to actively prevent and treat heart failure caused by pneumonia, various heart diseases, and acute and chronic nephritis, as well as shock caused by various severe infections, and organophosphate poisoning, etc., to prevent the occurrence of pulmonary edema. Antibiotics should be used in a timely manner. In daily life, it is necessary to enhance nutrition, have a reasonable diet, eat more vitamin-rich foods, and exercise appropriately.

　　Blood gas analysis shows severe hypoxemia, with decreased arterial blood oxygen and PCO2, which can decrease due to overventilation, manifesting as respiratory alkalosis. Both arterial blood PO2 and PCO2 can decrease. X-ray examination shows interstitial pulmonary edema with cord-like shadows; lymphatic dilation and interlobular septal effusion are manifested as oblique and straight lines in the hilum area and horizontal lines at the base of the lung, respectively, as Kerby A and B line shadows. Alveolar edema can be seen as small patchy shadows, and as the course progresses, shadows tend to merge near the hilum and at the base of the lung, forming typical butterfly-like shadows or bilateral diffused flocculent shadows, causing the heart shadow to be blurred. It can be accompanied by interlobar and pleural effusions.

　　Dietary suggestions for pediatric pulmonary edema patients mainly include the following points: 1. Avoid eating cold and cool foods. 2. Avoid eating fishy and smelly substances. 3. Avoid seafood and foods with strong刺激性.

　　First, treatment

　　The aim of treatment is to improve gas exchange, rapidly reduce fluid accumulation, and remove the cause of the disease.

　　1. Improve lung ventilation and gas exchange function

　　To relieve hypoxia, first aspirate sputum to keep the airway open. For those with mild pulmonary edema and not severe hypoxia, low-flow oxygen through a nasal cannula can be provided. If pulmonary edema is severe and hypoxia is significant, the oxygen concentration can be increased accordingly, even using 100% oxygen inhalation at the beginning. Mechanical ventilation treatment is used in the following situations:

　　(1) There is a large amount of frothy sputum and respiratory distress.

　　(2) When the shunt between arteries and veins increases, if the oxygen concentration is increased to 50% to 60% and the arterial blood oxygen partial pressure is still below 6.7 to 8.0 kPa (50 to 60 mmHg), it indicates that the pulmonary arteriovenous shunt exceeds 30%.

　　(3) Increased arterial carbon dioxide partial pressure: Before artificial ventilation is applied, it is best to remove the foam as much as possible. If the intermittent positive pressure ventilation uses 50% oxygen inhalation and the arterial oxygen partial pressure is still below 8 kPa (60 mmHg), then positive end-expiratory pressure breathing should be used. According to the condition, PEEP should be gradually increased from small to large, while blood gas monitoring should be performed, and the oxygen concentration inhaled should be kept as low as possible or equal to 50%. Appropriate PEEP can maintain a basically normal oxygen partial pressure, and the carbon dioxide partial pressure will not rise, and it will not have a significant impact on the circulation.

　　2. Take measures to drive the edema fluid back into the blood circulation

　　(1) Rapidly acting diuretics: For example, furosemide is effective for pulmonary edema, and symptoms can improve before diuresis due to extra-renal effects, redistribution of blood, and blood flow from the pulmonary circulation to the systemic circulation. 5 to 15 minutes after the injection of furosemide (Lasix), pulmonary capillary pressure can be reduced, and then the renal effect appears more slowly: diuresis and excretion of sodium and potassium. After a large amount of diuresis, pulmonary blood volume decreases, and pulmonary edema can be improved.

　　(2) Endotracheal positive pressure ventilation: Increases the average alveolar pressure, reduces the transmural pressure difference across the pulmonary capillaries, and allows the edema fluid to return to the capillaries.

　　(3) Reducing the return of blood to the heart: ① Limb tourniquets and head elevation to reduce venous return to the heart, which can redistribute the increased pulmonary blood volume throughout the body. ② Morphine causes peripheral vascular dilation, reduces venous return to the heart, decreases preload, and can also reduce anxiety and lower the basal metabolism, which can be effective.

　　3. Targeted treatment for the cause

　　If dehydration therapy is used for high blood volume; digitalis preparations such as digoxin (lanatoside C) and ouabain (ouabain K) are used for left heart failure. Alpha-adrenergic blocking agents such as phentolamine 5mg can be injected intravenously to dilate blood vessels, reduce peripheral circulation resistance and pulmonary blood volume, and have a good effect. In recent years, sodium nitroprusside has been used for intravenous drip to reduce the cardiac preload and afterload, enhance myocardial contractility, lower blood pressure, and has a good effect on pulmonary edema.

　　4. Reducing pulmonary capillary permeability

　　Corticosteroids are effective for non-cardiogenic pulmonary edema caused by increased capillary permeability, such as pulmonary edema due to inhalation of chemical gases, respiratory distress syndrome, and septic shock. Hydrocortisone can be used intravenously at a dose of 5-10mg/(kg/d). The drug should be discontinued as soon as the condition improves. The use of antibiotics is effective for pulmonary edema caused by increased capillary permeability due to infection-induced toxicity.

　　5. Other treatments

　　If severe acidosis is appropriately treated with alkaline drugs such as sodium bicarbonate or trimethylamine N-oxide (trimethylolamine), the pulmonary vessels that have contracted can dilate after acidosis correction, the pulmonary capillary hydrostatic pressure decreases, and pulmonary edema is reduced. When lung injury may be caused by toxic oxygen free radicals, antioxidants can be used for treatment to clear oxygen free radicals and reduce pulmonary edema.

　　II. Prognosis

　　Active treatment can turn a critical condition into a safe one for the child, but the mortality rate is high if heart failure cannot be effectively controlled.