Pediatric respiratory failure

　　1. Pathogenesis

　　The causes of respiratory failure can be divided into three major categories: respiratory tract obstruction, pulmonary parenchymal lesions, and respiratory pump abnormalities, which are interrelated.

　　1. Classification based on age

　　(1) Neonatal stage: Generally refers to respiratory failure or other systemic diseases appearing within 28 days after birth. It is often caused by asphyxia, hypoxia, underdeveloped lung, aspiration of amniotic fluid meconium, pulmonary or systemic infection, etc. In addition, congenital malformations and developmental disorders can also lead to obstruction of the upper and lower respiratory tract, diaphragmatic hernia compressing the lungs, and other causes of respiratory failure.

　　(2) Infant stage: Often caused by bronchopneumonia, central infection, etc., and can also be due to incomplete development of the airway and pulmonary immune system, making it easy to be infected by bacteria and viruses, leading to pneumonia and respiratory failure.

　　(3) Children's stage: Often develops from pneumonia, congenital heart disease, persistent asthma, infectious diseases, and failure of extrapulmonary organs, etc. In addition, trauma, surgical trauma, airway foreign bodies, drowning, and poisoning can also seriously affect respiratory function, leading to acute respiratory failure.

　　2. Classification based on central and peripheral etiology

　　(1) Central: Primary injury to the brain, brain edema, or intracranial hypertension affecting the normal function of the respiratory center, leading to abnormal impulse discharge of central respiratory motor neurons, resulting in abnormal respiratory rate and rhythm, mainly characterized by abnormal ventilation function. This includes intracranial infection, hemorrhage, cranial trauma, asphyxia, and hypoxia. Drug poisoning, acidosis, and liver and kidney dysfunction can also lead to central respiratory failure.

　　(2) Peripheral: Primary in the respiratory organs, such as airway, lung, chest wall, and respiratory muscle lesions, or secondary to various diseases in organ systems outside the lungs and chest.

　　3. Classification based on infectious and non-infectious etiology

　　(1) Infectious diseases: Such as bacterial, viral, fungal, and protozoal pneumonia complicated with respiratory failure, or sepsis and other systemic infections leading to acute pulmonary inflammation, injury, edema, hemorrhage, and other lesions. Central infection is also an important cause of respiratory failure.

　　(2) Non-infectious: Central and peripheral respiratory failure caused by factors such as surgery, trauma, aspiration, drowning, and poisoning.

　　4. Meningitis

　　Combination of respiratory failure or multiple organ failure with respiratory failure.

　　5. Classification based on pathophysiological characteristics

　　(1) Acute respiratory failure: It is usually an acute onset with persistent hypoxemia, requiring emergency resuscitation.

　　(2) Chronic respiratory failure: It is often characterized by progressive damage to the pulmonary basic disease, leading to decompensation, hypercapnia, and acidosis.

　　(3) Oxygen and carbon dioxide levels: There is clinical evidence to diagnose respiratory failure as type I (hypoxemia) and type II (hypoxemia with hypercapnia) based on blood gas analysis.

　　Second, pathogenesis

　　The etiology is caused by upper and lower respiratory tract obstruction, pulmonary diseases, central nervous system diseases, or myopathy, which severely damages respiratory function, preventing effective gas exchange and leading to hypoxemia, CO2 levels being normal or decreased (Type I), or increased (Type II), resulting in a decrease in lung volume, reduced compliance, and increased respiratory function, a series of physiological dysfunction and metabolic disorders. The normal progression of ventilation and gas exchange depends on the regulation of the respiratory center. A healthy thorax, respiratory muscles, and neural control, unobstructed airways, mature alveoli, and normal pulmonary circulation are necessary. Any cause that severely damages one or more of these links can lead to disorders in the process of ventilation and gas exchange, resulting in respiratory failure. Due to the different etiology and pathophysiological basis, relying solely on one standard as the guide for all respiratory failures is not comprehensive enough. According to clinical manifestations, combined with blood gas analysis, etc., it can be divided into two types: gas exchange and ventilation function failure.

　　1. Type I respiratory failure

　　The main cause is the failure of gas exchange function, mainly due to pulmonary parenchymal lesions. This is caused by the impairment of gas exchange between alveoli and blood and the abnormal ventilation/perfusion ratio, which prevents the lung from having an adequate amount of oxygen reaching the pulmonary capillaries, resulting in low oxygen in arterial blood, while CO2 excretion remains normal or even increases, with PaCO2 being normal or decreased. Some individuals may develop respiratory alkalosis due to compensatory increased breathing rate, which often occurs in extensive pulmonary lesions. This includes bacterial, viral, and fungal infections, inhalation pneumonia, interstitial pneumonia, inhalation of irritant gases, respiratory distress syndrome, shock lung, pulmonary edema, and extensive atelectasis, etc. When at rest and breathing indoor air at sea level atmospheric pressure, the characteristic changes in blood gas are PaO2

　　(1) Gas diffusion impairment: Due to severe changes in alveolar capillaries and a decrease in the effective capillary bed caused by pulmonary congestion, pulmonary edema, alveolitis, etc., as well as conditions such as emphysema and pulmonary embolism, which lead to dysfunction in gas diffusion. Since the diffusion capacity of CO2 is 20-25 times greater than that of O2, in the area where blood flow is sufficient, not only does CO2 retention not occur, but under the stimulation of low oxygen, the alveoli overventilate, expelling more CO2, resulting in an increase in pH value, but not being able to absorb more O2, manifesting as hypoxemia. If there is also an increased heart rate, there is no sufficient time for diffusion, leading to respiratory failure.

　　(2) Uneven ventilation and abnormal V/Q ratio: The efficiency of alveolar gas exchange depends on the ratio of alveolar minute ventilation to the minute blood flow of the alveolar surrounding capillaries. If respiratory tract diseases are present, in the areas where alveolar ventilation is insufficient, the ventilation/perfusion ratio is less than 0.8, the lung tissue still maintains blood perfusion, and the venous blood is not fully oxygenated before entering the artery, causing intrapulmonary shunting and hypoxemia. This is often seen in atelectasis. If the ventilation/perfusion ratio is greater than 0.8, it means that the ventilation in the lesion area is still relatively good, but the blood flow decreases, and the inhaled gas entering this area cannot perform normal gas exchange, resulting in ineffective ventilation. This increases the volume of dead space air, reduces the alveolar gas volume, causing hypoxemia, and requires an increase in the number of breaths to increase ventilation to compensate, maintaining or even lowering PCO2. This is common in diffuse pulmonary vascular diseases.

　　2, Type II respiratory failure

　　主要以通气衰竭为主, due to pulmonary reasons (airway obstruction, increased physiological dead space) or extrapulmonary reasons (abnormalities in the respiratory center, chest wall, respiratory muscles). It is accompanied by hypoxemia and hypercapnia. Any lesion that weakens pulmonary dynamics or increases resistance can cause it. Due to the decrease in total ventilation volume, alveolar ventilation volume also decreases. Even if the total ventilation volume does not decrease, due to increased residual volume, alveolar ventilation volume will also decrease, resulting in hypoxemia and CO2 retention. Clinical manifestations include respiratory distress, shortness of breath, severe cyanosis, thick or large amounts of sputum in the airways, which may be accompanied by obstructive emphysema or regional atelectasis. Children may be restless or have impaired consciousness. Blood gas analysis shows PaCO2 greater than 6.67 kPa (50 mmHg), and PaO2 decreases to less than 8 kPa (60 mmHg). This type can be divided into two main groups:

　　(1) Restrictive respiratory failure: Seen in conditions such as chest wall deformities, pleural thickening, pleural effusion or pneumothorax, pulmonary fibrosis, etc., which cause decreased elasticity of the chest wall or lung tissue. In addition, it can also be caused by neuromuscular diseases such as polyneuritis, poliomyelitis, respiratory muscle paralysis, etc. Respiratory center depression or loss of function, such as中毒 of morphine, barbiturates, anesthetics, etc., severe brain hypoxia, encephalitis, meningitis, increased intracranial pressure, etc., restrict the respiratory action, reducing the amount of oxygen entering the alveoli and the elimination of CO2, leading to hypoxemia and CO2 retention.

　　(2) Obstructive respiratory failure: Mainly refers to the discomfort or difficulty in breathing caused by obstruction in the lower respiratory tract. It is most common in conditions such as bronchiolitis, emphysema, bronchial asthma, and mediastinal tumors, which compress or block the airways, increasing expiratory resistance, insufficient alveolar ventilation, and even airless areas in some regions. The total lung capacity and vital capacity are normal, even increased, but the residual volume is significantly larger compared to the total lung capacity. The maximum ventilation volume decreases, and the forced vital capacity is significantly prolonged. Sometimes, the two types are mixed, all showing hypoxemia. Due to its rapid onset, the increased CO2 partial pressure cannot be compensated in time by the bicarbonate reserve retained in the kidneys, resulting in respiratory acidosis. Hypercapnia increases pulmonary artery resistance, dilates cerebral blood vessels, leading to increased intracranial pressure and cerebral edema. Both types of respiratory failure mentioned above have hypoxemia, while CO2 retention is only seen in type II, but it can also occur in the late stage of type I. Central nervous system and neuromuscular diseases can only cause type II respiratory failure, while diseases affecting the lungs and bronchial tubes can cause both type I and type II. If only type I is present, the lungs must be involved.

　　The main complications include gastrointestinal bleeding, arrhythmia, pneumothorax, DIC, superficial venous thrombosis, pulmonary embolism, complications of tracheal intubation or resection, secondary infection, and others.

　　2. Development of organ failure outside the lungs Prolonged hypoxemia can lead to functional failure of both pulmonary and extrapulmonary organs. This is mainly due to the massive accumulation of inflammatory cells in the lungs, releasing pro-inflammatory mediators into the circulation, attacking extrapulmonary organs, leading to functional and structural damage of extrapulmonary organs, which can develop into multiple organ dysfunction and failure.

　　1. Development of severe lung injury and acute respiratory distress syndrome Central respiratory failure can develop into ventilator-associated pneumonia and lung injury. Poor respiratory management during prolonged mechanical ventilation can lead to maldevelopment of airway alveoli, respiratory tract bacterial infection, progression to pneumonia, and exacerbation of respiratory failure. Chemotherapy and immunosuppression, intestinal ischemia and hypoxia-reperfusion injury, and other factors can lead to severe pulmonary infectious injury and develop into ARDS.

　　1. Respiratory system

　　Due to the small lung capacity in children, the lung compensatory ventilation mainly relies on the increase in respiratory frequency to meet the metabolic needs. When the respiratory frequency exceeds 40 times/min, the effective alveolar ventilation shows a downward trend. Therefore, dyspnea is often manifested as shallow and rapid breathing, and infants and young children can even reach 80-100 times/min, showing tracheal retraction signs. After the respiratory muscles become fatigued, the breathing rate slows down, accompanied by severe hypoxemia and high carbon dioxide retention, leading to various clinical abnormal manifestations. When the blood oxygen saturation reaches 12.0 kPa (90 mmHg), it can produce anesthetic effects on the respiratory center, and the respiratory movement can only be maintained by the stimulation of hypoxemia on the chemoreceptors. At this time, if high-concentration oxygen is administered, it may反而 suppress respiration.

　　2. Nervous system

　　During hypoxemia, symptoms such as restlessness, confusion, drowsiness, coma, seizures, and central respiratory failure with irregular breathing rhythm and tidal breathing may occur. In the late stage of respiratory failure, changes in pupil size may occur when the optic nerve is compressed.

　　3. Cardiovascular system

　　In the early stage of hypoxemia, heart rate increases, cardiac output improves, and blood pressure rises; in the later stage, heart rate slows down, heart sounds become dull, blood pressure decreases, and arrhythmia occurs.

　　4. Other organ systems

　　Hypoxemia can lead to vasoconstriction of visceral vessels, gastrointestinal bleeding and necrosis, abnormal increase of metabolic enzymes in liver function damage, and kidney function damage can lead to symptoms such as proteinuria, oliguria, and anuria.

　　5. Acid-base imbalance and water-salt electrolyte disorder

　　Hypoxemia and acidosis cause abnormal metabolic function of tissue cells, combined with insufficient energy intake, restricted fluid replacement, diuretic use, and other factors, which can lead to hyperkalemia, hypokalemia, hyponatremia, hyperchloremia, and hypocalcemia in children. The kidney's regulatory role in acid-base, water-salt electrolyte balance is limited, especially in hypoxemia when renal blood flow decreases, further limiting the kidney's regulatory function, which can exacerbate systemic acid-base imbalance and water, salt, and electrolyte disorders.

　　It is necessary to actively treat the diseases that cause respiratory failure. When treating shock and severe infection, it is important to control the infusion rate and balance the intake and output, avoid long-term inhalation of high-concentration oxygen, which is an effective measure to prevent acute respiratory failure. The clinical application of blood gas微量analysis can be used to observe the changes in functional state, which is helpful for early detection of abnormalities, analysis of etiology, and timely treatment to save lives.

　　1. Urinalysis and serum creatinine

　　For those with normal results, renal acidosis can be ruled out.

　　2. Blood gas analysis

　　It can accurately reflect the specific conditions of hypoxia and acidosis in the body during respiratory failure, the method is simple, and since the application of微量determination, it can be repeated multiple times to observe the dynamic changes, and at the same time, it can also understand the compensation degree of the body for acidosis and circulatory function, and make a comprehensive judgment with clinical phenomena, simple ventilation volume determination, electrolyte examination, etc., which is of great significance for guiding treatment.

　　3. Heart, liver, kidney function and electrolytes

　　Serum myocardial enzyme spectrum, blood urea nitrogen, creatinine, alanine aminotransferase, electrolyte determination, etc., are helpful for the diagnosis of heart, kidney, liver function damage and electrolyte disorder.

　　4. Vital capacity

　　Bedside measurement of vital capacity, the first second forced vital capacity or peak expiratory flow rate (PEFR) can help understand the extent of ventilation damage, such as when the vital capacity is 1/2 of the predicted value, mechanical ventilation should be considered; when it is less than 1/3 of the predicted value, immediate mechanical ventilation should be performed. An electrocardiogram, chest X-ray, B-ultrasound, CT, and other examinations should be performed.

　　Children with respiratory failure should eat easily digestible, nutritious food after treatment, and those with severe conditions should mainly consume liquid and semi-liquid foods. The diet should not be too salty, and should avoid sweet and greasy foods, as well as spicy and stimulating foods..

　　1. Treatment principles

　　To increase PaO2 and SO2, and decrease PaCO2. Children have a rapid progression of the disease and a high mortality rate, so active treatment should be implemented.

　　1. Treatment of the etiology

　　Various effective measures are taken for the direct causes of respiratory failure. In particular, it is important to promote the recovery of lesions that cause respiratory failure, such as the control of infection during pneumonia, the treatment of cerebral edema in central nervous system diseases, and the treatment of pulmonary edema in ARDS children. Symptomatic treatment to improve blood gas is of great importance when the primary disease cannot be immediately relieved; however, the focus of respiratory dysfunction varies. The focus of children with respiratory tract obstruction is on improving ventilation, while the focus of ARDS children is on improving gas exchange, and for pneumonia, both aspects should be considered. Therefore, correct diagnosis is the premise of rational treatment, and only by having a clear understanding of the pathophysiological characteristics of respiratory failure in children can different treatment plans be adopted for different disease conditions.

　　2. Oxygen therapy

　　For those with respiratory insufficiency, inhaling low to moderate concentration oxygen (0.3～0.5) for several hours can increase blood oxygen saturation (SO2 > 90%). For acute hypoxia, use moderate concentration oxygen (0.4～0.5), and for chronic hypoxia, provide low concentration oxygen (0.3～0.4). For respiratory failure patients, inhaling oxygen for 12～24h can relieve hypoxemia, and cyanosis and dyspnea will gradually subside. Long-term inhalation of low concentration oxygen generally does not produce serious adverse reactions. However, inhaling oxygen greater than 80% for 24～48h can cause airway inflammation and edema. Even severe oxidative damage to the airway mucosa. High blood oxygen levels can lead to retinopathy. The improvement of arterial oxygen levels must be associated with the improvement of hypoxia symptoms, as the ability of tissues to take up oxygen is affected by factors such as the oxygen dissociation curve, hemoglobin levels, and cardiac output.

　　3. Airway management

　　Maintain respiratory tract humidification and atomization to prevent excessive drying and necrosis of the airway epithelial cells. Secretions in the airway can be cleared by methods such as back blows, airway atomization, or the use of drugs like沐舒坦 to expectorate. For those with congenital or acquired airway development leading to ventilation obstruction, or with carbon dioxide retention, tracheal intubation, mechanical ventilation, and necessary surgical treatment should be provided to relieve airway obstruction and repair congenital malformations such as fistulas. After tracheal intubation, children should be instilled with normal saline into the trachea every 1～2h, followed by negative pressure airway aspiration.

　　4. Mechanical ventilation

　　(1) General principles of parameter setting: Adjust the tidal volume and ventilation frequency to maintain relatively stable ventilation volume, and control PaCO2 within 4.7～6kPa (35～45mmHg). The ventilation frequency for newborns and infants under 3 months old is 40～50 times/min, for toddlers is 30～50 times/min, and for children is 20～40 times/min. The tidal volume during volume control or pressure control is 6ml/kg. If FiO2 > 40% is required to maintain SO2 > 85%, the end-expiratory positive pressure (PEEP) should be set at 2～4cmH2O.

　　(2) Evaluation of mechanical ventilation effects: To determine the appropriateness of alveolar ventilation volume and oxygenation status, the following formula can be used to judge the potential ventilation and gas exchange efficiency: a/A(PO2) - PaO2/PAO2, where PAO2 = FiO2 × (PB - PH2O) - PaCO2/R, PAO2 is the alveolar oxygen partial pressure, PB is the atmospheric pressure at sea level (760mmHg), PH2O is the alveolar water vapor pressure (47mmHg), and R is the respiratory quotient (0.8). If a/A > 0.5, it indicates normal or mild respiratory insufficiency; a/A

　　(3) Hyperventilation: It is not recommended to use hyperventilation methods as they may cause a significant decrease in cerebral blood flow in newborns and infants, leading to ischemic and hypoxic brain injury. For those with poor ventilation effects, it is permissible to have hypercapnia, i.e., PaCO2 can be maintained at 7～9kPa (50～65mmHg) without adjusting the high tidal volume and peak airway pressure. If necessary, the ventilation frequency can be increased to 50～70 times/min to increase the minute ventilation volume.

　　5. Respiratory Stimulants

　　For central acute respiratory failure, drugs such as nikethamide (coramine) and loxapine hydrochloride (lobeline) can be used to stimulate the respiratory center, but their efficacy is not durable, and the airway must be confirmed to be open when using them. Neonates generally do not use these drugs. Nikethamide (coramine) can be administered intramuscularly, subcutaneously, or intravenously, with a dose of 75mg per dose for those under 6 months, 125mg per dose for those aged 1-3 years, and 175mg per dose for those aged 4-7 years. Loxapine hydrochloride can be administered subcutaneously or intramuscularly at a dose of 1-3mg per dose, and intravenously at a dose of 0.3-3mg per dose, with repeat administration every 30 minutes if necessary.

　　6. Reduction of Intracranial Pressure

　　In cases of cerebral edema, the principle is to adopt a 'gradual dehydration and supplementation' approach, control the intake and output of fluids, and achieve a mild degree of dehydration. Mannitol is commonly used, with a intravenous bolus dose of 0.25-0.5g/kg, repeated every 4-6 hours. Generally, intracranial pressure begins to decrease 20 minutes after administration. Alternatively, mannitol-glycerol/sodium chloride (compound glycerol) (0.5-1.0g/kg) can be alternated, every 4-6 hours, until symptoms subside, at which point the medication can be gradually discontinued. Diuretics such as furosemide are commonly used, administered intramuscularly or intravenously at a dose of 1-2mg/kg, with neonates requiring an interval of 12-24 hours. The main adverse reactions include dehydration, hypotension, hyponatremia, hypokalemia, hypochloremia, and hypocalcemia. Those with existing water and electrolyte imbalances should pay attention to timely correction.

　　7. Correction of Acidosis

　　(1) Respiratory acidosis: The main metabolic imbalance during respiratory failure is respiratory acidosis. Generally, it is necessary to maintain an open airway, stimulate respiration, and, if necessary, use mechanical ventilation to reduce carbon dioxide in the tissues and circulatory blood.

　　(2) Metabolic acidosis is treated with alkaline drugs, such as sodium bicarbonate, which neutralizes fixed acids in the body, increases plasma HCO3-, and corrects acidosis. In addition, acidosis can stimulate bronchospasm and reduce the effect of bronchodilators, and sodium bicarbonate can alleviate bronchospasm. Hypoxemia and acidosis can lead to myocardial paralysis and vasoconstriction of small pulmonary vessels, and the administration of sodium bicarbonate can have a cardiac-stimulating and pulmonary vasodilating effect, which is beneficial for improving pulmonary blood perfusion. Generally, 5% sodium bicarbonate is used, with a concentration of 1ml=0.6mmol, and the dose is about 2-3mmol (3-5ml)/kg per day, with half the dose (1-1.5mmol/kg) initially administered. The calculation method is: HCO3-(mmol) = 0.3 × BE × body weight (kg). When administered intravenously or by slow injection, 5% sodium bicarbonate can be diluted to a 1.4% concentration with lactic acid-Ringer's solution or glucose physiological saline to reduce the irritation of the alkaline solution to the venous vessels. If alkaline fluid is supplemented too quickly, or if ventilation and peripheral circulation are not improved in a timely manner, metabolic alkalosis may occur, which can lead to coma and cardiac arrest. In the event of metabolic alkalosis, ventilation can be rapidly and appropriately reduced to produce respiratory acidosis, physiological saline can be supplemented, or oral ammonium chloride, intravenous or oral potassium chloride can be administered to correct the condition.

　　8. Application of Cardiac Glycosides and Vasoactive Drugs

　　Doxorubicin preparations, diuretics, and agents for adjusting vascular tone can be used in cases of persistent hypoxemia with concurrent heart failure.

　　(1) Digoxin (Cedilanide) and digitoxin: In cases of myocardial hypoxia during respiratory failure, it is easy to cause digitalis poisoning, so it is considered to reduce its dosage.

　　(2) Dopamine and dobutamine: Exciting the β1 receptor of the heart, dilating renal, cerebral, and pulmonary vessels, increasing renal blood flow and urine output, they are the main drugs for shock and refractory heart failure. Their half-life is very short, and they must be administered continuously by intravenous infusion. Dopamine 2-10μg/(kg·min), dobutamine 2-20μg/(kg·min), can be used in combination, starting from low doses.

　　(3) Phentolamine: As an α-adrenergic antagonist, it can directly dilate peripheral small arteries and capillaries, significantly reduce peripheral vascular resistance and cardiac afterload, and increase cardiac output. It is suitable for respiratory failure in diseases such as pulmonary vasoconstriction caused by hypoxia, severe pneumonia, acute pulmonary edema, and congestive heart failure. The dose is intravenous infusion of 0.1-0.3mg per time, diluted with 5%-10% glucose saline, and infused at a rate of 2-6μg per minute. Pay attention to correcting hypotension and arrhythmias during use, and supplement blood volume in cases of toxic shock.

　　(4) Nitric oxide (NO) inhalation: Newborns with hypoxic respiratory failure and persistent pulmonary hypertension can be treated with NO inhalation. The initial dose is 10-20ppm, for 3-6 hours, then changed to 5-10ppm, which can maintain for 1-7 days or longer until the hypoxia condition is fundamentally relieved. Furosemide can be used to promote lung fluid absorption and reduce cardiac workload in cases of acute pulmonary edema and acute heart failure. 9. Diuretics in respiratory failure with acute pulmonary edema and acute heart failure.

　　II. Prognosis

　　Take positive and effective measures to treat the underlying disease and triggering factors, alleviate hypoxia and carbon dioxide retention, and prevent complications. Type I respiratory failure aims to correct hypoxia, and Type II respiratory failure also requires increasing alveolar ventilation. Therefore, keeping the respiratory tract unobstructed, actively controlling infection, and providing oxygen rationally are the main measures for rescuing children with respiratory failure. Timely removal of the primary disease or trigger can alleviate the condition. Chronic respiratory failure can generally alleviate the condition after treatment, the key is prevention. Patients with failure of two or more organs, young children, those with malnutrition, accompanied by convulsions, and coma have a high mortality rate.