Severe acute pancreatitis (SAP) is easily complicated by acute respiratory distress syndrome (ARDS) in adults, which is a serious stage or type of acute lung injury (ALI), most likely to occur in the acute response period, pancreatic necrosis secondary to infection and after surgical treatment, mainly due to increased pulmonary capillary permeability, pulmonary interstitial edema, reduced pulmonary surface active substances, and alveolar atrophy. The alveoli are prone to atrophy; the hypercoagulable state of blood leads to pulmonary microvascular embolism and a series of other pathologies. ARDS is a common and serious complication of severe acute pancreatitis. According to statistics, 14.2-33% of patients with acute severe pancreatitis have progressive respiratory distress, and it is more common in first-episode patients. In patients with respiratory distress, the death rate is as high as 30-40%. The clinical features are frequent and distressed breathing, progressive hypoxemia, and X-ray showing diffuse alveolar infiltrates.
The syndrome is quite similar to infantile respiratory distress syndrome, but its etiology and pathogenesis are not identical, so in 1972 Ashbauth proposed the name adult respiratory distress syndrome to show the difference. Now it is noted that this syndrome can also occur in children, so European and American scholars discussed and reached a consensus to replace adult (adult) with acute (acute), called acute respiratory distress syndrome, the abbreviation is still ARDS.
1. Pathogenesis
ARDS caused by acute pancreatitis has many causes, and there is no definite conclusion. a large amount of pancreatic enzymes into the blood during SAP causes extensive vascular damage, and a large amount of disordered body fluids into the third interstitial hypovolemic shock and inadequate pulmonary perfusion, pancreatic enzymes activate multiple systems such as coagulation, fibrinolysis, complement and kinin causing pulmonary microthrombosis and embolism, histamine and 5-hydroxytryptamine and other vasoactive substances reverse the damage to the pancreas The two cause and effect to form a vicious circle and involve other organs, eventually leading to a serious outcome of multi-organ failure.
1.1 Role of pancreatic enzymes
SAP complicated by ARDS is the result of pulmonary circulatory disorders caused by the multifactorial involvement of pancreatic enzymes. Glycoenzymes appear to be harmless to the tissues, while protein and lipid enzymes are important factors in the pathogenesis. The pancreatic enzymes include trypsinogen, chymotrypsinogen, elastase, and collagenase. Among them, chymotrypsinogen and elastase pro have the most important roles. Activated trypsin activates almost all pancreatic enzymes and also activates factor VII, which in turn activates several enzyme systems such as coagulation, fibrinolysis, and complementation. Human trypsin (Try) can be divided into Try-Ⅰ and Try-Ⅱ. Try-Ⅰ is a cationic protein and Try-Ⅱ is an anionic protein. Try in normal human blood is about 300-460ng/dl and can be higher than 10 times when acute pancreatitis is present. Elastase plays a major role in pulmonary hemorrhage and pulmonary edema, and also causes destruction of blood vessel walls, while it also hydrolyzes elastic fibers and acts on a variety of other protein substrates, such as hemoglobin, casein, fibrin, and albumin.
Lipase classes include lipase, co-lipase, cholesterol lipase, and phospholipase A pro. The first three are mainly used to produce free fatty acids (FFA) by hydrolyzing the corresponding substrates. FFA can cause both tissue damage and cytotoxic products, which can cause cell degeneration, necrosis, and lysis, and can cause significant damage to the lung. Phospholipase A (PLA) decomposes lecithin and also produces FFA and lysolecithin. PLA can be activated by Try, and PLA can be divided into two types, PLA1 and PLA2, the latter is stable, and the PLA generally produced refers to PLA2. the role of PLA: hydrolysis of lecithin, producing FFA and lysolecithin; hydrolysis of lung surface active substances, causing pulmonary atelectasis; hydrolysis of phospholipids on cell membranes, affecting cell membrane permeability; hydrolyze phospholipid-containing enzymes on mitochondrial membranes, thus affecting the oxidative phosphorylation process of cells; reduce the stability of lysosomes in lung cells, causing their release, thus destroying tissues and causing abnormal lung perfusion. In acute pancreatitis, in most cases, there is a high cardiac output and reduced peripheral vascular resistance in a state of hyperdynamic circulation, which may be associated with a significant increase in pulmonary arteriovenous shunts. The phenomenon of under-perfusion of one part of the lung tissue and over-perfusion of another part of the lung tissue, it may be another characteristic of pancreatogenic lung injury.
1.2 Role of coagulation system
In acute pancreatitis, Try is released into the blood, and activated Try activates several enzyme systems in the blood and changes the viscosity of the blood. Inadequate lung perfusion, reduced lung function, reduced synthesis of surface active substances, local accumulation of metabolites, and high permeability if the pulmonary vasculature is damaged. As severe dehydration in acute pancreatitis leads to a hypercoagulable state of blood, while the intima is often endothelial, the collected platelets, leukocytes and red blood cells embolize the microvessels, which can cause pulmonary thrombosis and embolism, and on the basis of embolism release vasoactive substances such as histamine and 5-hydroxytryptamine, causing pulmonary vasoconstriction, intima damage, increased permeability and pulmonary edema formation.
1.3 Role of the complement system
Complement is a group of immunoglobulin molecules in the blood that, once activated, form a chain reaction and produce many active fragments and complex molecules, leading to multiple damaging effects. For example, C3a, C5a and C567 can cause histamine release from paravalvular mast cells, resulting in vascular dysfunction and endothelial damage. Complement (C3) is activated by Try, and C3 can also be indirectly activated by activating factor VII. Complement damage is both systemic and pulmonary in nature.
1.4 Other
(1) oxygen free radicals: In recent years, the lung damage caused by oxygen free radicals in pancreatitis has also attracted much attention. Such as O2-, H2O2, OH-, they are peroxidation, decomposition of phospholipids released after the substance, causing vascular dysfunction, endothelial disorders, increased permeability, but also bronchial smooth muscle contraction, mucosal edema, etc..
(2) Transmitters: In some patients, due to acute abdominal pain, the small arteries of the lungs are spasmed by nerve reflexes, together with the action of substances such as catecholamines and histamines. Histamine can also cause contraction of small veins in addition to contraction of small arteries.
(3) SIRS: SAP is often accompanied by systemic inflammatory response syndrome (SIRS) (SIRS diagnostic criteria: body temperature >38°C or 100 times/min; respiration >22 times/min; or PaCo2 12.0×109/L or 0.10). , ARDS is the pulmonary manifestation of the excessive systemic inflammatory response syndrome caused by SAP. Therefore, patients with SAP who meet more than two of the SIRS criteria should be considered as high-risk patients and alerted to the occurrence of ARDS.
(4) Other: such as abdominal distension, diaphragm elevation and pleural exudation in acute pancreatitis, which can affect breathing. In a few patients, fibrin increases during acute pancreatitis and accumulates in the lungs, seriously affecting gas exchange.
2.Clinical manifestations
In the early hours of the syndrome, the patient may have no respiratory symptoms. Subsequently, the respiratory rate is accelerated and shortness of breath is gradually aggravated. No abnormal pulmonary signs are found, or a small wet woven woven mat can be heard during inspiration. Arterial blood gas analysis shows low PaO2 and PaCO2. As the disease progresses, the patient feels respiratory distress, tightness in the chest, inspiratory effort, cyanosis, often accompanied by irritability and anxiety, extensive interstitial infiltration in both lungs, which may be accompanied by odd vein dilatation, pleural reaction or a small amount of fluid accumulation. Respiratory alkalosis occurs due to hyperventilation caused by marked hypoxemia and a decrease in PaCO2. Respiratory distress cannot be improved with the usual oxygen therapy. If these conditions continue to worsen, respiratory distress and cyanosis continue to worsen, and the chest radiograph shows a large fusion of infiltrative shadows in the lungs, which may develop into “white lung”. Respiratory muscle fatigue leads to hyperventilation, CO2 retention, and mixed acidosis. In later stages, heart failure and peripheral circulatory failure develop. Some patients develop multi-organ failure.
Diagnostic criteria for ALI.
① Primary cause of ARDS is present;
②Acute onset;
③Oxygenation index (arterial partial pressure of oxygen/inhaled oxygen concentration, PaO2/FiO2) ≤ 40 kPa (300 mmHg);
④Pulmonary radiographs showed diffuse infiltration of both lungs;
⑤ Pulmonary capillary wedge pressure (PCWP) ≤ 18 mmHg or no clinical evidence of cardiogenic pulmonary edema. diagnostic criteria for ARDS: add oxygenation index (PaO2/FiO2) ≤ 26.7 kPa (200 mmHg) to the above diagnostic criteria for ALI.
3.Treatment
The key to the treatment of ARDS complicated by SAP is to actively treat pancreatitis and stop the inflammatory reaction from further damage to the lungs, but it is more urgent to correct the patient’s severe hypoxic state in time to win valuable time for treating pancreatitis. In respiratory support therapy, it is important to prevent complications such as crush injuries, secondary respiratory tract infections and oxygen toxicity.
3.1 Active treatment of pancreatitis
ARDS is one of the most serious complications of severe acute pancreatitis and a major cause of death, and most of them can still be saved if diagnosed and treated early. However, while dealing with ARDS, SAP should be treated actively. If pancreatitis continues to deteriorate without targeted treatment, ARDS will not improve either.
3.2 Respiratory support treatment
The correction of hypoxia in ARDS patients is urgent. Oxygen can be administered by continuous positive airway pressure (CPAP) through the mask, but most of them need to inhale oxygen by mechanical ventilation. In general, if FiO2>0.6, PaO2 is still <8kPa(60mmHg), and SaO2<90%, a comprehensive treatment based on positive end-expiratory pressure (PEEP) should be used. 1969 Ashbaugh first reported the use of PEEP to treat 5 patients with ARDS, and 3 survived. PEEP is now used as an important measure to rescue ARDS. PEEP improves the respiratory function of ARDS, mainly by opening the atrophied bronchi and closed alveoli through its positive end-expiratory pressure and increasing the functional residual air (FRC). PaO2 and SaO2 increase with increasing PEEP, and systemic oxygen transport increases without affecting cardiac output. The optimal PEEP should be the level of PEEP where SaO2 reaches more than 90% and FiO2 drops to the safe limit [generally 1.47kPa(15cmH2O)]. PEEP should be started from a low level of 0.3-0.5kPa(3-5cmH2O), up to 2.0kPa, and gradually increase to the optimal PEEP, such as PEEP>1.47kPa( 15cmH2O) and SaO2<90%, it may be possible to increase FiO2 for a short period of time (no more than 6h is appropriate) so that SaO2 reaches more than 90%. The recommended methods are assisted controlled ventilation or intermittent command ventilation with moderate PEEP; low tidal volume ventilation with moderate PEEP; modified extracorporeal membrane oxygenator (ECMO), etc. When the condition is stabilized, gradually reduce FiO2 to below 50%, and then reduce PEEP to ≤0.49kPa (5cmH2O) to consolidate the therapeutic effect. When PaO2 reaches 10.7kPa (80mmHg), SaO2 ≥ 90%, FiO2 ≤ 0.4 and stable for more than 12 hours, PEEP can be gradually reduced to discontinuation.
The most common and fatal complication of mechanical gas itself is pneumatic injury. Due to the extensive inflammation, congestion and edema, and alveolar atrophy in ARDS, mechanical ventilation often requires high peak inspiratory pressure, which, together with high levels of PEEP, will cause overinflation of less diseased and more compliant lung units and alveolar rupture. When PEEP > 2.45 kPa (25 cmH2O), the incidence of concurrent pneumothorax and mediastinal emphysema is reported to be 14%, and the morbidity and mortality rate is almost 100%. Now some scholars advocate low tidal volume and low ventilation, even allowing some hypoventilation and mild carbon dioxide retention, so that the peak inspiratory pressure (PIP) <3.92kPa (40cmH2O) <1.47kPa (15cmH2O).
3.3 Maintain appropriate blood volume
SAP is a serious “retroperitoneal burn”, accompanied by severe hypovolemia, and even hypovolemic shock, which must be supplemented with blood volume. -1000ml/d). In the case of hemodynamic stability, diuretics may be used as appropriate to reduce pulmonary edema. The rehydration volume should maintain the PCWP between 1.87 and 2.13 kPa (14-16 cmH2O). Blood should never be transfused in excessive amounts, the drip rate should not be too fast, and fresh blood should preferably be input. Blood in stock for more than 1 week contains micro particles, which can cause microembolism and damage the endothelial cells of pulmonary capillaries, and a microfilter must be added. In the case of increased endothelial cell permeability, colloid can seep into the interstitium and aggravate pulmonary edema, so colloid fluid should not be given in the early stage of ARDS. However, if there is low serum protein concentration then it is a different story.
3.4 Application of adrenal corticosteroids
Glucocorticoids protect capillary endothelial cells, prevent leukocytes and platelets from aggregating and adhering to the wall to form microthrombi, stabilize lysosomal membranes, reduce complement activity, inhibit phospholipid metabolism on cell membranes, reduce the synthesis of arachidonic acid, prevent the production of prostaglandins and thromboxane A2, protect lung type II cells from secreting surface active substances, have anti-inflammatory and promote interstitial fluid absorption, relieve bronchospasm, and inhibit It has anti-inflammatory and interstitial fluid absorption, relieves bronchospasm and inhibits lung fibrosis. At present, it is believed that hormones can be applied in the early stage of ARDS caused by non-infection. Dexamethasone 60-80mg/d, or hydrocortisone 1000-2000mg/d for 2 days, and stop for 1 to 2 days if effective. However, the routine application of corticosteroids to prevent and treat ARDS is not advocated, and the use of hormones with sepsis or severe respiratory tract infection is contraindicated.
3.5 Nutritional support and correction of metabolic disorders
Patients with ARDS are in a high metabolic state, and should be supplemented with calories and high-protein and high-fat nutrients in a timely manner. Strong nutritional support should be given as early as possible, nasal feeding or intravenous supplementation, and the total caloric intake should be maintained at 83.7~167.4kJ (20~40kCal/kg). Attention should also be paid to the correction of acid-base metabolism disorders and electrolyte metabolism disorders.
3.6 Postural therapy
Changing the patient’s position, especially the prone position, has been considered by many scholars to be an effective method for treating ARDS. There are reports of changes in solid lung shadows and improvements in oxygenation parameters within minutes of changing from supine to prone position. The mechanism of action of the position change is not only the displacement of the solid area, but may be due to the altered intrathoracic pressure gradient in the prone position resulting in increased residual pulmonary function, improved local motion of the diaphragm, redistribution of blood flow and better drainage of airway secretions. Although, certain conditions and measures are required to adopt the prone position in critically ill patients, adopting the prone position does improve the pulmonary ventilation/perfusion ratio and reduce intrapulmonary shunts.
3.7 Other treatments
(1) Lung surface active substance replacement therapy At present, there are naturally extracted and artificially prepared surface active substances at home and abroad, which have good effect in treating infant respiratory distress syndrome, and exogenous surface active substances only temporarily increase PaO2 in ARDS.
(2) Nitric oxide (NO) NO is a diastolic factor produced by vascular endothelial cells, which has a wide range of physiological activities and is involved in the pathophysiological processes of many diseases. It is generally believed that NO enters the better ventilated lung tissue and dilates the pulmonary vasculature in that area, causing a low ventilation-to-flow ratio to flow to the dilated vasculature, improving the ventilation-to-flow ratio and reducing intrapulmonary shunts to lower the concentration of oxygen absorption. In addition NO reduces pulmonary artery pressure and pulmonary vascular resistance without affecting the vasodilation and cardiac output of the body circulation. It has been reported that the combination of inhaled NO with intravenous application of almitrine bismyslate has a synergistic effect on improving gas exchange and reducing elevated mean pulmonary arterial pressure. The latter can cause vasoconstriction in poorly ventilated pulmonary areas and blood flow to better ventilated pulmonary areas; and stimulate peripheral chemoreceptors to enhance respiratory drive and increase ventilation; its possible increase in pulmonary artery pressure can be offset by NO. The application of NO in clinical practice has yet to be studied in depth, and there are many specific operational issues to be resolved.
(3) oxygen radical scavengers, antioxidants peroxidase (SOD), catalase (CAT), can prevent acute lung injury caused by the oxidation of O2 and H2O2; uric acid can inhibit the production of O2, OH and PMNs respiratory burst; vitamin E has some antioxidant effectiveness.
(4) Lipoxygenase and cyclooxygenase inhibitors such as ibuprofen can reduce thromboxane A2 and prostaglandins, inhibit complement binding to PMNs, and prevent PMNs from aggregating in the lungs.
(5) Immunotherapy The treatment of ARDS by neutralizing pathogenic factors, counteracting inflammatory mediators and inhibiting effector cells is currently well studied with anti-endotoxin antibodies, anti-TNF, IL-1, IL-6, IL-8, and antibodies or drugs against cell adhesion molecules.