The herbicidal effect of paraquat was discovered in the late 1950s and it was first marketed in 1962. At present, paraquat is the second largest product in the world herbicide market and has been registered for use in more than 100 countries. It has been registered for use in more than 100 countries. It has also been widely used in most areas of China. Physical and chemical properties of paraquat Paraquat is a blue-colored liquid, the original drug is odorless and can be miscible with water and ethanol. Molecular formula C12H14N2?2X (X=Cl, CH3SO4) Molecular weight 257.2 (2Cl) PH-value: 2.6 Paraquat ion is stable in acidic and neutral solutions, but decomposes when it meets alkali and under the condition of UV. Paraquat is passivated by soil, and it can combine with clay and organic matter rapidly and lose biological activity. Absorption and excretion Paraquat can be absorbed through intact skin, respiratory tract and digestive tract, but the absorption is not complete, after absorption, it is distributed to all tissues and organs of the body with blood, but the content in lung is very high, often ten to tens of times greater than the content in blood. It is rarely degraded in the body and is often excreted in its original form in urine and feces. It is reported that the plasma concentration is highest in 90 min after poisoning and can drop by 50% after 24 hours. The duration is related to the amount absorbed and usually lasts 3-5 days, but it lasts longer if the blood concentration is high. Toxicity of paraquat Paraquat is moderately toxic. But it is very toxic to human. The amount of human oral poisoning is about 10-15ml of 20% paraquat solution or 2-3g of pure product. The prominent manifestation of human poisoning is multi-organ damage or failure with acute chemical interstitial lung lesion and rapidly developing interstitial lung fibrosis. The mortality rate of severe poisoning is as high as 60%-80%. The incidence of paraquat poisoning With the surge of demand for paraquat in agriculture and forestry, the incidence of clinical paraquat poisoning has also increased significantly. Now it has become the second pesticide poisoning after organophosphorus pesticide poisoning in terms of incidence. According to the current development trend, it may become the first pesticide poisoning soon. But the mortality rate is always in the first place. Pathogenesis and pathology of paraquat poisoning Paraquat has irritating and corrosive effects on skin and mucous membrane, and systemic poisoning can cause multi-system damage, especially lung damage is more serious. It can cause lung congestion, hemorrhage, edema, hyaline membrane formation, degeneration, hyperplasia, fibrosis and other changes. In addition, it can cause damage to liver, kidney, heart, pancreas and gastrointestinal tract and involve circulation, nerves, blood, bladder and other systems and organs. The pathogenesis and pathology of paraquat poisoning The mechanism of poisoning has not been elucidated yet. Most scholars believe that paraquat is an electron receptor, which can be actively transported by lung type I and II cells and taken up into the cells. The formation of excess superoxide anion radicals (O=) and hydrogen peroxide (H2O2) can cause lipid peroxidation in cell membranes of lung, liver and many other tissues and organs, and inhibit energy synthesis, interfere with cell metabolism, and cause direct and indirect tissue cell damage. This can cause damage and failure of multiple systems and organs. Pathology After 24 hours of paraquat ingestion in human, lung congestion, edema, hemorrhage and weight increase, and dark red bruises visible to the naked eye on pleural surface and septal surface are unique to this disease. The histological changes were diffuse capillary endothelial cell and alveolar epithelial cell damage, inflammatory cell infiltration mainly by neutrophils, alveolar wall edema, forming extensive alveolitis lesions; alveolar epithelial degeneration and exfoliation, necrosis; intra-alveolar cavity hemorrhage, followed by fibrin exudation, while alveolar hyaline membrane generation. 6 days later, the alveolar cavity exudate began to mechanize, fibroblast hypertrophy, secretion of slender collagen fibers, forming more sparse fibrous tissue. Sparser fibrous tissue was formed, and images of intra-alveolar fibrosis were seen. The liver is stagnant and shows betel liver changes with cloudy and swollen hepatocytes with vacuolar degeneration and focal necrosis. Myocardial cells are cloudy and swollen, with scattered foci of myosoluble necrosis at various sites. The renal proximal tubules were swollen with focal necrosis and regeneration. Clinical experience and treatment of 206 cases of paraquat poisoning The clinical treatment of 206 cases of paraquat poisoning admitted to our hospital in the past 7 years is presented. The results are summarized as follows, together with the results of the “Clinical study of acute paraquat poisoning” of the National Science and Technology Support Program (Project No. 2006BAI06B01-) jointly undertaken by us and the School of Public Health of Shanghai Fudan University. Clinical data General data: There were 206 cases in this group, including 76 males and 130 females, with the oldest age being 70 years old and the youngest being 3 years old. Among them, there were 37 cases of mild poisoning; 126 cases of severe poisoning; 43 cases of very severe poisoning. The oral dosage was 2-500ml, including 28 cases below 10ml, 67 cases from 11ml-30ml, 87 cases above 30ml, with an average of 52.2ml (all patients were asked to simulate the oral dosage with water, except for those who were not clear). Clinical manifestations The cases in this group were classified according to exposure dose, urinary paraquat concentration and clinical manifestations: mild poisoning, severe poisoning and very severe poisoning (outbreak type). Mild poisoning: the intake amount is less than 10ml, the urinary paraquat concentration is less than 10μg/ml, and the multi-organ function is mildly damaged. Very severe poisoning: the intake amount is more than 30ml, urinary paraquat concentration is more than 30 micrograms/ml, and combined with multiple organ function failure. The rest is severe poisoning. Early symptoms of poisoning cases are nausea, vomiting, pain in oropharynx, posterior sternum and epigastrium, acute upper gastrointestinal corrosive inflammatory manifestations such as oral mucosa congestion, edema, erosion and bleeding. Very severe cases of poisoning were often accompanied by dry mouth, irritability, psychiatric symptoms, acidosis, hypokalemia and enhanced coagulation mechanism. Clinically 32 of these cases were accompanied by gastrointestinal bleeding manifestations. In 76 cases, chest tightness, breath-holding, shortness of breath, panic, abdominal distension and inability to eat began to appear after the second or third day. 34 cases were combined with jaundice, tarry stools, oliguria and other manifestations of lung, liver, kidney, heart and gastrointestinal damage. Among them, 12 cases showed pancreatic damage, elevated pancreatic amylase and significantly increased blood glucose. These symptoms peaked on days 5-7. Respiratory failure was the main cause, followed by combined liver and kidney failure. In patients with very severe poisoning, the above symptoms were obviously aggravated and appeared early, and were accompanied by mental symptoms such as irritability, delirium, acidosis, enhanced coagulation mechanism and rapid onset of toxic shock or (and) ARDS All cases died of toxic shock or MOF within one week. Laboratory examination Based on the pathological changes, we believe that the substance of paraquat poisoning is a systemic chemical inflammatory reaction with pulmonary lesions as the main syndrome. Laboratory tests should focus on the systemic inflammatory response index. We set up the following examination items: blood routine; CRP; IL-6; NAA; tumor necrosis factor; and urinary routine, liver function, biochemistry, cardiac enzyme profile, pancreatic amylase; blood and urine paraquat content, etc. In 206 cases, WBC 8.4×109/L – 41.8×109/L, neutrophil percentage was 78%-95%, among which 24 cases were stained for neutrophil alkaline phosphatase (NAA), positive rate 72%-100%, score 216-600. C-reactive protein ( CRP) 2.6-15.2mg/L . In 136 cases, myocardial enzyme profile was elevated and sinus tachycardia was observed, including 7 cases with pericardial effusion. 193 cases showed varying degrees of impairment of liver and kidney function. The semi-quantitative detection of urinary paraquat was 3µg/ml-200µg or more/ml. Clinical treatment I. Gastrointestinal decontamination: “early, fast and thorough” is required. For those who are admitted to hospital within 24 hours of onset or those who still need gastric lavage, 15% bleach suspension (or activated charcoal) should be given for gastric lavage. All cases should be given 15% bleach suspension 300ml plus 20% mannitol 250ml (or 20% magnesium sulfate 100ml) for diarrhea, once every 3-6 hours, or alternatively, until there is no blue paraquat in the stool, which should be done within a few hours. For those who cannot eat due to pain in the oropharynx, it is prudent to insert a gastric tube to induce diarrhea by nasal feeding. Add 2-5% sodium carbonate to the gastric lavage for better effect. All cases were given semi-quantitative determination of paraquat in urine (paraquat test kit produced by Syngenta (China) Investment Co., Ltd.), and any urine test positive for paraquat and greater than 5 micrograms per milliliter was administered for hemodialysis. Hemodialysis (HD) was given in 28 cases, hemodialysis (HP) in 152 cases, bedside hemofiltration (CRRT) in 19 cases, and plasma exchange (PE) in 17 cases, of which: HD+HP in 16 cases and PE+CRRT in 9 cases. 8-24 h was administered once. If the body is in good condition, it will be performed once every 8 hours until the urine is negative for paraquat. Blood and urine paraquat tests were compared before and after each hemodialysis. The principle is to remove the toxin from blood as early as possible to reduce the transfer of toxin to tissues. The higher and average values of blood paraquat clearance by blood perfusion The higher value: 1.7ug/ml before perfusion, 0.62ug/ml after perfusion, the clearance rate was 63.53%. The mean value of blood paraquat concentration before and after the first perfusion in 9 patients The mean value: 1.72ug/ml before perfusion, 1.135ug/ml after perfusion, the mean clearance rate was 34.01%. 24-hour natural rate of decline of blood paraquat B15Q1 0.17 B15Q2 0.13 A12Q1 0.67 A12Q2 0.54 B14Q1 0.38 B14Q2 0.43 A22Q1 0.59 A22Q2 0.49 Mean value: 0.45 at 0 hours, 0.397 at 24 hours Percentage decline: 11.79% Units (ug/ml) III. Hydrotherapy: According to the research report, paraquat is rarely degraded in the body and is often excreted with urine and feces as intact protoplasm, a small amount can be excreted through breast milk, and about 30% of those who are poisoned through mouth are excreted with feces. Therefore, patients are not fasted in the treatment, encouraged to drink more water and eat normally. If the volume load can be tolerated, more fluids can be given and diuretics can be given at the same time in the early stage to promote the excretion of paraquat from the body as soon as possible. Once there is lung damage with exudation, water control should be given immediately and plasma substitution such as Van Boven should be given to reduce exudation. Drug treatment: All cases are given larger doses of glucocorticosteroids, and methylprednisolone (methylprednisolone) is generally given 3-6 mg/kg/d for 3-5 d, and then the dose is gradually reduced in parabolic or descending steps according to the condition until the condition is controlled. According to the heavy chemical inflammatory reaction of the organism caused by paraquat, ustekin or Isep and Asagil were given again to enhance the effect of eliminating chemical inflammation. Also all cases were given high doses of free radical scavengers, antioxidants and the so-called paraquat antagonists and competing agents. The drugs applied were: reduced glutathione (guladin or atomorelin 1.8g-2.4g iv drip qd), vitC 3.0g iv drip qd, vitE 0.1 tid, tretinoin 10mg tid, vitB1 200mg im qd, etc. Add ustekin 0.1-0.3MIU iv drip q12-q8h in the severe phase of inflammatory reaction of the organism; or Ixepro 25mg im qow; Asagil 1.0 iv drip q12h. Add high doses of drugs to improve microcirculation in the recovery period: Chuanxiong, compound salvia injection, etc. As well as supporting nutrition, symptomatic treatment, control v. Rational oxygen therapy: assisted breathing if necessary. Oxygen is prohibited in principle when there is no obvious hypoxia, only when SPaO2 is below 90% or PaO2 is below 60mmHg and meets the criteria of respiratory failure is given. If there is ARDS or obvious respiratory failure, give non-invasive or invasive ventilator-assisted breathing, apply synchronous mode (SIMV) plus positive end-expiratory pressure (PEEP) 3-15cmH20. note that the larger the PEEP, the greater the possibility of causing pneumothorax, ventilator-assisted breathing can prolong survival time, but it is difficult to reduce mortality, infection, etc. For those who had severe respiratory failure and intractable hypoxemia, the effect of drugs was not obvious, but other organs recovered well, we selected 2 cases for extracorporeal membrane lung (ECMO) treatment, both of which were maintained for more than 10 days, but finally abandoned because the lungs could not recover. 2 cases intended for lung transplantation also died because of the seriousness of the disease and could not wait for a donor. Clinical cure: 59 cases, cure rate 47.97% Clinical death: 64 cases, mortality rate 52.03% Follow-up results of improved cases and other cases: 206 cases Survival: 104 cases, survival rate 50.49% Death: 102 cases, mortality rate 49.51% Maximum oral dose for cured patients: 200ml, average oral dose 29.3ml The minimum oral dose for the deceased patients was 20 ml, and the average oral dose was 75.15 ml. All the cured patients were discharged from the hospital with chest X-ray, lung CT and pulmonary function examination: chest X-ray showed the elimination of inflammatory reaction; lung CT: 32 cases had mild pulmonary fibrosis; 11 cases had moderate pulmonary fibrosis and 8 cases had severe pulmonary fibrosis. Pulmonary function tests: 46 cases had mild diffusion dysfunction, 23 cases had moderate diffusion dysfunction, and 12 cases had severe diffusion dysfunction. At the follow-up visit after one month, all of them took care of themselves and most of them regained some working ability. Discussion Because of the active uptake and accumulation of paraquat by alveolar cells, the lung injury was the most prominent. This poisoning is likely to cause MODS or MOF and interstitial pulmonary edema, ARDS, hypoxemia and respiratory failure. Therefore, the main factor of death is lung damage. Very severe poisoning (explosive type) often occurs in toxic shock in hours or tens of hours due to the action of large amounts of toxic substances, and most deaths occur due to circulatory failure. Severe poisoning focuses on lung damage and is prone to respiratory failure or MOF. Paraquat poisoning has no special antidote yet, so finding an antidote is the fundamental treatment for this disease. To stop the absorption of paraquat and reduce the inflammatory reaction of tissues is the key to save and treat this disease at present. Through the clinical treatment of this group of cases, I have learned that the treatment of paraquat poisoning should be done every second, and it is very important to take comprehensive measures such as gastrointestinal purification, blood purification and drug treatment before the transfer of paraquat ions to tissue cells reaches lethal concentration. As long as the treatment is timely and appropriate, a considerable number of patients can be successfully treated. Gastrointestinal decontamination is the key to stop the continued absorption of paraquat. These measures include emetic, gastric lavage, diarrhea and enema, and the sooner, the earlier and more thorough the better. According to clinical observation, for those who cannot do gastrointestinal decontamination in a timely and thorough manner after taking large amount of oral dose (more than 20ml), blue paraquat can still be observed in the stool in about a week. Blood purification is the key to stop the transfer of paraquat to tissues, and the best time to carry out blood purification within 12h should be seized, but blood purification should be carried out as long as the urine is positive for paraquat. However, attention should be paid to early and timely clearance, such as once pulmonary damage occurs, blood purification should be cautious because heparinization on the basis of pulmonary damage can increase exudation significantly. As for the clearance of inflammatory factors, the pros and cons should be weighed according to the lung exudation. From the comparison of the effect of blood purification in this group of cases, PE+CRRT or HP+CRRT has the best effect. PE generally requires only two plasma volume changes (about 2000-2500ml each time), and the urine test can become weakly positive. The experimental data shows that the effect is good and the clearance rate is high, and the urine test before and after perfusion is significantly lower than the concentration of paraquat. The rest of the blood purification measures are not effective. MOF is the main cause of death in this disease, generally respiratory failure is the most prominent, followed by liver and kidney. However, once the lung damage reaches severe respiratory failure (when the shadow of the lung lesion reaches 60% or more on chest X-ray or CT), death will be unavoidable. Therefore, reducing lung injury, eliminating acute chemical interstitial pneumonia and inhibiting acute interstitial lung fibrosis are the keys to reduce mortality. Therefore, it is advisable to treat with rational application of glucocorticoids and the use of ustekin or Isep, Asagil has a certain effect of inhibiting the inflammatory response. Free radical scavengers and antioxidants have certain auxiliary therapeutic effects and should be actively applied. Whether the so-called competitive antagonists such as vitamin B1 and insulin have a role to be further verified, as there are no obvious side effects, they are used for the time being. In addition, symptomatic treatment, nutritional support, to maintain the restoration of important organ function, is also quite important. Ventilator-assisted breathing can indeed prolong the survival time of patients, but it cannot reduce the mortality rate. In conclusion, the treatment of paraquat poisoning should be highly valued, and every second should be taken into consideration, and comprehensive treatment and proper measures should be taken in order to improve the cure rate.