New Concepts in Rescuing Organophosphorus Pesticide Poisoning

Organophosphorus pesticide poisoning is one of the common poisonings in rural areas of China, which is often a concern for medical personnel because of its toxic effects. Since the 1960s, our hospital has gone through three stages to rescue organophosphorus pesticide poisoning: before 1992, we used atropine as the main drug, emphasized atropinization, and said “we would rather overdose than underdose”, and prepared our own 2% atropine injection (each 1 ml contains 20 mg of atropine), which is enough to explain our guiding ideology and the dosage of atropine at that time; the second stage was from 1993 to 1996, mainly using antiphosphorus injection and chlorophosphine; the third stage was using pentoxyquinum hydrochloride and chlorophosphine; and the third stage was using pentoxyquinum hydrochloride and chlorophosphine. 1996, mainly with antiphosphorus injection and chlorophosphamide; the third stage was with pentamidine hydrochloride and chlorophosphamide. Since 1993, we have mainly adopted the new concept of “treating the root cause as the mainstay” put forward by Prof. Zeng Fanzhong of the Institute of Toxicology and Pharmacology of the Academy of Military Medical Sciences (hereinafter referred to as the “Academy of Military Medical Sciences”) and other experts, and combined with the experience of our clinical work, we summarized this new concept as “two words, two lines, two points and two maintenance amounts.” The two words are “two lines, two points and two maintenance amounts”. Two words” are “treating the root cause as the mainstay, treating both symptoms and root cause; taking cholinesterase as the core, not based on atropinization”; “two lines” are “application of reanimators and anticholinergic drugs”; “two points” are (1) the end point of treatment of reanimators is the cholinesterase activity in whole blood reaches 50%~60% (the method of measuring cholinesterase activity in whole blood of the military academy of science and technology is referred to as “the whole-blood paper method”; (2) the end point of treatment of anticholinergic drugs is atropinization; “two points” are (1) the end point of treatment of reanimators is the activity of whole blood reaches 50%~60% (the method of determining cholinesterase activity in whole blood of military academy of science and technology is referred to as “whole-blood paper method”; “two points” are The end point of anticholinergic drug treatment is atropine; “two maintenance two” refers to the maintenance amount of atropine in enzyme aging and intermediate syndrome. After our clinical confirmation in the past 10 years, it can really improve the rescue work of organophosphorus pesticide poisoning. Yu Jun, Department of Emergency Medicine, Lingwu People’s Hospital 【Treatment of the root causes and symptoms】 First, treatment of the root causes (a) The main mechanism of organophosphorus pesticide poisoning is that the phosphorus acyl group in organophosphorus pesticide combines with choline esterase to form phosphorylase (also known as poisonous enzyme), and the loss of the enzyme activity can not break down the acetylcholine, which leads to the accumulation of acetylcholine in the neuron synapses and neuromuscular junctions, and then produces mushrooms, nicotinyl-like, nicotinamide-like, and other symptoms. As a result, acetylcholine accumulates in the synapses of neurons and neuromuscular junctions, resulting in the three major symptoms of muscarinic, nicotinic and central nervous system. Therefore, the early and sufficient use of reanimator should be the main treatment. Atropine is only effective for muscarinic symptoms, but not for nicotinic and central nervous system symptoms. Therefore, the use of reanimating agent should be emphasized when rescuing this disease. (ii) Thorough gastric lavage Thoroughly removing the poison in the stomach is a very important part of rescuing this disease. Our experience is that the principle of “repeated gastric lavage and continuous drainage” should be adopted. The reason is: ① in the clinical observation after thorough gastric lavage a few hours, can still smell the strong odor of organophosphorus poisons from the gastric juice; ② military academy of science and technology has done experiments with dogs, confirmed the existence of the “enterohepatic cycle”, the absorbed poisons can be secreted through the bile ducts or the gastric mucosa and then secrete into the gastrointestinal tract; ③ some people have been testing the concentration of poisons in the blood and gastric juice at the same time, it was confirmed that even if the concentration of blood toxins is 0, it can be detected from the gastric juice many times, up to 118 times. They believe that this may be related to the toxic residue in the gastric mucosa; (4) In a case of 72-hour death in our department, there was still a strong smell of DDV after the stomach was cut open in the autopsy, and the smell filled the autopsy room of about 30m2. Zhang Shuji et al. of our university also encountered a patient who died in 11 days, and the autopsy found that there was still a DDV odor in the intestinal lumen solution. Our specific approach is: the first gastric lavage to 20000 ~ 30000ml is appropriate, the usual method is to wash until odorless, the author believes that “odorless” is not good to grasp, it is appropriate to make the first gastric lavage is too much, the patient is difficult to tolerate, such as tap water gastric lavage, can lead to hypothermia, so the first gastric lavage should be a quantitative amount. Afterwards, the stomach can be pumped once every 2 to 4 hours, each time 5000 ml. The gastrointestinal decompression can be sustained during the period between pumping. Generally, 1~2 times for mild patients and 4~5 times for severe patients. When the condition improves, then remove the gastric tube. Gastric lavage for comatose patients should be inserted into the tracheal tube before washing the stomach to protect the airway and prevent aspiration. After inserting the tracheal tube, then insert the gastric tube, there may be some difficulties, then you can relax the intubation balloon, use the laryngoscope to expose the pharynx, use the long forceps or tissue tweezers, send the gastric tube into the esophagus, generally can be successful. At the same time of using reenergizer, apply anticholinergic drugs, available atropine or pentylenetetrazol hydrochloride. Because this kind of drugs can rapidly relieve muscarinic symptoms, especially airway secretion, bronchospasm and pulmonary edema, and immediately improve airway patency. 【Centered on cholinesterase, not based on atropinization】 In the past, the main indicator for the treatment of organophosphorus pesticide poisoning was atropinization, which required the achievement of pupil dilation, facial flushing, dry mouth, dry skin, and increased heart rate. In practice, it is very difficult to grasp, often lead to overdose, and sometimes the symptoms of atropine overdose can be similar to the symptoms of organophosphorus poisoning, and misdiagnosed as atropine insufficiency, presenting a vicious circle. Since the adoption of cholinesterase as the indicator of treatment, we have objective basis for the application of repleting agents and anticholinergic drugs, and it is easier to grasp. Generally speaking, the activity of cholinesterase is restored to 50%~60% (whole blood paper slide method), as the indicator of treatment. However, at present, cholinesterase is only used as a diagnostic basis in general hospitals, but not as a therapeutic indication. As there are many ways to test ChE, you should know the test method used in your hospital and its normal value range. Cholinesterase is divided into true cholinesterase (erythrocyte cholinesterase) and pseudo cholinesterase (plasma cholinesterase). The former is derived from nerve cells and bone marrow erythrocyte system, stored in nerve cells, neuromuscular junction and erythrocytes, which breaks down acetylcholine, and accounts for 60% of the whole blood cholinesterase; the latter is derived from hepatocytes and glands, and is stored in neuroglia, plasma, liver and intestinal mucous membranes. The latter is derived from hepatocytes and glands, stored in neuroglia, plasma, liver and intestinal mucosa, the substrate for its decomposition is unknown, accounting for 40% of whole blood. Therefore, the assay methods are different, and erythrocyte, plasma and whole blood choline esterase are measured separately. Because of the simplicity of plasma cholinesterase detection, it has been adopted by many organizations. China’s standard testing method is to use whole blood ferric hydroxamic acid colorimetric method, and this method is applied to test the cholinesterase value in the grading of the severity of organophosphorus pesticide poisoning in China. The results of the whole blood paper slide method are consistent with the whole blood iron hydroxamic acid colorimetric method, which is simple and reliable, and can be used as the basis of clinical treatment, and can be used in primary health centers. No matter what method is used, clinicians must contact with laboratory department, consult with relevant experts if necessary, and find out the relevant value that can guide the treatment. For example, at present, some units use the method of detecting plasma cholinesterase, and the normal value is 4000~10000 units, according to the experience of some experts, when the activity of cholinesterase reaches 2000 units, a small amount of atropine should be discontinued to maintain, or else it should be overdosed. The normal value of cholinesterase has a wide range, and the lowest value should be taken as the basis for calculating the percentage. Special attention should be paid to the fact that some test values are calculated in % and some in units, all of which should be paid attention to in practical work and should not be misinterpreted. On the question of atropinization: atropinization has been used as an indicator for the treatment of organophosphorus pesticide poisoning, but Zeng Fanzhong et al. proposed that the indications for atropinization should be dry mouth, dry skin and heart rate between 90 and 100 beats/min. Recently, foreign monographs on atropinization also emphasize the above problems, and no longer emphasize pupil dilation and facial flushing, and about 1/3 of patients’ pupils may not be dilated at all. Anticholinergic drugs are symptomatic treatments, a measure to fight against acetylcholine crisis, to achieve glandular secretion suppression, heart rate is a little fast, it can indicate that acetylcholine is suppressed to a certain degree, in which dry mouth can indirectly indicate the suppression of tracheal secretion, the author focuses on observing the dryness of the mouth and the axillae with or without perspiration as the end point of the use of anticholinergic drugs. In this way, the problem of atropine overdose can be avoided. This is the basic treatment for organophosphorus pesticide poisoning. To facilitate clinical observation, the author put forward the idea of “two lines”, one is to use reagents to detect cholinesterase activity; the other is to use anticholinergic drugs and observe atropine signs. I. Use of reanimators There are only two kinds of reanimators in China, namely, chlorophosphidine and dephosphidine, and it is generally recommended to use chlorophosphidine at present. Chlorophosphamide is a compound of chlorine and diphosphamide is a compound of iodine. Since the molecular weight of iodine is larger than that of chlorine, the potency ratio of chlorophosphamide and diphosphamide is 1:1.6, so 1g of chlorophosphamide is equivalent to 1.6g of diphosphamide. Chlorophosphamide can be injected intramuscularly or intravenously, generally it is recommended to be injected intramuscularly, or slowly intravenously in case of shock (about 20-30 minutes).0.5g of intramuscular injection of chlorophosphamide can make the blood concentration reach 4mg/ml, and the optimal blood concentration is 9-14mg/ml, so the maintenance dosage is more suitable for 1.0g each time. The half-survival period is 1.0~1.5 hours, so the drug can be given every 2 hours during the initial treatment, and the cholinesterase activity can be monitored at the same time, and the drug can be stopped and observed when it reaches 50%~60% (whole blood cholinesterase). There are three types of treatment process: (1) Increasing type: Cholinesterase increases gradually with the use of compounding agent to achieve the therapeutic goal; (2) Fluctuating type: The author once encountered that cholinesterase increased from 40% to 60% after the use of compounding agent, but it decreased to 40% after 2 hours of review; (3) Ineffective type: After the first dose, the cholinesterase will be decreased every 2 hours after the first dose is given.