Pathology of organic phosphorus poisoning
In the synapse slot, after causing depolarization in the post-synapse membrane, Acetylcholine is broken down by Acetylcholinesterase into Acetate and ineffective choline, ending the depolarization process.
Organic phosphorus-based insecticides are widely used in agriculture, they are used to kill insects through direct or systemic contact with plants and plants. In addition, these drugs are also used to kill some parasites in humans and animals such as lice and lice. As the development and use of these drugs become more and more popular, the poisoning of this drug is increasing in foreign countries as well as domestically. Organic phosphorus can cause potentially fatal symptoms. Therefore, organophosphorus exposure is a dangerous type of poisoning, so it is necessary to be diagnosed early and treated promptly, properly and fully to avoid death.
Organic phosphorus poisoning is more common in rural areas than in cities because it is widely used here, especially in agriculture, and occurs more often in summer than in winter. More in young people than in women. In people with chronic poisoning usually have lower poison concentrations than people who have never been poisoned. In the elderly, pregnant women and women with pre-existing chronic diseases often suffer more severe poisoning than ordinary people.
Mechanism of pathogenesis
Outline of synaptic conduction
When the neurone is stimulated, the cell depolarizes, the pulse is carried along the axon to the end, where the pulse creates a new stimulus that causes the Brown-moving Acetylcholine bags to collide with each other to release Acetylcholine, Acetylcholine pass through the synapse cleft to come into contact with the receptor of the post-synaptic membrane (muscle cell membrane ...), causing depolarization here, and causing muscle contraction.
In the synapse slot, after causing depolarization in the post-synapse membrane, Acetylcholine is broken down by Acetylcholinesterase into Acétate and ineffective choline, ending the depolarization process.
Mechanism of action of organic phosphorus-based pesticides
The organic phosphorus-based insecticide enters the body in combination with acetylcholinesterase to form a stable complex, the dissociation rate is considered to be zero. Therefore, acetylcholinesterase completely loses its hydrolysis effect, Acetylcholine.
Acetylcholinesterase is inactivated, only compensated for by Acetylcholinesterase neogenesis, which occurs very slowly after days, possibly weeks or even months.
Acetylcholine, which is not inactivated by Acetylcholinesterase, accumulates in the normal places where it is secreted in an excited state as well as in a state that thinks it is:
Interference practice of the entire sympathetic system.
Sympathomimetic ganglion (both orthogonal and parasympathetic) and motor plate interference.
Interrelated central nervous system.
Mechanism of direct action:
On Acetylcholine receptor sites. If the organic phosphorus-based insecticides are high in concentration and long-acting, the degenerative motor plate can be difficult to recover.
Effect of organic phosphorus-based pesticides
Due to the irreversible cholinesterase inhibitory mechanism, organic phosphorus produces the following three effects:
Effects in the form of Muscarine:
As a result of the stimulating effect on parasympathetic practice interferences, it causes signs of parasympathetic euphoria on smooth muscles, glands, heart ... The central nervous system suffers from this nonspecific effect. . (Stimulating or inhibiting)
Effects in the form of Nicotine:
The result is the effect on the sympathetic ganglia interference and a striated motor plate of which the most important is the respiratory muscle. Effects Nicotine is stimulating initially, lasts a short time, but then paralyzes the affected organs when the poisoning is severe and prolonged.
Effects on the central nervous system:
There are stimulants and then paralyzed when the intensity and duration of intoxication increases. The most important is the effect on eclipse centres.
Muscarine effects are easily neutralized by Atropine, less affected by oximes.
Effects Nicotine is influenced very little by Atropine and Oximes except for the movement plate, very well influenced by Oximes.
The effect of the central nervous system is quite well influenced by Atropine, not affected by Oximes.
Invasion, absorption, modification and elimination of organic phosphorus-based pesticides
Most of the organic phosphorus-based insecticides are strongly soluble in lipids, so they are easily absorbed through the skin and mucous membranes such as eye, digestive and respiratory mucosa, they are usually used in aerosol form after has been diluted hundreds, thousands of times.
The drug penetrates in all ways:
Skin, mucous membranes, especially when there are available lesions such as anointing scabies, eye splashes, skin contact when using drugs:
Respiratory: Such as inhalation of medicinal vapours when opening a closed container, inhalation of aerosols when injecting drugs
Gastrointestinal: Do commit suicide or mistakenly drink.
The absorption is very easy by all the above-mentioned lines very quickly and completely, the fastest is through the respiratory tract, and the slowest is through the skin. They can be partially neutralized by alkali and Hypochlorite.
In the body, they are degraded by hydrolysis and oxidizing enzymes, especially in the liver, but this degradation is very slow. For organic phosphorus combined with Acetylcholinesterase, only discharged in degraded form into Paranitrophenol.
Of the organic phosphorus, this phot (parathion) has the greatest toxicity, methyl parathion (wolfatox) on average, and malathion, on average. for example, poisoning dose of parathion is <5mg / kg body weight, methyl parathion is 5-50mg / kg body weight, malathion is 50-500mg / kg body weight. This toxicity increased dozens of times when two drugs were combined.
Potential time varies according to many factors.
Sugar penetration: from fast to slow: respiratory, digestive, skin.
The severity of intoxication:
The heavier the shorter the potential time. For example, on average poisoning, clinical symptoms usually appear after 1 hour, but severe cases are shorter after only 15-30 minutes and in very severe cases, from 30 minutes to 1 hour. died.
The younger the age the shorter the latency (because of the poor AchE concentration). In the elderly, symptoms of poisoning get worse.
Chronic infection factors:
People who had previously had potentially mild poisoning were also poisoned more quickly. People were chronically poisoned; the sign of poisoning was quicker and worse if there was an acute infection.
Stomach hungry, drinking:
Also poisoning by the gastrointestinal tract occurs more quickly.
Combining many toxic sugars:
L short latency.
The order in which the signs appeared
Muscarine-type control marks appear first. Nicotine and CNS signs are more difficult to separate and appear more slowly. But if severe poisoning, all 3 types of signs appear simultaneously.
The evidence marks on the organs
With the clearest mark of Muscarine, conjunctival hyperaemia, pupil atrophy may be as strong as a pin tip, but still responds to light, dysregulation, decreased intraocular pressure. The pupil atrophy is a very sensitive Muscarine mark, so it can be one of the markers to evaluate the severity at first unless the eye is directly affected by the insecticide because the drug is sprayed directly into the eye. and severe but may indicate mild systemic toxicity.
It is also the place where Muscarine signs are evident, congested, and sweating.
Muscarine control mark. Saliva is secreted a lot, increasing gastrointestinal secretion, especially gastric juice, increased peristalsis, smooth spasms of the digestive tract causing abdominal cramps, difficulty swallowing, nausea, vomiting. If severe poisoning affects the central nervous system, there is a sign of unconscious defecation.
Expression of three types of effects: Muscarine, Nicotine, CNS. The muscarine effect increases bronchial secretions causing coughing, increased secretion of phlegm, obstructing the bronchi to make it difficult to breathe, listening to small, wet explosions, and spasm of bronchial smooth muscles, causing more difficulty breathing.
Effects Nicotine paralyzing stage will paralyze the respiratory muscles, causing severe respiratory failure. This effect also causes tongue drop, causing tongue drop, and block the airways.
Effects of the central nervous system in the stage of paralysis will paralyze the respiratory centre, increase the effects mentioned above.
Acute respiratory failure, which is a natural manifestation of severe intoxication, is the primary cause of death.
Also exhibits a combination of 3 types of effects. Muscarine effects slow pulse, lower blood pressure.
Effects of Nicotine and CNS: causes sympathetic enhancement and stimulation of the cardiovascular regulatory centres, at least during the stimulation phase leading to rapid pulse, high blood pressure. During the paralysis phase of Nicotine, CNS, the signs can be reversed, which is cardiovascular collapse.
Manifestations of Nicotine and CNS effects.
Muscle fibrillation, actually vibrating muscle fibres, is an important sign that the poisoning is quite serious. It is important to look carefully to detect the chest, abdomen, arms, shoulders and thighs. It should be distinguished from muscle fibrillation because of cold
Stage muscle paralysis: muscle weakness then muscle paralysis, the most important is the respiratory muscles stop breathing. If prolonged poisoning, causing the movement plate to degenerate, the muscle paralysis will last a long time.
Central nervous system mark:
B premature now because of all 3 types of effects.
Muscarine and Nicotine induce cerebral gas deficiency and the direct CNS effect of organic phosphorus.
In the first phase is stimulation, restlessness, convulsions.
In the final stage, tendon reflexes decrease, then the loss of reflexes, coma, paralysis of the ecliptic nerve centres.
Fever can sign the CNS toxicity of organic phosphorus.
Can heal by itself if slightly poisoned. But if the poisoning is quite severe, the signs will increase gradually leading to coma, respiratory failure and death.
Get the right treatment
Muscarine markers decreased and disappeared first, then two signs of Nicotine and CNS also gradually improved. But if poisoning is too severe or treated slowly, initially the Muscarine symptoms decrease, the patient may wake up, but then the Nicotine markers and CNS become worse and lead to respiratory failure and death. death.
The main cause of death was a respiratory failure in most cases.
Implementing the quadrants
Based on the questioning of the patient, ask the patient's relatives, especially based on the special odour of the pesticide in the breath, in the vomit, on the clothes, on the patient's skin, based on specific clinical signs Muscarine markers with or not combined with the markers of Nicotine and CNS.
Subclinical is needed in mild cases, with unknown toxicity by assaying plasma butyrocholinestérase or acetylcholinesterase in erythrocytes. These two rates decreased. In fact, this reduction in two rates is not a true reflection, but the rate of Acetylcholinesterase in tissues is the ratio of the severity of poisoning: The rate of cholinesterase reduction <30% is mild poisoning, 50% is moderate poisoning. , reduction of> 70% is heavy.
Diagnose the severity
The patient's condition.
Sugar poisoning. Especially the drink and an empty stomach.
The amount of drug has entered the body.
Poisoning conditions (self-poisoning, or poisoning).
Time from poisoning to elimination of the drug from the body (gastric lavage) and proper treatment.
Treatment of the lower line well or not.
In short, all these conditions cause the greater the amount of drug to be absorbed into the body, the slower the proper treatment, the more severe the aggravation.
Severity diagnosis also bases on clinical signs, Nicotine markers and severe CNS, the higher the severity.
The decrease in the ratio of butyrylcholinesterase and Acetylcholinesterase does not completely reflect the severity.
In fact, asking the patient and doing a physical examination can quite accurately estimate the severity.
Light: Muscarine is light or pure.
Medium: Severe muscarine + Nicotine sign and moderate central TK.
Severe: Nicotine and CNS severe, muscarine markers may be present or not. Or the sign of moderate poisoning + severe factors due to questioning.
DDT poisoning (Dichloro-Diphényl-Trichloetan):
As a derivative of chlorobenzene, it is impermeable to the skin and only penetrates the digestive mucosa. Symptoms of poisoning are gastrointestinal disturbances, appearing 1-6 hours later such as vomiting, diarrhoea, abdominal pain. Effects on the nervous system, causing headache, paraesthesia, tremors, convulsions, seizure intensity depending on the concentration of DDT in the brain. Mild to severe signs are muscle fibrillation, increased reflexes, generalized spasms, convulsions, respiratory failure, apnoea, cardiac arrest and death.
As a derivative of Cyclohexane, also causes toxicity symptoms like DDT, but has a shorter latency.
Clinically resembles organic phosphor poisoning. The mechanism is the same. Treatment with Atropine, but do not use PAM because it aggravates poisoning.
The principles of treatment
Determination of toxicity: to determine whether it is organic phosphorus or not, based on asking patients, family members or people around; This is an insecticide that differs from the other commonly used drugs today, fungicides and herbicides. Drug names are often based on a list of commonly available organic phosphorus drugs on the market. Colour, taste and texture of the drug: Usually presented as a liquid, white, especially when mixed with water, has a milky white colour and has a very special strong smell, different from the smell of antiseptic. other coincidence.
Limit the number of toxins absorbed into the body and eliminate the toxins from the body.
Neutralizes the effect of the poison that has been absorbed.
Release of Acetylcholinesterase from organic Acetylcholinesterase-Phosphor complexes.
Symptomatic treatment is very important at times and can save the patient's life, such as epilepsy, low blood pressure, and apnoea using mechanical ventilation.
Eliminate toxins: T Uy along with poisoning:
Remove medication from the skin and mucous membranes: remove contaminated clothing, wipe the skin off, wash skin thoroughly with soap, or preferably water mixed with Bicarbonate or Hypochlorite.
If the medicine gets in the eyes, wash the eyes thoroughly.
If poisoned by inhalation, immediately remove the patient from the poisoned area, especially the patient to a cool, ventilated area to remove the drug through the respiratory tract.
Gastric lavage: applies to gastrointestinal poisoning. To be effective and not dangerous, it should be done in the following cases:
Rinse as soon as possible. Perform 6 hours before the poisoning.
The patient is not unconscious.
Before rinsing to inject Atropine first, the appropriate dose with the severity is usually 2mg and should be done at least 4 minutes (if intravenous) and 10 minutes (if intramuscular), as gastric lavage can do enhances the existing parasympathetic states and causes a lethal inhibitory reflex.
Gastric lavage should be done gently, avoiding further parasympathetic stimulation. Use water mixed with Bicarbonate, the amount of rinse is quite a lot until the odour is gone. Usually up to a few dozen litres of gastric lavage.
Early high dose atropine:
Mechanism of Action: Atropine is the most effective antagonistic inhibitor in acute organic phosphorus-based pesticide poisoning.
Strong antagonism on the Muscarine-type control markers expresses peripheral organs of practice.
The antagonistic effect is weaker on the CNS markers, on the sympathetic ganglion Nicotine markers, and is completely ineffective for the rhabdomyolysis due to the action plate.
Rate of action: Average dose of 2mg Atropine Sulphate or Tartrate intravenously: 1 minute after starting to work, if intramuscular or subcutaneous, 8 minutes later, and maximum effect after 6 minutes for IV and 35 minutes if intramuscular or subcutaneous.
Time and dosage of Atropine: Once the intoxication has been confirmed, then inject
Atropine as soon as possible.
Mild Poisoning: Even though there is no sign of poisoning, still inject 1-2mg of Atropine intramuscularly, repeat if needed 30 minutes apart. until muscarine is gone and no Atropine is visible. Thereafter, maintain mild Atropine satiety for 24 hours or more. Note: reduce the dose first, reduce the time after.
In case of moderate poisoning: intravenous injection of 3-5mg Atropine, repeat 2-4mg dose at intervals of 10-15 minutes until Muscarine sign disappears and mild Atropine satiety. Then maintain mild or moderate Atropine for 48 hours or more.
Severe poisoning: Especially when having difficulty breathing, convulsions, or coma, give 5 to 8mg of Atropine intravenously immediately. Repeat dose of 5mg at intervals of 5-8 minutes until convulsions have ceased and decreased bronchial secretion and salivation. Then return to the treatment plan for moderate-severe poisoning, until all signs of Muscarine are gone and there is no Atropine. Maintain moderate or high Atropine for 48 hours or more.
Response to Atropine and monitoring of patients: Early high dose Atropine improves the clinical picture, loses the mark of Muscarine, improves pulmonary ventilation, slows down the nerve centre, improves coma jerky and shortness of breath, but in very severe cases the improvement is only temporary. The patient was subsequently paralyzed with respiratory paralysis and Atropine was completely ineffective for motor paralysis.
For moderate or severe poisoning cases, when using Atropine at high doses, the patient should be closely monitored to adjust the dose, to detect signs of increasing exacerbation, when reducing Atropine dose. Close monitoring will detect the reappearance of poisoning signs.
Mild toxicity: dry mouth, lips, throat, causing difficulty swallowing, subjective hot feeling, a flushed face, rapid heart rate, difficulty urinating, dystrophy, making it difficult for near vision.
Moderate poisoning: the above symptoms increased, especially the peripheral temperature is high, drowsiness, constipation, urinary retention, dizziness, restlessness, talk a lot.
Severe poisoning: in addition to the above signs, signs of severe CNS are more pronounced with high fever, disorientation, psychotic hallucinations, hyperstimulation, delirium.
Principle of Atropine dose reduction: The dose should be reduced slowly and closely monitored for recurrent Muscarine marks or severe Nicotine signatures; therefore, it is necessary to reduce the dose in small increments and to reduce the dose before reducing Atropine injection.
Pralidoxime (P2AM = Pyridine 2 - Aldoxime Methiodide):
Mechanism of action: Pralidoxime has properties that act with the AchE - PHC complex to combine with organic phosphorus to help release AchE to react freely. But oximes need to be used early to be effective. The effect of oximes is most evident on the movement plate.
Speed of action: Intravenous injection, P2AM works very quickly, muscle weakness and muscle tremor decrease after only 5-30 seconds, maximum after 5-10 minutes.
Time and dosage: P2AM is injected 36 hours before. Intravenous injection of 1000-
2000mg slow (500 mg/min) can be repeated many times. However, in the case of heavy poisoning and phosphorus sources accumulate in the body for a long time, as in the case of slowly washed gastrointestinal poisoning, high doses of PAM can be used and lasts up to 5-7 days. In the case of moderate poisoning, the dose of PAM is 2 to 4 grams/day by intravenous route divided into 4 times. In the case of severe poisoning and accumulation source, use a combination of high doses and intravenous injection to maintain a high dose of PAM in the blood, the usual dose is 6 to 8 grams/day and lasts for weeks.
Respond to P2AM: the mark of the most responsive motion plate.
Respiratory clearance: aspiration of sputum to release signs of mild respiratory failure, if there is little response to treatment, an endotracheal tube should be placed.
Oxygen: When there is respiratory failure, high supply volume 8-10L / min or 3-4L / min, depending on severity (if there is chronic respiratory failure, oxygen supply is low 1-3L / min.)
Artificial respiration: is the necessary treatment means in severe cases, incomplete response to treatment, acute respiratory failure. CPR should be extended for a very long time, possibly 2-3 weeks. Therefore, it is necessary to have a new ventilator to ensure good and prolonged artificial respiration. It is necessary to clear the trachea and provide mechanical ventilation in a timely and timely manner.
Aminophylline or similar drugs are prohibited because Aminophylline has side effects of vomiting, dizziness, mental confusion, hypotension convulsions.
Shock resistance: by means of routine caution when taking antihypertensive drugs. Experience shows that if the other stages are solved well, the problem of shock resistance is less raised. If the blood pressure drops, it is necessary to rehydrate and give blood pressure drugs such as Dopamine and Dobutamine.
Infusion: not intended to discharge toxins but only to resist shock if any, to compensate for water loss through perspiration, vomiting, secretion and nourishment. The type and number of fluids will vary depending on the need. Infusion is also a means to introduce Atropine into the body and to comfort the patient.
Anticonvulsants: anxiety, anxiety, antiepileptic drugs such as diphenylhydantoin, mild sedative drugs, can be used to avoid the paralysis of the biological nervous organs. Morphine is prohibited for respiratory distress which is usually facilitated by Muscarine syndrome.
Superinfection prophylaxis: especially in the lungs, antibiotics should be used with a broad spectrum of activity such as the 3rd generation Cephalosporin groups such as Cefotaxime, Ceftriaxone dose 2-3 grams/day or Quinolone generation 2 such as Ofloxacin or Ciprofloxacin by intravenous pass.
Avoid foods containing lipids such as milk because it increases the absorption of the drug.
Follow up the patient
Monitor closely not only when the patient is lethargic, but even when awake and responding to treatment.
Follow-up for signs of serious complications and complications appearing, or severe signs that reappear after Atropine dose reduction, to have time management attitude.
Strict management of the distribution and use of organic phosphor-based pesticides.
Dissemination of the concept of drug toxicity widely to the general public, especially farmers and drug preservatives.
Disseminate major features of treatment down to the lower level. Especially the intestinal rinsing and early treatment with atropine with high doses.
If treated early and properly, mild cases have a good prognosis, but the prognosis for severe cases is still bad, especially with long-term respiratory failure. The cases of severe poisoning and acute coma and very early eczematous central disorder causing rapid death without resuscitation are often dead on the spot or on the way of transporting the patient to the hospital with cardiac arrest or discontinuation. breath.
Lack of organic phosphorus-based pesticide poisoning is a serious medical emergency that needs to be properly assessed in terms of severity, management, and early resolution with measures to remove toxins. High dose, repeated repetitive atropine, high and continuous dose of P2AM and need coordination and support for artificial respiration especially prolonged mechanical ventilation to prevent respiratory depression and apnoea in addition, measures to prevent stunning, prevent superinfection and nurture are also important supportive measures to help save the patient's life.