Organophosphate Toxicity

What is Organophosphate Toxicity?

Organophosphates are a type of chemical made from phosphoric acid and alcohol. They are commonly found in pesticides and herbicides, and can also be used in chemical warfare. Most people come into contact with organophosphates through the use of insecticides and herbicides. If organophosphates enter the body, they can block an enzyme called acetylcholinesterase (AChE), which leads to the overproduction of a chemical in the brain called acetylcholine. This can cause a condition known as cholinergic toxidrome, which affects various parts of the body and brain. Symptoms can start within minutes and can take several weeks to ease.

While organophosphate poisoning has decreased in developed countries due to stricter regulations on these chemicals, it remains a concern in developing countries. Pesticides, which often contain organophosphates, are commonly used in suicide attempts in these parts of the world because they are deadly and widely available. Therefore, in nations with a heavy reliance on agriculture and looser regulations on pesticides, organophosphate poisoning is more common. Research has shown that poisonings that are done on purpose generally lead to higher death rates than accidental exposure. The leading cause of death is respiratory failure caused by an overproduction of mucus and tightening of the airways. Prolonged toxicity and neurological issues like the intermediate syndrome are also well recorded. In developed countries, it’s crucial that healthcare workers can identify this toxicity, as organophosphates could potentially be used in acts of bio warfare. Antidotes and extensive supportive care are needed to effectively treat organophosphate toxicity and avoid severe illness and death.

The first organophosphate pesticide was created in the mid-1800s, but became more widely used after World War II. In the 1930s, they were first used as insecticides before the German military started using them as neurotoxins. The organophosphate chemicals sarin and VX were used as weapons by the Japanese cult Aum Shinrikyo in 1994 and 1995. The first reported case of VX being used in a bio warfare act was in 1997 with the murder of Kim Jong-nam at an airport in Malaysia. In March 2018, Sergei and Yulia Skripal were poisoned in England, causing also a police officer to be hospitalized due to exposure. This incident was marked by the use of an organophosphorus agent known as Novichok.

What Causes Organophosphate Toxicity?

Organophosphate toxicity refers to the harmful effects that can occur from exposure to certain chemicals, typically found in pesticides. This exposure can happen in various ways, such as through a person’s job, accidentally coming into contact with pesticides, intentional harmful exposure, or even chemical attacks. There are over 50,000 different compounds that have been developed and tested for use as pesticides.

In the United States, 37 types of organophosphate pesticides have been approved for use, each with the capacity to cause toxicity. In some parts of the world where regulation and control of chemicals are not as tight, more types of these pesticides are used. Exposure to these chemicals can happen by breathing them in, ingesting them, or through skin contact. While breathing in or ingesting these chemicals allows them to quickly get into the body, the effects of skin contact can vary widely.

The harmful impact, the time it takes for symptoms to appear, and how long they last all depend on how much was ingested, the way it entered the body, and the specific chemical involved. The World Health Organization (WHO) separates these chemicals into 5 groups, starting from “Extremely hazardous” to “Active ingredients unlikely to present acute danger in normal use.” This grouping is done based on a statistic called the median lethal dose (LD50), which measures how much of the chemical is lethal to 50% of rats exposed. However, this measurement doesn’t do a great job differentiating between chemicals in the same group that might be more toxic than others.

Risk Factors and Frequency for Organophosphate Toxicity

Data reviewed from the Toxic Exposure Surveillance System (TESS) showed that incidents involving exposure to a chemical called organophosphate peaked in 1997 with over 20,000 cases. However, by 2020, this number significantly dropped to around 2,000 cases, with no deaths reported. A big reason for this decrease was a decision by the U.S. Environmental Protection Agency to limit the use of organophosphate insecticides in homes between 2000 and 2005.

However, it’s important to note that these numbers, gathered from poison control centers, might not fully capture the real number of exposures in the U.S. This is because the information is either reported by the affected individuals themselves or comes from healthcare providers’ reports, both of which might underestimate the number of incidences or not correctly identify the specific compound involved.

Determining the real rate of organophosphate exposure worldwide is a challenge. We do know that pesticide self-poisoning, which includes organophosphates, affected about 372,000 people globally in 2007, making up about a third of all suicides worldwide. The World Health Organization estimated that unintentional pesticide poisonings in 1990 led to about 20,000 deaths, with more recent data from 2020 estimating about 740,000 such poisonings and around 7,500 deaths across 141 countries. However, the true numbers may be even higher due to problems with reporting and limited data.

Signs and Symptoms of Organophosphate Toxicity

When dealing with suspected cases of toxicity, it’s crucial to identify the specific substance involved and timing of exposure. This is particularly important in cases of intentional ingestion. If possible, try to obtain the pesticide container to provide information to professional toxicologists or the Poison Control Center. The time when symptoms appear and how serious they are can vary depending on several factors. These factors include how the exposure happened, the amount or dose, and the specific organophosphate compound involved.

People with severe organophosphate toxicity may show signs like unresponsiveness, small pupils, trembling, and sweating. They may also experience vomiting, diarrhea, excessive saliva, tears, and loss of bladder control. If organophosphates have been intentionally ingested, a smell of garlic or solvents may linger.

Two useful ways to remember the signs and symptoms of organophosphate poisoning and the associated receptor are the days of the week and the ‘DUMBELS’ mnemonic:

Monday = Dilated pupils
Tuesday = Rapid heartbeat
Wednesday = Weakness
Thursday = High blood pressure
Friday = Muscle twitchings

D = Diarrhea/sweating
U = Urination
M = Small pupils
B = Wheezing/excessive mucus in lungs
E = Vomiting
L = Tears
S = Salivation

Additional immediate symptoms may include anxiety, confusion, sleepiness, mood swings, seizures, hallucinations, headaches, insomnia, memory loss, and problems with breathing or heart rate. In fatal cases, the most common cause of death is failure to breathe due to constricted airways, excessive lung mucus, central respiratory depression, and weakened or paralyzed respiratory muscles. Those who survive acute poisoning may face other long-term complications.

Testing for Organophosphate Toxicity

When diagnosing organophosphate poisoning, which is a type of poisoning caused by certain pesticides or nerve gases, it’s crucial that doctors rely on their observations and start treatment as soon as possible, often before they receive the results from laboratory tests. If the patient shows symptoms such as small, pinpoint pupils, excessive sweating, and trouble breathing – or if they smell like garlic or petroleum – these can be telltale signs of organophosphate poisoning, even if the patient doesn’t recall being exposed to these substances.

Sometimes, doctors might give a small dose of a medicine called atropine if they suspect organophosphate poisoning, but aren’t sure. If the patient’s symptoms improve after the dose, then that ties the symptoms to organophosphate poisoning. However, this is not utterly reliable, especially in severe cases, and sometimes patients might not respond to the small dose, leading to a “false negative”.

Laboratories can measure the activity of certain enzymes called cholinesterases, which give an indication of the severity of organophosphate poisoning. However, these tests can be slow, complicated and the results can depend on a range of factors including the specific type of organophosphate and the patient’s overall health.

In particular, a type of cholinesterase found in red blood cells, known as RBC AChE, is known to closely link with the symptoms of organophosphate poisoning. However, they need to collect the blood sample in a certain type of tube, as some chemicals can interfere with the enzymes and skew the results.

During this process, doctors may also perform a range of other important tests to check the patient’s overall health. These can include a complete blood count which measures the cells in your blood, tests for basic metabolic functions and organ health, glucose levels, and in certain situations, a pregnancy test. They could also monitor the patient’s heart activity using a test known as an electrocardiogram, which often shows slow heart rate due to the effects of organophosphate on the nervous system.

Treatment Options for Organophosphate Toxicity

Before dealing with patients with organophosphate toxicity, which is a type of poisoning that can occur from exposure to certain pesticides or nerve gases, medical professionals need to protect themselves by wearing personal protective gear. This is done to avoid contamination from the substances the patients have been exposed to. Once the medical team is safely equipped, the next step is cleaning the patient. The patient will be washed thoroughly with soap and water several times to remove any remaining toxins. Special care must be taken around any body fluids, like vomit or diarrhea, as the harmful substances can be found in them. The patient’s clothes need to be discarded and their hair might have to be cut if it can’t be cleaned properly.

However, if the patient’s condition is severe, these cleaning procedures should not delay urgent medical treatment.

Ensuring the patient can breathe properly is a top priority when treating organophosphate poisoning. Some patients may need a tube placed in their airway due to difficulties breathing, seizures, or excess secretions. It’s also important to monitor the patient’s heart rhythms and oxygen levels during this time.

Atropine is a medication that is often used to treat organophosphate poisoning. It works by competing with a chemical called acetylcholine in the body, helping to reduce symptoms. If the patient doesn’t initially respond to atropine, the dose may be increased until the patient’s symptoms subside.

The goal of using atropine is to improve heart rate, blood pressure, and breathing. Patients with severe poisoning may need large amounts of atropine over an extended period of time. As atropine does not improve all symptoms associated with organophosphate exposure, patients must be closely monitored for issues with muscle function and breathing.

Another treatment for organophosphate poisoning is a medication called pralidoxime (2-PAM), which works by reactivating certain enzymes in the body and breaking down the toxin. However, the timing of this medication is crucial, and its effectiveness can vary based on the specific substance the patient was exposed to. There’s some debate about the effectiveness of pralidoxime, but it is generally recommended as a part of treatment.

Before administering pralidoxime, atropine should be given to the patient to prevent a deterioration of symptoms. The administration of pralidoxime needs to be done cautiously to prevent complications like cardiac arrest. Following an initial dose, the medication may need to be given continuously for several days.

For patients experiencing seizures, medications known as benzodiazepines may be given. There is also a possibility of using procedures like hemodialysis to remove the poison from the patient’s body, but this can depend on the specific type of organophosphate involved. Patients who have been poisoned should stay in the hospital for at least two days to be closely monitored, particularly for respiratory problems. However, patients who show no symptoms for 12 hours may be released from the hospital.

When a patient comes in with a complicated set of symptoms, it’s really important for the doctor to fully understand all the possible causes or conditions that might be causing these issues. Here’s a wide-ranging list of potential problems:

Gastroenteritis (an intestinal infection causing diarrhea, cramping, nausea, vomiting, and fever)
Myasthenia gravis (a chronic auto-immune disease that weakens the muscles)
Eaton-Lambert syndrome (a disorder where the nerves don’t communicate effectively with the muscles)
Guillain-Barre syndrome (a rare neurological disorder where the body’s immune system attacks the nerves)
Botulism (a rare, but serious illness caused by toxins that attack the body’s nerves)
Mushroom toxicity, specifically from the Clitocybe and Inocybe mushrooms
Nicotine poisoning, which includes something called green tobacco sickness
Hemlock poisoning (caused by a plant called Conium maculatum, or poison hemlock)
Carbamate toxicity (usually a result of being exposed to certain pesticides or medications)
And various types of medication or drug toxicity – including Carbachol, Methacholine, Arecoline, Bethanechol, Pilocarpine, Pyridostigmine, and Neostigmine

What to expect with Organophosphate Toxicity

The death rates caused by organophosphate insecticides, which are a type of bug-killer, can vary greatly around the world, ranging between 2% and 25%. The bug-killers most commonly related to deaths are fenitrothion, dichlorvos, malathion, and trichlorfon. The most common cause of death in these cases is when a person’s lungs stop working properly.

In 1993, a system was developed in India called the Peradeniya Organophosphorus Poisoning (POP) scale to determine how severe a case of organophosphate poisoning is and what kind of outcome might be expected. This was particularly useful in India because organophosphate toxicity was common and resources for handling severe cases were limited. The POP scale looks at six factors: pupil size, involuntary muscle twitching, breathing rate, slow heart rate, level of awareness, and seizures.

Healthcare professionals can use the POP scale before treating a patient for organophosphate poisoning. A higher score on the scale is usually related to worse outcomes, which may include death, the need for breathing support, or requiring high amounts of atropine, a medicine used to treat these poisonings, within the first day. However, the scale can’t predict the development of intermediate syndrome, a type of delayed reaction that may occur after poisoning.

Another study categorized organophosphate poisoning based on the POP score into three categories – mild (POP score of 0 to 3), moderate (POP score of 4 to 7) and severe (POP score of 8 to 11). Most patients (78.33%) had a mild case, while 21.66% had moderate cases, and no cases were severe. However, any patient that fell into the moderate category required breathing support, and there was a 30.8% death rate for these patients.

Possible Complications When Diagnosed with Organophosphate Toxicity

A situation called “intermediate syndrome” is a condition that leads to muscle weakness and can result in problems with breathing, without showing other typical signs of nerve or muscle issues. This usually shows up 24 to 96 hours after the start of organophosphate poisoning, and after the initial crisis period has ended. It is associated with muscle weakness near the center of the body and issues with nerves in the head, possibly leading to breathing problems. Despite these issues, patients are typically alert unless they are suffering from lack of oxygen or other complications. This syndrome can last for several weeks.

The muscles that bend the neck are often the first ones affected by this syndrome, so it’s crucial to watch closely for these signs. An easy way to check for this is to ask patients to lift their heads from the bed. It’s also worth noting that not everyone who gets the intermediate syndrome will experience problems with breathing. We still do not totally understand how this syndrome works, but it’s thought to come from issues in the junction where nerves and muscles connect.

An issue with the peripheral nerves can also show up days to weeks after severe poisoning, especially with certain chemical substances, including chlorpyrifos, dichlorvos, isofenphos, and methamidophos. The problem seems to come from inhibition of an enzyme involved with breaking down a major component within nerve tissue cell membranes. People with this condition can experience cramping in the leg muscles, numbness at the ends of their limbs, and unusual sensations in their limbs, which can develop into the loss of reflexes. If they survive this condition, they may still experience mental deficits like confusion, memory loss, lethargy, psychosis, irritability, and symptoms similar to Parkinson’s disease.

Preventing Organophosphate Toxicity

It’s important for patients to understand the correct way to store and handle organophosphates, a type of chemical. It’s crucial to remember that these chemicals should never be moved from their original containers to containers without labels. Those who handle these chemicals should always wear appropriate safety gear to protect both themselves and others around them. This is essential for everyone’s safety.

Frequently asked questions

Organophosphate toxicity is a condition that occurs when organophosphates, which are chemicals commonly found in pesticides and herbicides, enter the body and block an enzyme called acetylcholinesterase. This leads to the overproduction of a chemical called acetylcholine in the brain, causing a condition known as cholinergic toxidrome. Symptoms can range from mild to severe and can affect various parts of the body and brain.

Organophosphate toxicity is relatively common, with thousands of cases reported in the United States and hundreds of thousands of cases globally.

Signs and symptoms of Organophosphate Toxicity include: - Unresponsiveness - Small pupils - Trembling - Sweating - Vomiting - Diarrhea - Excessive saliva - Tears - Loss of bladder control - Smell of garlic or solvents if intentionally ingested To remember the signs and symptoms, two useful mnemonics are: Days of the week: - Monday: Dilated pupils - Tuesday: Rapid heartbeat - Wednesday: Weakness - Thursday: High blood pressure - Friday: Muscle twitchings DUMBELS: - D: Diarrhea/sweating - U: Urination - M: Small pupils - B: Wheezing/excessive mucus in lungs - E: Vomiting - L: Tears - S: Salivation Additional immediate symptoms may include: - Anxiety - Confusion - Sleepiness - Mood swings - Seizures - Hallucinations - Headaches - Insomnia - Memory loss - Problems with breathing or heart rate In fatal cases, the most common cause of death is failure to breathe due to constricted airways, excessive lung mucus, central respiratory depression, and weakened or paralyzed respiratory muscles. Survivors of acute poisoning may face other long-term complications.

Exposure to certain chemicals, typically found in pesticides, can cause Organophosphate Toxicity. This exposure can happen through a person's job, accidental contact with pesticides, intentional harmful exposure, or even chemical attacks.

Gastroenteritis, Myasthenia gravis, Eaton-Lambert syndrome, Guillain-Barre syndrome, Botulism, Mushroom toxicity (specifically from Clitocybe and Inocybe mushrooms), Nicotine poisoning (including green tobacco sickness), Hemlock poisoning (caused by Conium maculatum or poison hemlock), Carbamate toxicity, and various types of medication or drug toxicity (including Carbachol, Methacholine, Arecoline, Bethanechol, Pilocarpine, Pyridostigmine, and Neostigmine).

The types of tests that are needed for Organophosphate Toxicity include: - Observation of symptoms such as small, pinpoint pupils, excessive sweating, trouble breathing, and smelling like garlic or petroleum - Measurement of cholinesterase activity, particularly RBC AChE, in a blood sample collected in a specific type of tube - Other important tests to check overall health, including a complete blood count, tests for basic metabolic functions and organ health, glucose levels, and in certain situations, a pregnancy test - Monitoring heart activity using an electrocardiogram to detect slow heart rate due to the effects of organophosphate on the nervous system.

Organophosphate toxicity is treated through a combination of protective measures, cleaning procedures, and medication. Medical professionals first protect themselves by wearing personal protective gear to avoid contamination. The patient is then thoroughly washed with soap and water to remove any remaining toxins, with special care taken around body fluids. If the patient's condition is severe, urgent medical treatment should not be delayed. Ensuring proper breathing is a top priority, and some patients may need a tube placed in their airway. Atropine is often used to reduce symptoms by competing with acetylcholine in the body. Pralidoxime is another medication that can be used to break down the toxin, but its timing and effectiveness can vary. Seizures may be treated with benzodiazepines, and hemodialysis may be used in some cases. Patients should be closely monitored in the hospital, particularly for respiratory problems.

When treating Organophosphate Toxicity, there can be side effects or complications associated with the treatment. These include: - Atropine, which is commonly used to treat organophosphate poisoning, may not improve all symptoms and patients must be closely monitored for issues with muscle function and breathing. - The administration of pralidoxime, another medication used in treatment, needs to be done cautiously to prevent complications like cardiac arrest. - Patients may experience seizures, for which benzodiazepines may be given. - Hemodialysis may be used to remove the poison from the patient's body, but this depends on the specific type of organophosphate involved. - Patients may develop a condition called "intermediate syndrome" which can lead to muscle weakness and breathing problems. This syndrome can last for several weeks. - Peripheral nerve issues can occur days to weeks after severe poisoning, leading to symptoms such as cramping in the leg muscles, numbness in the limbs, and mental deficits like confusion and memory loss.

The prognosis for organophosphate toxicity can vary depending on the severity of the poisoning. In cases of mild toxicity, the prognosis is generally good, with most patients recovering without long-term complications. However, in moderate to severe cases, the prognosis can be more serious, with a higher risk of death and the need for breathing support. The development of intermediate syndrome, a delayed reaction that can occur after poisoning, is also a possibility.

A toxicologist or a doctor specializing in poison control should be consulted for Organophosphate Toxicity.