Background

• Organophosphate (OP) poisoning is a severe and potentially life-threatening condition that can occur due to exposure to certain chemicals commonly found in pesticides, insecticides, and nerve agents. Organophosphate compounds have a long and complex history, starting with their synthesis in the early 1800s. The first organophosphate compound, tetraethyl pyrophosphate, was synthesized in 1854. However, it was in the 1930s and 1940s that organophosphates were extensively investigated as insecticides. 
• During World War II, organophosphates were reintroduced worldwide for pesticide use. However, severe cases of organophosphate poisoning from suicide attempts and outbreaks of unintentional poisoning led to discovering of the mechanisms of organophosphate’s acute and chronic toxicity. 
• In the 1950s and 1960s, organophosphates became the most widely used class of insecticides. Still, their use declined in the 1970s and 1980s due to the development of resistance and concerns about their impact on the environment and non-target species. 
• Organophosphates have also been used as chemical warfare agents. During World War II, the German military developed a series of organophosphate-based nerve agents, including tabun, sarin, and soman. A fourth agent, VX, was later synthesized in England. 
• OP poisoning can occur through ingestion, inhalation, or skin exposure to OP compounds. Symptoms of OP poisoning can vary depending on the dose and duration of exposure. They can range from mild symptoms such as headache, dizziness, and nausea to more severe symptoms such as respiratory distress, seizures, and coma. 

Epidemiology

• The American Association of Poison Control Centres recorded 1474 single organophosphate insecticide exposures in 2021, with 15 severe effects and four deaths. Furthermore, 398 single exposures to organophosphate insecticides combined with other insecticides were reported, resulting in one primary outcome and one death.
• Pesticide poisonings, including those involving organophosphates, are a significant source of fatalities worldwide, particularly in countries where these compounds are easily accessible. There is evidence that children and other at-risk populations may be more susceptible to the effects of organophosphates, and further research is needed to understand this risk. 

Anatomy

Pathophysiology

• Organophosphates (OPs) are cholinesterase inhibitors, meaning they inhibit the activity of the enzyme acetylcholinesterase (AChE), which breaks down the neurotransmitter acetylcholine (ACh) at cholinergic synapses. This inhibition leads to an accumulation of ACh in the synapses, resulting in overstimulation of cholinergic receptors. 
• The clinical manifestations of OP poisoning are primarily due to overstimulation of cholinergic receptors, which can affect multiple organ systems. Mild to severe symptoms can include respiratory distress, miosis, headache, dizziness, weakness, tremors, seizures, and loss of consciousness. Respiratory failure and death can occur in severe situations. 
• The effects of OPs can be acute or chronic. Acute effects, such as intentional or accidental ingestion, are typically seen after a single high-dose exposure. Chronic effects are seen after repeated low-level exposures, as is common among individuals with occupational exposure to OPs. 
• In addition to their effects on cholinergic receptors, OPs may also have other toxic effects, including oxidative stress, inflammation, and apoptosis. These effects can damage the nervous system and other organs long-term. 

Etiology

• Organophosphate (OP) poisoning can occur through various routes, including ingestion, inhalation, dermal exposure, and ocular exposure. The most common route of OP exposure is through ingestion, which can occur accidentally, intentionally (suicide attempts), or through contaminated food or water. 
• Occupational exposure is another standard route of OP exposure. Workers in agriculture, pest control, and industrial settings are particularly at risk of exposure to OPs. These individuals may be exposed through inhalation of contaminated air, dermal absorption of OPs through the skin, or ingesting contaminated food or water. 
• In addition, OPs have been used as chemical weapons in military and terrorist attacks, leading to mass poisoning incidents. 

Genetics

Prognostic Factors

• High dose exposure: High levels of OPs can lead to more severe symptoms and a higher risk of complications. 
• Delayed treatment: A delay in initiating appropriate medical treatment can lead to the progression of symptoms and a poorer prognosis. 
• Prolonged cholinergic crisis: A prolonged cholinergic crisis, characterized by prolonged activation of acetylcholine receptors, can lead to respiratory failure, seizures, and other severe complications. 
• Age and overall health: Elderly individuals and those with underlying medical conditions may have a higher risk of complications and a poorer prognosis. 
• Type of OP: Some OPs are more toxic than others, and exposure to more toxic OPs may result in a poorer prognosis. 
• Comorbidities: Preexisting medical conditions, such as cardiovascular disease or respiratory illness, may worsen the prognosis of OP poisoning. 

Clinical History

• The clinical presentation of Organophosphate (OP) poisoning can vary widely depending on the severity and duration of the exposure, the type and amount of OP involved, and the individual’s age, comorbidities, and activity level at the time of exposure. 
• Age group: 
• In children, symptoms of OP poisoning may include nausea, vomiting, diarrhea, excessive salivation, and muscle weakness. 
• Symptoms may include headache, dizziness, nausea, vomiting, abdominal pain, diarrhea, blurred vision, confusion, tremors, and muscle weakness in adults. 

Physical Examination

• Neurological examination: Patients may present with confusion, disorientation, tremors, weakness, or seizures. In severe cases, they may be comatose or have respiratory arrest. 
• Cardiovascular examination: OP poisoning can cause hypertension, hypotension, tachycardia, or bradycardia. Cardiac arrhythmias may also occur in some cases. 
• Respiratory examination: OP poisoning can lead to respiratory distress, bronchoconstriction, wheezing, or bronchorrhea. 
• Ophthalmological examination: OP poisoning can cause miosis (pupillary constriction) and blurred vision. 
• Gastrointestinal examination: OP poisoning can cause abdominal pain, nausea, vomiting, and diarrhea. Hyperactive bowel sounds may also be present. 
• Skin examination: OP poisoning may sometimes cause sweating, flushing, or urticaria (hives). 

Age group

Associated comorbidity

• Individuals with preexisting medical conditions, such as respiratory or cardiovascular disease, may experience more severe symptoms and complications. 
• Individuals engaged in agricultural or pest control activities, who are at higher risk of OP exposure, may present with symptoms related to acute or chronic exposure. 

Associated activity

Acuity of presentation

• Acute presentation of OP poisoning may include rapid onset of symptoms, such as respiratory distress, seizures, or loss of consciousness, and may require immediate medical attention. 
• Chronic presentation of OP poisoning may include symptoms that develop over an extended period, such as headaches, fatigue, and cognitive impairment. 

Differential Diagnoses

• Cholinergic crisis: OP poisoning is a type of cholinergic crisis, but other causes include botulism, nerve agent exposure, and myasthenia gravis. Differentiation can be made based on the timing of onset, symptoms, and exposure history. 
• Seizures: OP poisoning can cause seizures, but other causes, such as epilepsy, stroke, or brain injury, should be ruled out. 
• Drug overdose: Symptoms of OP poisoning may overlap with those of other drug overdoses, such as benzodiazepines, opioids, or tricyclic antidepressants. History of drug use and toxicity testing may help make the diagnosis. 
• Metabolic disorders: Some metabolic disorders, such as uremia, hepatic encephalopathy, or hypoglycemia, may cause similar symptoms as OP poisoning. Laboratory tests can help differentiate these conditions. 
• Acute respiratory distress syndrome (ARDS): Severe cases of OP poisoning may lead to ARDS, which can also occur in the context of other infections or lung injuries. 
• Guillain-Barre syndrome: Rarely, OP poisoning can trigger an immune-mediated peripheral neuropathy resembling Guillain-Barre syndrome. 

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

• The first step in managing organophosphate poisoning is to remove the patient from the contaminated environment and prevent further exposure. This may involve decontaminating clothing and skin and providing fresh air in a safe environment. 

• The specific antidote for organophosphate poisoning is atropine, which is given to counteract the effects of the toxic chemical on the nervous system. Diazepam is also sometimes used to control seizures and muscle spasms associated with the poisoning. 

• In severe cases of organophosphate poisoning, mechanical ventilation may be necessary to support breathing. Hemodialysis or hemoperfusion may also remove toxic chemicals from the blood. 

• The management of organophosphate poisoning is divided into three phases: acute, intermediate, and late. In the acute phase, the focus is stabilizing the patient’s vital signs and administering the appropriate antidotes. In the intermediate phase, the focus is monitoring the patient for potential complications, such as respiratory failure or seizures. In the late phase, the focus is on long-term rehabilitation and management of any residual symptoms or disabilities. 

Medication

Future Trends

Media Gallary

References

• https://medlineplus.gov/ency/article/002832.html 
• https://www.ncbi.nlm.nih.gov/books/NBK470430/ 
• https://emedicine.medscape.com/article/167726-overview#a5