Organophosphates Poisoning is a serious medical emergency that occurs when a person develops an illness as a result of exposure to organophosphates (OPs). Organophosphates are chemicals extensively used in agriculture as insecticides. When humans—particularly agricultural workers—are exposed to large quantities, these chemicals can be severely harmful or fatal.

• Other Uses: They are also used as nerve agents in chemical warfare (e.g., Sarin gas, Soman, Tabun, VX) and occasionally as therapeutic agents (e.g., ecothiopate for glaucoma).
• Global Impact: There are no rules and regulations governing the purchase of these products in many regions, making them readily available "over the counter." This leads to an estimated 3 million exposures and 300,000 mortalities globally each year.
• Exposure Context: Exposure in an attempt to commit suicide is a key problem, particularly in developing countries, and is a more common cause of severe poisoning than the chronic exposure experienced by farmers or sprayers.

• Poison: A foreign chemical that is capable of producing a harmful effect on a biologic system (xenobiotic).
• Poisoning: The development of harmful effects on normal body functions following exposure to chemicals after it is swallowed, inhaled, injected, or absorbed cutaneously.

There are more than a hundred organophosphorus compounds in common use, classified according to their toxicity and clinical use:

• Parathion
• Fenthion
• Malathion
• Diazinon
• Dursban
• Quinalphos
• Prothoate

• Nearly 25 million cases of unintentional pesticide poisoning occur in the agricultural industry across the world each year.
• Globally, it is reported that 3 million or more people are exposed to OPs every year, accounting for approximately 300,000 mortalities.
• In the United States, there are around 8,000 exposures per year, with fewer deaths.
• Poisoning leads to significant morbidity and mortality each year in India. According to the National Crime Records Bureau of India, there were 27,657 deaths and suicides by poisoning in 2015.
• Cases are most common in regions where workers do not use or do not have access to protective gear, such as specialized suits or masks.
• Symptoms and complications vary wildly but can quickly escalate to death.

Organophosphates exert their acute toxic effects by causing massive overstimulation at cholinergic nerve terminals.

1. Normal Function: Acetylcholine (ACh) is a vital neurotransmitter found in the central and peripheral nervous systems, neuromuscular junctions, and red blood cells (RBCs). Normally, the enzyme acetylcholinesterase (AChE) catalyzes the rapid degradation of ACh into choline and acetic acid in the nerve synapse, ending the nerve signal.
2. The Toxic Mechanism: OP pesticides act by binding irreversibly to the AChE enzyme.
3. The Consequence: This binding severely reduces the ability of the enzyme to break down the neurotransmitter. This produces a massive, uncontrolled accumulation of ACh in the central and peripheral nervous systems.
4. The Result: This accumulation results in an acute cholinergic syndrome via continuous, unrelenting neurotransmission.

The clinical onset of cholinergic overstimulation can vary from almost instantaneous to several hours after exposure. Although most patients rapidly become symptomatic, the onset and severity of symptoms depend heavily on the specific compound, the amount, the route of exposure, and the rate of metabolic degradation in the patient's body.

• Ingestion: Through the Gastrointestinal (GI) tract (can be accidental or deliberate/suicidal).
• Cutaneous: Absorption directly through the skin (common in occupational exposure).
• Inhalation: Absorption through the lungs.

The length and strength of the exposure will determine the nature of the symptoms, which can range from mild to severe emergency-level toxicity.

• Blurry or impaired vision, watery/stinging eyes, narrowed pupils
• Nausea
• Runny nose, extra saliva
• Headache
• Muscle fatigue, weakness, or minor twitching
• Agitation and glassy eyes

• Dizziness, disorientation
• Very narrow pupils (miosis)
• Muscle tremors, pronounced twitching, and weakness
• Drooling, excessive phlegm
• Wheezing, coughing, and difficulty breathing
• Severe vomiting and severe diarrhea
• Sneezing and uncontrolled urination or bowel movements

• Extreme confusion or Coma
• Pinpoint narrow pupils
• Convulsions / Seizures
• Agitation
• Massive, excessive secretions (saliva, sweat, tears, mucus)
• Irregular or slow heartbeat (bradycardia)
• Collapsing
• Breathing that becomes ineffective or stops completely (respiratory arrest)

The accumulation of acetylcholine overstimulates two main types of receptors: Muscarinic and Nicotinic.

In addition to immediate symptoms, OP exposure can cause long-term complications depending on the extent of exposure:

• Paralysis
• Fertility issues
• Cancer
• Metabolic disorders (e.g., high blood sugar levels)
• Inflammation of the pancreas (Pancreatitis)
• Excess acid in the blood (Acidosis)
• Brain and nerve problems (Organophosphate-induced delayed polyneuropathy - OPIDN)

1. History: Determine the type of exposure (occupational, accidental, deliberate ingestion), time of exposure, and specific chemical if known.
2. Physical Examination: Look for classic signs (SLUDGE, miosis, garlic-like odor on breath).
3. Vital Signs: Depressed respirations, bradycardia, and hypotension are common, life-threatening findings.
4. Laboratory Investigations:
   • Plasma pseudocholinesterase levels: Normal is 3000–8000 U/L. In poisoning, serum levels may drop to < 1000 U/L.
   • RBC AChE level: A more accurate marker of nervous system AChE inhibition.
   • White blood cells (WBC): Leucocytosis is frequently seen.
   • ABG values: To rule out or confirm metabolic and/or respiratory acidosis.
   • Electrolytes: Potassium and magnesium levels are often decreased.
5. Imaging Studies:
   • Chest X-ray for aspiration pneumonia or pulmonary edema.
   • Electrocardiogram (ECG) for ventricular arrhythmias, prolonged QTc, or heart block.

Identify the specific nature of the poison (e.g., OP, carbamate, chloride, pyrethroid) to guide specific antidote therapy.

• Staff Safety: Staff must put on protective equipment before commencing treatment, including masks, gowns, eye protection, and specialized gloves (usually nitrile/rubber, as OPs penetrate latex). Staff involved in direct contact with the patient’s bodily secretions should immediately and thoroughly wash affected areas with soap and water.
• Physical Decontamination: Remove all clothing. Wash the patient thoroughly with soap and copious amounts of water.
• Gastric Decontamination: Gastric lavage should be done only after stabilizing the airway. It is generally given within 1 hour of ingestion. Activated charcoal (0.5–1 g/kg) can be given within 1 hour of ingestion to bind remaining poison in the gut, though some studies show limited benefit. Do not induce emesis.

• Airway: Maintain a clear airway via frequent suctioning of excessive secretions. Check the gag reflex. If absent, intubate before any stomach wash is performed to prevent aspiration.
• Breathing: Administer oxygen at 6 L/min. Intubation and mechanical ventilation are required if breathing is inadequate, oximetry is <90%, or the Glasgow Coma Scale (GCS) is <8.
• Circulation: Administer adequate intravenous (IV) fluids through a wide bore cannula to replace volume loss from severe vomiting and diarrhea.

Continuously monitor for fatal arrhythmias (e.g., ventricular tachycardia, Torsades de pointes) using an ECG.

• Protocol for Atropinisation: Atropinisation must be initiated as soon as the diagnosis is suspected. The aim is to keep the patient's airway dry. Administer Injection Atropine 2 mg IV bolus (or 0.05 mg/kg). The dose is then doubled every 5 minutes until adequate atropinisation is achieved.
• Signs of Atropinisation (Target End-Points):
  • Heart rate about 100/min
  • Pupils return to mid-position
  • Bowel sounds just heard (not hyperactive)
  • Clear lung sounds (secretions dry up)
  • Dry skin
• Signs of Atropine Toxicity (Anticholinergic Toxidrome): Care must be taken not to over-atropinise. Signs include: Dry mucus membranes ("dry as a bone"), mental status changes/delirium ("mad as a hatter"), flushed skin ("red as a beet"), severe mydriasis ("blind as a bat"), fever ("hot as hell"), severe tachycardia, hypertension, decreased bowel sounds, and urinary retention.
• Treatment for Toxicity: Atropine toxicity is treated with injection haloperidol (5 mg IM or IV) for agitation, and by immediately reducing or pausing the dose of atropine.

• Oximes (e.g., Pralidoxime/PAM): Given to reactivate the AChE enzyme and reverse nicotinic effects (muscle weakness/paralysis). Must be given early before the enzyme "ages."
• Antibiotics: Not usually indicated for OP poisoning itself. However, gastric lavage with an unprotected airway and/or a low GCS creates a massive risk for aspiration. If aspiration pneumonia is suspected (fever, leucocytosis, pulmonary infiltrates), broad-spectrum antibiotics (e.g., Ceftriaxone, Piperacillin/Tazobactam [Piptaz]) are indicated.
• Sedation: Agitation may indicate over-atropinisation, hypoxaemia, or distress. Intubated patients need a combination of an analgesic and a sedative (e.g., morphine + lorazepam infusion). Haloperidol may increase the seizure threshold and is not recommended unless patients are unresponsive to other drugs.
• Diuretics: Lasix (Furosemide) is the drug of choice if pulmonary edema persists even after full atropinisation has been achieved.