What are the symptoms, management, and complications of organophosphorus (OP) poisoning?

Organophosphorus Poisoning: Symptoms, Management, and Complications

Clinical Presentation

Muscarinic Symptoms

• Patients present with the classic "SLUDGE" syndrome: salivation, lacrimation, urination, defecation, gastrointestinal cramping, and emesis, along with bronchorrhea, bronchospasm, and bradycardia 1
• Miosis (pinpoint pupils), blurred vision, and excessive sweating are characteristic findings 1
• Respiratory secretions can be life-threatening, leading to respiratory failure if untreated 1

Nicotinic Symptoms

• Muscle fasciculations, tremors, and generalized weakness occur due to nicotinic receptor overstimulation 1, 2
• Tachycardia may paradoxically occur from nicotinic effects, creating a mixed clinical picture with both bradycardia and tachycardia 1
• Isolated nicotinic effects (fasciculations without muscarinic symptoms) can rarely occur, particularly in children but occasionally in adults 2

Central Nervous System Effects

• Seizures, agitation, confusion, and altered mental status are common 1
• Coma and respiratory depression occur in severe poisoning 1
• Delayed neuropsychiatric effects may persist 3

Severity Classification

• Mild symptoms: blurred vision, tearing, runny nose, drooling, chest tightness, tremors, nausea 4
• Severe symptoms: confusion, severe respiratory distress, severe muscle twitching, involuntary urination/defecation, convulsions, unconsciousness 4

---

Immediate Management Algorithm

Step 1: Personal Protection and Decontamination

• Healthcare providers must wear proper personal protective equipment (PPE) before patient contact to prevent secondary contamination 1
• Remove all contaminated clothing immediately and perform copious irrigation with soap and water for dermal exposure 1
• Wash hair and skin thoroughly with sodium bicarbonate or alcohol as soon as possible 4
• Ensure proper ventilation of treatment areas, as organophosphates can off-gas and affect staff 1

Step 2: Airway, Breathing, Circulation

• Secure airway early with endotracheal intubation for life-threatening poisoning, as observational data suggests better outcomes with early intubation 1
• Avoid succinylcholine and mivacurium (neuromuscular blockers metabolized by cholinesterase) as they are contraindicated and can cause prolonged paralysis 1, 4
• Provide supplemental oxygen and support ventilation as needed 1
• Establish IV access and administer fluids for volume resuscitation 1

Step 3: Atropine Administration (First-Line Antidote)

• Administer atropine 1-2 mg IV immediately for adults (0.02 mg/kg for children, minimum 0.1 mg, maximum single dose 0.5 mg) for severe manifestations including bronchospasm, bronchorrhea, seizures, or significant bradycardia 1, 4
• Double the dose every 5 minutes until full atropinization is achieved (dry lungs, adequate oxygenation, dry skin/mucous membranes, mydriasis) 1, 4
• Children require relatively higher doses than standard pediatric resuscitation doses 1
• Do NOT withhold atropine due to tachycardia—atropine-induced tachycardia is an expected pharmacologic effect and is NOT a contraindication to continued administration 1
• Maintain atropinization for at least 48-72 hours until cholinesterase activity reverses 1, 4
• Atropine infusion can be used for maintenance therapy after initial boluses 1

Critical Pitfall: Atropine should not be given in the presence of significant hypoxia due to risk of ventricular fibrillation—improve oxygenation first 4

Step 4: Pralidoxime (2-PAM) Administration (Oxime Therapy)

• Administer pralidoxime 1-2 g IV slowly (preferably by infusion over 15-30 minutes) as soon as possible after atropine 1, 4
• If infusion is not practical or pulmonary edema is present, give slowly over at least 5 minutes as a 50 mg/mL solution 4
• Maintenance therapy: 400-600 mg/hour for adults or 10-20 mg/kg/hour for children 1
• A second dose of 1-2 g may be given after one hour if muscle weakness persists 4
• Additional doses every 10-12 hours may be needed if weakness continues 4
• Pralidoxime is most effective when given early, before "aging" of the phosphorylated enzyme occurs (typically within 24-36 hours) 1, 4
• Do NOT withhold oximes when the class of poison is unknown (organophosphate vs. carbamate) 1
• Pralidoxime reactivates acetylcholinesterase and reverses both muscarinic and nicotinic effects that atropine cannot address 1, 3

Evidence Note: The American Heart Association gives pralidoxime a Class 2a recommendation with Level A evidence, indicating strong support despite some studies questioning efficacy 1

Step 5: Seizure Control

• Administer benzodiazepines (diazepam or midazolam) for seizures and agitation 1, 4
• Benzodiazepines should be given early and liberally for CNS symptoms 1

Step 6: Gastrointestinal Decontamination

• Gastric lavage may have a role but should only be undertaken once the patient is hemodynamically stable 5
• Activated charcoal is routinely used but its value has not been conclusively proven 3
• Consider continuing absorption from the lower bowel after ingestion—fatal relapses have occurred after initial improvement 4
• Additional pralidoxime doses may be needed every 3-8 hours if signs recur 4

---

Monitoring and Supportive Care

Continuous Monitoring (Minimum 48-72 Hours)

• All patients require observation for at least 48-72 hours, as delayed deterioration and relapses are common 1, 4
• Continuous cardiac monitoring for dysrhythmias 1
• Serial respiratory assessments for bronchorrhea resolution 1
• Monitor for signs of adequate atropinization (dry lungs, dry mucous membranes, mydriasis) 1
• Titrate the patient with pralidoxime as long as signs of poisoning recur 4

Metabolic Support

• Correct metabolic acidosis with sodium bicarbonate 1-2 mEq/kg IV if severe 6, 7
• Intravenous magnesium sulfate has been shown to decrease hospitalization duration and improve outcomes 6, 7
• Monitor electrolytes, particularly potassium 1

Medications to Avoid

• Do NOT use morphine, theophylline, aminophylline, reserpine, or phenothiazine-type tranquilizers in organophosphate poisoning 4
• Avoid succinylcholine and mivacurium for intubation 1, 4

---

Complications

Acute Complications

• Respiratory failure from bronchorrhea, bronchospasm, and respiratory muscle weakness is the leading cause of death 1, 5
• Aspiration pneumonia from excessive secretions 1
• Cardiac dysrhythmias and cardiovascular collapse 1
• Status epilepticus and cerebral hypoxia 1
• Acute renal failure 1

Intermediate Syndrome (24-96 Hours Post-Exposure)

• Delayed muscle weakness can occur 24-96 hours after acute exposure, even after initial improvement 1
• Proximal muscle weakness, respiratory muscle paralysis, and cranial nerve palsies develop 1
• This occurs even as cholinergic symptoms resolve 1
• Requires continued ventilatory support and monitoring 1

Late Complications

• Organophosphate-induced delayed polyneuropathy (OPIDP) can occur 1-3 weeks after exposure 3
• Myonecrosis and rhabdomyolysis from calcium overload in skeletal muscle 1
• Renal damage secondary to rhabdomyolysis 1
• Persistent neuropsychiatric effects 3

Atropine-Related Complications

• Hyperthermia (fever) from repeated atropine administration is expected and does NOT indicate treatment failure 1
• Hallucinations and CNS effects from high-dose atropine 1
• Never withhold or prematurely discontinue atropine due to fever—the risk of undertreating organophosphate poisoning far exceeds the risk of atropine toxicity 1

---

Special Considerations

Mechanism of Toxicity

• Organophosphates form a covalent bond with acetylcholinesterase causing permanent inactivation ("aging"), while carbamates spontaneously dissociate 1
• This irreversible inhibition leads to accumulation of acetylcholine at cholinergic synapses 3
• Both muscarinic and nicotinic receptors are overstimulated 1

Prognosis

• Case fatality is generally more than 15% despite treatment 5
• Early resuscitation with atropine, oxygen, respiratory support, and fluids improves oxygen delivery and outcomes 5
• Some organophosphates may prove very difficult to treat with current therapies, such that bans on particular pesticides may be the only method to substantially reduce mortality 5
• Treatment is most effective if initiated immediately after poisoning 4

Emerging Therapies

• Fresh frozen plasma (FFP) as a bio-scavenger to clear free organophosphates has been suggested 6, 7
• Sodium bicarbonate infusion to produce mild alkalinization may be effective 6
• Hemofiltration and antioxidants are being investigated 6, 7
• Recombinant bacterial phosphotriesterases show promise for delayed treatment 6

Contact Poison Control

• Contact poison control (1-800-222-1222 in the US) for expert guidance on specific case management 1