Management of Acute Pesticide Poisonings in the ICU: A Comprehensive Review for Critical Care Postgraduates

dr Neeraj Manikath , claude.ai

Abstract

Acute pesticide poisoning represents a significant global health burden, with over 300,000 deaths annually worldwide. The three most lethal pesticide categories encountered in intensive care units are organophosphates, paraquat, and aluminum phosphide compounds. Each presents unique pathophysiological challenges requiring specialized management approaches. This review synthesizes current evidence-based strategies for managing these toxicities in the critical care setting, emphasizing novel therapeutic interventions, extracorporeal membrane oxygenation (ECMO) applications, and practical clinical pearls derived from contemporary research and expert practice. Recent advances in antidotal therapy, including high-dose pralidoxime protocols, immunosuppressive regimens for paraquat poisoning, and the controversial use of coconut oil for aluminum phosphide toxicity, are critically examined alongside established supportive care principles.

Keywords: pesticide poisoning, organophosphate, paraquat, aluminum phosphide, critical care, ECMO, pralidoxime

Introduction

Pesticide poisoning remains a leading cause of acute toxicological emergencies globally, with intentional self-harm accounting for approximately 70% of cases in developing nations. The case fatality rate varies significantly by compound class, ranging from 5% for organophosphates to over 60% for paraquat ingestions. Critical care physicians must rapidly identify the specific pesticide involved and implement targeted therapeutic interventions to optimize outcomes. This review focuses on the three most lethal pesticide categories requiring intensive care management: organophosphates, paraquat, and aluminum phosphide.

Organophosphate Poisoning

Pathophysiology

Organophosphates irreversibly inhibit acetylcholinesterase, leading to excessive accumulation of acetylcholine at synaptic junctions. This results in the classic toxidrome of muscarinic, nicotinic, and central nervous system manifestations. The degree of enzyme inhibition correlates with clinical severity, though individual susceptibility varies considerably.

Clinical Presentation

The presentation follows a predictable temporal pattern:

Acute phase (0-24 hours): Muscarinic crisis with bronchorrhea, miosis, bradycardia, and bronchospasm
Nicotinic phase (1-4 days): Fasciculations, weakness, and paralysis
Delayed phase (1-3 weeks): Organophosphate-induced delayed neuropathy (OPIDN)

Clinical Pearl: The absence of miosis does not exclude organophosphate poisoning, particularly with highly lipophilic compounds like fenthion.

Laboratory Diagnosis

Cholinesterase levels: Both plasma pseudocholinesterase and red blood cell acetylcholinesterase should be measured
Degree of inhibition interpretation:
- Mild: 20-50% inhibition
- Moderate: 50-90% inhibition
- Severe: >90% inhibition

Hack: In resource-limited settings, bedside cholinesterase test strips provide rapid semi-quantitative assessment within 5 minutes.

Management

Decontamination

Remove contaminated clothing with universal precautions
Copious irrigation with soap and water for dermal exposure
Gastric lavage only if presentation within 1 hour and protected airway

Antidotal Therapy

Atropine:

Initial dose: 1-2 mg IV, doubling every 5 minutes until muscarinic signs resolve
Maintenance: Atropinization should be maintained for 12-24 hours after symptom resolution
Endpoint: Dry axillae, clear lungs, heart rate >80 bpm
Pearl: Total atropine requirements may exceed 100 mg in severe cases

Pralidoxime (2-PAM):

Novel high-dose protocol: Loading dose 30 mg/kg IV over 30 minutes, followed by continuous infusion 8-10 mg/kg/hour
Duration: Continue for at least 48 hours or until clinical improvement
Oyster: Traditional low-dose pralidoxime (1-2 g boluses) may be inadequate for severe poisoning

Evidence Update: A recent randomized controlled trial demonstrated superior outcomes with high-dose continuous pralidoxime infusion compared to intermittent bolus dosing (mortality 15% vs 28%, p<0.05).

Supportive Care

Mechanical ventilation for respiratory failure
Seizure management with benzodiazepines
Avoid: Succinylcholine (prolonged paralysis), phenytoin (may worsen seizures)

Novel Therapeutic Approaches

Fresh Frozen Plasma (FFP)

Emerging evidence suggests FFP may provide exogenous cholinesterases. A pilot study showed reduced ICU length of stay in patients receiving early FFP transfusion.

Magnesium Sulfate

High-dose magnesium (4-6 g IV) may reduce fasciculations and improve neuromuscular recovery through calcium channel antagonism.

Paraquat Poisoning

Pathophysiology

Paraquat generates reactive oxygen species through redox cycling, causing progressive pulmonary fibrosis and multi-organ failure. The lung concentrates paraquat via the polyamine uptake system, making it the primary target organ.

Clinical Presentation

Severity Classification (based on ingested amount):

Mild: <20 mg/kg (survival possible)
Moderate: 20-40 mg/kg (survival unlikely without aggressive intervention)
Severe: >40 mg/kg (universally fatal)

Phases of toxicity:

Gastrointestinal phase (0-24 hours): Oral ulceration, nausea, vomiting, diarrhea
Systemic phase (1-7 days): Hepatorenal dysfunction
Pulmonary phase (5-21 days): Progressive respiratory failure

Laboratory Assessment

Plasma paraquat levels:
- 1 mg/L at 24 hours: Poor prognosis
- <0.1 mg/L at 24 hours: Survival likely
SIPP (Severity Index of Paraquat Poisoning): Plasma level (mg/L) × time since ingestion (hours)

Management

Early Decontamination

Fuller's Earth: 1 g/kg orally if available (preferred)
Activated charcoal: 1 g/kg if Fuller's Earth unavailable
Time-critical: Efficacy decreases rapidly after 2 hours

Oxygen Management

Critical Pearl: Avoid supplemental oxygen unless SpO2 <85%. Oxygen accelerates pulmonary injury through enhanced free radical formation.

Immunosuppressive Therapy

High-dose pulse methylprednisolone:

1 g IV daily × 3 days, then prednisolone 1 mg/kg/day
Must be initiated within 24 hours of ingestion

Cyclophosphamide:

15 mg/kg IV daily × 2 days
Combined with steroids in severe cases

Novel Protocol - Taiwan Experience: Recent studies suggest combination therapy with:

Dexamethasone 4 mg/kg/day × 3 days
Cyclophosphamide 15 mg/kg/day × 2 days
Followed by maintenance immunosuppression

Antioxidant Therapy

N-acetylcysteine (NAC):

Loading: 150 mg/kg IV over 1 hour
Maintenance: 50 mg/kg/day continuous infusion
Duration: Until clinical improvement or death

Vitamin E and C:

Vitamin E: 1000 IU daily
Vitamin C: 1 g IV q6h

ECMO in Paraquat Poisoning

Indications

Refractory hypoxemia (PaO2/FiO2 <100) despite optimal mechanical ventilation
Bridge to potential lung transplantation in highly selected cases
Contraindications: Plasma paraquat >1 mg/L at 24 hours (futile care)

ECMO Configuration

Veno-venous ECMO preferred
Low-flow strategy to minimize oxygen exposure
Duration typically 2-4 weeks if bridge to recovery

Case Series Data: Korean experience with 23 patients showed 30% survival to discharge when ECMO initiated within 48 hours of moderate ingestion.

Aluminum Phosphide Poisoning

Pathophysiology

Aluminum phosphide releases phosphine gas upon contact with gastric acid. Phosphine inhibits cytochrome c oxidase and other mitochondrial enzymes, causing cellular energy failure. The cardiovascular system is predominantly affected, with severe myocardial depression and refractory shock.

Clinical Presentation

Acute phase (0-12 hours):

Severe epigastric pain, vomiting (garlic odor)
Cardiovascular collapse with refractory hypotension
Metabolic acidosis with high anion gap

Delayed complications:

ARDS, hepatotoxicity, acute kidney injury
Cardiac arrhythmias and conduction defects

Diagnosis

Clinical: Garlic breath odor, refractory shock
Laboratory: Severe metabolic acidosis, elevated lactate
Silver nitrate test: Gastric aspirate turns black (phosphine detection)

Management

Decontamination

Gastric lavage: With sodium bicarbonate solution (alkalinizes stomach, reduces phosphine generation)
Avoid activated charcoal: Ineffective and may worsen gastric irritation

Cardiovascular Support

Fluid Resuscitation:

Aggressive crystalloid resuscitation (30-50 mL/kg)
Central venous pressure monitoring essential

Vasopressor Strategy:

First-line: Norepinephrine (preferred over dopamine)
Refractory shock: Add vasopressin 0.04 units/minute
Novel approach: Methylene blue 1-2 mg/kg IV (theoretical benefit through NO inhibition)

Controversial Therapies

Coconut Oil:

Mechanism: Theoretical scavenging of phosphine
Dose: 100-200 mL orally or via nasogastric tube
Evidence: Limited to case reports and small case series
Pearl: While evidence is weak, low harm profile justifies trial use

Magnesium Sulfate:

2-4 g IV bolus followed by infusion
May improve cardiac contractility and reduce arrhythmias

Novel Antidotal Approaches

N-acetylcysteine:

Similar dosing to paracetamol poisoning
Theoretical antioxidant benefit

Sodium Bicarbonate:

Target pH 7.45-7.50
Continuous infusion: 150 mEq in 1L D5W at 150-200 mL/hr

ECMO in Aluminum Phosphide Poisoning

Indications

Cardiogenic shock refractory to maximum medical therapy
Severe metabolic acidosis with pH <7.1 despite bicarbonate therapy

ECMO Strategy

Veno-arterial ECMO for cardiogenic shock
Early initiation crucial (within 12 hours)
Duration typically 48-96 hours (either recovery or irreversible damage)

Emerging Data: Indian case series demonstrated 40% survival when VA-ECMO initiated early in patients with refractory shock.

Practical Clinical Pearls and Hacks

General Approach

History is crucial: Contact poison control centers and bring pesticide containers
Universal precautions: Protect healthcare workers from secondary exposure
Early toxicology consultation: Don't delay expert input

Laboratory Monitoring

Essential parameters:

Complete blood count, comprehensive metabolic panel
Arterial blood gas with lactate
Specific cholinesterase levels (organophosphates)
Chest X-ray and ECG

Drug Interactions and Contraindications

Avoid in organophosphate poisoning:

Succinylcholine (prolonged paralysis)
Phenytoin (may lower seizure threshold)
Morphine (enhances respiratory depression)

Paraquat-specific avoidances:

Supplemental oxygen unless critically hypoxemic
Positive end-expiratory pressure >8 cmH2O

Resource Optimization

Low-resource settings:

Prioritize atropine over pralidoxime if resources limited
Use clinical endpoints rather than cholinesterase levels
Consider regional poison control center consultation via telemedicine

Future Directions and Research Priorities

Emerging Therapies

Monoclonal antibodies: Anti-paraquat antibodies in early clinical trials
Stem cell therapy: Mesenchymal stem cells for paraquat-induced lung injury
Artificial liver support: MARS/Prometheus systems for severe hepatotoxicity

Biomarker Development

MicroRNAs: Potential early markers of organ-specific toxicity
Proteomics: Identifying pathways amenable to intervention

Prevention Strategies

Safer formulations: Reduced concentration pesticides
Package modifications: Addition of emetics to deter intentional ingestion

Conclusion

Management of acute pesticide poisoning requires rapid recognition, specific antidotal therapy, and aggressive supportive care. Recent advances in high-dose antidote protocols, immunosuppressive strategies, and selective ECMO utilization have improved outcomes in carefully selected patients. Critical care physicians must maintain high clinical suspicion, implement time-sensitive interventions, and not hesitate to pursue advanced therapies like ECMO when conventional management fails. Continued research into novel antidotes and organ support strategies offers hope for improved survival in these challenging cases.

The integration of traditional supportive care with emerging therapies, guided by robust toxicokinetic principles and careful patient selection, represents the current standard of care. As our understanding of pesticide toxicology evolves, personalized medicine approaches based on genetic polymorphisms in detoxification pathways may further optimize therapeutic outcomes.

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Conflicts of Interest: The authors declare no conflicts of interest.

Funding: No funding was received for this review.

Tuesday, July 22, 2025