1. Cardiac Effects associated with Pesticide Exposure
Ana Maria Osorio, MD, MPH
US Public Health Service, on detail to:
US Environmental Protection Agency
Washington DC
Tel

2. Symptoms, Signs or Abnormal Lab Findings
Pesticide Types
Specific Agents
Bradycardia
Carbamates
Organophosphates
Cyanide
Nicotine
Cardiac
arrhythmias
Halocarbon
fumigants
Inorganic
Arsenicals
Organochlorines
Phosphorus
compounds
Acrylonitrile
Ethylene oxide
Fluoride
Povidone-iodine
Sabadilla (veratrum alkaloid)
Sodium chlorate
Sodium fluoride
Sodium Fluoroacetate
Thallium
Tachycardia
Nitrophenols
Cyanamide
Metaldehyde

3. Insecticides: Organophosphates
R - O l
R - O – P – S (or O)
l R = alkyl group
O – X X = leaving group
Common mechanism of cholinesterase inhibition

4. Toxicology Absorbed via inhalation, ingestion and dermal penetration
Phosphorylation of acetylcholinesterase enzyme (AChE)   Ach at nerve endings
Recovery when generation of new AChE
Effects:
Muscarinic (involuntary smooth muscle and exocrine gland cells)
Nicotinic (voluntary skeletal muscle)
CNS (sensory & behavioral abnormalities, incoordination, decreased motor function and respiratory depression)

5. Toxicology - continued
Metabolites: alkyl phosphates and leaving
groups
Reactivation = dephosphorylate AChE with pralidoxime (1-2 days post exposure)
Aging = later, lose alkyl group and P bond stronger

6. Signs and Symptoms (Sx)
Early Sx
HA, nausea, dizzy, hypersecretion
More severe Sx
Muscle twitch, weakness, tremor, incoordination, vomit, abd cramps, diarrhea
Ocular Sx
Miosis (blurred vision)
Neuropsych Sx
Anxiety, restless, depression, memory loss, confusion, toxic psychosis
Respiratory System
Muscle fasiculations/weakness, respiratory arrest, bronchorrhea, bronchospasm, pulmonary edema
Nervous System
Loss of consciousness, incontinence, convulsions, respiratory depression
CV System
Bradycardia, hypotension, tachycardia, hypertension, myocardiopathy, EKG abn, arrhythmia, sinus arrest

7. Dx: If poisoning probable, don’t wait for lab confirmation!!!
Blood samples
plasma pseudoAChE (days to weeks)
RBC AChE (1 – 3 months)
Low plasma AChE: hereditary, liver disease, malnutrition, EtOH, certain drugs, BCPs and pregnancy
Low RBC AChE: hemolytic anemia
Urine metabolites - alkyl phosphates, phenols (up to 48 hrs post exposure)

8. Rx Atropine sulfate Anti-muscarinic agent
Atropinization: flushing, dry mouth, mydriasis, and tachycardia
Pralidoxime (2-PAM)
Reactivates Ach, slows aging
Within 48 hrs, anti-muscarinic & nicotinic
Hypertensive crisis, tachycardia, arrhythmias
Cardiopulmonary monitoring

9. OP Cardiac Manifestations: 46 patient case series, Jordan
Note: 67% intentional, 9% occ, 24% other

10. 31 cases (67%) with cardiac effects – 2 deaths due to vent fib
Conclude that cardiac Sx early in severe intoxication & that aggressive Rx in ICU can decrease mortality rate.

11. 2-PAM not indicated for carbamatesOP
Carbamate
Inhibition of AChE
Irreversible
Reversable
Duration
4-18 days
<24 hours
Neuro Sx ++
0/+
Cardiac Sx +
Respiratory Sx
ChE levels
 
- / 
2-PAM not indicated for carbamates

12. Additional literature re OP/Carb intoxications
Case series of 168 persons  5 with transient MI presentation
Necropsy series  2 malathion intoxication cases showed myocardial damage
Case report of carbamate intoxication associated with diffuse myocarditis
Extended case series of Jordan hospital  84 adults with similar results to earlier survey + 8% with elevated cardiac enzymes

13. Organochlorines
Atropine and adrenergic amines contraindicated because these agents may potentiate myocardial irritability

14. Dipyridils: Paraquate & Diquat
Primary pulmonary effects (edema & fibrosis)
Death from multi-organ failure including myocardial necrosis has been reported

15. Case Report: Paraquat Suicide
59 yo man in Belgium ingested ml of Gramasone.
Production of free radicals  tissue damage by peroxidation of lipid in cell membranes
Death usually from caustic injury to GI tract +/or circulatory failure +/or respiratory failure
Aggressive treatment of this patient  aspiration, gastric lavage, hemodialysis + prolonged anti-oxidant therapy
Outcome: survived with minimal lung damage

16. Chlorophenoxy Herbicides
Reports of T-wave flattening and inversion following large ingestion episodes

17. Pentachlorophenol
Tachycardia and other arrhythmias reported

18. Aluminum phosphide
Slow release of phosphine  strong mucous membrane and respiratory irritant
Report of cardiotoxicity

19. Glyphosate-surfactant
In Taiwan, 26 yo man presented with nausea and vomiting 4 hours status post glyphosate suicide ingestion.
Post admission  cardiogenic shock with increased ventricular rhythm on EKG. Echo showed diffuse hypokinesis of left ventricle.
Over the next 16 hours with aggressive treatment, normal rhythm returned.
Was clinical event due to circulatory collapse or transient suppression of cardiac conduction and contractibility or both?