Cardiac Effects associated with Pesticide Exposure

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Cardiac Effectsassociated withPesticide
Exposure

• Ana Maria Osorio, MD, MPH
• US Public Health Service, on detail to
• US Environmental Protection Agency
• Washington DC
• Tel [phone]
• E-mail Osorio.AnaMaria_at_epa.gov

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InsecticidesOrganophosphates
R - O
l R - O P S (or O)
l R
alkyl group O X
X leaving group Common mechanism of
cholinesterase inhibition
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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)

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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

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Signs and Symptoms (Sx)
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Dx If poisoning probable, dont 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)

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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

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OP Cardiac Manifestations46 patient case
series, Jordan
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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.
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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

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Organochlorines

• Atropine and adrenergic amines contraindicated
  because these agents may potentiate myocardial
  irritability

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DipyridilsParaquate Diquat

• Primary pulmonary effects (edema fibrosis)
• Death from multi-organ failure including
  myocardial necrosis has been reported

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Case ReportParaquat Suicide

• 59 yo man in Belgium ingested 50-60 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

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Chlorophenoxy Herbicides

• Reports of T-wave flattening and inversion
  following large ingestion episodes

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Pentachlorophenol

• Tachycardia and other arrhythmias reported

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Aluminum phosphide

• Slow release of phosphine ? strong mucous
  membrane and respiratory irritant
• Report of cardiotoxicity

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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?