Organophosphate and Carbamate poisoning

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Organophosphate and Carbamate poisoning

• Jung lung Hsu M.D.
• Department of Neurology
• Shin Kong WHS memorial hospital

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Introduction

• 2 major classes of insecticides organophosphates
  and carbamates
• Organophosphate compounds80 of
  pesticide-related hospitalization
• Organophosphate more common use in agricultural
  and home use rapid hydrolysis into harmless
  compounds

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Pathophysiology

• Organophosphate (OP) insecticides permanently
  bind to cholinesterase molecular
• Carbamate is reversible bind with cholinesterase
• OP irreversible binding cholinesterase as
  inhibitor for 24-48h, than irreversible destroyed
• Carbamate-cholinesterase bond reverses
  spontaneously 4-8 h, hielding a normal
  cholinesterase molecular

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intoxication

• Cholinesterase is presenting in synapse.
• Acetylcholine (Ach) is present throughout the
  autonomic and central nervous system, as chemical
  neurotransmitter at pre- and post-ganglionic
  parasympathetic synapses, preganglonic
  sympathetic synapse and neuromuscular junction
• Normally, Ach rapidly hydrolyze into inactive
  fragments of choline and acetic acid

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• Two principle cholinesterase
• erythrocyte (RBC), true cholinesterase
  (acetylcholinesterase)
• Serum cholinesterase (pseudocholinesterase) in
  serum, liver, heart, pancreas, brain
• Inhibition of cholinesterase lead to excessive
  accumulation of acetylcholine in synapses, which
  lead to cholinergic crisis)
• Intoxication produce central and peripheral
  nerve system
• Muscarinic receptor (postganglonic
  parasympathetic)
• Nicotinic receptor (autonomic and muscular
  junction)

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Exposure

• Contact of OP and Carbamate
• Oral
• Dermal
• Conjunctival
• Gastrointestinal
• Respiratory
• Cause agricultural use, accidental exposure,
  suicide

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• Intoxication onset of symptoms and signs vary
  with the route and degree of exposure
• Usually les than 12-24 h,
• Symptoms may persist day to weeks
• Carbamate less toxic and poor CNS penetration
  than Organophosphate

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Clinical presentation

• Mild to moderate poison alert and oriented,
  headache, dizziness, blurred vision, weakness, in
  coordination, muscle fasciculation, tremor,
  diarrhea, abdominal cramping
• Severe intoxication incontinence, convulsion,
  alter mental status
• Chronic intermediate dose exposure manifested as
  nonspecific symptoms including weak, fatigue,
  malaise, anorexia

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Cholinergic excess

• Muscarinic overstimulation -increase
  parasympathetic tone
• Miosis
• Hypersecretion of salivary, lacrimal, and
  bronchial gland
• Bronchoconstriction
• Nausea, vomiting, diarrhea, urine and fecal
  incontinence
• Bradycardia
• SLUDGE (salivation, lacrimation, urination,
  diarrhea, gastrointestinal, emesis)

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• Nicotinic effect
• Muscle fasciculations, cramping and muscle
  weakness
• Overstimulation of nicotinic receptor in
  sympathetic ganglia overwhelm parasympathetic
  stimulation produce tachycardia, hypertension,
  stimulate adrenal gland
• Cholinergic excess in CNS
• Delirium, confusion, coma and seizure
• Cause of death respiratory failure combined with
  depress CNS and increase bronchial secretion

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Laboratory finding

• Routine lab finding nonspecific nonketotic
  hyperglycemia, hypokalemia, leukocytosis,
  pulmonary edema
• CVS tachycardia is more common due to both
  sympathetic and parasympathetic stimulation
• Arrhythmia first transient phase of intense
  sympathetic tone cause sinus tachycardia
  following by extreme parasympathetic tone cause
  sinus bradycardia

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Diagnosis

• Classic presentation of serious OP poisoning
  agitation/coma with diaphoresis, pinpoint pupil,
  muscle fasculations, bradycardia and respiratory
  distress
• Increase oral and bronchial secretions with urine
  and bowel incontinence

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• Definite diagnosis of OP intoxication
• Decreased cholinesterase activity in the blood
• RBC cholinesterase is more accurate but less
  available, serum cholinesterase is more sensitive
  but less specific
• Mild case deceased cholinesterase lever to
  20-50, severe case decreased less than 10
• Some chronic, lowgrade intoxication may show
  normal level of cholinesterase
• Carbamate poisoning is less useful due to
  cholinesterase level may return to normal in 4-8
  hr

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Management

• Clinical suspect patient
• Asymptomatic patient observe 6-8 hr
• Severe case respiratory support and
  decontamination, use specific antidotes
• Establishment of airway
• Initial objective treatment establishment of
  airway and adequate ventilation
• Usually patient presents with respiratory
  distress, excessive secretion, bronchospasm

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Atropine use

• Atropine
• Atropine is competitively blocking the action of
  Ach at muscarinic receptor (not nicotinic
  receptor), decrease parasympathetic stimulation
• Use repeat dose of atropine until atropinization
  (mydriais, tachycardia flushing, xerostoma)
  appear. (dry of secretion is endpoint)
• Adult dose 2mg iv/5-15min
• Child dose 0.05mg/Kg repeat 15min

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Decontamination

• After initial stabilization, the patient should
  be decontaminated
• Remove exposure clothing and vigorous washing of
  skin with soap

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Ipecac, Charcoal, Cathartic

• Patient ingested OP should use gastric emptying
• Use Ipecac induced emesis for gastric lavage

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Pralidoxime

• Pralidoxime (PAM) is antidote for primary OP
  intoxication but not for carbamate poisoning
• PAM reverse the cholinergic nicotinic effects
• PAM
• reactivation of cholinesterase by cleavage of
  phosphorylated active site
• Direction reaction and detoxification of
  unbounded organophosphate molecular
• Endogenous anti-cholinergic effect

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• PAM
• Initial dose 1g iv over 15-30 min
• Pediatric dose 20-50 mg/Kg over 15-30 min
• Subsequent dose may repeated 1-2 hr after initial
  dose and every 10-12 hr
• Reversal of muscle weakness and fasciculation
  usually begins within 10-40 min
• Treatment usually continuous 24-48 hr