Organophosphorus poision. TREATMENT & MANAGEMENT

1. ORGANOPHOSPHORUS
POISIONING
DR ANKIT GAJJAR
MD, IDCCM, IFCCM, EDIC
CONSULTANT INTENSIVIST

2. • USE
• CLASSIFICATION
• TYPES
• METABOLISM
• CLINICAL FEATURES
• DIAGNOSIS
• MANAGEMENT

3. USE
• Agriculture as a pesticide
• Household chemical
• Nerve agents in chemical warfare

4. CLASSIFICATION
• Based on toxicity & clinical use
• Highly Toxic: Agriculture insecticides (parathion)
• Intermediate toxic: Animal insecticides
(trichlorfon)
• Low toxic: Household application & Field spray
(malathion, diazinon)

5. EXPOSURE

6. ABSORPTION ROUTE
• Ingestion (Accidental or Suicidal)
• Cutaneous
• Inhalation

7. PHARMACOKINETICS
• Most of are highly lipid soluble
• Well absorbed from skin, mucous membrane,
conjunctiva, GI tract and Respi tract
• Easily cross BBB
• Metabolism by oxidation in liver & esterase
hydrolysis
• Redistribution is common

8. MOA

9. MOA
• OP inactivates AChE by phosphorylation in synapses,
on RBC membrane & butyrylcholinesterase in plasma
• Accumulation of Ach throughout the Nervous system
– overstimulation of muscarinic & nicotinic receptors
• Aging occurs when phosphorylated AChE loses alkyl
side chain
OP vs Carbamates
• Same MOA but in carbamtes binding occurs
reversible so no Aging

10. AGEING
• DIETHYL – 50% by 33 hrs
- PAM useful for 5 days
• DIEMETHYL – 50 % by 3 hrs
- PAM useful for 12 hrs
• 5-ALKYL GROUP – no use of PAM

11. MOA
Sequelae of AchE
• Spontaneous reactivation
• Reactivation by PAM
• Irreversible binding by permanent enzyme
inactivation (Aging)
• Onset and severity depends on compound,
route of exposure and metabolism

12. CLINICAL FEATURES
Garlic smell

13. CLINICAL FEATURES

14. CNS
Type 1 Paralysis / Acute Paralysis
• During initial cholinergic phase
• Due to large number of Ach at muscarinic &
nicotinic receptor
• Patient may need venti support
• Fasciculation, twitching, weakness

15. CNS
• Type 2 Paralysis / Intermediate Syndrome
(IMS)
- Downregulation of presyneptic & postsyneptic
receptor
- Inadequate oxime treatment
• Lipid soluble agents
• 24-96 hours after ingestion
• Progressive muscle weakness – Ocular, Neck,
Proximal limb, Respiratory muscle
• Treatment – supportive (3-4 weeks)

16. CNS
• Type 3 Paralysis / OP Induced delayed
Polyneuropathy (OPIDN)
• After 2-4 weeks
• Distal limb weakness
• Sensory loss
• Weakness & ataxia
• Recovery takes 1-2 yrs

17. CNS
• Delayed OP Encephalopathy (DOPE)
• Normal sensorium to progressive coma
• Can be extrapyramidal side effects
• Clinically brain dead
• Neuroimaging & CSF normal
• Prognosis good

18. DIAGNOSIS
• H/O exposure
• Typical garlic smell
• SLUDGE
• Plasma butyryl cholinesterase / RBC AChE

19. DIAGNOSIS
PLASMA
BUTYRYLCHOLINESTERASE
RBC CHOLINESTERASE
Easily asses Not readily available
Does not correlate with clinical
severity
Correlate with the neuronal activity &
severity
Used to detect exposure to OP Marker of severity
Rising trend suggest that OP is
eliminated
Slow recovery (1% / day)
Response to Antidote therapy is less Increase activity after PAM therapy
Levels altered in malnutrition, chronic
illness & chronic liver disease
Levels altered in Hbpathies &
Thalassemia

20. TREATMENT
• ABC
• DECONTAMINATION
• Gastric Lavage – 1-2 hrs
• Activated Charcoal – 1-2 hrs
• Atropine
• PAM

21. TREATMENT
• ATROPINE
• Blocks muscarinic receptors
• Incremental dose regimen – double the dose every 5
minutes – 10-20% infusion
• Intermittent bolus – 2-5 mg / 10-15 minutes
• Continuous infusion
• End point of atropine
- Reduce secretion
- SBP > 80
- HR > 80

22. TREATMENT
• Atropine toxicity
- Fever, Delirium, urinary retention, tachycardia
• Discontinue if toxicity
• Restart with 70-80% of previous rate
• Glycopyrrolate can be used

23. TREATMENT
• PRALIDOXIME
• Reactivation of AChE
• MOA – PAM binds to OPC causing the compound to
break its bond with AChE
• Mainly affect PNS only, CNS penetration is limited
• Enhance recovery of NM transmission at nicotinic
synapses
• Enhance activity at muscarinic site as well, reducing
Atropine requirement

24. TREATMENT
• DOSE – 30 mg/kg bolus f/b 8 mg/kg/hr
• End Point - Clinical recovery or 12-24 hrs after
atropine stopped
• Rapid infusion – tachycardia, laryngospasm

25. TREATMENT
• MgSO4
Reduce Ach at motor end plate
• CLONIDINE
Reduce Ach synthesis & release
• FFP