This document discusses organophosphate poisoning. It begins by introducing organophosphates as a group of chemicals used in domestic and industrial settings that act as acetylcholinesterase inhibitors. It then describes the chemical structure and mechanisms of organophosphates, their routes of entry into the body, and how they cause toxicity by inhibiting acetylcholinesterase. The document goes on to describe the clinical features, phases, and syndromes of organophosphate poisoning as well as their treatment, which involves stabilization, decontamination, administration of the antidotes atropine and pralidoxime, and supportive care.

1. ORGANOPHOSPHATE
POISONING
By: Nandinii Ramasenderan

2. Introduction:
• Organophosphate (OP) compounds are a diverse group of chemicals used
in both domestic and industrial settings.
• Examples of organophosphates include insecticides (malathion, parathion,
dichlorvos, and diazinon)
• Worldwide mortality studies report mortality rates from 3-25 %
• Mortality rates depend on the type of compound used, amount ingested,
general health of the patient, delay in discovery and transport, insufficient
respiratory management, delay in intubation, and failure in weaning off
ventilatory support.

3. -OPs are esters of phosphoric acid and its derivates.
-Comprises a central phosphorus atom (P) and the characteristic phosphoric (P=O) or
thiophosphoric (P=S) bond.
-The symbol X represents the leaving group, which is replaced (by nucleophilic substitution)
by the oxygen of serine in the AcHE active site.
The rate of AcHE inhibition depends on the leaving group; higher tendency of leaving results
in higher affinity of the inhibitor to the enzyme.
Chemical structure:

4. Route of entry:

5. Acetylcholinesterase (AChE)
AChE is an enzyme that degrades the neurotransmitter acetylcholine
↗AChE

6. Pathogenesis:

7. Clinical
features

8. Mnemonic for muscarinic signs & symptoms:
• S – Salivation D – Diaphoresis & diarrhoea
• L- Lacrimation U - Urination
• U – Urinary incontinence M - Miosis
• D – Diarrhoea + diaphoresis B – Bradycardia, bronchospasm
• G – GI upset E – Excess
• E –Emesis L – Lacrimation &
S - Salivation

9. Clinical phases:
1.Initial life-threatening acute cholinergic crisis
2.Intermediate syndrome (IMS)
3.Organophosphate induced delayed polyneuropathy (OPIDN)

11. INTERMEDIATE SYNDROME
• Characterized by absent muscarinic symptoms with continued
nicotinic symptoms and persistent AChE inhibition
• Onset = 24 – 72 hrs after acute cholinergic crisis
• Pathophysiology – inadequate oxime dosing
-Most likely due to lesions in post synaptic striated muscle regions
- Myonecrosis due to oxidative cellular damage
Later studies – down regulation or desensitization of nicotinic ACh receptors at post junctional
membrane

12. Patients at risk
• Poisoning due to OPs with delayed metabolism
• Severe poisoning
• Elevated muscle enzymes
• Delayed or inadequate oxime therapy

13. Clinical features – NICOTINIC SYMPTOMS
• Paralysis of proximal limb muscles, neck flexors, cranial nerves,
respiratory muscles, decreased DTR
• Rapid onset of difficulty in breathing

14. Treatment of IMS
• Mainly supportive treatment
• Complete recovery in 4-18 days if adequate ventilatory support is
provided
• Oximes - preventive

15. OP INDUCED POLYNEUROPATHY (OPIDN)
Delayed mixed sensorimotor peripheral neuropathies
• 7-14 days after exposure
• Pathophysiology : Inhibition of neuropathy target esterase(NTE )
• C/o: Symmetric, peripheral neuropathies
Motor > sensory
Ataxia, gait disturbances
• Fate – self-resolution / persistent deficits

16. Investigations
ECG
Oxygen saturation
Blood gas analysis
Renal and hepatic function
Electrolytes
Glucose
Amylase
Urine toxicology

17. Grading of severity of poisoning
Biochemical Grading:
Red cell cholinesterase activity (% normal) Grade
• 20-50% Mild
• 10-20% Moderate
• <10% Severe

18. Assessment of severity of OP poisoning
GRADES CNS Secretions Fasciculations Hypotension
0 Awake, alert - - - Only history
1 Awake, alert + + -
2 Drowsy ++ ++ + (SBP <90)
3 Drowsy/
Comatose
++ ++ + Inc FiO2
4 Comatose +++ +++ + PaO2 < 60 on FiO2
>40, PaCo2 >45
Mechanical
ventilation reqd
Abnormal CXR
ICU admission if grade ≥ 2
Brent I., Wallace K., Burkhart O. & et al. Organophosphorus and carbamate insecticides, Methanol poisoning. Critical care
Toxicology.Diagnosis and management of the critically poisoned patient. Philadelphia, Elsevier Mosby, 2005 : pp 937-947.

19. Management of OP Poisoning
Hospitalization/ ICU
1. Initial stabilization
2. Reduction of exposure
3. Administration of specific antidote
4. Supportive treatment

20. Initial Stabilization of the patient
• Clear airway and
• Adequate ventilation because the patient with acute
organophosphate poisoning (ACC) commonly
presents with respiratory distress.
• Oxygen- Circulation- iv access

21. Decontamination
• Dermal spills—wash pesticide spills from the patient
with soap and water and remove and discard contaminated clothes,
shoes and any other material made from leather
• Gastric lavage—consider for presentations within 1 or 2 hours, when
the airway is protected. A single aspiration of the gastric contents may
be as useful as lavage
• Activated charcoal —50 g may be given orally or nasogastrically to
patients who are cooperative or intubated, particularly if they are
admitted within one or two hours or have severe toxicity

22. Antidotes in the treatment of OP poisoning
• Atropine- Reverses the muscarinic features.
• Oxime- Reactivate cholinesterase and reverses the
nicotinic features.

23. Atropine
• Initial dose: 0.5-2 mg IV every 5-10min until atropinization
• Continuous infusion (8mg atropine in 100ml NS) at rate of 0.02-
0.08mg/kg/hr (0.25-1.0 ml/kg/hr) with additional 1-5mg bolus
• May require about 40-1500mg/day
• For at least 5-7days
• Watch out for OVER ATROPINIZATION

24. Target end points for atropine therapy
• Clear chest on auscultation with no wheeze
• Heart rate> 80/min
• Pupils no longer pin point (does not imply that pupils must be dilated)
• Dry axilla
• Systolic BP > 80 mm Hg
Dilated pupils is not a reliable sign of initial atropinisation or end point
for atropine therapy

25. Pralidoxime
• An oxime that reactivates phosphorylated cholinesterase
• Effects: skeletal-neuromuscular junctions (counteracts weakness,
fasciculation and respiratory depression)
• Administration within 48 hours of poison ingestion
• IV 1-2gm in 100cc of NS over 30min (at a rate not exceeding
200mg/min), repeat in 1 hour if muscle weakness persist, then at 8-
12 hours interval if cholinergic signs recur
• Severe case: IV infusion 500mg/hr (max 12gm in 24hours)
• Started after maximal atropinization

26. OXIMES IN OP POISONING