Management of op poisoning

1. Organophosphorus Poisoning
Intern. Lokeshwor Maharjan

2. INTRODUCTION
 Organophosphorus (OP) compounds are used as
pesticides, herbicides, and chemical warfare
agents in the form of nerve gases.

3. Common dimethyl and diethyl phosphoryl
compounds
Dimethyl OPs Diethyl OPs
Parathion Methyl parathion
Diazinon Dichlorovos
Chlorpyrifos Dimethoate
Dichlorfenthion Malathion
Coumaphos Fenthio

4. Common OP pesticides with their brands
available in Nepal
OP pesticide Brands available
Methyl parathion Metacid, Parahit, Paradol
Dichlorovos Nuvan, DDVP, Nudan, Suchlor
Dimethoate Rogor, Roger, Rogohit
Chlorpyrifos Durmet, Dhanuban, Radar
Fenthion Dalf, Baytex
Profenofos Current
Quinalphos Krush
Monocrotophos Phoskill

5. Nerve Agents
 G agents-sarin, tabun, soman
 V agents-VX, VE

6. Carbamates
 Aldicarb
 Carbofuran
 Methomyl
 Baygon

7. Diagrammatic representation of the possible reactivation & ageing
reactions of AChE after inhibition by OP compounds

8. AGEING
 Irreversible inhibition of acetylcholinesterase due to phosphorylation
of the active site of the enzyme(serine hydroxl group) and with time
the enzyme-OP complex loses one alkyl group making it no longer
responsive to reactivating agents.
 Ageing time
 Dimethyl – 3.7 hours
 Diethyl – 31 hours
 Nerve agents – within minutes
 Carbamate-no ageing
 Spontaneous reactivation half life
 Dimethyl - 0.7hours
 Diethyl - 31 hours
 Carbamate-30-40 minutes

9. Clinical syndrome
1. Acute cholinergic syndrome
2. Intermediate syndrome
3. Organophosphate-induced delayed
polyneuropathy(OPIDN)

10. Acute cholinergic syndrome
 Muscarinic effect
 Nicotinic effect
 CNS effect

11. Muscarinic effects(parasympathetic)
 D iarrhoea, Abdominal cramps
 U rinary incontinence
 M iosis
 B radycardia, Hypotension, Ventricular tachycardia
 E mesis
 L acrimation
 S alivation
 Pulmonary oedema, bhronchospasm, bronchorrhea

12. Nicotinic effect(NMJ)
 Muscle fasciculation
 Muscle weakness
 Paralysis
 Respiratory failure
 Hyper-reflexia

13. Nicotinic effect(sympathetic)
 Tachycardia
 Mydriasis
 Hypertension
 Sweating

14. CNS effect
 Restlessness
 Seizures
 Coma
 Respiratory and circulatory depression

15. Intermediate syndrome
 Usually occurs after 24 to 96 hours of ingestion.
 last up to 5-14 days
 Approximately 10-40% of patients develop this
illness.
 Characterized by prominent weakness ocular
muscles to neck flexors, muscles of respiration
and proximal limb muscles.
 Require ventilatory care.

16. DELAYED POLYNEUROPATHY (OPIDN)
 Uncommon consequence of severe intoxication or intermittent and
chronic contact
 Due to inhibition of neuropathy target esterase (NTE) enzyme in
nervous tissues
 Chlorpyrifos(Durmet, Dhanuban, Radar) causes comparatively more
degree of inhibition of NTE
 Clinical manifestations are of distal symmetric sensory-motor
polyneuropathy (muscle cramp, distal weakness, parasthesia, ataxia,
diminished or absent reflexes, flaccid paralysis)
 usually begin 2-5 weeks after exposure and may last for years.
 No specific therapy but regular physiotherapy may limit the deformity.

17. PARADENIYA ORGANOPHOSPHORUS POISONING(POP scale)

18. DIAGNOSIS
 History of exposure to OP compounds.
 Characteristics manifestations like Pinpoint pupil, Muscle
fasciculation, characteristic (garlic) smell of stomach aspirate
 In case of doubt atropine challenge test can be done
1-2mg iv atropine is given, if it doesn’t produce dry skin,
dry mucosa, tachycardia and mydriasis in 15-20 minutes patient
has to be treated in the line of OP.

19. LAB TEST
 Limited value as treatment is usually required before test results are
available
 Level of plasma (pseudo) cholinesterase drops to less than 50%( Normal
value 3000-6000IU/L)
 Clinical severity has been graded on the basis of the pseudocholinesterase level
 Mild 20-50% enzyme activity
 Moderate 10-20% enzyme activity and
 Severe <10% enzyme activity
NB: True or erythrocyte cholinesterase correlates well with clinical severity but
is not available in most centres

20. TREATMENT
 General supportive treatment
 Specific Antidotal Treatment

21. General supportive treatment
1. Assessment of airways, breathing, and circulation
 Comatose or vomiting patients should be kept in lateral positioning and
consider of placement of Guedel’s airway or ET intubation.
 Frequent suctioning is essential as excessive oropharyngeal and respiratory
secretions may occlude the airway.
 Oxygen is needed in majority of these patients; and this can be assessed by
frequent assessment of arterial oxygen saturation.

22. 2. Decontamination
The clothes should be removed and the skin
vigorously washed with soap and water.
NB: Always remember to wear gloves so as to prevent
skin absorption of the poison.

23. 3. Gastric lavage
Should be considered in patients presenting within 1-2
hours of ingestion of poison
 Risks of gastric lavage include :
 Aspiration
 Hypoxia
 Laryngeal spasm
Administer activated charcoal 100gm(aprox. 1gm/kg) in 200-
500ml of water.

24. Specific Antidotal Treatment
 Atropine
 Has been cornerstone in the management of OP poisoning
 Atropine only blocks muscarinic effects whereas oximes reverse
both the nicotinic and muscarinic effects
 MOA: competitively at the peripheral and central muscarinic
receptors and antagonizes the parasympathetic effects of excess
Ach.

25. Target end-points for Atropine therapy
 Heart rate >80/ min
 Dilated pupils
 Dry axillae
 Systolic blood pressure >80 mm Hg
 Clear chest with absence of wheeze

26. HOW MUCH ATROPINE???
 Initial bolus of 3-5 ampoules of atropine (each
ampoule containing 0.6 mg)
 Subsequent doses doubled every 5 minutes until
atropinization is achieved
 When the patient achieves most of (at least 4 out of 5)
the target end-points for atropine therapy i.e. fully
atropinized

27. Scheme of atropinization

28. INFUSION ATROPINE
 10% of initial atropinizing dose per hour for first 24 hours
 Reduce by 20-30% every day of initial dose
 Tapper in this manner for 5 days
 Reduce dose if features of toxicity develop

29. What if you give too much ATROPINE?
 Hot as Hell
 Blind as a Bat
 Red as a Beet
 Dry as a Bone
 Mad as a hatter
That means hyperthermia, tachycardia, tremer,
restlessness, confusion, agitation, seizures

30. Oximes
 Oximes work by reactivating acetylcholinesterase that has been
bound to the OP molecule
 Eg. Pralodoxime(frequently used), obidoxime
 WHO recommended pralidoxime dose of
30 mg/kg bolus iv over 10-20 minutes followed by continuous
infusion of 8-10 mg/kg/hour till atropine no longer required or 7 days
(whichever later)
 Not recommended for carbamates

31. Benzodiazepines:
 Diazepam and other benzodiazepines are widely used
for the treatment of OP induced seizures and
restlessness and agitation

32. Pregnancy
 ingested OP insecticides during the second or third
trimester of pregnancy have been treated successfully
with atropine and pralidoxime

33. Diet
 Nill per oral during atropinization
 Once peristalsis sounds are heard start oral fluids and
gradually shift to soft food

34. Newer forms of therapies in OP
poisoning
 Sodium bicarbonate
 Adrenergic receptor α2 agonists like clonidine
 Magnesium sulphate
 Fresh frozen plasma
 Antioxidants
 Organophosphorus hydrolases
 Galyclidine (NMDA receptor antagonist)