organophosphorous poisoning in nepal and its management

1. ORGANOPHOSPHOROUS
POISONING
Dr. Amit Poudel
Patan academy of health science

2. • Poisoning has been a common cause of medical admissions and
deaths in Nepalese hospitals.
• 31% of all suicidal deaths are due to poisoning.
• OP compounds were the most common form of poisoning - 52% of
total cases.
• occupy the greatest burden of poisoning related morbidity and
mortality in Nepal

3. Compounds
• first used as an agricultural insecticide and later as potential chemical
warfare agents.
• are normally esters, thiol esters, or acid anhydride derivatives of
phosphorus containing acids.
• >100 OP pesticides used worldwide, the majority are dimethyl
phosphoryl or diethyl phosphoryl compounds.
• Nerve gas compounds like tabun, sarin, and soman are highly potent
synthetic toxic agents of this group.

4. Common dimethyl and diethyl phosphoryl
compounds

5. Common OP pesticides with their brands
available in Nepal

6. Mechanism of action
• OP compounds phosphonylate
the active site of
acetylcholinesterase (AChE),
inactivating the enzyme
• leading to the accumulation of
acetylcholine (ACh) in
cholinergic synapses

7. • Spontaneous hydrolysis of the OP-enzyme
complex allows reactivation of the enzyme.
• AChE-dimethyl OP complex spontaneously
reactivate in less than one day
• AChE-diethyl OP complex may take several
days and reinhibition of the newly activated
enzyme can occur significantly
• spontaneous reactivation can be hastened
by adding nucleophilic reagents like oximes,
liberating more active enzymes.

8. • loss of a chemical group from the OP-
enzyme complex prevents further
enzyme reactivation, a process termed
‘ageing’.
• After ageing has taken place, new
enzyme needs to be synthesised before
function can be restored.

9. • rate of ageing is an important determinant of toxicity
• dimethyl compounds (3.7 hours)
• diethyl compounds (31 hours)
• rapid after exposure to nerve agents (soman in particular) -ageing
within minutes

10. Signs and symptoms of OPC poisoning
Four clinical syndromes have been described:
1. Acute cholinergic syndrome (most common)
2. Sub acute proximal weakness (Intermediate syndrome)
3. Organophosphate induced delayed neuropathy (OPIDN)
4. Chronic organophosphate induced neuropsychiatric disorder (COPIND)

11. Acute cholinergic crisis
Muscarinic effects
•Cardiovascular - Bradycardia, hypotension
•Respiratory - Rhinorrhea, bronchorrhea, bronchospasm, cough,severe
respiratory distress
•Gastrointestinal - Hypersalivation, nausea and vomiting, abdominal pain,
diarrhea, fecal incontinence
•Genitourinary - Incontinence
•Ocular - Blurred vision, miosis
•Glands - Increased lacrimation, diaphoresis

12. Nicotinic effect
• muscle fasciculations
• cramping
• weakness
• diaphragmatic failure
• hypertension
• tachycardia
• mydriasis
• pallor

13. CNS effects
• Anxiety
• Emotional lability
• Restlessness
• Confusion
• Ataxia
• Tremors
• Seizures
• Coma

14. Intermediate syndrome
• usually occurs 24 to 96 hours after the ingestion of an OP compound
• after an initial cholinergic crisis but before the expected onset of
delayed polyneuropathy.
• Approximately 10-40% of patients treated for acute poisoning
develop this illness.
• characterized by prominent weakness of neck flexors, muscles of
respiration and proximal limb muscles.
• Mostly seen with fenthion, dimethoate and monocrotophos,

15. • muscle weakness may last up to 5-14 days
• condition regresses slowly if respiratory support is available.
• exact pathogenesis is unclear, the proposed mechanisms include
persistent inhibition of AChE leading to functional paralysis of
neuromuscular transmission, muscle necrosis, and oxidative free
radical damage to the receptors.

16. Delayed Polyneuropathy
• is an uncommon consequence of severe intoxication or intermittent and
chronic contact with OP pesticides as in occupational exposure.
• is due to inhibition of neuropathy target esterase (NTE) enzyme in nervous
tissues by certain OP compounds.
• often unrecognized in humans.
• distal symmetric sensory-motor polyneuropathy (distal weakness,
parasthesia, ataxia, diminished or absent reflexes).
• symptoms usually begin 2-5 weeks after exposure, and may last for years.
• OP pesticides can also cause chronic neurotoxicity and behavioural
impairment in some patients

17. Diagnosis
History and clinical features
• History of ingestion, availability of bottles
• typical clinical symptoms and signs help to diagnose the OP
poisoning.
• characteristic petroleum or garlic – like odour, which may be helpful
in establishing the diagnosis

18. Atropine challenge
• If doubt exists, a trial of 1 mg atropine in adults (or 0.01 to 0.02
mg/kg in children) may be employed.
• absence of signs or symptoms of anticholinergic effects following
atropine challenge strongly supports the diagnosis of poisoning with
an acetylcholinesterase inhibitor
• If pulse rate goes up by 25 per minute or skin flushing develops
patient has mild or no toxicity

19. RBC acetylcholinesterase
• Direct measurement of RBC acetylcholinesterase (RBC AChE) activity
provides the measure of the degree of toxicity
• the test is not usually available.
plasma (or pseudo) cholinesterase activity
• is more easily performed
• does not correlate well with severity of poisoning
• should not be used to guide therapy.
AChE and PChE activity can fall to about 80% of normal before any symptoms
occur and drop to 40% of normal before the symptoms become severe.

20. Chemical analysis of vomitus or gastric aspiration
• may identify the poison.
• Chemical analysis may also be particularly important in case of self-
poisoning using multiple compounds.
• Thus, after gastric lavage or vomiting, the aspirate or vomitus should
be preserved.

21. Grading of severity of poisoning
• Clinical Grading (Peradeniya organophosphorous score)
• Biochemical Grading

22. Peradeniya organophosphorous score (POP)

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

24. Treatment
General measures
• Rapid initial assessment of airways, breathing, and
circulation is essential.
• Comatose or vomiting patients should be kept in
lateral, preferably head down position with neck
extension to reduce the risk of aspiration.
• airway should be secured with proper positioning,
placement of Guedel’s airway or with endotracheal
intubation Frequent suctioning
• Oxygen
• clothes should be removed and the skin vigorously
washed with soap and water.

25. Gastric lavage
• may help to reduce the absorption of the ingested poison and should
be considered in patients presenting within 1-2 hours of ingestion of
poison.
• risks of gastric lavage include
• aspiration,
• hypoxia, and
• laryngeal spasm,

26. Treatment of Acute Toxicity
Atropine
• 2 – 5 mg IV bolus (0.05 mg/kg IV in children). (each ampoule
containing 0.6 mg)
• Check three things after five minutes: pulse, blood pressure and chest
crackles.
• Aim for heart rate >80 beats per minute, SBP > 80 mm Hg, and a
clear chest (atropine won't dry focal areas of aspiration).
• Double the atropine dose every five minutes if you have not achieved
these objectives.

27. • Review patient every 5 min.
• Once these parameters start improving, repeat last same or smaller
dose of atropine.
• If improvement in these parameters is persistent and satisfactory
after 5 min, now you can plan for atropine infusion.

28. 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

29. • When the patient achieves most of (at least 4 out of 5) the target
end-points for atropine therapy i.e., ‘fully atropinized’, an intravenous
infusion is set up to maintain the therapeutic effects of atropine.
• use 20% of initial atropinizing dose per hour for first 48 hours and
gradually taper over 5 -10 days, continuously monitoring the
adequacy of therapy.

30. • Atropine toxicity can result in
• agitation,
• confusion,
• hyperthermia,
• severe tachycardia
• can precipitate ischaemic events in patients with underlying coronary
artery disease.

31. Management of Atropine toxicity
• Stop the atropine infusion
• Check again after 30 min to see whether the features of toxicity have
settled
• If not, continue to review every 30 min or so
• When they do settle, restart at 70–80% of the previous rate
• The patient should then be seen frequently to ensure that the new
infusion rate has reduced the signs of atropine toxicity without
permitting the reappearance of cholinergic signs

32. Pralidoxime
• recommended in patients with evidence of cholinergic toxicity in
patients with organophosphorous poisoning.
• PAM is not recommended for poisoning due to carbamate poisoning.
• The standard recommended dose of PAM is 2 g (25 – 50 mg/kg in
children) IV over 30 minutes, with continue infusion at 8 mg/kg/hour
in adults (10 – 20 mg/kg/hour in children)
• Alternate dose- 1 gm of bolus followed by 0.5 to 1 gm 6 to 8 hourly in
adult patient.
• can be continued as per the severity of poisoning.

33. Point to remember
• Pralidoxime should not be administered without concurrent atropine,
to prevent worsening symptoms due to transient oxime induced
acetylcholinesterase inhibition
• Even the bolus dose of PAM is administered slowly
• a fast infusion can cause vomiting, hypertension, cardiac arrhythmia
or a cardiac arrest.

34. Giving fluids/ IV channel
Two IV drips should be set up
 One for fluid and drugs. Give 500–1000 ml (10–20 ml/kg) of
normal saline
 Other for atropine

35. Benzodiazepine therapy
• Diazepam 0.1 – 0.2 mg/kg/ IV,
• repeated as necessary, if seizures occur.
• early use of diazepam may reduce morbidity and mortality

36. Cause of Death in OPC poisoning
1. Immediate death:
– Seizures.
– Complex ventricular arrhythmias.
2. Death within 24 hours:
- Acute cholinergic crisis in untreated severe case
-Respiratory failure.
3. Death within 10 days of poisoning:
- intermediate syndrome.
Contd.

37. Cause of Death in OPC poisoning
3. Death within 10 days of poisoning:
- intermediate syndrome.
4. Late death:
- Secondary to ventricular arrhythmias, including Torsades de
Pointes, which may occur up to 15 days after acute
intoxication.

38. Thank you