Organophosphorous poisoning

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 : Acute cholinergic syndrome (most common) Sub acute proximal weakness (Intermediate syndrome) Organophosphate induced delayed neuropathy (OPIDN) 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. Late death: - Secondary to ventricular arrhythmias, including Torsades de Pointes, which may occur up to 15 days after acute intoxication.

38. Thank you