ORGANOPHOSPHATES and PARAQUAT Poisoning

1. ORGANOPHOSPHATESand PARAQUAT Poisoning Zarmehri B.

2. Case presentation • A 40-years-old farmer man presents to emergency department of a local hospital with confusion, emesis, diarrhea, salivation and lacrimation.

3. In history, he has no medical illness, but he has been on an antidepressant medication from 2 weeks ago. He has no allergy history. • Vital signs at presentation are blood pressure of 110/70 mmHg, pulse rate of 65bpm, respiratory rate of 35/min and temperature of 37°C.

4. His O2 Saturation is 85% at room air. • Physical examination reveals copious respiratory secretion, crackles in lung auscultation and miotic pupils.

5. Organophosphates • Acephate, • Malathion, • Parathion, • Chlorpyrifos

6. Systemic absorption of organophosphates occurs by inhalation and after mucousmembrane, transdermal, transconjunctival, and GI exposure.

7. Pathophysiology • Organophosphate and carbamate compounds inhibit the enzyme cholinesterase. • Acetylcholinesterase (true or red blood cell acetylcholinesterase) is found primarily in erythrocyte membranes, nervous tissue, and skeletal muscle. • Plasma cholinesterase (pseudocholinesterase) is found in the serum, liver, pancreas, heart, and brain.

8. Inhibition of cholinesterase leads to acetylcholine accumulation at nerve synapses and neuromuscular junctions, resulting in overstimulation of acetylcholine receptors→cholinergic crisis that manifests as a central and peripheral clinical toxidrome.

9. Aging • Aging is a term describing the permanent, irreversible binding of the organophosphorus compound to the cholinesterase. • Once aging occurs, the enzymatic activity of cholinesterase is permanently destroyed, and new enzyme must be resynthesized over a period of weeks. • Antidotes must be given before aging occurs to be effective.

10. Clinical Features • In acute organophosphate poisoning, most poisoned patients are symptomatic within the first 8 hours and nearly all within the first 24 hours. • Acute organophosphate poisoning results in CNS, muscarinic, nicotinic, and somatic motor manifestations

13. Acetylcholine is the presynaptic neurotransmitter at nicotinic receptorsin the sympathetic ganglia. • Inhibition of acetylcholinesterase at these locations results in sympathetic stimulation, producing pallor, mydriasis, tachycardia, and hypertension.

14. In most patients, parasympathetic stimulation usually predominates, but mixed autonomic effects are common. • Nicotinic stimulation at neuromuscularjunctions results in muscle fasciculations, cramps, and muscle weakness.

15. This syndrome may progress to paralysis and areflexia, making it difficult to detect seizure activity. • Respiratory muscle paralysis can lead to ventilatory failure.

16. An intermediate syndrome may occur 1 to 5 days after an organophosphate exposure, reported in up to 40% of patients following ingestion. • Clinical features include paralysis of neck flexor muscles, muscles innervated by the cranial nerves, proximal limb muscles, and respiratory muscles; respiratory support may be needed.

17. Aggressive, early antidote therapy and supportive measures may prevent or ameliorate the severity of this syndrome. • Symptoms usually resolve within 7 days.

18. Chemical warfare nerve agents, such as soman, sarin, tabun, and VX, are organophosphate compounds that inactivate acetylcholinesterases. • They are rapid acting and extremely potent; death can occur within minutes of inhalation or dermal exposure, as occurred in the subway terrorist attack in Tokyo 1985.

22. Diagnosis • Diagnosis and treatment are based on history and the presence of a suggestive toxidrome. • Laboratory cholinesterase assays take time and have limitations, and waiting for results delays administration of potentially life-saving therapy.

23. Organophosphate insecticide poisoning should be considered in the differential diagnosis of a patient with altered mental status and pinpoint pupils. • Miosis and muscle fasciculations are considered reliable signs of organophosphate toxicity.

24. A prolonged QTc interval correlates with severity and mortality in severe organophosphate poisoning.

25. Treatment • Airway Control, • Intensive Respiratory Support, • General Supportive Measures, • Decontamination, • Prevention of Absorption, • Administration of Antidotes

26. Therapy should not be withheld pending determination of cholinesterase levels.

28. Oxygen, • Cardiac Monitor, • Pulse Oximeter. • 100% Nonrebreather Mask

29. Coma, seizures, respiratory failure, excessive respiratory secretions, or severe bronchospasm necessitate endotracheal intubation. • A nondepolarizing agent should be used when neuromuscular blockade is needed. • Succinylcholine is metabolized by plasma butyrylcholinesterase, and therefore, prolonged paralysis may result.

30. Hypotension is initially treated with fluid boluses of isotonic crystalloid. • It is unlikely that gastric lavagewill be of benefit except in patients who present within 2 hours after a large ingestion.

31. Activated charcoal is sometimes recommended because organophosphates do bind in vitro. • Urinary alkalinizationis often used in Brazil and Iran for organophosphate poisoning, but there is no controlled evidence that shows benefit.

32. Atropine • The dose of atropine is repeated every 5 minutes until copious tracheobronchial secretions attenuate; large amounts may be necessary, in the order of hundreds of milligrams in massive ingestions. • Pupillary dilatation is not a therapeutic end point. • Tachycardiais not a contraindication to the use of atropine in organophosphorus poisoning.

33. 2 to 6 milligrams IMshould be considered when IV access is not possible. • Normally, this initial dose of atropine should produce antimuscarinic symptoms; therefore, absence of anticholinergic symptoms after an initial dose is indicative of organophosphate poisoning.

34. Importantly, atropine does not reverse muscle weakness.

35. Pralidoxime • Pralidoxime reverses muscle paralysis, muscarinic, nicotinic, and CNS symptoms if given early, before aging occurs. • Although pralidoxime is more effective in acute than in chronic intoxications, it is recommended for use even after >24 to 48 hours after exposure.

36. The pralidoxime dose recommended by the World Health Organization is a 30-milligram/kg IV bolus followed by an IV infusion of 8 milligrams/kg per hour. • Pralidoxime should be continued for 24 to 48 hours.

37. Pralidoximeis not recommended for asymptomatic patients or for patients with known carbamate exposures presenting with minimal symptoms.

38. Seizures are treated with airway protection, oxygen, atropine, and benzodiazepines. • Atropine may prevent or abort seizures due to cholinergic overstimulation that occur within the first few minutes.

39. Disposition • Minimal exposures may require only decontamination and 6 to 8 hours of observation in the ED to detect delayed effects. • Admission to the intensive care unit is necessary for significant poisonings.

40. PARAQUAT

41. A 34 years old man was referred from a nearby town to our academic hospital with abdominal pain, nausea, vomiting, icter, and decreased level of consciousness from 12 hours ago. • In history, he declared that he had drunk a glass of green colored herbicide 2 days ago as a suicidal attempt.

42. 4 hours after the ingestion, he was brought to the local hospital by his family. After gastric lavage, charcoal administration and 24 hours observation, he was discharged from the hospital while he was nearly asymptomatic.

43. 12 hours later, nausea, vomiting, icter, and decrease level of consciousness started. He was brought to the hospital again and then was referred to our referral academic center. • The patient had no past medical history or drug history. • On the admission the patients vital signs was: BP: 110/70 mmHg, PR; 90/min, RR: 26/min, T: 38.3 ° C, O2 saturation: 95%.

44. The patient was confused. • His physical examination showed icter, pulmonary rales, normal heart sounds, diffuse abdominal tenderness without rebound or guarding, and 2+ pitting edema in lower extremities.

45. According to unknown poisoning and pulmonary ralesand for ruling out organophosphate poisoning, the treating physician tried atropinechallenge test that was ineffective. • Additionally, serum and red blood cell acetylcholinesteraseenzymatic activity was normal, so organophosphate poisoning was ruled out.

46. Urine toxicologic screen test also revealed negative result. • Finally, according to multi-organ failure, a probable diagnosis of paraquat poisoning was made. • Few days later, following finding a container of paraquat in patient's home, the diagnosis was confirmed…..

47. Paraquat is a severe local irritant and devastating systemic toxin. • A lethal oral dose of the 20% concentrate solution is about 10 to 20 mL in an adult and 4 to 5 mLin a child.

48. Paraquat is then distributed to most organs, with the highest concentrations found in the kidneys and lungs. • Paraquat actively accumulates in the alveolar cells of the lungs, where it is transformed into a reactive oxygen species, the superoxide radical.

49. Clinical Features

50. Multisystem effects include GI tract corrosion, acute renal failure, cardiac failure, hepatic failure, and extensive pulmonary injury. • Typically, manifestations of renal failure and hepatocellularnecrosis develop between the second and fifth days, with progressive pulmonary fibrosis leading to refractory hypoxemia 5 days to several weeks later.