مسمومیتها در اطفال (مسمومیت با سموم ارگانوفسفره)

2. مسمومیتها در اطفال (مسمومیت با سموم ارگانوفسفره) دکتر نسترن ایزدی مود استاد گروه سم شناسی بالینی 25 آذر ماه 1397

3. منابع Goldfrank’sToxicologic Emergencies, 2015. www.emedicine/Emergency medicine/Toxicology

6. سموم با سمیت بالا: کشاورزی (پاراتیون) سموم با سمیت کم : منازل (مالاتیون)

7. سموم با سمیت متوسط : دامپروری (کلرپیریفوس)

8. اطفال تمایل دارند هر چیزی را تست کنند و به دهانشان ببرند!!

9. Exposures • Accidental • Intentional

12. Epidemiology of Organophosphate Poisoning in the Tshwane District of South Africa (2017)

13. جذب : گوارشي ؛ پوستي ؛ تنفسي ؛ چشمي • متابوليسم : كبد • دفع : دفعمتابوليتها ازطريق ادرار • نيمه عمر دفعي : 2/89ساعتدرمالاتيونو2/1روزدرمتيل پاراتيون • متوسط دوز کشنده: LD50 • دیازینون :۱۰۰ تا ۱۵۰ mg/Kg  • مالاتیون: ۱۰۰۰ تا ۳۵۰۰ mg/Kg • پاراتیون : 50 mg/kg

14. مكانيسم اثرمهار كننده غیر قابل برگشت آنزيم كليناستراز (پلاسما و گلبول قرمز) شروع علا ئم : خوراکی (چند دقيقه تا 2 ساعت) پوستی (تا 12 ساعت) استنشاقی (تا نیم ساعت)

15. 1-علائم موسكاريني اسهال، درد شکمی،بی اختیاری ادرار و مدفوع، هيپو تانسيون

16. 2-علائم نيكوتيني (ضعف)

17. sinus tachycardia Midriasis علائم نيكوتيني fasciculation • هيپر تانسيون

18. 3-علائم سيستمعصبي مركزي • اضطراب • گيجي • كما • تشنج • دپرسیون مركز تنفس و قلبي

19. Children often do not present with the classic syndrome . • More commonly, they experience CNS effects with seizures, lethargy, stupor, coma, and muscle weakness and flaccidity • Watch out for chemical aspiration pneumonia as a lot of the organophosphate pesticides have a petroleum base.

22. تشخیص مسمومیت LABORATORY detect cholinesterase levels (1) RBC (2) Plasma Do not wait for cholinesterase levels to start antidote Clinical signs: Miosis, increased secretions, odor Atropine (Test)

23. Management of OPs Poisoning • Emergency management • A,B,C,D (Antidote) • ABCD (Intubation, Suctioning , Oxygen, Mechanical Ventilator) • Atropine • Pralidoxime

24. Atropine • competitive acetylcholine antagonist at muscarinic receptor subtypes M1, M2, M3, M4, and M5 • Muscarinic and CNS effects • IV, IO, IM, Endotracheal, SC • IV: Heart (2-4 min); CNS(30-60 min) • IM : sialorrhea (30-60 min)

25. Atropine • IV (preferred method of administration) • Amp:0.5 mg/ml, 1 mg/ml, 10 mg/ml • Oxygen • 0.01 mg/kg IV, repeat every 1-5 min. until full atropinization (secretions are inhibited) or signs of atropine toxicity appear (delirium, hyperthermia, muscle twitching). • Infusion 0.02-0.08mg / kg/h (depends on patient)(The elimination half-life of : 2 hours)

26. Atropine • Maintain some degree of atropinization for at least 48 hours and until any depressed blood cholinesterase activity is reversed. • Atropine should never be stopped abruptly. Close observation is required as reboundOP toxicity may occur due to their lipid solubility. When the patient improves, the dose should be tapered slowly over 24 hours. • Avoid use of succinylcholine, morphine, ….. • Hypersensitivity reactions to atropine

27. Atropine overdose: dizziness, ataxia, disorientation, agitation, hallucinations, delirium, tremor, or seizures. • Treatment: supportive therapies and physostigmine 0.5-1 mg in children Repeated doses may be required

28. موارد منع مصرف: • حساسيت به آتروپين ،گلوكوم زاويه بسته ، چسبندگي عدسي و عنبيه،تاكيكاردي، بيماريهاي انسداد دستگاه گوارش، ايلئوس، كوليت اولسروز شديد، مگا كولون سمي ناشي از كوليت اولسراتيو، بيماريهاي كبدي ، بيماريهاي كليوي ،مياسنتي گراويس ، آسم، تيروتوكسيكوز

29. پرالیدوکسیم • 1- برداشتن مهارکننده آنزیم استیل کولین استراز • 2- به ارگانوفسفات ها متصل می گردد و پیوند آلکیل فسفات- کولین استراز را می شکند • 3- آنتی کولینرژیک • داروی کمکی و نه جایگزین برای آتروپین • موثر نبودن در همه سموم ارگانو فسفره

30. پرالیدوکسیم • Nicotinic (muscle weakness and respiratory depression) • IV (preferred method of administration): 1- LOADING DOSE FOLLOWED BY CONTINUOUS INFUSION • 20-50 mg / Kg bolus IV infusion over 30 minutes > 12 years • 1.0-2.0 g at < 0.2 g/min in 200 mL saline < 12 years • 20-50 mg/kg body weight in 100 mL saline • followed by 10-20 mg / Kg /hour infusion.

31. INTERMITTENT INFUSION • Initial dose: 20 to 50 mg/kg (maximum 2000 mg/dose) IV 15-30min-A second dose of 20 to 50 mg/kg may be indicated after about 1 hour if muscle weakness is not relieved.-Repeat dosing every 10 to 12 hours as needed • -Pulmonary edema:dose diluted to a 50 mg/mL solution as a slow IV injection over at least 5 minutes-A second 20 to 50 mg/kg dose may be given after about 1 hour if muscle weakness has not been relieved.-Additional doses may be given every 10 to 12 hours if muscle weakness persists.

32. 2- Intramuscular dosing • < 40 kg: 15 mg/kg per single dose; 45 mg/kg total (3 injection) dose>= 40 kg: 600 mg per single dose; 1800 mg total (3 injection) doseMILD SYMPTOMS: Give weight appropriate dose (see above) intramuscularly; allow 15 minutes for drug to take effect-If symptoms persist after 15 minutes, give a second dose; allow 15 minutes for drug to take effect.-If mild symptoms persist, a third dose may be given. • SEVERE SYMPTOMS: Administer three weight appropriate doses intramuscularly in rapid succession.

33. If the patient does not receive an oxime, organophosphates cause irreversible inhibition of cholinesterase enzymes, resulting in excess accumulation of acetylcholine at muscarinic and nicotinic receptors, and in the periphery and central nervous system.

34. تشنج: • میدازولام 0.1- 0.3 mg /kg • دیازپام: 0.2-0.5 mg/kg (5-10 mg) • آژیتاسیون: • بنزودیازپینها

35. Decontamination • Gastric Lavage + Activated charcoal • Dermal or ocular Decontamination

36. Dermal exposure: • Decontamination: • Remove contaminated clothing. • Wash the skin with water and soap, including the hair, beneath the nails and umbilical for three times.

37. 24 hours observation in asymptomatic patient • 24-48 hours after discontinuation of antidote • Infusion of higher doses of sodium bicarbonate (5 mEq/kg in 60 minutes followed by 5–6 mEq/kg/day) was shown to be useful. • Intravenous MgSO4 (4 g) given in the first day after admission have been shown to decrease hospitalization period and improve outcomes in patients with OP poisoning.

38. Summary • ABCD (Intubation, Suctioning , Oxygen, Mechanical Ventilator) • Antidotes: • Atropine-Pralidoxime • Benzodiazepines • Decontamination • Gastric Lavage + Activated charcoal • Dermal or ocular Decontamination

39. نکات قابل توجه • سموم در مکانهای دور از دسترس کودکان نگاه داشته شود. • Ensure proper storage and labeling of pesticides • Don't store highly toxic pesticides, especially agricultural pesticides, in homes • Discard or clean pesticide-contaminated containers and equipment separately. Keep well out of children's contact. • Wash potentially contaminated work clothes separately from family laundry. Wash fruits and other fresh produce; promote consuming organic produce

40. با تشكر از حسن توجه شما عزيزان

41. Case 1 • 4 y.o. male brought in ED • lethargic • Vomit • Respiratory Rate :12 /min • BP: 100/78 • Odor • Miosis

42. 1-Emergency management A,B,C,D (Antidote)

43. A: Airway compromise -Vomiting (Suctioning) -Lethargic

44. A: Airway compromise • Airway, • Intubation, Ventilator

45. B: Breathing difficulties

46. B: Breathing management • Oxygen • Intubation, • Mechanical Ventilation • Antidote : Naloxone, Atropine

47. C: Circulation Problems • Pulse (rate, regularity,…), • Skin (Color, Temperature, …), • Blood pressure • Circulation • -Insert Intravenous line(IV) • - Normal Saline • -Cardiac monitor • -ECG • Manage Hypotension, arrhythmia

48. Sodium Bicarbonate Hypotension Arrhythmia, Wide QRS > 0.1 s, R avR  3 mm 1-2 mEq / kg bolus , Infusion (1-3 mEq /kg in serum) + repeated bolus (ABG) End point: Serum pH ( 7.45-7.55)

49. D: “Coma Cocktail” • Dextrose (D20-25W: 1-2 cc/kg in pediatrics) • Oxygen • Naloxone • Thiamine

50. Gastric Empyting • Case by Case Analysis • Nature of the poison • Patient • Risks (Risk/benefit) gastric emptying should be a selective not a routine procedure