OPC Poisonig Slide ,Treatment and Data analysis.

This a Opc Poisonig Slide ,Treatment and Data analysis.

1. OPC P OISONING By Dr. Shoily Datta Intern Doctor Medicine Unit – Green M. Abdur Rahim Medical College & Hospital, Dinajpur .

2. 4/23/2019 W hat is OPC ? O PC means organophosphorus compounds. A widely used pesticides especially in developing countries .

3. 4/23/2019 H ere G for german origin & V for venomous Some Organophosphorus Compound

4. Some OPC Available in Bangladesh Dimethyl compounds ( ageing 3.7 hours) Malathion Dichlorvos Dimethoat Fenthion Diethyl compounds ( 31 hrs ) Chlorpyrifos Diazinon Parathion Quinalphos

5. 4/23/2019 ONSET,SEVERITY,DURATION Depend on R oute of exposure A gent involvement I nhalation ingestion N erve agent insecticide

6. C hemical warfare agent A griculture I ndustry M edicine F lame retardants G asoline additives P lasticizers C leaning agent W ater treatment chemicals C hemotherapeutical agents U se of OPC

7. Inhibition of acetyl cholinesterase leads to the accumulation of acetylcholine at cholinergic synapses, interfering with normal function of the autonomic, somatic, and central nervous systems. This produces a range of clinical manifestations, known as the acute cholinergic crisis Ach Acetyl Cholinesterase Breakdown products O P C OX IMES C N S N I C M U S Atropine Mechanism of T oxicity of Organophosphorus Compounds

8. Acetylcholinesterase ( AChE ) AChE is an enzyme that degrades the neurotransmitter acetylcholine ↗ AChE Fig : Mechanism of toxicity of organophosphorus compounds

9. The first is the acute toxicity is due to the irreversible inhibition of acetylcholinesterase ( AChE ),which subsequently led to accumulation of acetylcholine at * Muscarinic receptors - in cholinergic receptor cell. *Nicotinic receptors in skeletal neuromuscular junction and autonomic ganglia. * Central Nerves System . Toxic Effects

10. The second effect is arising from single or repeated exposure to OPC. With degeneration of the axon and the myelin both central and peripheral nervous system, which is known as oganophosphate -induced delayed polyneuropathy. Toxic Effects

11. 4/23/2019 Three clinical syndromes have been described : Acute cholinergic syndrome (most common) Sub acute proximal weakness (Intermediate syndrome) Organophosphate Induced Delayed Polyneuropathy (OPIDN) Signs and Symptoms of OPC Poisoning

12. O ccurs within a few minutes of exposure U sually lasts for 48 to 72 hrs . N icotinic or muscarinic feature combindly present F ollowing oral ingestion vomiting & profuse diarrhoea typical . F ollowing inhalation B ronchoconstriction,bronchorrhoea and salivation cause severe R espiratory compromise D iagnostic feature is muscle fasciculation although this is often absent . P atient may developed flaccid paralysis which affect respiratory & O cular muscle & result in respiratory failure Ataxia, coma ,convulsion may occur Cardiac abnormalities & on ECG torsades de pointes may occur Extrapyramidal features :Pancreatitis Hepatic dysfunction pyrexia Acute Cholinergic Phase

13. 4/23/2019 Cholinergic Features of OPC Poisoning

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15. IMS occurs due to dysfunction of the post-synaptic neuromuscular junction Pathogenesis unclear. But thought to be due to persistent inhibition of acetyl cholineasterase IMS develop about 24-96 hours after OPC induced intoxication Respiratory insufficiency may occur at the onset of IMS. The patient is usually conscious. Muscles innervated by cranial nerves show varying degree of weakness. External ocular muscles are most commonly affected Weakness is bilateral and symmetrical Patient cannot raise the head from bed. There is no sensory impairment. There is increased in respiratory rate , sweating , restlessness and later cyanosis . If untreated the patient may soon become unconscious and die. Intermediate Syndrome (IMS)

16. Organophosphorus induced delayed polyneuropathy (OPIDN) occurs following a latent period of 2-4 weeks after exposure by any route. The cardinal symptoms are distal weakness and in some cases paraesthesia in the distal parts of the limbs, foot drops, wrist drop and claw hands are inevitable consequences. Pyramidal signs may appear after a few weeks or few months. Recovery is variable and the condition may be permanent. Severe cases progress to complete paralysis , impaired respiration and death. Organophosphate Induced Delayed Polyneuropathy (OPIDN)

17. Clinical Grading Biochemical Grading Clinical grading: based on - 1.Miosis 2.Fasciculation 3.Respiratory Rate 4.Bradycardia 5.Level of consciousness *Mild(0-3), *Moderate(4-7), *Severe(8-11) Grading of Severity of Poisoning

18. Grading of Severity of Poisoning Biochemical Grading: Red cell cholinesterase activity (% normal) Grade 20-50% Mild 10-20% Moderate <10% Severe

19. 4/23/2019 D eterminant of toxicity T he rate of ageing is an important for d eterminant of toxicity W hat is ageing A geing duration for different OPC D imethyl compound: 3.7 h rs D iethyl compound: 31 hrs N erve agent: within minutes A geing : Ach-E has Two ends , normally Ach-E bind s Ach with its 2 end and then Ach breaks down into A cetic acid and choline. I n OPC poisoining OPC binds to one end of Ach-E and prevent breakdown of Ach . B ut within a time period binding of OPC to Ach-E spontaneously hydrolysed and normal functionng of Ach-E A chieved. A fter this time period binding of OPC to Ach-E become permanent and no activation of Ach-E occurs even with pralidoxime , it is called ageing.

20. R outine inv: CBC: leukocytosis RBS: hypoglycemia LFT: increased PT U rine R/E: proteiurea S.amylase: raised ECG: arrythmia torsades de pointes C hest X ray: pulmonary odema Oxygen saturation Blood gas analysis S pecial inv: D irect measurement of opc E stimation of red cell cholinesterase S pirometry H istopathology All patients and their attendants should be repeatedly encouraged to bring the sample to the health facility for diagnosis and management . Investigations

21. Hospitalization/ ICU Initial stabilization Reduction of exposure Administration of specific antidote Supportive treatment Clear airway and Adequate ventilation because the patient with acute organophosphate poisoning commonly presents with respiratory distress. Oxygen- high flow circulation- by iv access Management of OPC Poisoning Initial Stabilization of the Patient

22. Recovery Position: The head, neck and body should be in a straight line so that the tongue will not block the throat, and vomit or saliva can come out of the mouth. Turn the patient's face towards you, and tilt it back with the jaw jutting forward. Take the patient's upper arm and place the hand under the face Place the patient's other arm across the chest. Now position the upper leg so that the bent knee rests on the ground and supports the patient's body and lower leg keep straigh t Clear airway and Adequate Ventilation

23. Dermal spills —wash pesticide spills from the patient with soap and water and remove and discard contaminated clothes, shoes and any other material made from leather Gastric lavage —consider for presentations within 1 or 2 hours, when the airway is protected. A single aspiration of the gastric contents may be as useful as lavage Activated charcoal without cathartic —50 g may be given orally or nasogastrically to patients who are cooperative or intubated, particularly if they are admitted within one or two hours or have sever toxicity Decontamination

24. There are two antidotes in the treatment of OPC poisoning: Atropine - Reverses the muscarinic features. Oxime -     Reactivate cholinesterase and reverses the nicotinic features . Try test dose of atropine Conventional Vs Evidence-Based Practice Antidotes in the Treatment of OPC Poisoning Dosage Regimens of Atropine

25. Test dose of Atropine: It is preferable to initiate the antidote therapy with a 'test dose' of parenteral atropine- sulphate (1.2 mg in adults and 0.01 mg/kg in children IV) This therapeutic test provides a measure of severity of organophosphate poisoning. If the signs of atropinisation occur rapidly, it is unlikely that the poisoning is severe or it may not be OPC poisoning . 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 Dosage Regimens of Atropine cont.

26. Dosage Regimen of Atropine Evidence - Based Give first dose atropine immediately 1.8–3 mg (3 to 5 ampoules) rapidly IV into a fast-flowing IV drip 1ampoule contains 0.6 mg atropine sulphate Don’t delay starting atropine if oxygen is unavailable

27. Dosage regimens are usually designed according to the severity of poisoning and to the signs of atropinisation I n mild poisoning test dose 1 mg atropine, if atropinization then 24 hrs obsevation M oderate poisoning not respond to test dose of atropine shoud give increased dose o f atropine 2 to 5 mg i/v & repeat in 2-5 mg every 5-10-15 minutes. After initial atropinization, maintain the atropinization by reducing the dose or increasing the duration between doses of atropine. In most severe cases continuous intravenous infusion of atropine require d at the rate of .02 to .08 mg/kg/hr & titrated against the response Repeated doses of atropine should be administered until signs of atropinisation appear. Dosage Regimens of Atropine: Conventional Practice

28. After 3-5 minutes of atropine administration record followings :- (1 ) Chest auscultation : Clear with no wheeze ( 2) Blood pressure: SBP > 80 mm/Hg (3) heart rate: > 80 beats/min (4) Pupil: no longer pinpoint (5) Dry axilla These are the Target E nd point s of a tropinization Assess – is the Patient Atropinised ?

29. A uniform improvement in most of the five parameters is required, not improvements in just one. Pupil dilatation is sometimes delayed. and the other parameters may improve more rapidly, it is reasonable to observe air entry on chest auscultation, heart rate, and blood pressure as the main parameters for adequate atropinisation. When all the parameters are satisfactory, the patient has received enough atropine and is “atropinised” Assess – is the Patient Atropinised ?

30. Continuation of Bolus Atropine Loading to Reach Atropinisation If after 3–5 min a consistent improvement across the five parameters has not occurred. Then Continue to double the dose every 3-5 minutes until atropinisation has been achieved Do not simply repeat the initial dose of atropine Atropinise the patient as quickly as possible

31. Atropine treatment after atropinization Once atropinized , set up an infusion using one of the two IV cannulae In the infusion, give 10–20% of the total atropine that was required to load the patient every hour I f very large dose required then less dose can be used L arger dose required if oxime not avaiable Giving Fluids / IV Channel

32. Follow up every 15 min with five parameter If recurrence of bronchospasm or bradycardia , give further boluses of atropine Once the patient settled then follow up hourly for the first 6 hours to check that the atropine infusion rate is sufficient and that there are no signs of atropine toxicity As the required dose of atropine falls, observation for recurrence of cholinergic features can be done less often (every 2–3 hours) However, regular observation is still required to spot patients at risk of, and going into, respiratory failure The most important Observation of the Patient

33. Peripheral effect Dry mouth Mydriasis Blurred vision Hot dry skin Tachycardia Look for retention of urine Central effect Hyperpyrexia Restlessness Anxiety Excitement Hallucination Delirium Mania Cerebral depression Coma Hot as a hare Blind as a bat Dry as a bone Red as a beet Mad as a hen Atropine Toxicity or when Atropine not Administer

34. A tropine should only be stopped if signs of over atropinization such as fever,muscle fasciculation & delerium are present T reatment of atropine toxicity Stop the atropine infusion D iazepam for convulsion Benzodiazepines are usually given intravenously as required for agitation or seizures—with doses starting at: Diazepam 5-10 mg (0.05-0.3 mg/kg/dose), Lorazepam 2-4 mg (0.05-0.1 mg/kg/dose), or Midazolam 5-10 mg (0.15-0.2 mg/kg/dose) P hysostigmine for peripheral effect P yrexia should be contolled by anti pyretics Management of Atropine Toxicity

35. 4/23/2019 Check again after 30 min to see whether the features of toxicity have settled If not, continue to review every 30 min 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 Management of Atropine Toxicity cont.

36. Reduces morbidity and mortality Shortens the length of hospital stay Requires a shorter time to atropinization Requires less frequent follow-up Maintain sustain blood levels of atropine Lower incidence of atropine toxicity Less IMS Special circumstances with atropine therapy As atropine can induce VT & VF in a severely hypoxic patient, hypoxia should be corrected before administration of atropine As severely poisoning patients exhibit marked atropine resistance, they may require up to 2-3 times the standard dose of atropine. Advantages of Rapid Incremental Dose Atropinization Followed by Atropine Infusion

37. Praliodoxime is used in conjunction with atropine in moderate and severe poisoning . It has a strong synergistic effect with atropine and provides a dose sparing effect on the amount of atropine Loading dose 30 mg/kg of pralidoxime over 10–20 min, followed by continuous infusion of 8–10 mg/kg per hour until clinical recovery (12 hours after stopping administration of atropine) Dosage Regimen of Pralidoxime Pralidoxime

38. Mild biochemical signs of liver toxicity. Too rapid administration will result in vomiting, tachycardia and hypertension (especially diastolic hypertension). Very few cases of pralidoxime toxicity have been reported. Dizziness, blurred vision, diplopia, headache, nausea and tachycardia have been reported if the rate of administration exceeds 0.5 gm per minute. Side Effect of Pralidoxime Pralidoxime Toxicity

39. Currently obidoxime has been introduced. It crosses blood brain barrier more than pralidoxime Where obidoxime is available, a loading dose of 250 mg is followed by an infusion giving 750 mg every 24 hours Obidoxime

40. M anagement of respiratory insufficiency : I n respiratory fa ilure : A rtificial respiration P ulmonary odema needs high conc O2 & diuretics I n aspiration pneumonia high dose antibiotic s M aintainence of circulation by i/v fluids T reatment of convulsion by diazepam & a nd other complications Fl uid & electrolyte balance C ontrol of infections M aintainence of nutrition C ontrol of body temperature by sponging, fanning. Supportive Treatment

41. Vital signs Signs of Atropinisation Effect of oxime Toxicity of atropine and oxime RBC and plasma AChE level Recurrence of symptoms on withdrawal of antidote Restart the treatment promptly if recurrence occurs Patient’s general condition Follow up of the Patient

42. Consider discharge from ICU to medical ward once stable for 12 hours after oxime Stable for 48 hours after discharge from intensive care unit- consider disposition and psychiatric review Disposition

43. Signs of Atropinization / Target end­points for Atropine therapy ™ Clear chest on auscultation with no wheeze ™ Heart rate >80 beats/min ™ Pupils no longer pinpoint ™ Dry axillae ™ Systolic blood pressure >80 mmHg ALGORITHM: MANAGEMENT OF ORGANOPHOSPHATE POISONING Suspected OP Test Dose to confirm OP poisoning: • Count existing heart rate of the patient. •Give2 ampoule(1.2mg) injection Atropine IV stat and after (2-3 mins ) count the heart Go for Test Dose Test rate again. • If it is more than 20 from the base line 2 amp atropine(1.2mg) heart rate, then it is unlikely of OP IV stat poisoning . •External decontamination with water •Removal of clothing •Avoid contamination of other personnel •Gastric lavage within 1 hr of ingestion •Follow ABC management protocol. Confirmed OP Poisoning •Start intensive Atropine therapy • Inj Pralidoxime if available •Inj. Atropine 2-5 amp (1.2 -3mg) IV stat followed by doubling of doses every 5 mins interval until full Atropinization * occurs. •Don’t simply repeat the initial dose; rather continue to double each time. During this time check the five parameters every 10 mins interval. Plus •Inj. Pralidoxime chloride :1-2 g/IV stat (adult); 30 mg/kg IV over 15-30 mins (in children). • If no improvement repeat after 1 hour, then every 8-12 hour until improvement. No obvious symptoms of OP Poisoning Exposure Likely Observe for 24 Exposure Unlikely hours and reassess for care •If Atropine toxicity develops, stop infusion. •Review every 30 mins interval till the toxicity settles. •Restart infusion at 70-80% of the previous rate. • Monitor frequently • Ensure new infusion rate reduce Atropine toxicity. •Once Atropinized calculate the total amount required and give 10- 20% of it per hour through infusion (normal saline) as maintenance. •At this stage review the parameters at 30 mins interval for 3 hours, followed by hourly for 6 hours and 3-6 hourly for next 24-48 hours. •If Atropinization is lost at any point,eg; bronchospasm, bradycardia etc. start giving bolus dose again until they disappear and add 20% of bolus requirement to infusion per hour. •After symptomatic improvement and excluding late signs of toxicity discharge with appropriate follow up. Atropine toxicity: Restlessness, tachycardia, fixed dilated pupil, hyperpyrexia, dry mouth, blurred vision, delirium, coma etc. ALGORITHM : MANAGEMENT OF ORGANOPHOSPHATE POISONING

44. 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 . Late death: - Secondary to ventricular arrhythmias, including Torsades de Pointes, which may occur up to 15 days after acute intoxication. Cause of Death in OPC Poisoning

45. Huge amount ingested Delay in hospitalization Delay in starting treatment Neglected Lack of standardized treatment protocol Atropine toxicity Lack of frequent monitoring Lack of ICU support including poor financial condition Treatment seeking behavior Factors Related to Death in OPC Poisoning

46. Deaths usually occur within the first 24 hours in untreated cases and within 10 days in treatment failure cases. If there has been no anoxic brain damage, recovery will usually occur within 10 days, although there may be residual sequelae. Prognosis of Organophosphorus Insecticide Poisoning

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