Op Poisoning

14,683 views

Published on

2 Comments
70 Likes
Statistics
Notes
No Downloads
Views
Total views
14,683
On SlideShare
0
From Embeds
0
Number of Embeds
33
Actions
Shares
0
Downloads
0
Comments
2
Likes
70
Embeds 0
No embeds

No notes for slide

Op Poisoning

  1. 1. Organophosphorus Insecticides and Nerve Gas Agents Poisoning Mentor: Dr A M V R Narendra MD DM Presenter: Dr Bhavanadhar P (MD) Jr Resident Dept of General Medicine, NIMS, Hyd. 18-AUG-2009
  2. 2. Introduction <ul><li>Organophosphorus (OP) compounds - pesticides, herbicides, and chemical warfare agents i.e., nerve gases. </li></ul><ul><li>OP pesticide intoxications are estimated at 3 million per year worldwide with approximately 300 000 deaths. </li></ul><ul><li>Most of the OP pesticide poisoning and subsequent deaths occur in developing countries following a deliberate self ingestion. </li></ul><ul><li>The fatality rate following deliberate ingestion of OP pesticides in developing countries in Asia is approx 20% and may reach upto 70%. </li></ul>
  3. 3. Compounds <ul><li>OP compounds were first developed by Schrader shortly before and during the Second World War. </li></ul><ul><li>These compounds are normally esters, thiol esters, or acid anhydride derivatives of phosphorus containing acids. </li></ul><ul><li>Of the more than 100 OP pesticides used worldwide, the majority are either dimethyl phosphoryl or diethyl phosphoryl compounds </li></ul>
  4. 4. <ul><li>Others: </li></ul><ul><li>Acephate </li></ul><ul><li>Dimethoate </li></ul><ul><li>Ethion </li></ul><ul><li>Fentrothion </li></ul><ul><li>Moncrotofos </li></ul><ul><li>Phenthoate </li></ul><ul><li>Phorate </li></ul><ul><li>Phosphamidon </li></ul><ul><li>Profenofos </li></ul>
  5. 5. <ul><li>Nerve gas compounds are highly potent synthetic toxic agents. </li></ul><ul><li>G agents like Tabun, sarin, and soman are absorbed by inhalation or percutaneously; they are volatile and disappear rapidly after use. </li></ul><ul><li>V agents are contact poisons unless aerosolised, and contaminate ground for weeks or months. </li></ul><ul><li>They are related to OP pesticides but have much higher acute toxicity, particularly percutaneously. The toxicology and management of nerve agent and pesticide poisoning are similar </li></ul>
  6. 6. Mechanism of Toxicity <ul><li>OP’s inactivate acetylcholinesterase (AChE) by phosphorylation leading to the accumulation of acetylcholine (ACh) at cholinergic synapses </li></ul><ul><li>And subsequent over-activation of cholinergic receptors at the NMJ and in the autonomic and CNS. </li></ul><ul><li>The rate and degree of AChE inhibition differs according to the structure of the OP compounds and the nature of their metabolite. </li></ul>
  7. 7. <ul><li>In general, pure thion compounds are not significant inhibitors in their original form and need metabolic activation (oxidation) in vivo to oxon form. </li></ul><ul><li>E.g., parathion has to be metabolized to paraxon in the body so as to actively inhibit AChE. </li></ul><ul><li>Carbamates differ in mechanism, that the same enzyme is reversibly inhibited and are sometimes useful as medicines (neostigmine, pyridostigmine) as well as insecticides (carbaryl) </li></ul>
  8. 8. Diagrammatic representation of the possible reactivation & ageing reactions of AChE after inhibition by OP compounds
  9. 9. <ul><li>After the initial inhibition and formation of AChEOP complex two further reactions are possible: </li></ul><ul><li>(1) Spontaneous reactivation of the enzyme </li></ul><ul><li>- this may occur at a slow pace, much slower than the enzyme inhibition and requiring hours to days to occur. </li></ul><ul><li>- the rate solely depends on the type of OP compound, </li></ul><ul><li>- spontaneous reactivation t 1/2 of 0.7 hrs for dimethyl and 31 hrs for diethyl compounds. </li></ul><ul><li>- the spontaneous reactivation can be hastened by reagents like oximes. These agents thereby act as an antidote in OP poisoning </li></ul>
  10. 10. <ul><li>(2) Ageing </li></ul><ul><li>- with time, the enzyme-OP complex loses one alkyl group making it no longer responsive to reactivating agents. </li></ul><ul><li>- ageing depends on - pH, temp, and type of OP compound; </li></ul><ul><li>- dimethyl OP’s have ageing t ½ of 3.7 hours whereas it is 33 hours for diethyl OP’s. </li></ul><ul><li> - hence, oximes are hypothetically useful before 12 hours in dimethyl OP’s poisoning. </li></ul><ul><li>- However, in diethyl OP intoxication they may be useful for many days. </li></ul><ul><li>- Nerve agents (especially soman) undergo ageing within minutes </li></ul>
  11. 11. Clinical Manifestations <ul><li>The onset, severity and duration of poisoning depend on the route of exposure and agent involved. </li></ul><ul><li>Sequential triphasic illness follows OP intoxication : </li></ul><ul><ul><li>Acute Cholinergic Crisis </li></ul></ul><ul><ul><li>Intermediate Syndrome (IMS) </li></ul></ul><ul><ul><li>Organophosphate-Induced Delayed Polyneuropathy (OPIDN ). </li></ul></ul>
  12. 12. Acute Cholinergic Crisis <ul><li>Accumulation of acetylcholine (ACh) causing excessive stimulation of cholinergic receptors at various organs. </li></ul><ul><li>Ach is the principle neurotransmitter in various synapses: parasympathetic system, autonomic ganglia, NMJ and central nervous system. </li></ul><ul><li>These acute manifestations can be broadly divided into muscarinic, nicotinic, and central nervous system (CNS) effects. </li></ul><ul><li>Practical significance of this classification is that atropine only blocks muscarinic effects whereas oximes reverse both the nicotinic and muscarinic effects </li></ul>
  13. 13. Summary of clinical features and antidotes in Acute Cholinergic Crisis
  14. 14. <ul><li>SLUDGE </li></ul><ul><li>Salivation </li></ul><ul><li>Lacrimation </li></ul><ul><li>Urine incontinence </li></ul><ul><li>Diarrhoea, </li></ul><ul><li>Gastrointestinal cramps </li></ul><ul><li>Emesis) </li></ul><ul><li>DUMBELS </li></ul><ul><li>Diarrhoea </li></ul><ul><li>Urination </li></ul><ul><li>Miosis </li></ul><ul><li>Bronchospasm,Bronchorrhea </li></ul><ul><li>Emesis </li></ul><ul><li>Lacrimation </li></ul><ul><li>Salivation </li></ul>Various mnemonics have been used to describe the muscarinic signs of OP poisoning:
  15. 15. <ul><li>Heart rate and blood pressure can be potentially misleading findings as increase or decrease can occur in both vital signs. </li></ul><ul><li>Dose dependent effects : </li></ul><ul><li>Muscarinic < Nicotinic < CNS </li></ul><ul><li>Tachycardia/Hypertension – s/o severe poisoning </li></ul><ul><li>Patients can also develop pancreatitis, hypo or hyperglycaemia and acute renal failure during this phase </li></ul>
  16. 16. Depending on the severity of the exposure, the spectrum of the clinical presentation varies <ul><li>Mild </li></ul><ul><li>Small or pinpoint pupils </li></ul><ul><li>Painful, blurred vision </li></ul><ul><li>Runny nose and eyes </li></ul><ul><li>Excess saliva </li></ul><ul><li>Eyes look &quot;glassy&quot; </li></ul><ul><li>Headache, Nausea </li></ul><ul><li>Mild muscle weakness </li></ul><ul><li>Localized muscle twitching </li></ul><ul><li>Moderate </li></ul><ul><li>Pinpoint pupils, conjunctival injection </li></ul><ul><li>Dizziness, disorientation </li></ul><ul><li>Coughing, wheezing, sneezing </li></ul><ul><li>Drooling, bronchorrhoea, bronchospasm </li></ul><ul><li>Breathing difficulty </li></ul><ul><li>Marked muscle twitching, tremors </li></ul><ul><li>Muscle weakness, fatigue </li></ul><ul><li>Severe </li></ul><ul><li>Pinpoint pupils </li></ul><ul><li>Confusion </li></ul><ul><li>Agitation </li></ul><ul><li>Convulsions </li></ul><ul><li>Copious secretions </li></ul><ul><li>Cardiac arrhythmias, Collapse </li></ul><ul><li>Respiratory depression, Respiratory arrest </li></ul><ul><li>Coma </li></ul><ul><li>Death </li></ul>
  17. 17. <ul><li>Prognosis in acute poisoning may depend -> </li></ul><ul><ul><li>dose and toxicity of the ingested OP (e.g., neurotoxicity potential, half life, rate of ageing, pro-poison or poison), and </li></ul></ul><ul><ul><li>whether dimethyl or diethyl compound. </li></ul></ul><ul><li>The time of death after exposure may range from <5 min to nearly 24 hours -> dose, route of administration, agent and availability of treatment. </li></ul><ul><li>Respiratory failure and hypotension are the immediate causes of death in acute stage. </li></ul><ul><li>Delay in discovery and transport, insufficient respiratory management, aspiration pneumonia and sepsis are common causes of leading to death. </li></ul>Prognosis
  18. 18. Intermediate syndrome <ul><li>The intermediate syndrome is a distinct clinical entity that occurs 24 to 96 hours after the ingestion of an OP compound; </li></ul><ul><li>Approximately 10-40% of patients treated for acute poisoning develop this illness. </li></ul><ul><li>The onset of the IMS is often rapid, with progression of muscle weakness from the </li></ul><ul><ul><li>ocular muscles to the neck (the patient cannot raise their head from the pillow) </li></ul></ul><ul><ul><li>proximal limbs, </li></ul></ul><ul><ul><li>to the respiratory muscles (intercostals and diaphragm) over the course of 24 hours. </li></ul></ul>
  19. 19. <ul><li>Increasing respiratory difficulty causes anxiety, sweating and use of accessory muscles of respiration. </li></ul><ul><li>If endotracheal intubation and ventilation are not instituted early, cyanosis, coma and death follow rapidly. Paralysis may continue for 2-18 days. </li></ul><ul><li>Proposed mechanisms include </li></ul><ul><ul><li>persistent inhibition of AChE leading to functional paralysis of neuromuscular transmission, </li></ul></ul><ul><ul><li>muscle necrosis, and </li></ul></ul><ul><ul><li>oxidative free radical damage to the receptors </li></ul></ul>
  20. 20. Organophosphate-induced delayed polyneuropathy (OPIDN) <ul><li>This occurs about 1-3 weeks after acute exposure and an uncertain period following chronic exposure, due to degeneration of long myelinated nerve fibres. </li></ul><ul><li>Mechanism is inhibition of neuropathy target esterase (NTE) enzyme in nervous tissues by certain OP compounds (chloropyriphos) </li></ul><ul><li>A distinct acute or intermediate phase may not always precede its development </li></ul>
  21. 21. Symptoms <ul><li>Cramping muscle pains in the legs numbness and paraesthesiae in the distal upper and lower limbs. </li></ul><ul><li>Acute weakness of the lower limbs follows and spreads to the hands, causing a shuffling gait, and footand wrist-drop. </li></ul><ul><li>Muscle wasting and deformity, such as clawing of the hands, follow. </li></ul><ul><li>Sensory loss is variable and is often mild and inconspicuous. </li></ul>
  22. 22. Signs <ul><li>Physical examination reveals symmetrical flaccid weakness of the distal muscles, especially in the legs. </li></ul><ul><li>Tendon reflexes are reduced or lost, absent ankle reflexes being a constant feature. </li></ul><ul><li>Later, mild pyramidal tract signs (spasticity, hypertonicity, hyper-reflexia and clonus) may develop. </li></ul>
  23. 23. Figure showing effects of OP poisoning
  24. 24. Diagnosis <ul><li>Diagnosis of OP poisoning depends on the H/o exposure to OP compounds, characteristic manifestations of toxicity and improvements of the signs and symptoms after administration of atropine. </li></ul><ul><li>This may be aided by insisting that the pt’s party to search for a possible poison container in the vicinity of the pt. </li></ul><ul><li>Garlic-like smell is an added clinical sign especially if the patient has ingested sulphur containing OP compound. </li></ul>
  25. 25. <ul><li>Cholinesterase (ChE) estimations (plasma butyryl cholinesterase and red cell AChE) are the only useful biochemical tool for confirming exposure to OPs, but are a poor guide to management and prognosis. </li></ul><ul><li>Clinical severity graded on the basis of the pseudocholinesterase level </li></ul><ul><ul><li>mild 20-50% enzyme activity, </li></ul></ul><ul><ul><li>moderate 10-20% enzyme activity </li></ul></ul><ul><ul><li>severe <10% enzyme activity </li></ul></ul><ul><ul><li>though the enzyme activity does not correlate well with clinical severity </li></ul></ul>
  26. 26. <ul><li>BuChE activity </li></ul><ul><ul><li>Easily assayed </li></ul></ul><ul><ul><li>Response to antidotal therapy less </li></ul></ul><ul><ul><li>Does not correlate well with neuronal effects </li></ul></ul><ul><ul><li>Levels altered in malnutrition, chronic illness, cirrhosis, infections </li></ul></ul><ul><li>RBC AChE activity </li></ul><ul><ul><li>More difficult to assay </li></ul></ul><ul><ul><li>Increased activity after pralidoxime therapy </li></ul></ul><ul><ul><li>Correlates well with predictable neuronal effects and severity as well </li></ul></ul><ul><ul><li>Levels altered in hemoglobinopathies, thalassemia </li></ul></ul>On the other hand, true or erythrocyte cholinesterase correlates well with clinical severity but is not available in most centres, especially in developing countries
  27. 27. <ul><li>Analytical identification of OP compound in gastric aspirate or in the body fluids gives the clue that pt has been exposed to OP compound. </li></ul><ul><li>However in doubtful cases and especially if laboratory facilities are not available, 1mg atropine can be given intravenously. </li></ul><ul><li>If this does not produce marked anticholinergic manifestations, anticholinesterase poisoning should be strongly suspected </li></ul>
  28. 28. Treatment: Acute Cholinergic crisis <ul><li>Decontamination and Supportive therapy </li></ul><ul><li>Blockade of Muscarinic activity with ATROPINE </li></ul><ul><li>Reversal of cholinesterase inhibition with OXIME nucleophiles </li></ul><ul><li>Correction of Metabolic abnormalities </li></ul>
  29. 29. Decontamination and Supportive therapy <ul><li>Protection of the health care staff </li></ul><ul><li>ABC(Airway, Breathing & Circulation) </li></ul><ul><ul><li>Comatose or vomiting patients should be kept in lateral, preferably head down position with neck extension to reduce the risk of aspiration. </li></ul></ul><ul><ul><li>Patent airway should be secured with placement of Guedel’s airway or with endotracheal intubation especially if the patient is unconscious, fitting, or vomiting. </li></ul></ul><ul><ul><li>Frequent suctioning is essential as excessive oropharyngeal and respiratory secretions may occlude the airway. </li></ul></ul><ul><ul><li>Need for o2 therapy this can be assessed by frequent assessment of arterial oxygen saturation </li></ul></ul>
  30. 30. Decontamination: <ul><li>Skin decontamination. </li></ul><ul><ul><li>The skin and clothes of these patients are frequently contaminated with poison and vomiting. </li></ul></ul><ul><ul><li>Hence should be removed and the skin vigorously washed with soap and water </li></ul></ul><ul><li>Gastric lavage. </li></ul><ul><ul><li>Gastric lavage should be considered in patients presenting within 1-2 hours of ingestion of poison. </li></ul></ul><ul><ul><li>Risks of gastric lavage include aspiration, hypoxia, and laryngeal spasm, and these can be reduced with proper management of airway </li></ul></ul>
  31. 31. <ul><li>Activated charcoal </li></ul><ul><ul><li>Activated charcoal helps to reduce the poison load by adsorbing it; </li></ul></ul><ul><ul><li>Though its efficacy has not been conclusively proven in humans, single to multiple dose activated charcoal is routinely used in clinical practice. </li></ul></ul><ul><li>AVOID cathartics and induced emesis </li></ul>
  32. 33. <ul><li>Specific antidote for muscarinic effects ; no effect on nicotinic symptoms. </li></ul><ul><li>It reverses life threatening features that can result in death -> central respiratory depression, bronchospasm, excessive bronchosecretion, severe bradycardia, and hypotension </li></ul><ul><li>Current guidelines recommend the use of bolus doses to attain target endpoints, followed by setting up an infusion to maintain these end-points. </li></ul>Atropine
  33. 34. <ul><li>Target end-points for Atropine therapy </li></ul><ul><ul><li>Heart rate >80/ min </li></ul></ul><ul><ul><li>Dilated pupils </li></ul></ul><ul><ul><li>Dry axillae </li></ul></ul><ul><ul><li>Systolic blood pressure >80 mm Hg </li></ul></ul><ul><ul><li>Clear chest on auscultation with resolution of bronchorrhea (absence of wheeze and crepts) </li></ul></ul><ul><li>Recommended dose is an initial iv bolus of 1.8-3mg with subsequent doses doubled every 5 minutes until atropinization is achieved.(0.05mg/kg in children) </li></ul><ul><li>Maintenance dose: 20% of initial atropinizing dose per hour for first 48 hours and gradually taper over 5 -10 days, continuously monitoring the adequacy of therapy.(0.02-0.08mg/kg/hr) </li></ul>
  34. 35. <ul><li>Look for atropine TOXICITY </li></ul><ul><li>Agitation, confusion, hyperthermia, urinary retention and severe tachycardia that can precipitate ischaemic events in patients with underlying coronary artery disease. </li></ul><ul><li>Close observation and dose adjustment is essential to avoid the features of both under- and over-atropinization. </li></ul><ul><li>Anticholinergic agent glycopyrrolate along with atropine can be used in order to limit the central stimulation produced by atropine </li></ul>
  35. 36. Oximes <ul><li>Oximes work by reactivating acetylcholinesterase that has been bound to the OP molecule. </li></ul><ul><li>Pralidoxime is the most frequently used oxime worldwide; other members include obidoxime, and experimental HI 6 and HLO 7. </li></ul><ul><li>They can be highly effective in restoring skeletal muscle strength and improving diaphragmatic weakness where atropine has virtually no effect. </li></ul><ul><li>The therapeutic window for oximes is limited by the time taken for ‘ageing’ of the enzyme-OP complex, because ‘aged’ enzyme can no longer be reactivated by oximes </li></ul>
  36. 37. <ul><li>WHO recommends pralidoxime dose of 30 mg/kg bolus iv followed by continuous infusion of 8mg/kg/hour </li></ul><ul><li>Infusion continued until recovery : </li></ul><ul><ul><li>12 hrs after atropine has been stopped. </li></ul></ul><ul><ul><li>BChE noted to increase. </li></ul></ul><ul><li>Dizziness, headache, blurred vision, and diplopia, are common side effects of oxime therapy. </li></ul><ul><li>Rapid administration may lead to tachycardia, laryngospasm, muscle spasm, and transient neuromuscular blockade. </li></ul>
  37. 38. Intermediate syndrome <ul><li>Ventilatory support should be instituted before a pt develops resp failure to maintain a PaO2 > 97 mmHg (>13kPa), PaCO2 of 30-45 mmHg (4-6 kPa) and pH > 7.3. </li></ul><ul><li>Diazepam or midazolam may be used for sedation during ventilation. Weaning from respiratory support should be initiated as early as possible. </li></ul><ul><li>Parenteral nutrition is often required. </li></ul><ul><li>Unless OPIDN develops, recovery from IMS is complete with adequate ventilatory care </li></ul>
  38. 39. OPIDN <ul><li>There are no specific therapeutic measures. </li></ul><ul><li>Regular physiotherapy may reduce deformity caused by muscle-wasting. </li></ul><ul><li>Recovery from OPIDN is incomplete and may be limited to the hands and feet, although substantial functional recovery after 1-2 years may occur in younger patients . </li></ul>
  39. 40. Figure showing effects of OP poisoning
  40. 41. 30 mg / kg bolus 8 mg / kg / hr 4 mg / kg bolus 0.5 mg / kg / hr

×