Toxicology 101


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Toxicology 101

  1. 1. Toxicology 101 Case Based Learning The Emergency Medicine approach to the poisoned patient Nikita Joshi MD Emergency Department Academic Fellow njoshi8@GMAIL.COM @njoshi8
  2. 2. Rules of Today • VERY interactive • If you don’t know what something is, raise your hand, we will learn all the facts together • I will call on you • You will be doing multiple mini presentations • There are no wrong questions/answers
  3. 3. We love tox! Vietnam War Ricin poisoning Don’t drink the Kool Aid Indian school children Bulgarian Dissident Writer James Town Massacre Kool Aid – laced with cyanide – inhibits cytochrome C oxidase Organophosphates – inhibition of acetylcholinesterase Ricin – inhibits protein synthesis Dioxin – defoliant – form of organophosphate
  4. 4. This is our specialty! • Immediate intervention with antidotes • Control of airway • Multiple patients • Multisystem involvement • Hyperbaric Chamber • Toxicology Fellowship • EMS training • Hazmat • Disaster Medicine
  5. 5. Definition • Study of adverse effects of chemicals on living organisms • Study of symptoms, mechanisms, treatment & detection of poisoning (wikipedia)
  6. 6. A good toxicologist … • Pathophysiology • Biochemistry • Pharmacology • Organic Chemisty
  7. 7. Approach to Patient • Scene Safety • Decontamination • Airway • Breathing • Circulation • Physical Exam • Labs • Antidotes • Disposition
  8. 8. Toxicology Physical Exam • Vital Signs: HR BP RR O2 Sat T • Neuro • Eye • Cardiac • Respiratory • Abdominal • Bladder • Skin
  9. 9. Toxidromes • Sympathomimetics • Cholinergic • Anticholinergic • Opioids • Narcotics
  10. 10. 5 yo boy is the victim of a massive apartment building fire. He was found by police unconscious and with scorch marks on his body. His clothes have been scorched. His family are on their way by another ambulance.
  11. 11. Considerations in Fire Victims Emergency Department Management •Initial approach •Medications administered •Emergency interventions •Consults Carbon Monoxide Poisoning •Clinical manifestations •Diagnostic tests •Antidote Carbon Monoxide Poisoning •Epidemiology •Pathophysiology Hyperbaric Chamber •How does it work •Special considerations •How do you know if it is successful •Transfer indications
  12. 12. Mini Presentations
  13. 13. Emergency Department Management • Airway – inhalation injury – inflammation, edema • Breathing – burned skin preventing chest rise • Circulation – volume loss • Other related trauma: broken bones, chemical exposure, parkland formula for fluid
  14. 14. Carbon Monoxide • Majority of exposure are fire victims • Incomplete combustion of carbonaceous fossil fuel (complete combustion leads to CO2) • Poor outcomes: extremes of age, pregnant women (fetus), preexisting coronary artery disease, respiratory disease
  15. 15. CO Binds Hemoglobin Platelet hemoproteins Myoglobin Cytochrome oxidase
  16. 16. Hemoglobin – doesn’t allow blood to bind with oxygen, decreases the amt of oxygen in the body Myoglobin – muscle cell hypoxia Cytochrome oxidase – impairs mitochrondrial utilization of oxygen Brain – causes lipid peroxidation
  17. 17. Clinical Symptoms • Brain: headache, dizziness, nausea, vomiting, blurred vision, altered mental status, seizure, coma • Cardiac: exertional dysnea, weakness, angina, palpitations, tachycardia, tachypnea, hypotension, myocardial ischemia • Lungs: ARDS, pulmonary edema
  18. 18. Tests • Carbon Monoxide Blood Levels • Normal 1-2% • Smokers: 5-10% • 10-20 – flu like symptoms • 30 – headaches, confusion • 40-50 – loss of consciousness • 60-70 – seizure, cardiac collapse, death • 80- rapidly fatal
  19. 19. Antidote = Oxygen! Hyperbaric Chamber •When to transfer? – Evidence of end organ damage – CO level > 25, >15 if pregnant/child •Mechanism: – Decreases half life of CO – Displaces CO from myoglobin and cytochrome oxidase in tissue – Increases O2 concentration in blood
  20. 20. August 21, 2013 Sarin was used in the attack in the Ghouta region of Damascus in Syria.
  21. 21. Considerations in Organophosphate Poisonings Emergency Department Management •Initial approach •Role of decontamination Clinical Manifestions of Organophosphates •Muscarinic •Nicotinic Organophosphate Poisoning •Epidemiology •Pathophysiology Treatment: Atropine, 2-PAM •How does it work •Special considerations •How do you know if it is successful •Transfer indications
  22. 22. 23 Mini Presentations
  23. 23. Emergency Department Management • All personnel must wear protective equipment: organophosphates are absorbed by all routes (inhalation, skin, oral, ocular, parenteral) • Some OP are lipophilic and can penetrate latex and vinyl gloves • Patients must have clothing removed and discarded in well ventilated area • Leather is a great absorbent for OP • 90% of toxin is absorbed from skin • Do NOT transport pt with clothing (if possible)
  24. 24. Mechanism of Toxicity • OP binds to cholinesterase enzymes (AChE), preventing breakdown of released acetylcholine with resultant accumulation of AChE at muscarinic and nicotinic receptors • Leading to overstimulation and cholinergic excess
  25. 25. Clinical Manifestations Excess AChE at muscarinic and nicotinic receptor – predominant findings are based upon the specific agent
  26. 26. Muscarinic: SLUDGE & KILLER B’s • S Salivation, Sweating, Seizures • L Lacrimation • U Urination • Defecation, Diarrhea • G Gastric Emptying (Vomiting), GI Upset (Cramps) • E Emesis • M Muscle Twitching or Spasm • B Bradycardia • B Bronchorrhea • B Bronchoconstriction • B ? Miosis (pupil constriction)
  27. 27. Nicotinic: Autonomic Ganglia • Diaphoresis • Mydriasis (dilated eye) • Tachycardia • Hypertension Neuromuscular Junction • Fasciculations • Muscle weakness • Paralysis
  28. 28. Atropine • Competitive antagonist of Ach at muscarinic (M1, M2, M3) receptors in CNS and periphery • No effect on nicotinic receptors • End point to treatment is drying of secretions • Give 0.5mg, keep doubling dose until bronchorrhea is controlled every 2-3 minutes
  29. 29. Pralidoxime (2-PAM) • Forms complex with OP bound AChE • Then the OP-2PAM breaks off, leaving the AChE to be free for metabolism • Unfortunately may not be helpful in all cases of poisoning
  30. 30. EMS brings a 20 yo woman who is a college student at Stanford. After failing her final test and being ridiculed at the football game, she went to her dorm room, wrote a suicidal note, and ingested the entire bottle of Amitriptyline that she had just refilled earlier today. Her roommate found her somnolent but arousable. Her current vitals: HR 120 BP 100/60 RR 10, FSG 130.
  31. 31. Considerations in TCA Poisonings Emergency Department Management •Initial approach •Airway management •Important questions to ask EMS EKG as Screening Tool •Describe important EKG findings •Describe pathophysiology of EKG findings •Explain biochemistry of the findings Clinical Manifestations of TCA poisoning •Mechanism of action of TCA •Physical exam findings Treatment: Sodium Bicarbonate •Mechanism of action •How to administer •How to know if it is successful
  32. 32. Mini Presentations
  33. 33. Initial ED Management • Airway • Breathing • Circulation • Other signs of trauma • Smells • EKG • Antidote
  34. 34. TCA MOA Depression State • Block reuptake of norepinephrine, dopamine, and serotonin at the central presynaptic terminals • This increases synaptic catecholamines Overdose State • Initial release of catecholamine can induce transient hypertension followed by catecholamine depletion and relative hypotension
  35. 35. TCA Effects Anticholinergic (Anti Muscarinic) • Central effects: agitation, lethargy, hallucinations, hyperthermia, ataxia, choreoathetoid movements, seizure, coma • Peripheral effects: dilated pupils, dry, flushed skin, decreased bowel sounds, urinary retention. Sodium Channel Blocker • EKG Findings Alpha 1 adrenergic receptor blocker • Vasodilation leads to hypotension Antihistamine • Sedation and seizure
  36. 36. Physical Exam • Sinus tachycardia • Hypotension – refractory hypotension is likely the most common cause of death from TCA overdose • Hyperthermia – antimuscarinic effect • Decreased respiratory rate – CNS depression • Anticholinergic: dilated pupils, tachycardia, dry, hot/flushed skin, decreased bowel sounds, urinary retention
  37. 37. EKG as a Screening Tool 1985 Landmark Study – Boehnert and Lovejoy: 49 pts, QRS duration is better predictor of effects than TCA concentration QRS < 100 msec no significant toxicity QRS > 100 msec 1/3 had seizures QRS < 160 msec ½ had vent. dysrhythmias
  38. 38. EKG as a Screening Tool Niemann and Bessen 1986: Right axis deviation between 130-270 degrees were noted in pts poisoned with TCA RAD + QRS prolonged + QT prolonged + tachycardia = PPV of 66% and NPV 100% of TCA poisoning Efficiency of EKG as diagnostic test was 97%
  39. 39. EKG • Block fast inward sodium channels. • Type 1A antidysrhythmic effects on myocardial conduction system. • Phase 0 depolarization is prolonged with resultant QRS widening and characteristic wide complex dysrhythmia
  40. 40. Therapy • Sodium Bicarbonate • Start if QRS > 100, bolus 1-2mEq/kg • If the QRS narrows while giving NaBicarb, then you have a winner, and can start a drip • 3 amps NaBicarb in 1L D5W, infuse 2X maintainence
  41. 41. 6 yo boy brought by mother who is convinced that he was bit by a spider last weekend while at her ex-husband’s house. He is a no good...
  42. 42. Brown Recluse Spider • Little spider with tiny violin on thorax, legs are as long as 1-5 cm, but body is <1cm • South central US • Prefer dry, dark sheltered areas (shoes) • Evolution of lesion: Necrotic Arachnidism • 2-6 hrs – pruritus, tenderness, erythema, edema • 6-12 hrs – irregular area of erythema surrounded by ischemic pallor • 1-7 days – slow healing ulcer • Venom is cytotoxic • Hyaluronidase, lipase, ribonuclease, deoxyribonuclease • Sphingomyelinase D: involved in complement activation, tissue necrosis, red blood cell lysis • Treament: hyperbaric oxygen, dapsone, antihistamines, antibiotics, dextran, glucocorticoids, vasodilators, heparin, nitroglycerin, electric shock, antivenom • There is NO concensus • No clinical trials
  43. 43. Poison Control
  44. 44. Further Resources