toxicology 101
DESCRIPTION
TRANSCRIPT
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Toxicology 101Case Based Learning
The Emergency Medicine approach to the poisoned patient
Nikita Joshi MDEmergency Department
Academic Fellow
@njoshi8
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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
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We love tox!
Vietnam War
Ricin poisoning
Don’t drink the Kool AidIndian school children
Bulgarian Dissident Writer
James Town MassacreKool Aid – laced with cyanide – inhibits cytochrome C oxidase
Organophosphates – inhibition of acetylcholinesterase
Ricin – inhibits protein synthesis
Dioxin – defoliant – form of organophosphate
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This is our specialty!
• Immediate intervention with antidotes
• Control of airway
• Multiple patients
• Multisystem involvement
• Hyperbaric Chamber
• Toxicology Fellowship
• EMS training
• Hazmat
• Disaster Medicine
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Definition
• Study of adverse effects of chemicals on living organisms
• Study of symptoms, mechanisms, treatment & detection of poisoning (wikipedia)
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A good toxicologist …
• Pathophysiology• Biochemistry• Pharmacology• Organic Chemisty
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Approach to Patient
• Scene Safety• Decontamination• Airway• Breathing• Circulation• Physical Exam• Labs• Antidotes• Disposition
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Toxicology Physical Exam
• Vital Signs: HR BP RR O2 Sat T• Neuro• Eye• Cardiac• Respiratory• Abdominal• Bladder• Skin
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Toxidromes
• Sympathomimetics• Cholinergic• Anticholinergic• Opioids• Narcotics
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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.
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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
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Mini Presentations
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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
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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
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CO BindsHemoglobin
Platelet hemoproteinsMyoglobin
Cytochrome oxidase
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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
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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
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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
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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
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August 21, 2013 Sarin was used in the attack in the Ghouta region of Damascus in Syria.
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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
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Mini Presentations
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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)
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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
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Clinical Manifestations
Excess AChE at muscarinic and nicotinic receptor – predominant findings are based
upon the specific agent
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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)
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Nicotinic:
Autonomic Ganglia• Diaphoresis• Mydriasis (dilated eye)• Tachycardia• Hypertension
Neuromuscular Junction• Fasciculations• Muscle weakness• Paralysis
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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
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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
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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.
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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
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Mini Presentations
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Initial ED Management
• Airway• Breathing• Circulation• Other signs of trauma• Smells• EKG• Antidote
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TCA MOADepression
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
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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
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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
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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
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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%
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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
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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
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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...
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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
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Poison Control
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Further Resources