Toxicology 101Case Based Learning

The Emergency Medicine approach to the poisoned patient

Nikita Joshi MDEmergency Department

Academic Fellow

njoshi8@GMAIL.COM

@njoshi8

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

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

This is our specialty!

• Immediate intervention with antidotes

• Control of airway

• Multiple patients

• Multisystem involvement

• Hyperbaric Chamber

• Toxicology Fellowship

• EMS training

• Hazmat

• Disaster Medicine

Definition

• Study of adverse effects of chemicals on living organisms

• Study of symptoms, mechanisms, treatment & detection of poisoning (wikipedia)

A good toxicologist …

• Pathophysiology• Biochemistry• Pharmacology• Organic Chemisty

Approach to Patient

• Scene Safety• Decontamination• Airway• Breathing• Circulation• Physical Exam• Labs• Antidotes• Disposition

Toxicology Physical Exam

• Vital Signs: HR BP RR O2 Sat T• Neuro• Eye• Cardiac• Respiratory• Abdominal• Bladder• Skin

Toxidromes

• Sympathomimetics• Cholinergic• Anticholinergic• Opioids• Narcotics

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.

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

Mini Presentations

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

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

CO BindsHemoglobin

Platelet hemoproteinsMyoglobin

Cytochrome oxidase

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

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

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

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

August 21, 2013 Sarin was used in the attack in the Ghouta region of Damascus in Syria.

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

23

Mini Presentations

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)

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

Clinical Manifestations

Excess AChE at muscarinic and nicotinic receptor – predominant findings are based

upon the specific agent

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)

Nicotinic:

Autonomic Ganglia• Diaphoresis• Mydriasis (dilated eye)• Tachycardia• Hypertension

Neuromuscular Junction• Fasciculations• Muscle weakness• Paralysis

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

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

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.

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

Mini Presentations

Initial ED Management

• Airway• Breathing• Circulation• Other signs of trauma• Smells• EKG• Antidote

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

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

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

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

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%

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

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

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...

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

Poison Control

Further Resources