Introduction to Toxicology

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Introduction to Toxicology

• Richard W. Stair, MD, FACEP

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Toxic Trivia

• About 4 million toxic exposures annually
• Fewer than 1 of overdose patients that reach the
  hospital result in fatality
• But 13-35 mortality if arrive in deep coma
• One fourth of suicide attempts are via drugs

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Its Not Just Swallowing Pills

• Ingestions account for 79 of exposures
• Others
• 7 dermal
• 6 ophthalmologic
• 5 inhalations
• 3 stings and bites
• .3 injection

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Toxic Trivia II

• Leading causes of pharmaceutical death
• Analgesics
• Tricyclic antidepressants
• Sedative/hypnotics
• Stimulants and street drugs
• Cardiovascular drugs
• Alcohols

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7 Mechanisms of Toxicity

• 1. Interfere with O2 transport or tissue
  utilization of oxygen
• (example cyanide, CO)
• 2. Affect CNS
• (example cocaine, sedatives)
• 3. Affect ANS
• (example organophosphates)

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7 Mechanisms of Toxicity

• 4. Affect lungs
• (example paraquat)
• 5. Affect cardiovascular system
• (example TCA, Ca channel blockers)
• 6. Direct local damage
• (example acids, bases)
• 7. Delayed effects on liver or kidneys
• (example acetaminophen, metals)

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Initial Assessment

• Primary Survey
• Airway (with C spine protection)
• Breathing
• Circulation
• Disability
• Exposure

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Obtaining the History

• Remember the AMPLE history
• Allergies, Medications, Past medical and surgical
  history,
• Last meal, Events leading to presentation
• When in a jam, remember the Ps
• Paramedics
• Parents
• Pals
• Physicians
• Pharmacists

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Physical Exam

• Vitals
• Often times no significant physical
  findings,especially if exposure early
• Beware of changes
• Odors may give clue to substance
• Look for easily recognizable toxidromes

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Odors as Clues to Toxins

• Acetone acetone, acidosis
• Alcohol NOT with ethylene
• glycol
• Bitter almonds cyanide
• Hemp (burnt rope) marijuana
• Garlic arsenic
• Rotten eggs disulfiram, H2SO4

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Toxidromes

• Anticholinergic
• Cholinergic
• Sympathomimetic
• Opioid

• Phencyclidine Syndrome
• Torsion Head and Neck Syndrome

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Anticholinergic Syndrome

• Dry as a bone (dry skin, urinary retention)
• Red as a beet (flushing)
• Blind as a bat (mydriasis)
• Hot as Hades (hyperthermia)
• Mad as a hatter (hallucinations)

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Cholinergic Syndrome

• Think DUMBELS
• Defecation
• Urination
• Miosis
• Bronchospasm
• Excessive salivation
• Lacrimation
• Seizures

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Sympathomimetic Syndrome

• Hyperthermia, hypertension, tachycardia,
  mydriasis, psychosis, convulsions
• Mimics Anticholinergic except WET compared to DRY
• sweating, urination and defecation (NOT
  retention)

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Opioid Syndrome

• Triad of
• Respiratory depression
• Coma
• Pinpoint pupils
• Also see
• Hypotension
• Hypothermia
• Bradycardia

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The Other Toxidromes

• Torsion Head Neck
• dysphonia
• oculogyric crisis
• rigidity
• torticollis
• tremors

• Phencyclidine (PCP)
• rotatory nystagmus
• miosis
• combativeness
• Crazy and No pain

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Evaluation of Toxicity

• Evaluate the SATS
• Substance
• Amount
• Time of exposure
• Symptoms
• Regional Poison Control Center

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Management

• Most toxic exposures will get better simply with
  meticulous supportive care
• Not everybody needs the full court press
• Issues to address
• frequent assessment
• decontamination
• enhancement of elimination
• Antidotes
• disposition

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Frequent Assessment

• Do they need to be here at all?
• Beware of the Stable patient
• Consider possible polysubstance exposures
• Be prepared for deterioration
• IV access
• Cardiac monitor
• Pulse oximetry

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Decontamination Methods

• Aim is to prevent absorption and minimize
  exposure
• Many standard practices now virtually extinct
• Forced emesis, forced lavage, charcoal anytime
• Removal of contaminated clothing, substances on
  skin or in eyes
• Charcoal
• Gastric lavage
• Whole Bowel Irrigation

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Charcoal

• Works by substances being adsorbed to the
  surface, which is size dependent
• Window of opportunity around one hour post
  ingestion
• Has some indications for multiple dosing
• drugs that have enterohepatic circulation
• drugs that can be eliminated by gut dialysis

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Charcoal Contraindications

• Charcoal doesnt bind CHARCOAL
• Caustics and corrosives
• Heavy metals
• Alcohols
• Rapid absorption (cyanide, strychnine)
• Chlorine and iodine
• Other agents insoluble in water
• Aliphatics (petroleum distillates)
• Laxatives (Mg, K, Na)

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Charcoal Contraindications

• Loss of protective reflexes
• drugs likely to cause rapid depressed
  consciousness or early seizures
• infants lt 6 months of age
• ingested foreign body
• neurologically impaired
• absent bowel sounds or obstruction
• unstable patients

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Multi-dose CharcoalEnterohepatic Circulation

• Chloral hydrate
• colchicine
• digitalis preparations
• glutethimide
• isoniazid
• methaqualone

• NSAIDS
• phencyclidine
• phenothiazines
• phenytoin
• salicylates
• TCAs

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Multi-dose CharcoalGut Dialysis

• Pretty Damn Short QTc
• Phenobarbital
• Dapsone
• Salicylates
• Quinine
• Theophylline
• Carbemazepine

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Decontamination Methods

• Gastric lavage
• Used far less now than in past
• Having your stomach pumped, with large tube
  inserted into stomach, suctioned, and lavaged
• Risk of perforation, aspiration, and simply not
  working
• Contraindicated in comatose or seizing patients,
  unprotected airways, extended release preparations

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Decontamination Methods

• Whole Bowel Irrigation
• cleanses gut of intoxicants
• PEG solutions at 2 Liters/hour
• effective for use in LA preparations, body
  packers/stuffers, and some substances poorly
  absorbed by charcoal (ex iron)
• contraindicated if hematemesis, ileus,
  obstruction, perforation, or peritonitis

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Enhancement of Elimination

• In other words, get rid of the toxin faster
• Cathartics - used, but no study showing benefit
• Alkalinization salicylates
• Hemodialysis
• Hemoperfusion

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Hemodialysis

• Invasive, time consuming procedure
• Patients unstable despite supportive treatment
• Drugs must be amenable to hemodialysis
• Must have small volume of distribution (ie, drug
  must be in plasma, not tissues)
• Must not be tightly protein bound

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Hemodialysis

• I STUMBLE (the common ones)
• Isoniazid
• Salicylates
• Theophylline
• Uremia
• Methanol
• Barbiturates
• Lithium
• Ethylene glycol

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Antidotes

• Very limited number of antidotes given the vast
  array of pharmaceuticals and chemicals
• Coma Cocktail
• glucose
• thiamine
• naloxone
• NOT flumazenil

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Common Antidotes

• Toxin
• APAP
• Tricyclics
• Opiates
• Organophosphates
• Heavy metals
• Ca and beta blockers
• Iron
• Digoxin

• Antidote
• N acetylcysteine
• Na bicarbonate
• Naloxaone
• 2 PAM
• BAL
• Glucagon
• Desferoxamine
• Dig Fab (Digibind)

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Common Antidotes

• Toxin
• Methanol, ethylene glycol
• Methemoglobinemia
• Anticholinergics
• Isoniazid
• Snakebites

• Antidote
• Fomepizole (Antizole)
• Methylene blue
• Physostigmine
• Pyridoxine
• Antivenom

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Agitated, Violent, and Psychotic Patients

• Reports of sudden death from overzealous physical
  restraint
• Must maintain safe environment for the patient,
  other patients, staff (and yourself)
• Combination of Physical and Chemical Restraints

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Ancillary Testing

• EKG and cardiac monitor, pulse oximetry
• Consider acetaminophen and salicylates
• Acid-base status determinations
• MUDPILES, etc
• Osmolal gap determination
• 2Na BUN/2.8 glu/18 EtOH/4.6
• Directed toxicology (very limited role)

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Directed Toxicology Tests

• Comatose Tox screen, glu, NH4, CT scan, CSF
  analysis
• Respiratory toxin ABG, CXR, spirometry,
  pulse ox
• Cardiac toxin EKG, ECHO, cardiac enzymes,
  hemodynamic monitoring

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Directed Toxicology Tests

• Hepatic Toxin LFTs, NH4, glu, coags,
  amylase
• Nephrotoxin Chem 7, UA, serum urine
  osmolarity, 24 hr urine heavy
  metals
• Bleeding Coags, platelets, FSP,
  fibrinogen, TS

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High Risk Patients (ICU wannabees)

• Needs circulatory or respiratory support
• altered mental status gt 3 hours
• seizures
• arrhythmia
• second or third degree heart block
• widened QRS
• unresponsive to verbal stimuli
• arterial pCO2 gt 45 mmHg

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Disposition

• Home if stable after appropriate evaluation and
  observation period, unintentional or simple
  gesture with support structure
• Psychiatry evaluation if intentional, or risk to
  harm self or others
• Admission if unstable, long-acting or sustained
  release, needing therapies