Download Toxicology I

Poisoning/Overdose
General Management
Poisoning is Exposure to substance that is toxic in
any amount
Overdose
Exposure to substance in
excess amount
resulting in toxic effects
1998 TESS* Data
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2,241,082 reported human exposures
97.9 % at home
Peak volume 4pm-10pm
91% of calls 8pm-midnight
*The Toxic Exposure Surveillance System (US based)
Exposures by Age
• < 6 years old
• < 3 years old
Fatalities
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775 fatalities
0.03% of total exposures
ages 20 - 49 years = 56%
>6 years = 2.1%
52.7%
39.6%
Number of Substances
• 92.8% of all cases--one
substance
• 44.7% of fatal cases-->2
substances
Management Location
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Managed on site
75.2%
Treated, released at ER only 12.3%
Admitted to critical care
2.7%
Refused referral *
2.0%
Therapy
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No therapy
11.9%
Observation only
12.7%
Decontamination only 59.6%
Activated charcoal
6.8%
Ipecac
1.2%
Most Common
Substances
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Cleaning substances
Analgesics
Cosmetics
Plants
Foreign bodies
Cough, cold
Bites, stings
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Insecticides, pesticides, rodenticides
Sedative, hypnotics, antipsychotics
Antidepressants
Hydrocarbons
Alcohols
10.2%
9.6%
9.4%
5.5%
4.6%
4.5%
4.1%
3.9%
3.2%
3.0%
3.0%
2.5%
Largest Number of
Deaths
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Analgesics
Antidepressants
Stimulants, street drugs
Cardiovascular medication
Sedatives, hypnotics
Alcohols
264
152
118
118
89
56
Indicators
• Sudden onset of CNS signs:
– Seizures
– Coma
– Decreased LOC
– Bizarre behavior
• Sudden onset of:
– Abdominal pain
– Nausea
– Vomiting
Indicators cont
• Sudden onset of unexplained
illness
• Bizarre, incomplete, evasive
history
• Trauma
(>50% of adult trauma EtOH,
drug-related)
• Pediatric patient with arrhythmias
History
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What?
How much?
How long?
Multiple substances?
Treatment attempted? How?
Whose advice?
• Psychiatric history?
• History of suicide?
Scene Survey
• Check out scene for :
–1
–2
–3
–4
• Where do you look for clues?
General Management
• Support ABC’s
– Secure airway, secure with advanced
airway if needed
– Ensure adequate oxygenation, ventilation
– Maintain adequate circulation
• Monitor ECG
• Obtain vascular access
• Manage hypotension initially with
volume
• Use vasopressors cautiously
General Management
• Keep patient calm
• Maintain normal body temperature
• Evaluate nature/toxicity of poison
– Check container, package insert, poison center
information
– Treat the patient, not the poison
General Management
• Rule out (differential diagnosis)
– Trauma
– Neurological disease
– Metabolic disease
• Base general management on route of pois
entry
Poison Entry
• Ingestion
• Inhalation
• Prevent absorption from GI
tract
• Remove from exposure;
Support oxygenation,
ventilation
• Absorption
• Remove from skin
surface
• Injection
• Slow movement from
injection site
throughout body
Ingested Poisons
Objective
Remove from GI tract before
absorption occurs
Ipecac
• RARELY used anymore
• If used, has to have been initiated
within few minutes after ingestion
• Vomiting in 20-30 minutes
• Only removes about 32% of
contaminate
• Many contraindications
Ipecac
• Dose
– 15 cc if 12 months to 12 years old
– 30 cc if >12 years old
• Follow with 2-3 glasses of water
• Keep patient ambulatory if
possible
Ipecac
• If no vomiting after 20 minutes,
repeat
• When emesis occurs, keep head
down
• Collect, save vomitus for analysis
Ipecac
• Contraindications
– Comatose or no gag reflex
– Seizing or has seized
– Caustic (acid or alkali) ingestion
– Low viscosity hydrocarbon ingestion
– Late term pregnancy
Ipecac
• Contraindications
– Severe hypertension, cardiovascular
insufficiency, possible AMI
– Ingestion of:
• Strychnine
• Phenothiazines (Thorazine, Stellazine,
Compazine)
• Tricyclic antidepressants
• Iodides
• Silver Nitrate
Lavage
• Commonly used in ED’s
• Removes about 31% of
substance
• Helps get activated charcoal in
patient, especially if patient is
unconscious
• Not helpful for sustained release
tablets
• Will not remove large tablets
Activated Charcoal
• Adsorbs compounds, prevents
movement from GI tract
• Very effective at adsorbing
substances
• Binds about 62% of toxin
• Dose
– 5 - 10X estimated weight of ingested
chemical
Activated Charcoal
• Inactivates Ipecac
• Do not give until vomiting stops
• Do not give with
– Cyanide
– Methanol
– Tylenol (+)
• Containers must be kept airtight
• Can be given PO via slurry or by
NG
Inhaled Poisons
Objective: Move to fresh air;
optimize ventilation and protect
personnel from exposure
Absorbed Poisons
Objective: Remove poison from
skin
Liquid: Wash with copious
amounts of water
Powder: Brush off as much as
possible, then wash with copious
amounts of water
Protect personnel from exposure
Dilute / Irrigate / Wash
• Use soap, shampoo for hydrocarbons
• No need for chemical neutralization heat produced by reaction could be
harmful
Eye Irrigation
• Wash for 15 minutes
• Use only water or balanced salt
solutions
• Remove contact lenses
• Wash from medial to lateral
Examples of Specific Toxins
Acids
• Examples
– Toilet bowl cleaner
– Rust remover
– Phenol (carbolic acid)
– Hydrochloric acid
• Severe burning of stomach
• Absorption, systemic acidemia
Acids
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Loss of airway = most immediate threat
Secure airway against edema
IV with RL, NS for volume loss
Emesis, gastric lavage contraindicated
Dilution with water, milk NOT recommended
Alkalis
• Examples
– Drain cleaner
– Washing soda
– Ammonia
– Lye (sodium hydroxide)
– Bleach (sodium hypochlorite)
• Severe burning of esophagus,
stricture formation
Alkalis
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Loss of airway = most immediate threat
Secure airway against edema
IV with LR, NS for volume loss
Emesis, gastric lavage contraindicated
Dilution with water, milk NOT recommended
Hydrocarbons
• Examples
– Kerosene
– Gasoline
– Lighter fluid
– Turpentine
– Furniture polish
Hydrocarbons
• Signs/Symptoms
– Choking, coughing, gagging
– Vomiting, diarrhea, severe
abdominal pain
– Chemical pneumonitis, pulmonary
edema
If the patient is coughing,
aspiration has occurred
Methanol
methyl alcohol
wood alcohol
wood naphtha
Methanol
• Sources
– Industry
– Household solvents
– Paint remover
– Fuel, gasoline additives
– Canned heat
– Windshield washer antifreeze
Methanol
• Toxic dose
– Fatal oral: 30-240ml
– Minimum: 100 mg/kg
– Example
• Windshield washer fluid 10% Methanol
• 10 kg child needs only 10 cc to be toxic
Methanol
• Mechanism of toxicity
– Methanol slowly metabolized to
formaldehyde
– Formaldheyde rapidly metabolized
to formic acid
• Acidosis
• Ocular toxicity
Methanol Metabolism
H
Methanol
H C OH
Alcohol dehydrogenase
H
O Formaldehyde
H C
H
Aldehyde dehydrogenase
O Formic Acid
H C
OH
O
H C
_
O
H+
Cyanide
But first…
• A little review of
biochemistry
and biophysics
Staying alive requires energy...
• The natural tendency of the
universe is for things to
become more disorderly.
• This trend toward disorder is
called entropy.
• Complex systems (including
us) don’t tend to last long,
unless…
• They have a constant supply
of energy to combat entropy.
Organisms capture and store the energy
they need in the form of...
Adenosine Triphosphate (ATP)
• The “currency” cells use
to pay off the energy
debt built up fighting
entropy.
• Formed by capturing
energy released as the
cell breaks down large
molecules through
glycolysis and the
Krebs Cycle.
Putting It All Together
• Cells have to have energy to stay alive.
• Cells get energy by breaking down glucose in two phases:
glycolysis and the Krebs Cycle.
• Glycolysis yields 2 ATP and pyruvate.
• Pyruvate is changed to acetate (acetyl-CoA) and sent to
the Krebs Cycle.
• The Krebs Cycle strips hydrogen and electrons off acetate
and feeds them into the electron transport chain.
• Movement of electrons down the transport chain releases
energy which is trapped as ATP.
• At the end of the chain, the electrons combine with
hydrogen and oxygen to form water.
• CN messes with this !
Cyanide
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Chemical, plastic industries
Metallurgy, jewelry making
Blast furnace gases
Fumigants, pesticides
Present in various plants
– apples, pears, apricots, peaches, bitter
almonds
• Remember there is CN gas released
by BURNT plastics (e.g fire!!)
Cyanide Antidote Kit
• Amyl nitrite, sodium nitrite
– Only be used in serious cyanide poisonings
– Can induce life-threatening tissue hypoxia
secondary to methemoglobinemia
• Sodium thiosulfate
– Can be used by itself
– Is relatively benign
Salicylates
Salicylates
• Examples
– Aspirin
– Oil of wintergreen
• Uses
– Analgesics
– Antipyretics
– Anti-inflammatories
– Platelet function inhibitors
Salicylates
• Mechanism of Toxicity
– Direct stimulation of respiratory center,
causing respiratory alkalosis
– Irritation of gastrointestinal tract, causing
decreased motility, pylorospasm,
nausea, vomiting, hemorrhagic gastritis
– Decreased prothrombin levels/platelet
dysfunction, causing prolonged clotting
times
– Uncoupling of oxidative phosphorylation
Results of Oxidative Phosphorylation
Uncoupling
• ATP production decreases, resulting in CNS and
cardiovascular failure.
• Cells attempt to compensate by increasing the rate they
process glucose anaerobically through glycolysis.
• Lactic and pyruvic acids accumulate, leading to metabolic
acidosis.
• Hypoglycemia results as liver sugar stores are depleted.
• In absence of sugar cells begin to metabolize lipids, ketone
bodies are produced, acidosis worsens.
• Energy normally trapped as ATP is wasted as heat, causing
a rise in body temperature.
• The rise in body temperature accelerates metabolism,
increasing tissue oxygen demand and worsening acidosis.
Salicylates
Clinical Presentation: Acute Toxicity
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Vomiting
Lethargy
Hyperpnea
Respiratory
alkalosis
– Metabolic
acidosis
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Coma
Seizures
Hypoglycemia
Hyperthermia
Pulmonary
edema
Salicylates
• Clinical Presentation: Chronic
Toxicity
– Usually young children, confused
elderly
– Confusion, dehydration, metabolic
acidosis
– Higher morbidity, mortality than
acute overdose
– Cerebral, pulmonary edema more
common
Salicylates
• Acute Toxicity Management
– Oxygen, monitor, IV
– GI tract decontamination
– Activated charcoal
– Replace fluid losses, but do NOT
overload
– Control hyperthermia
Salicylates
• Acute Toxicity Management
– Bicarbonate for metabolic acidosis
– D50W for hypoglycemia
– Diazepam for seizures
Acetaminophen
Acetamophen
• Examples
– Tylenol
– Tempra
– Many drugs contain this also
• Uses
– Analgesic
– Antipyretic
Acetaminophen
• Mechanism of toxicity
– N-acetyl p-benzoquinonimine,
normal product of acetaminophen
metabolism, is hepatotoxic
– Normally is detoxified by glutathione
in liver
– In overdose, toxic metabolite
exceeds glutathione capacity,
causes liver damage
Acetaminophen
• Management
– Induce emesis
– Do NOT give activated charcoal in
general
– Give specific acetaminophen
antidote
Acetaminophen
• The specific antidote for acetaminophen toxicity.
Mucomyst
• N-acetylcysteine
Another sulfur-containing amino acid
Substitutes for glutathione.
Allows continued detoxification of NAPBQI.
140mg/kg initially followed by 70mg/kg every 4 hours
17 times.
Tastes, smells like rotten eggs
Mix with chilled fruit juice to decrease odor, taste
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More to come
• Review
– Cocaine OD
– TCA OD
– Opoid OD
– MDMA - E
– GHB