Introduction to Toxicology

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Introduction to
Toxicology
Medical Toxicology....
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Is a board-accredited specialty requiring at
least two years of training after residency
in either emergency medicine, pediatrics,
internal medicine or preventative medicine.
Deals with the “diagnosis, management
and prevention of poisoning and other
adverse health effects due to medications,
occupational and environmental toxins,
and biological agents”
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This lecture will condense this
information into two parts:
•
The approach to the poisoned patient
Case scenarios
•
Part I: Approach to the poisoned
patient.
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“Attempts to identify the poison should not delay
care.”
Initial management of the poisoned patient begins
with the ABC’s.
ACLS algorithms apply in toxicology with only a
few exceptions.
Once these are stable, begin considering how to
minimize bioavailability. Then you may begin
your history and physical.
History: find out all of this
information:
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The question words:
Which drug(s) were taken?
When was it taken?
How much was taken?
How was it taken?
Why was it taken?
Was anything else taken? (Consider coingestants: other things which may be in this
person’s medicine cabinet.)
History continued....
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Patients who overdose or use illicit drugs
may be unreliable.
Gather info from paramedics, family,
friends, the PCP, old medical records, pill
bottles the patient has on them, their
occupational environment or by having
people return to the scene where the
incident took place.
History continued....
Obtain a clinical history from
family/friends or paramedics:
- patient’s behavior prior to arrival
- changing vital signs
- seizures
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Physical Examination:
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Vital Signs: You MUST obtain a full set of
vital signs, including blood glucose.
Vital signs are the key to your initial
management of the patient....
Vital signs: Pulse
Bradycardia
(P.A.C.E.D.)
Propanolol, poppies
Anticholinesterases
Clonidine, CCB’s
Ethanol
Digoxin
Tachycardia
(F.A.S.T.)
Freebase
Anticholinergics/
Antihistamines
Amphetamines
Sympathomimetics
Solvents
Theophylline
Vital signs: Temperature
Hypothermia
(C.O.O.L.S.)
Carbon monoxide
Opiates
Oral hypoglycemics
Liquor
Sedatives/Hypnotics
Hyperthermia
(N.A.S.A.)
N.M.S., Nicotine
Antihistamines
Salicylates
Sympathomimetics
Anticholinergics
Antihistamines
Vital signs: Blood pressure
Hypotension
(C.R.A.S.H.)
Clonidine, CCB’s
Reserpine
Antihypertensives
Antidepressants
Aminophylline
Sedative/Hypnotics
Heroin (opiates)
Hypertension
(C.T.S.C.A.N.)
Cocaine
Thyroid supplements
Sympathomimetics
Caffeine
Anticholinergics
Amphetamines
Nicotine
Vital signs: Respiration rate
Hypoventilation
(S.L.O.W.)
Sedative/Hypnotics
Liquor
Opiates
Weed (marijuana)
Hyperventilation
(P.A.N.T.)
PCP
Pneumonitis
Noncardiogenic
pulmonary edema
Toxic met. acidosis
Physical: Neurologic exam
Mental status
(AEIOU TIPS)
Alcohol
Endocrine/Epilepsy
Intoxication
Oxygen
Uremia
Trauma/Tumor
Infection
Psychological
Shock/Strokes
Seizures
(OTIS CAMPBELL)
Organophosphates
Tricyclics
INH/Insulin
Sympathomimetics
Camphor/Cocaine
Amphetamines
Methylxanthines
PCP
Benzo withdrawal
Ethanol
Lead, Lithium
Lidocaine, Lindane
Physical exam: Pupils
Miosis
(C.O.P.S.)
Cholinergics
Clonidine
Opiates
Organophosphates
Pontine bleed
Phenothiazines
Sedatives/Hypnotics
Mydriasis
(A.A.A.S)
Antihistamines
Antidepressants
Anticholiergics
(Atropine)
Sympathomimetics
(Cocaine)
Physical: Dermatological exam
Diaphoresis
Red Skin
Blue Skin
(S.O.A.P.)
CO
Cyanosis
Sympathomimetics
Boric Acid
MetHb
Organophosphates
Anticholinergics
ASA
PCP
Blistering
Barbituates, CO, Sedative hypnotics, snake/spider bites
Odors...
Bitter almonds:
Mothballs:
Garlic:
Peanuts:
Carrots:
Rotten eggs:
Wintergreen:
Gasoline:
Fruity:
Pears:
Cyanide
Camphor
Organophosphates, Arsenic
Rodenticide
Water hemlock
Sulfur dioxide, HS
Methyl salicylates
Hydrocarbons
DKA, Isopropanol
Chloral hydrate
Epidemiology of Toxicology...
The majority of poisonings were
unintentional.... But, the majority of
deaths secondary to poisoning were
intentional.
Most poisonings are by ingestion and most
poisonings occur at home.
Epidemiology continued...
The most commonly reported poison?
Analgesics!
The least commonly reported?
Alcohol!
Which is associated with the most deaths?
Analgesics!
Which is associated with the least deaths?
Hydrocarbons!
The number one poisonous killer?
Carbon monoxide!
Lab tests/Diagnostics...
EKG. Why?
To look for conduction delays and ischemia.
(sympathomimetics, B-blockers, TCA’s, digoxin,
CCB’s, CO)
CMP. Why?
To calculate anion gap and osmolality. (CAT MUD
PILES and ME DIE mnemonics)
Tylenol and Aspirin levels. Why?
Because of the frequency of abuse and co-ingestion.
Lab tests/diagnostics continued...
Serum volatiles (this tells you quantitative amounts
of alcohols). Why? When?
With AMS of unknown etiology, for legal purposes,
for unexplained osmolar gaps.
Drug screens. Why? When?
With urine: Screening purposes only. (This rarely
changes your management)
With blood: For quantitative information regarding
specific ingestants.
Imaging...
Chest XR:
(Pulmonary Edema)
(M.O.P.S.)
Meprobamate
Methadone
Opiates
Phenobarbital
Propoxyphene
Salicylates
KUB:
(C.O.I.N.S.)
Chloral hydrate
Cocaine packets
Opiate packets
Iron (Heavy metals)
Neuroleptics
Sustained release/
enteric coated tabs.
Management...
“Coma cocktail” (Dextrose, Narcan,
Thiamine)
- Check blood sugars (the sixth vital sign)
- Narcan has side effects too!
- Thiamine for the malnourished
Flumazenil is reserved for people who we
overdose with benzos!
Management (GI decontamination)
Syrup of ipecac: Is not used
 Gastric lavage:
- Used with “moderate to severe
overdoses” within an hour of ingestion.
-There is a highly variable outcome with
this intervention.
-Lavage is contraindicated with ingestion of
corrosives.
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GI decontamination continued...
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Activated charcoal:
- Purported to be superior to lavage
- Used in toxic ingestions within an hour of
the ingestion.
- Dosed as 1g/kg or 10:1 ratio of charcoal to
poison
- Given as single dose or multiple dose
Multiple dose
Not adsorbed
(A.B.C.D.)
Antimalarials
Aminophylline
ASA (?)
Barbiturates
B-Blockers (?)
Carbamazepine
Dapsone
Dilantin (?)
(C.H.A.R.C.O.A.L.)
Caustics/Corrosives
Heavy metals
Alcohols
Rapid onset cyanide
Chlorine/Iodine
Other insolubles (tabs)
Aliphatics
Laxatives
GI decontamination...
Cathartics:
- Given with charcoal to enhance
elimination
- Unproven efficacy when used alone.
Whole bowel irrigation:
- May be effective for things not adsorbed
by charcoal
- Used for body stuffers/packers
Decontamination via enhanced
elimination...
Hemodialysis:
(I.S.T.U.M.B.L.E.)
Isopropanol
Salicylates
Theophylline
Uremia
Methanol
Barbiturates
Lithium
Ethylene glycol
Urine Alkalinization:
ASA, Phenobarbital
(Alkalinizing the urine with
NaHCO3 to trap ions of weakly
acidic agents to promote
excretion).
Titrate NaHCO3 to maintain
urinary pH of 7.5-8.0.
Management (Antidotes)...
Toxin
Acetaminophen
Anticholinergics
Arsenic/Lead
B-Blockers
Benzos
CO
Cyanide
Digoxin
Ethylene glycol/Methanol
Iron
INH
Lead/Mercury
Methemoglobinia
Opioids
Organophosphates
TCA’s
Antidote
N-acetylcysteine
Physostigmine
BAL chelation
Glucagon
Flumazenil
O2, HBO
Nitrites
Digibind
Fomepizole/Ethanol
Deferoxamine
B6/Pyridoxine
Succimer/DMSA
Methylene blue
Naloxone
Atropine
Sodium bicarbonate
Pitfalls...
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Ingestion of multiple agents is common
Dangerous drug combinations
Drugs masking the effects of other drugs
All altered mental status is not tox.
Consider trauma (head bleeds) and
metabolic causes (DKA, Thyroid, etc)
Pearls...
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Always begin with airway, breathing,
circulation. The poisoned patient is not
exempt from this mantra.
ACLS protocols generally apply to
poisoned patients.
Treat the patient, not the poison. Observe
vital signs and provide supportive care
constantly.
Part II: Case studies
Case 1:
Mr. Smith, a 28 year old male presents in police custody
complaining of chest pain. He has no other past medical
history. No history of cardiac disease.
Patient further states that his chest pain began tonight about one
to two hours after he was arrested by police. No history of
trauma.
Social history=Smokes 1 pack/day. Occasional EtOH.
Family History= No cardiac deaths.
Mr. Smith
Physical exam...
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General: Patient very agitated, clutching his chest.
Vitals: P 140, BP 220/130 RR-28 Temp- 103.2F
Eyes: Pupils 7mm, equal, EOMI
Lungs: Clear Bilaterally
Heart: Regular rate and rhythm, 2+/6 systolic
murmur
Abd: Soft, Non-Tender, BS+
Neuro: No focal deficits.
Skin: Diaphoretic
Differential diagnosis???
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Sympathomimetics (cocaine? amphetamines?)
Anticholinergics?
Thyroid disease?
Solvents?
Antihistamines?
Undiagnosed hypertension?
Acute MI?
Malingering? (Why did his symptoms begin an
hour after the arrest? Why not immediately?
What do you want to order?
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EKG? (grossly abnormal vital signs)
CMP?
TSH?
UTox?
Serum volatiles?
Imaging?
Cardiac enzymes?
EKG:
How should this person’s cocaine
related chest pain be managed?
1.
2.
3.
4.
Benzodiazepines- First line therapy (in high
doses)
Nitroglycerin- for control of ischemic pain and
HTN
Labetalol- alpha/beta blocker (the use of
propranolol will leave the alpha portion
unopposed theoretically exacerbating cocaine's
toxicity). Alternatively, phentolamine could be
used.
Nitroprusside- for refractory HTN
This person ingested bags of cocaine. What
is the best method of GI decontamination?
Ipecac
Whole Bowel Irrigation
Cathartics
Activated Charcoal
Dialysis
Urine alkalinization
Gastric lavage
Should other services be involved?
If so, whom?
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Tox!
Surgery (Why?)
Cardiology (Why?)
The outcome....
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The patient's chest pain and hypertension eventually resolve
with large doses of nitroglycerin and benzodiazepines.
The patient is administered activated charcoal and
polyethylene glycol solution by the ED physician.
Because of the ST segment elevations, the cardiologist elects
to give thrombolytics.
Since thrombolytics were "on board" the general surgeon
refuses to take the patient to the OR for exploratory
laparotomy and removal of the cocaine packets.
The patient is transferred to the ICU, where he eventually
recovers and is discharged with a 10% ejection fraction.
Case 2
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The patient is a 18 year old male presenting to the
ED by paramedics after found at home
unresponsive, face down in bed. According to
friends, the patient had consumed two beers and
a glass of wine earlier that day following a period
of depression. The patient was orally intubated in
the field by paramedics after no response to D50
and naloxone administration.
Physical exam:
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General: Patient responsive only to deep painful
stimuli
Vitals: BP 150/70, HR=92, RR=24, T=95.4F
Lungs: CTA, BS Equal, (Intubated)
CV: RRR, no murmur
Abd: Soft, Non-Tender, No Trauma, No Masses
Rectal: Normal Tone, HemeNeuro: DTR's Hyporeflexive, Withdraws to
Painful Stimuli
Differential diagnosis??
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Alcohol intoxication?
Carbon monoxide?
Sedatives/Hypnotics? (benzos?
barbiturates? muscle relaxants?)
Tylenol?
Trauma?
Large doses of narcotics?
What do you want to order?
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CBC?
CMP?
Serum osmolality?
Serum volatiles?
Urine toxicology screen for drugs of abuse?
EKG?
Results:
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CBC: WBC 29K HCT=45
Lytes: Na=145 Cl=105 K=5.2 HCO3=5
BUN/Cr: 28/1.8 Glucose 180
Osm: 370 (Measured)
ETOH: 46
Calcium 7.0
Toxicology Screen: Pending
Toxic Alcohols: Pending
What is his anion gap? What is his osmolar gap?
AG: 20. Osmolar gap: 370 – (2(Na) + Glu/18 +BUN/2.8
+ETOH/4.6) = 50! (50 is greater than 10, so..... )
Results continued...
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EKG shows NSR. No interval changes. No
ST, T or Q wave changes. Normal axis.
Normal R wave progression
CXR: Shows normal sized heart and
mediastinum. No effusions or infiltrates.
No acute disease. ETT in proper position.
How do you want to manage this
patient?
Supportive care only
 Gastric lavage
 Hemodialysis
Is there a potential antidote for this?
YES! Fomepizole!
We don’t have any fomepizole. But we do
have ethanol!
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Outcome...
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With a strong clinical suspicion for toxic alcohol ingestion, an
ethanol drip is ordered, but due to pharmacy delay, the
patient is orally loaded with 85 proof whiskey obtained from
another patient in the ER waiting room.
Urine is positive for calcium oxalate crystals. Dialysis is
initiated by the renal service, after which an ethylene glycol
level of 310 mg/dl returns 12 hours later.
The patient recovers with mild renal insufficiency, and is
subsequently followed-up by the psychiatric service for his
depression.
References...
1. Erickson TB et al. Toxicology Update: A Rational Approach to
Managing the Poisoned Patient. Emerg Med Pract. 2001;
3(8): 1-28
2. Tuckler, Victor. Introduction to Toxicology handout
3. Rivers, Carol S. Preparing for the Written Board Exam in
Emergency Medicine. 5th Ed. Volume II. PP 735-738
4. “Case studies in Toxicology” available at:
http://www.uic.edu/com/er/toxikon/cases/allcase.htm
5. http://www.med.umich.edu/lrc/baliga/case02/images/infMI2.
jpg
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