Toxicology
UNC Emergency Medicine
Medical Student Lecture Series
Objectives
• General approach to the poisoned
patient
• Toxidromes
• Specific antidotes
• Decontamination and enhanced
elimination
General Approach
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ABC’s
History
Physical examination
Labs, imaging
Diagnosis, antidotes
Disposition
ABC’s
Airway
• Airway obstruction can cause death after poisoning
– Flaccid tongue
– Aspiration
– Respiratory arrest
• Evaluate mental status and gag/cough reflex
• Airway interventions
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Sniffing position
Jaw thrust
Head-down, left-sided position
Examine the oropharynx
Clear secretions
Airway devices: nasal trumpet, oral airway
• Intubation?
– Consider naloxone first
Breathing
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Determine if respirations are adequate
Give supplemental oxygen
Assist with bag-valve-mask
Check oxygen saturation, ABG
Auscultate lung fields
– Bronchospasm: Albuterol nebulizer
– Bronchorrhea/rales: Atropine
– Stridor: Determine need for immediate intubation
Circulation
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IV access
Obtain blood work
Measure blood pressure, pulse
Hypotension treatment:
– Normal saline fluid challenge, 20 mL/kg
– Vasopressors if still hypotensive
– PRBC’s if bleeding or anemic
• Hypertension treatment:
– Nitroprusside, beta blocker, or nitroglycerin
• Continuous ECG monitoring
– Assess for arrhythmias, treat accordingly
Supportive Care
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Foley catheter
Rectal temperature
Accucheck, treat hypoglyemia
Coma cocktail
– Thiamine: 100 mg IV, before dextrose
– Dextrose: 50 grams IV push
– Naloxone: 0.01 mg/kg IV
Supportive Care
• Treat Seizures
– Lorazepam 2 mg IV, may repeat as needed
– Dilantin 10 mg/kg IV
• Control agitation
– Haldol 5-10 mg IM
– Ativan 2-4 mg IM or IV
– Geodon 20 mg IM
• Think about trauma
REASSESS
. . . frequently
History
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What, when, how much, why?
Rx, OTC, herbals, supplements, vitamins
Talk to family, friends, EMS
Pill bottles, needles, beer cans, suicide note
Call pharmacy
Allergies, medical problems
Physical examination
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Vital signs: BP, HR, RR, T, O2 sat
Mouth: odors, mucous membranes
Pupils
Breath sounds
Bowel sounds
Skin
Urination/defecation
Neurologic exam
Essential Laboratory Tests
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Electrolytes
Glucose
BUN and creatinine
LFT’s, CK
Urinalysis, urine drug screen
Etoh, alcohol screen
Serum osmolality
Acetaminophen, salicylates
Specific drug levels
Pregnancy test
Anion Gap
• Na – (HCO3 + Cl)
• Normal: 8-12 mEq/L
• Causes:
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Methanol
Uremia
DKA
Paraldehyde, phenformin
Iron, isoniazid, ibuprofen
Lithium, lactic acidosis
Ethylene glycol
Strychnine, starvation, salicylates
Osmolar Gap
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Calculated osmolality – measured osmolality
2(Na) + glucose/18 + BUN/2.8
Normal = 285-290 mOsm/L
Gap > 10 mOsm/L suggests the presence of extra
solutes:
– Ethanol, methanol
– Ethylene glycol, isopropyl alcohol
– Mannitol, glycerol
• Clinical Pearl: Anion gap acidosis with an osmolar
gap should suggest methanol or ethylene glycol
poisoning
Electrocardiogram
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Prolonged QRS
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Sinus bradycardia/AV block
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TCAs
Phenothiazines
Calcium channel blockers
Beta-blockers, calcium channel
blockers
TCAs
Digoxin
organophosphates
Ventricular tachycardia
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Cocaine, amphetamines
Chloral hydrate
Theophylline
Digoxin
TCAs
Diagnosis
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May not identify ingested substance(s)
Provide ABCs and supportive care
Give antidote when appropriate
Call regional poison control center
– Carolinas Poison Center, Charlotte
– 800-848-6946
Disposition
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Case-based
ICU admission
Period of observation
Psychiatric evaluation
Toxidromes
Cholinergic Toxidrome
Diarrhea
Urination
Miosis
Bradycardia
Bronchospasm
Emesis
Lacrimation
Limp
Salivation, sweating
Salivation
Lacrimation
Urination
Defecation
GI upset
Emesis
Cholinergics
• Organophosphates
– Irreversibly bind cholinesterases
• Carbamate
– Reversibly bind cholinesterases, poor CNS penetration
• Muscarinic and nicotinic effects
• Pesticides, nerve agents
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Military personnel
Field workers, crop dusters
Truckers
Pest control, custodial workers
• Antidote
– Atropine for muscarinic effects
– Pralidoxime reverses phosphorylation of cholinesterase
Anticholinergics
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Atropine
Scopolamine
Glycopyrrolate
Benztropine
Antispasmotics
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Dicyclomine
Hyoscyamine
Oxybutynin
clidinium
• TCAs
• Mydriatics
• Antihistamines
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Chlorpheniramine
Cyproheptadine
Hydroxyzine
Diphenhydramine
Meclizine
promethazine
• Antipsychotics
– Clozapine
– Olanzapine
– Thioridazine
• Jimson weed
Anticholinergic Toxidrome
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Dry mucus membranes (Dry as a bone)
Mental status changes (Mad as a hatter)
Flushed skin (Red as a beet)
Mydriasis (Blind as a bat)
Fever (Hot as a hare)
Tachycardia
Hypertension
Decreased bowel sounds
Urinary retention
Seizures
Ataxia
Toxidromes
• Opioids
– Respiratory depression
– Miosis
– Hypoactive bowel sounds
• Sympathomimetics
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Hypertension
Tachycardia
Hyperpyrexia
Mydriasis
Anxiety, delirium
Clinical Pearl: Sweating differentiates sympathomimetic
and anticholinergic toxidromes
Antidotes
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Acetaminophen
Organophosphates
Anticholinergic
Arsenic, mercury, gold
Benzodiazepines
Beta blockers
Calcium channel block
Carboxyhemoglobin
Cyanide
Digoxin
N-acetylcysteine
Atropine, pralidoxime
physostigmine
dimercaprol
flumazenil
glucagon
calcium
100% O2
nitrite, Na thiosulfate
digoxin antibodies
Antidotes
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Ethylene glycol
Heparin
Iron
Isoniazid
Methanol
Methemoglobin
Opioids
Salicylate
TCA’s
Warfarin
fomepizole, HD
protamine
deferoxamine
pyridoxime
fomepizole, HD
methylene blue
naloxone
alkalinization, HD
sodium bicarbonate
FFP, vitamin K
Decontamination
Principles of Decontamination
• External
– Protect yourself and others
– Remove exposure
– Irrigate copiously with water or normal
saline
– Don’t forget your ABC’s
• Internal
– Patient must be fully awake or
intubated
– Most common complication is
aspiration
– Very little evidence for their use
Decontamination
• Skin
– Protect yourself and other HC
workers
– Remove clothing
– Flush with water or normal saline
– Use soap and water if oily substance
– Chemical neutralization can
potentiate injury
– Corrosive agents injure skin and can
have systemic effects
Decontamination
• Eyes
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remove contact lens
Flush copiously with water or normal saline
Use local anesthetic drops
Continue irrigation until pH is normal
Slit lamp and fluorescein exam
Decontamination
• Inhalation
– Give supplemental humidified oxygen
– Observe for airway obstruction
– Intubate as necessary
GI Decontamination
• Syrup of ipecac
– Within minutes of ingestion
– Aspiration, gastritis, Mallory-Weiss tear, drowsiness
– Rarely, if ever, given in ED
• Gastric lavage
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Does not reliably remove pills and pill fragments
Used 30-60 minutes after ingestion
Useful after caustic liquid ingestion prior to endoscopy
Not used for sustained release/enteric coated ingestions
Perforation, nosebleed, vomiting, aspiration
• Recent studies suggest that activated charcoal alone is just as
effective as gut emptying followed by charcoal.
GI Decontamination
• Activated charcoal
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Limits drug absorption in the GI tract
Within 60 minutes of ingestion
Patient must be awake or intubated
Vomiting, aspiration, bezoar formation
Contraindication: bowel obstruction or ileus
with distention
– 1 gram/kg PO or GT
Activated Charcoal
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Lithium
Iron
Alcohols
Lead
Hydrocarbons
Caustics
GI Decontamination
• Cathartics
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Hasten passage of ingestions or AC
Contraindications: obstruction or ileus
Severe fluid loss, hypernatremia, hyperosmolarity
10% magnesium citrate 3ml/kg or 70% sorbitol 1-2
…./kg
• Whole bowel irrigation
– Large ingestions, SR or EC tablets, packers (ex.
cocaine)
– Contraindications: obstruction or ileus
– Aspiration, nausea, may decrease effectiveness of
charcoal
Enhanced Elimination
• Urinary manipulation
– Forced diuresis
– Alkalinization
• Repeat-dose activated charcoal
– Very large ingestions of toxic substance
– Sustained release and enteric coated preparations
• Carbamazepine, phenobarbital, phenytoin
• Salicylate, theophylline, digitoxin
• Hemodialysis, Hemoperfusion
• Peritoneal dialysis, Hemofiltration
Enhanced Elimination
• Does the patient need it?
– Severe intoxication with a deteriorating
condition despite maximal supportive care
– Usual route of elimination is impaired
– A known lethal dose or lethal blood level
– Underlying medical conditions that can
increase complications
Specific Toxins
• Acetominophen
• Salicylates
• Tricyclic Antidepressants (TCA)
Acetominophen (apap)
Magic number to remember is 140
• Max dose:
– 4g/day adults
– 90 mg/kg day kids
• Peak serum levels: 4 hours after overdose
• What are the three methods of APAP
metabolism?
– Glucuronidation (90% normal thru pathway)
– Sulfonation
– P450 mixed oxidase enzymes (5% nl thru pathway)
Acetominophen (apap)
• Toxicity
• 140mg/kg acute ingestion
• Direct hepatocellular toxicity with
centrolobular distribution (hepatic
vein)
• Can also have renal damage and
pancreatitis
Stages of Tylenol Toxicity
• I (0-24hrs): n/v, but most asymptomatic
• II latent stage (24-48hrs): subclinical increase
in ast/alt/bili
• III hepatic stage (3-4dys): liver failure, ruq
pain, vomiting, jaundice, coagulopathy,
hypoglycemia, renal failure, metabolic
acidosis
• IV recovery stage (4dys-2wks): resolution of
hepatic dysfunction
Need 4 hour level and
N-acetylcysteine (NAC)
• Dx: 4 hour level compared to
the Rumack and Matthews
nomogram
• 150ug/ml at 4 hours
• Rx: NAC 140mg/kg then
70mg/kg every 4 hours for 17
doses
• We Have PO and IV dosing
• Only useful for one time
ingestion (not chronic
ingestions)
Acetominophen (apap)
• If time of ingestion unknown, draw level
immediately and again at 2-4 hours.
• Labs: LFTs, coags, lytes, aspirin, ETOH,
tox screen
NAC indications
• Ingestions with potential toxicity
• Late presentations with potential or
ongoing toxicity
• Chronic overdose with evidence of
hepatic damage
Tylenol Overdose Disposition
• Admit if…..
– Known toxicity / potential toxic levels
– Lab evidence of hepatic damage
– Unknown time of ingestion and sx
consistent with toxicity
– Unknown ingestion time with
measurable acetaminophen levels.
Salicylates (asa)
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Weak acid, rapidly absorbed
Enteric coated has delayed absorption
Toxic dose: 160 mg/kg
Lethal dose 480 mg/kg
Mixed respiratory alkalosis-metabolic acidosis
Stimulates respiratory drive causing hyperventilation,
but limits ATP production metabolic acidosis
• Oil of wintergreen, 1ml = 1400mg
Salicylates Symptoms
• Tachypnea, tachycardia,
hyperthermia
• Resp alkalosis-metabolic
acidosis
• Altered serum glucose
• AG metabolic acidosis
(MUDPILES)
• Dehydration (vomiting,
tachypnea, sweating)
• Abd pain/n/v
• Tinnitus, hearing loss
• lethargy, seizures,
altered mental status
• Noncardiogenic
pulmonary edema
Evaluation of ASA Overdose
• Lytes, ABG, LFTs, CBC,
preg.test, urine PH
• Serum salicylate levels
(toxicity at 25mg/dl)
• Toxicity correlates POORLY
with levels
• Evaluation with DONE
nomegram based on single
ingestion of regular ASA at
levels drawn 6 hrs after
ingestion
• Underestimates toxicity in
cases of severe acidemia or
chronic ingestion
Therapy for ASA Overdose
• ABC’s
• Activated charcoal
• Urinary alkalinization (start if serum level is greater
than 35mg/dl)
– 3 amps bicarbinate in 1 L D5W at 150 ml/hr
• By increasing urinary pH to greater than 8, ASA
gets trapped in tubes and cannot be reabsorbed
• Dialysis for severe acidemia, volume overload,
pulmonary edema, cardiac or renal failure, seizures,
coma, levels > 100mg/dl in acute ingestion, or >
60-80 mg/dl in chronic ingestion
Disposion for ASA Overdose
• Pt gets charcoal and remain asymptomatic
after 6-8 hours = Possible D/C
• Sustained release requires longer
observation period
• Pts with toxic levels, symptomatic, or
develop symptoms = Admission
TCA (Tricyclic Antidepressants)
• Leading cause of death by intentional overdose
• Blocks sodium channels
• Death by cardiovascular dysrhythymias and
cardiovascular collapse
• Most TCA’s have anticholinergic effects
– Dry skin, blurry vision, hot
• Severe OD: hypotension, seizures, respiratory
depression
• In severe cases: ARDS, rhabdomyolisis, DIC
GET AN EKG
What do you see?
Prolonged QRS, sinus tachycardia, “tall R in R” – tall R wave in lead aVR
Treatment of TCA Overdose
• Sodium Bicarbinate
– Initial bolus of 2 amps
– Drip 3 amps in 1 L D5W at 150 ml/hr
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Titrate for serum pH of 7.45-7.5
IV fluids
Lidocaine for perisistent arrhythymias
AVOID Class Ia drugs (procainimide
quinidine)
Thank You!
Any Questions?
References
• Poisoning & Drug Overdose, California Poison
Control System. KR Olson, 3rd edition,
Appleton & Lange, 1999.
• Emergency Medicine Board Review Series. L
Stead, Lippincott Williams & Wilkins, 2000.
• Emergency Medicine, A comprehensive study
guide. Tintinalli, 6th edition, McGraw Hill,
2004.