Toxicology

UNC Emergency Medicine

Medical Student Lecture Series
 Objectives
• General approach to the poisoned
patient
• Toxidromes
• Specific antidotes
• Decontamination and enhanced
elimination
 General Approach
• 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
– 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
• 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
• 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
• 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
• What, when, how much, why?
• Rx, OTC, herbals, supplements, vitamins
• Talk to family, friends, EMS
• Pill bottles, needles, beer cans, suicide not
• Call pharmacy
• Allergies, medical problems
 Physical examination
• 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
• 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:
– Methanol
– Uremia
– DKA
– Paraldehyde, phenformin
– Iron, isoniazid, ibuprofen
– Lithium, lactic acidosis
– Ethylene glycol
– Strychnine, starvation, salicylates
 Osmolar Gap
• 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
• Prolonged QRS
– TCAs
– Phenothiazines
– Calcium channel blockers
• Sinus bradycardia/AV block
– Beta-blockers, calcium channel
blockers
– TCAs
– Digoxin
– organophosphates
• Ventricular tachycardia
– Cocaine, amphetamines
– Chloral hydrate
– Theophylline
– Digoxin
– TCAs
 Diagnosis
• 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
• Case-based
• ICU admission
• Period of observation
• Psychiatric evaluation
Toxidromes
 Cholinergic Toxidrome
Diarrhea Salivation
Urination Lacrimation
Miosis Urination
Bradycardia Defecation
Bronchospasm GI upset
Emesis Emesis
Lacrimation
Limp
Salivation, sweating
 Cholinergics
• Organophosphates
– Irreversibly bind cholinesterases
• Carbamate
– Reversibly bind cholinesterases, poor CNS penetration
• Muscarinic and nicotinic effects
• Pesticides, nerve agents
– Military personnel
– Field workers, crop dusters
– Truckers
– Pest control, custodial workers
• Antidote
– Atropine for muscarinic effects
– Pralidoxime reverses phosphorylation of cholinesterase
 Anticholinergics
• Atropine • Antihistamines
• Scopolamine – Chlorpheniramine
• Glycopyrrolate – Cyproheptadine
• Benztropine – Hydroxyzine
– Diphenhydramine
• Antispasmotics
– Meclizine
– Dicyclomine
– promethazine
– Hyoscyamine
– Oxybutynin
• Antipsychotics
– – Clozapine
clidinium
– Olanzapine
• TCAs
– Thioridazine
• Mydriatics
• Jimson weed
 Anticholinergic Toxidrome
• 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
– Hypertension
– Tachycardia
– Hyperpyrexia
– Mydriasis
– Anxiety, delirium

Clinical Pearl: Sweating differentiates sympathomimetic

and anticholinergic toxidromes
 Antidotes
• Acetaminophen N-acetylcysteine
• Organophosphates Atropine, pralidoxime
• Anticholinergic physostigmine
• Arsenic, mercury, gold dimercaprol
• Benzodiazepines flumazenil
• Beta blockers glucagon
• Calcium channel block calcium
• Carboxyhemoglobin 100% O2
• Cyanide nitrite, Na thiosulfate
• Digoxin digoxin antibodies
 Antidotes
• Ethylene glycol fomepizole, HD
• Heparin protamine
• Iron deferoxamine
• Isoniazid pyridoxime
• Methanol fomepizole, HD
• Methemoglobin methylene blue
• Opioids naloxone
• Salicylate alkalinization, HD
• TCA’s sodium bicarbonate
• Warfarin 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
– 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
– 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
– 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
• Not good for:
– Lithium
– Iron
– Alcohols
– Lead
– Hydrocarbons
– Caustics
 GI Decontamination
• Cathartics
– 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)
• 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, • Abd pain/n/v
hyperthermia • Tinnitus, hearing loss
• Resp alkalosis-metabolic • lethargy, seizures,
acidosis altered mental status
• Altered serum glucose • Noncardiogenic
• AG metabolic acidosis pulmonary edema
(MUDPILES)
• Dehydration (vomiting,
tachypnea, sweating)
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
• 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.