Toxicology

Objectives
General approach to the poisoned
patient
Toxidromes
Specific antidotes
Decontamination and enhanced
elimination
 General Approach
ABCs
History
Physical examination
Labs, imaging
Diagnosis, antidotes
Disposition
ABCs
 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
PRBCs 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
LFTs, 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
Hydroxyzine
Benztropine
Diphenhydramine
Antispasmotics Meclizine
Dicyclomine promethazine
Hyoscyamine
Antipsychotics
Oxybutynin
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
TCAs sodium bicarbonate
Warfarin FFP, vitamin K
Decontamination
 Principles of Decontamination
External
Protect yourself and others
Remove exposure
Irrigate copiously with water or normal
saline
Dont forget your ABCs
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
ABCs
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 TCAs 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.