1. UNC Emergency Medicine Medical Student Lecture Series
Toxicology
UNC Emergency Medicine
Medical Student Lecture Series

3. Objectives General approach to the poisoned patient Toxidromes
Specific antidotes
Decontamination and enhanced elimination

4. General Approach ABC’s History Physical examination Labs, imaging
Diagnosis, antidotes
Disposition

5. ABC’s

6. 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
Patient awake – A’s done, don’t need to do anything
Gag – use a tongue blade
Oropharynx – for FB
Airway devices – oral airway, but if you are considering this, the patient should probably be intubated
Intubation – if the depressed respiratory status is due to opioids or benzodiazepines, these may eliminate the need for intubation

7. 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
Respirations – are they breathing 14 times a minutes or 4
Bag/mask – to support inadequate respirations, as you prepare for intubation
Stridor – Gama hydroxybutyric acid is sometimes made with lye, can cause airway burns and edema

8. 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
Fluids – decrease challenge with h/o heart failure/renal failure/hepatic failure
With tachycardia: do not give BB alone, you can worsen HTN if it is caused by alpha adrenergic stimulation as with cocaine
IV access: 2 large bore IVs

9. 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
Foley catheter – monitor UOP, obtain urine drug screen
Rectal temperature – oral temp can be inaccurate, especially in mouth breathers
warm or cool as indicated. Remember you can use paralysis for hyperthermia
Hypoglycemia – get a bedside finger stick or treat empirically
Thiamine – if they look malnourished, alcoholic. It’s not routinely given to children. Give before sugar to prevent wernicke korsakoff syndrome

10. Supportive Care Treat Seizures Control agitation Think about trauma
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
Treat seizures – don’t mistake ridigity for seizures

11. REASSESS frequently

12. History 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
What did they take,
when did they take it, important for treatment and disposition
how much, was it a toxic ingestion
why, was it a suicide attempt
Do they have allergies, comorbidities – check old chart

13. Physical examination Vital signs: BP, HR, RR, T, O2 sat
Mouth: odors, mucous membranes
Pupils
Breath sounds
Bowel sounds
Skin
Urination/defecation
Neurologic exam
Mouth – caustic ingestions, Lye is sometimes used to make GBH
Skin – warm, dry, red, sweaty, bruises, track marks, rashes
Neurologic – are they moving their extremities, look for any focal paralysis, look globally
for muscle rigidity, check their reflexes including their response to pain if altered

14. 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
Electrolyes: hyponatremia – lithium intox from DI, amitriptyline
hypokalemia – theophylline, B2 agonist, acidosis
Gives you clues to the ingested substance and helps you prevent dangerous complications
Look for an anion gap
Glucose - BB, caffeine, theophylline -- can cause hyoglycemia
propranol, insulin, salcylates – can cause hyperglycemia
BUN/creatinine to evaluate renal function
Tylenol, ethylene glycol, heavy metals (PCP, amphet, cocaine through rhabdo)
LFTs – tylenol, arsenic, ethanol, iron, valproic acid
CK – rhabdo, rigidity, arrhythmias - PCP, cocaine, amphetamines
Urinalysis – hemoglobinuria, myoglobinuria, crystalluria
Urine drug screen – beware of cross reactivity, ie. Diphenhydramine, methadone, dextromethorphan can make PCP screen +
Osmolality to calculate osmolar gap. Increased by ethanol, isopropyl alcohol, methanol, mannitol, magnesium

15. 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

16. Osmolar Gap Calculated osmolality – measured osmolality
2(Na) + glucose/18 + BUN/2.8
Normal = 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

17. Electrocardiogram Prolonged QRS Sinus bradycardia/AV block
TCAs
Phenothiazines
Calcium channel blockers
Sinus bradycardia/AV block
Beta-blockers, calcium channel blockers
Digoxin
organophosphates
Ventricular tachycardia
Cocaine, amphetamines
Chloral hydrate
Theophylline

18. 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

19. Disposition Case-based ICU admission Period of observation
Psychiatric evaluation
Case based depending on type of ingestion, amount, time, symptoms
ICU admission for any symptomatic patient or asymptomatic with significant ingestion who may later become symptomatic

20. Toxidromes

21. Cholinergic Toxidrome
Diarrhea Salivation
Urination Lacrimation
Miosis Urination
Bradycardia Defecation
Bronchospasm GI upset
Emesis Emesis
Lacrimation
Limp
Salivation, sweating
Limp – paralysis, fasiculations, hyporeflexia

22. Cholinergics Organophosphates Carbamate
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
Irreversibly bind cholinesterases – acetylcholine supply increases and you exhaust the postsynaptic neuronal transmission in the CNS and PNS
Muscarinic – parasympathetic effects
Nicotinic – gives you muscular effects
OP – physostigmine, neostigmine
Carb – antihelmintic, insecticides

23. Anticholinergics Atropine Scopolamine Glycopyrrolate Benztropine
Antispasmotics
Dicyclomine
Hyoscyamine
Oxybutynin
clidinium
TCAs
Mydriatics
Antihistamines
Chlorpheniramine
Cyproheptadine
Hydroxyzine
Diphenhydramine
Meclizine
promethazine
Antipsychotics
Clozapine
Olanzapine
Thioridazine
Jimson weed

24. 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
Amanita muscaria mushroom

25. Toxidromes Clinical Pearl: Sweating differentiates sympathomimetic
Opioids
Respiratory depression
Miosis
Hypoactive bowel sounds
Sympathomimetics
Hypertension
Tachycardia
Hyperpyrexia
Mydriasis
Anxiety, delirium
Clinical Pearl: Sweating differentiates sympathomimetic
and anticholinergic toxidromes

26. 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
Physostigmine – for CNS effects. Side effects: seizures, vomiting, diarrhea, abdominal cramping
indications: tachydysrhythmias with hemodynamic compromise, intractable seizures or
severe agitation or psychosis.
Contraindications: conduction disturbances, prolonged QRS, PR

27. 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

28. Decontamination

29. 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
External – skin, eyes, inhalation
Internal – GI decontamination methods

30. 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
Systemic effects – formaldehyde can can acidosis and formate poisoning,
hydrofluoric acid can cause hypocalcemia and hyperkalemia

31. 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
Get ophthomalogy invovled early, especially if this is a site threatening exposure

32. Decontamination Inhalation Give supplemental humidified oxygen
Observe for airway obstruction
Intubate as necessary

33. GI Decontamination Syrup of ipecac Gastric lavage
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 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.
SR/EC ingestions – whole bowel irrigation is preferred method

34. 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 charchoal – again, no real good evidence to use it, but we do
for a number of reasons: relatively harmless
theoretical benefit
feel like we’re doing something
and, it is the standard of care

35. Activated Charcoal Not good for: Lithium Iron Alcohols Lead
Hydrocarbons
Caustics

36. GI Decontamination Cathartics Whole bowel irrigation
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
Cathartics –
hasten passage ….. But no evidence that they decrease morbidity or mortality and they can cause
significant fluid loss and lyte imbalances.
Large ingestions, especially if not adsorbed to charcoal

37. 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
Forced diuresis can cause fluid overload
Alkalinization as in salicylate poisoning
Hemoperfusion – similar equipment and access, blood pumped through a column containing an adsorbant material like charcoal
less dependent on molecular size, solubility, and protein binding, achieves greater clearance rates for most drugs
Peritoneal dialysis and hemofiltration – less invasive than above, used for a continuous removal over time in a non-critical patient.
Role in acute poisonings is unclear.

38. 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
It the patient stable, will supportive care alone enable recovery, is there an antidote?
Indications include:
Usual route – lithium overdose in a patient with renal failure

39. Specific Toxins Acetominophen Salicylates
Tricyclic Antidepressants (TCA)

40. Acetominophen (apap) Max dose:
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)

41. Acetominophen (apap) Toxicity 140mg/kg acute ingestion
Direct hepatocellular toxicity with centrolobular distribution (hepatic vein)
Can also have renal damage and pancreatitis

42. 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

43. 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)

44. Acetominophen (apap)
If time of ingestion unknown, draw level immediately and again at 2-4 hours.
Labs: LFTs, coags, lytes, aspirin, ETOH, tox screen

45. NAC indications Ingestions with potential toxicity
Late presentations with potential or ongoing toxicity
Chronic overdose with evidence of hepatic damage

46. 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.

47. Salicylates (asa) Oil of wintergreen, 1ml = 1400mg
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

48. 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

49. 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

50. 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 > mg/dl in chronic ingestion

51. 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

52. 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

53. GET AN EKG What do you see?
Prolonged QRS, sinus tachycardia, “tall R in R” – tall R wave in lead aVR

54. 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
IV fluids
Lidocaine for perisistent arrhythymias
AVOID Class Ia drugs (procainimide quinidine)

55. Thank You!
Any Questions?

56. 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.