This document discusses toxicologic emergencies. It provides statistics on poisonings in the US and outlines the evaluation and management of poisoned patients. Key aspects of the history and physical exam are reviewed. Common toxidromes such as anticholinergic, opioid, and serotonin syndrome are described. Methods of decontamination, enhanced elimination, and use of antidotes are also outlined. Two case examples involving acetaminophen toxicity and carbon monoxide poisoning are then presented and discussed.

1. Toxicologic
Emergencies
Emergency Medicine Clerkship Lecture Series
Primary Authors:
Michael Levine, MD, Susan E. Farrell, MD
Reviewer: Michael Beeson, MD

2. EPIDEMIOLOGY
• In 2004, more than 2.4 million toxic
exposures reported to U.S. Poison
Control Centers
• 1183 deaths
• Over half of poisonings occur in
children under 5 years of age

3. EVALUATION OF THE
POISONED PATIENT
• History
• Physical Exam
• Vital signs
• Pupil exam
• Skin findings
• Mental status
• Search for a toxidrome

4. MANAGEMENT OF THE
POISONED PATIENT
• A-B-C-D-E’s: ACLS measures as appropriate
• IV, O2, cardiac monitoring, ECG
• Determine blood glucose in all “intoxicated”
patients. (Empiric dextrose administration is indicated for all
patients with altered mental status if bedside glucose determination
is not available)
• Thiamine and naloxone empirically as indicated
• Decontamination
• Enhanced elimination
• Antidotal therapy
• Supportive care

5. HISTORY
• Name and amount of agent(s)
• Type of agent (immediate release, sustained
release)
• Time of ingestion/exposure
• Route of ingestion/exposure
• Any co-ingestants (including prescription, OTC’s,
recreational drugs, herbals, chemicals, metals)
• Reason for ingestion/exposure (e.g. accident,
suicide attempt, therapeutic misuse,
occupational)
• Search exposure environment for pill bottles,
drug paraphernalia, suicide note, chemical
containers

6. PHYSICAL EXAM: VITAL SIGNS
• Assess and manage the A-B-Cs:
• Blood pressure
• Heart rate
• Respiratory rate
• Tachypnea: Salicylates
• Bradypnea: Opioids
• Respiratory depth
• Hyperpnea: Salicylates
• Shallow respirations: Opioids
• Temperature
• Hyperthermia: Serotonin syndrome, NMS, malignant
hyperthermia, anti-cholinergic toxidromes, salicylates
• Hypothermia: Narcotic or sedative-hypnotic agents

7. PHYSICAL EXAM: PUPILS
• Size
• Large: Anticholinergic or
sympathomimetic toxidrome
• Small: Cholinergic toxidrome
• Pinpoint: Opioid toxidrome
• Nystagmus: Check for horizontal,
vertical, or rotatory (ethanol, phenytoin,
ketamine, PCP)

8. PHYSICAL EXAM: SKIN
• Temperature:
• Hyperpyrexia: Anticholinergic or
sympathomimetic toxidromes,
salicylates
• Moisture:
• Dry: Anticholinergic toxidrome
• Moist: Cholinergic, sympathomimetic
• Color: Cyanosis, pallor, erythema

9. PHYSICAL EXAM: OVERALL EXAM
• Physiologic stimulation: Everything is “up”:
• Elevated temperature, HR, BP, RR, agitated
mental status
• Sympathomimetics, anticholinergics, central
hallucinogens, some drug withdrawal states
• Physiologic depression: Everything is “down”:
• Depressed temperature, HR, BP, RR,
lethargy/coma
• Sympatholytics, cholinergics, opioids,
sedative-hypnotics
• Mixed effects: Polysubstance overdose,
metabolic poisons (hypoglycemic agents,
salicylates, toxic alcohols)

10. TOXIDROMES
• Anticholinergic
• Cholinergic
• Opioid
• Sympathomimetic
• Serotonin syndrome
• Sympatholytic
• Sedative-hypnotic

11. TOXIDROMES:
ANTICHOLINERGIC
• VS: Hyperthermia, tachycardia, elevated BP
• CNS: Agitation, delirium, psychomotor activity,
hallucinations, mumbling speech, unresponsive
• Pupils: Mydriasis (minimally reactive to light)
• Skin: Dry, warm, and flushed
• GI/GU: Diminished BS, ileus, urinary retention
• Examples: Atropine, antihistamines, CADs,
cyclobenzaprine, phenothiazines, Datura spp.
• Remember: “Dry as a bone, Red as a beet,
Blind as a bat, Mad as a hatter, and hotter
than hell”

12. TOXIDROMES:
CHOLINERGIC
• VS: Bradycardia, high or low BP, tachypnea or
bradypnea
• CNS: Agitation, confusion, seizures, coma
• Pupils: Miosis, eye pain, lacrimation
• Skin: Diaphoresis
• GI/GU: Salivation, vomiting, diarrhea, incontinence
• Musculoskeletal: muscle fasciculations, weakness,
paralysis
• Examples: Organophosphate and carbamate
insecticides, nerve agents, cholinesterase inhibitors
(physostigmine, edrophonium), nicotine
• Remember: “SLUDGE” Salivation, Lacrimation,
Urinary incontinence, diarrhea, Gastrointestinal emesis

13. TOXIDROMES:
OPIOID
• VS: Hypothermia, bradycardia, normal or low
BP, bradypnea
• CNS: Lethargy, coma
• Pupils: Miosis (exceptions: meperidine, DXM)
• Skin: Cool, pale or moist, evidence of recent or
remote needle injection possible
• Misc: Hyporeflexia, pulmonary edema, seizures
(meperidine and propoxyphene), ventricular
dysrhythmias (propoxyphene)
• Examples: Morphine and the synthetic opioids;
(Note: clonidine can look like an opioid)

14. TOXIDROMES:
SEDATIVE-HYPNOTIC
• VS: Hypothermia, normal or bradycardic HR,
hypotension, bradypnea
• CNS: Drowsiness, dysarthria, ataxia, lethargy,
coma
• Pupils: Midsize or miosis, nystagmus
• Misc: Hyporeflexia; (possible breath odors)
• Examples: Alcohols, benzodiazepines,
barbiturates, zolpidem, chloral hydrate,
ethchlorvynol

15. TOXIDROMES:
SEROTONIN SYNDROME
• VS: Hyperthermia, tachycardia, hypertension,
tachypnea
• CNS: Confusion, agitation, lethargy, coma
• Pupils: Mydriasis
• Skin: Diaphoretic, flushed
• Neuromuscular: Hyperreflexia, tremor, clonus,
rigidity
• Examples: Combinations that increase 5-HT
stimulation (MAOIs, SSRIs, NSRIs, meperidine,
L-tryptophan, dextromethorphan, trazadone,
linezolid)

16. TOXIDROMES:
SYMPATHOLYTICS
• VS: Bradycardia, hypotension, bradypnea,
hypopnea
• CNS: Normal, lethargy, coma, seizures
• Pupils: Mid size to miotic
• Examples: Alpha1-adrenergic antagonists,
beta-adrenergic antagonists, alpha2-adrenergic
agonists, calcium channel blockers

17. TOXIDROMES:
SYMPATHOMIMETICS
• VS: Hyperthermia, tachycardia, hypertension,
tachypnea, hyperpnea
• CNS: Enhanced alertness, agitation, delirium,
seizures, coma
• Pupils: Mydriasis
• Skin: Diaphoretic, hot
• Neuromuscular: Hyperreflexia
• Examples: Cocaine, phencyclidine,
phenylethylamines (amphetamines)

18. SEIZURE-INDUCING DRUGS
OTIS CAMPBELL
• O – Organophosphates
• T – TCAs
• I – Insulin, Isoniazid (INH)
• S – Sympathomimetics, salicylates, sulfonylureas
• C – Cocaine, camphor, carbamazepine, carbamates, CO
• A – Amphetamines, amantadine
• M – Methylxanthines, meperidine, mushrooms (Gyromitra
species)
• P – Phenothiazines, propoxyphene, phencyclidine
• B – Benzodiazepine/sedative-hypnotic withdrawal
• E – Ethanol withdrawal
• L – Lidocaine, lead
• L – Lithium, Lindane® (hexachlorocyclohexane)

19. DECONTAMINATION
• Activated charcoal: 1g/kg
• The primary means of GI decontamination, IF it is warranted.
• Some agents for which AC has reduced adsorptive capacity:
metals (lead, iron), lithium, pesticides, hydrocarbons, alcohols,
caustics, solvents
• Contraindications: bowel obstruction/perforation, unprotected
airway, caustics and most hydrocarbons
• Whole bowel irrigation: PEG sol 1 – 2 l/h (adults); 500ml/h (ped)
• Indications: toxic foreign bodies (e.g. body packers), sustained
release products, lithium and metals
• Contraindications: as for charcoal
• Gastric lavage:
• Indications: patients with life threatening ingestions (especially if
no adequate antidote available) presenting within 1 hour of
ingestion
• Contraindications: corrosive ingestions, hydrocarbons
• Syrup of ipecac: not recommended

20. ENHANCED ELIMINATION
• Methods to increase the clearance of a substance from
the body:
• Multiple dose activated charcoal: phenobarbital,
theophylline, carbamazepine, dapsone, quinine
• Urinary alkalinization: salicylates
• Hemodialysis:
• Substance characteristics: water-soluble, low
molecular weight (<500 D), low protein binding,
small volume of distribution (< 1L/kg), low
endogenous clearance
• Charcoal hemoperfusion: similar to HD; in addition,
substance adsorbed to AC

21. ANTIDOTES
TOXIN ANTIDOTE
Acetaminophen N-Acetylcysteine
Anticholinergic agents Physostigmine
Benzodiazepines Flumazenil
Beta blockers or calcium IV fluids, calcium, glucagon, insulin (HIE)
channel blockers
Carbon monoxide O2
Cardiac glycosides Digoxin-specific Fab fragments
Cocaine (or other Benzodiazepines
sympathomimetics)
Cyanide Amyl nitrate, sodium nitrate, sodium
thiosulfate, hydroxycobalamin
Ethylene glycol 4-Methylpyrazole, ethanol

22. ANTIDOTES
TOXIN ANTIDOTE
Heparin Protamine sulfate
Hydrofluoric acid Calcium gluconate
Iron Desferoxamine
Isoniazid Pyridoxine
Lead DMSA or BAL/CaNa2-EDTA
Mercury BAL
Methanol 4-Methylpyrazole, ethanol
Opioids Naloxone
Organophosphates/ Atropine + pralidoxime
carbamates
Sulfonylureas Glucose + octreotide
(or meglitinides)
Tricyclic antidepressants Sodium bicarbonate, benzodiazepines

23. TOXICOLOGY CASE 1
• A 23 year old female presents via EMS after
ingesting 100 tablets of acetaminophen (APAP)
immediate release preparation, 500mg tablets
• The ingestion occurred 24 hours ago
• She has had several episodes of non-bloody,
non-biliary emesis
• Serum acetaminophen level drawn on arrival:
40mg/dL

24. TOXICOLOGY CASE 1(cont’d)
• Vital signs: T 98.5˚F, HR: 110 bpm, RR 20,
BP 110/68, SaO2: 97% on RA
• Labs include:
• PT/INR/PTT: 14.2s/1.4; PTT: 80s
• BUN/Creat: 47mg/dL/1.8mg/dL
• Serum glucose: 80mg/dL
• AST: 5,423 IU/L ALT: 6,087 IU/L

25. APAP TOXICITY
• Four stages to toxicity:
• I: 0-24 hours: Asymptomatic, or mild anorexia,
nausea, vomiting, malaise
• II: 24-48 hours: Transaminase levels start to rise at
12 hours; Abdominal pain, RUQ tenderness, vomiting,
oliguria
• III: 72-96 hours: Transaminases peak at 72 hours;
PT rises, multi-system organ failure or recovery
• IV: 4d-2 weeks: Resolution of hepatotoxicity
• Toxicity results from accumulation of a toxic metabolite:
N-acetyl-para-benzoquinoneimine (NAPQI) relative to
endogenous glutathione
• Toxic single ingestion is 150 mg/kg

26. APAP TOXICITY
• At therapeutic doses:
• 90% of APAP is conjugated and renally
excreted
• 2-4% is metabolized via P450 enzymes to
NAPQI
• NAPQI is quickly conjugated to glutathione to
a non-toxic metabolite
• In an overdose, glutathione stores are depleted,
NAPQI accumulates leading to hepatotoxicity

27. RUMACK-MATTHEW
NOMOGRAM

28. N-Acetylcysteine
• PO dosing: 140 mg/kg load, followed by
70mg/kg q4h x17 doses
• IV dosing: 150 mg/kg load over 15 min,
followed by 50mg/kg over 4 hours,
followed by 100 mg/kg over 16 hours
• Prolonging the initial loading period for IV
NAC may reduce the incidence of
anaphylactoid reactions

29. APAP TRANSPLANT
GUIDELINES
• King’s College guidelines
• pH < 7.3 after fluid resuscitation
or
• PT > 100
• Creatinine > 3.4
• Grade III or IV encephalopathy
• Lactate > 3.5mmol/L

30. TOXICOLOGY CASE 2
• A 20 year old male presents via EMS after his
neighbor found him unresponsive. The patient is
comatose
• The neighbor developed a headache and
nausea after spending 10 minutes in the
patient’s house
• It is winter, and the patient had been using a
camp stove for heat

31. TOXICOLOGY CASE 2 (cont’d)
• VS: T: 98.9˚F, HR: 110 bpm, RR: 6,
BP: 150/100 mmHg, SaO2: 99%.
• Moans to painful stimuli with no focal neurologic
deficits
• Pupils 4mm, sluggishly reactive
• Skin notable for central cyanosis
• Blood glucose: 90mg/dL
• ECG: Sinus tachycardia, normal intervals,no
evidence of acute ischemia
• Labs include: COHb: 60%

32. CO TOXICITY
• 17,115 cases of CO exposure reported to US
Poison Control Centers in 2004
• CO is a colorless, odorless, non-irritating gas
• Sources of CO exposure include:
• Smoke
• Car exhaust
• Propane powered vehicles or engines
• Hibachi grills and kerosene heaters
• Methylene chloride

33. CO TOXICITY
• CO combines with Hgb to form
carboxyhemoglobin (COHb)
• COHb has 240 X the affinity for O2
• CO + Hgb  shifts the O2 dissociation curve to
the left: oxygen delivery to tissues is reduced
• CO can cause hypotension via CO-induced
cGMP production and increased NO production
• CO can inhibit electron transport which limits
ATP production
• CO is associated with microvascular damage
and inflammation in the CNS

34. CLINICAL EFFECTS OF CO
COHb% Signs/Symptoms
<5% None or mild HA
10% Slight HA, dyspnea on vigorous exertion
20% Throbbing headache, dyspnea with
moderate exertion
30% Severe HA, irritability, fatigue, dim vision
40-50% Tachycardia, confusion, lethargy, syncope
50-70% Coma, seizures, death
> 70% Rapidly fatal

35. CO TOXICITY
• CO poisoning is frequently misdiagnosed: symptoms are
nonspecific
• Need a high index of suspicion
• Consider CO poisoning:
• Multiple patients with similar complaints, especially
from the same household
• Vague, flu like symptoms without fever or
lymphadenopathy
• Winter, environmental history and exposures
• Uncommon presentation of syncope
• Normal COHb levels
• 0-5% in non-smokers
• up to 10% in smokers > 1ppd

36. PULSE OXIMETRY
• Noninvasive measure of functional
hemoglobin oxygen saturation
• Does not measure hemoglobin
species that cannot carry oxygen
• MetHb
• COHb
• Co-oximeter measures fractional
hemoglobin oxygen saturation

37. PULSE OXIMETRY GAP
Severe CO poisoning
• Significant dyshemoglobinemia results in a
divergence between functional and
fractional hemoglobin oxygen saturation
• In patients with markedly elevated COHb
levels, pulse oximetry can overestimate
O2Hb%
• In severe CO poisoning, the pulse
oximetry gap approaches the COHb level

38. CO TREATMENT
• Oxygen!!
• The half life of COHb decreases with
inspired O2 concentration:
• t1/2 at room air: 4-6 hours
• t1/2 at “100%” O2 via NRB at 1 ATM: 90 min
• t1/2 at 100% O2 via ETT at 1 ATM: 60 min
• t1/2 at 100% O2 at 3 ATM (HBO): 23 minutes

39. HYPERBARIC OXYGEN
• The rationale behind HBO therapy for CO:
• Decrease the incidence of delayed neurologic
sequelae
• Should be started within 6 hours
• HBO indications are controversial, but generally
include:
• COHgb > 25-40%
• Altered Mental Status or history of same (syncope)
• Arrhythmias
• Symptoms of cardiac ischemia
• COHgb > 15% if pregnant

40. TOXICOLOGY CASE 3
• A 22 year old male brought via EMS after being
found “drunk.” He was found near an empty
bottle of window-washer fluid
• The patient had threatened suicide earlier in the
day

41. TOXICOLOGY CASE 3 (cont’d)
• Labs include:
• Serum glucose: 124 mg/dL
• Sodium: 130 mEq/L; K: 3.7 mEq/L; Cl: 88
mEq/L; Bicarbonate: 12 mEq/L; BUN: 22
mg/dL; Creatinine 1.5 mg/dL
• Anion gap of 30
• Serum ethanol: non-detectable
• Serum APAP/ASA: non-detectable
• Serum osmolality: 324 mOsm/kg

42. TOXIC ALCOHOLS
• Most commonly: methanol, isopropanol,
and ethylene glycol (EG)
• Should be suspected based on:
• history, physical exam, lab
abnormalities
• The degree of intoxication correlates with
the number of carbons in the alcohol:
• Methanol < ethanol or ethylene glycol
< isopropanol

43. TOXIC ALCOHOL LABS
• All toxic alcohols cause an osmolar gap
• Methanol and EG cause an increased anion gap
acidosis
• Isopropanol causes ketosis without acidosis
• Osmolar gaps can be present early after
ingestion, but will be absent after the alcohol is
metabolized
• Anion gap acidosis can be absent early after
ingestion, but will develops after methanol or EG
metabolism

44. “GAPS”
Anion gap
Gap’s
Osmolar gap
Time

45. METHANOL
• Methanol (CH3OH):
• window-washer fluid, anti-icing agents,
solvents, varnish/paint removers, some
anti-freezes
• Methanol intoxication:
• “Snow storm” blindness (edema of the
optic disk/nerve)
• Abdominal pain, nausea, vomiting
• Lethargy, coma

46. METHANOL METABOLISM
Methanol
Alcohol dehydrogenase*
Formaldehyde
Aldehyde dehydrogenase
Formic acid
Folate
CO2 + H2O
* Inhibited by 4-methylpyrazole or ethanol

47. ISOPROPANOL
• Isopropanol (CH3-CHOH-CH3):
• The most intoxicating alcohol
• Osmolar gap, followed by ketosis
• Metabolized to acetone by alcohol
dehydrogenase

48. ETHYLENE GLYCOL
• Ethylene glycol C(OH2) – C(OH2) sources:
• Antifreeze, brake fluid, anti-icing solutions, solvents
• If fluorescein has been added to an EG-
containing antifreeze, the patient’s urine may
fluoresce under Wood’s lamp
• Metabolized to:
• Glycolic acid: anion gap acidosis
• Oxalic acid, combines with calcium, causing calcium
oxylate crystal deposition and hypocalcemia
• Calcium oxylate deposition in the renal tubules
causes acute renal failure

49. ETHYLENE GLYCOL
METABOLISM
Ethylene glycol
Alcohol dehydrogenase*
Glycoaldehyde
Aldehyde dehydrogenase
Glycolic acid
Lactate dehydrogenase
Glyoxylic acid
Pyridoxine, Mg Thiamine
Glycine + α-OH-β-
Benzoic acid Oxalic acid ketoadipic acid
*Inhibited by 4-methylpyrazole or ethanol
Pyridoxine, Mg, and thiamine are co-factors for their respective reactions

50. TREATMENT
• Methanol or EG: 4-methyl-pyrazole (4-MP,
fomepizole)
• 4-MP inhibits alcohol dehydrogenase activity
• Ethanol also competes for active sites on alcohol
dehydrogenase and inhibits methanol and EG
metabolism
• Potential adverse effects of ethanol infusion:
• Intoxication, hypotension, pancreatitis, gastritis,
hypoglycemia, or phlebitis
• Hemodialysis clears the toxic alcohol and
corrects acid/base abnormalities

51. TREATMENT (cont’d)
• EG: Other cofactors to enhance nontoxic
metabolism:
• thiamine, pyridoxine, magnesium
• Methanol: Other cofactors to enhance
nontoxic metabolism:
• folic acid (or folinic acid)
• Treatment of Isopropanol ingestion:
• Supportive care
• H2 blockers or proton-pump inhibitors
• Ensure that no other toxic alcohol is present

52. TOXICOLOGY CASE 4
• A 3 year old male is brought by his parents 1
hour after he is found with one of his
grandmother’s sustained – release verapamil
tablets in his mouth
• A pill count shows 1 additional tablet might be
missing
•
The child is asymptomatic

53. TOXICOLOGY CASE 4 (cont’d)
• Vital signs: T: 98.6˚F, HR: 80 bpm, RR: 22,
BP:100/60, SaO2: 99%
• Initial labs:
• Na: 140 mEq/L; K: 3.7 mEq/L; Cl: 113 mEq/L;
Bicarbonate: 22 mEq/L; BUN: 12 mg/dL; Creatinine
0.8 mg/dL. Serum glucose: 120mg/dL
• ECG: normal sinus rhythm, normal intervals.
• Two hours later: the patient is less arousable
• Vital signs: HR: 50 bpm, RR: 18, BP: 70/40
SaO2: 99%
• ECG: junctional bradycardia, normal QRS and QTc
intervals
• Serum glucose: 190 mg/dL

54. CALCIUM CHANNEL BLOCKER
(CCB)
• Classes of CCB approved in the US:
• Phenylalkylamines: Verapamil
• Verapamil: Effects cardiac myocytes and electrical
conduction system ( decreased contractility, AV nodal
conduction delay and block)
• Benzothiazepines: Diltiazem
• Benzothiazepines: Effects cardiac myocytes, electrical
conduction system, and peripheral vascular smooth muscle
cells
• Dihydropyridines: Nifedipine, amlodipine, nicardipine
• Dihydropyridines: Effects peripheral vascular smooth muscle
cells ( peripheral vasodilation, decreased peripheral
vascular resistance)
• In overdose, the selectivity of the CCB classes may be
lost

55. CCB TOXICITY
• CCBs:
• Block L-type calcium channels
• Inhibit intracellular calcium influx
• In overdose:
• Verapamil or diltiazem: Bradycardia and hypotension
• Dihydropyridines: Hypotension and tachycardia
• Insulin release from pancreatic β-cells depends on L-
type calcium channels; hyperglycemia can occur after
CCB overdose
• The degree of hyperglycemia may correlate with the
severity of the overdose

56. CCBs versus BETA BLOCKERS
• β1 antagonism:
• Decreased cardiac contractility
• Reduced AV nodal conduction
• β2 antagonism:
• Increased smooth muscle tone…bronchospasm
• Labetolol:
• 7:1 β:α antagonist activity
• Βeta adrenergic antagonists:
• Inhibit gluconeogenesis and glycogenolysis
• Hypoglycemia can occur in overdose
• Seizures can occur in overdose (propranolol)

57. CCB and BETA BLOCKER
TREATMENT
• Ensure ABCs
• Improve heart rate and blood pressure:
• Atropine: Often fails to improve HR
• Calcium: Used in both CCB and Beta blocker toxicity;
Improves HR and contractility
• Glucagon: Improves myocardial contractility
• Direct α agonist agents: Increase peripheral vascular
resistance
• (Epinephrine has both β1 and α1 agonist effects)

58. CCB/BETA BLOCKER TX
• Therapies unique to CCB or β blocker involve:
• IV fluids – Offsets hypotension induced by peripheral
vasodilation
• Calcium – Calcium competitively overcomes blockade
of the voltage-sensitive calcium channels
• Glucagon: Acts on adenylate cyclase independently
of the β receptor to convert ATP into cAMP
• Epinephrine: Binds to β receptors to convert
adenylate cyclase into cAMP
• Insulin: Promotes increased uptake and utilization of
carbohydrates by cardiac myocytes (primarily used
only for CCB toxicity

59. Hyperinsulinemic Euglycemia (HIE)
• Normally: Cardiac myocytes preferentially
metabolize glucose; in shock states, metabolism
is dependent on free fatty acids
• Hyperinsulinemic euglycemic (HIE) therapy:
shifts myocardial metabolism from FFA to
carbohydrates
• HIE:
• Insulin (0.5-1 unit/kg bolus, followed by 0.5-1
unit/kg/hr)
• Dextrose (1 amp D50, or continuous D10 infusion)
• Watch for hypokalemia and hypophosphatemia
• HIE therapy: Associated with rapid, dramatic
improvement in cardiovascular hemodynamics

60. CARDIAC GLYCOSIDES
• Digoxin: A cardiac glycoside used for the
treatment of CHF and atrial fibrillation
• Mechanism of action:
• Inhibits Na/K/ATPase, leading to:
• Increased intracellular sodium/calcium exchange
• Increased intracellular calcium
• Increased extracellular potassium
• Digoxin
• Increases excitability and automaticity of cardiac
myocytes
• Decreases conduction velocity at the AV node

61. CARDIAC GLYCOSIDE TOXICITY
• Cardiac glycosides:
• Foxglove, oleander, lily of the valley, red squill
• Secretions of Bufo toads (e.g. Colorado river toad)
• Symptoms of toxicity:
• Nausea and vomiting
• Weakness, lethargy, confusion
• Visual disturbances
• Acute toxicity:
• Serum potassium is elevated, predictive of mortality.
• Chronic toxicity:
• Precipitated by hypokalemia, hypomagnesemia, renal failure
• Digoxin toxicity can occur with therapeutic digoxin levels

62. CARDIAC GLYCOSIDE TOXICITY:
THE ECG
• Nearly every dysrhythmia has been associated
with digoxin toxicity
• PVCs are the most common ECG abnormality
• Bidirectional ventricular tachycardia and
accelerated junctional rhythms with nodal block
are relatively specific for cardiac glycoside
toxicity, but are less common

63. CARDIAC GLYCOSIDE TOXICITY:
TREATMENT
• Digoxin-specific Fab fragments indications:
• Hyperkalemia (K > 5.0)
• Life-threatening arrhythmias
• Phenytoin or lidocaine:
• May suppress ventricular dysrhythmias if
digoxin-specific Fab is unavailable
• Correct hypokalemia, hypomagnesemia
• Calcium therapy for hyperkalemia should be
avoided with concomitant digoxin toxicity

64. TOXICOLOGY CASE 5
• A 42 year old woman presents via EMS after
she was found unresponsive at home
• Vital signs: T 99.8˚ F, HR: 121 bpm, RR: 14; BP:
97/52; SaO2: 93% on RA
• PE: Disheveled, minimally responsive female;
pupils: 8 mm, minimally reactive; dry lips and
mucous membranes; tachycardia, absent bowel
sounds; skin warm and flushed

65. TOXICOLOGY CASE 5 (cont’d)
• The patient is placed on a cardiac monitor and
IV access is obtained
• Shortly after an ECG is performed, the patient
has a brief, generalized tonic-clonic seizure

66. TCA ingestion
Note the tachycardia, QRS prolongation, tall R wave in aVR, and the rightward
deflection of the terminal 40 msec of aVR.

67. TRICYCLIC ANTIDEPRESSANT
TOXICITY
• TCA toxicity:
• Sodium channel blockade: conduction delay
• Alpha1 adrenergic blockade: hypotension
• Cholinergic (muscarinic) blockade: mydriasis, dry
mucous membranes, tachycardia, ileus, urinary
retention
• Histamine blockade
• Treatment:
• Sodium bicarbonate
• Direct alpha1 adrenergic agents as pressors
• Benzodiazepines as seizure prophylaxis/treatment
• NaHCO3 is indicated for any QRS > 100 ms

68. TRICYCLIC ANTIDEPRESSANT
TOXICITY
• The risk of ventricular dysrhythmias and
seizures correlates with QRS prolongation
• ECG findings suggestive of TCA toxicity
include:
Tachycardia
Prolonged PR, QRS intervals
Tall R wave in aVR
Rightward deflection of terminal 40 msec in aVR
• NaHCO3 is indicated for any QRS > 100 ms

69. In Summary
Approach all patients in a systematic
fashion
Toxic exposures most often only require
supportive care
Be aware of toxic exposures that require
specific antidotes
Most toxic exposures are unintentional
Consider contacting a regional poison
control center for all but the most straight
forward cases