Call Girls Kochi Just Call 9907093804 Top Class Call Girl Service Available
Toxicology Emergencies CDEM
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
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”
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
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
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
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
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
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
