Download Toxicology

General Management of
the Poisoned Patient
Medical Student/Intern
Lecture
Emergency Medicine
Who is a poisoned patient?
• Sometimes it’s
obvious and
sometimes not
• Poisoning is on
the differential
for almost every
complaint
• Having a general
approach is useful
Case Presentation
• 15 year old female is brought in by
parents 1 hour after a witnessed
ingestion of “pain pills”
• She appears drowsy
• VS: T 98oF, HR 75, BP 120/70, RR 8, O2
Saturation 88% on room air
• Her physical exam is remarkable for
drowsiness, hypoventilation, and the
following physical finding:
Pinpoint pupils
Questions
• What toxidrome does this patient have?
• What laboratory values are useful in the
diagnosis of a poisoned patient?
• Does she need GI decontamination?
• What treatments may be beneficial at
this point?
History to Obtain
• What was the toxin involved?
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Helpful but not absolutely required
May send family/EMS back to scene
• What was the time of ingestion?
• If unknown, when was patient last
seen?
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Interpretation of levels
History
• What toxins are around the house?
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Medications for others in the house
including pets
Over the counter preparations
Cleaning supplies
Chemicals in the garage or elsewhere
Physical Findings
• Some physical findings are of
particular importance to toxicology
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Vital signs including temperature
Pupillary size
Skin – Dry or moist?
Bowel sounds – diminished?
Track marks?
Pressure sores or compartment
syndrome?
Physical Findings
• Is there a toxidrome present?
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Adrenergic or Sympathomimetic
Cholinergic
Anticholinergic
Opioid
• Many toxins fall into these broad
categories
• Treatment will be similar across any
category
Sympathomimetic
Toxidrome
• Excess of catecholamines
• “Fight or Flight” response
• Dilated pupils, tachycardia,
hypertension, agitation/seizures,
diaphoresis
• Cocaine, amphetamines, “Ecstasy” or
MDMA, Ritalin, caffeine, theophylline
are examples of sympathomimetic
agents
Cholinergic Toxidrome
• Excess of Acetylcholine
• Sedation, pinpoint pupils,
neuromuscular paralysis,
bradycardia, SLUDGE syndrome,
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Salivation, Lacrimation, Urination,
Defecation, GI motility, Emesis
• Seen in organophosphate and
carbamate insecticide poisoning
Anticholinergic Toxidrome
• Acetylcholine activity is blocked at
muscarinic receptors leading to:
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Mad as a hatter – delirium and
hallucinations
Dry as a bone – dry skin
Red as a beet – flushed skin
Blind as a bat – widely dilated pupils
Hot as Hades – low grade fever
Also significant tachycardia
• Seen with many prescription and OTC
agents including antihistamines,
phenothiazines, TCAs
Opioid Toxidrome
• Stimulation of opioid receptors
• Triad of miosis, CNS depression,
and hypoventilation
• Agents that cause this include:
heroin, morphine, hydrocodone
and oxycodone
Pinpoint pupils
• Not many agents cause this finding
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COPS mnemonic
C – Clonidine, Carbamates
O – Opioids, organophosphates
P – Phenothiazines
S – Sedative/hypnotics
Summary
Syndrome
Pupils Heart Skin
rate
GI
motility
Sympathomimetic
(cocaine)
large
small
Cholinergic
(organophosphate)
large
Anticholinergic
(diphenhydramine)
Opioid (heroin)
small
up
wet
down
down
wet
up
up
dry
down
normal normal down
Toxidromes
• If present, toxidromes may be
helpful both diagnostically and
therapeutically
• Many toxins do not produce a
classic toxidrome
What toxidrome does our
patient have?
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Pin point pupils
Respiratory depression
CNS depression
Opioid toxidrome is present
Diagnosis
• What laboratory measures might
be useful?
• Is there an antidote?
• Are extracorporeal removal
measures effective or indicated?
• Can we anticipate any
complications that may develop?
Use of the
Laboratory
Laboratory tests
• Some “laboratory toxidromes”
exist and have important
implications for diagnosis and
treatment
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Anion gap metabolic acidosis
Sympathomimetic
Sodium channel blockade
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Anion gap metabolic
acidosis
“MUDPILES”
Methanol
Notice how many of
Uremia
these are toxins
Diabetic ketoacidosis
Paraldehyde
Iron, INH
Lactic acidosis
Ethylene glycol, Ethanol ketoacidosis
Salicylates
Sympathomimetic
• Increased catecholamine surge will
typically produce
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Hypokalemia
Hyperglycemia
Metabolic acidosis, low bicarbonate
Potential rhabdomyolysis due to
extreme agitation
Sodium Channel Blockade
• Prolongation of the QRS interval seen in
many drug overdoses
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Tricyclic antidepressants
Cocaine
Propoxyphene
Diphenhydramine
• What starts out as QRS prolongation
may degenerate into malignant
ventricular dysrhythmias
Sodium Channel
Blockade
1
0
Na rushes in
2
3
4
Phase 0 corresponds to the QRS interval on ECG
Sodium Channel
Blockade
1
0
Na rushes in
2
3
Sodium channel
blockade causes
the phase 0 slope
to be delayed resulting
in prolongation of
the QRS complex
4
Sodium channel blockers tend to
give a rightward axis on ECG
S in Lead I
R in Lead aVR
S in Lead aVL
This is a “fingerprint”
pattern for sodium
channel blocker
(such as TCA) toxicity
What about urine drug
screens?
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Limited value for intentional ingestions
Rarely changes pt management
Screens for drugs of abuse
Tend to be sensitive not specific
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False (+) common
• Reliance on them may mislead you
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For example, believing an opioid ingestion
has been “ruled out” by a negative UDS
Urine drug screens
• Selective use
• Altered mental status of
unknown etiology
• Pediatric cases of
poisoning or suspected
abuse
• Seizures, MI?
Specific drug levels
• Acetaminophen level is indicated on ALL
overdose patients
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Ubiquitous toxin with significant toxicity
Asymptomatic presentation
Easily treatable with time sensitive antidote
• Specific drug levels may be indicated for
some toxins
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Iron, theophylline, aspirin, phenytoin,
digoxin for example
Use of the Laboratory
• There is no test for everything
• Get a rapid glucose on all AMS pts
• “Tox panel” includes
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Chemistry panel
ECG
APAP level
UPT in females
CPK in patients found down or agitated
Specific drug levels when the toxin has
easily measurable levels such as phenytoin
Bedside diagnostic tests
• Sometimes response to an antidote
can be a diagnostic test
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Naloxone reverses opioid intoxication
Physostigmine reverses
anticholinergic intoxication
Atropine improves cholinergic
intoxication
What labs should we get
in our patient?
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Chemistry panel
ECG
Acetaminophen level
UPT
Would a urine drug screen be
helpful? Probably not
Is there a bedside test we
can perform here?
• Naloxone administration
• In opioid intoxication will have a
dramatic and rapid response
• Small dose in opioid addicts as this
may precipitate withdrawal
• Our patient receives 1.0 mg of
naloxone IV and has a dramatic
response
Decontamination
GI Decontamination
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Ipecac
Gastric lavage
Activated charcoal
Multidose activated charcoal
Whole bowel lavage
Supportive care
Syrup of Ipecac
• Induces emesis within 20-30 minutes of
administration
• Old recommendations: Every household
should have a bottle
• New recommendations: Probably very
few indications for syrup of ipecac
• Studies have shown that SOI removes a
variable amount of ingested toxin, no
improvement in outcomes
Syrup of Ipecac
• Refractory emesis may preclude
administration of other therapies
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Activated charcoal
Oral N-acetylcysteine
• For some toxins, onset or presence
of vomiting important clinically.
Ipecac will mask these findings
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Iron, theophylline
Mushroom intoxication
Gastric Lavage
• Attractive idea
• Pills are not likely to
fit through the tube
• 40 french tube
• Not associated with
improved outcomes
• Can remove some
drug within 1 hr
• Complications
include esophageal
perforation and
aspiration
pneumonia
40 French tube
Gastric Lavage
• Consider for:
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Life threatening ingestion
Within one hour post ingestion
Toxin without an effective treatment
• Generally used less as studies
show limited benefit and nontrivial complication rate
Activated Charcoal
• Large surface area
• Adsorbs to toxins and
prevents absorption
in the GI tract
• Complications include
bowel obstruction,
vomiting with
aspiration
Activated
Charcoal
PHAILS to be effective in:
• Pesticides
• Hydrocarbons
• Alcohols
• Iron
• Lithium
• Solvents
When to use Activated
Charcoal?
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1-2 hours post ingestion
Ingestion expected to produce toxicity
Substance known to adsorb to charcoal
Benefits felt to exceed risks
1 gram/kg typical dose + sorbitol
Multidose or late charcoal for:
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Theophylline overdose
Evidence of continuing absorption late
• Aspirin or SR preparations)
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Cocaine body packers
Whole Bowel
Irrigation
• Administration of
large amounts of GoLightly via NG tube
• Flush the toxin out of
the system
• Run until clear
effluent
• No proven clinical
advantage
• Rarely used
Whole Bowel Irrigation
• May consider in rare cases where
lethal doses of toxin are in the GI
tract and continuing absorption
suspected
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Cocaine body packers
Sustained released cardiac toxins
such as calcium channel blockers
• Consider toxicology consult before
beginning this therapy
Does our patient need GI
Decontamination?
• Ipecac? No
• Lavage? Probably not
• Activated charcoal?
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Possibly
Watch CNS status to prevent
aspiration
Medical Management
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ABC’s
GI decontamination when indicated
Watch for complications
Supportive care
Antidotal therapy
Complications of overdose
Aspiration pneumonia
• Obtunded patients
cannot protect
their airway
• Toxins cause
emesis
• Good airway
management can
be preventive
Rhabdomyolysis
• Agitation leads to
muscle breakdown
• CNS depression leads
to
8 Hours
a muscle crush injury
or
Later….
compartment syndrome
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Patients “found down”
• Good hydration
• Follow CPK’s
• Clue: RBC on urine dip
but none on microscopic
Anoxia
• Anoxic brain and
organ injury due to
CNS depression,
hypotension,
hypoventilation with
hypoxia
• End organ damage
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Renal failure
Myocardial infarction
Ischemic CVA
“The big three”
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Aspiration pneumonia
Rhabdomyolysis
Anoxia
Cause most of the morbidity and
mortality from overdoses
• Particularly seen in “found down”
patients
A note on seizures…
• Toxin induced seizures may require
specific therapy
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Pyridoxine in Isoniazid overdose
• Benzodiazepines and barbiturates
are the first line agents to treat
toxin induced seizures
• Phenytoin often not effective
Labs return on the patient:
• Chemistry panel is normal
• UPT is negative
• ECG is normal sinus rhythm with
normal intervals
• Acetaminophen level is 250
mcg/ml
Now what? Is specific
antidotal therapy
indicated?
Antidotal therapy
Toxin
Acetaminophen
Arsenic
Beta blockers
Black widow spider toxin
Calcium channel blockers
Cyanide
Digoxin
Ethylene glycol, methanol
Iron
Isoniazid
Lead
Methemoglobinemia
Opioids
Organophosphates
Salicylates
Thallium
Tricyclic antidepressants
Valproic acid hepatotoxicity
Antidote
N-acetylcysteine
DMSA
Glucagon
Specific antivenin
Calcium, glucagon, Insulin/glucose
Amyl nitrite, sodium thiosulfate, sodium nitrite
Digibind (Fab fragments)
Ethanol, fomepizole
Deferoxamine
Pyridoxine
EDTA, DMSA, BAL
Methylene blue
Naloxone
Atropine, pralidoxime
Sodium bicarbonate
Prussian Blue
Sodium bicarbonate
Carnitine
Antidotal therapy
• Reverse or counteract the effects of poison
• Competitive antagonist
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Narcan for opioids
• Receptor agonist
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Calcium for calcium channel blocker
• Inhibit metabolism
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Fomepizole for ethylene glycol
• Bind/remove toxin
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Digibind for digoxin
• Reactivate enzymes
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Pralidoxime for organophosphates
• However most toxins do not have an antidote
Our patient has an elevated
acetaminophen level.
Should we treat her?
Acetaminophen
• Toxic via a metabolite
formed by p450
metabolism
• Minimum dose to cause
toxicity
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7.5 gm or 150 mg/kg in
adult
200 mg/kg in children
Acetaminophen
metabolism
O
HN
Glucuronide
40-65%
20-45%
Sulfate
(increased
in children)
OH
Acetaminophen
Glutathione
Normally
Detoxifies
NAPQI
Mercapturic
acid
(nontoxic)
P450 mixed
function oxidase
(5-15%)
Unchanged
in urine
O
N
Glutathione
O
NAPQI
Hepatic adduct
formation, cell
death
Centrilobular
necrosis
Phases of acetaminophen toxicity
• Phase I (0.5-24 hour) – nausea,
anorexia, malaise
• Phase II (24-72 hour) – “quiescent”
phase, LFT’s start to rise, RUQ pain
• Phase III (72-96 hour) – Hepatic
necrosis, jaundice, encephalopathy
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Most deaths occur here
• Phase IV (4 days–2 weeks) - recovery
Hepatotoxicity
• NAPQI binds to cell proteins and
leads to cell death
• Why centrilobular?
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This area contains the most p450 and
the least glutathione
• Liver and kidneys contain p450
• Injury is evident once glutathione
stores reach 30% of baseline
What decision rule can
help us decide whether or
not to treat a patient with
an acute acetaminophen
ingestion?
Rumack-Matthew Nomogram
• Sensitive predictor of hepatotoxicity
• Failure rate approaches zero over
the past 25 years of use
• Useful only with levels obtained
between 4 - 24 hours post ingestion
• Single acute ingestion
N-acetylcysteine
(NAC) is antidotal
Repletes glutathione
Mucomyst® for oral use
Acetadote® for IV infusion
Dosing
• Oral NAC
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140 mg/kg loading dose then 70 mg/kg q4
hours for 17 more doses
Must dilute at least 1:1 due to taste
• IV NAC
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150 mg/kg over 1 hr, 50 mg/kg over 4 hr,
then 16 mg/kg over 16 hours, continue if
needed
Call Poison Control, pharmacy, or toxicology
for dosing
Does our patient need to be
loaded with NAC?
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Initial level was 1 hour post ingestion
Need a 4 hour level to plot on nomogram
If it is toxic, start NAC
Treatment < 8 hours post ingestion
virtually eliminates hepatotoxicity
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Can wait on the 4 hour level prior to NAC
administration in early presenter
The 4 hour level is 160 µg/ml…
This falls above the treatment line
on the Rumack-Matthew nomogram
therefore antidotal therapy is indicated
200
150
Log
[Serum]
µg/ml
6.25
24
4
Time (hours)
Case Presentation
6 year old male with an accidental ingestion
of Tofranil presents to the PICU comatose,
hypotensive, with this rhythm.
Questions
• What kind of rhythm is this?
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Wide complex tachycardia
• What kind of drug is Tofranil?
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Imipramine, a tricyclic antidepressant
• What is the mechanism for the wide
complex tachycardia?
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Sodium channel blockade
• What antidote may be useful?
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Sodium bicarbonate
Treatment With Na+
Bicarbonate
One minute after 100 mEq sodium bicarbonate
Bicarbonate as an antidote
• Used for cardiac toxicity due to sodium
channel blocking agents
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Tricyclic antidepressants
Cocaine
Class I antiarrhythmics
Phenothiazines
• Indications:
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Wide QRS >100-120 ms
Dysrhythmias
Hypotension
Bicarbonate as an antidote
• Alkalinization of serum may help
with specific toxins
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Salicylates – facilitates elimination
and keeps toxin out of the tissues
Tricyclic antidepressants
Methanol intoxication
What makes a toxin
dialyzable?
• Small size
• Less protein binding
• Small volume of distribution

More in serum, less in tissues
• Charge
Dialyzable Toxins
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Salicylates
Theophylline
Lithium
Alcohols
Pediatric considerations
• Beware of the accidental ingestion in
children less than 5 years old
• Some detective work may be required
to determine the toxin involved
• Children are more susceptible to some
toxic effects such as
methemoglobinemia, hypoglycemia,
seizures, dysrhythmias
Pediatric considerations
• “One pill can kill” a child
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Calcium channel blockers
Beta blockers
Sulfonylureas
MAO inhibitors
Cyclic antidepressants
Methemoglobin inducers (pyridium,
dapsone)
Theophylline
Pediatric considerations
• High morbidity and mortality in
pediatric ingestion
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Hydrocarbons such as lamp oil
Insecticides
Methyl salicylate
• oil of wintergreen, ben-gay
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Caustic agents
• household cleaners
The Poison Center as a Resource
1-800-222-1222
962-2323
• Open 24/7
• Provides information to
the public and health
care providers

On drugs, plants,
chemicals, venoms, etc.
• RNs and Pharmacists
• Medical Back-up
• Resources
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Computer database
MEDLINE
Take Home Points
• Toxidromes are helpful if recognized
• GI decontamination may be useful
• Understand the role of laboratory
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APAP, Chem-7 and ECG on every overdose
• Supportive care and recognize
complications
• Antidotal therapy in selected cases
• Know your resources!
Any questions?