Toxidromes

Bill D. Hampton, D.O.

Emergency Physician
Holy Family Memorial
15 September 2012

Lecture Outline

Definitions
Basic Principles
Toxicology ABCDEs
Key History & Physical Findings
Toxidromes
Cases / Specific Agents
Antidotes
Quiz / Summary

Definitions / Terminology

Overdose
Exposure
Ingestion
Poisoning

Definitions / Terminology
Overdose - The intentional or unintentional
giving or taking by mouth of a medication in
toxic doses.
Ingestion - The intentional or unintentional
giving or taking by mouth of a medication in
doses that are not toxic.

Definitions / Terminology
Exposure - coming in contact with a toxic
substance other than ingestion (inhalation,
skin, or ocular contact).
Poisoning - The ingestion of or exposure to a
non-medical substance that produces
toxicity.

Basic Principles of Toxicology

Reduce exposure
Reduce absorption

...Prevention
.....Charcoal

Increase elimination

..WBI

Know when to intervene

.Antidotes

Supportive care

ABCDEs

Specific Therapy &

Antidotes...

1-800-222-1222

ABCDEs of Toxicology
A Airway
B Breathing
C Circulation
D Decontamination / DONT
E Exposure / Enhanced Elimination
If you dont follow these rules all the
time, every time, it is just a matter of
time until you permanently injure or kill a
patient.

Airway

A - Airway
What is so important about the
airway in poisoned patients?
Aspiration is a dreaded consequence of overdose.
Mortality increases from 0.4% to 8.5% with
aspiration.
Charcoal aspiration, although rare, can be
catastrophic.
Poisoned patients will rapidly lose their airway;
expect them to crash.

Breathing

B - Breathing
Ventilatory failure is
the most common
cause of death in the
poisoned patient.

Not convinced?

Nearly 15,000 people die every year of overdoses involving

prescription painkillers.
Policy Impact: Prescription Painkiller Overdoses, National Center for Injury Prevention and Control Division of Unintentional Injury
Prevention, Centers for Disease Control and Prevention, November 2011.

Circulation

C - Circulation
Not just pulse & blood pressure:
cardiac conduction and toxicity.
1) Hypotension & Bradycardia
2) Hypertension & Tachycardia
3) QRS widening
4) QT prolongation

Think,
cardiac
conduction.

Decontamination
D.O.N.T.

D Decontamination & DONT

D.O.N.T.:
D - Dextrose
O - Oxygen
N - Narcan
T - Thiamine

5-year-old boy in status epilepticus

911 call for with 5-year-old male with a
complaint of seizure.
You are unable to get IV access in field.
Has been seizing for 10 minutes with no
prior history of seizure.
Only recent illness is a cold.
Nice way to begin a Saturday morning
shift

5-year-old boy in status epilepticus

Allgs, Meds, PMHx, SocHx all .
No obvious signs of trauma.
Mom hysterical and smells of etOH.
Now what??

Diastat?
Rectal temp?
IM Ativan?
IO access?
Intubate?

5-year-old boy in status epilepticus

Accucheck = 23.
D25 given and seizure immediately stops.
Patient drank etOH left out from parents party
the night before hypoglycemia.
Parents counseled about pediatric accidental
toxciologic ingestion & patient DCd home after
short ED observation.

DONT Dextrose

The only fuel the brain can use is glucose.

If you dont have enough glucose to feed
your brain, you (and your friends) will notice
the difference.
Glucosethere simply is no substitute.

DONT Oxygen
According to Dr. Hampton,
the only contraindication
to giving oxygen to any
patient with altered mental
status is?

DONT Narcan

Naloxone (Narcan) should

be administered to any
patient with intact ABCs
and altered mental status.
Give enough so that s/he
breathes spontaneously,
but not so much that the
patient becomes a PITA.

DONT Thiamine
Give 100 mg IV push (very safe)
Give to all alcoholics, cachetic, or
malnourished patients
Give immediately in emergencies
Goal is to prevent Wernickes
Encephalopathy and Korsakoffs
Psychosis

D - Decontamination
What else do you need to know?
1) Syrup of Ipecac
2) Gastric lavage
3) Activated charcoal
4) Whole bowel irrigation

D - Decontamination
Syrup of Ipecac
What does this mean??

POLICY STATEMENT

After reviewing the evidence,

Poison Treatment in the Home the AAP believes that ipecac
PEDIATRICS Vol. 112 No. 5
should no longer be used
November 2003, pp. 1182-1185
routinely as a home treatment
strategy, that existing ipecac in
the home should be disposed of
safelyThe first action for a
caregiver of a child who may have
ingested a toxic substance is to
consult with the local poison
control center.

D - Decontamination
Syrup of Ipecac

Multiple studies have shown limited efficacy even with
immediately induced emesis.

NOT recommended as inpatient or outpatient
decontamination procedure.

Furthermore, delays other potentially life-saving
interventions (charcoal)
Position paper: Ipecac syrup.
J Toxicol Clin Toxicol - 01-JAN-2004; 42(2): 133-43
From NIH/NLM MEDLINE
There is no evidence from clinical studies that
ipecac improves the outcome of poisoned patients
and its routine administration in the emergency
department should be abandoned.

D - Decontamination
Syrup of Ipecac

So what is Syrup of
Ipecac useful for?

D - Decontamination

Lois: whoever
Now
but
Chris:
Peter:
Stewie:
Brian:
Who
Alright,
that
Good.
Well,
Get
Okay.
I
Peter.
Im
Oh,
DadIm
Okay,
Hows
Alright,
Cool,
You
Oh
Lois!
Nothing
Ooh,
Oh!
No,
I
think
dont
is,
starting
my
wants
the
boy!
know,
Ino
cool.
uh,
Lois,
Oh,
Im--
here
feel
everybody
one
you
Okay.
goes
Peter,
Good
God!
alright.
phone!
wanna!
please!
That
that
yet.
scared.
chowder?
God!
fine.
Idown.
guys,
Lois,
to
we
dont
the
so
My
Ifeel
is
Imeans
need
go.
think
Call
longest
far.
some
IWhy
get
insides
No
Iguess
doing?
dont
know
funny.
Igot
know
9-1--
in
you
more,
its
didnt
Ieight
tasty
here!!
wanna!
win!
ifwithout
all
Im
are
to
you
somebody
gone.
no
hold
crates
anybody
stuff.
gonna--
on
I guys
get
more!
fire!
I--
puking
my
to
Thats
of
had
ears.
eat--
who
tell
Ipecac
gets
any
from
wont
you?!
of
the
the,
be
that
from
last
having
uh,
pie
Mort,
piece
bake
already
any--
all
sale
of on
piethat
my
in the
tab.
Lois--
fridge.

D - Decontamination
Gastric Lavage

Basics:

NOT the same as an NGT--involves a large-bore OGT

Performed in left-lateral decubitus position with a
protected airway and a cooperative patient.

D - Decontamination
Gastric Lavage
And now that you know how to do
it properly

Dont.

Who volunteers for this?

At 5 minutes90% recovery
At 10 minutes.45% recovery
At 19 minutes30% recovery
Vale JA, Position Statement: Gastric Lavage, J Toxicol Clin Toxicol - 2004; Vol. 42, No. 7: 933-943.

D - Decontamination
Activated Charcoal
Mechanism of Action:
Binds to (adsorbs) toxic substance to prevent
absorption from gut.
Indications:
Routinely used in toxic ingestions, greatest
efficacy when given within 60 minutes postingestion.
Non-adsorbables: (Charcoal PHAILS)
P - Pesticides, K+

I - Iron

H - Hydrocarbons
A - Acids, alkali, alcohols

L - Lithium
S - Solvents

D - Decontamination
Activated Charcoal
Contraindications:

Unprotected airway

Absent or hypoactive bowel sounds
Administration:

1st dose only should be given with
sorbitol

10:1 ratio of charcoal to toxin minimum
25-50gm dose in adult (e.g.: 10gm
overdose = 100gm charcoal dose)

D - Decontamination
Whole Bowel Irrigation
Potential Uses:

Sustained-release CCB overdose

Sustained-release -blocker overdose

Body stuffers & packers

Iron overdose

Large lead paint chip ingestion

Exposure

23-y/o female with cardiac arrest

911 call for 23-y/o unresponsive female.
Initial EMS assessment shows hypoventilation
cardiac arrest on scene.
Intubated and CPR initiated.
Allgs: Unknown
Meds: Unknown
PMHx: Unknown
SocHx: Unknown
What do you want to do next?

23-y/o female with cardiac arrest

ED Course: Intubation & ventilation continued.
ACLS protocols followed and pulse & BP
restored. GCS remains at 3.
Ultimate cause of arrest identified following
admission to the ICU. What was it?
A. Battles sign
B. Rectal temp 106.4F
C. CSF positive for Neisseria meningitidis
D. CT brain shows central pontine myelinolysis
E. Four 100mcg Fentanyl patches found on the
patients back

E - Exposure
Strip them and flip them.

Altered mental status in

the young adult
occult trauma
or toxicology

History
Physical

Toxicology Management
Resuscitation & Work-up

A -Airway
B - Breathing
C - Circulation
D - Decontamination /
DONT
E - Exposure /
Enhanced Elimination

Tox-focused Hx
Vitals / Physical Exam
Toxidromes
Diagnostic tests

Toxicologic History
Often incomplete or unreliable.
Remember the 5Ws and 2Hs:
What was ingested?
Why intentional or accidental?
When was the ingestion?
Where did the ingestion take place?
Who ingested the drug?
How route of administration
How much obtain all pill bottles at scene

Medical History
Past Medical History- previous drug
overdoses, complicating medical
problems (liver or renal dysfunction)
Past Surgical History
Social History
Family History
Medications
Allergies

Toxicologic Physical Exam

Key Physical Findings:
Mental Status
Vital Signs (including patient weight)
Pupil Size / Nystagmus
Skin / Sweating / Needle Tracks
Does the patient fit into a toxidrome?

Toxidromes
Portmanteau word
a combination of two (or more) words or morphemes
into one new word. A portmanteau word typically
combines both sounds and meanings.
Toxic - of, pertaining
to, affected with, or
caused by a toxin or
poison.

Syndrome - a group of
symptoms that together are
characteristic of a specific
disorder, disease, or the like.

Toxidromes
Anticholinergic
Cholinergic
Sedative-Hypnotic
Stimulant
Opioid
Opioid withdrawal

11-year-old male with AMS

11-year-old male brought by Mom for acting
weird.
Pt. is tachycardic and looks warm and flushed.
He appears to be hallucinating.
No PMHx, allergies, or Rx meds. Mom
adamantly denies drug/etOH use.
Hes really responsiblehe takes his own
allergy medicine whenever he needs it.
Now what?

11-year-old male with AMS

Vitals: 100.2F, 132, 20, and 116/78.
Physical exam: pupils dilated and poorly
reactive to light.
Patient is clearly agitated and appears to be
hallucinating.
Which toxidrome is this?

Anticholinergic
Hot as a hare, red as a beet, dry as a bone,
blind as a bat, and mad as a hatter.
fever

decreased bowel sounds

agitation

ileus

tachycardia

seizures

flushed, dry skin

blurred vision

hallucinations

mydriasis

urinary retention

myoclonus

dry mucous membranes

choreoathetosis

psychosis

coma

Anticholinergic Toxidrome
diphenhydramine (Benadryl)
Hot as a hare, Red as a beet, Dry as a
bone, Blind as a bat, Mad as a hatter.
Examples: antihistamines, antidiarrheals, atropine, Jimson
weed, some mushrooms, TCAs, etc.
Sx: tachycardia, dryness, ileus, urinary retention, dilated
pupils, fever.
Tx: treat agitation with benzodiazepines.
Avoid: phenothiazines (e.g. Haldol)

62-y/o male with sudden onset

SOB, vomiting, and diarrhea.
Patient brought by EMS for vomiting, diarrhea, and
apparent SOB.
Hes puking and crapping all over our rig, Doc. We really
dont have much of a history. Neighbor called it in.
They live out in the country.
VS: bradycardic (HR 50). Wheezing respirations (RR
32). BP 180/78. SaO2 91%. Afebrile.
PE: Pupils are pinpoint. Pt. appears to be
simultaneously drooling & crying and is incontinent of
urine & stool. He vomits several times. He is holding
his abdomen and appears to be in pain. He is
wheezing.
Now what?

62-y/o male with sudden onset

SOB, vomiting, and diarrhea.
EMTs report they are developing similar
symptoms (less severe) en route.
You wisely set up a decontamination zone in the
ambulance bay.
Wife arrives several minutes later. Denies any
PMHx, meds, or allergies.
He was spraying in the garden earlier to stop the
bugs from eating everythingI think he spilled
it on himself.
Which toxidrome is this?

Cholinergic
Cholinergic (muscarinic):
S.L.U.D.G.E. M.D. and the Killer Bs
Salivation

Miosis

Lacrimation

Diaphoresis

Urination
Defecation (diarrhea)

Bradycardia

GI distress (crampy
abdominal pain)

Bronchoconstriction

Emesis

Bronchorrhea

Organophosphate Exposure
Organophosphates inactivate acetylcholinesterase
(AChE) precipitating a cholinergic crisis.

PNS & Muscarinic receptors

Inactivated AChE
ACh
increased parasympathetic
tone and cholinergic crisis
(SLUDGE MD BBB)

Organophosphate
Exposure
Sources: Organophosphates and carbamates are widely
used as pesticides.
MOA: They inhibit the enzyme acetylcholinesterase,
decreasing the breakdown of acetylcholine at
cholinergic synapses.
Organophosphates vs. Carbamates: Whereas the
organophosphates may cause permanent inhibition of
the enzyme, carbamates have a transient & reversible
effect. Many of these agents are well absorbed
through intact skin.

Organophosphate
Exposure
Treatment:
Remove all contaminated clothing and wash all exposed
areas with soap and water.
Atropine and pralidoxime (2-PAM)
Atropine is not an antidote, but can reverse excessive
muscarininc stimulation alleviating bradycardia,
abdominal cramps, bronchospasm, and hypersalivation.
Pralidoxime (2-PAM) restores acetylcholinesterase
Why 2-PAM? In those who go untreated, the
organophosphates binding to acetylcholinesterase may
become irreversible (the so-called aging effect). Because
carbamates have a transient effect, pralidoxime therapy is
not needed.

17-y/o unresponsive female

911 call for a 17-year-old female found
unresponsive at home.
Pt. is comatose with poor respiratory effort,
withdraws to pain.
Pt. administered Narcan (naloxone) en route
with no effect. Accu = 108.
Patient has a history of depression, anxiety,
and insomnia.
Which toxidrome is this?

Sedative-Hypnotic
BZDs, Rx sleep aids (Ambien,
Lunesta), barbiturates, ethanol,
Etomidate, propofol, etc.
sedation

delirium

slurred speech

dysesthesias

shallow respirations

diplopia

confusion

coma

ataxia

paresthesias

blurred vision

nystagmus

Sedative-Hypnotic
Examples: Klonopin, Versed,
Valium, Ativan, Xanax, etc.
Sx: respiratory depression, ataxia,
hypotension, hypothermia, coma.
Tx: supportive care.
Romazicon (flumazenil) may cause
intractable seizures; only appropriate for
reversal in procedural sedation with NO
history of chronic BZD use.

24-y/o out of control male

24-year-old male via police for out of control
behavior after traffic stop.
Pt. is handcuffed but still fighting vigorously
with 2 escorting officers.
Appears red-faced, sweaty, and is cursing
and spitting. Only vitals are HR = 140s and
RR = 32.
Patient is from out of town and has never
been seen in the ED before.
Now what?

24-y/o out of control male

Police state patient is staying at local hotel;
they were called for noise c/os.
Pt. appears to be hallucinating, is talking nonstop, and is tremulous and agitated.
Allgs:
Meds:
PMHx:
SocHx: none of your business!
Which toxidrome is this?

Stimulant
Sympathomimetics, cocaine,
crystal meth, Sudafed, TCAs,
MAOIs, diet pills, etc.
tachycardia

diaphoresis

restlessness

insomnia

tremor

seizures

hypertension

hallucinations

excessive speech

excessive motor activity

Stimulant
Treatment: Benzodiazepines, benzodiazepines,
and then some more BZDs.
Titrate dose: to vital signs and mental status.
Disposition: Dependent on response to
treatment, stimulant, and chronicity of abuse.

Stimulant
Bath Salts
Synthetic designer compounds
3,4-methylenedioxypyrovalerone
(MDPV) or mephedrone
Not used for bathing; are intended for substance abuse.
Potent inhibitors of the dopamine and norepinephrine transporters, 9fold and 13-fold more potent than cocaine.
Signs and symptoms: agitation, tachycardia, hallucinations, psychosis,
and aggressive behavior.
Severe hyperthermia (T > 106F) has been reported.
Management: rapidly gain control of agitation with benzodiazepines,
secure the airway, and administer appropriate IV fluids.
Borek HA, Holstege CP. Hyperthermia and Multiorgan Failure After Abuse of "Bath Salts" Containing 3,4-Methylenedioxypyrovalerone Ann
Emerg Med 2012 Mar 2.
Centers for Disease Control and Prevention . Emergency department visits after use of a drug sold as "bath salts" - Michigan, November 13:
2010 - March 31; 2011; MMWR Morb Mortal Wkly Rep. 2011;60:624-627.

2-y/o unresponsive male

2-year-old male arrives via EMS with
unresponsiveness.
Pt. was at home with grandma when noticed
to have responsiveness.
On arrival has respiratory effort, cool skin,
pulse, and BP = 78/40.
Pulse Ox = 99% on 100% NRB.
Accucheck = 88.

2-y/o unresponsive male

Grandma arrives and denies trauma.
Patient was acting normally < 1 hour ago,
then noted to have unsteady gait and
mental status. Called 911.
ABC okfor now. No response to D25 and
oxygen.
Pupils pinpoint.
Which toxidrome is this?

Opioid
Heroin, morphine, codeine,
hydrocodone, oxycodone,
fentanyl, meperidine, etc.
miosis

depressed mental status

bradycardia

slow respiratory rate

unresponsiveness

decreased bowel sounds

hypothermia

Opioids
Treatment: Narcan (naloxone)
Adult dose 0.4 2mg IVP
Peds dose 0.1mg/kg IVP
Duration of action ~60 to 90 minutes
Beware premature disposition in a longacting opioid overdose!

46-y/o female with nausea/vomiting

Presents ambulatory to ED c/o two-day hx of N/V
and crampy abdominal pain.
Patient appears sweaty & ill.
Allgs: Toradol, ibuprofen.
Meds: Oxycontin IR, Kadian, Duragesic patch,
hydrocodone, and Flexeril.
PMHx: Fibromyalgia, chronic LBP.
SocHx: PPD, occas. etOH, denies illicits.
Vitals: Afebrile, HR 116, RR 18, BP 108/72, 98%
Now what?

46-y/o female with nausea/vomiting

Pt. admits to being discharged from the Pain
Clinic.
Denies any illicit drug use.
Physical exam notable for hyperactive bowel
sounds, and cold sweaty skin.
Which toxidrome is this?

Opioid withdrawal
Opioid withdrawal:
The Eight Ps

pupils dilated

pain (crampy abdominal)

peristalsis

pooping

puking

piloerection

perspiration

pissed off

Toxidromes

Bonus
Toxidrome!

19-y/o with altered mental status

19-year-old female arrives via private auto for
confusion and erratic behavior.
Pt. is unable to give any meaningful history.
She is confused, flushed, sweaty, and has tremors
and muscle hypertonicity.
Patient is well known to your ED for multiple previous
psych visits for self-mutilation and polypharmacy.
Now what?

19-y/o with altered mental status

Vital signs: HR = 144, RR = 28, BP = 167/98.
Axillary temp = 102.6F.
Parents state that she had been doing well.
Patient saw her psychiatrist last week, who
increased her anti-depressant by half a tablet.
Her only other recent healthcare encounter was
to have her wisdom teeth removed. But
parents told the oral surgeon about her
previous drug use, and the patient was
prescribed a non-narcotic pain reliever.

19-y/o with altered mental status

Allgs: NKDA
Meds: sertraline (Zoloft), valproic acid (Depakote),
tramadol (Ultram), ondansetron (Zofran), and
OTC cough syrup (for insomnia).
PMHx: Depression, Bipolar, Insomnia
PSHx: Recent wisdom tooth extraction
SocHx: +1/2 ppd, denies etOH, h/o polypharmacy
PE: Pupils are 5mm bilaterally, heart tachy, lungs
CTA, Abdomen benign, Pulses +3/4 x 4, GCS =
13. Tremulous, sweaty, and ill appearing.
Jerky movements noted.
Which toxidrome is this?

Serotonin
Syndrome
A predictable, dosedependant consequence
of excess serotonin
Can be seen in infants, children, adults, and elderly
Usually combination of meds, but can occur on 1st dose
Usually some combination of triad: AMS, autonomic
hyperactivity, and neuromuscular abnormalities
Tx: BZDs, aggressive supportive care (IVF), and removal of
the offending agent(s); cyproheptadine is also recommended
Boyer, Edward W., MD, Shannon, Michael, MD, The Serotonin Syndrome, New England Journal of Medicine, 17 March 2005:
1112-1120.
Zand, Ladan MD; Hoffman, Scott J., MD; et. a., 74-Year-Old Woman With New-Onset Myoclonus, Mayo Clinic Proceedings,
October 2010:955-958.

Serotonin Syndrome

Boyer, Edward W., MD, Shannon, Michael, MD, The Serotonin Syndrome, New England Journal of Medicine,
17 March 2005: 1112-1120.

Distinguishing Toxidromes
The Toxicology Handshake
Hot & Wet?
Hot & Dry?
Hot & Shaky?
Sympathomimetic = hot, sweaty, agitated
Anticholinergic = hot, dry, agitated / hallucinating
Serotonin Syndrome = hot, wet, neuromuscular sx

Toxicology

Two teenage girls trying to get high

Police request medical evaluation as part of
domestic dispute 911 call.
Two teenage girls (15 & 16 y/o) with history
of unknown ingestion.
Both claim it was her idea.
Ingestion occurred about 4 hours ago.
Normal vital signs.
No past medical history.

Two teenage girls trying to get high

Police cannot find any prescription drugs in
either home.
Girls are requesting medical release in order
to not be late for school.
Now what??

Two teenage girls trying to get high

CBC, CMP, EKG, UA, HCG, KUB, UDS,
etOH are all negative.
Aspirin and acetaminophen levels ordered.
Serum acetaminophen > 140 in both.

Acetaminophen (Tylenol)
Cytochrome P-450 metabolism requires
glutathione.
Saturation of glucuronidation & sulfonation
pathways rapid depletion of glutathione.
Accumulation of toxic metabolite (Nap-Q) direct
hepatocellular toxicity.
Toxic ingestion 140mg/kg (7-10 gm in adults).
4-hour level > 140 is potentially toxic.

N-acetylcysteine (Mucomyst)

NAC has glutathionelike substrate which

binds to toxic
intermediates.
Dose is 140mg/kg load
then 70mg/kg for 17
doses.
Safe in pregnancy.
Rumack-Matthew Nomogram

Pop Quiz Question #1

How do you change the timing/dosage of
activated charcoal when administering Nacetylcysteine (Mucomyst)?
A. Charcoal must be given 30 min. before Mucomyst.
The
dose
of
charcoal
is
based
on
the
B. Charcoal must be given 30 min. after Mucomyst.
acetaminophen
dose
of charcoal, regardless(10:1
of whenratio).
it is
C. amount
Double the of
administered.
D. Mucomyst must NOT be used if giving charcoal; use IV
It doesnt
matter
when
it is given with regard
preparation
(Acetadote)
instead.
E. Charcoal is unnecessary
if giving Mucomyst or Acetadote.
to N-acetylcysteine.
Spiller HA, Krenzelok EP, Grande GA, et al. A prospective evaluation of the effect of activated charcoal before oral N-acetylcysteine in acetaminophen
overdose. Ann Emerg Med. 1994 Mar; 23(3): 519-23.
Montoya-Cabrera MA, Escalante-Galindo P, Nava-Jurez A, et al. [Evaluation of the efficacy of N-acetylcysteine administered alone or in combination with
activated charcoal in the treatment of acetaminophen overdoses (Spanish)]. Gac Med Mex.1999 May-Jun; 135(3): 239-43.
Buckley NA, Whyte IM, O'Connell DL, et al. Activated charcoal reduces the need for N-acetylcysteine treatment after acetaminophen (paracetamol) overdose.
J Toxicol Clin Toxicol. 1999; 37(6): 753-7.
Spiller HA, Sawyer TS. Impact of activated charcoal after acute acetaminophen overdoses treated with N-acetylcysteine. J Emerg Med. 2007 Aug; 33(2): 1412.

N-acetylcysteine (Acetadote)
150mg/kg IV x 1 dose over 1 hour.
50mg/kg IV x 1 dose over 4 hours.
100mg/kg IV x 1 dose over 16 hours.
Severe, anaphylactoid reactions have
been reported.
IV formulation has NOT been shown
more effective than the oral
preparation.

Pop Quiz Question #2

What is the most commonly reported adverse effect
of intravenous acetylcysteine, when administered as
an antidote for acetaminophen poisoning?

The most commonly reported adverse effects of

A. Hypotension
IV acetylcysteine are anaphylactoid reactions
B. Vomiting
(rash, pruritus, angioedema, bronchospasm, and
C. Prolonged QT interval
hypotension)
which occur in about 8% of patients
D. Dizziness
within 2 hours
after the initial infusion.
E. Anaphylactoid
reaction
New England Journal of Medicine, Volume 359(3): pg. 285.

Cases

78-y/o found in garage with AMS

911 call by neighbor for male patient found lying
on garage floor with sonorous respirations.
Pt. is comatose on arrival, but old records are
available.
Allgs: NKDA
Meds: multiple
PMHx: HTN, CADz, chol, DJDz
PSHx: CABG
SocHx: Recently widowed. x 3.

78-y/o found in garage with AMS

Vitals: HR 66, RR 8, BP 186/92, SaO2 86%
Accu = 208
No response to naloxone.
Pupils are mid-range and poorly reactive.
Begins to seize shortly after arrival in ED.
Labs: Na+ 153, K + 5.4, Cl- 108, HCO3- 5, BUN
5.9, Cr 17, Glucose 196.
Serum osmolarity 487 mOsm.
Now what??

Toxic Alcohols: Methanol

In paint thinner, windshield washer, wood alcohol, gas
tank additives.
Creates an anion gap metabolic acidosis.

Methanol

Formaldehyde

alcohol
dehydrogenase

Formic acid

formaldehyde
dehydrogenase

Symptoms (often delayed): seizures, respiratory failure, N/V,

profound acidosis, pancreatitis, blindness.
Treatment: Antizole (fomepizole, 4-MP) or ethanol drip, then
hemodialysis.

Toxic Alcohols: Methanol

Diagnosis: Profound acidosis, blindness, retinal
edema, pancreatitis
Methanol is non-toxic--its breakdown products
are not
Windshield washer fluid makes it easier to see
thru glass, but if you drink it, you can go blind.
If co-ingested with etOH: acidosis & symptoms will be
delayed until BAL falls below 100 mg/dL

Toxic Alcohols:
Ethylene Glycol
In antifreeze, paint, solvents
Sweet taste, no odor.
Creates an anion gap metabolic acidosis.

E. Glycol

Glycoaldehyde

alcohol
dehydrogenase

Glycolic acid
Oxalic acid

Symptoms: CNS depression, intoxication without etOH odor,

anion gap acidosis, anuria, d osmol gap.
Treatment: Antizole (fomepizole, 4-MP) or ethanol drip,
supplemental pyrodixime & thiamine, hemodialysis.

Toxic Alcohols:
Ethylene Glycol
Causes renal failure from oxalate crystals in
kidney.
Antifreeze keeps your radiator flowing, but if
you drink it, it will plug up your kidneys.
If co-ingested with etOH: acidosis & symptoms will be
delayed until BAL falls below 100 mg/dL

Toxic Alcohols:
Isopropyl Alcohol

Rubbing alcohol
CNS depression greater than ethanol
Metabolized to acetone. Pulmonary excretion.
Sx: hemorrhagic gastritis, pulmonary edema
Ketosis without acidosis (normal anion gap)
Tx: supportive care measures; hemodialysis

Toxic Alcohols:
Isopropyl Alcohol

Usually benign
Ketosis without acidosis
May also see hypotension
Twice as drunktwice as sicktwice as long.

Cases

3-year-old male in shock

911 call for critically ill 3-year-old male.
Pt. is hypotensive & bradycardic with capillary
refill and responsiveness.
PMHx, allergies, meds unknown. Pt. is staying with
Grandpa while parents are on vacation.
Grandpa mentions that he spilled my pill box the
other day.
Grandpas Meds: Baby ASA,
metoprolol, and Verapamil.
Now what??

C - Circulation
Hypotension & Bradycardia
-Blockers & CCBs
-Blockers
Decrease intracellular cAMP
whose phosphorylation effects
normally facilitate Ca++ entry
into the cell

Calcium Channel
Blockers
Directly impair Ca++
entry into myocardial
cells

Common toxicity mechanism is

available intracellular Ca++

C - Circulation
Hypotension & Bradycardia
-Blockers & CCBs

C - Circulation

C - Circulation
Hypotension & Bradycardia
-Blockers & CCBs
High Dose Insulin Euglycemic Therapy (HDIET):
During drug-induced shock, metabolic demands shift
Preferred myocardial energy substrate shifts from free fatty acids to
carbohydrates
Supplemental insulin supports carbohydrate metabolism
Improved function following insulin treatment occurs without an
increase in myocardial work
Dose: 0.5 1.0 Units / kg / hour of regular insulin; and supplement
glucose as necessary; frequent accuchecks (expect 30-60 min.
before effects seen)

In the toxicology workup, how useful is

the Urine Drug Screen?

contact
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to
but
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But
and
The
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then
Nice
When
it
For
ended
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more
the
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the
wood
crack
now
came
web,
given
winter
a
THC,
until
mate
spiders
hammock,
the
up
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the
scientists
cocaine
didnt
spider
Mr.
their
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a
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came,
spider
got
Crack
the
minute
behind
active
behavior
caffeine
effects
build
took
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gave
spider
restraining
where
cant
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most
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web.
the
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itof
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lay
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popped
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Service,
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all
structure
the
in
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day
spider
creatures
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had
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all
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over
go.
100 young.

Cases

Good Samaritan from local fire with

severe smoke inhalation.
Local man collapses while attempting to
rescue animals from burning pet shop.
Patient complained of SOB, weakness,
dizziness, nausea.
He initially seemed confused then collapsed,
was noted to be bradycardic & hypertensive.

Good Samaritan from local fire with

severe smoke inhalation.
Vitals: HR 115, RR 32, BP 86/45, Pulse
oximetry is 99% on RA.
PE: No signs of thermal burns, patient is
clearly obtunded, no obvious trauma.
Your EMS student thinks pt. has stinky
breath, but no one else can smell anything.
Now what??

 Industrial sources (plastics, solvents, chemical

synthesis, etc.)
 Consider in every smoke-inhalation patient you see;
cyanide can be produced from wood & silk when it burns,
as well as household plastics and plastics used in the
construction of new buildings
 Iatrogenic sources (sodium nitroprusside)
 Consider in every unexplained lactic acidosis patient
 Consider in any chemist / jeweler presenting to ER

Toxins that Interfere with Mitochondria:

o Consider the following toxins when confronted with an
unexplained lactic acidosis

Clinical Presentation:

1) Cyanide

Altered Mental Status

2) Hydrogen sulfide

Profound lactic acidosis

Patient Population:
Chemists
Jewelers (electroplating industry)

Hydroxocobalamin

Vitamin B12 is cyanocobalamin.

Hydroxocobalamin is pre-vitamin B12.
Hydroxocobalamin irreversibly binds cyanide
cyanocobalamin.
Cyanokit was approved by the FDA in 2007 as an antidote
for cyanide poisoning. Cost is $650 per dose.
The starting dose for adults is 5 g (i.e., both 2.5 g vials),
administered by IV infusion over 15 minutes.
Depending on the severity of the poisoning and the clinical
response, a second dose of 5 g may be administered by IV
infusion up to a total dose of 10 g .

Cases

Skip to
Summary

14-y/o female with agitation,

hallucinations, and disorientation.
Found at her school attempting to climb the walls and
brought to school nurse calls 911.
According to parents healthy and without complaints
that a.m. No PMHx.
PE: Confused, mildly agitated, unable to give history
VS: BP 100/65, HR 105, Temp 98.0F, RR 20.
HEENT: Lateral and vertical nystagmus, pupils equal
and reactive at 4 mm, otherwise unremarkable
exam.
Now what??

14-y/o female with agitation,

hallucinations, and disorientation.
Pt had ingested 8 Coricidin
tabs before school (DXM 30
mg, Chlorpheniramine
maleate 4 mg per tab).
Within 4 hours the patients
Mental Status improved and
she confirmed history and
admitted to wanting to get
high.

Dextromethorphan
Sources:
Alka-Seltzer Plus Cold &
Cough Medicine, Coricidin HBP Cough
and Cold, Dayquil LiquiCaps, Dimetapp
DM,
Robitussin
cough
products,
Sudafed cough products, Triaminic
cough syrups, Tylenol Cold products,
Vicks 44 Cough Relief products and
Vicks NyQuil LiquiCaps.

AKA: Dex, DXM, Robo, Skittles, Syrup, Triple-C, and Tussin.

Pathophysiology:
Agonist activity on serotonergic neurotransmission (inhibits
sertonin reuptake)
Dextrorphan NMDA receptor antagonist (like PCP &
ketamine)

Why is Dextromethorphan popular?

Cheap
Legal
Readily available
over the counter
Web sites praise
drug as safe if used
responsibly.

How does the patient present?

Blurred vision
Miosis or Mydriasis
Tachycardia
Respiratory Depression
Ataxia, choreoathetosis, dystonia, seizure,
psychosis, or even coma.

Pop Quiz Question #3

What substance on the urine drug
screen will test falsely positive with a
significant dextromethorphan
ingestion?
A.
B.
C.
D.
E.

THC / Cannabis
Opioids
Amphetamines / Methamphetamines
PCP
Cocaine

UDS will be falsely

positive for PCP at higher
doses.

Dextromethorphan
Treatment

Activated charcoal
Narcan (naloxone) possibly of benefit
Seizures: treat with BZDs
Monitor for hypertension
Treat hyperthermia with external cooling
Dystonic Reaction: Benztropine 1-2mg IV or
Diphenhydramine 1mg/kg/dose IV over 2 min
Educate the patient & family

Cases / Specific Agents

Acetaminophen
Anticholinergics
Bath Salts
Benzodiazepines
-Blockers
Calcium Channel Blockers
Carbon Monoxide
Cyanide

Dextromethorphan
Ethylene glycol
Isopropyl Alcohol
Methanol
Opioids
Organophosphates
Sedative-hypnotics
SSRIs

Quiz
Summary

Quiz
There is no quiz.
This lecture is too long as it is.
If he doesnt stop soon, Im
going to pee my pants.

Summary

Management Approach of
the Poisoned Patient

A Airway

Tox-focused Hx

B Breathing

Physical Exam

C Circulation

Toxidrome
recognition

D Decontamination /
DONT
E Exposure / Enhanced
Elimination

Diagnostic tests

Good supportive care

is all that is needed
in the vast majority
of tox cases.

Remember,
it can
always
be tox.

References
American College of Surgeons, Advanced Trauma Life Support for Doctors Student Manual, 2004.
Boyer, Edward W., MD, Shannon, Michael, MD, The Serotonin Syndrome, New England Journal of
Medicine, 17 March 2005: 1112-1120.
Buckley NA, Whyte IM, O'Connell DL, et al. Activated charcoal reduces the need for N-acetylcysteine
treatment after acetaminophen (paracetamol) overdose. J Toxicol Clin Toxicol. 1999; 37(6):
753-7.
Bukata, Richard, MD. New Cyanide Drug Effective but Costly, Emergency Medicine News, Vol. 29, No 12,
December 2007, 17-18.
Cochens, Amy, WSLH (Wisconsin State Lab of Hygiene) Advanced Chemist. Dextromethorphan Use and
Abuse in DUI Investigations, Powerpoint presentation, at the 13th Annual International
Association of Chiefs of Police (IACP) Drug Recognition Experts (DRE) Conference, July 31August 2, 2007, in Las Vegas, Nevada. Internet access date 12 March 2008.
http://www.slh.wisc.edu/wps/wcm/connect/extranet/ehd/toxicology/alcohol.php
Cook, Eric, DO. Clinical Lecture, Introduction to Toxicology, December 2005, Powerpoint and lecture.
Erickson, Timothy B., MD. The National Emergency Medicine Board Review, Toxicology, 2006, audio CD
& written summary.
Erowid. Dextromethorphan, http://www.erowid.org/chemicals/dxm/. Website accessed 12 March 2008.
Goldfrank, et. al. Goldfranks Toxicologic Emergencies, 8th ed., 2006.
Management of Alcohol Withdrawal Delirium, Practice Guideline Committee, American Society of Addiction
Medicine (Archives of Internal Medicine 2004; 164:1405-1412).
Montoya-Cabrera MA, Escalante-Galindo P, Nava-Jurez A, et al. [Evaluation of the efficacy of N-acetylcysteine administered alone or in combination with
activated charcoal in the treatment of acetaminophen overdoses (Spanish)]. Gac Med Mex.1999 May-Jun; 135(3): 239-43.
Position paper: Ipecac syrup. J Toxicol Clin Toxicol - 01-JAN-2004; 42(2): 133-43. From NIH/NLM MEDLINE
Position statement: gastric lavage. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. Vale
JA - J Toxicol Clin Toxicol - 2004; Vol. 42, No. 7: 933-943. From NIH/NLM MEDLINE
Slovis, Corey, MD. Emergency Medicine Reviews and Perspectives, The Alcoholic Patient, May 2007, audio CD.
Spiller HA, Krenzelok EP, Grande GA, et al. A prospective evaluation of the effect of activated charcoal before oral N-acetylcysteine in acetaminophen
overdose. Ann Emerg Med. 1994 Mar; 23(3): 519-23.
Spiller HA, Sawyer TS. Impact of activated charcoal after acute acetaminophen overdoses treated with N-acetylcysteine. J Emerg Med. 2007 Aug; 33(2):
141-2.
Tintinalli. Emergency Medicine: A Comprehensive Study Guide, 6th ed., 2005.
Traub, Stephan, MD. Emergency Medicine Reviews and Perspectives, Toxicology ABCs, October 2005, audio CD.
Zand, Ladan MD; Hoffman, Scott J., MD; et. a., 74-Year-Old Woman With New-Onset Myoclonus, Mayo Clinic Proceedings, October 2010:955-958.

D.

O.