Toxicology
Medical Student Lecture
2015
History
Tox MATTERS
•
•
•
•
•
•
•
M edication
A mount/concentration
T ime
T aken
E mesis?
R eason
S igns/symptoms
Physical Exam
•
•
•
•
•
•
•
•
VITALS!
General appearance
Pupils
Skin (Wet/dry? Flushed?)
GI (bowel sounds?)
Neuro (clonus? Reflexes?)
MSK tone
Psych (hallucinating? Oriented?)
Toxicology Workup
Toxicology Workup
• EKG
• Labs:
– BMP (why?), tylenol level
– If suspected:
• ASA, lithium, VPA, toxic alcohols, osmolality,
etc
Case 1
• 22 yo M brought in by friends
– 70, 110/60, 4, 70% RA, 97.8 F
What do you need to know?
PE
•
•
•
•
•
•
General: unresponsive
Skin: blue, dry
HEENT: pupils 2mm
MSK: decreased tone
Neuro: no clonus, not moving extremities
GI: decreased BS
Antidote?
Antidote?
• Narcan!
Antidote?
• Narcan!
• He wakes up immediately and wants to
put his clothes on and go home.
– Do you let him?
– What questions can you ask to make sure
that it is safe for him to leave?
Case 2
• 25 yo F who presents via EMS. She
was found outside running around her
neighborhood without clothes on.
Physical Exam
• 120, 130/85, 15, 100% RA, 100.5
• General: looking around room, not engaged
in conversation w/ you.
• HEENT: pupils 6mm, equal
• Skin: flushed on face and on chest, no sweat
in axillae
• GI: decreased BS
• Neuro: no rigidity, no clonus
• Psych: mumbles incoherently, picking at
things in the air, not oriented
Toxidrome?
Anticholinergic Toxicity
•
•
•
•
•
•
•
Hot as a hare
Mad as a hatter
Red as a beet
Blind as a bat
Dry as a bone
Tachy as a $20 suit
Naked as a jaybird
Usual Suspects
• Antihistamines
– Benadryl (Tylenol PM), Doxylamine (NyQuil)
• Antipsychotics
– Seroquel, clozaril, olanzapine
• Cyclic antidepressants
– Amitriptyline, imipramine, nortriptyline
• Plants
– Jimsom weed
The list goes on…
Treatment?
Treatment?
• Antidote is physostigmine.
– Inhibits acetylcholinesterase
– Can save an intubation
Treatment?
• Physostigmine
– Available only as an IV preparation
– Onset of action is within minutes
– Dose can be repeated q 10-15 min
– T1/2 is 16 minutes, but duration of action is
usually much longer
Physostigmine & TCA OD
• Physostigmine was used often in the
1970s to treat undifferentiated delerium
• Case report by Pentel in 1980 re: 2
patients who suffered asystole after
receiving physostigmine for TCA
overdoses
• Since then the antidote has greatly
fallen out of favor
Physostigmine - Indications
• Anti-cholinergic manifestations without
evidence of QRS or QTc prolongation,
such as:
–
–
–
–
–
–
Agitation
Hypertheria
Hallucinations
Delerium
Seizures
coma
• The patient to use this in is a known
non-TCA anti-cholinergic overdose
Physostigmine –
Contraindications
• Definite contraindications:
– Suspicion of TCA ingestion
– Widened QRS on ECG
Case 3
• 35 yo M who presents altered. He was
found by EMS outside a club. Someone
called because he was acting strangely.
He is angry and has required multiple
doses of benzos in the rig.
– Vitals:
• 140, 160/90, 18, 96% RA, 99.5 F
Physical Exam
• General: angry, shouting at people in
the room
• HEENT: pupils 6mm, equal
• Skin: no flushing. +Diaphoresis
• GI: normal BS
• Neuro: no rigidity, no clonus
• Psych: angry, delusional, but knows
where he is.
Toxidrome?
Toxidrome?
• Sympathomimetic toxicity
– Symptoms:
• anxiety, delusions, diaphoresis, hyperreflexia, mydriasis,
paranoia, piloerection, and seizures
• hypertension, and tachycardia.
– Common substances:
• Amphetamines/methamphetamine, cocaine, theophylline
– It may appear very similar to the anticholinergic
toxidrome, but is distinguished by hyperactive
bowel sounds and sweating.
Treatment
• Benzos, benzos and…
Treatment
• Benzos, benzos and…
MORE BENZOS!
Case 4
• 45 yo Mexican migrant worker who
presents from his work. He is having a
lot of difficulty breathing, per EMS.
Physical Exam
• 50, 120/80, 30, 85% NRB, 98.6 F
• General: confused male with obvious difficulty
breathing
• HEENT: pupils 2mm, tearing, runny nose
• CV: brady
• Resp: diffuse wheezing, decreased BS
throughout
• Skin: diaphoretic
• Neuro: normal m tone, he is confused, pulling
at his lines
• GU: urine in pants
Toxidrome?
Toxidrome?
• Cholinergic
Toxidrome?
• Cholinergic
– Symptoms:
• bronchorrhea, confusion, defecation, diaphoresis,
diarrhea, emesis, lacrimation, miosis, muscle
fasciculations, salivation, seizures, urination, and
weakness, bradycardia, hypothermia, and tachypnea.
– Substances that may cause this toxidrome include
carbamates, mushrooms, and organophosphates.
Cholinergic Toxidrome
• Common mnemonic:
– SLUDGE
• Salivation, Lacrimation, Urination, Diarrhea,
Gastrointestinal distress, and Emesis
– DUMBBELLS
• Diarrhea, Urination, Miosis, Bradycardia,
Bronchorrhea, Emesis, Lacrimation, Lethargy
and Salivation
Treatment
Treatment
• 2-PAM (pralidoxime) and atropine
– “reactivates” acetylcholinesterase so that it
can again break down Ach
– Atropine works in conjunction with this
(competitive antagonist for M receptor)
Case 5
• 66 yo Farmer who presents obtunded.
Found by a family member in the
garage. Family was very worried about
him because he wasn’t “acting right.”
Was slurring his speech initially. Per
EMS, became more unresponsive in the
rig.
PE
•
•
•
•
•
•
•
110, 100/68, 30, 100% RA, 98.7F
General: obtunded
HEENT: pupils midrange, reactive
CV: tachy, no murmurs
Resp: no wheeze/rhonchi
Skin: dry
Neuro: normal m tone, no clonus
Workup
• EKG: sinus tachycardia
• BMP:
Na 162
K 7.2
Cl 119
HCO3 4
BUN/Cr 18/3.04
Glucose 280
Workup, cont’d
• ABG
6.7/24.8/90/4
Workup, cont’d
ABG
6.7/24.8/90/4
Osmolality
391
ETOH
0.0
What’s next?!
Calculations
• AG = Na - (Cl +HCO3)
• Calculated osmolality = 2 x [Na mmol/L] +
[glucose mg/dL /18] + [urea mg/dL /2.8]
• Osmolar gap = measured osm - calculated
• A normal osmol gap is < 10 mOsm/kg
Calculations, cont’d
• AG = 39
• Osmolar gap = 391 - 346 = 45
What’s causing the gap?
Ethylene Glycol Toxicity
• Found in antifreeze
• Tastes sweet (bad for babies and
animals)
• Metabolites cause high AG acidosis
• Ca oxalate crystals form in kidneys
causing ARF
• Antidote: fomepizole
Case 6
• 20 yo F with hx of depression brought
by mother after she said she took “a
handful” of OTC Tylenol after getting a
text that her boyfriend was breaking up
with her.
PE
•
•
•
•
•
•
•
98.8, 86, 20, 98%,120/90
General: Alert, tearful, NAD
HEENT: pupils midrange, reactive
CV: RRR, no m/r/g
Resp: no wheeze/rhonchi
Skin: warm, well perfused
Neuro: normal m tone, no clonus
What do you need to know?
What do you need to know?
• 1 hour prior to arrival
• Pt texted her friend right after ingestion
and friend called pts mother right after
What do you want to do now?!
Initial Labs
• BMP: Na 136, K 4.3, Cl 106, HCO3 20,
BUN/Cr normal
• EKG normal
• APAP 250 mcg/ml
• Alk phos 87, Tbili 0.3, AST 21, ALT 25
Should we start N-Acetylcystine (NAC)?
4 hour APAP level
APAP 80 mcg/mL
Rumack-Matthew Nomogram
• Published 1975
• Based on a
retrospective analysis
of previous APAP
overdoses and their
clinical outcomes
• Original line at
200mcg/mL, but
moved to 150 at
urging of FDA
• 200 still the treatment
threshold in Europe
APAP metabolism
N-Acetylcystine
• Provides a substrate for sulfation
• Regenerates glutathione (GSH)
• GSH reduces NAPQI, allowing it to be
cleared via the kidneys
Other indications for NAC
• Unknown time of ingestion and a serum APAP
concentration >10 mcg/mL OR evidence of liver
injury (elevated AST/ALT)
• Pts with delayed presentation (>24 hours after
ingestion) with lab evidence of liver injury and a
history of excessive APAP ingestion
Other toxidromes
• Sedative-hypnotics
– Benzos, alcohol, GHB
– Supportive care
• ASA toxicity
– Elevated everything (BP, pulse, RR, temp)
– Bicarb gtt, dialysis