toxicology medical student lecture 2015. history tox matters m edication a mount/concentration t ime...

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.

• 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 162K 7.2Cl 119HCO3 4BUN/Cr 18/3.04Glucose 280

Workup, cont’d

• ABG6.7/24.8/90/4

Workup, cont’d

ABG6.7/24.8/90/4

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