Medical Student Lecture 2015 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? You have to let him if he is now normal. Ask what he took. If he injected heroin, he’s probably fine. If he ingested something like percocet, you have to do a tylenol level. If he took something like methadone he needs to stay in the hospital.

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 Antipsychotics Cyclic antidepressants 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: Common substances: 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)? No. 4 hour APAP level should be drawn if certain of time of ingestion.

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 ASA toxicity Benzos, alcohol, GHB Supportive care ASA toxicity Elevated everything (BP, pulse, RR, temp) Bicarb gtt, dialysis