Clinical Pathological Case Presentation

NACCT 2003

Jerry D. Thomas, MDGeorgia Poison Center

Emory University School of Medicine

What We Know

CC: Dyspnea

HPI: History of IVDA Progressive dyspnea for 2 days No fevers, chills, cough or chest pain Treated for PCP with TMP/SMX and transferred Denies recent cocaine, heroin, or methamphetamine Took 2 carisoprodol tablets in last 24 hours Took “the shit that killed [rock star]”

What We Know

PMH Previously healthy Rehab admissions HIV negative one year ago Known 2 carisoprodol, TMP/SMX

What We Know

Social History Unemployed and lives with girlfriend Smokes 1 ppd cigarettes and marijuana IVDA cocaine, heroin, and methamphetamine

Medications and Allergies None

What We Know

Physical Exam Afebrile Tachycardic and tachypneic Hypoxic

O2 saturation 82% on RA and 91% on 100% NRB Abnormals

RR-30

What We Know

CV – Tachycardic but no rubs or murmurs (gallop?)

Neck - ? JVD

Lungs – Diffuse rales bilaterally

Extremities – Track marks in the left antecubital fossa and tattoos on chest and arms

What We Know

Labs WBC: 15.9 k/mm3

HCT: 45.0 % Platelets: 240 k/mm3

Differential59.9% Neutrophils26.3% Lymphocytes6.2% Monocytes

What We Know

Labs NA 138 meq/L K 4.6 meq/L CL 105 meq/L HCO3 23 meq/L BUN 12 mg/dL Cr 0.7 mg/dL Glu 141 mg/dL Ca 8.6 mg/dL

What We Know

Labs ABG on Room Air

pH 7.4 pCO2 34 mmHg pO2 46 mmHg HCO3 23 meq/L

ECG Sinus tach, QRS 88 ms, QTC 390 ms, no ectopy or

ischemia

What We Know

Urine Drug Screen Amphetamines – Negative Cocaine – Negative THC – Positive Benzodiazepine – Negative Barbiturates – Negative TCAs – Negative

ASA/APAP/ EtOH Nondetectable

What We Would Like To Know!

Better physical exam

Clinical course prior to presentation

Cardiac echo

CVP

When did he last use his usual drugs?

What type of DOA screen

Which freaking rock star!!!

Clinical Picture Due to:

Noncardiogenic Pulmonary EdemaCardiogenic Pulmonary Edema/Myocardial Infarction/Cardiomyopathy/Endocarditis/Valve or leaflet ruptureAspiration PneumonitisToxic InhalantsMyocardial Depressant Effects of ToxinTalc Emboli

Developing a Differential

Pulmonary Edema Cardiogenic Noncardiogenic

Drugs of Abuse

Rock Stars

Systems Analysis

Rock Star Deaths

Pulmonary Edema Drug Abuse

Cardiogenic versus Noncardiogenic Pulmonary Edema (NCPE)

Cephalization of Pulmonary Vessels

Cardiomegaly

Pulmonary Capillary Wedge Pressure > 20 mm Hg

NCPE sometimes classified with ARDS

Cardiogenic Pulmonary Edema

Acute Poisoning

Adrenergic Agonists -Myocardial Infarction Ergotamines Cocaine Amphetamines Ephedrine

After Mark Kirk CPC NACCT 2000

Cardiogenic Pulmonary Edema

Acute Poisoning

Carbon Monoxide

Arsenic

Antineoplastic Agents Interferon Cyclophosphamide Anthracycline

Cardiogenic Pulmonary Edema

Chronic ExposureIpecacEthanolThiamine/Carnitine/Selenium DeficiencyHypophosphotemiaCobalt Doxorubicin

Cardiogenic Pulmonary Edema

Acute PoisoningCalcium Channel AntagonistsBeta-Adrenergic AntagonistsSodium Channel Blockers Type IA antidysrhthmics Amantadine/Antihistamines TCA/Quinine/Chloroquine Cocaine/Propoxyphene

Pulmonary EdemaMedicinal: aldesleukin, amantadine, amiloride, amiodarone, ammonium chloride, bleomycin, boric acid,

buflomedil, carteolol, chlorhexidine gluconate, chloroxylenol, cocaine, codeine, colchicine, cytarabine, desipramine, dibenzepin, dipyridimole, doxepin, esmolol, ethchlorvynol, glutethimide, haloperidol, heroin, imipramine, iodine, iron, ketorolac, lindane, methadone, methamphetamine, methyprylon, minoxidil, morphine, nalbuphine, naproxen, nifedipine, nimodipine, nitrofurantoin, nortriptyline, opium, oxycodone, paclitaxel, paraldehyde, pentazocine, phenobarbital, phenol, phenolphthalein, phenylbutazone, pilocarpine, povidone-iodine, propofol, propoxyphene, propranolol, protamine, rifampin, ritodrine, sodium chloride, sotalol, tenecteplase, terbutaline, tocainide, verapamil, vinorelbine, zinc sulfate

Nonmedicinal: 1,2-dibrom-3-chloropropane, dibromoethane, acetaldehyde, acrolein, aldicarb, aluminum phosphide, ammonia, benzene, blasticidin s, bromophos, carbaryl, chenopodium oils, chlorfenvinphos, chlorine, chloracetophenone, chlorobenzylidene malonitrile, chlorform, chloropicrin, chlorpyrifos, copper, coumaphos, cresols, cyanide, demeton-s-methyl, diazinon, diborane, dichlorvos, dicrotophos, diethylene glycol, dimethylnitrosamine, dioxathion, disulfoton, endosulfan, ethion, ethylene dichloride, ethylene glycol, ethylene oxide, fensulfothion, fenthion, freon, gasoline, hydrazine, hydrogen chloride, hydrogen fluoride, hydrogen sulfide, jet fuel-5/jet fuel-8, malathion, mercury, methidathion, methiocarb, methomyl, methyl bromide, methyl parathion, nickel, nickel carbonyl, nitrogen dioxide, osmium, parathion, phosdrin, phosgene, phosphine, profenofos, propoxur, pyrethrins, selenium, sodium azide, sulfur dioxide, sulfuryl fluoride, terbufos, tetraethyl pyrophosphate, thallium sulfate, titanium, toluene, trichloroethane, trichloroethylene, trimellitic anhydride, turpentine oil, uranium, vanadium, zinc phosphide

Biologicals: Arizona bark scorpion, autumn crocus, betel nut, box jellyfish, clove, eucalyptus oil, funnel web spider, germanium

What Causes Pulmonary Edema?

What doesn’t cause pulmonary edema?

Etiologies of NCPE

Direct Injury Aspiration Inhalational injuries Near drowning Pulmonary contusion Diffuse Pulmonary infection

Perina DG. Noncardiogenic pulmonary edema. Emerg Med Clinics of NA 2003;21:385-393.

Noncardiogenic Pulmonary Edema

Adult Respiratory Distress SyndromeOpioids/NaloxoneSalicylatesIrritant GasesAmphetamines/ CocaineThiazide DiureticsAmiodarone/ Amphotericin/ Vinca Alkaloids/ Colchicine/ Ethchlorvynol

Indirect Injury

Systemic Sepsis and septic shockBlood products transfusion reactionHigh altitude effectsDrug overdoseNeurogenic insultsPancreatitisCardiopulmonary bypassSevere non-thoracic traumaFat emboliAir emboli

Indirect Injuries

Uremia

Coagulopathies

DIC

Common drugs

Drug OD Heroin Methadone Aspirin Propoxyphene Ethchlorvynol

Reed CR, et al. Drug-Induced Noncardiogenic Pulmonary Edema. Chest 1991;100:1120-1124.

NCPE

Inhaled toxins Smoke Ammonia Chlorine Nitrous oxide Phosgene Methylene chloride

Rock Star Deaths

Where did I keep those notes from Erickson’s lecture? Heroin

Tommy Bolin, Sid Vicious, Janis Joplin, Billie Holliday, Dee Dee Ramone, Lance Krantz, Jan McAdam, Paula Yates, Eddy Shaver, Will Clay, Stacy Guess, Brad Nowell, Frankie Lymon, Neil Storey, Gregory Herbert, Judee Sill, Rick Evers, Roy Montrell, Danny Whitten, Dave Waller

Cocaine Shannon Hoon, Wells Kelly, DJ Screw, Bobby Sheehan, Tommy Bolin, David Ruffin

Barbiturates Jimi Hendrix, Judy Garland, Brian Epstein

Amphetamines Hank Williams

Other Zac Foley, Rob Pilatus, Elvis Presley, Keith Moon

I need an Atypical Rock Star Death

Everything this guy usually takes could cause this!

UDS negative for opiates, cocaine and amphetamines ? False negatives

Synthetic opiate

Keith Moon Heminevrine- Chlormethiazole being used for EtOH

addiction.

Screw It

Differential too large

I’ve got better things to do

I’m not feeling the love

I need a new system approach

EKR Systems Approach to CPCs

Apologies to Dr. Elizabeth Kubler-Ross

Denial

I am good enough and smart enough and doggone it, people like me.

I have plenty of time to figure out the CPC!

Anger

How the hell do they expect me to figure out this CPC!

Everything has a case report associating it with pulmonary edema!

Where are my fellows when I need them!

Bargaining

Who can I bribe to figure out this CPC?

How can I cheat if at all possible?

Depression

My differential just keeps getting larger.

Maybe there will be another blackout.

What do 4 out of 5 toxicologists recommend for an overdose?

Acceptance

OK, the differential is enormous and there is little to narrow down the field so what answer is the most satisfying intellectually for an NACCT CPC?

What Would Elvis Do?

What didn’t Elvis do?

The Shit That Killed Elvis

Elvis died in the bathroom.Slang term for high grade marijuanaPercodanDemerolAmphetaminesMyriad sedative hypnotics Methaqualone Barbiturates Ethchlorvynol

Marijuana

UDS positive for THC Doesn’t usually cause pulmonary edema Possible contaminant

PCP Ketamine Paraquat

Methaqualone

Used by Elvis

Reports of Pulmonary Edema

Schedule I since 1984 and reports are infrequent

Kids are making everything these days

Ethchlorvynol

Placidyl – sedative,hypnoticUsed by ElvisCauses NCPE when injected not usually when taken orallyAfter IV injection causes a minty taste in the mouth then dyspneaAbbott discontinued production in 1999.Is it available?

Ethchlorvynol

The following ethchlorvynol cases have been reported to AAPCC TESS since 1/1/2000:

50 human cases as substance 1, no deaths

90 human cases total as one of the involved substances, no deaths

Does it Fit?

Miller, KS, et al. Bilateral exudative pleural effusions following intravenous ethchlorvynol administration. Chest 1989;95:464-465.

Conces, DJ, et al. Pulmonary edema induced by intravenous ethchlorvynol. Am J Emerg Med 1986;4:549-551.

Glauser FL, et al. Ethchlorvynol (Placidyl) – induced pulmonary edema. Ann Intern Med 1976;84:46-68.

Burton WN, et al. Adult respiratory distress syndrome after Placidyl abuse. Crit Care Med 1980;8:48-49.

Swearingen PV. Placidyl and pulmonary edema. Ann Int Med 1976;84:614-615.

Yell RP. Ethchlorvynol overdose. Am Journ of Emerg Med 1990;8:246-250.

Treatment

Supportive Care PEEP Usually resolves within 72 hours

Animal studies did show possible benefit in pretreatment with cyclooxygense inhibitors

Nesiritide Bobadilla RV, et al. Nesiritide treatment of

noncardiogenic pulmonary edema. Annals of Pharmacotherapy. 2003;37(4):530-533.

Other guesses

Talc emboli

Marijuana contaminant

Just about anything