Lessons Learned from Poison Control M A R C H 1 0 T H , 2 0 1 6 - - PDF document

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M A R C H 1 0 T H , 2 0 1 6

HALLAM GUGELMANN, MD MPH

M E D I C A L T O X I C O L O G I S T U N I V E R S I T Y O F C A L I F O R N I A A T S A N F R A N C I S C O A S S I S T A N T M E D I C A L D I R E C T O R C A L I F O R N I A P O I S O N C O N T R O L S Y S T E M , S A N F R A N C I S C O D I V I S I O N E M E R G E N C Y M E D I C I N E A T T E N D I N G C P M C S T L U K E ’ S H O S P I T A L S A N F R A N C I S C O , C A L I F O R N I A

Lessons Learned from Poison Control

Disclosures

— I have nothing to disclose

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The California Poison Control System

— Poison Control Centers:

critical role in chemical and drug exposures

¡ 24/7 reliable information ¡ Disaster surveillance ¡ Passive data mining ¡ Alert, experienced professionals

Poison Control Staff

— Highly trained, licensed, certified experts

¡ PharmDs and nurses with extensive training ¡ Non-licensed information providers ÷ Handle simpler calls ÷ Use approved protocols ÷ Supervised by licensed specialists

— Back-up by board-certified MD toxicologists

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CPCS Public Health Surveillance… Case 1. The Pet Shop Employee

— A healthy 32 year old

male

¡ Cleaning an aquarium ¡ Superficial abrasions to 3

fingers of right hand — Goes home

¡ 2 hours later: ÷ Diffuse weakness ÷ Shivering & Myalgias

— 16 hours after exposure:

÷ Collapses at work ÷ Dizzy, slurred speech ÷ Glassy eyes

— Clinical course:

¡ Numbness and pain

spreading up affected arm

¡ EKG showing sodium

channel disturbance

¡ Rhabdomyolysis ¡ 48 hours of paresthesias,

weakness, muscle pains — 4 weeks later:

¡ Full resolution of

symptoms The Culprit:

• Toxicon. 2008 Jun 15;51(8):1535-7.

wikipedia.org

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Poison Control and the Esoteric Case

— Palytoxin, from zoanthid anemones,

some predatory fish

¡ Goldspot herring, boxfish, filefish,

parrotfish, some crabs — Mechanism:

¡ Deranges cell membrane proteins ¡ Sodium and potassium flow into cells

— Broad range of clinical findings:

¡ Dizziness, perioral and limb

paresthesias, weakness

¡ Nausea, vomiting, diarrhea,

abdominal pain

¡ Hypertension, bradycardia,

dysrhythmias

¡ Rhabdomyolysis, acute renal failure,

anuria

¡ Myalgias, muscle spasms, respiratory

distress, arthralgia, acute hyperkalemia, acute hyperphosphatemia

For more information: thepoisonreview.com wikipedia.org

Toxicology Esoterica: La fée verte

— What is absinthism?

¡ Seizures, impaired speech,

hallucinations, coma

— What’s to blame?

¡ Thujone? ÷ Seizures at high concentrations… ÷ Absinthe contains less than 35 mg/L

• f thujone

¡ Cheap absinthe: ÷ Copper sulfate & antimony chloride:

additives to obtain the green color and milky opalescent effect

• HUTTON I (2002) CURR DRUG

DISCOV 9:62–64

Pablo Picasso The Absinthe Drinker (1902) Dalmatian sage—common flavoring herb—contains more than 50 % thujone in its oil

http://www.picassoandmatisse.com/

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Case 2. An Irritated Eye…

— Healthy 45 year old plant nursery employee:

¡ Right eye irritation while at work ¡ Vital signs from triage: ÷ BP 125/87 HR 83 Temp 37.4C RR 12 ¡ First thing you see:

Pupils…

Musculature and Innervation Mydriasis Miosis Constrictor (sphincter)

cholinergic stimulation via CN III

Inhibition

anticholinergics

Stimulation

• pioids, pilocarpine,
• rganophophates

Dilator (radial)

sympathetic innervation

Stimulation

catecholamines, cocaine, meth…

Inhibition

clonidine Images: Wikipedia

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Relevant: What is cornpicker's eye?

Answer:

— Mechanized combines are used

to harvest corn and cornstalks.

— Dried Datura plants in the field

are pulverized into a dust containing belladona alkaloids.

— This dust can become airborne;

contact with the eyes cause mydriasis, and inhalation can cause systemic anticholinergic symptoms as well.

• KRENZELOK E. DATURA
• POISONING. 48(2):

104-110

Images: Wikipedia

The Diligent Occupational Medicine Doctor asks:

— What plants were you working with?

Brugmansia

Images: Wikipedia

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Pupils…

Musculature and Innervation Mydriasis Miosis Constrictor (sphincter)

cholinergic stimulation via CN III

Inhibition

anticholinergics

Stimulation

• pioids, pilocarpine,
• rganophophates

Dilator (radial)

sympathetic innervation

Stimulation

catecholamines, cocaine, meth…

Inhibition

clonidine Images: Wikipedia

Case 2 – continued…

— Datura sap had gotten in the patient’s eye — She was sent home, and her symptoms resolved over

then next 24 hours

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Case 3. On the subject of eyes...

— 30 year old male veteran

¡ 3 deployments to Afghanistan

— Ocular complaints:

¡ Persistent image in his visual field after staring then

looking away

¡ Also: ÷ Field of points of light throughout his vision ÷ Junctions of high contrast seen as through a prism

— Toxic exposures:

¡ Depleted uranium ¡ Single IED exposure resulting in loss of

consciousness and persistent tinnitus

¡ Remote LSD use

Medical Toxicologist Consultation

Palinopsia Visual Snow

— Staring at an object,

then shifting his gaze to a blank screen results in a persistent image of the object

— Constant field of

multiple points of light

What is the patient exhibiting?

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Ocular Toxins

— Disconjugate gaze

¡ Botulism ¡ Elapids ¡ Paralytic shellfish poisoning ¡ Tetrodotoxin

— Funduscopic changes

¡ Carbon monoxide ¡ Cyanide ¡ Ergot alkaloids ¡ Methanol

— Nystagmus

¡ Carbamazepine ¡ Ethanol ¡ Phencyclidine

— Papilledema

¡ Amiodarone, lead, vitamin A Image: Goldfrank’s Toxicologic Emergencies, 9th Ed.

Palinopsia Visual Snow

— Staring at an object,

then shifting his gaze to a blank screen results in a persistent image of the object

— Constant field of

multiple points of light

What is the patient actually exhibiting?

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Xenobiotics and Palinopsia?

— Trazodone, nefazodone, risperidone

¡ 5HT2a modulators

— Clomiphene, topiramate

¡ GABA disruption-mediated? ¡ Clomiphene has been associated with

permanent palinopsia

— Mirtazapine

¡ Visual trails predominantly, meets Naranjo

Criteria

— Zosuquidar

¡ Antineoplastic

— Maprotiline, Interleukin 2

¡ Links are somewhat questionable…

Could this be toxicologic?

— Palinopsia:

¡ Broad range of illicits and pharmaceuticals that could have

caused the problem.

¡ No clear intervention available.

— What about depleted uranium?

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Depleted Uranium Bullets

— Used in armor-piercing bullets

and defensive plating

¡ Medical radiation shielding

— Byproduct of enriched uranium

production

¡ Both nuclear reactor and nuclear

weapons byproduct — 68.4% denser than lead — Natural uranium is ~0.70% 235U — Depleted uranium has 0.2% 235U

Uranium ore à uranium oxide (U3OX) àUF6 (gas) Separate 234U 235U 238U via gas chromatography

Images: Wikipedia

Clinical Effects of Depleted Uranium

— Various forms in nature and after absorption — Dermal exposure:

¡ Animal studies: 7g/kg à dermal damage, renal failure

— Respiratory exposure:

¡ Inhalation: ÷ 85% deposited in bones, 15% in renal proximal tubules

— Embedded fragments:

¡ Friendly fire and shrapnel exposure ¡ Generally removed to decrease risk of absorption

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Case 3. Could this be toxicologic? Maybe.

— Palinopsia:

¡ Caused by a broad range of drugs ¡ Depleted uranium-induced? Unlikely.

— Visual snow:

¡ May be linked to a history of LSD use ¡ Commonly migraine-related

— No known treatments for either

Toxicology Esoterica: The Cost of Being Callipygian

— 27 year old female — Shortness of breath and

wheezing 18 hours after undergoing a buttock enhancement procedure

— Could her presentation

and the procedure be related?

— Gluteal enhancement:

¡ Silicone implants ¡ Polyacrylamide hydrogel ¡ Liposuction contouring

via autologous fat transfer

¡ Polymethyl-methacrylate

(PMMA) — Possible complications of

PMMA:

¡ Anaphylactoid reactions ¡ Inflammation, infections ¡ Emboli

2009: Former Miss Argentina dies after a PMMA buttock injection embolizes to her lungs, and possibly brain.

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Case 4. Out cold

— An occupational medicine nurse at a chicken waste

rendering plant is called to help.

Rendering: reclaiming fats and protein from animal waste tissue.

Associated with bovine spongiform encephalopathy.

— A blocked condenser connected to a storage vessel

had been cleared, and the resulting gas emission knocked three workers unconscious

— EMS crews call Poison Control en route to the

hospital

What are “knockdown gases”?

— Cyanide — Hydrogen sulfide

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H2S: Hydrogen Sulfide

— Flammable, colorless, heavier than air — Rotten egg or cabbage smell — Found in sewage sludge, decaying

• rganic matter, petroleum refineries…

— Clinically:

¡ Perceived odor ÷ (0.025 ppm) ¡ Conjunctivitis ¡ Olfactory paralysis ÷ (100-150ppm) ¡ Knockdown ÷ DLH 100ppm ¡ Pulmonary edema ÷ (300-500ppm) ¡ Death ÷ (600-800ppm)

“Gas eye” Keratoconjunctivitis associated with exposure to low levels of H2S (e.g sour gas plants). Associated with reversible chromatic distortion

• ther vision changes

Sometimes with blepharospasm, tearing, photophobia.

Guidotti TL. Occ Med 1996. 46(5):367-371

Oxidative Phosphorylation

— Mitochondrial energy

production:

Glucose Pyruvate FADH NADH Electron Transport Chain glycolysis citric acid cycle e-

Images: Wikipedia

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Cytochrome C Oxidase Inhibition

— E.g., H2S and cyanide

¡ Attaches to iron (Fe3+ affinity) ¡ Blocks electron transport to O2 ¡ Aerobic production of ATP stops:

Glucose Pyruvate FADH NADH Electron Transport Chain glycolysis citric acid cycle e- Lactate

Toxicology Esoterica: Travel and Backwash

— What is bleed air?

¡ Pyrolyzed engine oils and hydraulic fluids

that leak into aircraft cabin and flight deck air supply systems

¡ Tricresylphosphates (TCPs) et al.

TCP UPDATE: “TCP concentrations reported in the literature are much too low to explain the health effects reported by pilots.”

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Case 4. Hydrogen Sulfide

— Diagnosis:

¡ Context: few other “knockdown” gas scenarios ¡ Rotten egg odor (may be absent due to olfactory paralysis) ¡ Blackened coins in victims’ pockets (silver sulfide production)

— Do NOT enter area without self-contained breathing

apparatus

— Cases:

¡ Two patients recovered at work ¡ The third recovered after 3 days of hospitalization for delayed

pulmonary edema.

Case 5. A Shaky Computer Programmer in the Occupational Medicine Clinic

— A 52 year old male computer

programmer

¡ Requesting to be moved away from the printer

— Complaints:

¡ Slight tremor in both hands ¡ Chronic gingivostomatitis ¡ From colleagues: he seems more irascible than

usual…

— PMH: Hypertension

¡ Used to smoke but now “vaping”

— Surveillance labs from the past year:

proteinuria

— His occupational medicine doctor calls…

“Does this sound like a toxic exposure?”

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Case 5. Exposure history…

— The patient has worked next to the printer for a week — No other known occupational exposures

¡ Tobacco: 5 year pack history ¡ EtOH: 1-2 beers per week maximum ¡ Medications: HCTZ ¡ No herbal medications or supplements

— Hobbies?

¡ Computer games ¡ Gold reclaiming…

Gold Reclaiming

• Elemental mercury combines with

gold to form an amalgam

• Heating evaporates mercury…

Mercury

— Elemental mercury is poorly-absorbed

¡ Can cause toxicity when inhaled or in large ingestions

— Inorganic mercuric salts are also poorly absorbed — Organic mercury:

¡ Antiseptics – low skin penetration ¡ Methylmercury – in fish ¡ Dimethylmercury – analytic chemistry reagent, associated with

severe delayed toxicity

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Mercury Toxicity by Type

N Engl J Med. 2003 Oct 30;349(18):1731-7.

Mercury Exposure

— Inhalation of mercury vapor:

¡ Severe chemical pneumonitis, noncardiogenic pulmonary edema ¡ Chronic: ÷ Tremor, neuropsychiatric disturbances, and gingivostomatitis.

÷ Intention tremor of the fingers à facial tremor à choreiform movements of the

limbs

¡ Erethism:

÷ Shyness, withdrawal, and depression, with explosive irritability and

frequent blushing — Inorganic mercuric salt ingestion:

¡ Hemorrhagic gastroenteritis and abdominal pain

— Dimethylmercury:

¡ Minimal exposures have been lethal ¡ Crosses the blood–brain barrier easily ¡ May form a complex with cysteine

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Mercury Exposure: Treatment

— Metallic (elemental) mercury

¡ Remove patient from exposure source ¡ Oral succimer (DMSA) or oral unithiol (DMPS) may enhance

urinary mercury excretion

÷ Effect on clinical outcome has not been fully studied

— Inorganic mercury salts

¡ IV unithiol or IM BAL ¡ Oral succimer as a follow-up to DMPS or BAL treatment

— Organic mercury

¡ Methylmercury: oral succimer and oral N-acetylcysteine may

be effective in decreasing mercury levels in tissues, including the brain.

— 4 million children are legally employed in

the US

¡ Additional 1-2 million employed in

violation of the Fair Labor Safety Act

— Massachusetts Poison Control System

reviewed adolescent workplace exposures from 1991-1996

Poison Centers and Surveillance

—

269 incidents found

—

Exposures included:

¡ Cleaners, hydrocarbons, glues, pesticides

—

Outcomes:

¡ 58% required medical evaluation ¡ 43 (15.9%) had moderate or severe outcome

Occupational toxic exposures are an underrecognized adolescent injury. Poison Control Center data can be used to fill this surveillance gap.

Arch Pediatr Adolesc Med. 2000;154:234-239

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Question 1. What resources can Poison Control offer?

• A. Specialized pharmacist, nurse and toxicologist

advice

• B. 24/7 coverage
• C. Passive data mining
• D. Disaster surveillance
• E. All of the above

Question 2. Which of the following is a “knockdown” gas?

• A. Nitrogen
• B. Mercury vapor
• C. Hydrogen sulfide
• D. Carbon monoxide
• E. Toluene fumes

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Question 3. Which are manifestations of mercury poisoning?

• A. Chemical pneumonitis
• B. Noncardiogenic pulmonary edema
• C. Gingivostomatitis
• D. Neuropsychiatric disturbances, including explosive

irritability

• E. All of the above

References

—

Olson, K.R. et al. Poisoning & Drug Overdose: Fifth Edition. Lange Medical Books/McGraw-Hill. 2007

—

N Engl J Med. 2003 Oct 30;349(18):1731-7.

—

http://en.wikipedia.org/wiki/Cytochrome_c_oxidase#mediaviewer/ File:Cytochrome_C_Oxidase_1OCC_in_Membrane_2.png

—

Ann Plast Surg. 2011 Sep;67(3):209-14.

—

Critchley M. Types of visual perseveration: ‘‘Palinopsia’’ and ‘‘illusory visual spread.’’ Brain 1951;74:267-99.

—

• Optometry. 2010 Aug;81(8):394-404. doi: 10.1016/j.optm.2009.12.010. Palinopsia. Abert B1, Ilsen PF.

—

• Brain. 2014 May;137(Pt 5):1419-28. doi: 10.1093/brain/awu050. Epub 2014 Mar 18. 'Visual snow' - a disorder distinct from

persistent migraine aura. Schankin CJ1, Maniyar FH, Digre KB, Goadsby PJ.

—

Visual perceptual abnormalities: hallucinations and illusions. Norton JW, Corbett JJ. Semin Neurol. 2000;20(1):111-21. Review.

—

Surv Ophthalmol. 2014 Jul 2. pii: S0039-6257(14)00128-3. doi: 10.1016/j.survophthal.2014.06.003. [Epub ahead of print] Palinopsia revamped: A systematic review of the literature. Gersztenkorn D1, Lee AG2.

—

Arch Ophthalmol. 1996 Jan;114(1):47-50. Persistent palinopsia following ingestion of lysergic acid diethylamide (LSD). Kawasaki A1, Purvin V.

—

Arch Ophthalmol. 1995 Apr;113(4):482-4. Visual disturbance secondary to clomiphene citrate. Purvin VA.

—

https://commons.wikimedia.org/wiki/File:Brugmansia_(detail).jpg#/media/File:Brugmansia_(detail).jpg

—

http://upload.wikimedia.org/wikipedia/commons/thumb/c/cf/Combine_at_work.jpg/800px-Combine_at_work.jpg

—

http://upload.wikimedia.org/wikipedia/commons/8/8c/Dilated_pupils_2006.jpg

—

http://www.easynotecards.com/uploads/513/15/_32ca0c8e_1396a4f1b6c__8000_00000014.png

—

• Toxicon. 2008 Jun 15;51(8):1535-7.

—

Ann Emerg Med. 2014 Dec;64(6):633-6. doi: 10.1016/j.annemergmed.2014.06.001. Epub 2014 Jul 3. Hyperkalemia, hyperphosphatemia, acute kidney injury, and fatal dysrhythmias after consumption of palytoxin-contaminated goldspot

• herring. Wu ML1, Yang CC2, Deng JF3, Wang KY4.

—

www.thepoisonreview.com

—

Hutton I (2002) Curr Drug Discov 9:62–64

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Image Credits Questions?