Introduction to Toxicology

Medical Toxicology....

Is a board-accredited specialty requiring at least two years of training after residency in either emergency medicine, pediatrics, internal medicine or preventative medicine.

Deals with the “diagnosis, management and prevention of poisoning and other adverse health effects due to medications, occupational and environmental toxins, and biological agents”

This lecture will condense this information into two parts:

• The approach to the poisoned patient

• Case scenarios

Part I: Approach to the poisoned patient.

“Attempts to identify the poison should not delay care.”

Initial management of the poisoned patient begins with the ABC’s.

ACLS algorithms apply in toxicology with only a few exceptions.

Once these are stable, begin considering how to minimize bioavailability. Then you may begin your history and physical.

History: find out all of this information:

The question words: Which drug(s) were taken? When was it taken? How much was taken? How was it taken? Why was it taken? Was anything else taken? (Consider co-

ingestants: other things which may be in this person’s medicine cabinet.)

History continued.... Patients who overdose or use illicit

drugs may be unreliable. Gather info from paramedics, family,

friends, the PCP, old medical records, pill bottles the patient has on them, their occupational environment or by having people return to the scene where the incident took place.

History continued.... Obtain a clinical history from

family/friends or paramedics: - patient’s behavior prior to arrival - changing vital signs - seizures

Physical Examination: Vital Signs: You MUST obtain a full

set of vital signs, including blood glucose.

Vital signs are the key to your initial management of the patient....

Vital signs: Pulse Bradycardia Tachycardia (P.A.C.E.D.) (F.A.S.T.) Propanolol, poppies Freebase Anticholinesterases Anticholinergics/ Clonidine, CCB’s Antihistamines Ethanol Amphetamines Digoxin

SympathomimeticsSolventsTheophylline

Vital signs: TemperatureHypothermia Hyperthermia(C.O.O.L.S.) (N.A.S.A.)Carbon monoxide N.M.S., NicotineOpiates AntihistaminesOral hypoglycemics SalicylatesLiquor SympathomimeticsSedatives/Hypnotics Anticholinergics

Antihistamines

Vital signs: Blood pressureHypotension Hypertension(C.R.A.S.H.) (C.T.S.C.A.N.)Clonidine, CCB’s CocaineReserpine Thyroid

supplementsAntihypertensives SympathomimeticsAntidepressants CaffeineAminophylline AnticholinergicsSedative/Hypnotics AmphetaminesHeroin (opiates) Nicotine

Vital signs: Respiration rateHypoventilation Hyperventilation(S.L.O.W.) (P.A.N.T.)Sedative/Hypnotics PCPLiquor Pneumonitis Opiates NoncardiogenicWeed (marijuana) pulmonary edema

Toxic met. acidosis

Physical: Neurologic examMental status Seizures(AEIOU TIPS) (OTIS CAMPBELL)Alcohol OrganophosphatesEndocrine/Epilepsy TricyclicsIntoxication INH/InsulinOxygen SympathomimeticsUremia Camphor/CocaineTrauma/Tumor AmphetaminesInfection MethylxanthinesPsychological PCPShock/Strokes Benzo withdrawal

EthanolLead, LithiumLidocaine, Lindane

Physical exam: PupilsMiosis Mydriasis(C.O.P.S.) (A.A.A.S)Cholinergics AntihistaminesClonidine AntidepressantsOpiates AnticholiergicsOrganophosphates (Atropine)Pontine bleed SympathomimeticsPhenothiazines (Cocaine)Sedatives/Hypnotics

Physical: Dermatological examDiaphoresis Red Skin Blue Skin(S.O.A.P.) CO CyanosisSympathomimetics Boric Acid MetHbOrganophosphates AnticholinergicsASAPCPBlisteringBarbituates, CO, Sedative hypnotics, snake/spider

bites

Odors... Bitter almonds: CyanideMothballs: CamphorGarlic: Organophosphates,

ArsenicPeanuts: RodenticideCarrots: Water hemlockRotten eggs: Sulfur dioxide, HSWintergreen: Methyl salicylatesGasoline: HydrocarbonsFruity: DKA, IsopropanolPears: Chloral hydrate

Epidemiology of Toxicology... The majority of poisonings were

unintentional.... But, the majority of deaths secondary to poisoning were intentional.

Most poisonings are by ingestion and most poisonings occur at home.

Epidemiology continued...The most commonly reported poison?Analgesics!The least commonly reported? Alcohol!Which is associated with the most deaths?Analgesics!Which is associated with the least deaths?Hydrocarbons!The number one poisonous killer? Carbon monoxide!

Lab tests/Diagnostics... EKG. Why?To look for conduction delays and ischemia.(sympathomimetics, B-blockers, TCA’s,

digoxin, CCB’s, CO)CMP. Why?To calculate anion gap and osmolality. (CAT

MUD PILES and ME DIE mnemonics)Tylenol and Aspirin levels. Why?Because of the frequency of abuse and co-

ingestion.

Lab tests/diagnostics continued...Serum volatiles (this tells you quantitative

amounts of alcohols). Why? When?With AMS of unknown etiology, for legal

purposes, for unexplained osmolar gaps.Drug screens. Why? When?With urine: Screening purposes only. (This

rarely changes your management)With blood: For quantitative information

regarding specific ingestants.

Imaging...Chest XR: KUB:(Pulmonary Edema) (C.O.I.N.S.)(M.O.P.S.) Chloral hydrateMeprobamate Cocaine packetsMethadone Opiate packetsOpiates Iron (Heavy metals)Phenobarbital NeurolepticsPropoxyphene Sustained release/Salicylates enteric coated tabs.

Management...“Coma cocktail” (Dextrose, Narcan,

Thiamine)- Check blood sugars (the sixth vital

sign)- Narcan has side effects too!- Thiamine for the malnourishedFlumazenil is reserved for people who

we overdose with benzos!

Management (GI decontamination) Syrup of ipecac: Is not used Gastric lavage: - Used with “moderate to severe

overdoses” within an hour of ingestion. -There is a highly variable outcome with this intervention.

-Lavage is contraindicated with ingestion of corrosives.

GI decontamination continued... Activated charcoal:

- Purported to be superior to lavage - Used in toxic ingestions within an

hour of the ingestion. - Dosed as 1g/kg or 10:1 ratio of

charcoal to poison - Given as single dose or multiple dose

Multiple dose Not adsorbed(A.B.C.D.) (C.H.A.R.C.O.A.L.)Antimalarials Caustics/CorrosivesAminophylline Heavy metalsASA (?) AlcoholsBarbiturates Rapid onset cyanideB-Blockers (?) Chlorine/IodineCarbamazepine Other insolubles

(tabs)Dapsone AliphaticsDilantin (?) Laxatives

GI decontamination...Cathartics: - Given with charcoal to enhance

elimination - Unproven efficacy when used alone.Whole bowel irrigation:

- May be effective for things not adsorbed by charcoal

- Used for body stuffers/packers

Decontamination via enhanced elimination...Hemodialysis: Urine Alkalinization:(I.S.T.U.M.B.L.E.) ASA, PhenobarbitalIsopropanol (Alkalinizing the urine withSalicylates NaHCO3 to trap ions of weaklyTheophylline acidic agents to promoteUremia excretion). Methanol Titrate NaHCO3 to maintain Barbiturates urinary pH of 7.5-8.0.LithiumEthylene glycol

Management (Antidotes)...Toxin AntidoteAcetaminophen N-acetylcysteineAnticholinergics PhysostigmineArsenic/Lead BAL chelationB-Blockers GlucagonBenzos FlumazenilCO O2, HBOCyanide NitritesDigoxin Digibind Ethylene glycol/Methanol Fomepizole/EthanolIron DeferoxamineINH B6/PyridoxineLead/Mercury Succimer/DMSAMethemoglobinia Methylene blueOpioids NaloxoneOrganophosphates AtropineTCA’s Sodium bicarbonate

Pitfalls... Ingestion of multiple agents is

common Dangerous drug combinations Drugs masking the effects of other

drugs All altered mental status is not tox.

Consider trauma (head bleeds) and metabolic causes (DKA, Thyroid, etc)

Pearls... Always begin with airway, breathing,

circulation. The poisoned patient is not exempt from this mantra.

ACLS protocols generally apply to poisoned patients.

Treat the patient, not the poison. Observe vital signs and provide supportive care constantly.

Part II: Case studies

Case 1: Mr. Smith, a 28 year old male presents in police custody

complaining of chest pain. He has no other past medical history. No history of cardiac disease.

Patient further states that his chest pain began tonight about one to two hours after he was arrested by police. No history of trauma.Social history=Smokes 1 pack/day. Occasional EtOH.Family History= No cardiac deaths.

Mr. Smith

Physical exam... General: Patient very agitated, clutching his

chest. Vitals: P 140, BP 220/130 RR-28 Temp- 103.2F Eyes: Pupils 7mm, equal, EOMI Lungs: Clear Bilaterally Heart: Regular rate and rhythm, 2+/6 systolic

murmur Abd: Soft, Non-Tender, BS+ Neuro: No focal deficits. Skin: Diaphoretic

Differential diagnosis??? Sympathomimetics (cocaine? amphetamines?) Anticholinergics? Thyroid disease? Solvents? Antihistamines? Undiagnosed hypertension? Acute MI? Malingering? (Why did his symptoms begin an

hour after the arrest? Why not immediately?

What do you want to order? EKG? (grossly abnormal vital signs) CMP? TSH? UTox? Serum volatiles? Imaging? Cardiac enzymes?

EKG:

How should this person’s cocaine related chest pain be managed?1. Benzodiazepines- First line therapy (in

high doses) 2. Nitroglycerin- for control of ischemic pain

and HTN3. Labetalol- alpha/beta blocker (the use of

propranolol will leave the alpha portion unopposed theoretically exacerbating cocaine's toxicity). Alternatively, phentolamine could be used.

4. Nitroprusside- for refractory HTN

This person ingested bags of cocaine. What is the best method of GI decontamination?

IpecacWhole Bowel IrrigationCatharticsActivated CharcoalDialysisUrine alkalinizationGastric lavage

Should other services be involved? If so, whom? Tox! Surgery (Why?) Cardiology (Why?)

The outcome.... The patient's chest pain and hypertension eventually

resolve with large doses of nitroglycerin and benzodiazepines.

The patient is administered activated charcoal and polyethylene glycol solution by the ED physician.

Because of the ST segment elevations, the cardiologist elects to give thrombolytics.

Since thrombolytics were "on board" the general surgeon refuses to take the patient to the OR for exploratory laparotomy and removal of the cocaine packets.

The patient is transferred to the ICU, where he eventually recovers and is discharged with a 10% ejection fraction.

Case 2 The patient is a 18 year old male presenting

to the ED by paramedics after found at home unresponsive, face down in bed. According to friends, the patient had consumed two beers and a glass of wine earlier that day following a period of depression. The patient was orally intubated in the field by paramedics after no response to D50 and naloxone administration.

Physical exam: General: Patient responsive only to deep

painful stimuli Vitals: BP 150/70, HR=92, RR=24, T=95.4F Lungs: CTA, BS Equal, (Intubated) CV: RRR, no murmur Abd: Soft, Non-Tender, No Trauma, No

Masses Rectal: Normal Tone, Heme- Neuro: DTR's Hyporeflexive, Withdraws to

Painful Stimuli

Differential diagnosis?? Alcohol intoxication? Carbon monoxide? Sedatives/Hypnotics? (benzos?

barbiturates? muscle relaxants?) Tylenol? Trauma? Large doses of narcotics?

What do you want to order? CBC? CMP? Serum osmolality? Serum volatiles? Urine toxicology screen for drugs of

abuse? EKG?

Results: CBC: WBC 29K HCT=45 Lytes: Na=145 Cl=105 K=5.2 HCO3=5 BUN/Cr: 28/1.8 Glucose 180 Osm: 370 (Measured) ETOH: 46 Calcium 7.0 Toxicology Screen: Pending Toxic Alcohols: Pending What is his anion gap? What is his osmolar gap? AG: 20. Osmolar gap: 370 – (2(Na) + Glu/18

+BUN/2.8 +ETOH/4.6) = 50! (50 is greater than 10, so..... )

Results continued... EKG shows NSR. No interval

changes. No ST, T or Q wave changes. Normal axis. Normal R wave progression

CXR: Shows normal sized heart and mediastinum. No effusions or infiltrates. No acute disease. ETT in proper position.

How do you want to manage this patient? Supportive care only Gastric lavage Hemodialysis Is there a potential antidote for this? YES! Fomepizole! We don’t have any fomepizole. But we

do have ethanol!

Outcome... With a strong clinical suspicion for toxic alcohol

ingestion, an ethanol drip is ordered, but due to pharmacy delay, the patient is orally loaded with 85 proof whiskey obtained from another patient in the ER waiting room.

Urine is positive for calcium oxalate crystals. Dialysis is initiated by the renal service, after which an ethylene glycol level of 310 mg/dl returns 12 hours later.

The patient recovers with mild renal insufficiency, and is subsequently followed-up by the psychiatric service for his depression.

References... 1. Erickson TB et al. Toxicology Update: A Rational

Approach to Managing the Poisoned Patient. Emerg Med Pract. 2001; 3(8): 1-28

2. Tuckler, Victor. Introduction to Toxicology handout3. Rivers, Carol S. Preparing for the Written Board

Exam in Emergency Medicine. 5th Ed. Volume II. PP 735-738

4. “Case studies in Toxicology” available at: http://www.uic.edu/com/er/toxikon/cases/allcase.htm

5. http://www.med.umich.edu/lrc/baliga/case02/images/infMI2. jpg