Think Like a Toxicologist

Steven A. Seifert, MD, FACMT, FAACT

Professor, Department of Emergency Medicine

Medical Director, New Mexico Poison Center

sseifert@salud.unm.edu

The Poisoning Problem Poisoning is the #1 cause of trauma-

related deaths (estimated 50,000/yr) > 2.3 m exposures reported to US

Poison Centers in 2013 52% in children < 6 Reason:

Intentional 16%; Unintentional 84% Deaths

1190 (0.05%) 19% of unintentional deaths therapeutic

error

Poison Center System American Association of Poison Control

Centers (AAPCC) (www.aapcc.org) Center accreditation Specialist in poison information (SPI)

certification National Poison Data System

Data Use Annual Report (281 pages) publically available:

www.aapcc.org Federal advocacy

55 Regional Poison Centers Save lives / Save money / Deliver regional

benefits Cost avoidance Indirect (and direct) patient care / consultation Demographics / Toxicosurveillance Continuity of Care Research Prevention/Education

Susan Smolinske, PharmD, DABAT,Managing Director

Heather Admin Asst.

Holly, PharmD, CSPI

Damon, PharmD, CSPI

Karen, PharmD

Stevie, PharmD, CSPI

Jennifer, PharmD, CSPI

LaDonna PharmD, CSPI

Sara, PharmD, CSPI

Rose, PharmD, CSPI

Lee, PharmD, CSPI

Gordon, PharmD, CSPI

Suzi

Drug Info.

Steven Seifert, MD Medical Director

Poisoning Morbidity and Mortality

Morbidity Moderate and major effects: 138,000 =

5.7 % of exposures (NPDS) Mortality

~1,500 deaths reported to PCs = 0.05% of exposures

0.0022% of pediatric exposures 20 deaths in NM (2013)

NM deaths = 0.1% of exposures (double national average)

Management Site

74% Managed outside of healthcare facility

22.4% Managed in healthcare facility 3.3% Admitted to ICU

Top 5 Substances in Human Exposures

1. Analgesics (primarily APAP)2. Cosmetics / Personal Care Products3. Cleaning Substances4. Sedative/Hypnotics/Antipsychotics5. Foreign Bodies/Misc

Top 5 Substances in Pediatric Exposures

1.1. Cosmetics and Personal Care Cosmetics and Personal Care ProductsProducts

2.2. AnalgesicsAnalgesics

3.3. Cleaning substancesCleaning substances

4.4. Foreign Bodies / MiscForeign Bodies / Misc

5.5. Topical PreparationsTopical Preparations

Top 10 Categories in Fatalities1. Sedative/Hypnotics/Antipsychotics2. Cardiovascular Drugs3. Opioids4. Acetaminophen Combinations5. Stimulants and Street Drugs6. Acetaminophen Alone7. Alcohols8. Antidepressants9. Serotonin Reuptake inhibitors10. Antihistamines

Evidence-based Practice

Grade “A” studies on GI decontamination; antidote development & use; enhanced elimination, etc.

Consensus documents Triage criteria Managements

Example: Trends in GID: 1986-04

0

5

10

15

1986 2004

Ipecac

Lavage

Char coal

IpecacLavageCharcoal

%

0.2

5.6

0.6613.3

1.6

5.2

Anchor Bias/Hidden Tox Context of discovery may predispose to Context of discovery may predispose to

too rapid attribution of toxicologic etiologytoo rapid attribution of toxicologic etiology ““Facts” are fluid Facts” are fluid Beware anchor biasBeware anchor bias

Keep tox in differential / Occult Keep tox in differential / Occult presentationspresentations CO; APAPCO; APAP Drug accumulation (ASA, Dig, Li, Phenytoin)Drug accumulation (ASA, Dig, Li, Phenytoin) Drugs of abuse (myriad presentations/hidden Drugs of abuse (myriad presentations/hidden

hx)hx) Drug-drug/Drug-food interactionsDrug-drug/Drug-food interactions Adverse drug effectsAdverse drug effects WithdrawalWithdrawal

One More Thing

Use a drug-drug interaction tool Use a drug-drug interaction tool with EVERY prescription you writewith EVERY prescription you write

CaseCase

17 yo f, unresponsive at home in the 17 yo f, unresponsive at home in the morningmorning Empty pill bottles belonging to her Empty pill bottles belonging to her

parentsparents OxycodoneOxycodone AtenololAtenolol GabapentinGabapentin SertralineSertraline MetforminMetformin

Case

SocHx: Stressful home situation / recent

departure of father No prior history of overdose or self-

harm Patient’s medications: None Allergies: None

Think Like A Toxicologist What’s the DDx? What is the “standard” workup of the

unresponsive patient w/ tox in the ddx What are the expected toxic effects of

the known or suspected substances? Does the clinical presentation match?

Pharmacodynamics: What additive, antagonistic, and/or

synergistic effects might be anticipated? Pharmacokinetics:

What duration of effects anticipated?

Think Like A Toxicologist What evaluations would be helpful

Clinical exam Labs Other diagnostic tests

What are the tox-specific managements Decontamination? Specific antidotes? Enhanced elimination? Symptomatic/supportive care?

Case: What’s the DDx? Causes of unresponsiveness?Causes of unresponsiveness?

Acute medication/substance overdoseAcute medication/substance overdose InfectionsInfections Metabolic disordersMetabolic disorders Trauma / ICB / Endocrine / etc.Trauma / ICB / Endocrine / etc.

Standard” workup of the unconscious / Standard” workup of the unconscious / unresponsive patient w/ tox in the ddxunresponsive patient w/ tox in the ddx BMPBMP ECGECG Acetaminophen (APAP); SalicylateAcetaminophen (APAP); Salicylate Other tests based on history / exam / Other tests based on history / exam /

contextcontext

Case: Physical Exam

Vitals: HR 52, BP 70/48, RR

8, Sat 84% Temp 37 General:

Unresponsive HEENT:

Membranes moist Supple neck Pupils 1-2mm; react

poorly

CV: Bradycardia Lungs: Clear Abdomen: Benign;

no BS Skin: Warm, dusky,

dry Neuro: Non-focal

OxycodoneAtenololGabapentinSertralineMetformin

Labs / Other Tests

CBC – Normal Chem 7

Na 140 K 4.1 Cl 100 Bicarb 15 Bun 18 Cr 0.9 Glucose 55 Anion Gap ? Lactate 8

Urine pregnancy Negative

ASA = undetectable

APAP = 230 mg/dL U Tox

positive for opioids ECG

Sinus @ 50; QRS 80; QTc 560

OxycodoneAtenololGabapentinSertralineMetformin

What’s Going On?

Medication effectsMedication effects Oxycodone: CNS; RR; pupils; Opioid Oxycodone: CNS; RR; pupils; Opioid

ToxidromeToxidrome Atenolol: BP; Heart RateAtenolol: BP; Heart Rate Gabapentin/Sertraline: Additive CNSGabapentin/Sertraline: Additive CNS Sertraline: CNS depression; QTc Sertraline: CNS depression; QTc

prolongationprolongation Metformin: Hypoglycemia; Lactic Metformin: Hypoglycemia; Lactic

acidosis (MALA)acidosis (MALA)

OxycodoneAtenololGabapentinSertralineMetformin

What is a Toxidrome? What is a Toxidrome? = Toxic Syndrome= Toxic Syndrome

Collection / Constellation of findings that Collection / Constellation of findings that suggest a substance or substance classsuggest a substance or substance class Allows you to refine ddx, anticipate effects, Allows you to refine ddx, anticipate effects,

choose specific managements, avoid choose specific managements, avoid problemsproblems

Where to focus your attentionWhere to focus your attention VitalsVitals PupilsPupils Overall physical examinationOverall physical examination Think autonomic nervous system!Think autonomic nervous system!

Opioid Toxidrome

Miosis (+/-) Hypoventilation

(decreased resp. rate!)

Coma Bradycardia Hypotension

Anticholinergic Toxidrome

TachycardiaHTNUrinary retentionDecreased bowel soundsDry skinSeizuresHyperthermia

Cholinergic Toxidrome “SLUDGEB…B…B…

BAM” Sialorrhea Lacrimation Urination Diarrhea Gastric upset Emesis

Bradycardia, Bronchorrhea, Bronchospasm

Abdominal pain Miosis

Sympathomimetic Toxidrome

Diaphoresis Mydriasis Tachycardia Hypertension Hyperthermia Seizures

Other Toxidromes

Non-specific sedative-hypnotics Metabolic acidosis Serotonin syndrome Neuroleptic malignant syndrome Withdrawal syndromes Others

Management: Initial Steps Pre-hospital

Dextrose Oxygen Naloxone Thiamine

In-hospital / Supportive Care ABCs Monitor IV Oxygen Perfusion

Tox-specific Managements GI-decontamination?

Applicable < 5% of cases Mostly activated charcoal (AC); rarely

lavage or Whole Bowel Irrigation Specific Antidotes?

Indications; proper use; contraindications Enhanced elimination techniques?

Volume of distribution? Protein binding? Other properties?

Urine alkalinization; Multi-dose AC; Hemodialysis; Cardio-pulmonary bypass (ECMO)

Common Tox Presentations Agitation

Benzos; Ketamine; Propofol; RSI; Avoid neuroleptics Rhythm disturbances

Tachycardia: Usually does not require tx Calcium channel blockers; Avoid b-blockers

Bradycardia: Tx symptomatic Atropine; pacer

Hypotension Positioning; fluid expansion; pressors Empiric: Dopamine; NE; Neosynephrine;

Vasopressin Specific: Glucagon (b-blockers); Insulin (Ca-channel

blockers Seizures

Benzos; Pyridoxine; Levetiracetam; Propofol; Avoid phenytoin

Lipophilic cardiotoxics: Lipid emulsion; ECMO

Case: Management

Naloxone to reverse opioid effects Must be titrated to effect and avoid withdrawal

Atropine / Glucagon for b-blocker bradycardia/hypotension

Optimization of K, Ca, Mg for QTc, monitoring and preparedness to manage Torsades de Pointes

Monitoring of acidosis; bicarbonate if needed; hemodialysis if needed

N-acetylcysteine for elevated acetaminophen level

Nomogramfor Acute Acetaminophen

Exposures Use nomograms

and resources properly Do not send pre-4h

APAP Know application of

nomogram

Information Resources

MicroMedex (PoisIndex) Library Database (“M”)

Up-to-Date Library Database (“U”)

Other texts/pubmed/ etc. Use with expert guidance

2014.8 National Poison Data System New Mexico Poison Center Website National PC Number: 1-800-222-1222 Recent completion of clinical and

database studies Ongoing research

BWS AV Database studies Participation in ACMT ToxIC database Methamphetamine course (Aug 21)

Your Primary Resource in Poisoning

New Mexico Poison Center 1-800-222-1222

nationwide 2-2222 from within

UNMH Poison Specialists

24/7/365 Medical Toxicologist

always available