think like a toxicologist steven a. seifert, md, facmt, faact professor, department of emergency...
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Think Like a Toxicologist
Steven A. Seifert, MD, FACMT, FAACT
Professor, Department of Emergency Medicine
Medical Director, New Mexico Poison Center
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