1. Opioid Overdose and Cardiac Arrest
Joseph Yanta, MD
Clinical Assistant Professor, Division of Medical Toxicology, Department of Emergency Medicine, UPSOM
Assistant Medical Director, Pittsburgh Poison Center

2. Presenter Disclosure Information
Joseph H. Yanta, MD Opioid Overdose and Cardiac Arrest Financial Disclosure: No relevant financial relationship exists

3. Session Objectives
Understand the incidence and prevalence of opioid-related death
Understand how outcomes after opioid-related out-of-hospital cardiac arrest (OOHCA) differ from non-opioid-related OOHCA
Understand other cardiac-related consequences opioids and opioid abuse

4. Game Plan Epidemiology Pathophysiology Prognosis
Opioid-induced dysrhythmia
Drug adulterants and cardiovascular pathology
Challenges in drug testing

5. Definitions
Opiate = alkaloid with opioid receptor binding derived from the poppy plant
Morphine
Codeine
Thebaine
Opioid = an agonist of opioid receptors
Semisynthetic: heroin, hydromorphone, oxycodone, etc.
Synthetic: fentanyl, methadone, tramadol, etc.
Opiate is to opioid as square as rectangle
Narcotic includes opioids as well as all other illegal drugs

6. Opioid Death Epidemiology
19,000 deaths per year due to prescription opioid overdose
52 deaths deaths per day
More than 10,500 deaths per year due to heroin
29 deaths per day
More people die from opioid overdose than either car accidents or gun violence
Available data likely underestimate true number of deaths
Drug overdose death involving opioids, by type of opioid, United States,

7. Opioid Death Epidemiology
Pennsylvania had the 8th-highest rate of drug overdose deaths in 2014
21.9/100,000
2,732 deaths overall
West Virginia had the highest

8. Opioid Death Epidemiology
Allegheny County Data
2015: 424 opioid overdose deaths
70% men
86% white
28% between ages 25-34
37% increase compared to 2014
234 deaths so far in 2016 (as of July 31)

9. Opioid Death Pathophysiology
Opioid agonism of m2-opioid receptors results in respiratory depression
Death due to asphyxiation and subsequent cardiovascular collapse and arrest
Complicated by: ischemic liver/kidney injury, rhabdomyolysis, aspiration pneumonitis, pulmonary edema

10. Opioid Overdose and OOHCA
Scant data exist comparing opioid- and non-opioid-related OOHCA
Elmer J, Lynch MJ et al. Recreational Drug Overdose-related Cardiac Arrests: Break on Through to the Other Side. Resuscitation. 2015; 89:177.

11. Opioid Overdose and OOHCA
Patients suffering overdose-related OOHCA (compared to non-overdose-related) are:
Younger
Healthier at baseline
More likely to present with a non-shockable rhythm, i.e. PEA or asystole
More likely to have worse initial neurologic examination
Survival, neurologic outcomes, length of stay do not differ from non-overdose-related subjects
Despite poorer initial neurologic examination

12. Post-Arrest Management
Little data exist to differentiate post-arrest management of the poisoned patient from the non-poisoned patient
Aggressive temperature control (euthermia) is still (probably) beneficial
Consideration for coronary disease in appropriate patients

13. Post-Arrest Challenges
Neuroprognostication
Hypothermia drug kinetics
Withdrawal syndromes
Management of multisystem organ injury
Rhabdomyolysis
Acute liver injury
Acute kidney injury

14. Challenges in Drug Testing
Urine drug immunoassays imply presence of drug, not causation
“Opiate” screen = morphine screen
Heroin metabolized to morphine
Positive screen does not prove causality
Negative screen does not disprove causality
So, the basic urine drug immunoassay screen is USELESS
Negative on “Opiate” Urine Drug Immunoassay
Methadone
Fentanyl (and derivatives)
Buprenorphine
Oxycodone (often)
Hydrocodone (sometimes)
Oxymorphone
Tramadol

15. Opioid-Associated Dysrhythmia
Propoxyphene – essentially unavailable in the United States
Sodium channel blockade
Methadone
Doses >100 mg/day associated with increased risk of sudden death
Inhibits Ikr resulting in QT prolongation

16. Drug Adulteration
Adulterant = intentional inclusion of xenobiotic in drug sample for dilution, synergistic, or maleficent intent
Contaminant = unintentional inclusion of a xenobiotic, usually as result of poor laboratory technique
E.g. lead, other heavy metals, codeine, MPTP

17. CV-Active Drugs as Adulterants
Quinine/quinidine
Procaine
Diltiazem
Atropine
Verapamil
Arsenic
Lidocaine
Clenbuterol
Caffeine

18. Thank you for your attention!
UPMC Medical Toxicology Service
via MedCall:
Thank you for your attention!
Questions?