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

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

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

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

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

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, 2000-2014 www.cdc.gov/drugoverdose/data/analysis.html

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

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)

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

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.

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

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

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

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

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

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

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

Thank you for your attention! UPMC Medical Toxicology Service via MedCall: 412.647.7000 Thank you for your attention! Questions?