Deaths Involving Fentanyl, Fentanyl Analogs, and U-47700 — 10 States, July–December 2016

Julie K. O'Donnell, PhD; John Halpin, MD; Christine L. Mattson, PhD; Bruce A. Goldberger, PhD; R. Matthew Gladden, PhD

Disclosures

Morbidity and Mortality Weekly Report. 2017;66(43):1197-1202. 

In This Article

Abstract and Introduction

Introduction

Preliminary estimates of U.S. drug overdose deaths exceeded 60,000 in 2016 and were partially driven by a fivefold increase in overdose deaths involving synthetic opioids (excluding methadone), from 3,105 in 2013 to approximately 20,000 in 2016.[1,2] Illicitly manufactured fentanyl, a synthetic opioid 50–100 times more potent than morphine, is primarily responsible for this rapid increase.[3,4] In addition, fentanyl analogs such as acetylfentanyl, furanylfentanyl, and carfentanil are being detected increasingly in overdose deaths[5,6] and the illicit opioid drug supply.[7] Carfentanil is estimated to be 10,000 times more potent than morphine.[8] Estimates of the potency of acetylfentanyl and furanylfentanyl vary but suggest that they are less potent than fentanyl.[9] Estimates of relative potency have some uncertainty because illicit fentanyl analog potency has not been evaluated in humans. This report describes opioid overdose deaths during July–December 2016 that tested positive for fentanyl, fentanyl analogs, or U-47700, an illicit synthetic opioid, in 10 states participating in CDC's Enhanced State Opioid Overdose Surveillance (ESOOS) program.* Fentanyl analogs are similar in chemical structure to fentanyl but not routinely detected because specialized toxicology testing is required. Fentanyl was detected in at least half of opioid overdose deaths in seven of 10 states, and 57% of fentanyl-involved deaths also tested positive for other illicit drugs, such as heroin. Fentanyl analogs were present in >10% of opioid overdose deaths in four states, with carfentanil, furanylfentanyl, and acetylfentanyl identified most frequently. Expanded surveillance for opioid overdoses, including testing for fentanyl and fentanyl analogs, assists in tracking the rapidly changing illicit opioid market and informing innovative interventions designed to reduce opioid overdose deaths.

The 10 states reporting data abstracted information from preliminary death certificates and medical examiner/coroner reports on unintentional and undetermined opioid overdose deaths using standard definitions for variables. Data were entered into the State Unintentional Drug Overdose Reporting System (SUDORS), the component of ESOOS designed for tracking fatal opioid overdoses.§ For each death, available data on demographic characteristics, circumstances of the overdose collected from death scene investigations (e.g., evidence of illicit drug use), and results of forensic toxicology testing were entered into SUDORS. Opioid overdose deaths occurring during July–December 2016 with positive test results for fentanyl, fentanyl analogs, and U-47700 in 10 states are described, and key demographic and overdose circumstance factors are stratified by substance. Full toxicology findings of decedents were reviewed, including the presence of heroin, cocaine, and methamphetamine. Because heroin involvement in overdose deaths is difficult to distinguish from prescription morphine, deaths in which heroin was confirmed by toxicologic findings were combined with deaths in which heroin was suspected because morphine was detected and death scene evidence suggested heroin use. The use of medical examiner/coroner reports, previously unavailable across states, provides unique insights into specific substances and circumstances associated with overdoses, which can inform interventions.

Fentanyl was detected in 56.3% of 5,152 opioid overdose deaths in the 10 states during July–December 2016 (Figure). Among these 2,903 fentanyl-positive deaths, fentanyl was determined to be a cause of death by the medical examiner or coroner in nearly all (97.1%) of the deaths. Northeastern states (Maine, Massachusetts, New Hampshire, and Rhode Island) and Missouri** reported the highest percentages of opioid overdose deaths involving fentanyl (approximately 60%–90%), followed by Midwestern and Southern states (Ohio, West Virginia, and Wisconsin), where approximately 30%–55% of decedents tested positive for fentanyl. New Mexico and Oklahoma reported the lowest percentage of fentanyl-involved deaths (approximately 15%–25%). In contrast, states detecting any fentanyl analogs in >10% of opioid overdose deaths were spread across the Northeast (Maine, 28.6%, New Hampshire, 12.2%), Midwest (Ohio, 26.0%), and South (West Virginia, 20.1%) (Figure) (Table 1).

Figure.

Percentage of opioid overdose deaths testing positive for fentanyl and fentanyl analogs, by state — 10 states, July–December 2016

Fentanyl analogs were present in 720 (14.0%) opioid overdose deaths, with the most common being carfentanil (389 deaths, 7.6%), furanylfentanyl (182, 3.5%), and acetylfentanyl (147, 2.9%) (Table 1). Fentanyl analogs contributed to death in 535 of the 573 (93.4%) decedents. Cause of death was not available for fentanyl analogs in 147 deaths.†† Five or more deaths involving carfentanil occurred in two states (Ohio and West Virginia), furanylfentanyl in five states (Maine, Massachusetts, Ohio, West Virginia, and Wisconsin), and acetylfentanyl in seven states (Maine, Massachusetts, New Hampshire, New Mexico, Ohio, West Virginia, and Wisconsin). U-47700 was present in 0.8% of deaths and found in five or more deaths only in Ohio, West Virginia, and Wisconsin (Table 1). Demographic characteristics of decedents were similar among overdose deaths involving fentanyl analogs and fentanyl (Table 2). Most were male (71.7% fentanyl and 72.2% fentanyl analogs), non-Hispanic white (81.3% fentanyl and 83.6% fentanyl analogs), and aged 25–44 years (58.4% fentanyl and 60.0% fentanyl analogs) (Table 2).

Other illicit drugs co-occurred in 57.0% and 51.3% of deaths involving fentanyl and fentanyl analogs, respectively, with cocaine and confirmed or suspected heroin detected in a substantial percentage of deaths (Table 2). Nearly half (45.8%) of deaths involving fentanyl analogs tested positive for two or more analogs or fentanyl, or both. Specifically, 30.9%, 51.1%, and 97.3% of deaths involving carfentanil, furanylfentanyl, and acetylfentanyl, respectively, tested positive for fentanyl or additional fentanyl analogs. Forensic investigations found evidence of injection drug use in 46.8% and 42.1% of overdose deaths involving fentanyl and fentanyl analogs, respectively. Approximately one in five deaths involving fentanyl and fentanyl analogs had no evidence of injection drug use but did have evidence of other routes of administration. Among these deaths, snorting (52.4% fentanyl and 68.8% fentanyl analogs) and ingestion (38.2% fentanyl and 29.7% fentanyl analogs) were most common. Although rare, transdermal administration was found among deaths involving fentanyl (1.2%), likely indicating pharmaceutical fentanyl (Table 2). More than one third of deaths had no evidence of route of administration.

*CDC's Enhanced State Opioid Overdose Surveillance program funded 12 states through a competitive application process in fiscal year 2016. Data were available for this report for 10 of the 12 states. https://www.cdc.gov/drugoverdose/foa/state-opioid-mm.html.
Maine, Massachusetts, Missouri (data available for 22 counties), New Hampshire, New Mexico, Ohio, Oklahoma, Rhode Island, West Virginia, and Wisconsin
§State Unintentional Drug Overdose Reporting System (SUDORS) estimates of opioid-involved overdose deaths might differ from those of the National Vital Statistics System because SUDORS uses preliminary death certificate data and collects additional information from medical examiner and coroner reports, which are abstracted within 8 months of death. In SUDORS, an opioid-involved overdose death either was identified through review of the medical examiner/coroner report or had International Classification of Disease, Tenth Revision (ICD-10) underlying cause-of-death codes X40–44 (unintentional) or Y10–Y14 (undetermined) and multiple cause-of-death codes T40.0, T40.1, T40.2, T40.3, T40.4, or T40.6 on the death certificate. Data for this report were downloaded on September 5, 2017.
A confirmed heroin death is defined as a death that tested positive for the heroin metabolite 6-acetylmorphine. The heroin metabolite 6-acetylmorphine, however, rapidly metabolizes to morphine, and thus a death involving heroin might only test positive for morphine, which is also present in deaths involving prescription morphine. A suspected heroin death is one in which testing for morphine is positive and the decedent also has a history of heroin use or death scene evidence indicating illicit drug use or injection in the absence of any evidence of prescription drug use or use of prescription morphine. https://www.ncbi.nlm.nih.gov/pubmed/25041514.
**Illicitly manufactured fentanyl is more easily mixed with white powder heroin, which is primarily sold east of the Mississippi River, than with black tar heroin. Although white powder heroin dominates the heroin market in the Northeast, the heroin market in Missouri includes both white powder heroin and black tar heroin. This might, in part, explain the high percentage of fentanyl overdoses documented in the state. Additional information available at https://www.justice.gov/archive/ndic/dmas/Midwest_DMA-2011(U).pdf.
††Data on whether fentanyl analogs contributed to the death in which they were detected was not available for 20.4% of deaths with fentanyl analogs. As new fentanyl analogs emerged, they were captured as free text (without the option to indicate whether they contributed to the death) until being added to the menu of substances in the toxicology portion of SUDORS.

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