Position Paper: Recommendations for the Investigation, Diagnosis, and Certification of Deaths Related to Opioid and Other Drugs.

The National Association of Medical Examiners convened an expert panel to update the association's evidence-based recommendations for investigating and certifying deaths associated with opioids and other misused substances to improve death certificate and mortality data for public health surveillance. The recommendations are as follows:1. Autopsy provides the best information on a decedent's medical condition for optimal interpretation of toxicology results, circumstances surrounding death, medical history, and scene findings. The panel considers autopsy an essential component of investigating apparent overdose deaths.2. Scene investigation includes reconciling prescription information and medication counts. Investigators should note drug paraphernalia or other evidence of using intoxicating substances.3. Retain blood, urine, and vitreous humor whenever available. Blood from the iliofemoral vein is preferable to blood from more central sites.4. A toxicological panel should be comprehensive, including potent depressant, stimulant, and antidepressant medications. Detecting novel substances present in the community may require special testing.5. When death is attributed to a drug or combination of drugs (as cause or contributing factor), the certifier should list the drugs by generic name in the autopsy report and death certificate.6. The best classification for manner of death in an overdose without any apparent intent of self-harm is "accident."

Trends in fentanyl and fentanyl analogue-related overdose deaths - Montgomery County, Ohio, 2015-2017.

INTRODUCTION: There is a lack of information on illicitly manufactured fentanyl and fentanyl analogue-related (IMF) unintentional overdose death trends over time. The study analyzes IMF-related unintentional overdose fatalities that occurred between July 2015 and June 2017 in Montgomery County, Ohio, an area with the highest rates of unintentional overdose mortality in Ohio. METHODS: LC-MS/MS-based method was used to identify fentanyl analogs and metabolites in 724 unintentional overdose death cases. The Chi-square statistic was used to assess differences over time in demographic and drug-related characteristics. RESULTS: The number of unintentional overdose death cases testing positive for IMFs increased by 377% between second half of 2015 and first half of 2017. The majority of decedents were white (82.5%) and male (67.8%). The proportion of fentanyl-only (no other analogs) cases declined from 89.2%-24.6% (p < 0.001), while proportion of fentanyl analogue-containing cases increased from 9.8%-70.3% (p < 0.001) between the second half of 2015 and first half of 2017. The most commonly identified fentanyl analogs were carfentanil (29.7%), furanyl fentanyl (14.1%) and acryl fentanyl (10.2%). Proportion of IMF cases also testing positive for heroin declined from 21.6% to 5.4% (p < 0.001), while methamphetamine positive cases increased from 1.4%-17.8% (p < 0.001) over the same time period. DISCUSSION: Emergence of fentanyl analogs contributed to substantial increases in unintentional overdose deaths. The data indicate a growing overlap between the IMF and methamphetamine outbreaks. Continuous monitoring of local IMF trends and rapid information dissemination to active users are needed to reduce the risks associated with IMF use.

Child Fatalities Due to Heroin/Fentanyl Exposure: What the Case History Missed.

This case report presents three unrelated children found to have heroin and/or fentanyl in their systems after general unknown systematic toxicological analysis (STA). The first case involves an 11-month-old male found unresponsive at their residence. The scene response suggested a potentially unsafe sleeping condition or a sudden unexplained infant death. The second case is a 14-month-old female found unresponsive after eating soft candies, suggesting that a choking related death may have occurred. The third case is a 12-year-old male found unresponsive in bed and foaming from the mouth. Gum was removed from the child's airway, suggesting another choking related death. The STA included a 14-drug category enzyme linked immunosorbant assay (ELISA) screening in whole blood. Cases 1 and 3 were presumptively positive for fentanyl, while Case 2 was presumptively positive for opiates and fentanyl. Reflex confirmation was performed in blood, urine and gastric contents, by solid-phase extraction (SPE) for 12 opiates including morphine and 6-monoacetylmorphine (6MAM) by gas chromatography-mass spectrometry (GC-MS) and for fentanyl, norfentanyl, and novel analogs, by liquid chromatography tandem mass spectrometry (LC-MS-MS). High concentrations of fentanyl and 6MAM in the gastric contents of Case 1, along with the presence of diacetylmorphine, suggested probable enteral ingestion of heroin and fentanyl, separately or in a combined formulation. Interpretation of the toxicology results could not determine a probable route of exposure to heroin/fentanyl in Case 2, however, the cause of death was clearly related to this drug mixture. In Case 3, the presence of acetylfentanyl suggested an illicit fentanyl exposure. The intention of this case report is to demonstrate the need for a STA approach for all non-trauma postmortem cases regardless of case circumstances, age or suspicion of drug use.

Overdose Deaths Related to Fentanyl and Its Analogs - Ohio, January-February 2017.

Ohio is experiencing unprecedented loss of life caused by unintentional drug overdoses (1), with illicitly manufactured fentanyl (IMF) emerging as a significant threat to public health (2,3). IMF is structurally similar to pharmaceutical fentanyl, but is produced in clandestine laboratories and includes fentanyl analogs that display wide variability in potency (2); variations in chemical composition of these drugs make detection more difficult. During 2010-2015, unintentional drug overdose deaths in Ohio increased 98%, from 1,544 to 3,050.* In Montgomery County (county seat: Dayton), one of the epicenters of the opioid epidemic in the state, unintentional drug overdose deaths increased 40% in 1 year, from 249 in 2015 to 349 in 2016 (estimated unadjusted mortality rate = 57.7 per 100,000) (4). IMFs have not been part of routine toxicology testing at the coroner's offices and other types of medical and criminal justice settings across the country (2,3). Thus, data on IMF test results in the current outbreak have been limited. The Wright State University and the Montgomery County Coroner's Office/Miami Valley Regional Crime Laboratory (MCCO/MVRCL) collaborated on a National Institutes of Health study of fentanyl analogs and metabolites and other drugs identified in 281 unintentional overdose fatalities in 24 Ohio counties during January-February 2017. Approximately 90% of all decedents tested positive for fentanyl, 48% for acryl fentanyl, 31% for furanyl fentanyl, and 8% for carfentanil. Pharmaceutical opioids were identified in 23% of cases, and heroin in 6%, with higher proportions of heroin-related deaths in Appalachian counties. The majority of decedents tested positive for more than one type of fentanyl. Evidence suggests the growing role of IMFs, and the declining presence of heroin and pharmaceutical opioids in unintentional overdose fatalities, compared with 2014-2016 data from Ohio and other states (3-5). There is a need to include testing for IMFs as part of standard toxicology panels for biological specimens used in the medical, substance abuse treatment, and criminal justice settings.