J Forensic Sci, November 2014, Vol. 59, No. 6 doi: 10.1111/1556-4029.12541 Available online at: onlinelibrary.wiley.com PAPER PATHOLOGY/BIOLOGY; TOXICOLOGY Kristen J. Mertz,1 M.D., M.P.H.; Jennifer K. Janssen,2 M.S.; and Karl E. Williams,2 M.D. Underrepresentation of Heroin Involvement in Unintentional Drug Overdose Deaths in Allegheny County, PA ABSTRACT: Drugs contributing to overdose deaths are listed on death certificates, but their validity is rarely studied. To assess the accuracy of “morphine” and “codeine” listings on death certificates for unintentional overdose deaths in Allegheny County, PA, investigative and laboratory reports were reviewed. Deaths were reclassified as heroin-related if documentation showed 6-monoacetylmorphine in blood or urine, “stamp bags” or drug paraphernalia at scene, history of heroin use, or track marks. Deaths were considered morphine-related if notes indicated morphine use, prescription, or morphine at scene, or codeine-related if the codeine blood level exceeded morphine. Of 112 deaths with morphine but not heroin listed on the death certificate, 74 met heroin criteria and 21 morphine criteria. Of 20 deaths with both morphine and heroin listed, only one met morphine criteria. Of 34 deaths with codeine listed, only five were attributed to codeine. Consideration of patient history, death scene evidence, and expanded toxicology testing may improve the accuracy of death certificate drug listings. KEYWORDS: forensic science, overdose, poisoning, heroin, morphine, opioid analgesics The recent rise in drug overdose deaths in the US has been linked to an increase in the abuse and misuse of opioid analgesics (1,2). CDC reports that death certificate information indicates that opioid analgesics now account for more overdose deaths than heroin and cocaine combined (3). The accuracy of drug listings on death certificates, however, is rarely verified. A review of unintentional drug overdose deaths from 2008 through 2010 at the Allegheny County Office of the Medical Examiner (ACOME) in Pittsburgh, PA, indicated that heroin was listed as a contributing cause on 171 death certificates (unpublished data). The review also revealed 132 deaths with “morphine” listed on the death certificate, unexpected given the limited availability of pharmaceutical morphine as a drug of abuse compared with heroin. We were concerned about misclassification of heroin deaths as morphine deaths, given that heroin rapidly metabolizes to morphine. Similarly, we suspected that codeine was too often listed as a contributing cause of death (34 deaths), given that it can be detected as an impurity in heroin or morphine (4). We report here the results of an in-depth analysis of unintentional overdoses with morphine or codeine on the death certificate. Methods The Allegheny County Office of the Medical Examiner (ACOME) is charged with investigating all unnatural or suspicious 1 Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261. 2 Allegheny County Office of the Medical Examiner, 1520 Penn Avenue, Pittsburgh, PA 15222. Received 20 April 2013; and in revised form 13 Sept. 2013; accepted 12 Oct. 2013. © 2014 American Academy of Forensic Sciences deaths. All suspected drug overdoses reported to the office are screened for multiple drugs, including opiates by enzyme-linked immunosorbent assay (ELISA) with confirmation and quantitation by gas chromatography/mass spectrometry. ACOME also conducts external exams or full autopsies, on-site investigations, and interviews with next-of-kin for all suspected overdose deaths. The pathologist involved in the case completes the cause-of-death section of the death certificate and includes a list of drugs he believes contributed to death. We reviewed toxicology results, autopsy reports, and investigative reports for all deaths investigated by ACOME in 2008 through 2010 with “drugs and/or poisoning” listed as cause of death, “accidental” listed as manner, and “morphine” listed on the death certificate drug list. Deaths were reclassified as heroin deaths if reports indicated known heroin use; drug paraphernalia, typical glassine “stamp bags,” or heroin at the scene; track marks; or presence of 6-MAM at levels less than the limit of quantitation (5 ng/mL) but above the limit of detection. Morphine was considered a cause of death if the decedent had a prescription for morphine or a history of morphine use or abuse, or if morphine was found at the scene. Cases not meeting the criteria for heroin deaths or morphine deaths remained classified as morphine deaths for lack of a better determination. Toxicology results for all deaths with codeine listed on the death certificate were also reviewed. If the codeine concentration was greater than the morphine concentration, we assumed that codeine administration was responsible (5–7). If codeine was detectable only in urine and morphine or 6-MAM was detected, or if the codeine concentration was less than that of morphine, we assumed that codeine represented an impurity in commercial morphine or heroin and that codeine did not contribute to the death (4,7,8). 1583 1584 JOURNAL OF FORENSIC SCIENCES FIG. 1––Unintentional drug overdose deaths involving heroin, morphine, or codeine according to death certificates and after reclassification, Allegheny County, 2008-2010. Results Of 112 unintentional poisoning deaths with morphine but not heroin listed on the death certificate, 74 (66%) met our criteria for heroin involvement. Of these 74 decedents, a history of heroin use was noted for 52, drug paraphernalia or stamp bags (often both) were found at the scene for 33, heroin verified by drug chemistry was found at the scene for 7, and track marks were noted on 5; 6-MAM was detected in blood or urine of 17 although at a level <5 ng/mL for 11. Almost half (47%) of the 74 deaths involved more than one of these criteria. For the 112 deaths with morphine but not heroin listed on the death certificate, toxicology results indicated that morphine was detected in all of these cases; however, only 21 of these deaths satisfied our criteria for morphine-related deaths, based on a history of morphine use/abuse, having a prescription for morphine, or morphine found at the scene. Another 19 with morphine detected did not meet our criteria for implicating heroin; thus we left them classified as morphine. Of the 20 deaths with both heroin and morphine listed on the death certificate, all 20 met our criteria for heroin involvement, but only one met our criteria for morphine involvement. For 34 deaths with codeine listed on the death certificate, only 5 (15%) met our criteria for codeine involvement with codeine level greater than morphine level. For 28 deaths, codeine was most likely detected as an impurity in morphine or heroin. One death had no evidence of codeine. Our review led to revisions in the number of unintentional overdose deaths attributed to heroin, morphine, and codeine in Allegheny County in 2008 through 2010 (Fig. 1). According to drugs listed on death certificates, heroin was involved in 171 deaths, morphine in 132, and codeine in 34. After this review, we attributed a total of 245 deaths to heroin, including the 171 originally identified from death certificates plus 74 identified by this review, 41 to morphine, and five to codeine. Discussion Over 27,000 persons per year die from unintentional drug overdoses in the United States (9). Public health officials rely on death certificates for assessing the contribution of specific drugs to overdose deaths, but the validity of death certificate information is rarely evaluated. In Allegheny County, we found that morphine was overreported as a cause of death on death certificates; heroin was most likely responsible for a majority of deaths attributed to morphine. Other jurisdictions suspect that some heroin deaths are misclassified as morphine deaths (10), but the extent of the problem nationwide is unknown. In Allegheny County, we also found that codeine was most likely overreported as a cause of unintentional drug overdose deaths. If other jurisdictions are similarly overreporting morphine and codeine, national data on unintentional poisoning may overestimate the contribution of prescription opiates and underestimate heroin involvement. Medical examiners (MEs) and coroners are responsible for investigating poisoning deaths and for completing the cause-ofdeath section of the death certificate. When determining which drugs contribute to death, pathologists must consider multiple factors, such as drug combinations, levels and ratios; drug history of the decedent; evidence at the scene of death; and time lapse from overdose to autopsy (11,12). Merely listing drugs detected by toxicology on the death certificate is misleading; thorough investigation is needed to supplement toxicology results. Given that morphine is a metabolite of heroin and codeine, its detection could indicate the use of one of these drugs or morphine sulfate. Also drug impurities may give misleading results, as codeine did here. In some situations, additional toxicology studies may help classify cases. Detection of 6-MAM confirms heroin involvement but it rapidly breaks down in the blood and may not be detectable even when heroin is involved; 6-MAM is more stable in urine or vitreous fluid (13). ACOME does a basic drug screen and targeted 6-MAM testing on urine when available but does not test vitreous fluid for 6MAM, so some heroin cases may have been missed. Targeted testing of the vitreous for 6-MAM may be useful when urine is not available or when blood tests suggest but cannot confirm heroin involvement (13,14). National surveillance of the drug overdose epidemic is often based on death certificate data which is not always accurate or complete. National guidelines to encourage more thorough review and documentation of the cause of death on death certificate may help to standardize practices and improve data quality. For opiate overdose deaths, consideration of the decedent’s drug history, evidence from the death scene, and expanded testing for 6-MAM in the vitreous humor may correctly identify more heroin deaths. A more accurate picture of the drug death epidemic can strengthen medical, legal, and rehabilitation programs designed to prevent these premature deaths. Acknowledgments We thank the staff of the ACOME for maintaining the data management system and providing data for this investigation. We also thank Valerie Alstadt of the University of Pittsburgh for her review of deaths attributed to morphine, including review of investigators’ reports and toxicology results. References 1. Paulozzi LJ, Budnitz DS, Xi Y. Increasing deaths from opioid analgesics in the United States. Pharmacoepidemiol Drug Saf 2006;15:618–27. 2. Warner M, Chen LH, Makuc DM. Increase in fatal poisonings involving opioid analgesics in the United States, 1999–2006. NCHS Data Brief 2009;22:1–8. 3. 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Pragst F, Spiegel K, Leuschner U, Hager A. Detection of 6-acetylmorphine in vitreous humor and cerebrospinal fluid – comparison with urinary analysis for proving heroin administration in opiate fatalities. J Anal Toxicol 1999;23:168–72. Additional information and reprint requests: Kristen J. Mertz, M.D., M.P.H. University of Pittsburgh 512 Parran Hall 130 DeSoto Street Pittsburgh, PA 15261 E-mail: mertzk@edc.pitt.edu