Publications by authors named "Sandra C Bishop-Freeman"

10 Publications

  • Page 1 of 1

Pediatric opioid fatalities: What can we learn for prevention?

J Forensic Sci 2021 Apr 23. Epub 2021 Apr 23.

North Carolina Office of Chief Medical Examiner, Raleigh, NC, USA.

The aim of this study was to highlight 19 cases investigated by the North Carolina Office of the Chief Medical Examiner over the last 12 years involving accidental or undetermined manner of death opioid ingestions leading to fatalities in young children. These pediatric ingestions have closely mirrored the opioid epidemic in adults transitioning from prescription medications to illicit drugs including fentanyl and fentanyl analogues. Unlike a typical adult ingestion for purposes of self-harm or pleasure, poisonings in toddlers and infants are usually the result of curiosity, exploration, a decreased sense of danger, or imitation of adult or older sibling behavior. Eleven of the decedents were between the ages of 8 and 24 months. Among the cases were 12 prescription opioid exposure deaths and 7 illicit drug poisonings. A majority of the decedents were found unresponsive in an unkept home and/or in unsafe sleeping spaces with easy access to drugs or drug materials, which stresses the importance of safe pediatric sleeping conditions. After a complete pathological investigation, several of the cases had physical or scene evidence demonstrating that foil, plastic, or paper small enough to be ingested can contain enough potent opioid to cause death. Details from the toxicological investigation are included for each case to provide postmortem whole blood drug concentrations for forensic practitioners. Accidental pediatric poisonings are preventable. Risk reduction through improving awareness and education of the dangers of opioids is a key factor in mitigating these tragedies.
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http://dx.doi.org/10.1111/1556-4029.14725DOI Listing
April 2021

Death from Poppy Tea Consumption.

J Anal Toxicol 2020 Oct;44(7):734-740

Office of the Chief Medical Examiner, 4312 District Dr, Raleigh, NC, 27607, USA.

The historical practice of brewing poppy tea for its opioid-like effects is reoccurring with modern-day substance users. We present four postmortem cases with toxicology results that serve as case studies for the potential hazards of poppy tea ingestion. There is limited information regarding the risks of this practice due to the variability of the morphine content of the opium exuded from the plant. While internet tea recipes offer guidance, differences in poppy cultivation, washing, and infusing time are some of the reasons why the beverage may contain inconsistent and clinically significant alkaloid concentrations for each preparation. Variability in opioid tolerance along with additional drugs taken will impact the overall degree of toxicity experienced from the opiates in the tea. Advancements in the genetic modification of the poppy plant could greatly alter the ratio of alkaloids seen in biological fluids and will be highly dependent on the source of the poppy product. The blood concentrations of free morphine and free codeine in cases 1-3 where the toxicity from the tea was considered the primary cause of death were 0.94 and 0.11 mg/L, 0.62 and 0.034 mg/L, and 0.16 and 0.010 mg/L, respectively. The urine concentrations of morphine and codeine were 13 and 0.94 mg/L in case 1 and 16 and 1.6 mg/L in case 2, respectively. The opium alkaloids thebaine and laudanosine were identified qualitatively by our routine organic base/neutral drug detection procedure.
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http://dx.doi.org/10.1093/jat/bkaa093DOI Listing
October 2020

Evaluation of Synthetic Cannabinoid Metabolites in Human Blood in the Absence of Parent Compounds: A Stability Assessment.

J Anal Toxicol 2021 Feb;45(1):60-68

Center for Forensic Science Research and Education (CFSRE) at the Fredric Rieders Family Foundation, 2300 Stratford Ave, Willow Grove, PA 19090, USA.

Synthetic cannabinoids represent a chemically diverse class of novel psychoactive substances (NPS) responsible for large analytical and interpretative challenges for forensic toxicologists. Between 2016 and 2019, the three most prevalent synthetic cannabinoids in the United States were MMB-FUBINACA (FUB-AMB), 5F-MDMB-PINACA (5F-ADB) and 5F-MDMB-PICA, based on results from seized drug and toxicology testing. In 2018, accurate determination of synthetic cannabinoid positivity was brought into question as it was determined that the metabolites of these drug species were present in the absence of parent compounds in forensically relevant blood samples. During this study, the stability of MMB-FUBINACA, 5F-MDMB-PINACA and 5F-MDMB-PICA was evaluated, as well as the characterization of breakdown products. A liquid-liquid extraction method was assessed for recovery of basic parent compounds and acidic metabolites and deemed fit for use in this study. Analysis was performed by liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) using a SCIEX TripleTOF® 5600+. All three synthetic cannabinoids were found to be unstable when stored in blood at either room temperature or refrigerated; all analytes were considerably more stable when stored in the freezer. All three synthetic cannabinoids degraded to their respective butanoic acid metabolites: MMB-FUBINACA 3-methylbutanoic acid, 5F-MDMB-PINACA 3,3-dimethylbutanoic acid and 5F-MDMB-PICA 3,3-dimethylbutanoic acid. All three of these metabolites were studied and determined to be stable in blood at all storage conditions. Considering these results, our laboratory continued testing for synthetic cannabinoid metabolites in blood samples and found 83 positives (21%) for only a synthetic cannabinoid metabolite. A case report is presented herein where 5F-MDMB-PINACA 3,3-dimethylbutanoic acid was identified in the absence of 5F-MDMB-PINACA. Forensic toxicologists should be aware of the results of this study as they directly impact analytical consideration for test development and implementation, as well as interpretation of findings.
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http://dx.doi.org/10.1093/jat/bkaa054DOI Listing
February 2021

False-Positive Enzymatic Alcohol Results in Perimortem Specimens.

Lab Med 2020 Jul;51(4):394-401

Center for Forensic Sciences, RTI International, Research Triangle Park, NC.

Herein, we present 2 cases referred to the North Carolina Office of the Chief Medical Examiner (NC OCME) in which ethanol results reported by different hospital laboratories, using alcohol dehydrogenase (ADH)-based assays, were positive, whereas results of headspace gas chromatography testing performed in the NC OCME laboratory were negative. Literature reports suggest that false-positive ethanol measurements from ADH-based assays can occur when a combination of elevated lactate and lactate dehydrogenase (LD) are present in the specimen. The results were reported in perimortem specimens collected from 2 children with unrelated medical conditions. The cases and associated clinical parameters are considered based on the lactate/LD explanation for the false-positive results, to facilitate the recognition of circumstances that can produce erroneous serum ethanol results.
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http://dx.doi.org/10.1093/labmed/lmz082DOI Listing
July 2020

Effects of Bariatric Surgery Observed in Postmortem Toxicology Casework.

J Anal Toxicol 2019 Sep;43(8):651-659

Center for Forensic Sciences, RTI International, Research Triangle Park, NC, USA.

Bariatric surgery has been on the rise and patients often have multiple indications for pre- and post-operative pharmacotherapy. Procedures target the stomach and/or small intestine and affect weight loss through restriction, malabsorption, or a combination of the two. The absorption and/or metabolism of drugs via the gastrointestinal tract could be altered by different mechanisms. Several cases at the North Carolina Office of the Chief Medical Examiner's Toxicology Laboratory (NCOCME) have raised questions about the potential impact of these procedures on the disposition of drugs in the body and how that altered disposition may affect cause and manner of death. Overmedication and postmortem redistribution are not enough to explain the phenomena seen in some NCOCME bariatric surgery-related casework. Case examples include a 46-year-old female with a history of Roux-en-Y gastric bypass (RYGB) who suffered a witnessed collapse. Toxicological findings included elevated concentrations of oxymorphone at 0.49 mg/L in vena cava blood. A 67-year-old female, who died from vomiting and bacterial gastritis one day after placement of two intragastric weight-loss balloons, had elevated concentrations of duloxetine at 1.4 mg/L in the iliac vein blood and 9.3 mg/kg in the liver. Her medication was strictly controlled by her sister and gastric contents were without intact tablets or residue at autopsy.
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http://dx.doi.org/10.1093/jat/bkz062DOI Listing
September 2019

Degradation of Bupropion: Implications for Interpretation of Postmortem Case Data.

J Anal Toxicol 2018 Oct;42(8):525-536

North Carolina Office of the Chief Medical Examiner, Raleigh, NC, USA.

The interpretation of postmortem bupropion is often a challenge to the forensic toxicology community because of the instability of the parent compound. At the North Carolina Office of the Chief Medical Examiner (NC OCME) toxicology laboratory, one of the active metabolites, threobupropion, is used as a complementary indicator for the extent of exposure to the parent compound. Metabolite data will address postmortem normal concentrations as well as when bupropion was attributed to the cause of death. For 55 natural cases where bupropion was unattributed to the cause of death, the blood and liver mean threobupropion concentrations were 1.8 mg/L and 12.1 mg/kg, respectively, with median concentrations of 1.5 mg/L and 10 mg/kg, respectively. For the 51 suicidal ingestion cases when bupropion was attributed to the cause of death, the blood and liver mean threobupropion concentrations were 15.8 mg/L and 131.5 mg/kg, respectively, with median concentrations of 13.5 mg/L and 110 mg/kg, respectively. The laboratory completed a stability study over the course of 50 days to evaluate how bupropion and threobupropion degrade in postmortem blood, liver and liver homogenate. The samples were subjected to forensically relevant conditions by storing them at room temperature (RT, 20°C), refrigerated (4°C) and frozen (-20°C). While the concentration of bupropion decreased in all specimens, the rate of degradation of the RT samples was the most dramatic. The threobupropion metabolite appeared to be relatively stable. The postmortem case data along with the evaluation of potential degradation products should provide an overall picture to assist the toxicological community with the interpretation of bupropion found in routine casework.
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http://dx.doi.org/10.1093/jat/bky058DOI Listing
October 2018

Benzonatate Toxicity: Nothing to Cough At.

J Anal Toxicol 2017 06;41(5):461-463

North Carolina Office of the Chief Medical Examiner, Raleigh, NC, USA.

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http://dx.doi.org/10.1093/jat/bkx021DOI Listing
June 2017

Loperamide-Related Deaths in North Carolina.

J Anal Toxicol 2016 Oct 29;40(8):677-686. Epub 2016 Jul 29.

North Carolina Office of the Chief Medical Examiner, Raleigh, NC 27607, USA.

Loperamide (Imodium) has been accepted as a safe, effective, over-the-counter anti-diarrheal drug with low potential for abuse. It is a synthetic opioid that lacks central nervous system activity at prescribed doses, rendering it ineffective for abuse. Since 2012, however, the North Carolina Office of the Chief Medical Examiner has seen cases involving loperamide at supratherapeutic levels that indicate abuse. The recommended dose associated with loperamide should not exceed 16 mg per day, although users seeking an opioid-like high reportedly take it in excess of 100 mg per dose. When taken as directed, the laboratory organic base extraction screening method with gas chromatography-mass spectrometry/nitrogen phosphorus detector lacks the sensitivity to detect loperamide. When taken in excess, the screening method identifies loperamide followed by a separate technique to confirm and quantify the drug by liquid chromatography-tandem mass spectrometry. Of the 21 cases involving loperamide, the pathologist implicated the drug as either additive or primary to the cause of death in 19 cases. The mean and median peripheral blood concentrations for the drug overdose cases were 0.27 and 0.23 mg/L, respectively. Furthermore, an extensive review of the pharmacology associated with loperamide and its interaction with P-glycoprotein will be examined as it relates to the mechanism of toxicity.
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http://dx.doi.org/10.1093/jat/bkw069DOI Listing
October 2016

Loperamide-Related Deaths in North Carolina.

J Anal Toxicol 2016 Oct 29;40(8):677-686. Epub 2016 Jul 29.

North Carolina Office of the Chief Medical Examiner, Raleigh, NC 27607, USA.

Loperamide (Imodium) has been accepted as a safe, effective, over-the-counter anti-diarrheal drug with low potential for abuse. It is a synthetic opioid that lacks central nervous system activity at prescribed doses, rendering it ineffective for abuse. Since 2012, however, the North Carolina Office of the Chief Medical Examiner has seen cases involving loperamide at supratherapeutic levels that indicate abuse. The recommended dose associated with loperamide should not exceed 16 mg per day, although users seeking an opioid-like high reportedly take it in excess of 100 mg per dose. When taken as directed, the laboratory organic base extraction screening method with gas chromatography-mass spectrometry/nitrogen phosphorus detector lacks the sensitivity to detect loperamide. When taken in excess, the screening method identifies loperamide followed by a separate technique to confirm and quantify the drug by liquid chromatography-tandem mass spectrometry. Of the 21 cases involving loperamide, the pathologist implicated the drug as either additive or primary to the cause of death in 19 cases. The mean and median peripheral blood concentrations for the drug overdose cases were 0.27 and 0.23 mg/L, respectively. Furthermore, an extensive review of the pharmacology associated with loperamide and its interaction with P-glycoprotein will be examined as it relates to the mechanism of toxicity.
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http://dx.doi.org/10.1093/jat/bkw069DOI Listing
October 2016

Postmortem levetiracetam (Keppra®) data from North Carolina.

J Anal Toxicol 2012 Jul 25;36(6):422-8. Epub 2012 May 25.

North Carolina Office of the Chief Medical Examiner, Chapel Hill, NC, USA.

Levetiracetam (Keppra®) is one of the newer anticonvulsant drugs used to treat seizures. Since 2003, the North Carolina Office of the Chief Medical Examiner Toxicology Laboratory has collected quantitative levetiracetam data in samples for 56 postmortem cases. The data presented herein will provide the forensic community with concentrations to assist in the interpretation of levetiracetam in postmortem blood. Decedents were divided into two groups according to manner of death as determined by the medical examiner for the purposes of studying levetiracetam concentrations. There were equal numbers of natural (N = 28) and non-natural deaths (N = 28). These data were subsequently divided into subgroups for further study to explore the therapeutic range of levetiracetam and how it relates to postmortem data. The cases not certified as natural were investigated to study levetiracetam concentrations in cases where it was determined to contribute to the cause of death (attributed) and those where it was not (unattributed). Until now, the literature has only reported levetiracetam overdoses in which the individuals have recovered with respiratory support. Discussed are two suicidal drug deaths from 2010 that are noted to have elevated levels of levetiracetam, 190 and 35 mg/L. Also included in the complete data set are postmortem concentrations for five patients under the age of 10 with levetiracetam ranging from 1.4 to 50 mg/L. This paper will also address the adverse effects of the drug and explore its potential risk for suicide.
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http://dx.doi.org/10.1093/jat/bks052DOI Listing
July 2012