Background: Prenatal exposure to fentanyl may lead to Neonatal Abstinence Syndrome (NAS), a constellation of symptoms observed when newborns begin withdrawing from addictive substances such as opioids. The use of umbi...Background: Prenatal exposure to fentanyl may lead to Neonatal Abstinence Syndrome (NAS), a constellation of symptoms observed when newborns begin withdrawing from addictive substances such as opioids. The use of umbilical cord tissue segments (UC) for newborn toxicology has been increasing due to its apparent long detection window, sensitivity, and ease of collection. However, very little has been reported in the literature concerning the prevalence of in utero exposure to fentanyl and co-exposure with other commonly abused substances. Specific aim: The specific aims of this retrospective study are twofold. We will report prevalence of neonatal exposure to fentanyl for a nationwide high-risk population using UC submitted to a national reference laboratory for routine forensic toxicology analysis and the co-exposure patterns observed for these fentanyl-exposed neonates. Methods: A secondary analysis was performed using historical data for UC received between January 1, 2020 and December 31, 2020 for routine forensic toxicology analysis. Results: During the study period, our laboratory received 23,104 UC for analysis and 9667 (41.8%) of those UC were positive for at least one drug. The prevalence of fentanyl detection was 1.9% (n = 429). Of these 429 specimens there were 407 UC where both fentanyl and norfentanyl were detected. There were 14 UC where only fentanyl was detected and 8 UC where only norfentanyl was detected. When detected, the median concentrations of fentanyl and norfentanyl were 4029 pg/g (IQR: 1696, 9230 pg/g) and 10,756 pg/mg (IQR: 3925, 25,288 pg/g), respectively. Of the 429 positive fentanyl and/or norfentanyl UC, 33 (7.7%) were only positive for fentanyl and/or norfentanyl. Of the 396 polypositive UC, morphine was the highest co-exposure with 243 UC (56.6%) being positive for both fentanyls and morphine. The second most prevalent co-exposure observed was methamphetamine/amphetamine (n = 173;40.3%) followed by cannabinoids (n = 113;26.3%) and benzoylecgonine (cocaine metabolite;n = 106;24.7%). Conclusions: Nonmedical use of fentanyl is an alarming trend in this country including this maternal demographic reported here. Fentanyl was typically found with other commonly abused substances.展开更多
Abuse of drug substances and resultant overdose deaths are no longer very straightforward—viz., attributable to a single chemical entity of known purity. The reality is that most overdose deaths involve polysubstance...Abuse of drug substances and resultant overdose deaths are no longer very straightforward—viz., attributable to a single chemical entity of known purity. The reality is that most overdose deaths involve polysubstance use (i.e., the use of combinations of substances). Further, the combinations are often of unknown purity, and even of unknown composition. Overdose deaths are at all-time highs. The depressing statistics are monitored and reported by several international and governmental organizations such as the WHO (World Health Organization), CDC (Centers for Disease Control and Prevention), several Institutes of the NIH (National Institutes of Health), Regulators, and Enforcement Agencies (e.g., DEA). The information is disseminated for free for review and use. But it is our observation that although numeric presentation is helpful and adequate for professionals, the non-expert and the visual learner often find a visual representation clearer and compelling. With this in mind, we present the “gestalt” of polysubstance use and overdose using available maps of the data. The previous article in the series considered the opioids. This one considers amphetamines and cocaine, and places the rise in opioid-associated overdose deaths in the context of other abused drugs.展开更多
<span style="font-family:Verdana;">The </span><span style="font-family:Verdana;">“</span><span style="font-family:Verdana;">opioid crisis</span><sp...<span style="font-family:Verdana;">The </span><span style="font-family:Verdana;">“</span><span style="font-family:Verdana;">opioid crisis</span><span style="font-family:Verdana;">”</span><span style="font-family:""><span style="font-family:Verdana;"> has had a tremendous impact not only on its victims, but also on the practice of medicine, pain patients, and society in general. Unfortunately, efforts to “stem the tide” have not been successful at reducing overdose deaths. Counterbalancing the many ardent efforts to eliminate overdose deaths (such as the current widespread availability and use of opioid-receptor antagonists such as naloxone) is influx of the illicit fentanoids (</span><i><span style="font-family:Verdana;">i.e</span></i><span style="font-family:Verdana;">., fentanyl and analogs). In addition to their high-potency, the fentanoids differ in surprising ways from more “traditional” opioids such as morphine and heroin. This uniqueness contributes to a reduced effectiveness of opioid receptor antagonists in the treatment of opioid overdose. Further greatly complicating overdose treatment is polysubstance abuse (e.g., an opioid plus a benzodiaze</span><span style="font-family:Verdana;">pine). The non-opioid in the combination is not responsive to an opio</span><span style="font-family:Verdana;">id-recep</span></span><span style="font-family:Verdana;">- </span><span style="font-family:""><span style="font-family:Verdana;">tor antagonist, which imparts additional challenges. Thus, the new reality in</span><span style="font-family:Verdana;">troduces complications that negatively impact efforts to reverse </span></span><span style="font-family:Verdana;">“</span><span style="font-family:Verdana;">opioid</span><span style="font-family:Verdana;">”</span><span style="font-family:""><span style="font-family:Verdana;"> overdose. New approaches to improve outcomes in individuals who experience </span><span style="font-family:Verdana;">respiratory depression due to fentanoid-induced or polysubstance-induced</span><span style="font-family:Verdana;"> over</span></span><span style="font-family:Verdana;">- </span><span style="font-family:Verdana;">dose are needed. Approaches that harmonize with the new reality, perhaps something like a non-opioid </span><span style="font-family:Verdana;">“</span><span style="font-family:Verdana;">agnostic</span><span style="font-family:Verdana;">”</span><span style="font-family:Verdana;"> pharmacologic ventilatory stimulant, would provide a welcome addition to the current choices.</span>展开更多
文摘Background: Prenatal exposure to fentanyl may lead to Neonatal Abstinence Syndrome (NAS), a constellation of symptoms observed when newborns begin withdrawing from addictive substances such as opioids. The use of umbilical cord tissue segments (UC) for newborn toxicology has been increasing due to its apparent long detection window, sensitivity, and ease of collection. However, very little has been reported in the literature concerning the prevalence of in utero exposure to fentanyl and co-exposure with other commonly abused substances. Specific aim: The specific aims of this retrospective study are twofold. We will report prevalence of neonatal exposure to fentanyl for a nationwide high-risk population using UC submitted to a national reference laboratory for routine forensic toxicology analysis and the co-exposure patterns observed for these fentanyl-exposed neonates. Methods: A secondary analysis was performed using historical data for UC received between January 1, 2020 and December 31, 2020 for routine forensic toxicology analysis. Results: During the study period, our laboratory received 23,104 UC for analysis and 9667 (41.8%) of those UC were positive for at least one drug. The prevalence of fentanyl detection was 1.9% (n = 429). Of these 429 specimens there were 407 UC where both fentanyl and norfentanyl were detected. There were 14 UC where only fentanyl was detected and 8 UC where only norfentanyl was detected. When detected, the median concentrations of fentanyl and norfentanyl were 4029 pg/g (IQR: 1696, 9230 pg/g) and 10,756 pg/mg (IQR: 3925, 25,288 pg/g), respectively. Of the 429 positive fentanyl and/or norfentanyl UC, 33 (7.7%) were only positive for fentanyl and/or norfentanyl. Of the 396 polypositive UC, morphine was the highest co-exposure with 243 UC (56.6%) being positive for both fentanyls and morphine. The second most prevalent co-exposure observed was methamphetamine/amphetamine (n = 173;40.3%) followed by cannabinoids (n = 113;26.3%) and benzoylecgonine (cocaine metabolite;n = 106;24.7%). Conclusions: Nonmedical use of fentanyl is an alarming trend in this country including this maternal demographic reported here. Fentanyl was typically found with other commonly abused substances.
文摘Abuse of drug substances and resultant overdose deaths are no longer very straightforward—viz., attributable to a single chemical entity of known purity. The reality is that most overdose deaths involve polysubstance use (i.e., the use of combinations of substances). Further, the combinations are often of unknown purity, and even of unknown composition. Overdose deaths are at all-time highs. The depressing statistics are monitored and reported by several international and governmental organizations such as the WHO (World Health Organization), CDC (Centers for Disease Control and Prevention), several Institutes of the NIH (National Institutes of Health), Regulators, and Enforcement Agencies (e.g., DEA). The information is disseminated for free for review and use. But it is our observation that although numeric presentation is helpful and adequate for professionals, the non-expert and the visual learner often find a visual representation clearer and compelling. With this in mind, we present the “gestalt” of polysubstance use and overdose using available maps of the data. The previous article in the series considered the opioids. This one considers amphetamines and cocaine, and places the rise in opioid-associated overdose deaths in the context of other abused drugs.
文摘<span style="font-family:Verdana;">The </span><span style="font-family:Verdana;">“</span><span style="font-family:Verdana;">opioid crisis</span><span style="font-family:Verdana;">”</span><span style="font-family:""><span style="font-family:Verdana;"> has had a tremendous impact not only on its victims, but also on the practice of medicine, pain patients, and society in general. Unfortunately, efforts to “stem the tide” have not been successful at reducing overdose deaths. Counterbalancing the many ardent efforts to eliminate overdose deaths (such as the current widespread availability and use of opioid-receptor antagonists such as naloxone) is influx of the illicit fentanoids (</span><i><span style="font-family:Verdana;">i.e</span></i><span style="font-family:Verdana;">., fentanyl and analogs). In addition to their high-potency, the fentanoids differ in surprising ways from more “traditional” opioids such as morphine and heroin. This uniqueness contributes to a reduced effectiveness of opioid receptor antagonists in the treatment of opioid overdose. Further greatly complicating overdose treatment is polysubstance abuse (e.g., an opioid plus a benzodiaze</span><span style="font-family:Verdana;">pine). The non-opioid in the combination is not responsive to an opio</span><span style="font-family:Verdana;">id-recep</span></span><span style="font-family:Verdana;">- </span><span style="font-family:""><span style="font-family:Verdana;">tor antagonist, which imparts additional challenges. Thus, the new reality in</span><span style="font-family:Verdana;">troduces complications that negatively impact efforts to reverse </span></span><span style="font-family:Verdana;">“</span><span style="font-family:Verdana;">opioid</span><span style="font-family:Verdana;">”</span><span style="font-family:""><span style="font-family:Verdana;"> overdose. New approaches to improve outcomes in individuals who experience </span><span style="font-family:Verdana;">respiratory depression due to fentanoid-induced or polysubstance-induced</span><span style="font-family:Verdana;"> over</span></span><span style="font-family:Verdana;">- </span><span style="font-family:Verdana;">dose are needed. Approaches that harmonize with the new reality, perhaps something like a non-opioid </span><span style="font-family:Verdana;">“</span><span style="font-family:Verdana;">agnostic</span><span style="font-family:Verdana;">”</span><span style="font-family:Verdana;"> pharmacologic ventilatory stimulant, would provide a welcome addition to the current choices.</span>
