Fast increase of postmortem fentanyl blood concentrations after transdermal application: A call to careful interpretation

Reiter, Alonja; Mueller, Alexander; Otto, Benjamin; Anders, Sven; Falckenberg, Maja; Iwersen‐Bergmann, Stefanie; Andresen‐Streichert, Hilke

doi:10.1016/j.forsciint.2019.109896

Cited by 6 publications

(6 citation statements)

References 20 publications

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“…The measured fentanyl concentration (quantitative value) in our case was almost never seen after a normal dose of fentanyl when looking at previously reported measurements which can be seen in Table 1 [16,17]. Although large interpatient variability was to be expected due to all the above mentioned issues [8], postmortem fentanyl concentrations higher than 50 µg/L are mostly seen after fatal fentanyl intoxications [17,18]. This also seems to be independent of the administered dose of fentanyl patches [16], suggesting the amount of patches will only speed up the time that is needed to reach the lethal dose.…”

Section: Discussionsupporting

confidence: 47%

“…However, in some cases it can be useful to quantify postmortem drug concentrations in order to further establish the lethal dose of fentanyl for instance. When measuring postmortem quantitative concentrations, careful interpretation of these values is necessary as postmortem fentanyl concentrations do not resemble ante mortem concentrations [8]. Also, there is a minimal availability of postmortem cases in which opioid use is known, which makes comparison between cases hard.…”

Section: Introductionmentioning

confidence: 99%

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Case report on postmortem fentanyl measurement after overdose with more than 67 fentanyl patches

Peeters

Vleut

Tan³

et al. 2021

Forensic Toxicol

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Purpose Fentanyl is an analgesic that is frequently prescribed, which resulted in non-intentional as well as intentional misuse and deaths. Here, we present a postmortem case of a patient who clearly died of a fentanyl overdose due to an extensive number of fentanyl patches combined with oral intake of fentanyl and cocaine. We aimed to show how postmortem analysis can be used to interpret postmortem fentanyl concentrations in unique cases like the one we present. Case description A 23-year-old male was found dead in his bedroom with 67 non-prescribed patches of fentanyl on his body. In the room, there also were fentanyl tablets of 100 µg and cocaine powder, which had possibly also been taken by the deceased. To confirm the cause of death, urine and subclavian blood were retrieved to perform a standard postmortem toxicology screening. The toxicological screening revealed the presence of several drugs, including cocaine, fentanyl, lidocaine and paracetamol. Further analysis of the quantitative postmortem values of fentanyl with ultra-performance liquid chromatography-tandem mass spectrometry revealed a fentanyl concentration of 57.9 µg/L. Considering several issues around postmortem drug analyses, this value seemed to be in line with concentrations found in previously reported postmortem cases. Conclusion We were able to confirm the expected cause of death with an extensive toxicological screening in combination with the circumstantial evidence. We identified fentanyl as most important cause for the fatal outcome in this specific case and simultaneously contributed to the limited availability of knowledge on postmortem fentanyl concentrations.

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Section: Discussionsupporting

confidence: 47%

Section: Introductionmentioning

confidence: 99%

Case report on postmortem fentanyl measurement after overdose with more than 67 fentanyl patches

Peeters

Vleut

Tan³

et al. 2021

Forensic Toxicol

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“…Extraction procedures utilized for LC–MS/MS quantitative methods are more expansive due to the applicability to multiple matrix types. While LLE [21,38,39,40,41,42,43,44,45] and SPE [23,37,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70] remain the most common techniques, PP [17,71,72,73,74,75,76,77,78,79,80,81,82], simple dilution [11,14,37,83] solvent extraction [82,84,85], SLE [86,87] and QuECHeERs [16,71,88] have been described as suitable extraction techniques among their evaluated scenarios. In some studies, sample pretreatment techniques such as PP and physical preparations (grinding [89,90], pulverization [62], and digestion [37]) were employed before extraction.…”

Section: Resultsmentioning

confidence: 99%

“…Extraction procedures utilized for LC-MS/MS quantitative methods are more expansive due to the applicability to multiple matrix types. While LLE[21,38,39,40,41,42,43,44,45] and SPE[23,37 ,46 ,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66 ,6 7,68,69,70] remain the most common techniques, PP[17,71,72,73,74,75,76,77,78,79,80,81,82], simple dilution…”

mentioning

confidence: 99%

Review of analytical methods for screening and quantification of fentanyl analogs and novel synthetic opioids in biological specimens

Palmquist

Truver

Shoff

et al. 2023

Journal of Forensic Sciences

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Fentanyl, fentanyl analogs, and other novel synthetic opioids (NSO), including nitazene analogs, prevail in forensic toxicology casework. Analytical methods for identifying these drugs in biological specimens need to be robust, sensitive, and specific. Isomers, new analogs, and slight differences in structural modifications necessitate the use of high‐resolution mass spectrometry (HRMS), especially as a non‐targeted screening method designed to detect newly emerging drugs. Traditional forensic toxicology workflows, such as immunoassay and gas chromatography mass spectrometry (GC–MS), are generally not sensitive enough for detection of NSOs due to observed low (sub‐μg/L) concentrations. For this review, the authors tabulated, reviewed, and summarized analytical methods from 2010–2022 for screening and quantification of fentanyl analogs and other NSOs in biological specimens using a variety of different instruments and sample preparation approaches. Limits of detection or quantification for 105 methods were included and compared to published standards and guidelines for suggested scope and sensitivity in forensic toxicology casework. Methods were summarized by instrument for screening and quantitative methods for fentanyl analogs and for nitazenes and other NSO. Toxicological testing for fentanyl analogs and NSOs is increasingly and most commonly being conducted using a variety of liquid chromatography mass spectrometry (LC–MS)‐based techniques. Most of the recent analytical methods reviewed exhibited limits of detection well below 1 μg/L to detect low concentrations of increasingly potent drugs. In addition, it was observed that most newly developed methods are now using smaller sample volumes which is achievable due to the sensitivity increase gained by new technology and new instrumentation.

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“…10 Fentanyl plasma or blood concentrations do not correlate well with transdermal fentanyl doses, and furthermore, post-mortem fentanyl concentrations can be considerably higher than the plasma concentrations of living subjects wearing fentanyl patches due to postmortem redistribution. 11 Reiter et al 12 studied the post-mortem increase of fentanyl blood concentrations in ten palliative care patients that died following treatment with fentanyl patches with delivery rates of 12-150 μg/h. The post-mortem blood fentanyl concentration was above 10 µg/l in two out of 25 measurements from five subjects having patches of 50-75 μg/h.…”

Section: Discussionmentioning

confidence: 99%

Death in Sauna Associated With a Transdermal Fentanyl Patch

Kriikku

Ojanperä

Lunetta

2020

Am J Forensic Med Pathol

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We present a case of an accidental fatal fentanyl overdose caused by increased uptake of the drug from a transdermal patch while experiencing the heat of a sauna.The transdermal patch administers fentanyl at a relatively constant rate through the skin. However, in the subcutaneous tissue blood circulation greatly influences the rate of this drug's systemic intake. In the present case, an elderly woman with multiple health conditions was prescribed fentanyl patches but was unaware of the risks associated with external heat sources when one wears the patch. She was found dead in the sauna with a post-mortem femoral blood concentration of fentanyl that was elevated (15 µg/L). The cause of death was determined to be fatal poisoning by fentanyl with the contributing factor of external heat from the sauna.Risks associated with transdermal administration of a potent opioid like fentanyl are widely described in the scientific literature and described in the manufacturer's summary of product characteristics. Physicians and pharmacists should take particular care to ensure that patients understand these risks.

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Fast increase of postmortem fentanyl blood concentrations after transdermal application: A call to careful interpretation

Cited by 6 publications

References 20 publications

Case report on postmortem fentanyl measurement after overdose with more than 67 fentanyl patches

Case report on postmortem fentanyl measurement after overdose with more than 67 fentanyl patches

Review of analytical methods for screening and quantification of fentanyl analogs and novel synthetic opioids in biological specimens

Death in Sauna Associated With a Transdermal Fentanyl Patch

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