Deaths After Intravenous Misuse of Transdermal Fentanyl

Lilleng, Peer Kåre; Mehlum, Lars Ivar; Bachs, Liliana; Morild, Inge

doi:10.1520/jfs04143

Cited by 52 publications

(29 citation statements)

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“…The second group involves deaths due to fentanyl derived from commercially available transdermal patches [15][16][17][18][19]. Although many of these deaths have occurred with dermal use, misuse of patches by the oral, inhalational, or intravenous route are well described [8,[20][21][22][23][24]. In the USA, there has been a substantial increase in prescription opioid abuse and deaths, which includes both oral dosage formulations as well as transdermal patches.…”

Section: Discussionmentioning

confidence: 99%

Reliability of Postmortem Fentanyl Concentrations in Determining the Cause of Death

2012

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Introduction Transdermal fentanyl, an opioid used for management of marked pain, also is abused and may cause death. Methods We reviewed medical examiner reports of 92 decedents who had one or more fentanyl transdermal patches on their body and had fentanyl detected in their postmortem toxicology analysis. Results The manners of death included 40 accidents, 36 natural, 8 suicides, 5 therapeutic complications, and 3 undetermined deaths. Among the accidental fentanyl intoxication deaths, 32 of 37 involved substance abuse. The majority (95 %) of the 37 accidental deaths involving fentanyl were multi-drug intoxications. The substance abuse deaths had a mean fentanyl blood concentration (26.4 ng/ml or μg/L) that was over twice that of the natural group (11.8 ng/ml). Our analysis suggests a relationship between total patch dosage and mean postmortem fentanyl concentration up to the 100-μg/h dose. Conclusions The very wide and overlapping ranges of postmortem fentanyl concentrations effectively nullify the utility of correlating the dose and expected postmortem concentration for any particular death. Based on the variable relationship between dose and blood concentration, the antemortem dose cannot be reliably predicted based on the postmortem concentration. This does not, however, render the medical examiner/coroner unable to determine the cause and manner of death because the toxicology results are only one datum point among several that are considered. Although there was a weakly positive relationship between body mass index and fentanyl concentration, further research is needed to determine whether adipose tissue represents a significant depot for postmortem release of fentanyl.Keywords Toxicology . Fentanyl . Fatality . Forensic pathology . Transdermal . Intoxication Fentanyl, a synthetic phenylpiperidine, is a prescription opioid that is used for management of marked pain and the induction of anesthesia [1][2][3]. It has agonist activity at the μ-opioid receptor that results in analgesia and euphoria and is a schedule II medication that has a high potential for abuse. It may be administered by intravenous, transdermal, epidural, transmucosal, and inhalational routes. Due to slow absorption, the transdermal route is prescribed only for treatment of chronic pain. Transdermal (TD) delivery occurs by passive diffusion of fentanyl through the epidermis and dermis into the systemic circulation. Due to fentanyl's lipophilicity, it rapidly diffuses through the epidermis but is delayed by the water-rich dermis. This results in a depot of fentanyl at the epidermis-dermal junction, which explains both the slow onset and prolonged effects of TD fentanyl that may continue even after removal of an unspent patch.We have reviewed 92 deaths in which the decedent was found to be using one or more fentanyl patches. The causes of death, indication for use, evidence of abuse, postmortem toxicologic results with concentrations, and the epidemiology are examined and discussed. Our goal is to examine the relationship between the...

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Section: Discussionmentioning

confidence: 99%

Reliability of Postmortem Fentanyl Concentrations in Determining the Cause of Death

2012

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“…[29] In the same study, fentanyl was found to be more likely to be associated with alternative routes of abuse than other prescription opioid analgesics (i.e., abuse via routes other than that intended or via inhalation, injection or chewing); 70% of individuals abusing transdermal fentanyl and 69% of those abusing sublingual fentanyl reported other routes of abuse compared with 3-13% for other drugs. [29] Other routes of abuse that have been reported for transdermal fentanyl formulations include application of multiple patches, [38] placing the patch in the mouth, [39][40][41] chewing or sucking, [42][43][44] swallowing whole, [45,46] injection of extracted patch contents, [47][48][49] smoking [50,51] and rectal insertion. [52] Patches may also be boiled to make a "tea", which can be ingested or injected.…”

Section: Differences In Routes Of Abuse Between Formulationsmentioning

confidence: 99%

Routes of abuse of prescription opioid analgesics: a review and assessment of the potential impact of abuse-deterrent formulations

Gąsior

Bond

Malamut

2015

Postgraduate Medicine

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Prescription opioid analgesics are an important treatment option for patients with chronic pain; however, misuse, abuse and diversion of these medications are a major global public health concern. Prescription opioid analgesics can be abused via intended and non-intended routes of administration, both intact or after manipulation of the original formulation to alter the drug-delivery characteristics. Available data indicate that ingestion (with or without manipulation of the prescribed formulation) is the most prevalent route of abuse, followed by inhalation (snorting, smoking and vaping) and injection. However, reported routes of abuse vary considerably between different formulations. A number of factors have been identified that appear to be associated with non-oral routes of abuse, including a longer duration of abuse, younger age, male sex and a rural or socially deprived location. The development of abuse-deterrent formulations of prescription opioid analgesics is an important step toward reducing abuse of these medications. Available abuse-deterrent formulations aim to hinder extraction of the active ingredient, prevent administration through alternative routes and/or make abuse of the manipulated product less attractive, less rewarding or even aversive. There are currently five opioid analgesics with a Food and Drug Administration abuse-deterrent label, and a number of other products are under review. A growing body of evidence suggests that introduction of abuse-deterrent opioid analgesics in the USA has been associated with decreased rates of abuse of these formulations. The availability of abuse-deterrent formulations therefore appears to represent an important step toward curbing the epidemic of abuse of prescription opioid analgesics, while ensuring the availability of effective pain medications for patients with legitimate medical need.

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“…To decrease the amount of co-eluting compounds in the extract, an additional alkaline wash step was added to the SPE protocol. The optimal organic content of the alkaline wash solvent was determined by several washes with increasing amounts of MeOH in the alkaline solvent (10,20,30,40,50,60,70,80,90% MeOH). Elution of the analytes was first seen when washing with solvent containing 70% MeOH, therefore, the alkaline wash step was set at MeOH-H 2 O-ammonium hydroxide (68.5:29.5:2).…”

Section: Me Re and Pementioning

confidence: 99%

Development and validation of a sensitive ultra performance liquid chromatography tandem mass spectrometry method for the analysis of fentanyl and its major metabolite norfentanyl in urine and whole blood in forensic context

Verplaetse

Tytgat

2010

Journal of Chromatography B

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Deaths After Intravenous Misuse of Transdermal Fentanyl

Cited by 52 publications

References 0 publications

Reliability of Postmortem Fentanyl Concentrations in Determining the Cause of Death

Reliability of Postmortem Fentanyl Concentrations in Determining the Cause of Death

Routes of abuse of prescription opioid analgesics: a review and assessment of the potential impact of abuse-deterrent formulations

Development and validation of a sensitive ultra performance liquid chromatography tandem mass spectrometry method for the analysis of fentanyl and its major metabolite norfentanyl in urine and whole blood in forensic context

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