Fatal Overdose Due to Prescription Fentanyl Patches in a Patient With Sickle Cell/β-Thalassemia and Acute Chest Syndrome

Biedrzycki, Olaf J.; Bevan, David; Lucas, Sebastian

doi:10.1097/paf.0b013e318187de71

Cited by 31 publications

(19 citation statements)

References 20 publications

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“…The first is those who administer fentanyl intravenously, often in localized epidemics associated with illicitly produced fentanyl [10][11][12][13][14]. 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].…”

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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“…In another report, tryptase levels in the blood were significantly elevated in conjunction with sickle crisistype pain and acute chest syndrome following a fatal overdose of fentanyl in a patient with sickle cell/b-thalassemia. 31 Elevation of tryptase was suggested to be associated with opioid-induced acute anaphylaxis, but its significance in sickle pathophysiology leading For personal use only. on May 10, 2018. by guest www.bloodjournal.org From to death remained unclear.…”

Section: Discussionmentioning

confidence: 99%

Mast cell activation contributes to sickle cell pathobiology and pain in mice

Vincent

Vang

Nguyen

et al. 2013

Blood

187

260

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Key Points• Inhibition of mast cells with cromolyn or imatinib results in reduced systemic inflammation and neurogenic inflammation in sickle mice.• Pharmacological inhibition or genetic depletion of mast cells in sickle mice ameliorates chronic and hypoxia/reoxygenationinduced pain.Sickle cell anemia (SCA) is an inherited disorder associated with severe lifelong pain and significant morbidity. The mechanisms of pain in SCA remain poorly understood.We show that mast cell activation/degranulation contributes to sickle pain pathophysiology by promoting neurogenic inflammation and nociceptor activation via the release of substance P in the skin and dorsal root ganglion. Mast cell inhibition with imatinib ameliorated cytokine release from skin biopsies and led to a correlative decrease in granulocyte-macrophage colony-stimulating factor and white blood cells in transgenic sickle mice. Targeting mast cells by genetic mutation or pharmacologic inhibition with imatinib ameliorates tonic hyperalgesia and prevents hypoxia/reoxygenation-induced hyperalgesia in sickle mice. Pretreatment with the mast cell stabilizer cromolyn sodium improved analgesia following low doses of morphine that were otherwise ineffective. Mast cell activation therefore underlies sickle pathophysiology leading to inflammation, vascular dysfunction, pain, and requirement for high doses of morphine. Pharmacological targeting of mast cells with imatinib may be a suitable approach to address pain and perhaps treat SCA. (Blood. 2013;122(11):1853-1862

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“…There is a substantial overlap between FENS and opioids in the spectrum of pathological findings (Biedrzycki, Bevan, & Lucas, ). Post‐mortem examinations do not show pathognomonic or specific changes in intoxications involving novel compounds, even though FENS are obtained through innovative modifications of the chemical structure of FEN.…”

Section: Discussionmentioning

confidence: 99%

“…There is a substantial overlap between FENS and opioids in the spectrum of pathological findings (Biedrzycki, Bevan, & Lucas, 2009).…”

Section: Pathological Findingsmentioning

confidence: 99%

Fentanyl novel derivative‐related deaths

Giorgetti

Centola

Giorgetti

2017

Human Psychopharmacology

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Fatal Overdose Due to Prescription Fentanyl Patches in a Patient With Sickle Cell/β-Thalassemia and Acute Chest Syndrome

Cited by 31 publications

References 20 publications

Reliability of Postmortem Fentanyl Concentrations in Determining the Cause of Death

Reliability of Postmortem Fentanyl Concentrations in Determining the Cause of Death

Mast cell activation contributes to sickle cell pathobiology and pain in mice

Fentanyl novel derivative‐related deaths

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