Postmortem Redistribution of Fentanyl in Blood

Olson, Kent D.; Luckenbill, Kristin; Thompson, Jonathan; Middleton, Owen; Geiselhart, Roberta; Mills, Kelly; Kloss, Julie; Apple, Fred S.

doi:10.1309/ajcp4x5vhfsoerft

Cited by 62 publications

(31 citation statements)

References 16 publications

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“…In the living, the dose administered generally correlates with measured blood concentrations. In the postmortem setting, however, there are several factors that may affect the concentration and should be considered when interpreting postmortem concentrations [7,[25][26][27][28][29]. These include tolerance, postmortem intervals and redistribution, and metabolism.…”

Section: Discussionmentioning

confidence: 99%

“…Fentanyl, which has a large volume of distribution, may exhibit postmortem redistribution with heart-femoral blood ratios that ranged from 0.7 to 4.6 (mean 1.6) in 13 deaths with fentanyl transdermal patches [15,25]. The degree of a One death with a prolonged hospitalizations was excluded because fentanyl was detected only in the postmortem vitreous sample b Two natural deaths were excluded because fentanyl was detected but could not be quantitated Fig.…”

Section: Discussionmentioning

confidence: 99%

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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%

Section: Discussionmentioning

confidence: 99%

Reliability of Postmortem Fentanyl Concentrations in Determining the Cause of Death

2012

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“…The mean ratio value obtained by them in autopsies of 20 cadavers were even higher, i.e. 6.21 with a range of 1.91-12.11 [46]. The above-mentioned ratios were poorly correlated with the postmortem interval [118].…”

Section: Opioidsmentioning

confidence: 85%

“…The mean heart to femoral blood ratio was 3.6 (range 1.9-5.4) [118]. Also, high fentanyl concentrations in ventricular tissue were determined by Olson et al [46]. The mean ratio value obtained by them in autopsies of 20 cadavers were even higher, i.e.…”

Section: Opioidsmentioning

confidence: 87%

“…Since differences among heart and femoral blood are often observed for fentanyl in postmortem examinations, inter alia, it is the myocardium that is suspected of falsely elevating the heart blood fentanyl level [46,118]. In light of that, Luckenbill et al [118] settled the question of the ratio of fentanyl concentration in heart tissue to that in the femoral vein.…”

Section: Opioidsmentioning

confidence: 99%

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Plasma vs heart tissue concentration in humans – literature data analysis of drugs distribution

Tylutki

Polak

2015

Biopharm & Drug Disp

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ABSTRACT:Little is known about the uptake of drugs into the human heart, although it is of great importance nowadays, when science desires to predict tissue level behavior rather than to measure it. Although the drug concentration in cardiac tissue seems a better predictor for physiological and electrophysiological changes than its level in plasma, knowledge of this value is very limited. Tissue to plasma partition coefficients (Kp) come to rescue since they characterize the distribution of a drug among tissues as being one of the input parameters in physiologically based pharmacokinetic (PBPK) models. The article reviews cardiac surgery and forensic medical studies to provide a reference for drug concentrations in human cardiac tissue. Firstly, the focus is on whether a drug penetrates into heart tissue at a therapeutic level; the provided values refer to antibiotics, antifungals and anticancer drugs. Drugs that directly affect cardiomyocyte electrophysiology are another group of interest. Measured levels of amiodarone, digoxin, perhexiline and verapamil in different sites in human cardiac tissue where the compounds might meet ion channels, gives an insight into how these more lipophilic drugs penetrate the heart. Much data are derived from postmortem studies and they provide insight to the cardiac distribution of more than 200 drugs. The analysis depicts potential problems in defining the active concentration location, what may indirectly suggest multiple mechanisms involved in the drug distribution within the heart.

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Fentanyl Analogues

Barceloux

2012

Medical Toxicology of Drug Abuse

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Postmortem Redistribution of Fentanyl in Blood

Cited by 62 publications

References 16 publications

Reliability of Postmortem Fentanyl Concentrations in Determining the Cause of Death

Reliability of Postmortem Fentanyl Concentrations in Determining the Cause of Death

Plasma vs heart tissue concentration in humans – literature data analysis of drugs distribution

Fentanyl Analogues

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