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

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.

Sub-Part-Per-Billion Level Sensing of Fentanyl Residues from Wastewater Using Portable Surface-Enhanced Raman Scattering Sensing

Detection of illicit drug residues from wastewater provides a new route toward community-level assessment of drug abuse that is critical to public health. However, traditional chemistry analytical tools such as high-performance liquid chromatography in tandem with mass spectrometry (HPLC-MS) cannot meet the large-scale testing requirement in terms of cost, promptness, and convenience of use. In this article, we demonstrated ultra-sensitive and portable surface-enhanced Raman scattering sensing (SERS) of fentanyl, a synthetic opioid, from sewage water and achieved quantitative analysis through principal component analysis and partial least-squares regression. The SERS substrates adopted in this application were synthesized by in situ growth of silver nanoparticles on diatomaceous earth films, which show ultra-high sensitivity down to 10 parts per trillion in artificially contaminated tap water in the lab using a commercial portable Raman spectrometer. Based on training data from artificially contaminated tap water, we predicted the fentanyl concentration in the sewage water from a wastewater treatment plant to be 0.8 parts per billion (ppb). As a comparison, the HPLC-MS confirmed the fentanyl concentration was below 1 ppb but failed to provide a specific value of the concentration since the concentration was too low. In addition, we further proved the validity of our SERS sensing technique by comparing SERS results from multiple sewage water treatment plants, and the results are consistent with the public health data from our local health authority. Such SERS sensing technique with ultra-high sensitivity down to sub-ppb level proved its feasibility for point-of-care detection of illicit drugs from sewage water, which is crucial to assess public health.

Continuous infusion versus intermittent bolus doses of fentanyl for analgesia and sedation in neonates: an open-label randomised controlled trial

ObjectiveAdequate data on fentanyl pharmacokinetics in neonates are lacking. The study was performed to compare serum concentrations and clinical outcome between continuous infusion (CI) and intermittent bolus (IB) doses of fentanyl for analgesia and sedation in neonates.MethodsIn this open-label randomised controlled trial, neonates requiring 24–48 hours of mechanical ventilation and fentanyl administration were recruited. In CI regimen, 1 mcg/kg loading dose was followed by 1 mcg/kg/hour infusion. In IB regimen, 1mcg/kg/dose was administered every 4 hours.Maximum six blood samples were collected in 48 hours from each baby at prespecified time points for estimating serum fentanyl concentration. Secondary outcomes were pain scores (Neonatal Infant Pain Scale and Neonatal Pain, Agitation and Sedation Scale for acute and ongoing pain, respectively) and incidence of adverse effects of fentanyl.Results100 neonates were recruited, 53 in CI and 47 in IB group. In CI regimen, median (IQR) serum fentanyl concentration was 0.42 (0.35, 0.46) to 0.61 (0.47, 0.89) ng/mL throughout the infusion period. In IB regimen, median (IQR) peak concentration ranged from 2.21 (1.82, 3.55) to 3.61 (2.91, 4.51) ng/mL and trough concentration 0.41 (0.33, 0.48) to 0.97 (0.56, 1.25) ng/mL for various doses.Median (IQR) peak concentration (Cmax, 3.06 (1.09, 4.50) vs 0.78 (0.49, 1.73) ng/mL; p<0.001) was significantly higher and area under concentration-time curve (AUC0–24, 19.6 (10.4, 33.5) vs 13.2 (10.8, 22.6) µg·hour/L; p=0.12) was higher (though not statistically significant) in IB than CI regimen. Pain scores and adverse effects were comparable between the two regimens.ConclusionCI regimen of fentanyl produces steady serum concentrations, whereas IB regimen produces wide fluctuations in serum concentration with high-peak concentrations. A serum fentanyl concentration of 0.4–0.6 ng/mL produces adequate analgesia and sedation in neonates.Trial registration numberCTRI/2014/11/005190.

Bioequivalence and safety of a novel fentanyl transdermal matrix system compared with a transdermal reservoir system

Objectives: Fentanyl is a potent synthetic opioid used for the management of chronic pain. A newer transdermal matrix system was developed and compared with a reservoir system used in the United States.Setting: An open-label, single-center, randomized, two-period crossover study was conducted to evaluate the bioequivalence of the transdermal matrix system to the transdermal reservoir system. Seventy-four subjects completed treatment with both the reservoir system (100 μg/h) and the matrix system (100 μg/h), each applied for 72 hours. After application of the first system, subjects completed a 9-day washout and then crossed over to receive the other system for another 72 hours.Main outcome measure: Blood samples for the determination of serum fentanyl concentrations were taken in each treatment period for up to 120 hours following application.Results: The ratios of geometric means for maximum fentanyl concentration (Cmax) and area under the concentration-time curve (AUClast and AUC∞ ) were 106 percent, 110 percent, and 110 percent, respectively. The 90% confidence intervals for the ratios of the geometric means were contained within the bioequivalence criteria of 80-125 percent. The matrix system adhered well to skin. Systemic and topical safety profiles were comparable between treatments.Conclusions: The transdermal fentanyl matrix system adhered well, was well tolerated, and produced systemic exposures of fentanyl that were bioequivalent to the reservoir system.