INTRODUCTION: Non-pharmaceutical fentanyl and its analogs have driven striking increases in opioid-associated overdose deaths. These highly potent opioids can be found at low concentrations in biological specimens. Little is known regarding the concentrations of these substances among survivors of non-fatal overdoses. In a locale where fentanyl is responsible for the majority of non-fatal opioid overdoses, we compared the concentration of fentanyl in blood to naloxone dosing in the presence and absence of a concurrent sedative-hypnotic exposure. METHODS: In this pilot study, we enrolled adult patients presenting to the emergency department (ED) who: (1) arrived after an overdose requiring naloxone for the reversal of respiratory depression; and (2) who required venipuncture or intravenous access as part of their clinical care. Blood specimens (n = 20) underwent comprehensive toxicology testing, including the quantitation of fentanyl, fentanyl analogs, and naloxone, as well as the detection of common sedative-hypnotics and a wide range of other illicit and pharmaceutical substances. We then compared fentanyl concentrations to naloxone dosing in participants with and without a concomitant sedative-hypnotic exposure. RESULTS: Nineteen of twenty participants (95%) were exposed to fentanyl prior to their overdose; the remaining participant tested positive for heroin metabolites. No participants reported pharmaceutical fentanyl use. Fentanyl analogs - acetylfentanyl or carfentanil - were present in three specimens. In 11 cases, fentanyl and its metabolites were the only opioids identified. Among the fentanyl-exposed, blood concentrations ranged from < 0.1-19 ng/mL with a mean of 6.2 ng/mL and a median of 3.6 ng/mL. There was no relationship between fentanyl concentration and naloxone dose administered for reversal. We detected sedative-hypnotics (including benzodiazepines, muscle relaxants, and antidepressants) in nine participants. Among the sedative-hypnotic exposed, fentanyl concentrations were lower, but naloxone dosing was similar to those without a concomitant exposure. CONCLUSIONS: In this study, we found that: 1) fentanyl was present in the blood of nearly all participants; 2) fentanyl concentrations were lower among study participants with concomitant sedative-hypnotic exposure; and 3) the dose of naloxone administered for overdose reversal was not associated with the measured fentanyl concentration in blood specimens. Our results underscore the role that tolerance and concomitant drug exposure play in the precipitation and resuscitation of management of opioid overdose.

INTRODUCTION: The adulteration of heroin with non-pharmaceutical fentanyl and other high-potency opioids is one of the factors contributing to striking increases in overdose deaths. To fully understand the magnitude of this problem, accurate detection methods for fentanyl and other novel opioid adulterant exposures are urgently required. The objective of this work was to compare the detection of fentanyl in oral fluid and urine specimens using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) in a population of heroin users presenting to the Emergency Department after overdose. METHODS: This was a prospective observational study of adult Emergency Department patients who presented after a reported heroin overdose requiring naloxone administration. Participants provided paired oral fluid and urine specimens, which were prepared, extracted, and analyzed using a dual LC-QTOF-MS workflow for the identification of traditional and emerging drugs of abuse. Analytical instrumentation included SCIEX TripleTOF(R) 5600+ and Waters Xevo(R) G2-S QTOF systems. RESULTS: Thirty participants (N = 30) were enrolled during the study period. Twenty-nine participants had fentanyl detected in their urine, while 27 had fentanyl identified in their oral fluid (overall agreement 93.3%, positive percent agreement 93.1%). Cohen's Kappa (k) was calculated and demonstrated moderately, significant agreement (k = 0.47; p value 0.002) in fentanyl detection between oral fluid and urine using this LC-QTOF-MS methodology. Additional novel opioids and metabolites, including norfentanyl, acetylfentanyl, and U-47700, were detected during this study. CONCLUSION: In this study of individuals presenting to the ED after reported heroin overdose, a strikingly high proportion had a detectable fentanyl exposure. Using LC-QTOF-MS, the agreement between paired oral fluid and urine testing for fentanyl detection indicates a role for oral fluid testing in surveillance for nonpharmaceutical fentanyl. Additionally, the use of LC-QTOF-MS allowed for the detection of other clandestine opioids (acetylfentanyl and U-47700) in oral fluid.

OBJECTIVE: To compare user self-identification of nonpharmaceutical fentanyl exposure with confirmatory urine drug testing in emergency department (ED) patients presenting after heroin overdose. METHODS: This was a cross-sectional study of adult ED patients who presented after a heroin overdose requiring naloxone administration. Participants provided verbal consent after which they were asked a series of questions regarding their knowledge, attitudes and beliefs toward heroin and nonpharmaceutical fentanyl. Participants also provided urine samples, which were analyzed using liquid chromatography coupled to quadrupole time-of-flight mass spectrometry to identify the presence of fentanyl, heroin metabolites, other clandestine opioids, common pharmaceuticals and drugs of abuse. RESULTS: Thirty participants were enrolled in the study period. Ten participants (33%) had never required naloxone for an overdose in the past, 20 participants (67%) reported recent abstinence, and 12 participants (40%) reported concomitant cocaine use. Naloxone was detected in all urine drug screens. Heroin or its metabolites were detected in almost all samples (93.3%), as were fentanyl (96.7%) and its metabolite, norfentanyl (93.3%). Acetylfentanyl was identified in nine samples (30%) while U-47700 was present in two samples (6.7%). Sixteen participants self-identified fentanyl in their heroin (sensitivity 55%); participants were inconsistent in their qualitative ability to identify fentanyl in heroin. CONCLUSIONS: Heroin users presenting to the ED after heroin overdose requiring naloxone are unable to accurately identify the presence of nonpharmaceutical fentanyl in heroin. Additionally, cutting edge drug testing methodologies identified fentanyl exposures in 96.7% of our patients, as well as unexpected clandestine opioids (like acetylfentanyl and U-47700).