Sentanyl: a comparison of blood fentanyl concentrations and naloxone dosing after non-fatal overdose

Abstract

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.

Keywords:

• Fentanyl
• overdose
• novel psychoactive
• opioid
• naloxone

Author contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Sam Ontiveros, Katherine Devin-Holcombe, Brittany Chapman, Roland C. Merchant, Sarah Marks, and Kavita Babu. Analytical testing and interpretation were performed by Alex Krotulski, Melissa Fogarty, Hai Trieu, and Barry Logan. The first draft of the manuscript was written by Alex Krotulski, Brittany Chapman, Sarah Marks, Roland C. Merchant and Kavita Babu. All authors commented on previous versions of the manuscript, and all authors read and approved the final manuscript.

Previous presentations

Results of this study were submitted for presentation to the 2018 North American Congress of Clinical Toxicology.

Disclosure statement

The authors have no conflicts of interest to report.

Additional information

Funding

Research reported in this manuscript was supported by the National Institute on Drug Abuse of the National Institutes of Health under award number R21DA046734. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.