Multiple fatalities in the North of England associated with synthetic fentanyl analogue exposure: Detection and quantitation a case series from early 2017

Highlights

• Synthetic fentanyls are almost always detected in cases where there is misuse of heroin.

• Carfentanil is reported as being 10,000 times more potent than morphine.

• Standard toxicology screens do not always detect the low concentrations of synthetic fentanyls.

• Synthetic fentanyls must be tested for in drug deaths where other drug concentrations are low.

Abstract

Background

Synthetic fentanyl analogues are highly potent opioid drugs which have no pharmaceutical use in humans. We detected the synthetic fentanyl analogues; carfentanil, butyryl fentanyl, fluorobutyrylfentanyl, furanylfentanyl, and alfentanil as well as fentanyl itself in 25 cases in early 2017. There have been no previous reports of synthetic fentanyl deaths in the United Kingdom (UK).

Methods

Cases in which the history clearly stated drug use but where a post mortem blood morphine concentration was lower than would be expected to explain the sudden death, were referred for further analysis by high resolution accurate mass (HRAM) mass spectrometry.

Results

25 post mortem cases in which synthetic fentanyl analogues were implicated in the cause of death were reported from January to May 2017. No cases were seen in June 2017. The age range was 21–54 years and 22 were male. There was a history of heroin use, or markers of heroin use on toxicology screening in 21/25 cases. Carfentanil and fentanyl were detected in 7 cases. Multiple synthetic fentanyl analogues were present in 13 cases, with the remaining 5 cases having only carfentanil present. Synthetic fentanyl analogues were detected in combination with other drugs in all cases. Significant concentrations of ethanol were detected in only 2 cases. The concentration range of carfentanil in blood was 90–4004 pg/mL. Of note, the 3 cases in which ante mortem carfentanil was quantified ranged from 21 to 98 pg/mL. In all cases, death was attributed to combined central nervous system depression.

Conclusions

This paper highlights a new and rapid emergence of these drugs into the UK illicit drug arena. Synthetic fentanyl analogues represent a significant challenge both analytically and clinically within the groups who misuse drugs. It is worthwhile considering the possibility of the presence of these drugs in cases in which a toxicological cause of death is not apparent analytically but there is a history of drug use and circumstantial evidence exists to support a drug-related death as the most likely cause. It may be that synthetic fentanyl analogues should be screened for routinely to avoid reporting any false negative results, but the cost implications and viability of this have not been fully evaluated.

Introduction

In the United States (US), there was a 72.2% increase in synthetic opioid related deaths from 2014 to 2015, while ‘heroin’ deaths increased by 20.6% in the same period [1]. The data for the United Kingdom (UK) is less well defined. There are no previous reports of synthetic fentanyl deaths in the UK. This paper will report deaths associated with synthetic fentanyl analogues in the UK.

Fentanyl is a potent μ-opioid agonist which has been used therapeutically in humans as both an analgesic and to enhance anaesthesia for many decades. Delivery is via transdermal patches, transmembrane absorption of fentanyl “lollipops” or intravenously. Fentanyl has a potency 50–100 times greater than morphine and 30–50 times greater than heroin [2], [3]. Fentanyl was first reported in the heroin supply in 1979 in Orange County, California [4] with fentanyl now being a highly sought-after street drug [5]. Synthetic analogues of fentanyl are employed in veterinarian medicine for the sedation of large animals but have no role in humans due to their enhanced potency. Carfentanil is reputed to be some 10,000 times more potent than morphine [6], [7]. The routes of administration for carfentanil reported on user websites include nasally, rectally, intravenously and sublingually [8], [9].

There have been intermittent reports in the US describing fentanyl and fentanyl analogue-related deaths in illicit-drug users, but often with minimal analytical confirmation of the synthetic analogues, although there has been a recent report of 13 post mortem cases from the Mid-West US including carfentanil quantitations [10]. There is a well-controlled, primarily ante mortem study, of all toxicity in Sweden being achieved through the STRADA project which includes synthetic fentanyl analogues [11]. There are also individual case studies reported internationally [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23]. However, there are very few cases involving carfentanil [19], the primary finding in all our cases, that have been reported in the peer reviewed literature.

It has been reported in the US that in 2016 an unprecedented surge in the number of heroin overdose cases associated with fentanyl use was observed, with a projected total of over 10,000 fentanyl related deaths in 2016 based on data from the preceding two years [24]. However, analytical confirmation has not been reported for many of these cases, so it is possible that these deaths were associated with fentanyl analogues rather than fentanyl itself [25]. There were reports of over 400 cases in the US in 2016 with many occurring in Ohio but the details are not in the public domain [25].

Toxicity from accidental exposure to carfentanil has also been reported in a single case report of a game keeper who suffered opioid toxicity and required naloxone after minimal facial contact from an animal tranquiliser dart solution [26]. The suspected use of carfentanil in a terrorist attack on a Moscow theatre in 2002 may have contributed to the death of 125 individuals. Although the Russian authorities have never admitted its use, analysis of clothing that had been stored revealed the presence of carfentanil [27]. This paper aims to describe the detection and quantitation, along with demographics and associated drugs in the first reported cases of deaths associated with synthetic fentanyls in the UK.