The first reported UK fatality related to gamma-butyrolactone (GBL) ingestion

Introduction

Gamma-butyrolactone (GBL) is rapidly metabolized to gamma-hydroxybutyrate (GHB) in vivo following ingestion. GBL and GHB cause similar clinical features in users, and both of these agents are widely used as recreational drugs due to their mood-enhancing, stimulant and prosexual effects, particularly on the nightclub scene.

In 2003, GHB was classified in the UK as a Class C controlled substance under the Home Office Misuse of Drugs Act (1971). GBL is currently not classified in the UK and many other countries in the world; the UK Home Office Advisory Council on the gbl kaufen Misuse of Drugs is currently consulting on proposed changes to the legal status of GBL, and the related compound 1,4-butanediol (1,4BD).

There are numerous reported fatalities related to GHB ingestion. However, although there has been media coverage in the lay press of potential GBL-related fatalities in the UK,there have only been three previous reports of GBL-related fatality, two in Germany and one in the USA. We report here the first case of a fatality related to isolated GBL toxicity in the UK, which we feel supports the case for classifying GBL similar to that of GHB.

Case report

A 25-year-old man, with no significant previous medical history, was found unconscious in bed by his partner. There was a history of ingestion of GHB the previous evening while out clubbing. He had returned home ‘acting strangely’ six hours prior to being found. His partner commenced basic cardiopulmonary resuscitation after calling an ambulance. When the ambulance service arrived, he was found to be in asystole and therefore resuscitation was continued. On arrival in A&E, 40 minutes after being found ‘collapsed’, he remained in asystole. He was intubated (note was made of vomit in his airway) and resuscitation continued using standard Advanced Life Support (ALS) protocols. A pre-intubation arterial blood gas revealed a profound acidosis (pH <6.80, lactate >15 mmol/L, pO2 0.9kPa, pCO2 10.9kPa).

After four ALS cycles, he remained in asystole and therefore resuscitation was discontinued in view of the prolonged out-of-hospital cardiac arrest.

Toxicological screening

Analysis of the biological samples for ‘total’ GBL was performed by gas chromatography-mass spectrometry (GC-MS), after conversion of any GHB present to GBL. The total GBL concentration was 282 mg/L. Ephedrine was detected at a subtherapeutic concentration (0.05 mg/L). No other drugs or ethanol were detected on comprehensive toxicological analysis of blood and urine, and no ethanol was detected in the vitreous humour sample. The liquid (Figure 1) ingested by the deceased was analysed by diamond ATR infra-red spectroscopy (IR) and found to contain GBL, with no GHB detected. It is therefore highly likely that the total GHB/GBL found on postmortem analysis of the deceased was due to ingestion of GBL.

Discussion

We report here the first UK case of a fatality related to confirmed, isolated GBL toxicity. There have only been three reports published previously of confirmed GBL-related fatalities, two in Germany and one in the USA. GBL is widely used in the UK chemical industry and it is reported that over 1000 tonnes are imported into the UK per year for industrial purposes. It is used as an intermediate solvent in numerous chemical processes, as a solvent in the electronics industry and in the production of domestic and industrial cleaning products and paints.

There is the potential for postmortem production of GHB in urine samples stored for prolonged periods of time and for postmortem redistribution of GHB. However, the total GBL concentration (282 mg/L) seen in this patient is in the range reported in previous GHB/GBL-related fatalities and cases of severe GHB toxicity. In one series of 49 GHB-related deaths, the mean femoral blood GHB concentration was 292 mg/L and in a series of 18 GHB intoxications in which toxicological screening was undertaken, all three patients with a GHB concentration of greater than 220 mg/L had a GCS of 3/15.

GBL is rapidly metabolized to gamma-hydroxybutyrate (GHB) in vivo and ingestion of both of these agents, and the other GHB precursor 1,4-BD, cause similar clinical features and complications. In a recent large UK series (n=158) of acute GHB/GBL toxicity, 47.4% of patients had a GCS ≤ 8/15 on presentation to A&E. GHB and GBL are both widely used as recreational drugs due to stimulant effects, particularly on the nightclub scene. There is some evidence of increasing recreational use of GBL in a number of countries, and there has been a year-on-year increase in the GBL:GHB ratio in patients presenting with GBL/GHB toxicity to our clinical service in London. It is likely that, at least in part, this is related to the disparity in the legal status of GBL and GHB and, therefore, the easier availability of GBL to users.

GHB was classified under the Misuse of Drugs Act, 1971, in the UK in 2003, due to deaths associated with its use and the potential for it to be used for drug-facilitated sexual assault (DFSA), and is also classified in most other countries in the world. However, GBL remains legal in many countires. The UK Home Office Advisory Council on the Misuse of Drugs (ACMD) has recommended that GBL and 1,4-BD are brought under control gbl kaufen of the Misuse of Drugs Act 1971. However, in view of the numerous legitimate industrial uses of these chemicals, the UK Home Office is currently consulting on the options for classification and, in particular, what if any arrangements should be made for licensing for industrial use of GBL and 1,4-BD.

Conclusions

Based on this fatality related to GBL ingestion, and the evidence of increasing recreational use of GBL, we would fully support a change in the legal status of GBL to bring it in line with the classification of GHB under the Misuse of Drugs Act 1971, and that this should happen as soon as is practical.