Background To describe the epidemiological profile and clinical manifestations of liquid ecstasy (GHB) poisonings.
Methods All cases of GHB poisoning or overdose admitted to the Emergency Department (ED) of the Hospital Clinic (Barcelona) between 2000 and 2007 were recorded.
Results A total of 505 patients (mean age 24.7 years, 68% men) were included. Most patients were brought to the hospital by ambulance (98%), during the weekend (89%) and during the early morning (75%). Symptoms began in a public place in 97%. Reduced consciousness was the most important clinical manifestation: 72% of patients had a Glasgow Coma Score of ≤12. 76% of patients had consumed other drugs: ethanol (64%), amphetamines and derivates (30%), cocaine (28%), ketamine (11%), cannabis (9%) and others (5%). Treatment was required in 26% of cases and an antidote was administered in 35 cases with no response. There were no deaths. The combined GHB group had a longer time to complete recovery of consciousness (71±40 vs 59±40 min, p<0.001) and a higher percentage of patients with severely reduced consciousness at ED arrival (54% vs 37%, p=0.01), need for treatment (29% vs 16%, p<0.01) and need for mechanical ventilation (3% vs 0%, p<0.05) compared with the pure GHB group.
Conclusions GHB intoxication leading to reduced consciousness is a frequent reason for ED admission, above all in young people and in the early morning at the weekend. Symptoms are more severe in patients who have taken GHB in combination with other substances of abuse.
- Coma of unknown origin, drug abuse
- GHB overdose
- liquid ecstasy
- mental health
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Liquid ecstasy, also known as ‘fantasy’, is the street name of gamma-hydroxybutyric acid (GHB), a physiological neurotransmitter synthesised in 1960 as an alternative anaesthetic because of its ability to induce sleep and reversible coma.1 Liquid ecstasy has no toxicological or chemical similarity to the amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA), popularly known as ecstasy. Illicit consumption of GHB by young people in the USA at discos, raves or as part of the drug scene began in the 1970s. The drug arrived in Europe in the early 1990s and the first GHB confiscation by Spanish police was reported in 1997. Cases of severe intoxication (including death) have been increasingly reported in parallel to the spread of the drug.2 As in other drug overdoses, emergency departments (ED) play a pivotal role in the identification and treatment of these patients.3 Between 2000 and 2001, the ED at Hospital Clinic, Barcelona attended 104 cases of GHB intoxication, the second most common cause of ED admission for illicit drugs after cocaine during this period.4
However, these data and those of neighbouring hospitals, showed it was difficult to separate the signs and symptoms of GHB intoxication from those of other substances simultaneously abused by most GHB users, with studies showing simultaneous ethanol consumption in 73% of cases and ingestion of other illicit drugs in 86%.5 After nearly 8 years, the authors have collected data from a large sample of patients, of whom a significant number had only taken GHB.
The objectives of this study were to describe the clinical and epidemiological profile of GHB intoxication in 505 consecutive patients, and to define the clinical profile of GHB intoxication alone in order to determine whether there was any difference in the clinical profile and outcomes when GHB is consumed in combination with other substances of abuse.
Material and methods
An observational study was carried out in a tertiary university hospital, with a target population of 500 000 people. The ED attends over 125 000 patients a year and is organised into clinical units.6 All toxicological admissions (excluding chemical burns) are seen in a medical unit. Between April 2000 (when the first case of GHB overdose was identified) and December 2007, all toxicological emergencies, including those caused by illicit drug consumption, were recorded. As part of the routine Toxicological Unit duties, every Monday all toxicological cases seen in the ED the previous week are systematically and retrospectively reviewed.
GHB overdose was defined as any patient admitted to the ED due to ingestion of recreational drugs who reported using GHB. From January 2000, urine samples from suspected cases were analysed for GHB by gas chromatography-selected ion monitoring-mass spectrometry (HP5971) after liquid–liquid extraction and derivatisation of extracted GHB with BSTFA to confirm GHB consumption. As this test is not routinely immediately available in the emergency laboratory, the samples were kept at 4°C for processing on the following working day morning. Once ED physicians became familiarised with the clinical profile (around 2002), analyses for GHB were only made in cases where there were doubts about the clinical profile or the reports from patients or the people accompanying them, or if criminal use was suspected.
Demographic variables, (age, sex, date and hour of ED admission); clinical variables (temperature, heart rate, respiratory rate, Glasgow Coma Scale (GCS) score, and systolic and diastolic blood pressure); laboratory data (electrolyte levels and blood counts); and urine toxicology screening findings (ethanol, opiates, cocaine, amphetamine, benzodiazepines and cannabis) were recorded. Toxicological screening was not performed routinely but was based on clinical utility. Using the methodology employed in the authors' laboratory, a positive result for cannabis can be obtained for 7–10 days after cannabis consumption, 2–3 days after cocaine consumption, 2–3 days after opiate consumption, 2–3 days after methadone consumption and 2–3 days after amphetamine-MDMA consumption. In patients without toxicological analysis, the ingestion of other drugs was considered to be that reported by the patient. Clinical complications during the time required to regain complete consciousness were recorded. Recovery time was defined as the time from initial ED admission to the recovery of complete consciousness (GCS score=15).
Patients were divided into two groups: patients who denied the ingestion of other drugs (including alcohol but excluding tobacco) and/or in whom the toxicological screening was negative for all screened drugs (pure GHB group), and patients who admitted the co-ingestion of other drugs and/or in whom the drug screening was positive (combined GHB group).
The results are expressed as percentages (qualitative variables) or mean±SD (quantitative variables). Comparisons were made using the χ2 test (or Fisher's exact test if the number of expected cases was less than 5) and an unpaired Student t-test respectively. The level of statistical significance was established as p<0.05.
Five-hundred and thirty-one GHB intoxications were identified. The annual distribution is shown in figure 1. Twenty-six cases were excluded due to lack of data or because patients were discharged from the ED against medical advice after refusing treatment. The final sample was 505 patients; 120 in the pure GHB group (24%) and 385 in the combined GHB group (76%). Toxicological analysis was performed in 174 of these patients: 31 from the pure GHB group (with no other drugs detected aside of GHB), and 143 from the combined GHB group. The analysis resulted in reallocation of two patients initially included in the pure GHB group to the combined GHB group because they were positive for cannabis and cocaine respectively. Table 1 shows the other drugs identified in the combined GHB group, of which ethanol (64%), MDMA (30%) and cocaine (29%) were the most frequent. Of note, in 91% of cases results of toxicological analysis matched with drugs directly reported by patients.
The motive for seeking medical help was reduced consciousness in all cases. Eighty-four per cent of patients (424/505) were still suffering some degree of reduced consciousness (GCS <15) at ED admission. In 98% of cases, patients were brought to the ED by ambulance, in 1% by police and in 1% by friends. GHB was laboratory-confirmed in 111 patients (22%). Most GHB intoxications were admitted to the ED at night (80% between 00.00 and 08:00) and at the weekend (82% between 16:00 on Friday and 08:00 on Monday) (figure 2).
There were no significant clinical or demographic differences between the two study groups, except that severely reduced consciousness was more frequent in the combined GHB group (p=0.01; table 2) and patients required more time to regain complete consciousness (15 points in the GCS; p<0.001). Hypotension was very infrequent (2%). The most frequent signs and symptoms were neurological (headache, instability, disorientation, dysarthria, convulsions), behavioural (disinhibition, aggressiveness, emotional lability), gastrointestinal (nausea, vomiting, abdominal pain), respiratory (dyspnoea, cough) and cardiovascular (chest pain, palpitations).
Table 3 shows patient outcomes. Patients in the combined GHB group more frequently received treatment, including only supportive treatment (p<0.01), but there were no significant differences between specific treatments. Mechanical ventilation was only required for 3% of patients in the combined GHB group (p<0.05). Antidotes were administered in 35 cases (7%), of whom 34 received naloxone alone or combined with flumazenil; no significant improvements in the level of consciousness were recorded. No patient was administered physostigmine. No patient died in the ED.
In recent decades, many ED in developed countries have observed a change in drug-related admissions, with a decline in heroin-related cases and a substantial increase in cases due to cocaine and synthetic drugs.7–9 In recent years, GHB overdoses have increasingly been seen in the ED of large cities such as Barcelona, reflecting increased recreational use. GHB, together with cocaine, ecstasy (MDMA), methamphetamine, LSD, phencyclidine and ketamine are the most-characteristic ‘club drugs’.10
Admissions due to GHB consumption were more frequent during the weekend and at night.11 Although the incidence of GHB overdose was not analysed by days of the week, easy consumer access to GHB sometimes results in epidemic waves of overdoses (three or more patients attended in the same ED in less than 24 h), sometimes in the context of mass events.12 No investigation was made into the reasons for GHB consumption. However, the organoleptic characteristics of GHB mean it is often implicated in crimes such as robbery and rape, and it is widely used by homosexual men as an aphrodisiac during sex.13
The GHB overdoses in this study represent 13% of ED admissions due to an adverse reaction or poisoning resulting from a drug of abuse in Hospital Clinic, Barcelona, with a mean incidence of 66 cases/year of GHB overdose, although a decreasing trend has been observed in the last three years. In terms of the target population, this represents one GHB overdose attended at ED per 8333 persons/year. However, many GHB poisonings are resolved in situ by ambulance staff and paramedics and do not reach hospital because spontaneous recovery is often very rapid. These cases are not included in this study, but should be taken into account when estimating the true rate of GHB intoxications.
The clinical profile of GHB poisonings or overdoses varies according to the dose and to any substances co-ingested. The main symptom is a normally self-limiting episode of relatively sudden reduced consciousness, which may evolve to a short-lasting, deep, hypotonic, hyperreflective coma and, characteristically, sudden awakening.14 The present results show that when GHB is consumed in combination with other drugs (including alcohol; the combined GHB group), the duration and profundity of coma is greater than when GHB is taken alone (the pure GHB group), which is probably the explanation for the greater requirement for mechanical ventilation. To the authors' knowledge, this is the first study to demonstrate a greater clinical risk of complications in patients taking GHB in combination with other drugs in a large series of patients.
Although reduced consciousness was the main reason for ED admission in the present series, 91% of patients were discharged in <12 h, confirming the short elimination half-life (42 min) and good prognosis of GHB overdoses.15 Studies have shown that coma time does not vary significantly according to whether antidotes are used or not. Naloxone and flumazenil seem to have no role in this poisoning unless there is simultaneous benzodiazepine or opiate ingestion.16 The use of physostigmine is controversial, but most reports have found that it provides no clinical benefit.17–19 In addition, it reduces the convulsive threshold and may cause heart block.18 After recovery from coma, amnesia with respect to the preceding events is common.20
Severe GHB poisoning should form part of the differential diagnosis of cases of coma of unknown origin admitted to the ED.21 Given the short coma time and the lack of complications and mortality normally seen, the fundamental treatment of patients with GHB overdoses is general support, as there is no scientific evidence for the utility of antidotes.22 The main difficulty in confirming the diagnosis is that toxicological analyses for GHB are not routinely available.23 Nonetheless, deaths due to GHB overdoses in Barcelona cannot categorically be ruled out because the final coroner's report diagnosis has not been investigated for deaths in people who did not attend the ED but died at home or elsewhere.
A possible limitation of the present study was that laboratory confirmation of GHB was only obtained in 111 patients (22%), and that GHB consumption was defined according to patient report. However, another study in Hospital Clinic, Barcelona found that toxicological analysis confirms the patient's report of GHB consumption in more than 85% of cases, and therefore that reported and real consumption may be considered to be similar.24 In addition, negative analyses for GHB do not always exclude consumption, as the half-life of elimination is very short. In the present study, when the authors recorded patient report and toxicological results, a reasonably high match was found, therefore it is believed that the study conclusions can be made with confidence.
The recreational use of GHB, marketed to young consumers in 10 millilitre bottles of a colourless, odourless, insipid liquid, gives the consumer a false sensation of safety and low risk. In addition, ED physicians reading a study such as this may only appreciate that in more than 500 overdoses of GHB there was no death. However, it should be remembered that GHB severely depresses the central nervous system and this action may be potentiated by the simultaneous use of other drugs, with potentially fatal consequences, as shown by some reports.25 These potentially critical patients should receive the same quality care afforded to any other patient in the ED.
Provenance and peer review Not commissioned; externally peer reviewed.