Background

In the current scientific literature the distinction between endogenous gamma-hydroxybutyric acid (GHB), the drug sodium oxybate and illicitly manufactured GHB is somewhat vague.1 This report refers to GHB as a reputed neurotransmitter and gamma aminobutyric acid (GABA) metabolite, that is endogenously synthesised by neurons in the brain2; to sodium oxybate as the identical compound of GHB that is manufactured and distributed by the pharmaceutical industry as Xyrem;1 and to illicit GHB as all illegally manufactured GHB, sodium oxybate and street drug products that are intended to be GHB and/or (partially) contain the compound of GHB.1

Since illicit GHB is supposedly used for its euphoric and aphrodisiac-like effects, as well as for its enhancing effects on social behaviour, it has become progressively popular as a party drug.1 3 Besides the well-known positive effects associated with illicit GHB, the association between its abuse and frequent overdoses, coma and (severe) intoxications resulting into recurrent presentations at emergency departments, as well as hospital admissions, are also well documented.4–7 Following the popularity of illicit GHB a general trend of increase in abuse was seen after it first emerged, even though overall prevalence numbers remain relatively low.8 However, since comparable systematic data on user prevalence between different countries is lacking, because of different user populations and patterns, a comprehensive overview is being hindered.9 For example, in the Netherlands, Norway, and the UK, the estimated prevalence for current illicit GHB use in the general population ranges from 0.1% to 1.3%, whereas rates limited to specific subpopulations, for example partygoers, are considerably higher.10–12 Nevertheless, the profile of a European intoxicated by illicit GHB is being described as: a young man (mean age 31 years) in need of medical care for changed behaviour and a reduced consciousness, primarily during the weekend.9

Illicit GHB withdrawal symptoms can vary from mild symptoms consisting of tremors, tachycardia, anxiety, insomnia, hypertension, nausea and vomiting to severe symptoms including hallucinations, delusions, rhabdomyolysis, seizures and delirium.3 The severity of these withdrawal symptoms mostly depends on the frequency of ingestion of the illicit GHB and severe withdrawal can occur within an interval of 1–8 hours of ongoing usage.3

Despite that illicit GHB abuse poses a sizeable toxic health effect in the emergency setting, there are no specific epidemiologic descriptors known regarding the abuse of this drug during pregnancy. Even though this information lacks, illicit GHB abuse during pregnancy certainly presents a huge clinical challenge, partly due to the absence of evidence-based and practiced-based guidelines and treatment options for the (severe) withdrawal symptoms within this specific patient population.

This case report presents the case of a pregnant woman in her late twenties with illicit GHB withdrawal symptoms who was seen at the emergency department of a hospital in the Netherlands.

Case presentation

Initially the woman, known with no relevant medical history and no family history, was presented to the neurologist with a seizure of unknown cause. However, after having admitted the use of illicit GHB, temazepam and baclofen, the liaison psychiatrist was consulted. In addition, examination revealed dilated pupils, sweating, tremor, tachycardia and bradyphrenic thinking.

Investigations

Further somatic screening revealed a large laceration of the chin as a result of a fall due to the seizure, a left-sided mandibular fracture with no (intra)cerebral bleeding on the CT scan, and a urinary drug test positive for benzodiazepines. Screening for illicit GHB was not part of the standard drug-testing panel. This is often the case in emergency settings, because of the short half-life of illicit GHB. In addition, heteroanamnesis disclosed that she was pregnant for 29 weeks. Subsequently, a cardiotocography was made, which showed no foetal stress.

Differential diagnosis

This case concerns a healthy young woman with no previous medical history and without a relevant family history. She was presented while being intoxicated with polypharmacy with clinical symptomatology of dilated pupils, sweating, tremor, tachycardia and bradyphrenic thinking. In addition, somatic screening revealed no other significant leads. Thus, the seizure was classified as a severe withdrawal symptom. Thereafter, illicit GHB was prioritised by anamnesis and heteroanamneses as the main drug responsible for her withdrawal symptoms. Furthermore, anamnesis revealed that according to herself she had used a few tablets of temazepam and baclofen to temper the occurring illicit GHB withdrawal symptoms.

Treatment

After presentation the large laceration of the chin was immediately stitched. Thereafter, she was motivated for voluntary admission at the in-hospital psychiatry department for further treatment by a multidisciplinary team. After admission, diazepam orally was started to treat the withdrawal symptoms and by titration a total dosage of 15 mg was reached within the first 24 hours. Thereafter, all withdrawal symptoms seemed to be in complete remission and the tapering-off of the diazepam to a dosage of 5 mg/day was reached in over a week. During the tapering-off of the medication she continuously had a resting heart rate varying between 80 and 90 beats/min and she had trouble sleeping. For the latter mirtazapine 15 mg was started without satisfactory result. On reaching a dosage of 2.5 mg/day of the diazepam in more or less one and a half weeks she became agitated, disorganised and suffered from visual hallucinations. Following this acute change in mental status she suddenly presented herself with erratic behaviour by diving ‘head first’ onto the ground and by trying to burn her own leg with a lighter. Sodium oxybate was started in a dosage of 1050 mg to treat the change in her mental state, which was indicated as an illicit GHB withdrawal delirium; by titration a dosage of 1950 mg per every 2 hours was reached. At the same time diazepam was completely stopped. Parallel to treatment by medication she was voluntarily limited in her freedom of movement by physical restrains to prevent further self-harm. If at any point in time it was possible to alternatively provide adequate one-on-one supervision during this period, either by medical staff or family, the physical restrains were removed. In addition, a second CT scan of the head and neck was made, which showed no additional trauma. After the start of the sodium oxybate she stabilised quickly and it was possible to completely remove the physical restrains after approximately 5 days. Thereafter, the complete tapering-off of the sodium oxybate was reached in less than a week in steps of 300 mg at a time. After treatment with sodium oxybate was stopped no signs of relapse of withdrawal symptoms were seen. Mirtazapine was continued with sufficient effect, since she did not have any further sleeping difficulties. Following her recovery of a withdrawal delirium she was operated with success for her mandibular fracture, while remaining admitted in the in-hospital psychiatry department for the duration of her pregnancy.

Outcome and follow-up

After having been pregnant for 37 weeks she was transferred to the obstetrics department to initiate the start of her labour, because of pre-eclampsia. She gave birth to a healthy daughter. Thereafter, both mother and daughter were discharged from the hospital in good condition, under the close supervision of the Child Protection Service and an outpatient psychiatry unit specialised in the treatment of addiction. Further follow-up after discharge is not available.