Continuing Education Activity
Gamma hydroxybutyrate (GHB) is pharmaceutically manufactured as sodium oxybate for the treatment of narcolepsy. This formulation is considered a Schedule III drug in the United States and is sometimes abused. In Europe, GHB is also still therapeutically used as an anesthetic and for the treatment of alcohol and opiate dependence. Since there is no specific antidote to reverse the toxicity, aggressive supportive care including mechanical ventilation may be required. Severe withdrawal symptoms are life threatening and can last up to 15 days. Patients should be treated with benzodiazepines and managed in the intensive care unit. Parents and guardians should be educated about safe storage of this agent to prevent accidental poisoning in children. This activity outlines the potential for abuse of this drug, reviews treatment for patients who have overdosed on it, and identifies the role of the interprofessional team in improving outcomes for patients that use gamma hydroxybutyrate.
Objectives:
- Identify the pathophysiology of gamma hydroxybutyrate toxicity.
- Describe when gamma hydroxybutyrate toxicity should be included on differential diagnosis.
- Explain the management of gamma hydroxybutyrate toxicity.
- Outline interprofessional team strategies to improve care coordination to advance recognition and management of gamma hydroxybutyrate toxicity and improve patient outcomes.
Introduction
First synthesized in 1960, gamma hydroxybutyrate (GHB) was originally used as an anesthetic. While it did not gain much esteem in health care due to poor analgesia and adverse effects, including seizure-like activity, GHB gained significant popularity as a sleep aid, bodybuilding, and weight loss supplement. GHB was prohibited by the United States Food and Drug Administration in 1990 and is currently a Schedule I drug in the United States. It has been labeled a date rape drug and is also illicitly used for recreational purposes, particularly at dance clubs and raves. Street names include G, Gamma OH, Georgia Home Boy, Liquid Ecstasy, and Liquid X.[1][2][3][4]
Etiology
Clandestine production of GHB contributes to its abuse. GHB is easily manufactured and available on the street as a powder or more often, a clear, odorless liquid sold in mini shampoo bottles. It has a salty or soapy taste, but only a small capful is needed for the immediate euphoric high that users seek. Alcohol or other coingestants may mask the taste. Strength and purity vary widely, which makes it difficult to determine the toxic dose that a user ingests accurately. Furthermore, misinformation on the internet downplays the potentially lethal effects of GHB toxicity and boosts its popularity as a bodybuilding or club drug.
Epidemiology
The prevalence of GHB use in the United States is not well known due to limited data. Mortality and morbidity data is also limited partly because GHB is easily mistaken for other drugs and not tested on routine drug screens. The available data reveals that the majority of GHB users are young adult white, middle-class males. User subgroups include recreational party drug users and homosexual males. Reports indicate that concurrent use of other drugs such as alcohol (76%), cocaine, marijuana, ketamine, MDMA (ecstasy) and methamphetamines is common in GHB-related emergency department visits.[5][6][7]
Pathophysiology
GHB is endogenously found in the brain and is a precursor of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). It acts on both GABA-B and GHB receptors. GHB has a biphasic effect on dopamine. Lower doses stimulate dopamine release by binding GHB receptors. Higher doses initially inhibit dopamine release via agonist effects on GABA-B receptors, leading to neuro-inhibition and central nervous system (CNS) depression, but after that increase dopamine release via the GHB receptor. While this accounts for both the sedative and excitatory effects of GHB, the mainstay of GHB toxicity is central nervous system and respiratory depression.
Gamma-butyrolactone and 1,4-butanediol, previously sold as industrial solvents or dietary supplements, are GHB substitutes that rapidly convert to GHB following oral ingestion, thereby producing the same clinical effects of GHB toxicity.
Toxicokinetics
GHB is rapidly absorbed in the body with a quick onset of action between five minutes to 15 minutes, with users often reporting an initial period of euphoria. The clinical symptoms and duration of GHB toxicity are dose-dependent; peak plasma concentrations and clinical effects are reached between 30 minutes to 60 minutes, and duration of action is two to four hours. The elimination half-life ranges from 20 minutes to 60 minutes. Lower doses of GHB (10 mg/kg) have amnestic and variable sedative effects. Doses of 20 mg/kg to 30 mg/kg lead to cycles of rapid eye movement (REM) sleep. Higher doses (50 mg/kg) result in bradycardia, respiratory depression, and coma. Co-intoxicants, especially alcohol, can further augment the effects and duration of symptoms.
History and Physical
GHB users often experience an initial disinhibition and euphoria as quickly as 15 minutes following ingestion. The classic presentation of GHB toxicity is a sudden onset of coma followed by an abrupt awakening within several hours. Symptoms are dose-related with higher doses causing more severe respiratory and CNS depression. It is not unusual for users to become agitated or combative before, during, or after a prolonged period of somnolence or coma. Additional CNS findings include amnesia, myoclonic activity, and seizure-like effects. Bradycardia, hypotension, apnea, vomiting, and hypothermia may also occur.
It is often difficult to obtain a reliable history due to patients’ altered mental status. Clues to GHB toxicity may include empty mini shampoo bottles in their possession, attendance at a party or nightclub, or possible sexual assault.
Evaluation
GHB toxicity is a clinical diagnosis. Blood or urine testing for GHB is not routinely available in the hospital setting. Diagnostic confirmation via gas chromatography and mass spectrometry is possible but may take up to seven to 14 days for results. A urine drug screen may aid in identifying or excluding coingestants. As with any potential intoxicated patient, a fingerstick glucose, blood alcohol level, acetaminophen level, and salicylate level should be obtained. A CT scan of the head or other radiological tests may be indicated if any injury or trauma is suspected.[8][9][10]
Treatment / Management
There is no antidote for GHB toxicity. The mainstay of treatment is airway protection and monitoring. Management should also include cardiorespiratory monitoring, pulse oximetry, and capnography if available. Patients may develop severe respiratory depression or apnea, and therefore immediate evaluation of the airway is paramount. In milder cases, supplemental oxygen with or without a nasopharyngeal airway is sufficient until the patient awakens. In more severe cases, endotracheal intubation may be necessary. GHB-intoxicated patients usually do not require any sedation while mechanically ventilated and will precipitously awaken and potentially extubate themselves or require sudden extubation. Severe bradycardia can be treated with atropine, and hypotension is often sufficiently managed with intravenous (IV) fluids. If there is any concern for opioid co-ingestion and toxicity, IV naloxone should be strongly considered. Patients can often be safely discharged home once they are awake, symptom-free, and all other co-intoxications or injuries are ruled out.
Differential Diagnosis
- Acute subdural hematoma in the ED
- Emergent management of subarachnoid haemorrhage
- Epidural hematoma in emergency medicine
Pearls and Other Issues
GHB is pharmaceutically manufactured as sodium oxybate for the treatment of narcolepsy. This formulation is considered a Schedule III drug in the United States. In Europe, GHB is also still therapeutically used as an anesthetic and for the treatment of alcohol and opiate dependence.
Withdrawal symptoms have been reported in chronic or dependent users after cessation of the drug. Early or mild symptoms of anxiety, tremors, tachycardia, and insomnia can quickly progress within 24 hours to severe and refractory agitation with autonomic instability. Severe withdrawal symptoms are life threatening and can last up to 15 days. Patients should be treated with benzodiazepines and managed in the intensive care unit.
Enhancing Healthcare Team Outcomes
GHB is pharmaceutically manufactured as sodium oxybate for the treatment of narcolepsy. This formulation is considered a Schedule III drug in the United States. In Europe, GHB is also still therapeutically used as an anesthetic and for the treatment of alcohol and opiate dependence. The agent is often misused. After prolonged used and sudden cessation, withdrawal symptoms have been reported in chronic or dependent users after cessation of the drug. The management of GHB overdose is by an interprofessional team. Since there is no specific antidote to reverse the toxicity, aggressive supportive care including mechanical ventilation may be required. Severe withdrawal symptoms are life threatening and can last up to 15 days. Patients should be treated with benzodiazepines and managed in the intensive care unit. Parents should be educated about safe storage of this agent to prevent accidental poisoning in children.
Gamma-Hydroxybutyrate Toxicity