DESCRIPTION
USES
This substance may be used therapeutically but can also be subject to abuse. |
Treatment for narcolepsy Treatment for alcoholism Anesthetic agent Euphoric “Date rape” agent “Growth Hormone booster” “Aphrodisiac” “Muscle builder” (although effectiveness has never been proven) |
INTERVENTION CRITERIA
The correct identification of the substance is important. If the symptoms are inconsistent with those described in the literature, or the history is considered unreliable, other substances may need to be considered. |
Medical assessment and observation is recommended for: - Any suspected ingestion in children The risks of decontamination outweigh any benefits, and should not be attempted. |
Medical assessment and observation is recommended for: - Any suspected ingestion - Exposures with intent to self-harm The risks of decontamination outweigh any benefits, and should not be attempted. History of dose ingested is not a reliable guide to management. |
All patients require medical attention. |
If medical observation is required, the patient must be monitored for 4 hours following exposure for onset or worsening of symptoms. |
If the patient is asymptomatic at the end of the observation period, and provided that appropriate assessment and investigations have been completed, they may be: Discharged into the care of a reliable observer, or Referred for psychological assessment if the overdose or exposure was with intent to self-harm |
Serum concentrations do not aid management. |
Monitor: Level of consciousness Heart rate Blood pressure Respirations Seizure activity |
Admission to an intensive care environment is recommended for patients who develop significant signs of toxicity including: CNS depression requiring intubation Respiratory depression Aspiration pneumonitis Hemodynamic instability |
TREATMENT
TREATMENT SUMMARY
Emergency stabilization may be required for respiratory depression and/or pulmonary aspiration, immediate assessment and management of respiratory compromise is a priority. Due to fast onset of action, gastrointestinal decontamination is not recommended. There is no proven antidote for poisoning. Extracorporeal elimination techniques would not be anticipated to be of clinical benefit in the majority of patients as most will satisfactorily recover with adequate airways management alone. Supportive care is the mainstay of management, with primary emphasis on airway management and cardiovascular support. Airway protection including endotracheal intubation and/or assisted ventilation may be necessary due to respiratory depression and aspiration risk. Seizures may rarely occur and, in the presence of coma, indicate anoxia: manage the airway and ensure adequate ventilation. Should repetitive seizure occur in a well ventilated patient treat with a benzodiazepine, or if still refractory, a barbiturate. Myoclonic jerking is a recognized re-emergence phenomenon and single episodes do not require treatment. Other complications such as bradycardia, hypotension, hypothermia, and gastrointestinal upset should be treated along usual guidelines. A sedative-hypnotic withdrawal syndrome is recognized after chronic abuse of this compound and may last 3 to 21 days. Benzodiazepines are usually effective to relieve symptoms, but high doses may be required. Severe cases of GHB withdrawal may be refractory to benzodiazepines and benefit from treatment with baclofen or barbiturates. Consultation with a medical toxicologist or poison center is recommended for cases of refractory GHB withdrawal. Weakness, headache, fatigue, and nausea lasting 3 days after ingestion may occur. However, if significant CNS depressant effects persist beyond 8 hours, alternative causes should be investigated. |
EMERGENCY STABILIZATION
Ensure Adequate Cardiopulmonary Function |
Ensure the airway is protected if compromised (intubation may be necessary). |
Establish secure intravenous access if hypotensive. |
Airway Breathing Blood pressure Heart rate/rhythm Core body temperature Blood oximetry |
DECONTAMINATION
Decontamination Not Recommended |
Absorption is too rapid for decontamination to be effective.
|
Supportive care is likely to be successful without decontamination.
|
ANTIDOTE(S)
There Are No Antidotes For This Substance |
There are no specific antidotes for this overdose.  Agents including naloxone, flumazenil, and physostigmine have been investigated as potential antidotes. None have shown consistent results in reversing intoxication. |
ENHANCED ELIMINATION
Enhanced Elimination Not Recommended |
There is limited information regarding use of hemodialysis, hemoperfusion, hemodiafiltration, or hemofiltration to enhance elimination. GHB has minimal protein binding, a low molecular weight,  and a relatively small volume of distribution,    suggesting use of extra-corporal techniques may enhance its elimination. However, it would not be anticipated to be of benefit in the majority of patients as GHB has a rapid clearance and short duration of clinical effects. |
SUPPORTIVE CARE
Closely monitor: Level of consciousness Respiratory function Gag reflex For signs of sedative-hypnotic withdrawal |
Respiratory compromise is the most critical problem in severe poisoning. Intense respiratory support, when needed, constitutes the most vital supportive measure. Rapid sequence induction with endotracheal intubation and/or assisted ventilation may be required.  |
Monitoring for respiratory failure should include: Chest auscultation Oxygen saturation Blood gas analysis |
Manage respiratory failure following standard treatment protocols. |
Aspiration is a significant risk. Protection and careful monitoring of the airway is required if aspiration is suspected. Oxygen should be administered and artificial ventilation may be required.  |
Monitor: Airway Breathing Pulse oximetry Blood gas analysis Chest x-ray |
Profound coma is characteristic and generally short-term. Airway protection may be required, endo-tracheal intubation and even ventilation may on occasion be necessary.  |
Closely monitor level of consciousness. |
Manage coma following standard treatment protocols. |
Myoclonic jerking is recognized as a re-emergence phenomenon (sometime mistaken for seizure activity) and does not require treatment. However, tonic-clonic seizures may occur and should be treated with standard protocols. Anoxia is an important precipitant and adequate airways and ventilation must be ensured. |
Observe the patient closely for onset of seizure activity. |
Bradycardia may occur in moderate to severe intoxication. Pharmacological intervention is rarely required in patients with hemodynamically stable bradycardia. Atropine may be useful in the presence of hemodynamically-unstable bradycardia.  |
Monitor: Heart rate/rhythm Blood pressure ECG |
Manage bradycardia following standard treatment protocols. |
Metabolic acidosis is reported in severe cases. Acid-base abnormalities should be sought and appropriately treated. In severe, refractory acidosis, hemodialysis may be required.  |
Monitor: Blood gases Plasma lactate |
Manage metabolic acidosis following standard treatment protocols. |
Monitor for: Insomnia Confusion Hallucinations Autonomic instability Tachycardia Hypertension Diaphoresis Tremor Increased creatine kinase |
Manage withdrawal following standard treatment protocols. |
DISCHARGE CRITERIA
Patients may, if initially symptomatic, be discharged following 4 hours of observation. Symptomatic patients may discharged subsequent to becoming stable and asymptomatic.  Children should not be discharged at night. |
FOLLOW UP
Medical follow-up is unlikely to be required, as long as recovery from any complications is complete. Psychiatric intervention may be necessary depending on the circumstances of the exposure. |
PROGNOSIS
Following appropriate supportive care the prognosis is good. |
SIGNS AND SYMPTOMS
The correct identification of the substance is important. If the symptoms are inconsistent with those described in the literature, or the history is considered unreliable, other substances may need to be considered. |
Other drug/compounds are commonly co-ingested with this substance and may significantly influence the clinical picture.  With mild toxicity, gastrointestinal upset may occur and CNS effects predominate including CNS depression, euphoria, ataxia, disorientation, dizziness, and occasionally miosis and nystagmus. Sudden drowsiness followed by profound coma is a characteristic presentation; a GCS of 3 is not uncommon. Recovery is sometimes accompanied by emergence phenomena including myoclonic jerking, transient confusion, and agitation and combativeness.  Persistent symptoms of weakness, headache, fatigue, and nausea lasting three days after ingestion has been noted,  and a withdrawal syndrome is described.   |
Onset/Duration of Symptoms |
Mild Gamma-Hydroxybutyrate Toxicity | Moderate Gamma-Hydroxybutyrate Toxicity | Severe Gamma-Hydroxybutyrate Toxicity | Euphoria Drowsiness Dizziness Confusion Disorientation Vomiting | Bradycardia Hypotension Myoclonic jerking Hypothermia (mild) Agitation Ataxia Miosis | Respiratory depression Profound coma Rhabdomyolysis Seizure Respiratory arrest |
|
ACUTE EFFECTS (ORGAN SYSTEM)
Incoordination   Dysarthria   Headache   Euphoria   Amnesia   Vertigo  Disinhibition  Delusions  Bruxism (teeth grinding)  Extrapyramidal side effects  Dystonias  Athetoid posturing  Tremor   |
Chest tightness   Palpitations  ECG changes U waves  Transient P-wave inversion  Elevation of the ST segments  QTc prolongation  Right bundle-branch block   First-degree atrioventricular block  Atrial fibrillation   Asystole  |
Cyanosis   Tachypnea  Pneumothorax  Pulmonary edema   |
Nausea  Salivation   Abdominal pain  |
Hypernatremia (if large doses of the sodium salt ingested)  |
Nausea and vomiting   Diarrhea   Abdominal pain  Dyspnea  Tachypnea  Miosis  |
TOXICITY
The correct identification of the substance is important. If the symptoms are inconsistent with those described in the literature, or the history is considered unreliable, other substances may need to be considered. |
HUMAN
The toxic dose in children has not been established. |
Sucked on 2 nail polish remover pads containing 84% GBL, 10% butoxyethanol, 2% diethylene glycol, 1% panthenol, and 1% propylene glycol(ingested) 9 month male: Sucked on pads for less than a minute; within 15 minutes, he vomited and became drowsy; after 30 minutes comatose with a GSC of 3; was give oxygen en route to hospital; presented to ED 60 minutes post ingestion, GSC had improved to 6, hypotension, bradycardia, shock and mild respiratory acidosis; by 90 minutes GSC recovered to 12; hyperalert and extremely giddy for several hours Supportive care, including fluid resuscitation Recovered 8 hours post ingestion Sucked on nail polish remover pads containing 84% GBL, 10% butoxyethanol, 2% diethylene glycol, 1% panthenol, and 1% propylene glycol(ingested) 15 month female: initially asymptomatic but within 5 minutes became wobbly and "high"; on arrival by ambulance cyanotic with labored breathing and GSC of 3, initially heart rate of 180/min, pupils constricted and sluggishly reactive; on arrival to ED 30 minutes later, remained cyanotic, hypnotic, unresponsive, and bradycardic; her capillary refill time was prolonged; also oral and glottic edema; despite fluid resuscitation, she had marked abdominal distention and surgical emphysema; chest radiograph revealed aspiration Supportive care, including intubation, fluid resuscitation, chest drains, and respiratory support Recovered after 5 days in ICU, was discharged after 13 days. No long term respiratory or neurological difficulties. |
10 mg/kg | Anterograde amnesia, hyptonia, and euphoria | 20 to 30 mg/kg | Drowsiness, a normal sequence of REM and non-REM sleep, and myoclonus | 50 mg/kg | Anesthesia and unconsciousness | >50 mg/kg | Decreased cardiac output, severe respiratory depression, seizure-like activity, coma |
Sodium hydroxide may be inappropriately used in the preparation of gamma hydroxybutyrate forming a caustic mixture.  |
ANIMAL
Sodium Gamma Hydroxybutyrate: LD50 Oral, Rat | 9,690 mg/kg9,690 mg/kg/ |
LD50 IP, Rat | 1,650 mg/kg1,650 mg/kg/ |
LD50 IP, Mouse | 3,330 mg/kg3,330 mg/kg/ |
|
BIOLOGICAL LEVELS - TOXIC
Blood concentrations do not aid patient management. |
REPRODUCTION
PREGNANCY
GHB crosses the placenta.  Therapeutic GHB/sodium oxybate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.  There are no adequate and well-controlled studies in pregnant women. Animal studies in rats and rabbits have shown no clear evidence of developmental toxicity. In rats administration of 150, 350, or 1,000 mg/kg/day throughout pregnancy and lactation resulted in increased stillbirths and decreased offspring postnatal viability and body weight gain at the highest dose tested. Gamma hydroxybutyrate is not reported as teratogenic when injected into fertile chicken eggs.  |
LACTATION
GHB is excreted into human breast milk.  GHB may affect the infant. Taking GHB is not considered acceptable when breastfeeding. The manufacturers of therapeutic GHB/sodium oxybate only recommend use while breast feeding when the potential benefit out weighs the risk.  |
TOXIC MECHANISM
Gamma hydroxybutyrate (GHB) is a water-soluble four carbon molecule normally found in the human body. It is formed from the precursor molecule gamma butyrolactone (GBL) and is metabolized to succinic semialdehyde and the neurotransmitter gamma-aminobutyric acid (GABA).  The greatest concentration of GHB in humans is in the basal ganglia. Mechanism of Action HUMAN Gamma hydroxybutyrate (GHB) acts as: - An inhibitory neurotransmitter regulating dopaminergic neurons - A central nervous system depressant with euphoria-inducing capabilities Has a general anesthetic effect caused via: - Suppression of the entire cerebrospinal axis, and - Muscular relaxation by direct action on the spinal cord, rather than neuromuscular junction.  ANIMAL GHB alters dopaminergic activity: Either by reducing dopaminergic activity in the basal ganglia - Possibly due to the inhibition of dopamine-releasing nerve cells Or by stimulating dopamine release However, the direction is dependent on several undefined variables. GHB has binding affinity for two receptor sites in the central nervous system - GHB-specific receptor - The GABAB receptor GHB might mediate some of its effects (alteration in dopaminergic activity) through interaction with the GABA B receptor.  |
THERAPEUTIC DRUG INFORMATION
KINETICS
ABSORPTION
Effect of Food Reduces mean peak plasma concentrations, increases median time to peak concentration, and decreases the area under the plasma concentration-time curve Bioavailability 26% First Pass Metabolism Extensive  Time to Peak Plasma Levels |
DISTRIBUTION
Distribution - Rapid

Plasma Protein Binding - Limited

Lipid Solubility Crosses the placenta  Is excreted in breast milk  |
METABOLISM
Metabolism - Hepatic

Major Metabolic Pathways Parent: - Following oxidation to succinate and entry into the Krebs cycle, gamma hydroxybutyrate is almost completely metabolized to water and carbon dioxide.
 
First Pass Metabolism - Significant

|
ELIMINATION
Excretion Urine - 2 to 5% excreted unchanged
 
Lungs - Excreted as carbon dioxide
Time to Completion - 4 to 8 hours
 
|
IDENTIFICATION
PRODUCT INFORMATION
This substance may be available in a stated dosage, however, this should be treated with some caution particularly if obtained illicitly, due to variables such as uncontrolled manufacturing process, inappropriate packaging, and product bulking. |
OTHER NAME(S)
Gamma hydroxybutyric acid: 4-Hydroxybutanoic acid |
4-hydroxy butyrate | 4-hydroxybutanoic acid | Gamma-hydrate | gamma-Hydroxybutyrate | Gamma-hydroxybutyric acid | GBH | GHB | Sodium oxybate | Sodium oxybutyrate | |
|
Alcover | Aminos | Blue Thunder | Cherry Menth | Cherry Meth | Date Rape Drug | Easy Lay | Everclear | Fantasy | Fingernail Polish Remover | Flower Power | G | G caps | G juice | Gamma 10 | Gamma Date Rape Drug | Gamma-OH | GBH | Georgia Home Boy | GH Buddy | GHB | GHBees (GHB and 2C-B) | Ghbers | GHGold | Gina | Goop | Great Hormones | Great Hormones at Bedtime | Grevious Bodily Harm | Grievous Bodily Harm | G-Riffic | G-Riffick | H2O | Ink Jet Cartridge Cleaner | Jib | Liquid E | Liquid Ecstasy | Liquid Fantasy | Liquid G | Liquid X | Max (GHB and Amphetamines) | Mills | Nail Polish Remover | Natural Sleep 500 | Organic Quaalude | Oxy-Sleep | Paint Stripper | Phantasy | Plant Food | PMSomax | Puritech | Rejoov | Salty water | Scoop | Sleep-500 | Soap | Somatomax | Somsanit | Swirl | Thundar nectar | Tranquili G | Vita-G | Water | Wazz | White Magic Cleaner | Womans Viagra |
|
CODES
ATC CLASSIFICATION
Anesthetics, General - Other General AnestheticsAnesthetics, General N01A X Other Nervous System Drugs - Other Nervous System DrugsOther Nervous System Drugs N07X X |
CAS NUMBER
Gamma Hydroxybutyrate: 591-81-1 Sodium Gamma Hydroxybutyrate: 502-85-2 |
PHYSICOCHEMICAL PROPERTIES
Molecular Weight | 104.10 104.10% degrees C |
GAMMA HYDROXYBUTYRATE SODIUM: Molecular Weight | 127.09 127.09% degrees C |
Solubility | Water: highly soluble |
|
Attempts to avoid detection: Artificial flavoring Artificial coloring Mixed in: Fruit drinks Bottled water Sold as cleaning products, e.g. CD cleaner Testing: Gamma butyrolactone (GBL) and 1,4 butanediol are rapidly metabolized to gamma hydroxybutyrate (GHB): Routine drug screen will not detect GHB Tests must be targeted specifically for GHB Urine testing should be used |
Do Not Archive. This document is current on day of issue,
NZ: 21.Jan.2021 |