Gamma hydroxy butyric acid (GHB) withdrawal management

GHB is a naturally occurring neurotransmitter which is a GHB receptor agonist, and is a weak GABA-b agonist. At low dose, it causes euphoria. It is sedative and amnestic. It has a narrow therapeutic window and overdose can result in cardio-respiratory arrest.

In Australia, it is used mostly recreationally. However regular heavy use can result in the development of dependence and in these situations sudden cessation can result in a withdrawal syndrome.

Gamma butyrolactone (GBL) and 1,4 butanediol (BD) are precursors of GHB. They are rapidly metabolised to GHB and in effect have identical clinical features. GBL is thought to be about twice as potent as GHB, with quicker onset and decay in action. 1,4 butanediol is slower in onset of action than GHB.

GHB has a short half-life and is often not detected by urine toxicology screening tests. It can be detected using mass spectroscopy, but delays in this process make screening not that useful clinically. Diagnosis is therefore based on history either from the patient or from third parties.

GHB is a colourless, odourless liquid of variable concentration. A standard illicit dose is around 1 to 2mL but the therapeutic window is narrow.

Toxicity depends on dose, the person’s weight, tolerance, individual susceptibility, and other substances the person has consumed. In the context of illicit drugs where concentrations and doses are approximate at best, it is difficult to predict dose-effect profiles. Doses in excess of 2mls are likely to be increasingly toxic with sedation and cardiorespiratory depression.

GHB withdrawal syndrome

Features of GHB withdrawal are similar to alcohol withdrawal. Withdrawal severity varies considerably from mild through to severe. A small number develop prominent delirium and psychotic features, sometimes needing intensive care.

Bell et al (1) describe criteria based on expert opinion which might place an individual at risk of withdrawal if:

  • >4 ml GHB on a daily basis or
  • GHB > 6 times daily every day or
  • a history of severe withdrawal symptoms or
  • currently dependent upon other drugs (including benzodiazepines or alcohol).

Severity of withdrawal relates to amount used. 4mls per day is likely to be a low threshold for withdrawal. Those people using more than 30mls per day are very likely to experience severe withdrawal.

Common features of withdrawal usually appear six to 24 hours after the patient’s last drink and include:

  • tremor
  • sweats
  • nausea and/or vomiting, poor appetite, diarrhoea
  • headache
  • anxiety/restlessness.

Other signs of withdrawal syndrome include:

  • elevated heart rate and blood pressure
  • seizures
  • development of confusion or delirium.

More severe withdrawal can be prolonged.

Agitated delirium can be the primary presentation. This can be confused with intoxication with a hallucinogen or stimulant.

On occasions with severe withdrawal, rhabdomyolysis with secondary renal failure can occur.

Wernicke-Korsakoff Syndrome has been described in association with GHB withdrawal.

Management of GHB withdrawal

Overview

  • Generally managed with benzodiazepines. In extreme situations high doses may be required. (5)
  • Planned mild withdrawal can be managed in community.
  • Unplanned more severe withdrawal needs inpatient management.
  • Those who inadvertently go into GHB withdrawal due to a hospital admission for another reason (surgical, medical, obstetric or psychiatric in nature) will require withdrawal management in hospital whilst admitted for the co-occurring conditions (see 'Inpatient Management below).
  • Resistance to benzodiazepine therapy can occur requiring high dependency care and possible use of phenobarbitone or other agents.

Aims

Withdrawal management focuses on:

  • prevention of severe withdrawal
  • reducing the risk of injury (self/others) due to altered mental state
  • reducing the risk of dehydration, electrolyte and nutritional imbalance
  • preventing seizures
  • identification and treatment of concurrent medical conditions that can mask or mimic withdrawal or complicate the withdrawal process.

Assessment

Take a drug and alcohol history.

  • Include tobacco, alcohol, benzodiazepines, methamphetamine and other stimulants, opioids, cannabis at least.
  • Determine frequency, quantity, route of administration and when last used.

Thorough assessment is required to exclude serious medical conditions which may simulate the abovementioned features of withdrawal.

Determine pre-existing medical conditions. (These would include severe liver disease, severe COPD or severe OSA). Try to obtain some corroborative history.

Undertake a comprehensive physical examination.

Investigations as indicated. Not required if mild withdrawal anticipated.

Inpatient management

Criteria

Inpatient management is generally indicated if patients:

  • Require admission to hospital for other medical, surgical or psychiatric reasons
  • Have been using more than 30mls/g per daily for more than 2 weeks
  • Has been dosing frequently more than 3 times per day
  • Have previously experienced severe withdrawal including psychosis or delirium or seizures
  • Are currently confused or hallucinating
  • Have been using several substances from which they are likely to withdraw
  • Have significant active physical comorbidities (e.g. severe liver disease, renal disease).

Seek advice via DACAS (Drug and Alcohol Clinical Advisory Service on 7087 1742 or if non urgent email HealthDACASEnquiries@sa.gov.au)

Monitoring

A validated instrument such as the CIWA-Ar (PDF 45KB) should be used to assess withdrawal severity and track changes in withdrawal over time, as per Statewide Clinical Guideline for Management of Patients at risk of Alcohol Withdrawal.

Medications

Diazepam as per CIWA-Ar score for alcohol withdrawal. Lorazepam may need to be considered if severe liver disease; respiratory compromise e.g. severe COPD or OSA or in the elderly population group. (1mg lorazepam = approx. 10mg diazepam)

NOTE

  • Exercise care when administered in conjunction with opioids or other CNS depressants. (as per Alcohol Withdrawal Management Guideline)
  • If more than 120mg diazepam PO is required in first 24 hours, consult with Intensive Care Specialist. Airway support may be needed.
  • If the person becomes confused, consult with Intensive Care Specialist.
  • If more than 200mg is needed in first 24 hours, treatment with IV phenobarbitone may be required.

Outpatient management

Criteria

If the GHB withdrawal is planned then milder levels of withdrawal can be managed in community settings (2).

If community withdrawal management being considered then:

  • Patients must have a responsible other person with them during withdrawal to oversee medication use, and detect deterioration.
  • Patients should be clinically reviewed daily for at least five days to ensure a benign trajectory for the withdrawal episode.
  • Arrangements for urgent transfer to an inpatient facility should be considered.
  • A clinician should be available for advice over the full 24 hour period, for the first five days.

Monitoring and supervision

Assess the patient at least daily face to face.

Ensure that the other responsible person knows who to call for advice, and has a letter outlining the current treatment plan for an Emergency Department if this is part of the plan.

If withdrawal not controlled within the first 12 hours, (eg CIWA-Ar score > 8) consider transfer to hospital.

Medications

Commence diazepam as soon as subjective withdrawal is being experienced.

Day 1 Diazepam 10mg 6 hourly
Day 2 Diazepam 10mg 6 hourly
Day 3 Diazepam 10mg 8 hourly
Day 4 Diazepam 10mg 12 hourly
Day 5 Diazepam 5mg mane - 10mg nocte
Day 6 Diazepam 5mg 12 hourly
Day 7 Diazepam 5mg nocte

Withhold medication and seek advice from clinician if sedation score 2 or more (unable to remain awake).

After care

  • Explain to the patient the toxic effects of GHB and the nature of GHB withdrawal.
  • Determine whether the patient wants assistance afterwards with ceasing or reducing their GHB or other drug use. If being managed as an inpatient then refer to the hospital DASSA Consultation Liaison Service, or call the Alcohol and Drug Information Service 1300 13 1340 for advice on follow up.
  • If the person is unclear about further use or wishes to continue to use GHB then offer advice using the STAYING SAFE mnemonic (3).

S Seek medical attention immediately if you have taken too much GHB/GBL. Do not use other drugs in the hope of reversing the effects.

T Two or more substances used at the same time increase the risk of overdose Significantly (especially sedatives e.g. alcohol, ketamine).

A Always measure GHB/GBL doses accurately (use for example syringes or pipettes). Wait until the effects are felt and do not re-dose for at least two hours.

Y You should avoid using GBL on your own and always use in a safe place and with someone who has not taken it, as it is common to become unconscious.

I If you have used and are going to sleep, sleep on your side in case you are sick. Place sleeping or unconscious friends in the recovery position.

N Never drink GHB/GBL straight out of a bottle or pour a dose straight out of a bottle. Always dilute in water and add food colouring to avoid accidental drinking. Never keep GBL in drinks bottles, especially in public venues, where it might be drunk by others not aware of the content.

G GHB/GBL is physically addictive and dependence can happen quickly. Avoid frequent use, especially daily use.

S Severe and potentially serious GHB/GBL withdrawal symptoms occur if you are dependent and you miss a dose or reduce amounts taken abruptly.

A Acute withdrawal symptoms and have no GHB/GBL? Seek medical help immediately in an emergency department. It can be a very serious medical emergency.

F Find a medical support for planned GHB/GBL detoxification. Do not attempt to stop abruptly on your own. If you want to reduce your dose, do so in very small doses until you find medical support.

E Employ methods to stabilise your use; consumption diaries can be very helpful. Keep a GHB/GBL diary and record of your doses and times you use.

Resources


Further information and advice

Telephone: (08) 7087 1742 — 24 hours 7 days/week including public holidays or e-mail your enquiry to: HealthDACASEnquiries@sa.gov.au. Out of these hours, medically urgent calls from a hospital based Medical Consultant or country hospital medical officer/GP will always receive a response.

This service does not provide proxy medical cover and cannot assume responsibility for direct patient care.

(1) Bell J, Collins R. Gamma-butyrolactone (GBL) dependence and withdrawal. Addiction. 2011 Feb;106(2):442–7. doi: 10.1111/j.1360-0443.2010.03145.x.

(2) McDonough M, Kennedy N, Glasper A, Bearn J. Clinical features and management of gammahydroxybutyrate (GHB) withdrawal: a review. Drug Alcohol Depend. 2004 ;75:3– 9.

(3) Abdulrahim D & Bowden-Jones O, on behalf of the NEPTUNE Expert Group. Guidance on the Management of Acute and Chronic Harms of Club Drugs and Novel Psychoactive Substances. Novel Psychoactive Treatment UK Network (NEPTUNE). London, 2015.

Other references

Rama M. Kamal et.al. Pharmacological Treatment in c-Hydroxybutyrate (GHB) and c-Butyrolactone (GBL) Dependence: Detoxification and Relapse Prevention. CNS Drugs (2017) 31:51–64

Christopher N. Floyd & David M. Wood & Paul I. Dargan. Baclofen in gamma-hydroxybutyrate withdrawal: patterns of use and online availability. European Journal of Clinical Pharmacology (2018) 74:349–356