EM@3AM – Gamma-Hydroxybutyrate (GHB) Toxicity

Author: Erica Simon, DO, MHA (@E_M_Simon, EMS Fellow, SAUSHEC, USAF) and Daniel Sessions, MD (EM Associate Program Director, SAUSHEC, USA / Medical Toxicologist, South Texas Poison Center) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit, EM Attending Physician, SAUSHEC, USAF)

Welcome to EM@3AM, an emdocs series designed to foster your working knowledge by providing an expedited review of clinical basics. We’ll keep it short, while you keep that EM brain sharp.

A 19-year-old female presents to the ED by EMS for resolved altered mental status and respiratory depression. Prior to arrival, the woman was found minimally responsive (GCS 7; E(1),V(2), M(4)) at a house party. Initial VS: BP 118/76, HR 66, T 99.6 F oral, RR 6, SpO2 89% on room air. The patient’s roommate, having accompanied her to the party, identifies her as non-drinker due to religious beliefs.

The paramedic giving report notes an attempt at field intubation, which resulted in the patient gagging and becoming alert/severely agitated.

Repeat assessment:
GCS 14 (E(4),V(4), M(6))
VS: BP 120/78, HR 69, T 99.7 F oral, RR 12, SpO2 96% (2L NC)

What’s the next step in your evaluation and treatment?

Answer: Gamma-Hydroxybutyrate (GHB) Toxicity^1-4

• Drug Facts:^1,2
  • Mechanism of Action: GHB is a naturally occurring fatty-acid derivative of the neurotransmitter, GABA, which functions as an agonist of GHB and GABA_B receptors.
  • Indications: Originally marketed in the 1990s as a dietary supplement, sleep aid, and anesthetic,^1,2 the FDA has since banned the OTC sale of GHB due to its association with seizure-like activity and reflex autonomic activation.² Today GHB is available for the treatment of narcolepsy (trade name: Xyrem). Gamma butyrolactone and 1,4-butanediol are chemical precursors of GHB. They are frequently sold online and labeled “not for human consumption,” so as to avoid legal prosecution. Exposures to these products should be treated in the same manner as GHB toxicity.
  • Social Implications: GHB is often referred to as a “date rape drug.” Commonly available as an oral solution, its delivery as such has earned it the street names of “liquid ecstasy,” “soap,” and “salty water.”²
• Clinical Manifestations of Toxicity: The majority of GHB ingestions are mild and produce sedation and euphoria.² Delirium and agitation are common. Anterograde amnesia, bradycardia, and tonic-clonic seizures are well-documented side effects.¹ Severe GHB intoxication results in profound respiratory depression. Death may occur secondary to respiratory failure.² Among chronic abusers, a life-threatening withdrawal syndrome is described.
• Evaluation and Treatment:^2-4
  • Assess the ABCs and obtain VS.
    • The decision to intubate should be based upon the patient’s respiratory status and the ability to closely monitor oxygenation/ventilation in the ED.²
      • In the absence of co-ingestions, clinical effects of GHB commonly resolve within 3 hours in non-intubated patients, and within 8 hours in intubated patients.
    • Perform a thorough H&P:
      • If able, question the patient specifically regarding recreational GHB use and the possibility of sexual assault.
      • Look for signs of trauma: 5% of GHB related deaths occur secondary to trauma.³
    • Perform a toxicological evaluation as applicable (EKG, serum ETOH, serum salicylates, etc.)
    • Treatment:
      • Consult
      • Supportive care:
        • Airway reflexes frequently intact and hypersensitive: attempts at direct laryngoscopy may arouse the patient.¹

• Pearls:
  • Individuals may present to the ED requesting evaluation for unintended GHB ingestion:
    • The half-life of GHB is 20 minutes. GHB is not detectable by standard serum and urine toxicology screens due to its short half-life and its elimination through exhalation (metabolized to CO₂).²
    • Gas chromatography mass spectrometry will detect GHB up to 6-8 hours post administration, however, this form of advanced analysis is rarely available onsite.²
  • Patients with > 6 hours of CNS depression => evaluate for alternative etiologies if not previously performed (Altered mental status: AEIOU TIPS).¹
  • Chronic abusers: Cessation of GHB may be life-threatening and result in tremor, tachycardia, insomnia, anxiety, delirium, hypertension, coma, or death.⁴
    • Case reports detail the use of benzodiazepines, GABA_A agonists, and baclofen, a GABA_B agonist, for withdrawal therapy.⁴

 References:

1. Bebarta V. Common Drugs of Abuse. In Emergency Medicine Secrets. 6^th ed. Philadelphia, PA. Elsevier. 2016; 488-500.e1.
2. Jones A, Kugelberg F, Holmgren A, Ahlner J. Occurrence of ethanol and other drugs in blood and urine specimens from female victims of alleged sexual assault. Forensic Sci Int. 2008;181:40-46.
3. Zvosec D, Smith S, Porrata T, Strobl Q, Dyer J. Case series of 226 γ-hydroxybutyrate-associated deaths: lethal toxicity and trauma. Am J Emerg Med. 2011; 29:319-332.
4. LeTourneau J, Hagg D, Smith S. Baclofen and Gamma-Hydroxybutyrate Withdrawal. Neurocrit Care. 2008; 8(3): 430-433.

For Additional Reading:

Managing Sexual Assault in the Emergency Department:

Managing Sexual Assault in the Emergency Department