LabMed

Overdose of Gamma-Hydroxybutyrate (GHB)

At a Glance

Gamma-hydroxybutyrate (GHB) is an endogenous metabolite of gamma-aminobutyric acid (GABA), and its metabolism results in the production of carbon dioxide and water. The effects of GHB are dose-dependent: at low doses, the drug acts as a stimulant and an aphrodisiac; at high doses, the drug causes sedation and has developed a reputation as a "date-rape" drug.

Symptoms of intoxication with GHB include: euphoria, feelings of empathy, nausea, dizziness, drowsiness, agitation, depressed breathing, amnesia, and unconsciousness. A test to detect GHB is typically used in emergency medicine to diagnose a possible overdose, coma, or unexplainable seizures. A unique characteristic of GHB intoxication is sometimes seen as spontaneous recovery from a coma, which may only last a few hours.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

A blood or urine test should be ordered to confirm the clinical diagnosis; less than 5% of GHB is eliminated unchanged in urine. It is important to note that there are almost no commercially available assays for GHB; it is equally important to note that GHB is an endogenous compound, so a positive GHB toxicology test can only be considered positive if it is the established cut-off for blood (>10 mg/L) or urine (>10 mg/L). Depending on the dose, GHB can be detected for up to approximately 6-8 hours in blood and about 12 hours in urine.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications - OTC drugs or Herbals - that might affect the lab results?

As noted, GHB is a derivative of the endogenous substance GABA and will be present in patients even in the absence of GHB ingestion. GHB as a sodium salt is also available as a therapeutic drug for treatment of narcolepsy. In addition, Gamma-butyrolactone (GBL) and 1,4-butanedial (BD) are chemicals metabolized to GHB in the body if they are ingested orally. In some cases, patients may have obtained these substances, rather than GHB, for self-administration, because they may not be banned by law, depending on the country in question.

Most methods for GHB detection are chromatographic and performed in reference labs, and, therefore, the long turnaround time makes it difficult for the testing to have a direct impact in patient management. These types of methods are not prone to interference by structural analogs and other compounds that may be present in a patient specimen. There is one direct enzymatic assay available based on GHB dehydrogenase, and this method does exhibit some interference from GBL and ethanol at a concentration greater than 300 mg/dL.

What Lab Results Are Absolutely Confirmatory?

Because GHB is present as an endogenous compound, there is no absolutely confirmatory lab test for this compound. However, the presence of GHB in blood or urine at a concentration above the established cut-off is highly suggestive of exogenously administered GHB or one of its chemical precursors. Assay cutoffs are somewhat arbitrary, as there are no mandated guidelines for testing of this substance. Endogenous concentrations of GHB are typically less than 10 mg/L, so cutoffs are typically established somewhere between 5 and 10 mg/L.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Aside from GHB testing, there are no other confirmatory tests. However, as intoxication with GHB can cause significant central nervous system (CNS)depression, blood gas testing, co-oximetry, and cardiac monitoring are useful tests for following a patient with suspected GHB intoxication.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications - OTC drugs or Herbals - that might affect the lab results?

Storage conditions and preservatives can possibly cause artifactual results by increasing GHB concentration in vitro. Specimens stored at room temperature without sodium fluoride preservative can demonstrate an increase in GHB concentration after specimen collection. In addition, specimens collected in tubes with citrate preservative can have artifactually increased GHB concentrations. Inhibition of GHB dehydrogenase in vivo can increase endogenous GHB concentrations. Drugs and endogenous substances that can inhibit GHB dehydrogenase include barbiturates, valproic acid, salicylate, valproic acid, blood ketones, and phenylalanine degradation products.

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