Acute gamma hydroxybutyrate toxicity.

ne California Journal of Emerseocy Medicine 11:1, .Jmuary2001 SPECIAL,ARTICLE. First ojTwo Parts page 7 GHB is rapidly absorbed after oral adminisuation and the onset of svstemic effects occurs within minutes' GHB is a structural analogue of the inhibitory neurotransmitter gamma-aminobutyricacid (GABA). It readily crosses the blood brain barrier and may lead to general anesthesia and respiratory depression.' However, the exact mechanism by which GHB exerts its effects remains unclear. GBL is rapidly convened in vivo by peripheral lactonases to GHB. 1,4-BD is convened by alcohol dehydrogenase to gamma hydroxybutyraldehydeand then by aldehyde dehydrogenase to GHB? GHB is metabolived to carbon dioxide and water via the Kreb's cycle with no active metabolites.'. GHB and its precursors are abused recreationally for their disinhibitive, euphoric, and purported aphrodisiac effects. However, used in excess, significant toxicity may occur. Chin el al. described the clinical characteristics and course of GHB overdose. Of GHB ingestions presenting to the emergency department, profound decreased level of consciousness is typical. In addition, mild hypolhermia, asymptomatic bradycardin, d d acute respiratory acidosis, and emesis are frequent Coingestion of ethanol and other drugs is common and may contribute to the occasional hypotension that is observed. Rapid, spontaneous, recovery of consciousness is typical, often within 5 hours of ingestion. Although the comatose state induced by GHB is nonspecific, the rapid recovery of con.. sciousness from aseverely comatose state is considered the hallmark of GHB toxicity? Although recovery is typical. death bas occurred As predicted from the in with the coadministration of other vivo metabolism of GBL., and 1.4-BD to GHB, the clinical presenta- tion of toxicity of these agents has been identical to that of GHB? Both tolerance and physical dependence may occur with prolonged. and frequent use of GHB. Withdrawal from GHB and its precursors has been described. The withdrawal symptoms are very similar to those seen in ethanol withdrawal. Symptoms and signs include tremor, agitation. dinphoresis, hallucinations and tachycar- dia' Unlike with ethanol convulsions have not been reported with GHB withdrawal. Quantitative testing in both the serum and urine exists for GHB. Recently, methods have been developed that can differentiate between the presence of GHB and GBL. However, few laborato- ries perform GHB testing and currently no rapid test exists that would be immediately available to the treating emergency physician. Laboratory testing is most appropriate in situations such as possible date rape. or other forensic cases, in which confirnation of exposure may be critical. After ingestion. GHB is detectable in the s e m for approximately eight hours, and for slightly longer in the urine.') Treatment of GHB toxicity is supportive with airway protection being of primary importance. Because patients acutely intoxicated with GHB are expected to have a relatively rapid return U, conscious- ness, and have little reported aspiration, some experienced with GHB toxicity describe withholding endotrachenl intubation if a clear history of GHB ingestion exists. Wowever, as history is often unreliable. and coingestants may be present a conservative approach would certainly favor intubating the comatose patienr Hypotension should be mated with intravenous fluid and symptomatic bradycar- dia should be treated with atropine. Withdrawal has been success- fully treated with large doses of benzodiazepines and pbenobarbitnL ' I Aaron B Schneir, MD Division of Medical Toxicology Department of Emergency Medicine University of California San Diego Medical Center California Poison Control System San Diego, California Gamma hydroxybutyrate (GHB) is anamrally occwning substance in the brain with a strucme very similar to the major central nervous system inhibitory neurotransmitter, gamma-aminobutyricacid (GABA).' It was synthesized initially in the 1960s for use as a GABA analogue capable of crossing the blood brain barrier. Being acenual nervous system depressant, it was temporarily used as a geneml anesthetic. This use was cwtded secondary to recognition of the side effectsof petit and grand mal seizures, myoclonus, and vomiting' Rated - - on a studv showine that GHB adminisualion led to increased release of growth hormone,' the drug was marketed in the 1980s as an alleged growth hormone stimulator, and was sold in health food stores.' In addition, the euphoria-inducing property of GHB led to recreational abuse. Increasing reports of serious adverse effects from GHB misuse quickly led to d d n g the sale and manufacture of GHB illegal. On March 13,20W, GHB was made a schedule I drug by the D m 5 Legal use of GHB in the United States remains only for research on narcolepsy, a condition which appears to be effectively treated with GHB.6 Despite the schedule I classification. abuse of GHB contioues. GHB can be obtained illicitly and also made from home manufachuing kits? It has become a popular drug used at raves, and a dmg impli- cated in date rape owing to its property of rapid coma induction.' Two precursors to GHB, namely gamma-butylactone (GBL), and 1.4- buunediol(1.4-BD) have been marketed as alternatives to GHBP The FDA has asked for a voluntary recall of products containing GBL. some of which are solvents. GHB and its precmors are typically sold as liquids or white powders and are administered orally. GHB is referred to by various slang names, and a multitude of products contain the precursor; GBL and 1,4-BD. Below is a p d a l list of some of them Drug: GHB Synonyms: sodium oxybate, sodium oxybulyrate, gamma hydrate Slann: GBH. erievous bodily harm, Georgia home boy. easy lay. uquG ecstac$,-salty water . DN~: GBL Synonyms: Z(3H)-furanone diydro, butyrolactone, 4-butyrolactone, dihydro-Z(3H)-furanone Products: Renewtrient, Revivarant, Blue Nitro, Remforce Drng: 1.4-BD Synonyms: 1.4-retramethylene glycol, tetramethylene glycol, 1.4 tetramethylene Products: Enliven, Thunder Nectar, Pine Needle Exuact. Serenity