GHB Overdoses in the Emergency Department

Blood specimens from 146 suspected gamma.hydroxybutyrate (GHB) overdose cases, presenting to an emergency department in Washington State over a 12-month period, were analyzed for GHB and other drugs. Of these 146 patients, GHB was confirmed in approximately one-third of the patients (N = 54), sometimes in potentially toxic concentrations. These patients were aged between 17 and 59 years (median 28 years), and 83% were mate. Blood GHB concentrations ranged from 29 to 490 mg/L (mean 137 mg/L; median 103 mg/L). In 36 (67%) of the 54 patients, other drugs were additionally detected. Ethanol was measured in 22 (41%) patients, with concentrations ranging from 0.01 to 0.26 g/100 mL (median 0.04 g/100 mL). Other commonly co-administered drugs included 3,4-methylenedioxymethamphetamine, marijuana, methamphetamine, cocaine, and citalopram. Frequently observed clinical symptoms on admission for the GHB overdose group included copious vomiting, ataxia, lack of gag reflex, respiratory depression, mild acute respiratory acidosis, unconsciousness, and sudden altered states of consciousness. Many patients required intubation, and several became combative and required restraints. The majority of patients were discharged within 6 h of hospital admission. However, despite presenting with similar clinical symptoms on admission, GHB was not confirmed in 92 of the 146 overdose patients, suggesting that GHB overdose cases may frequently be indistinguishable from other drug overdoses or medical conditions. Introduction (GBL) and 1,4-butanediol (1,4-BD), convert to GHB within the human body following oral administration and are also recreationally abused. On February 18, 2000, GHB was placed in Federal Schedule I of the Controlled Substance Act, with GBL cited as both a list I chemical and a controlled substance analogue and 1,4-BD falling under the controlled substance analogue section (7,8). This scheduling has included a provision for medically formulated GHB to be placed in Federal Schedule [[[, and GHB is now available in the U.S. for the treatment of cataplexy associated with narcolepsy. The primary effects of GHB are those of a central nervous system (CNS) depressant. Clinical and adverse effects range from relaxation and euphoria, confusion, dizziness, drowsiness, nausea and vomiting, agitation, nystagmus, memory impairment, and somnolence to uncontrollable shaking or seizures, combativeness, sinus bradycardia, respiratory depression, and unarousable unconsciousness (2,3,9-13). The onset of effects is extremely rapid, and unconsciousness can occur within 10-20 rain. In Washington state, there has been an increasing number of patients presenting to emergency departments with signs of GHB intoxication or overdose. Unconsciousness may last anywhere from 1 to 6 h, and in extreme cases, death may occur. Blood specimens from 146 suspected GHB intoxications were sent to the Washington State Toxicology Laboratory (WSTL) to confirm the presence of GHB and other drugs. The drug results and presenting clinical symptoms of these patients are presented here. Gamma-hydroxybutyrate (GHB) was first used clinically as an anesthetic in the 1960s; however, its use was discontinued as it lacked analgesic properties and had an unpredictable duration of action, producing dramatic swings between consciousness and unconsciousness (1). Since then, GHB has been recreationally used by bodybuilders as an alternative to anabolic steroids to enhance muscle growth and by others for its intoxicating effects such as euphoria, reduced inhibitions, and sedation (2--6). Analogues of GHB, namely gamma-butyrolactone * Author to whom corres~ndence should be addressed. E-mail: fiona,[email protected] Methods Blood was obtained from suspected GHB overdose cases presenting to the emergency department of a major Seattle hospital over a 12-month period. Hospital records were reviewed for information regarding the circumstances, presenting vital signs, clinical signs and symptoms, and time spent in the emergency department. Suspected GHB-overdose patients with symptoms of unconsciousness, coma, vomiting, cessation of breathing, bradycardia and/or respiratory depression, were included. Upon presentation, a blood specimen was drawn by Reproduction (photocopying) of editorial content of this journal is prohibited wilhoul publisher's permission. 481 Journal of Analytical Toxicology, Vol. 28, September 2004 qualified medical personnel, either by venous puncture (vacutainer) or through a heparin lock. Because the hospital was unable to analyze for GHB, specimens were submitted to the WSTL for GHB confirmation, in addition to a comprehensive drug screen. Twenty milliliters of blood was collected in two 10mL gray-top blood tubes that contained sodium fluoride and potassium oxalate. On receipt of blood specimens at the laboratory, samples were stored at 4~ until tested. GHB was analyzed by gas chromatography-mass spectrometry (GC-MS) as previously described (14), using diethylene glycol as an internal standard. Blood was slightly acidified with patients were aged between 14 and 59 years (median 25 years), and 60% of the patients were male. A GHB overdose or intoxication was suspected based on the clinical symptoms on each patient admission. Such symptoms included confusion, disorientation, copious vomiting, ataxia, decreased heart rate and blood pressure, sinus bradycardia, respiratory depression, apnea, and sudden altered states of consciousness. However, of these 146 patients, GHB was detected in only 54 (37%) cases. These patients were aged between 17 and 59 years (median 28 years), and 83% were male. Blood GHB concentrations ranged from 29 to 490 mg/L (mean 137 mg/L; median 103 0.1N H2SO 4, then extracted twice in ethyl acetate. The analytes were derivatized to their TMS derivatives using BSTFA/1% TMCS. The assay had a limit of quantitation of 1 mg/L, defined as the lowest concentration at which the assay was determined to be linear. Calibration was determined to be linear up to 100 mg/L in blood, and the correlation coefficient was typically better than 0.990. Specimens with GHB concentrations above 100 mg/L were reanalyzed after dilution with blank matrix to within the linear range of the assay. All specimens underwent blood alcohol analysis for ethanol, methanol, acetone, and isopropanol by headspace GC with flame ionization detection. The limit of detection for ethanol was 0.005 g/100 mL. Methanolic extracts of blood specimens underwent a screen for drugs of abuse and several prescription drug classes using an enzyme multiplied immunoassay technique (EMIT). The EMIT procedure screened for cocaine metabolites (cutoff limit 100 ng/mL), opiates (10 ng/mL), amphetamines (100 ng/mL), carboxy-tetrahydrocannabinol (10 ng/mL), methadone (100 ng/mL), phencyclidine (10 ng/mL), propoxyphene (100 ng/mL), barbiturates (100 ng/mL), benzodiazepines (50 ng/mL), and tricyclic antidepressants (100 ng/mL). Additionally, n-butylchloride and ethyl acetate extracts of the blood specimens underwent separate screens for basic compounds and weak acidic and neutral compounds, respectively, using GC-M8.