Jo Ellen Dyer

Clinical course of γ-hydroxybutyrate overdose

STUDY OBJECTIVE To describe the clinical characteristics and course of γ-hydroxybutyrate (GHB) overdose. METHODS We assembled a retrospective series of all cases of GHB ingestion seen in an urban public-hospital emergency department and entered in a computerized database January 1993 through December 1996. From these cases we extracted demographic information, concurrent drug use, vital signs, Glasgow Coma Scale (GCS) score, laboratory values, and clinical course. RESULTS Sixty-one (69%) of the 88 patients were male. The mean age was 28 years. Thirty-four cases (39%) involved coingestion of ethanol, and 25 (28%) involved coingestion of another drug, most commonly amphetamines. Twenty-five cases (28%) had a GCS score of 3, and 28 (33%) had scores ranging from 4 through 8. The mean time to regained consciousness from initial presentation among nonintubated patients with an initial GCS of 13 or less was 146 minutes (range, 16-389). Twenty-two patients (31%) had an initial temperature of 35°C or less. Thirty-two (36%) had asymptomatic bradycardia; in 29 of these cases, the initial GCS score was 8 or less. Ten patients (11%) presented with hypotension (systolic blood pressure≤90 mm Hg); 6 of these patients also demonstrated concurrent bradycardia. Arterial blood gases were measured in 30 patients; 21 had a Pco2 of 45 or greater, with pH ranging from 7.24 to 7.34, consistent with mild acute respiratory acidosis. Twenty-six patients (30%) had an episode of emesis; in 22 of these cases, the initial GCS was 8 or less. CONCLUSION In our study population, patients who overdosed on GHB presented with a markedly decreased level of consciousness. Coingestion of ethanol or other drugs is common, as are bradycardia, hypothermia, respiratory acidosis, and emesis. Hypotension occurs occasionally. Patients typically regain consciousness spontaneously within 5 hours of the ingestion. [Chin RL, Sporer KA, Cullison B, Dyer JE, Wu TD: Clinical course of γ-hydroxybutyrate overdose. Ann Emerg Med June 1998;31: 716-722.].

γ-Hydroxybutyrate: A health-food product producing coma and seizurelike activity

Sixteen cases of adverse effects due to a new health-food product, gamma-hydroxybutyrate (GHB), were reported to the San Francisco Bay Area Regional Poison Control Center in the 5-month period from June to October 1990. Cases have also been reported in eight other states. Adverse effects included coma (four patients) and tonic-clonic seizurelike activity (two patients). Doses ranged from 1/4 teaspoon to 4 tablespoons. Acute symptoms resolved within 7 hours. GHB was investigated as an anesthetic agent during the 1960s until seizures and lack of analgesia precluded its use. It was recently introduced in the health-food market as a food supplement for body builders with claims of anabolic effects by stimulating growth hormone release. GHB remains under investigational new drug status with the Food and Drug Administration and is illegal for over the counter sale. The Food and Drug Branch of the California Department of Health Services has prohibited further sale of this product in California as have health departments in Florida and South Carolina; however, new cases continue to be reported. Health professionals should be aware of the potential health hazards of GHB.

Seizures associated with poisoning and drug overdose.

A retrospective review of cases consulted by the San Francisco Bay Area Regional Poison Control Center during a 2-year period was performed to determine the causes and consequences of seizures associated with poisoning and drug intoxication. Of 233 charts coded as involving seizures, 191 occurred in humans and were available for analysis. The leading causes of seizures reported to the Poison Control Center were cyclic antidepressants (55 cases, 29%); cocaine and other stimulants (55 cases, 29%); diphenhydramine and other antihistamines (14 cases, 7%); theophylline (10 cases, 5%); and isoniazid (10 cases, 5%). Stimulants and diphenhydramine were more likely than other drugs to produce brief, self-limited seizures. In contrast, poisoning by cyclic antidepressants, cardiodepressant antiarrhythmic agents, or theophylline was more likely to be associated with death. Seizures in elderly patients were more likely to result in complications and death. The frequency of seizure-related cases by substance type was also compared with the results of an earlier survey performed in 1981, and found a striking increase in the proportion of seizures caused by cocaine and (23% in 1988 to 1989 compared with 4% in 1981). Poison Control Center data can provide valuable information about the causes and consequences of drug-related medical complications, as well as highlight changing trends in drug-related injury.

Gamma-hydroxybutyrate and ethanol effects and interactions in humans

Background: Gamma-hydroxybutyrate (GHB) is a common drug of abuse that can produce serious toxicity, particularly when used with other sedatives. We examined the individual and combined effects of GHB and ethanol in human volunteers. Methods: Sixteen healthy adults (7 men) were given 50 mg/kg GHB (Xyrem), 0.6 g/kg ethanol in 2 doses, alone and combined in a double-blind, placebo-controlled, crossover study. Plasma concentrations, heart rate (HR), blood pressure (BP), and oxygen saturation (O2sat) were serially monitored for 24 hours. Results: Adverse events included 2 instances of hypotension and 6 episodes of vomiting with GHB-plus-ethanol ingestion. Oxygen saturation was decreased by GHB and ethanol individually, and maximally decreased by the drugs combined (max −2.1% ± 0.3%, P < 0.0001 vs placebo). Compared with baseline, systolic and diastolic BP were significantly decreased, and HR was increased by ethanol but not affected by GHB alone (maximum systolic BP change −15.7 ± 3.0 mm Hg, P = 0.0006; maximum HR change 13.5 ± 2.3 beats per minute, P = 0.006). Ethanol coingestion resulted in 16% higher GHB maximal plasma concentration and 29% longer elimination half-life, indicating possible enhanced bioavailability or reduced clearance of GHB caused by ethanol, however, these effects were not statistically significant. Conclusions: Modest doses of GHB do not affect hemodynamic function, but O2sat was decreased. Gamma-hydroxybutyrate-plus-ethanol resulted in more adverse effects, including gastrointestinal disturbances, hypotension, and decreased O2sat, but only minimal pharmacokinetic interactions were observed.

EXPERIENCES OF GAMMA HYDROXYBUTYRATE (GHB) INGESTION: A FOCUS GROUP STUDY

Abstract GHB (gamma hydroxybutyrate) is a significant new drug of abuse added to the United States Controlled Substance Act in 2000. The majority of the published literature on GHB consists of clinical case reports. mainly from emergency departments, and a collection of laboratory-based studies, focused mainly on anesthesia. While comments about the various experiences and behaviors of human users are often included in such studies or reports, these aspects of GHB are only just beginning to be systematically investigated or detailed. Reported here are data from a qualitative study using focus group methods on the consumption habits. experiences, and beliefs of GHB users. A total of 51 people, 30 men and 21 women, mean age of 31.1±7.6 years (range 18 to 52 years), who report having used GHB for an average of 4.3±2.5 years (range one to II years), were interviewed in 10 separate groups held in 2004. This article discusses broadly the general experience of the GHB high, major perceived benefits including sexual responses to the drug, perceived risks and dangers of ingestion, co-ingestion, and various contexts of use. It concludes with a discussion of the implications drawn from this information for clinicians treating patients who use GHB.

Clinical Pharmacology of 1,4-Butanediol and Gamma-hydroxybutyrate After Oral 1,4-Butanediol Administration to Healthy Volunteers

1,4‐Butanediol (BD) is converted to gamma‐hydroxybutyrate (GHB) after ingestion, and is associated with cases of dependence, coma, and death. The pharmacology of BD after oral ingestion has not been described in humans. Eight healthy volunteers (five men) were administered 25 mg/kg BD in a single oral dose after an overnight fast in a double‐blinded, placebo‐controlled, crossover study. Vital signs were monitored, and serial blood samples collected over 24 h for gas chromatography‐mass spectrometry analysis of BD and GHB levels. Subjective mood and symptoms responses were assessed by visual analog scale. All subjects completed the study without significant adverse effects. BD was quickly absorbed and cleared, with time to maximal plasma concentration of 24±12 min, and elimination half‐life (T1/2) of 39.3±11 min. BD was extensively converted to GHB, with a mean maximum GHB concentration of 45.6±19.7 mg/l reached 39.4±11.2 min after BD ingestion. GHB T1/2 averaged 32.3±6.6 min. Some subjects exhibited slow oral clearance of BD, which tended to correlate with a variant haplotype of the alcohol dehydrogenase gene ADH‐IB G143A. Mean CL/F was 151.5±176.5 ml/min kg for four subjects with variant haplotype versus 598.8±446.6 ml/min kg for four wild‐type subjects (P=0.061). Subjects reported feeling less awake and alert, less able to concentrate, and more lightheaded in the first 90 min after BD ingestion. Pulse oximetry readings were lower 45 min after BD dosing with a mean oxygen saturation of 98.5% with BD versus 99.6% with placebo (P=0.031). Transient increases in mean systolic and diastolic blood pressure were observed, but other vital signs remained unchanged. BD was extensively converted to GHB after oral administration, but significant inter‐individual variability in the rate of metabolism, possibly related to variants in ADH‐IB, was observed. At the modest dose studied, significant clinical effects were not seen.

High-risk behaviors and hospitalizations among gamma hydroxybutyrate (GHB) users.

Introduction: Little is known about behaviors linked to gamma hydroxybutyrate (GHB) morbidity. Methods: We surveyed 131 GHB users, using logistic regression to test the associations between the high risk behaviors and hospital treatment for GHB (26 [20%] of subjects). Results: Increased risk of GHB hospital treatment was associated with: co-ingestion of ethanol (OR 5.2; 95% CI 1.7–16), driving under the influence of GHB (OR 3.2; 95%, CI 1.3–7.8),use of GHB to treat withdrawal symptoms (OR 2.9; 95% CI 1.1–7.9), and co-ingestion of ketamine (OR 2.7; 95% CI 1.1–6.7). Conclusion: Targeted prevention activities could focus on selected high-risk behaviors.

Area-level socioeconomic status in relation to outcomes in γ-hydroxybutyrate intoxication

Background. Area-level socioeconomic status (SES) may play an important role in drug abuse patterns, including related health outcomes. This may be particularly relevant for γ-hydroxybutyrate (GHB), which is prototypical of “party” drug abuse. Methods. We retrospectively reviewed GHB-related cases reported to the California Poison Control System (CPCS; January 1, 1999 through June 30, 2007). We limited analysis to CPCS calls containing a residential zip code (ZC). The CPCS data were extracted for key case characteristics, including the residential ZC. We linked cases to corresponding 2000 U.S. Census data for area-level measures of SES and demographics. We used multiple logistic regression analysis to test the associations between area-level SES and GHB case severity, taking into account area-level demographics and individual-level GHB high-risk behaviors. Results. We analyzed 210 cases. Taking into account area-level demographics (age and racial mix; urbanicity) and GHB-related high-risk behaviors (use of GHB congeners; GHB-dependence; co-ingestion of other agents), we associated higher area-level SES with greater GHB case severity. There was 40% increased likelihood of major GHB adverse health outcomes for every 

Systematic Assessment of Gamma Hydroxybutyrate (GHB) Effects During and After Acute Intoxication

100,000 incremental increase in median home values (OR 1.41; 95% CI 1.1–1.8). For median annual household income (per 

The impact of gamma hydroxybutyrate (GHB) legal restrictions on patterns of use: Results from an International Survey

10,000), the association was similar (OR 1.39; 95% CI 1.0–1.9). Conclusion. Higher area-level SES is associated with greater GHB-related case severity. This study may serve as a model using a geographic information system (GIS) approach to study the population-based correlates of drugs of abuse reported through poison control surveillance.