sodium-oxybate and Poisoning

Sexual violence is a universal phenomenon without restriction to sex, age, ethnicity or social class that causes devastating effects in the physical and mental health spheres, in the short-term and long-term, such as pregnancy, sexually transmitted infections (STI) and greater susceptibility to psychiatric symptoms, especially depression. Some cases of sexual assault and rape are based on the use of so-called drug-facilitated sexual assault (DFSA), which cause victims' loss of consciousness and inability to defend, making them vulnerable to violence. Thus, this article aimed to review the literature on gender violence and the drugs used to facilitate sexual assault, addressing their mechanism of action and pharmacokinetics, as well as drug detection times in human body and types of forensic identification. It is understood that the knowledge of these drugs and their pharmacological and diagnostic mechanisms should be widely disseminated, especially about sensitivity tests and the time the drug remains in the body, which would validate the promotion of evidence to prove abuse, and, thus, being able to give a promising outcome to cases of aggression, which is extremely beneficial for women.

Topics: Adjuvants, Anesthesia; Alcohol Drinking; Anesthetics, Dissociative; Benzodiazepines; Crime Victims; Female; Gender-Based Violence; Humans; Ketamine; Molecular Structure; Poisoning; Sex Offenses; Sodium Oxybate; Substance Abuse Detection; Substance-Related Disorders; Unconsciousness

Topics: 2-Propanol; Anesthetics, Dissociative; Anti-Anxiety Agents; Ethylene Glycol; Flunitrazepam; Hallucinogens; Hospital Units; Humans; Ketamine; Methanol; N-Methyl-3,4-methylenedioxyamphetamine; Poisoning; Sodium Oxybate; Solvents

Gamma-hydroxybutyrate is a potent sedative-hypnotic agent and a popular drug of abuse. In the United States, gamma-hydroxybutyrate is a Schedule I controlled substance (sodium oxybate) with orphan drug status for the treatment of narcolepsy within approved clinical studies. Physostigmine is a carbamate inhibitor of acetylcholinesterase that is reported to attenuate the sedative effects of a number of drugs, including gamma-hydroxybutyrate. We reviewed the literature that pertains to the use of physostigmine to treat gamma-hydroxybutyrate-induced sedation.. A structured literature search was performed to identify articles in which physostigmine and gamma-hydroxybutyrate were mentioned. Keywords were used to identify relevant articles in the Medline database, and the reference sections of articles identified by this method were hand-checked to identify additional articles. Those articles that presented original evidence pertaining to the use of physostigmine to treat gamma-hydroxybutyrate-induced sedation were included in this review; those that did not were rejected.. The literature search identified 22 articles, six of which did not pertain to the subject matter. Of the 16 articles which remained, 12 were rejected because they offered opinions without presenting original evidence. Of the four articles that presented original evidence, there were no in vitro studies and no animal studies. There were two small case series in which physostigmine was given to treat acute gamma-hydroxybutyrate toxicity in an emergency department setting, and two larger series in which physostigmine was given to attenuate the sedation induced by gamma-hydroxybutyrate in a more structured anesthesia setting. Although these references report that physostigmine attenuates gamma-hydroxybutyrate-induced sedation, there are methodological flaws and confounding factors that limit the scope of the conclusions that can be drawn from them.. There is currently insufficient scientific evidence to support the routine use of physostigmine in the treatment of gamma-hydroxybutyrate toxicity. Further studies are needed to determine the role, if any, for physostigmine in this setting.

Topics: Cholinesterase Inhibitors; Emergency Medical Services; Humans; Hypnotics and Sedatives; Physostigmine; Poisoning; Sodium Oxybate

Topics: Amphetamines; Analgesics, Opioid; Anesthetics, Intravenous; Cocaine; Drug Overdose; Emergency Treatment; Heroin; Humans; Narcotics; Poisoning; Sodium Oxybate; Substance-Related Disorders

During the last six months, the Poison Control Centre at Bispebjerg Hospital, Copenhagen, Denmark, has observed an increasing number of patients intoxicated with GHB, a drug of abuse. The patients are often admitted to the emergency ward shortly after having taken the drug, unconscious or comatose. If younger patients present with these symptoms, intoxication with GHB should be seriously considered. The effects are seen within 15 to 30 minutes after oral ingestion of the drug. Spontaneous recovery usually occurs within three to five hours. The most common effects are mild euphoria, sedation, vomiting, somnolence, bradycardia, aggressive behaviour, apnoea, respiratory depression, and coma. Normally the patient breathes adequately, but insufficient respiration may occur and deaths have been described. The drug is often consumed together with alcohol and other drugs of abuse, which strengthens the effect of GHB. Treatment is symptomatic. A review of the literature with special emphasis on clinical effects included toxicology and treatment is given.

Topics: Central Nervous System Stimulants; Drug Overdose; Emergencies; Humans; Illicit Drugs; Poisoning; Sodium Oxybate; Substance-Related Disorders

A young woman with a history of several suicide attempts was admitted to the hospital after suspicion of a new intoxication without definite identification of the causing agent. The patient had a high anion gap metabolic acidosis (HAGMA) with respiratory compensation, a lactate gap and an osmolar gap at admission. Initial toxicological screening showed no abnormalities except for a weak positive gamma-hydroxy butyric acid (GHB) enzymatic screen in urine. This finding could not be confirmed using chromatographic analysis nor be explained by the presence of known cross-reacting substances like ethanol. In this case, falsely elevated urinary GHB screening was caused by the ingestion of ethylene glycol. To confirm that the interference was due to ethylene glycol or its metabolites, we performed a spiking experiment. Cross reactivity was linked to ethylene glycol and was low in our experiments (0.1-0.2%). Substantial amounts of ethylene glycol are required to slightly elevated GHB results, depending on the endogenous cutoff used. We can conclude that ethylene glycol can give rise to falsely elevated urinary GHB levels at ethylene glycol concentrations that are typically found in intoxications.

Topics: Acid-Base Equilibrium; Acidosis; Butyric Acid; Ethanol; Ethylene Glycol; Female; Humans; Poisoning; Sodium Oxybate

Topics: Humans; Infant; Poisoning; Sodium Oxybate

GHB related acids (3,4-dihydroxy butyric acid, 2,4-dihydroxy butyric acid and glycolic acid) are produced through oxidative GHB metabolism. These analytes could be potential biomarkers to ensure the diagnosis of a GHB intoxication and even prolong the detection window. Within this study, forensic routine cases were measured to consider the potential of additional gas chromatographic mass spectrometric analysis on these acids. 17 GHB positive real cases (10 serum samples and 7 urine samples) and 40 cases with suspicion of drugging in DFC cases and negative GHB results (21 serum samples and 19 urine samples) were evaluated. Increased GHB related acid concentrations were detected in all serum and most urine samples positive on GHB. In some GHB negative cases, especially in serum samples, concentrations of GHB related acids gave hints that GHB actually was taken. We recommend to use the following cut-offs for a more reliable interpretation of potential GHB intoxication cases: 3,4-OH-BA:>3 mg/L in serum and>50 mg/L in urine; 2,4-OH-BA:>2 mg/L in serum and>25 mg/L in urine; GA:>5 mg/L in serum and>400 mg/L in urine.

Topics: Biomarkers; Butyric Acid; Forensic Toxicology; Gas Chromatography-Mass Spectrometry; Glycolates; Humans; Poisoning; Sodium Oxybate; Succinic Acid

Many patients with gamma-hydroxybutyrate (GHB) poisoning are treated at the emergency primary health care (A&E clinic) level in Oslo. We describe the clinical picture of GHB poisoning and compare hospitalised patients with patients who were discharged from the main A&E clinic in Oslo.. We registered retrospectively all patients with the clinical diagnosis GHB poisoning at the Oslo Accident and Emergency Outpatient Clinic from 1 October 2013 to 30 September 2015. We only included cases where GHB was taken as an intoxicant.. We found 329 cases of GHB poisoning in the period. The median age was 30 years (interquartile range 25-36 years, range 15-56 years), and 228 (69 %) of the cases were men. GHB was taken as the only intoxicant in 128 cases (39 %), combined with alcohol in 96 (29 %) and with amphetamine in 65 (20 %). Reduced level of consciousness was observed in 218 cases (69 %), coma (Glasgow Coma Scale score ≤ 7) in 43 (14 %) and agitation in 117 (36 %). Compared with patients who were discharged from the A&E clinic, the 159 hospitalised patients (48 % of the total number) were more often comatose (23 % vs 5 %, p < 0.001) and agitated (43 % vs 28 %, p = 0.008). The median observation time at the A&E clinic prior to hospitalisation was 42 minutes (interquartile range 26 min - 1 h 23 min, range 2 min - 20 h 10 min) vs 3 h 1 min (interquartile range 1 h 32 min - 4 h 42 min, range 14 min - 15 h 37 min) for those who were discharged from the A&E clinic (p < 0.001).. Half of the patients with GHB poisoning were only treated at A&E clinic level. Many of those who were hospitalised had severe symptoms that quickly called for hospitalisation.

Topics: Adult; Ambulatory Care Facilities; Drug Overdose; Emergency Service, Hospital; Female; Humans; Male; Poisoning; Retrospective Studies; Sodium Oxybate

The purpose of this study was to identify the extent and types of drugs found in alleged drug facilitated sexual assaults (DFSA) in 37 states and 1 territory of the United States. In total, 1000 cases were reviewed. Between the cases that gender was provided (613), most of the victims (91.68%) were woman, mean age of 26.8 years old. Blood and/or urine samples were tested. Twenty-one point six percent of the cases were negative for intoxicating substances. A hundred and one different substances were detected. Overall, ethanol was the most prevalent substance, detected in 30.9% of the cases (309 cases), followed by cannabinoids (THC/THCCOOH/11-OH-THC) (28.8% of cases), amphetamine/methamphetamine (16.5% of cases), cocaine/metabolites (10.4% of cases), and clonazepam/metabolite (7.6% of cases). The mean, median and range concentrations of ethanol in blood (n = 309) were 98.6 mg/dL, 82.0 mg/dL and 9.2-366 mg/dL, respectively. Ethanol and cannabinoids were the most frequent combination found. The absence of alcohol and drugs in some cases may represent delay in collecting samples.

Topics: Adolescent; Adult; Age Distribution; Alprazolam; Benzodiazepines; Cannabinoids; Central Nervous System Depressants; Child; Child, Preschool; Clonazepam; Crime Victims; Ethanol; Female; Forensic Toxicology; Humans; Hypnotics and Sedatives; Illicit Drugs; Infant; Male; Middle Aged; Poisoning; Sex Distribution; Sex Offenses; Sodium Oxybate; United States; Young Adult

This article reports the concentrations of gamma-hydroxybutyrate (GHB) in femoral blood and bladder urine in a case series of drug intoxication deaths (N = 37). GHB was determined in blood (B-GHB) and urine (U-GHB) by a GC-FID-GBL method and 30 mg/L was used as a cut-off concentration for reporting positive results. The mean (median) and range of GHB concentrations in bladder urine were 2,818 mg/L (1,900 mg/L) and 120-13,000 mg/L, respectively. These concentrations were appreciably higher than those in femoral blood, 637 mg/L (260 mg/L) and 30-9,200 mg/L, respectively. Urine/blood ratios of GHB were highly variable (mean 8.99, median 5.33 and range 0.16-29.3). GHB is rapidly metabolized and cleared from the bloodstream, whereas there is no metabolism occurring in the urinary bladder. In five autopsy cases, U-GHB was lower than B-GHB, which suggests that these individuals died before equilibration of the drug in all body fluids and tissues. In the other 32 deaths, U-GHB was higher than B-GHB, sometimes appreciably higher, which points towards a longer survival time after intake or administration of GHB. The analysis of urine extends the window of detection of GHB by several hours compared with blood samples, depending in part on when the bladder was last voided before death. Furthermore, the urinary concentration of GHB gives a hint about the concentration in blood during the time that the urine was produced in the kidney and stored in the bladder since the previous void.

Topics: Adult; Autopsy; Databases, Factual; Female; Forensic Toxicology; Humans; Male; Poisoning; Postmortem Changes; Sodium Oxybate; Specimen Handling; Substance Abuse Detection; Substance-Related Disorders

Use of and acute poisoning by substances of abuse represent a major health problem and are often linked to social destitution. We describe associations between place of residence, living conditions and the incidence of poisoning by substances of abuse in Oslo.. All patients who were 12 years of age or older and resident in Oslo and who were treated for acute poisoning by substances of abuse at the Oslo Accident and Emergency Outpatient Clinic (OAEOC) were included prospectively for a continuous period of one year, from October 2011 to September 2012. The 15 districts of Oslo were categorised into three groups of living conditions, from the best (I) to the poorest (III) living conditions, based on the City of Oslo's living conditions index. Homeless people were grouped separately. The incidence of poisoning by substances of abuse treated in the OAEOC was estimated.. Of a total of 1,560 poisonings by substances of abuse, 1,094 cases (70%) affected men. The median age was 41 years. The most frequent toxic agents were ethanol, with 915 cases (59%), and heroin, with 249 cases (16%). The incidence of poisoning by substances of abuse treated in the OAEOC per year per 1,000 inhabitants amounted to 1.75 in living conditions group I, to 2.76 in living conditions group II and 3.41 in living conditions group III. Living conditions group III had a significantly higher incidence than living conditions group II (p < 0.001), and living conditions group II had a significantly higher incidence than living conditions group I (p < 0.001).. The incidence of acute poisoning by substances of abuse was higher, the poorer the living conditions in the district.

Topics: Acute Disease; Adolescent; Adult; Aged; Ambulatory Care Facilities; Analgesics, Opioid; Benzodiazepines; Central Nervous System Stimulants; Child; Ethanol; Female; Heroin; Humans; Ill-Housed Persons; Male; Middle Aged; Norway; Poisoning; Prospective Studies; Social Conditions; Socioeconomic Factors; Sodium Oxybate; Substance-Related Disorders; Urban Population

γ-Hydroxybutyrate (GHB), a common drug of abuse, is often coingested with ethanol. Increasing renal clearance via monocarboxylate transporter (MCT) inhibition represents a potential therapeutic strategy in GHB overdose, as does inhibition of GABAB receptors. In this study, we investigate toxicokinetic/toxicodynamic interactions between GHB-ethanol and efficacy of treatment options for GHB-ethanol intoxication in rats. Sedation was assessed using the endpoint of return-to-righting reflex. Respiration was assessed using plethysmography. Coadministration of 2.0 g/kg ethanol i.v. with 600 mg/kg GHB i.v. increased sleep time compared with GHB alone. Administration of ethanol to steady-state concentrations of 0.1-0.2% and 0.3-0.4% (w/v) did not affect toxicokinetics of 600 mg/kg GHB i.v., or respiratory rate, but did result in significantly lower peak tidal volumes compared with GHB alone. Oral administration of 2.5 g/kg ethanol had no significant effect on toxicokinetics of 1500 mg/kg orally administered GHB. Pretreatment with specific receptor inhibitors indicated no effect of GABAA receptor inhibition on sleep time or respiratory depression in GHB-ethanol intoxication. GABAB receptor inhibition partially prevented sedation and completely prevented respiratory depression. Ethanol increased fatality when administered at 0.1-0.2% (4 of 10) and 0.3-0.4% (9 of 10) versus 1500 mg/kg GHB i.v. alone (0 of 10). Treatment with the MCT inhibitor, l-lactate, significantly decreased sleep time after GHB-ethanol and decreased fatality at 0.1-0.2% (0 of 10) and 0.3-0.4% ethanol (5 of 10). Treatment with a GABAB receptor antagonist completely prevented fatality at 0.3-0.4% (0 of 10). These data indicate that ethanol potentiates the sedative and respiratory depressant effects of GHB, increasing the risk of fatality. MCT and GABAB receptor inhibition represent potentially effective treatments in GHB-ethanol intoxication.

Topics: Animals; Central Nervous System Depressants; Conscious Sedation; Drug Overdose; Ethanol; GABA-B Receptor Antagonists; Hypnotics and Sedatives; Lactic Acid; Male; Monocarboxylic Acid Transporters; Plethysmography; Poisoning; Rats; Rats, Sprague-Dawley; Respiratory Insufficiency; Respiratory Mechanics; Sodium Oxybate

Area-level socioeconomic status (SES) may play an important role in drug abuse patterns, including related health outcomes. This may be particularly relevant for gamma-hydroxybutyrate (GHB), which is prototypical of "party" drug abuse.. 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.. 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 $100,000 incremental increase in median home values (OR 1.41; 95% CI 1.1-1.8). For median annual household income (per $10,000), the association was similar (OR 1.39; 95% CI 1.0-1.9).. 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.

Topics: Adolescent; Adult; California; Censuses; Female; Humans; Illicit Drugs; Male; Poison Control Centers; Poisoning; Retrospective Studies; Socioeconomic Factors; Sodium Oxybate; Young Adult

To analyze changes in gamma-hydroxybutyrate (GHB) case reporting, we review GHB or congener drug cases reported to the California Poison Control System, comparing these to other data sets.. We identified cases from the California Poison Control System computerized database using standardized codes and key terms for GHB and congener drugs ("gamma butyrolactone," "1,4-butanediol," "gamma valerolactone"). We noted California Poison Control System date, caller and exposure site, patient age and sex, reported coingestions, and outcomes. We compared California Poison Control System data to case incidence from American Association of Poison Control Centers and Drug Abuse Warning Network data and drug use prevalence from National Institute for Drug Abuse survey data.. A total of 1,331 patients were included over the 5-year period (1999-2003). California Poison Control System-reported GHB exposures decreased by 76% from baseline (n=426) to the final study year (n=101). The absolute decrease was present across all case types, although there was a significant proportional decrease in routine drug abuse cases and an increase in malicious events, including GHB-facilitated sexual assault (P=.002). American Association of Poison Control Centers data showed a similar decrease from 2001 to 2003. Drug Abuse Warning Network incidence flattened from 2001 to 2002 and decreased sharply in 2003. National Institute for Drug Abuse survey time trends were inconsistent across age groups.. Based on the precipitous decrease in California Poison Control System case incidence for GHB during 5 years, the parallel trend in American Association of Poison Control Centers data, and a more recent decrease in Drug Abuse Warning Network cases, a true decrease in case incidence is likely. This could be due to decreased abuse rates or because fewer abusers seek emergency medical care. Case reporting may account for part of the decrease in the incidence of poison center contacts involving GHB.

Topics: Adolescent; Adult; Age Distribution; California; Causality; Child; Comorbidity; Databases, Factual; Female; Hospitalization; Humans; Male; Middle Aged; Poison Control Centers; Poisoning; Prevalence; Referral and Consultation; Retrospective Studies; Sex Distribution; Sodium Oxybate; Substance-Related Disorders; Survival Analysis

Prior animal studies have suggested that flumazenil may blunt GHB's sedative-hypnotic affects. We hypothesized that flumazenil would decrease the affects of GHB in a murine model of intoxication.. We performed a controlled, pilot experiment using 32 mice divided into 3 groups. All mice received intraperitoneal injections of GHB (1.5 g/kg). Group I received sham injections at time 0, and then GHB at 5 minutes. Group II received flumazenil (0.3 mg/kg) at time 0, and then GHB at 5 minutes. Group III received sham injection at time 0, then GHB at 5 minutes, and then 4 escalating flumazenil doses administered at 3-minute intervals (0.003 to 1 mg/kg). We measured certain functions: time to loss/recovery of righting reflexes (RR), time to sprawl/recovery of sprawl (postural tone [PT]), and death.. There were statistically significant delays in the loss of PT and shortened recovery time to RR in pre-treated mice (group II) versus controls (group I). There were no differences in group III versus group I for any outcome parameters.. In this model, pre-dosing flumazenil prior to GHB administration delayed clinical intoxication.

Topics: Animals; Antidotes; Behavior, Animal; Disease Models, Animal; Flumazenil; Mice; Pilot Projects; Poisoning; Posture; Reflex; Research Design; Sodium Oxybate; Time Factors

Gamma hydroxybutyrate (GHB) is widey used as a sexual enhancement drug, a euphoriant, muscle building agent, a sleep aid, a weight loss agent, and as a date rapeagent. Precursor ingredients such as gammabutyrolactone (GBL) and GHB recipes are available, especially via the Internet. This is a report of an organic inkjet cleaner containing a GHB precursor 1,4-butanediol and butylenegycol. A 26-y-o male fell unconscious during work being unresponsive, with constricted pupils, and convulsing, he did not respond to naloxone. A bottle labeled "Hurricane" was found in his pocket. Five h later the patient awoke and was subsequently discharged with all vitals normal. The patient had recently purchased "Hurricane" as a sleep aid and to treat his panic attacks. It is an organic product with active ingredients similar to ink jet cleaner, the key ingredient being 1,4butanediol, which is metabolized to GHB. In spite of legislative changes restricting GHB, the precursors remain available and continue a public health threat.

Topics: Adult; Coma; Diagnosis, Differential; Humans; Illicit Drugs; Male; Poisoning; Sodium Oxybate

Topics: Adult; Blood Pressure; Butylene Glycols; Charcoal; Consciousness Disorders; Delirium; Diagnosis, Differential; Electrocardiography; Gastric Lavage; Humans; Male; Poisoning; Sodium Oxybate; Sweating

Topics: 3-Hydroxybutyric Acid; Adult; Blood Chemical Analysis; Cross Reactions; Humans; Male; Poisoning; Sodium Oxybate

Gamma Hydroxybutirate (GHB) is unfamiliar to many physicians in Israel. Recently GHB has emerged as an illicit drug of misuse for its purported euphoric and aphrodisiac effect. The clinical effects can progress rapidly to respiratory arrest and death. We provide a description of a case of GHB poisoning, with a comprehensive review of the literature emphasizing the pharmacodynamics, clinical effect, and suggestions for management. Physicians are urged to become familiar with GHB.

Topics: Adult; Anesthetics, Intravenous; Female; Humans; Poisoning; Sodium Oxybate

Topics: Adolescent; Adult; Hallucinogens; Humans; N-Methyl-3,4-methylenedioxyamphetamine; Poisoning; Sodium Oxybate; Substance-Related Disorders

Topics: Adult; Coma; Female; Humans; Poisoning; Sodium Oxybate

Topics: Adult; Emergency Nursing; Female; Humans; Male; Poisoning; Sodium Oxybate

Topics: Disease Outbreaks; Emergencies; Humans; Poisoning; Population Surveillance; Sodium Oxybate; United States