Suspected GHB Overdoses in the Emergency Department

Couper, Fiona J.; Thatcher, Jayne E.; Logan, Barry K.

doi:10.1093/jat/28.6.481

Cited by 38 publications

(26 citation statements)

References 12 publications

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“…Consistent with reports of GHB use outside of the laboratory setting (eg Miotto et al, 2001;Degenhardt et al, 2002), GHB significantly increased same-day participant-ratings of headache and queasy or sick to stomach and next-day ratings of bad effects. Nausea, GI distress, diarrhea, or vomiting occurred during 41 and 78% of the sessions in which doses of 2-8 and 10-18 g/70 kg GHB were administered, respectively, which is consistent with the high frequency of adverse GI effects of GHB described in other clinical reports of GHB toxicity (eg Degenhardt et al, 2002;Couper et al, 2004;Liechti et al, 2006). Unlike GHB, reports of nausea, GI distress, diarrhea, or vomiting after doses of triazolam or pentobarbital occurred after only 4 and 14% of sessions,…”

Section: Discussionsupporting

confidence: 86%

Relative Abuse Liability of GHB in Humans: A Comparison of Psychomotor, Subjective, and Cognitive Effects of Supratherapeutic Doses of Triazolam, Pentobarbital, and GHB

Carter

Richards

Mintzer

et al. 2006

Neuropsychopharmacol

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Although preclinical studies suggest that GHB has low likelihood for abuse, case reports indicate that GHB is abused. This study evaluated the relative abuse liability of GHB in 14 volunteers with histories of drug abuse. Psychomotor, subjective, and cognitive effects of a broad range of GHB doses (2-18 g/70 kg), up to a dose that produced severe behavioral impairment in each participant, were compared to placebo and two abused sedative/hypnotic drugs, triazolam (0.5 and 1 mg/70 kg) and pentobarbital (200 and 400 mg/70 kg), under double-blind, double-dummy conditions at a residential research facility. In general, GHB produced effects similar to triazolam and pentobarbital, although GHB was not identified as a benzodiazepine or barbiturate by participants that correctly identified triazolam and pentobarbital as such. On most measures of likelihood of abuse (eg ratings of liking, reinforcing effects), effects of pentobarbital were significantly greater than those of triazolam, with GHB being intermediate. GHB produced significantly greater negative subjective effects, including nausea, than the other drugs. Memory impairment after GHB was less than that after triazolam and pentobarbital. Within participants, the dose-effect function for sedation was steeper for GHB than for triazolam and pentobarbital. Also, at higher doses, GHB was associated with greater sedation and more variability across participants in sedation. Taken together, these data suggest that the profile of effects of GHB only partially overlaps with that of triazolam and pentobarbital. Although the likelihood for GHB to be abused is intermediate to triazolam and pentobarbital, the possibility of accidental overdose (ie greater sedation than intended) with GHB appears to be greater.

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Section: Discussionsupporting

confidence: 86%

Relative Abuse Liability of GHB in Humans: A Comparison of Psychomotor, Subjective, and Cognitive Effects of Supratherapeutic Doses of Triazolam, Pentobarbital, and GHB

Carter

Richards

Mintzer

et al. 2006

Neuropsychopharmacol

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“…Couper and Logan [17] found mean and median concentrations of 87 mg/l and 95 mg/l in 13 subjects arrested for DUID with GHB in blood. Mean and median concentrations of GHB in blood of people admitted to an emergency department (N = 54) were higher 137 mg/l and 103 mg/l, respectively and their median age was 28 years [32].…”

Section: Discussionmentioning

confidence: 95%

Driving under the influence of gamma-hydroxybutyrate (GHB)

Jones

Holmgren

Kugelberg

2008

Forensic Sci Med Pathol

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We used an in-house forensic toxicology database (TOXBASE) to evaluate the occurrences of gamma-hydroxybutyrate (GHB) in blood samples from people arrested in Sweden for driving under the influence of drugs (DUID) between 1998 and 2007. Age, gender, and concentrations of GHB in blood were compared and contrasted when GHB was the only drug present and when it occurred along with other drugs. GHB was determined in blood by gas chromatography (GC) after conversion to gamma-butyrolactone (GBL) and analysis of the latter with a flame ionization detector. The cut-off concentration of GHB in blood for reporting a positive result was 8 mg/l, which served as limit of quantitation. The mean and median GHB concentrations were 89 mg/l and 82 mg/l, respectively (2(1/2) and 97(1/2) percentiles 12 and 220 mg/l) in 548 arrested drivers. These individuals were predominantly men (95%) with an average age of 26 +/- 5.5 years (range 15-50 years) and women (5%) were several years older with an average age of 32 +/- 8.0 years (range 19-47). There were 102 individuals (29%) who were arrested more than once with GHB in blood (average approximately 3 times per person) and one as many as 10 times. GHB was the only psychoactive substance detected in 215 cases (39%) at mean and median blood-concentrations of 91 mg/l and 83 mg/l, respectively. These concentrations were not significantly different from poly-drug users. A weak but statistically significant correlation existed between the concentration of GHB in blood and the person's age (N = 548, r = 0.135, P < 0.01). The signs of drug influence noted by arresting police officers included sedation, agitation, unsteady gait, slurred speech, irrational behavior, jerky body movements, dilated pupils, and spitting. The blood concentrations reported here are probably appreciably less than at time of driving (30-90 min earlier) owing to the short elimination half-life of GHB (t ((1/2)) = 30-40 min).

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“…To assess the effect of ethanol on GHB-induced respiratory depression, we chose two steady-state ethanol concentrations, a moderate, clinically relevant concentration of 0.1-0.2% (w/v), similar to blood alcohol levels reported in GHB overdose cases (Caldicott et al, 2004;Couper et al, 2004), and a high concentration of 0.3-0.4%. Our previous research evaluating the effect of GHB alone on respiration indicates the primary effect of GHB to be a decrease in respiratory rate, which is accompanied by a compensatory increase in tidal volume, allowing minute volume to be maintained until doses approach lethality (Morse et al, 2012).…”

Section: Treatment Of Ghb-ethanol Intoxicationmentioning

confidence: 99%

Toxicokinetics/Toxicodynamics ofγ-Hydroxybutyrate-Ethanol Intoxication: Evaluation of Potential Treatment Strategies

Morse

Morris

2013

J Pharmacol Exp Ther

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g-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 GABA B 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-torighting 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 GABA A receptor inhibition on sleep time or respiratory depression in GHB-ethanol intoxication. GABA B 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 GABA B 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 GABA B receptor inhibition represent potentially effective treatments in GHB-ethanol intoxication.

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Suspected GHB Overdoses in the Emergency Department

Cited by 38 publications

References 12 publications

Relative Abuse Liability of GHB in Humans: A Comparison of Psychomotor, Subjective, and Cognitive Effects of Supratherapeutic Doses of Triazolam, Pentobarbital, and GHB

Relative Abuse Liability of GHB in Humans: A Comparison of Psychomotor, Subjective, and Cognitive Effects of Supratherapeutic Doses of Triazolam, Pentobarbital, and GHB

Driving under the influence of gamma-hydroxybutyrate (GHB)

Toxicokinetics/Toxicodynamics ofγ-Hydroxybutyrate-Ethanol Intoxication: Evaluation of Potential Treatment Strategies

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