[From the Departments of Family Practice and Internal Medicine, Naval Hospital Jacksonville, Jacksonville, Fla.]

Abstract

Gamma-hydroxybutyric acid (GHB) has become a popular new drug of abuse. Its effects include euphoria and disinhibition. Recently, several cases have been reported in the literature of life-threatening or lethal ingestions. We report the case of a 17-year-old male who became unresponsive after taking GHB. Gamma-hydroxybutyric acid is used outside the United States to treat narcolepsy. In the past, it was touted as a muscle-bulking aid and was taken by body-builders. It has also been implicated as a drug involved in "date-rapes." Patients who ingest excessive GHB have a markedly altered level of consciousness, as did the patient in this illustrative case. Neostigmine and physostigmine show promise as potential reversal agents. Gamma-hydroxybutyric acid overdose should be considered in any patient with altered mental status and a history of recreational drug abuse.

Introduction

Gamma-hydroxybutyric acid (GHB), now a popular drug among recreational drug users, can lead to a severely depressed level of consciousness. Overdoses can be fatal. The drug has been studied for clinical usefulness, but much remains to be learned about its pharmacologic effects. Most states have now made possession of GHB a criminal offense. Physicians who work in emergency departments and acute care settings are often faced with the evaluation and management of patients who took something at a party and then have altered mental status. Ingestion of GHB should be considered in such cases.

Case Report

A 17-year-old male was brought by Emergency Medical Services to the emergency department after he was found unconscious at a party. No other historical information was available. During transport, he had received 2 mg of naloxone without apparent effect.

On arrival in the emergency room, he was entirely unresponsive, with a Glasgow Coma Scale of 3. An assessment of his airway, breathing, and circulation found no abnormalities. His heart rate was 62/min, and blood pressure was 130/82 mm Hg. He was afebrile, with a respiratory rate of 12/min and pulse oximetry of 100% on room air. Findings on examination of the head and neck were normal. Cardiac, pulmonary, abdominal, and skin examinations revealed normal findings. The patient was unresponsive to verbal and painful stimuli, and all extremities were flaccid. Pupils were 3 mm and only minimally responsive but symmetric. Deep tendon reflexes were present and symmetric but markedly decreased.

Laboratory investigation revealed a normal complete blood count, urinalysis, electrolyte panel, arterial blood gas, and liver function panel. Urine toxicology screen was negative for cocaine, amphetamines, benzodiazepines, cannabinoids, and opiates. His blood ethanol level was 0.040 mg/dL. The patient spontaneously awoke from this comatose state on his way back to the emergency room after computed tomography (CT) of the head showed normal findings. The total duration of unresponsiveness was approximately 3 hours. The patient admitted to taking a substance called "GHB" that he obtained from a friend at the party.

Discussion

Gamma-hydroxybutyrate (GHB) is a relatively new drug implicated in several fatal over-doses.[1] Street names include Liquid Ecstasy, Liquid X, Liquid E, Scoop, Easy Lay, Growth Hormone Booster, and G-Riffick. It is a naturally occurring substance in the human brain and was first synthesized in the 1960s. During the 1980s, GHB was sold over the counter in health food stores, marketed to body-builders as a growth-hormone stimulator to facilitate increasing muscle mass and fat catabolism. Abuse potential stems from GHB's ability to induce a euphoric state of relaxation and tranquility without a hangover effect. Additional effects of increased sensuality and disinhibition further explain its popularity. Gamma-hydroxybutyrate has been called a date rape drug by the lay press.[2] In 1990, the Food and Drug Administration banned sale of this drug. Since then, several states have included GHB as a controlled substance, making possession a criminal offense.

There are now many reports of intoxication with GHB. Patients who overdose on GHB have a remarkably diminished level of consciousness.[3] Other manifestations are variable and can include hypothermia, bradycardia, vomiting, or hypotension.[4] In a recent report of seven cases of GHB overdose, all patients had delirium and transient respiratory depression.[3] Also, a state of aggressive behavior was observed when the patient was stimulated during periods of frank apnea.[3]

Management of the patient who has over-dosed on GHB is supportive. Airway protection is paramount. Neither flumazenil nor naloxone has been successful in reversing the effects of GHB.[5,6] Physostigmine and neostigmine are potential reversal agents,[6] but use should be carefully considered due to the potential dangers of these compounds. Physostigmine penetrates the central nervous system more effectively than neostigmine[7] and may be the most effective reversal agent.[8] Atropine for symptomatic bradycardia is probably the most important pharmaceutical agent for use in resuscitation. Concomitant ingestion of other drugs of abuse should be suspected and managed accordingly. Gamma-hydroxybutyrate has been studied for clinical usefulness. It is used in treating narcolepsy in other countries.[9] It has also been studied for use in the treatment of alcohol and opiate withdrawal syndrome.[10,11]

Gamma-hydroxybutyrate has also been used as an anesthetic for a variety of procedures from labor to lung surgery.[6] Gamma-hydroxybutyrate has the unique facility of reducing tissue oxygen demands and has been studied as a potential agent for use in resuscitation. This effect, studied in such conditions as sepsis and myocardial infarction, may hold promise.[6]

Conclusion

Intoxication with GHB should be considered in patients who have altered mentation and a history of recreational drug abuse, particularly when presenting with profound bradypnea, bradycardia, and ethanol co-ingestion. Although the treatment is largely supportive, neostigmine or physostigmine may help in reversing the sedation. Future research may yield usefulness of the cytoprotective effects of the drug in seriously ill patients.

Reprint requests to Anthony J. Viera, MD, Naval Hospital Jacksonville, Department of Family Practice, 2080 Child St, Jacksonville, FL 32114.

References

1.Centers for Disease Control and Prevention: Gamma hydroxybutyrate use. MMWR 1997; 46:281-283

2."Date rape" drug linked to a death, 69 poisonings. Wall Street Journal April 4, 1997, p B8

3.Li J, Stokes SA, Wockener A: A tale of novel intoxication: seven cases of gamma-hydroxybutyric acid overdose. Ann Emerg Med 1998; 31:723-728

4.Chin RL, Sporer KA, Cullison B, et al: Clinical course of gamma-hydroxybutyrate overdose. Ann Emerg Med 1998; 31:716-722

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6.Li J, Stokes SA, Wockener A: A tale of novel intoxication: a review of the effects of gamma-hydroxybutyric acid with recommendations for management. Ann Emerg Med 1998; 31:729-736

7.Landsberg L, Young JB: Physiology and pharmacology of the autonomic nervous system. Harrison's Principles of Internal Medicine. Fauci A, Braunwald E, Isselbacher KJ, et al (eds). New York, McGraw-Hill, 14th Ed, 1998, pp 430-442

8.Henderson RS, Holmes CM: Reversal of the anaesthetic action of sodium gamma-hydroxybutyrate. Anaesth Intensive Care 1976; 4:351-354

9.Scharf MB, Fletcher KA, Jennings SW: Current pharmacologic management of narcolepsy. Am Fam Physician 1988; 38:143-148

10.Gallimberti L, Canton G, Gentile N, et al: Gamma-hydroxybutyric acid for treatment of alcohol withdrawal syndrome. Lancet 1989; 30:787-789

11.Gallimberti L, Schifano F, Forza G, et al: Clinical efficacy of gamma-hydroxybutyric acid in treatment of opiate withdrawal. Eur Arch Psychiatry Clin Neurosci 1994; 244:113-114