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Gamma Hydroxybutyrate

Gamma Hydroxybutyrate
24.Nov.2017-Expires: 7 days - Do not archive

DESCRIPTION

SUBSTANCE NAME

Gamma Hydroxybutyrate
 

USES

This substance may be used either therapeutically but can also be subject to abuse.

Treatment for narcolepsy
Treatment for alcoholism
Anesthetic agent
Euphoric
“Date rape” agent
“Growth Hormone booster”
“Aphrodisiac”
“Muscle builder” (although effectiveness has never been proven)
 

INTERVENTION CRITERIA

The correct identification of the substance is important. If the symptoms are inconsistent with those described in the literature, or the history is considered unreliable, other substances may need to be considered.
 

Intervention Level

Child

Medical assessment and observation is recommended for:
- Any suspected ingestion in children
 
The risks of decontamination outweigh any benefits, and should not be attempted.
 

Adult

Medical assessment and observation is recommended for:
- Any suspected ingestion
- Exposures with intent to self-harm
 
The risks of decontamination outweigh any benefits, and should not be attempted.
 
History of dose ingested is not a reliable guide to management.
 

Observation Period

Observation at Home

All patients require medical attention.
 

Medical Observation

If medical observation is required the patient must be monitored for 6 hours following exposure for onset or worsening of symptoms.
 
If the patient is asymptomatic at the end of the observation period, and provided that appropriate assessment and investigations have been carried out, they may be:
Discharged into the care of a reliable observer, or
Referred for psychological assessment if the overdose or exposure was with intent to self-harm
 

Investigations

Levels

Serum concentrations do not aid management.
 

Monitoring

Monitor:
Level of consciousness
Heart rate
Blood pressure
Respirations
Seizure activity
 

Admission Criteria

Admission to an intensive care environment is recommended for patients who develop significant signs of toxicity including:
CNS depression requiring intubation
Respiratory depression
Aspiration pneumonitis
Hemodynamic instability
 

TREATMENT

TREATMENT SUMMARY

Emergency stabilization may be required for respiratory depression and/or pulmonary aspiration, immediate assessment and management of respiratory compromise is a priority. Due to fast onset of action, gastrointestinal decontamination is not recommended.
 
There is no proven antidote for poisoning. Extracorporeal elimination techniques would not be anticipated to be of clinical benefit in the majority of patients as most will satisfactorily recover with adequate airways management alone.
 
Supportive care is the mainstay of management, with primary emphasis on airway management and cardiovascular support. Airway protection including endotracheal intubation and/or assisted ventilation may be necessary due to respiratory depression and aspiration risk. Seizures may rarely occur and, in the presence of coma, indicate anoxia: manage the airway and ensure adequate ventilation. Should repetitive seizure occur in a well ventilated patient treat with a benzodiazepine, or if still refractory, a barbiturate. Myoclonic jerking is a recognized re-emergence phenomenon and single episodes do not require treatment. Other complications such as bradycardia, hypotension, hypothermia, and gastrointestinal upset should be treated along usual guidelines.
 
A withdrawal syndrome is recognized after chronic abuse of this compound and may last 3 to 21 days. Benzodiazepines are usually effective to relieve symptoms. Weakness, headache, fatigue and nausea lasting 3 days after ingestion may occur. However, if significant CNS depressant effects persist beyond 8 hours, alternative causes should be investigated.
 
Emergency Stabilization
Decontamination
Ingestion
Antidote(s)
Enhanced Elimination
Supportive Care
Respiratory
Neurologic
Cardiovascular
Metabolic
Other
 

EMERGENCY STABILIZATION

Ensure Adequate Cardiopulmonary Function

Ensure the airway is protected if compromised (intubation may be necessary).
 

Cardiovascular

Establish secure intravenous access if hypotensive.
 

Emergency Monitoring

Airway
Breathing
Blood pressure
Heart rate/rhythm
Core body temperature
Blood oximetry
 

DECONTAMINATION

Ingestion

Decontamination Not Recommended

Absorption is too rapid for decontamination to be effective.

Supportive care is likely to be successful without decontamination.

ANTIDOTE(S)

There Are No Antidotes For This Substance

There are no specific antidotes for this overdose.[1]
 
Agents including naloxone, flumazenil, and physostigmine have been investigated as potential antidotes. None have shown consistent results in reversing intoxication.
 
Physostigmine is viewed as an unproven experimental antidote for this intoxication. It was initially investigated as a reversal agent in patients under GHB-induced anesthesia.[2][3] However, use following poisoning has produced differing results, with the majority of patients not showing response.[4][5][6] Reviews of the literature have shown there is not sufficient evidence to support the use of physostigmine in acute GHB overdose.[6][7] At this stage physostigmine is not recommended.[1]
 
Additionally, naloxone and flumazenil have been used following human poisoning, both have had limited effect on reversing toxicity.[8][9][10][11][12] Neither of these compounds can be recommended.[1]
 

SIGNS AND SYMPTOMS

The correct identification of the substance is important. If the symptoms are inconsistent with those described in the literature, or the history is considered unreliable, other substances may need to be considered.
 
Other drug/compounds are commonly co-ingested with this substance and may significantly influence the clinical picture.[1]
 
With mild toxicity, gastrointestinal upset may occur and CNS effects predominate including CNS depression, euphoria, ataxia, disorientation, dizziness, and occasionally miosis and nystagmus. Sudden drowsiness followed by profound coma is a characteristic presentation; a GCS of 3 is not uncommon. Recovery is sometimes accompanied by emergence phenomena including myoclonic jerking, transient confusion, and agitation and combativeness.[1]
 
With severe toxicity, sudden, profound coma, seizures, and respiratory arrest may occur. Further complications may include bradycardia, hypotension, and hypothermia. Deaths are reported.[1][13][14][15]
 
Persistent symptoms of weakness, headache, fatigue, and nausea lasting three days after ingestion has been noted,[16] and a withdrawal syndrome is described.[17][18]
 

Onset/Duration of Symptoms

In the majority of cases signs and symptoms develop within 1 hour of ingestion and resolve within 4 to 8 hours of onset.[8][19][20][21][22][23] Recovery from coma, if it occurs, is typically rapid, and may be indicated by initial GCS score.[19] Weakness, headache, fatigue, and nausea lasting three days after ingestion has been noted.[16]
 
A withdrawal syndrome which may begin within 1 to 12 hours of the last dose and may continue for 3 to 21 days is described.[17][18][24][25][26][27]
 

Severity of Poisoning

Mild Gamma-Hydroxybutyrate ToxicityModerate Gamma-Hydroxybutyrate ToxicitySevere Gamma-Hydroxybutyrate Toxicity
Euphoria
Drowsiness
Dizziness
Confusion
Disorientation
Vomiting
Bradycardia
Hypotension
Myoclonic jerking
Hypothermia (mild)
Agitation
Ataxia
Miosis
Respiratory depression
Profound coma
Rhabdomyolysis
Seizure
Respiratory arrest
 

REFERENCES

 
[1] Schep LJ, Knudsen K, Slaughter RJ, Vale JA, Mégarbane B. The clinical toxicology of gamma-hydroxybutyrate, gamma-butyrolactone and 1,4-butanediol. Clin Toxicol (Phila) 2012 Jul; 50 (6): 458-70.
[2] Holmes CM, Henderson RS. The elimination of pollution by a non inhalational technique. Anaesth Intensive Care 1978 May; 6 (2): 120-4.
[3] Henderson RS, Holmes CM. Reversal of the anaesthetic action of sodium gamma-hydroxybutyrate. Anaesth Intensive Care 1976 Nov; 4 (4): 351-4.
[4] Yates SW, Viera AJ. Physostigmine in the treatment of gamma-hydroxybutyric acid overdose. Mayo Clin Proc 2000 Apr; 75 (4): 401-2.
[5] Caldicott DG, Kuhn M. Gamma-hydroxybutyrate overdose and physostigmine: teaching new tricks to an old drug? Ann Emerg Med 2001 Jan; 37 (1): 99-102.
[6] Zvosec DL, Smith SW, Litonjua R, Westfal RE. Physostigmine for gamma-hydroxybutyrate coma: inefficacy, adverse events, and review. Clin Toxicol (Phila) 2007; 45 (3): 261-5.
[7] Traub SJ, Nelson LS, Hoffman RS. Physostigmine as a treatment for gamma-hydroxybutyrate toxicity: a review. J Toxicol Clin Toxicol 2002; 40 (6): 781-7.
[8] Ross TM. Gamma hydroxybutyrate overdose: two cases illustrate the unique aspects of this dangerous recreational drug. J Emerg Nurs 1995 Oct; 21 (5): 374-6.
[9] Thomas G, Bonner S, Gascoigne A. Coma induced by abuse of gamma-hydroxybutyrate (GBH or liquid ecstasy): a case report. BMJ 1997 Jan 4; 314 (7073): 35-6.
[10] Li J, Stokes SA, Woeckener A. A tale of novel intoxication: seven cases of gamma-hydroxybutyric acid overdose. Ann Emerg Med 1998 Jun; 31 (6): 723-8.
[11] Libetta C. Gamma hydroxybutyrate poisoning. [Letter] J Accid Emerg Med 1997 Nov; 14 (6): 411.
[12] Williams H, Taylor R, Roberts M. Gamma-hydroxybutyrate (GHB): a new drug of misuse. Ir Med J 1998 Mar-Apr; 91 (2): 56-7.
[13] Kraner J, Plassard J, McCoy D, Roraback J, Witeck M, Evans M. Fatal overdose from ingestion of 1,4-butanediol, a GHB precursor [abstract]. J Toxicol Clin Toxicol 2000; 38 (5): 534-5.
[14] Gamma hydroxy butyrate use--New York and Texas, 1995-1996. MMWR Morb Mortal Wkly Rep 1997 Apr 4; 46 (13): 281-3.
[15] Zvosec DL, Smith SW, McCutcheon JR, Spillane J, Hall BJ, Peacock EA. Adverse events, including death, associated with the use of 1,4-butanediol. N Engl J Med 2001 Jan 11; 344 (2): 87-94.
[16] Gilmore DA, Freed CR. Central nervous system depression and weakness following ingestion of gamma hydroxybutyrate [abstract]. Vet Hum Toxicol 1991; 33: 366.
[17] Craig K, Gomez HF, McManus JL, Bania TC. Severe gamma-hydroxybutyrate withdrawal: a case report and literature review. J Emerg Med 2000 Jan; 18 (1): 65-70.
[18] Galloway GP, Frederick SL, Staggers FE Jr, Gonzales M, Stalcup SA, Smith DE. Gamma-hydroxybutyrate: an emerging drug of abuse that causes physical dependence. Addiction 1997 Jan; 92 (1): 89-96.
[19] Chin RL, Sporer KA, Cullison B, Dyer JE, Wu TD. Clinical course of gamma-hydroxybutyrate overdose. Ann Emerg Med 1998 Jun; 31 (6): 716-22.
[20] Viswanathan S, Chen C, Kolecki P. Revivarant (gamma-butyrolactone) poisoning. [Letter] Am J Emerg Med 2000 May; 18 (3): 358-9.
[21] Dyer JE. gamma-Hydroxybutyrate: a health-food product producing coma and seizurelike activity. Am J Emerg Med 1991 Jul; 9 (4): 321-4.
[22] Rambourg-Schepens MO, Buffet M, Durak C, Mathieu-Nolf M. Gamma butyrolactone poisoning and its similarities to gamma hydroxybutyric acid: two case reports. Vet Hum Toxicol 1997 Aug; 39 (4): 234-5.
[23] Gunja N, Doyle E, Carpenter K, Chan OT, Gilmore S, Browne G, Graudins A. Gamma-hydroxybutyrate poisoning from toy beads. Med J Aust 2008 Jan 7; 188 (1): 54-5.
[24] Dyer JE, Roth B, Hyma BA. Gamma-hydroxybutyrate withdrawal syndrome. Ann Emerg Med 2001 Feb; 37 (2): 147-53.
[25] van Noorden MS, van Dongen LC, Zitman FG, Vergouwen TA. Gamma-hydroxybutyrate withdrawal syndrome: dangerous but not well-known. Gen Hosp Psychiatry 2009 Jul-Aug; 31 (4): 394-6.
[26] Wojtowicz JM, Yarema MC, Wax PM. Withdrawal from gamma-hydroxybutyrate, 1,4-butanediol and gamma-butyrolactone: a case report and systematic review. CJEM 2008 Jan; 10 (1): 69-74.
[27] Galloway GP, Frederick SL, Staggers F Jr. Physical dependence on sodium oxybate. [Letter] Lancet 1994 Jan 1; 343 (8888): 57.

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