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A Collapsed Giant Dr. Jacky Sia RHAED A Collapsed Giant Dr. Jacky Sia RHAED

TSKAED 1998 n n n No computer system No Toxicology database No CMS No TSKAED 1998 n n n No computer system No Toxicology database No CMS No internet No urinary test.

Case summary n n 39 -year Caucasian. 240 lbs giant. Well along Collapsed and Case summary n n 39 -year Caucasian. 240 lbs giant. Well along Collapsed and convulsion in gym.

DDx of collapse DDx of collapse

Reading! Reading!

Possible supplement n n n EFA: ephedrine, caffeine, aspirin. EFT: Ephedrine, Foskolin, Theophylline. Creatine. Possible supplement n n n EFA: ephedrine, caffeine, aspirin. EFT: Ephedrine, Foskolin, Theophylline. Creatine. Steroids: oral, injectable. Herbal extract. Thyroid extract. Many more….

Drugs before gym Drugs before gym

History n another 260 -lbs giant. History n another 260 -lbs giant.

Case summary n n n BP 138/86, P 76/min. Temp: 36. 8 C GCS: Case summary n n n BP 138/86, P 76/min. Temp: 36. 8 C GCS: 12/15 PERL: 3 mm Intermittent twitching of limbs Blood sugar: 6. 9 mmol. Systemic review were normal.

Case summary n n n ECG was normal. No urinary for toxicology kit (1998) Case summary n n n ECG was normal. No urinary for toxicology kit (1998) Valium 5 mg IVI. To RH medical ward. CBP, R/LFT, Toxicology screen, CT brain: normal.

Case summary n n Rapid recovery 2 hours later. DAMA despite twitching of limbs Case summary n n Rapid recovery 2 hours later. DAMA despite twitching of limbs and drooling of saliva. Dx: GHB (History) Reason for collapse: alcohol + GHB.

GHB poisoning GHB poisoning

Media interview Media interview

Male - not exemption Male - not exemption

Layman Diagnostic kit Layman Diagnostic kit

Layman Diagnostic kit Layman Diagnostic kit

History n n n 1980 s: over-the-counter in health stores. Abused as recreational drugs. History n n n 1980 s: over-the-counter in health stores. Abused as recreational drugs. 1991: ? Political reason. Banned for its excellent GA property.

GHB - naturally found n n n Hypothalamus Basal ganglia Kidney Heart Skeletal Brown GHB - naturally found n n n Hypothalamus Basal ganglia Kidney Heart Skeletal Brown fat tissue.

Physiology n n n 16 times increase in GH. Inhibit the protein breakdown. Facilitate Physiology n n n 16 times increase in GH. Inhibit the protein breakdown. Facilitate fat loss. Induce hypotonia. Enhance sexual arousal.

Physiology n n n Colorless, odorless, tasteless. Excellent sedation, amnesia. “Date-rape” drug: rapid incapacitation. Physiology n n n Colorless, odorless, tasteless. Excellent sedation, amnesia. “Date-rape” drug: rapid incapacitation. No toxic metabolites, only CO 2, H 2 O. Normalized after 2 - 5 hours.

GHB n Developed as an anesthetic due to similarity to GABA Initially marketed to GHB n Developed as an anesthetic due to similarity to GABA Initially marketed to bodybuilders, later became popular as a club drug.

GHB n Mechanism of Action n Structural similarity to GABA, but crosses the BBB GHB n Mechanism of Action n Structural similarity to GABA, but crosses the BBB Acts on GABA-B receptors Clinical manifestation n CNS depression/euphoria (20 -30 mg/kg) Coma and respiratory depression seen (50 -70 mg/kg) Headache, ataxia, confusion, myoclonus

GHB – Recovery Time Chin RL. Clinical Course of Gamma-Hydroxybutyrate Overdose. Annals of Emerg. GHB – Recovery Time Chin RL. Clinical Course of Gamma-Hydroxybutyrate Overdose. Annals of Emerg. Med. 1998: 31: 716 -722

GHB – Recovery Time GHB – Recovery Time

Elimination of GHB n n n GHB exhibits zero-order kinetics - it has no Elimination of GHB n n n GHB exhibits zero-order kinetics - it has no half-life. Time required to eliminate half a given dose increases as the dose increases. Everyone excretes GHB - it is a normal urinary metabolite. Concentrations < 10 ug/m. L may be considered normal.

Back to basic n n n House brewed in US. Different potencies, purities. Different Back to basic n n n House brewed in US. Different potencies, purities. Different side effects. Toxic effect unpredictable. 30 mg/kg to 60 mg/kg.

Therapeutic Value n n Sleeping disorder Narcolepsy Alcohol withdrawal Depression Therapeutic Value n n Sleeping disorder Narcolepsy Alcohol withdrawal Depression

Case series By Okun, Michael S; Doering, Paul L; Bartfield, Richard B (Emedicine abstract) Case series By Okun, Michael S; Doering, Paul L; Bartfield, Richard B (Emedicine abstract) 2000 Emergency Medicine. via Bell&Howell Information and Learning Company

Case series 1 Age 23 man GCS 3 Temp 35. 8 RR No Toxi Case series 1 Age 23 man GCS 3 Temp 35. 8 RR No Toxi screen BZ ET Withdraw + 30 min. , agitation

Case series 2 Age 20 man GCS 3 Temp 35. 8 RR Labour Toxi Case series 2 Age 20 man GCS 3 Temp 35. 8 RR Labour Toxi screen Alcohol ET Withdraw + 1 hr. , agitation

Case series 3 Age 20 lady GCS 3 Temp UK RR No Toxi screen Case series 3 Age 20 lady GCS 3 Temp UK RR No Toxi screen ET Withdraw BZ, Cocaine + 4 hours

Case series 4 Age 20 lady GCS 3 Temp 34. 6 RR Toxi screen Case series 4 Age 20 lady GCS 3 Temp 34. 6 RR Toxi screen ET Withdraw 8 / min -ve + 3 hours.

Case series 5 Age 28 man GCS 4 Temp 35. 7 RR Toxi screen Case series 5 Age 28 man GCS 4 Temp 35. 7 RR Toxi screen ET Withdraw Shallow Alcohol, cocaine + 1 hour

Case series 6 Age 22 lady GCS 3 Temp UK RR Toxi screen ET Case series 6 Age 22 lady GCS 3 Temp UK RR Toxi screen ET Withdraw Shallow Alcohol, Amphetamine -ve 7 hours

Retrospective - Chin RL n n n Ref 14 1993 to 1996 69% male Retrospective - Chin RL n n n Ref 14 1993 to 1996 69% male with mean age 28 years. Co-ingestion (alcohol, club drugs) Deep coma. Hypothermia. Bradycardia to AF; Hypotension. Respiratory acidosis.

Retrospective - Chin RL n n Ref 14 Must rule out AEIOU TIPS. Conservative Retrospective - Chin RL n n Ref 14 Must rule out AEIOU TIPS. Conservative approach if history is reliable. One study: 17/25 patients (GCS 3) NOT intubated. Emergence feature: myoclonic jerking, confusion and combativeness.

? Toxidrome ? Toxidrome

National laboratories n n n Lab tests not readily available. LOC: serum level 50 National laboratories n n n Lab tests not readily available. LOC: serum level 50 mg/d. L. Coma: serum level 260 mg/d. L.

Drugs Combinations! Drugs Combinations!

Lessons Lessons

Lessons n n n Wanchai: > 3 cases (1 M, 2 F) GHB: unreported? Lessons n n n Wanchai: > 3 cases (1 M, 2 F) GHB: unreported? History, clinical signs & suspicion. Intubate or not ? Supportive treatment. Further research: test kit.

References n n n n n Gal l imber ti L, Canton G, Gent References n n n n n Gal l imber ti L, Canton G, Gent i le N, e t al. Gamma hydroxybutyric acid for treatment of alcohol withdrawal syndrome. Lancet 1989; 2 (8666): 787 -9. 2. Chin MY, Krentzer RA, Dyer JE. Acute poisoning from gamma hydroxybutyrate in California. West J Med 992; 156(4): 380 -4. 3. Hodges B, Everett J. Acute toxicity from homebrewed gamma hydroxybutyrate. J Am Board Fam Pract 1998; 11(2): 154 -7. 4. John Mor g entha l e r and Dan Joy. Gamma - hydroxybutyrate. Smart drug news. September 10 th, 1994 [v 3 n 6]. 5. Ta kaha r a J, Yunok i S, Ya kushi j i W, e t a l. Stimulatory effects of gamma-hydroxybutyric acid on growth hormone and prolactin release in humans. J Clin Endocrinol Metab 1977; 44(5): 1014 -7. 6. Laborit H. Sodium 4 -hydroxybutyrate. Int J Neuropharmacol 1964; 3: 433 -52. 7. Laborit H. Cor relations between protein and serotonin synthesis during various activities of the central nervous system. Res Commun Chem Pathol Pharmacol 1972; 3(1): 51 -81.

References n n n n 8. Vickers MD. Gamma-hydroxybutyric acid. Int Anesthesiol Clin 1969; References n n n n 8. Vickers MD. Gamma-hydroxybutyric acid. Int Anesthesiol Clin 1969; 7(1): 75 -89. 9. Chin RL, Sporer KA, Cullison B, et al. Clinical course of gamma-hydroxybutyrate overdose. Ann Emerg Med 1998; 31(6): 716 -22. 10. Fadda F, Colombo G, Mosca E, et al. Suppression by g amma -hydroxybuty r i c a c id of e thanol withdrawal syndrome in rats. Alcohol 1989; 24(5): 447 -51. 11. Leikin JB, Paloucek FP. Poisoning & Toxicology Handbook, 2 nd ed. Hudson, Ohio, Lexi-Comp Inc. , 1995. 12. Baselt RC, Cravey RH. Disposition of Toxic drugs and Chemicals in Man, 4 th ed. Foster City, CA, CTI, 1995. 13. Ejjenhorn MJ, Schonwald S, Ordog G, et al. Drug of Abuse. In Ejjenhorn MJ(ed): Ejjenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning, 2 nd ed. Baltimore, Williams and Wilkins, 1997. 14. Chin RL, Sporer KA, Cullison B, Dyer JE, Wu TD: Clinical course of GHB overdose. Ann Emerg Med June 1998; 31: 716 -722. 15. David GEC, Fiona YC, Brian JB, Peter DF, Roger WB. Fatalities associated with theuse of GHB and its analogue in Australasia. MJA 2004; 181(6): 310 -313.