Hey Dude! How Did I Get Here?

1. Hey Dude! How Did I Get Here? Melinda Lucas, M.S., M.D., F.A.A.P. SouthWest Virginia Pediatric Conference, August 4-5, 2012

3. Disclosure Statement of Financial Interest Melinda Lucas DOES NOT have a financial interest/arrangement or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation.

4. Conflict of Interest Disclosure All individuals who participate in sponsored activities are expected to disclose any significant financial relationships that may pose a conflict with the principles of balance and independence. In the past 12 months neither Melinda Lucas nor any member of her family has had a financial or beneficial relationship with one or more of the following commercial entities: grant/research support, other remuneration (Speaker’s Bureau, honoraria, travel expenses, etc.), Major Stock/share holder (not mutual funds), Advisory Board; Ownership or Partnership.

5. Learning Objectives Develop a differential diagnosis for patients with hallucinations and an altered state of consciousness Understand the impact of social media on illicit drug usage Become familiar with the toxidromes for 2 designer drugs.

6. Alice In Wonderland 11 Year Old Female Fever, cough, Coryza, & Myalgias for 3 days Night-time Audio and Visual Hallucinations Pictures Zoomed in and out which scared her Alleged her parents were talking and moving in very, very slow motion

7. Alice in Wonderland Negative PMH; No Migraines Family History negative for Migraines, Tamiflu (oseltamivir phosphate) for 24 hours Vital Signs: Temp 36.8oC, Heart Rate 107 bpm, BP 92/68 mm Hg, Pulse Ox 98% Room Air Physical Exam: no meningeal irritation; Cranial Nerves 2-12 Normal, Cerebellar Function Normal Motor and Sensory Systems Normal

8. Alice in Wonderland • Labs: • CBC & diff Normal • CMP Normal • EBV Serology Negative • H1N1 PCR Positive • Clinical Course: • Flu symptoms resolved in 2 days • Neurological symptoms resolved in 2 days • Tamiflu stopped after 5 day course.

9. Alice in Wonderland First Described by John Todd, an English psychiatrist, in 1955 Disorienting Neurological Condition Temporary Condition

10. Alice in Wonderland • Visual Distortions • Micropsia • Macropsia • Distorted Perception of other Sensory modalities • Time • Touch • Sound

11. Alice in Wonderland • Associated with • Migraines • Brain Tumors • Psychoactive Drugs • Initial Presentation of Epstein-Barr Virus • Influenza • Usually Influenza A • Can be H1N1

12. Alice in Wonderland • Take Home Messages • Medical Illnesses can present with visual and auditory changes or hallucinations • Mental Health Problems can present with hallucinations • Psychotropic Drugs can also cause hallucinations and/or visual & auditory changes

13. The Spice Girl 17 year old girl 11 weeks gestation Bipolar Disorder and Depression History Stayed at friend’s house until afternoon Slept 2-6 p.m. Awoke with Nausea, dizziness, thirst, heart racing, unable to void Visual and Auditory Hallucinations Medications: Prenatal Vitamins

14. The Spice Girl • PMH: • Cutting Behaviors • 2 Inpatient Psychiatric Admissions • Psychiatric Medications self-discontinued • Last Psychiatric Visit > 1 year ago • Prior user of Cocaine and Cannabis • Smoker • Prenatal Care started 2 weeks ago • SH • Broke up with boyfriend recently • (father of unborn child)

15. The Spice Girl • PE: • Denies suicidal & homicidal tendencies • Denies thoughts of wanting to hurt unborn child • Vital Signs: Temp 97oF; HR 150; BP 115/51 mm Hg; Pulse Oximeter 100% Room Air • Alert, Anxious, awake • Warm, Dry Skin without flushing • PERRLA, No nystagmus, Pupils 3 mm • Dry Mouth • Normal Thyroid • Tachycardia without Murmur • Normal Neurological Exam except for visual and auditory hallucinations

16. The Spice Girl • Lab: • Normal Urine Drug Screen for amphetamines, barbiturates, benzodiazepines, cocaine, opiates, phencyclidine, cannabis using kinetic interactions of micro particles technique • Negative blood tests for ethanol, acetaminophen, salicylates • EKG with 130 beats per minute, QRS interval 86 milli seconds, QTc interval of 380 milliseconds, no ischemia, NOT SVT

17. The Spice Girl • Treatment • 20 mL/kg Normal Saline IV • Ultrasound of Pelvis with single live intrauterine pregnancy at 12 weeks 2 days • Admitted for Observation • 2 Episodes of hypotension (70/30 mm Hg) treated with IV NS – 20 mL/kg each • Hallucinations Resolved over 2 days • Confessed to ingestion of a powder from her mother’s spike rack to get high • instructions on T.V.

18. The Spice Girl • Nutmeg • Abortifacient by American & English women in late 19th & early 20th century. • Euphoric and Hallucinogenic effects with low cost and ease of availability • Spice obtained by grating the kernel within the fruit of the nutmeg tree. • Mace is made from the red-laced membrane surrounding the seed.

19. The Spice Girl • Nutmeg comes from the evergreen tree, Myristica fragrans, & is a mixture of compounds: • Aromatic (myristicin, elemicin, and safrole) • Terpene (eugenol and mace) • Compositions vary with differences in quality, storage, purifying and processing • Elemicin chemically closely resembles mescaline • Myristicin is closely related to 3-methoxy-4,5 methylenedioxyamphetamine.

20. The Spice Girl • Atropine-Like Syndrome or mistaken for pure antichoinergic toxicity • Dry mouth • Facial flushing • Nausea • Unsteadiness (dizzy) • Epigastric Pain • Urinary Retention • Blurred Vision

21. The Spice Girl • Sympathomimetic and Serotonergic Effects • Cardiovascular Effects • Sinus Tachycardia • Palpitations • Hypotension • Central Nervous System Effects • Hallucinations - 14% of users • Psychosis • Anxiety • Drowsiness • Fear • Paresthesias

22. The Spice Girl • Symptoms • Ingestions of >10 g of nutmeg • 1-3 whole nuts or 1-2 TBSP ground nutmeg • Appear 3-6 hours after ingestion • Duration of 24-48 hours • Treatment • Supportive care for agitation, hypotension, and psychiatric symptoms

23. Legal Highs • Nutmeg (Myristica fragrans) • Morning glory (Ipomoea violecea): • lysergic acid amide, a hallucinogen • Kava kava (Piper methysticum) • Kava lactones = sedation & hallucinations • Kratom (Mitragyna speciosa) • mitragynine, a low dose stimulent & high dose narcotic • Jimson Weed (Datura stramonium) • Belladonna alkaloids, atropine, scopolaine, hyoscyamine = delerium, hallucinations, anticholinergic syndrome • Salvia divinorium • Salvinorin A: subtle high to vivid psychedelic experience

24. The Spice Girl • Take Home Message • Sources of information may be from unverified sources such as T.V., online encyclopedias, You Tube, online “trip reports”, tweets & blogs, and “how-to” information on the Web • Conventional intoxicants and “legal highs” are a trend with adolescents. • Reliable web sites: • www.herbmed.org; www.mskcc.org/aboutherbs

25. Mountain Mike • 15 year old brought to ER by EMS for violence, crazy behavior, and visual hallucinations. • 15 minutes prior to calling EMS he took a Single Bong Hit from a water pipe. • Prior History of being high before, but not like this

26. Mountain Mike • Physical Exam • Restless, anxious • Oriented to person, place, time • Complains legs feel numb and twitchy • Vital Signs: HR 120 bpm; BP 135/85 mm Hg; afebrile; pulse oximeter 98% room air • PERRLA, EOMs intact, Pupils slightly dilated • Moist Membranes • Normal Thyroid

27. Mountain Mike • PE • Chest exam normal • CV exam no murmur or gallop; otherwise normal • Abdominal exam normal • Skin: sweaty, no flushing of skin, no rash • Neurological: Normal cranial nerves, no clonus, normal strength and sensation in extremities; fasciculations in quadricep muscles.

28. Mountain Mike • Lab • Glucose normal – not elevated or low • CMP: Potassium 2.9 mEq/L; normal otherwise • Ethanol negative • Urine radioimmunoassay (RIA) for amphetamines, barbiturates, benzodiazepines, cocaine, opiates , and phencyclidine (PCP) is negative. Positive for Tetrahydrocannabiol

29. Mountain Mike • Treatment • Lorazepam 2 mg IV • HR decreases to 95 bpm • Calmer • Observation for 6 hours • Confused as to how he got to hospital • 3 Friends taken to same hospital after trying a new marijuana for the first time

30. Mountain Mike • Acute Marijuana Intoxication • Increase Heart Rate • Increase Blood Pressure • Euphoria and a Sense of Detachment • Unpleasurable experience rare • inconsistent with patient’s prior history • Dysphoria with Large Doses and assosciated with panic, anxiety or depression – Not agitation • Agitation NOT TYPICAL • Hypokalemia NOT TYPICAL unless malnourished in a habitual drug user

31. Mountain Mike • New Marijuana • ? Grown with advanced horticultural techniques which have increased psychoactive potency • ? Marijuana with addition of another psychoactive substance such as • Ecstasy • Clenbuterol : B-adrenergic agonist • PCP: cyrstal joint, supergrass, dipper, illy, fry, wet • Freebase or Powdered Cocaine: dusting, snowcapping • ? Different botanical entity being smoked • Salvia divinorum: legal marijuana, herbal smoke, herbal marijuana • Mephedrone derived from khat plan (catha edulis) • ? Chemical entity being smoked • Herbal incense, herbal smoke • Potpourri • Incense • Mixture of 1 or more synthetic cannabinoids

32. Mountain Mike • Synthetic Cannabinoids • Different chemical structure than 11-nor-9-carboxytetrahydrocannabinol • Most common molecule tested in UDS • Gas chromatography-mass spectrometry in highly specialized laboratories • 4 Selected synthetic cannabinoids • JWH-018 • JWH-073 • CP-47,497 • HU-210

33. Mountain Mike • Synthetic Cannabinoids • Brand Names • K 2 after second highest mountain on earth • (28,251 ft • Deadly to inexperienced climbers • Spice after spice from Frank Herbert’s book Dune • JWH-018 • Sold over the Internet to a private residence for research laboratory purposes only and comes with a disclaimer • Sold at certain “convenience” stores • Sold at “head shops” or drug paraphenalia shops

34. Mountain Mike • K-2 or Spice Toxidrome • Hypokalemia • Tremors • Agitation • Hallucinations • Anxiety • Tachycardia • Elevated Blood Pressure • Pallor • Vomiting

35. Mountain Mike • Take Home Message • Anticipatory Guidance • Manufacture not regulated • Full range of immediate adverse effects unknown • Long-term consequences of synthetic cannabinoids and the derivatives are unknown • Tolerance and physiological withdrawal have been reported • If the symptoms do not add up, suspect “incense” • State-specific guidelines about possession exist • FDA bans sale and importation

36. Aggressive Andy 14 year old with ADHD brought to ED for a mental status exam by police Police called to residence by mother because patient threatening to kill her and destroying walls and furniture Mother states patient was in bedroom and emerged with intermittent confusion and aggression May have been hallucinating for several days, and seems to be hiding from someone, but no one around

37. Aggressive Andy Patient uncomfortable and complains of chest pain and his heart racing Intermittent racing of heart for several days Thoughts race through his brain Panicking as thoughts race Very hungry but cannot eat

38. Aggressive Andy • No medications • Self-stopped medications for ADHD years ago because they were costly • SH denies substance abuse initially but later admits to alcohol (three 12 packs each weekend), cigarettes (1 ppd), K-2 or Spice if horticultural marijuana not available (2-4 joints 2 times a day), mother’s Xanax, tried meth and cocaine recently • Admits to taking mother’s Xanax tonight and also the “white powder” she uses when upset and needs to laugh

39. Aggressive Andy • Physical Exam • HR 250 • BP 161/110 mm Hg • Temp 37.6oC • RR 22-30/minute • Restless - hands & feet in constant motion • No eye Contact • Very short attention span • Exasperated with all questions

40. Aggressive Andy • PE • Dilated, reactive pupils without nystagmus • Normal nares, nasal septum, oral pharynx • No goiter • Chest clear • CV with tachycardia, but normal pulses and perfusion and warm pink extremities • No liver or spleen enlargement • Sweaty skin

41. Aggressive Andy • PE • Cranial Nerves 2-12 intact, Motor strength and tone normal, normal DTR, alert and able to answer questions but concerned about chest pain, • Tremor in outstretched hands

42. Aggressive Andy • Lab • CMP normal • Glucose Normal • Ethanol Not detected • Commercial radioimmunoassay of urine for amphetamines, benzodiazepines, barbiturates, cannabis, cocaine, opoids was negative • CXR Normal • CT head Normal • EKG: SVT

43. Aggressive Andy • Treatment • IVF with 20 mL/kg Normal saline bolus • Adenosine X 2 with HR converting for 20 seconds • Response to Cardizem (diltiazem) with HR 220.

44. Aggressive Andy • Impression: • Compensated SVT • Hypertension unusual for SVT • Agitation and Aggression Worrisome for Safety of Health Care Providers, safety of patient • Overdose/Ingestion of ? Bath Salts or K-2 • Binge Drinking and habitual substance abuse • ADHD

45. Aggressive Andy Transfer to PICU requested - utilizing Helicopter Patient refused stretcher and restraints and became aggressive and threatening Helicopter Pilot refuses to fly uncooperative patient Ativan 4 mg IV given X 2 and patient settles Ground transport with EMS and helicopter crew transports patient to PICU Patient restrained and cooperative in SVT with talk down 2-4 hours later patient converts from “stable SVT” to NSR after maximum dose of cardizem bolus and drip used. Admits to snorting some salt Leaves AMA 2 days later with Mother and GF’s assistance

46. Aggressive Andy • Diagnosis of Exclusion • Urine Toxicology for PCP, Cocaine, Amphetamines • Serum Alcohol Level • BMP for Electrolyte Imbalances • Bedside Glucose • ABG as metabolic acidosis seen with sympathomimetic toxicology • CBC & Diff for infection or severe anemia • CT head for subarachnoid hemorrhage or hydrocephalus • 12 – Lead EKG for arythmia or ischemia • Consider Troponin, CPK-MB, Myoglobin

47. Aggressive Andy • Definitive Diagnosis • Specific high performance liquid chromatography/tandem mass spectroscopy of the urine for MDPV and Mephedrone

48. Aggressive Andy • Other Complications • Cardiac (up to 2 weeks later) • Tachycardia • Hypertension • Hyperthermia • Renal: • Rhabdomyolysis • Respiratory • Aspiration Pneumonia • Delerium

49. Aggressive Andy • Other Complications: • Neurological: • Seizures • Intracerebral Hemorrhage • Myopathy • Critical Illness Myopathy/Polyneuropathy • GI: intestinal infarction/ischemia • Other polydrug usage complications/contaminants • Manganism from potassium permanganate exposure

50. Aggressive Andy • Contaminants/ • Levamisole: agranulocytosis/thrombotic events • Hallucinations • Prolonged Anxiety • Seizures • Panic Attacks • Deaths