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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 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. 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. 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. 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 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 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. Alice in Wonderland First Described by John Todd, an English psychiatrist, in 1955 Disorienting Neurological Condition Temporary Condition Alice in Wonderland Visual Distortions Micropsia Macropsia Distorted Perception of other Sensory modalities Time Touch Sound Alice in Wonderland Associated with Migraines Brain Tumors Psychoactive Drugs Initial Presentation of Epstein-Barr Virus Influenza Usually Influenza A Can be H1N1 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 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 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) 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 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 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. 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. 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. 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 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 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 Legal Highs Nutmeg (Myristica fragrans) Morning glory (Ipomoea violecea): Kava kava (Piper methysticum) mitragynine, a low dose stimulent & high dose narcotic Jimson Weed (Datura stramonium) Kava lactones = sedation & hallucinations Kratom (Mitragyna speciosa) lysergic acid amide, a hallucinogen Belladonna alkaloids, atropine, scopolaine, hyoscyamine = delerium, hallucinations, anticholinergic syndrome Salvia divinorium Salvinorin A: subtle high to vivid psychedelic experience 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 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 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 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. 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 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 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 Mountain Mike New Marijuana ? Grown with advanced horticultural techniques which have increased psychoactive potency ? Marijuana with addition of another psychoactive substance such as ? Different botanical entity being smoked Ecstasy Clenbuterol : B-adrenergic agonist PCP: cyrstal joint, supergrass, dipper, illy, fry, wet Freebase or Powdered Cocaine: dusting, snowcapping 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 Mountain Mike Synthetic Cannabinoids Different chemical structure than 11-nor-9carboxytetrahydrocannabinol 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 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 Mountain Mike K-2 or Spice Toxidrome Hypokalemia Tremors Agitation Hallucinations Anxiety Tachycardia Elevated Blood Pressure Pallor Vomiting 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 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 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 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 Aggressive Andy Physical Exam HR 250 BP 161/110 mm Hg o Temp 37.6 C RR 22-30/minute Restless - hands & feet in constant motion No eye Contact Very short attention span Exasperated with all questions 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 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 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 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. 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 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 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 Aggressive Andy Definitive Diagnosis Specific high performance liquid chromatography/tandem mass spectroscopy of the urine for MDPV and Mephedrone Aggressive Andy Other Complications Cardiac (up to 2 weeks later) Tachycardia Hypertension Hyperthermia Renal: Respiratory Rhabdomyolysis Aspiration Pneumonia Delerium 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 Aggressive Andy Contaminants/ Levamisole: agranulocytosis/thrombotic events Hallucinations Prolonged Anxiety Seizures Panic Attacks Deaths Aggressive Andy Bath Salts Not Epsom salts or spa-type bath salts Drugs of abuse marketed with an innocent name Bypass current U.S. drug laws Known as White Rush Bath Salts Sold as “plant food” Sold as “insect repellant” Sold over the internet Sold at small convenience gas station markets Sold at selective stores like “head shops” Aggressive Andy Other Names for the bath salts Bliss Blue Silk Down2Earth White Horse Energizing Aromatherapy Ivory Wave Kamikaze Purple Wave Red Dove Vanilla Sky White Lightning Aggressive Andy Bath Salts White, tan, or brown powder Usually “clumpy” Encapsulated or crystal Packages of 50-200 mg or large vials of 500 mg of “cathinone” Pharmacological Effect depends on purity, concentration, and filler properties PO, Rectal insertion, Snorted (insufflated), Injected or Smoked Onset of action, Peak, and Duration depends on route of administration Aggressive Andy Sympathomimetic Toxidrome Insomnia Agitation Tachycardia/ SVT Hypertension Mydriasis Diaphoresis Tremor Aggressive Andy Other Substances Causing Sympathomimetic Toxidromes Amphetamine Methamphetamine Cocaine Prescription Drugs for ADHD Aggressive Andy DEA Schedule 1 Ecstasy (MDMA) Mushrooms (psilocybin) LSD Mescaline (peyote active ingredient) October 2011 Illegal to possess or sell the chemicals in bath salts or products containing them in the U.S. for 1 year Studies to be done to weigh whether they should be permanently banned Aggressive Andy Federal Analog Act: Any chemical “substantially similar” to a Schedule I (heroin and lysergic acid diethylamide (LSD) ) or Schedule II (methadone and injectable methamphetamine) to be treated as if it is also a controlled substance, with the caveat that the chemical has to be intended for human consumption. Marketed with the label “NOT FOR HUMAN CONSUMPTION” Aggressive Andy Bath Salts Stimulant derivatives of Schedule I chemical cathinone (bata-ketoamphetamine) from the Khat shrub, Catha edulis Mephedrone = 4-methylmethcathinone: popular Structurally like cocaine, amphetamine, & MDMA (ectasy) MDPV = 3,4-methylenedioxypyrovalerone: potent Inhibit reuptake of norepinephrine and dopamine Promote release of dopamine, noradrenalin, & serotonin Aggressive Andy Six Chemicals MDPV Mephedrone, 4-MMC 4-fluoromethcathinone 3-FMC 3,4-methylenedioxymethcathinone Flephedrone, 4-FMC 4-methylmethcathinone Methylone, MDMC 3,4-methylenedioxypyrovalerone 3-fluoromethcathinone Methedrone, BK-PMMA, PMMC 4-methoxymethcathinone Aggressive Andy European Club Scene in 2010 40% of 2,000 clubbers had used bath salts 30% of 2,000 clubbers used them in past month Use of ecstasy declined MDMA unavailable Instability of ecstasy market Internet English – Language sites selling bath salts 30 in 12/2009 70 in 3/2010 Poison Control Centers in U.S. 2009: No calls 2010: 303 Calls July 31, 2011: 4,100 calls Aggressive Andy Recreational Users report Euphoria Empathy Increased Alertness Improved Concentration and ability to focus Higher energy levels Sense of well-being (decreased hostility?) No hangover, or comedown or depression like amphetamines, cocaine, and ecstasy Aggressive Andy Health Care Providers Report Severe Paranoia Severe Anxiety Severe psychosis Severe Agitation Bizarre Behavior Tremors Delusions Persecutory Hallucinations Signs and Symptoms last for several DAYS Aggressive Andy Health Care Providers Report Palpitations Shortness of Breath Diaphoresis Hot Flashes Headaches Hyperthermia Overwhelming Thirst Polydipsia Jaw pain from bruxism (ecstasy & amphetamines) Signs & Symptoms like Amphetamine & Cocaine Intoxication – sympathetic nervous system stimulation Aggressive Andy Health Care Providers Notice Initially Combative Self-Destructive Suicidal Homicidal Violent Behavior without Warning Health Care Providers Notice Finally Suicidal Thoughts & Actions Extreme Sadness Depression Aggressive Andy Greatest Risk for Adverse Psychiatric Reactions Underlying Neurological Conditions Underlying Psychiatric Conditions Greatest Risk for Healthcare-directed Violence Male History of Violent Behavior, Psychiatric Illness, and/or drug or alcohol abuse Aggressive Andy Warning Signs for Patients at High Risk for Acting Out Speaking increasingly Loudly Abusive Language Clenched Fists Avoidance of eye contact Tense Posturing Pacing Aggressive Andy Successful Management Verbal Deescalating Techniques may not be successful if patient psychotic Sedation and nonrestrictive methods of restraint should be tried first Physical restraints probably needed POLICE USE TAZERS!! Aggressive Andy Management Sedatives in large doses & intubate to maintain airway Antipsychotic Medications Diazepam = Valium Lorazepam = Ativan Haloperidol = Haldol Ziprasidone = Geodon Monitor temperature Fatal Hyperthermia (Mephedrone) Serotonin Syndrome-Induced Hyperthermia Rhabdomyolysis RenalFailure Metabolic Acidosis DDIC – disseminated intravascular coagulation Coma Death Aggressive Andy Management: Protect Caregivers 50% ED staff become victims of patient violence 5% violent patient possess a concealed weapon Emergency Psychiatric Evaluation As Soon As Possible Body & Possession Search to remove objects of potential harm Notify Security Keep Exit to room available for providers “safety sitter” Aggressive Andy Treatment Anticipatory Guidance Unclear as to effects of metabolites Unclear as to chemicals included in “bath salts” No quality-control scrutiny Variable Potency leading to unintentional overdose Long-term consequences on brain function unknown Psychiatric Referral Consider Alcohol and Drug Withdrawal Program Law Enforcement: Charges for possession or for assault Aggressive Andy Increasing Concerns Parents Flashbacks Addiction Healthcare Workers Personal Safety Government Officials Legal System Schedule I Criminal Activity Aggressive Andy Take Home Message Designer Drugs are distributed in different ways The Internet makes the distribution of designer drugs spread more rapidly. The web makes alterations in drugs “easy” and readily available for the “chemist” Bath Salts are not benign but are readily available and can be deadly Web Site: www.erowid.org Thank you Any Questions? References Todd J. The syndrome of Alice in Wonderland, Can Med Assoc J. 1955; 73:701-704l Cinbis M, Aysun S. Alice in Wonderland syndrome as an initial manifestation of Epstein-Barr virus infection. Br J Ophthalmol. 1992; 76:316. Morishima T, Togashi T, Yokota S, et al. Encephalitis and encephalopathy associated with an influenza epidemic in Japan. Clin Infect Dis. 2002; 35:512-517. References Wade T, Morishima T, Okumura A, et al. Differences in clinical manifestations of influenze-associated encephalopathy by age. Microbiol Immunol. 2009; 53:8388. Maricich SM, Neul JL, Lotze TE et al. Neurological complications associated with influenze A in children during the 2003-2004 influenza season in Houston, Texas. Pediatrics. 2004; 114: e626-e633. Brock e, Varghese A, Rowe C, et al. Neurologic complications associated with novel influenza A (H1N1) virus infections in children – Dallas, Texas, May 2009. MMWR 2009;58(28):773-778. References Augarten A, Aderka D. Alice in Wonderland Syndrome in H1N1 Influenza: Case Report. PEC. 2011; 27(2):120. Green RC. Nutmeg poisoning. JAMA. 1959;171:1342-1344. Stein U, Grier H, Hentshel H. Nutmeg (myristicin) poisoning-report on a fatal case and a series of cases recorded by a poison information centre. Forensic Sci Int. 2001;118:87-90. References Sangalli BC, Chiang W. Toxicology of nutmeg abuse. Clin Toxicol. 2000;38:671-678. Carstairs SC, Cantrell PL. The spice of life: an analysis of nutmeg exposures in California. Clin Toxicol. 2011;49:177-180. Forrester MB. Nutmeg intoxication in Texas, 1998-2004. Hum Exp Toxicol. 2005;24:563-566. References Demetriades AK, Wallman PD, McGuiness A, et al. Low cost, high risk: accidental nutmeg intoxication. Emerg Med J. 2005; ;22:223-225. CDC. Emergency department visits after use of a drug sold as bath salts” – Michigan, November 13, 2010 to March 31, 2011. MMWR. 2011;60:1-4. Winstock AR, Mitcheson LR, Deluca P, et al. Mephedrone, new kid for the chop? Addiction. 2010;106:154-161. References Wood DM, Davies S, Greene Sl, et al. Case series of individuals with analytically confirmed acute mephedrone toxicity. Clin Toxicol. 2010;48:924927. Maskell PD, De Paoli g, Seneviratne C, et al. Mephedrone-related deaths. J Anal Toxicol. 2011;35:188-191. Paynter B. Big business of synthetic highs. Businessweek. http://www.businesswekk.com/magazine/content /11_26/b4234058348635.htm. References www.justice.gov/dea/pubs/pressrel/pr102111.html . Wood DM, Greene SL, Dargan PI. Clinical pattern of toxicity associated with the novel synthetic cathinone mephedrone. Emerg Med J. 2010;28(4):280-282. American Association of Poison Control Centers. Bath Salts Data. McGraw MM. Is your patient high on “bath salts”. Nursing 2012; 26-32. References Osterhoudt K. A Teenager with Agitation. Ped Emerg Care. 2010;26(6);462-465. American Association of Poison Control Centers. Marijuana and Synthetic Marijuana Data. American Association of Poison Control Centers. Nutmeg Data.