amy gutman md [email protected] ems medical director

Amy Gutman MD [email protected] EMS Medical Director

Impossible to cover all tox emergencies in 90 minutes! Review pharmacology, assessment & management Major players of illicit & prescribed medications commonly causing toxicity

Who: Group vs individual What: What & how much? Where: Is the scene safe? Why: SI vs accidental How: Route of exposure Ingestion, Inhalation, Absorbtion Social History Drugs, Alcohol, Smoking Allergies Medications Prescribed & Illicit PMH ODs, SI, HI, medical Hx Last Oral Intake Events W W W W W H

Vitals are Vital Physical exam clues help with identifying toxin In most cases, its not immediately important what toxin is, rather treating effects of the exposure Always assume patient is lying

Focus on supportive therapy rather than toxin identification as it is often complicated by a poor or creative historian 1. IV / O2 / Monitor 2. Airway management 3. Altered mental status (AMS) protocol including glucose check 4. Symptomatic management of nausea, vomiting, seizures 5. Early & effective decontamination For all toxins above steps are part of the general management

Miosis Sympathomimetics Cholinergics Clonidine Nicotine PCP Mydriasis Anticholinergics Opiates Sympathomimetics

Decreased Alcohols Barbituates Benzodiazepines Opiods Increased CO Cyanide Salicylates

Tachycardia Anticholinergics Antihistamines Antidepressants PCP Sympathomimetics Bradycardia Alpha, Beta & Calcium Channel Blockers Digoxin Cholinergics Cyanide Nicotine

Hypertension Anticholinergics Antihistamines Antidepressants PCP Sympathomimetics Hypotension CO Cyanide / Iron Antidepressants Opioids Sedative-Hypnotics

Hyperthermia Anticholinergics MAOIs PCP Salicylates Sympathomimetics Hypothermia Beta Blockers CO Cholinergics Ethanol Hypoglycemics Sedative-Hypnotics

Alcohols Anticholinergics Cholinergics Heavy Metals Beta Blockers CO Antidepressants Lithium Opiods PCP Antipsychotic Salicylates Sedative-Hypnotics

Based upon neurotransmitter stimulated or receptor triggered by a chemical reaction Symptoms result from having too much or too little of a neurotransmitter or chemical Most symptoms secondary to nervous system effects

Acetylcholine Dopamine Serotonin Norepinephrine

Primary neurotransmitter in brain reward pathways Dopaminergic drugs produce euphoria Over time neurons require more & more dopamine stimulation to produce euphoria, or tolerance

Dopamine stimulant fools neurons into releasing dopamine to send a pleasure message Also stimulates serotonin & norepinephrine Highly addictive, causing intense pleasurable rush followed by a euphoric high lasting for 12+ hours User experiences severe depression as euphoria dissipates Powder or clear chunky crystal from an odorless, bitter-tasting, crystalline powder that is ingested, snorted, injected or inhaled

#2 illicit drug worldwide, #1 illicit drug in US 20%-30% labs discovered after a fire or explosion Police & EMS most often injured during explosions Previously prescribed to treat obesity, sexual dysfunction, narcolepsy & ADHD Asian factories supply workers with meth to maintain productivity in tedious & repetitive tasks

Children at >25% of labs Sustain physical, developmental & psychological hazards 3x greater likelihood of physical & / or sexual abuse Likely to imitate parents' behaviors Hazard Exposure: Weapons / Explosives Rodent & insect infestation Rotten food & garbage Inoperative heater, air conditioner, toilets & running water Drug paraphernalia Dangerous animals You are a mandatory reporter, required to file a 51A

ACh is an excitability, arousal & reward neurotransmitter with effects on learning & memory Cholinergics produce mimic, or release acetylcholine Think Organophosphate Insecticides Bethanacol Edrophonium Physostigmine Pilocarpine Nicotine Toxicologic hallmark is DUMBELS / SLUDGE

Defecation / Diarrhea Urination Miosis Bronchorrhea/ Bradycardia Emesis / GI Distress Lacrimation Salivation Prehospital Management: Airway Management Seizure Management Gastric decontamination Atropine & Pralidoxime (2-PAM) - Mark I Kit

Substances that block or decrease ACh Antihistamines Antipsychotics / Antidepressants Belladonna / Mushrooms Muscle Relaxants & Antispasmodics Mydriatics Atropine Classified according to receptors affected: Antimuscarinics & Antinicotinics Considered least "fun" recreational drug Lack of euphoria Low risk of dependence

Hot as a Hare Fever Dry as a Bone Dry Skin / Xerostomia / Ileus / Urinary Retention Red as a Beet Flushed skin Mad as a Hatter Psychosis / Hallucinations / Delirium / Agitation / Amnesia Other Tachycardia Increased Intraocular Pressure / Mydriasis / Diplopia Ataxia / Choreoathetosis / Seizures / Coma Respiratory depression

Chief inhibitory neurotransmitter Disrupted GABA signal causes neuro & psychiatric pathologies including movement & anxiety disorders, epilepsy, schizophrenia & addiction Drugs affecting GABA receptors: Alcohol Barbiturates Benzodiazepines Baclofen Anti-epileptics Gamma-Hydroxybutyric acid (GHB) Propofol

GABA stimulating Widespread legal & illicit use Anxiety, depression, pain Date rape drug Toxicity worsened if used with alcohol or other sedatives SSX: AMS, amnesia, hallucinations Dizziness, ataxia, weakness, slurred speech Drowsiness, paradoxical agitation Blurred vision, nystagmus Respiratory depression Hypotension Coma / Death Management Charcoal w/ little prehospital utility & contraindicated if somnolent AMS Protocol & aggressive airway support Hypotension rare Search for another cause Never use benzodiazepine antagonist flumazenil

GABAenergic drugs Anesthesia plus Amnesia Drugs: Ketamine, Rohypnol, GHB SSX: Sedation, slurred speech, coma Confusion, delirium, hallucinations Paresthesias, dysesthesias Diplopia, blurred vision, nystagmus Ataxia

Disassociative amnestic / anesthetic structurally resembling PCP CNS depressant, rapid-acting general anesthetic, sedative- hypnotic, analgesic & hallucinogenic Symptoms Impaired motor function Pulmonary edema Delirium, hallucinations, out of body experiences, vivid Dreams Seizures, dystonia Vomiting Arrhythmias, cardiac arrest Coma Treatment: Benadryl for dystonia Benzodiazepines for sedation

Anticholinergic Dry skin, miosis Dopaminergic / Norepinephrine Agitation, delusions Opiate Altered pain perception Serotonin Altered perceptions GABA Inhibition: Excitation Same treatment guidelines as ketamine

GABAenergic anesthetic / sedative often used as a body- building aid Clear liquid, white powder, tablet or capsule often carried in a water bottle or eye dropper Used in combination with alcohol to increase effect

Amnesia + suggestiveness Hypothermia, lethargy, somnolence Dizziness, AMS Euphoria Vomiting Bradycardia Respiratory depression, coma Seizures, myoclonic jerking Avoid positional asphyxia Sudden airway collapse & aspiration Avoid respiratory depressants Unpredictable clinical course with rapid changes in mental & respiratory status Presentation & treatment mimic ETOH intoxication

Benzodiazepine, sedative-hypnotic, respiratory depressant, amnestic Date rape drug often placed in alcoholic drinks for ingestion Odorless, tasteless, dissolves easily Clonazepam often used as a roofie alternative SSX: Sedation, amnesia, suggestiveness Treatment: Supportive Often will not seek care until effects of drug wear off Suspected ingestions treated as criminal cases

Stress hormone & catecholamine synthesized from dopamine Fight-or-flight response increases HR, triggering release of glucose & increasing blood flow to muscle Increasing BP triggers compensatory baroreceptor reflex resulting in paradoxical bradycardia Typical Sympathomimetics Cocaine MDMA (Ecstasy) Phencyclidine (PCP) Amphetamine / Methamphetamine Ephedrine / 2 -agonists Caffeine Nicotine Dextromethorphan (DMX)

Tachycardia, arrhythmias HTN, aortic dissection, ICH Hyperthermia Agitation, delirium, seizures Myocardial infarction, angina Sympathomimetic Toxidrome HITTER Hallucinations Insomnia Tremor Tachycardia Excessive Speech & Motor Activity Restlessness

Arrhythmia management Reduce temperature Restrain to prevent harm Chemical > physical restraints Benzodiazepines, haloperidol Avoid beta blockers Leaves unopposed - adrenergic stimulation

Tachycardia / Arrhythmias HTN Occasionally hypotensive with reflexive bradycardia CNS stimulation Treatment: Sedation Treat hyperthermia

Feel Good Drug suppresses need to eat, sleep or drink Similarities to hallucinogens & amphetamines Ingested, inhaled, injected Often mixed with PCP Blocks reuptake & release of serotonin & dopamine Effects within 15 mins include euphoric & energy rush followed by a 2-3 hour plateau then fatigue

Malignant Hyperthermia DIC AMS, stroke Seizures, tremors Tachycardia, HTN, CHF Jaw Clenching, bruxism Nystagmus, mydriasis Hallucinations, panic attacks Syncope, vertigo Dehydration Secondary Hyponatremia Treatment Calm environment Active cooling if indicated Chemical / physical restraints

Mu-opiod receptor stimulation Narcotics Some sedative anesthetics SSX: Pinpoint pupils Respiratory depression Bradycardia, hypotension Hypothermia Pulmonary edema Seizures Treatment Naloxone / Narcan Airway management Symptomatic

Cough suppression via opiate agonist activity Effects related to ketamine, PCP, opiates OTC Robitussin Maximum Strength (not DM) cough syrup Disassociative anesthetic with a 2-4 hr duration Effects at low dosage similar to alcohol Carefree clumsiness / vertigo Vivid hallucinations (auditory, visual, tactile) AMS, violent outbursts, seizures, coma Hyperthermia, HTN, tachycardia Long Term ~ Olney's Lesions Brain vacuoles cause impaired memory & schizophrenia-like syndrome

Coricidin Cough & Cold Caps: 30 mg DXM + 4 mgs of Chlorphineramine maleate Respiratory depression occurs at twice recommended dose Treatment for suspected ingestion Benadryl for dystonic reactions Be wary of acute agitation, violent outbursts & psychotic outbursts

Even a single tablet of a beta blocker, calcium channel blocker, hypoglycemic agent or mood stabilizer can be fatal to a child Although most of these medications are dose dependant, they can have fatal effects with a single dose Many ODs are AMS + deadly prescribed polypharmacy Dont forget OTCs & herbs.

Prescribed for HTN, Angina, Hyperthyroid, Migraine, Glaucoma, SVT MOI 1 Cardiac & 2 peripheral influence Selective & non-selective agents Toxic Dose is 2-3 x therapeutic dose May still have symptoms at non- toxic dosages

Bradyarrhythmia Hypotension AMS Respiratory depression Seizure (pediatrics > adults) Prehospital Management Atropine Glucagon Transcutaneous Pacemaker Fluid resuscitation & vasopressors Dopamine Epinephrine

Treatment for: Angina, HTN, Migraine, SVT, ICH Nicardipine for intracranial processes Blocks calcium entrance into cardiac & smooth muscle cells Negative inotrope, chronotrope, dromotrope Decreased automaticity at SA & AV nodes Decreased PVR

Hypotension Bradycardia Arrythmias Respiratory depression Seizures Prehospital Management Atropine Glucagon Transcutaneous Pacemaker Fluid resuscitation & vasopressors Dopamine Epinephrine

Prescribed for HTN, withdrawal, migraine, ADHD, Tourettes adrenergic agonist Toxic effects mimic barbiturate / opiate OD Cardiovascular: bradycardia, arrhythmias, hypotension w/ refractory hypertension post abrupt withdrawal Neurological effects: miosis, respiratory depression, seizures, coma Treatment Atropine Narcan Glucose Transcutaneous Pacemaker Fluid resuscitation & vasopressors

Cardiac glycoside Looks like regular atrial fibtillation Prescribed for: CHF (Improves cardiac output), A-fib (antiarrythmic) Mechanism of Action Increased intracellular calcium & increases myocardial contractility Narrow therapeutic window SSX: Nausea/vomiting Mental status changes Cardiovascular symptoms

Arrhythmias ~ Any! PVC / PAC, AF, PAT w/block, bradycardia, VF, VT Hypotension Hyperkalemia CNS Delirium, lethargy, agitation, ocular disturbances (blue-green halos)

Gastric decontamination Never give calcium due to underlying hyperkalemia Atropine & transcutaneous Pacemaker Arrhythmia management Digibind: Life-threatening CV toxicity K + >5.5 mEq/L Level >10 ng/mL or ingested >10 mg

1 million ODs annually, 400 fatalities Increases norepinephrine & serotonin, histamine & acetylcholine Most Common Prescribed Amitriptyline (Elavil) Clomipramine (Anafranil) Desipramine (Norpramin) Doxepin (Sinequan) Imipramine (Tofranil) Nortryptyline (Pamelor)

Onset 90 mins 4 hours post ingestion Anticholinergic Hyperthermia, blurred vision, flushed skin, hallucinations, tachycardia, seizures Quinidine-like Negative inotrope, long QT, ventricular arrhythmias (torsades) -Adrenergic blockade Hypotension CNS Drowsiness, AMS, hallucinations, coma, seizures, mydriasis

Torsades Magnesium, overdrive pacing Arrythmias Standard protocols & meds Sodium bicarbonate, lidocaine, bretylium Procainamide & amiodarone contraindicated Seizures Benzodiazepines Hypotension Fluid resuscitation & vasopressors

Modulates anger, temp, aggression, mood, sleep, sexuality, appetite, metabolism & stimulates vomiting Drugs targeting serotonin used to treat psychiatric disorders Confusing name ~ Selective Serotonin Reuptake Inhibitors increase serotonin (serotonergic)

Most common prescribed anti-depressants Decrease serotonin (5HT) reuptake to increase serotonin levels SSX of OD: N/V Lethargy / Sedation Arrythmias AMS / Decreased LOC

Ingestions of multiple serotonergic agents Mortality 10-20% from CV & neurovascular collapse Triad of AMS, autonomic hyperactivity & neuromuscular abnormalities w/i 2 hrs of ingestion Neurobehavioral: AMS, agitation, seizures, hyperactivity Autonomic: Hyperthermia, diaphoresis, diarrhea, tachycardia, HTN, salivation Neuromuscular: Myoclonus, hyperreflexia, tremor, muscle rigidity

18 yo student admitted to the hospital with fever of 103.5, agitation, AMS, jerking motions Taking phenelzine (MAOI antidepressant), heroin & THC Given meperidine / demerol in the hospital for agitation, which increased agitation eventually leading to physical restraints 6 hrs later at a temp of 107 she arrested & died

Ms. Zion seen only by an intern & 2 nd year resident with responsibility for 40 pts in their 36 hour shift Instead of recognizing SSX of serotonin syndrome, treated pt for drug-related agitation & psychosis Zions father (a reporter for the NY Times) reported his daughters death in the NY Times, Newsweek, Washington Post & 60 Minutes In 1989 NY adopted an 80 hr resident work week w/ supervision guidelines All residencies adopt guidelines by 2004

Respiratory support Fever control Sedatives Muscle relaxants Serotonin Syndrome: Benzodiazepines, hydration, cooling Neuromuscular blockade Dantrolene (+/- as usually rx for neuroleptic malignant syndrome)

Serotoninergic stimulation Hallucinations Sweating Tachycardia Mydriasis No true withdrawal state Effects last 4 grams / 24 hrs No specific early symptoms or signs Treatment Gastric decontamination N-acetylcysteine (N-AC) Liver t">

Toxic ingestion 140 uM/L >4 grams / 24 hrs No specific early symptoms or signs Treatment Gastric decontamination N-acetylcysteine (N-AC) Liver transplant

2% (acute) & 25% (chronic) mortality Hallmark symptoms is a mixed acid-base disturbance GI: N/V, abdominal pain Reyes Syndrome (peds) CNS: Tinnitus, lethargy, seizures, Cerebral Edema, Irritability Pulmonary: Pulmonary edema (MCC death) Heme:Bleeding abnormalities Treatment: IVF Hemodialysis

GI: N/V/D Neuro: Tremor, seizures Vertigo, Coma Dysarthria, ataxia, choreoathetosis Hyperreflexia Confusion Opisthotonis Treatment Gastric lavage Urinary alkalinization & Hemodialysis Aminophylline

Seroquel Antipsychotics Alcohol Heroin Barbituates Combinations Thyroid medications Inhalants Tramadol Antibiotics Birth Control Pills Coumadin & Blood Thinners Marijuana Sleeping pills Ritalin

Most common poisoning death Vague symptoms related to exposure / dose: HA & flu-like symptoms Dizziness N/V Irritability, seizures, coma Cardiovascular collapse Treatment: Remove from affected area 100% O2 Hyberbaric O2 Treat for co-poisonings (i.e. cyanide)

Hydrogen cyanide ion halts cellular respiration by inhibiting an mitochondrial cytochrome c oxidase Histotoxic hypoxia as cells unable to use oxygen Seizures, apnea, pulmonary edema, cardiac arrest & death in mins Lower dosages: LOC, general weakness, giddiness, headaches, vertigo, confusion Skin color to turn pink from cyanide-hemoglobin complexes

Inhaled amyl nitrite, IV sodium nitrite, IV sodium thiosulfate +/- methemoglobin Hydroxocobalamin / Cyanokit antidote kits Vitamin B 12 binds cyanide to form harmless cyanocobalamin form of vitamin B 12, then eliminated through urine Administration of sodium thiosulfate improves ability of the hydroxocobalamin to detoxify cyanide poisoning Relatively expensive, not universally available, testing takes days

Airway control, seizure treatment & supportive management are key to toxicological emergencies Rely on physical examination rather than history Often the exact toxin(s) not known for days, if ever Poison Control (1-800-222-1222) & Medical Control are your best resources

amy gutman md [email protected] ems medical director

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