The Approach to the Poisoned Patient Toxicology Skills Workshop Regions Hospital Emergency Medicine Program

Initial Approach to the Patient with a Toxic Ingestion Develop a Systematic Approach Look for Toxidromes (“Talkingdromes”) Attention to ABCs and need for Antidote Know the Indications for Decontamination Procedures Enhance when possible and appropriate

Initial Management of Severe OD - ABCDE A – Antidote B – Basics ; ABCs C – Change catabolism D – Distribute differently; Decontamination E – Enhance elimination In the patient with an ingestion, remember the basics (Airway, Breathing, Circulation), but also start thinking early about antidote and eliminating the toxin if indicated. Time matters.

Initial Management; A = Antidote Toxin/Drug Oxygen CO, CN, H2S Naloxone Narcotics/Opiates NAC APAP, Carbon tet Atropine, Pralidoxime Organophosphates Calcium HF, Fl, Oxalates DMSA As, Lead, Hg Sodium Bicarbonate TCA

A = Antidote Antidotes Toxin/Drug Ethanol, 4MP EG, (methanol) Digoxin-specific Fab Digoxin Glucose Insulin Hydroxocobalamin* CN Physostigmine Anticholinergics, central Pyridoxine INH, hydrazines Glucagon Beta-blockers

Basics - ABCs Airway Breathing Circulation Do the DONT Dextrose Oxygen Naloxone Thiamine

Reduce Adsorption Vomiting (Ipecac) Activated Charcoal Gastric Lavage Never used in 21st century Generally not indicated or used in an ED setting Contraindicated in patients < 6 mos old, caustic ingestions, actual or potential loss of airway reflexes, need to give oral antidote Activated Charcoal Most effective if given within one hour Caution in the patient with altered mental status (need a protected airway) Not effective for hydrocarbons, metals (Lead, Iron, Lithium) Gastric Lavage Rarely used Consider in large, potentially life threatening ingestions not amenable to activated charcoal

E = Enhance Elimination Hemodialysis STUMBLE(D) - Dialysis Salicylates Theophylline Uremia Methanol Barbiturates, Bromide Lithium Ethylene Glycol Depakote (high levels) Pneumonic for which toxins are able to be removed via dialysis

The Patient with a Toxic Ingestion – H & P Focused History and Brief Tox Exam History: what-when-how much Reliability factor, relatives, paramedics Exam Vital signs Mental status Pupillary response Skin changes, Odors/other prominent features. M A T E R S Medication Amount Time Taken Emesis Reason Signs/symptoms Remember to focus on the time of ingestion, how much (ask paramedics or family for pill bottles, count pills if necessary), ask about vomiting. Pay attention on your physical to vital signs, mental status and Pupillary response as this may clue you in to a toxidrome.

History & Mini Tox Exam Exam Vital signs Pulse up or down or normal BP up or down or normal Temp up or down or normal Resp up or down or normal

Vital Signs Toxicity – Pulse Bradycardia (PACED) Propranolol or other Beta blockers, Poppies (opiates) Anticholinesterase drugs Clonidine, CCBs, Ciguatera Ethanol or other alcohols, Ergotamine Digoxin

Vital Signs Toxicity – Pulse Tachycardia (FAST) Free base or other forms of cocaine Anticholinergics, antihistamines, amphetamines Sympathomimetics (ephedrine, amphetamines), Solvent abuse Theophylline, Thyroid hormone Anticholinergic medications: antidepressants like doxepin, amitriptyline… furosemide digoxin nifedipine disopyramide

Vital Signs Toxicity – Temperature Hypothermia (COOLS) Carbon monoxide, Clonidine Opiates Oral hypoglycemics, Insulin Liquor Sedative-hypnotics

Vital Signs Toxicity – Temperature Hyperthermia (NASA) Nicotine, Neuroleptic malignant syndrome Antihistamines Salicylates, Sympathomimetics Anticholinergics, Antidepressants

Vital Signs Toxicity – BP Hypotension (CRASH) Clonidine, CCBs (and B-blockers) Reserpine or other antihypertensives Antidepressants, Aminophylline, Alcohol Sedative-hypnotics Heroin or other opiates

Vital Signs Toxicity - BP Hypertension (CT SCAN) Cocaine Thyroid supplements Sympathomimetics Caffeine Anticholinergics, Amphetamines Nicotine

Vital Signs Toxicity - Respirations Rapid Respiration (PANT) PCP, Paraquat, Pneumonitis (chemical) ASA and other salicylates, Amphetamines Non-cardiogenic pulmonary edema Toxin-induced metabolic acidosis Paraquat is used in pesticides

Vital Signs Toxicity - Respirations Slow Respirations (SLOW) Sedative-hypnoptics, Strychnine, Snakes Liquor Opiates, OPs Weed (marijuana) Other causes: Nicotine, Clonidine, Chlorinated HC

Exam – Mental Status Seizures? Hallucinations? CNS depressed?

Agents that Cause Seizures WITH LA COPS Withdrawals (alcohol, benzos) INH, Insulin, Inderal Tricyclics, theophylline Hypoglycemics; Hemlock, water; Haldol Lithium, Lidocaine, Lead, Lindane Anticholinergics, Antiseizure Hemlock is a plant

Agents that Cause Seizures WITH LA COPS Cocaine, Camphor, CN, CO, Cholinergics Organophosphates PCP, PPA, propoxyphene Sympathomimetics, Salicylates, Strychnine Phenylpropanolamine (PPA) is another one of the Ephedra alkaloids similar to ephedrine, epinephrine, methamphetamine, and amphetamines Strychnine is used in pesticides

Agents that Affect Pupil Size Miosis (COPS) Cholinergics, Clonidine Opiates, organophosphates Phenothiazines, pilocarpine Sedative-hypnotics, SAH MydriASis (A3S) Antihistamines, Antidepressants, Atropine Sympathomimetics

Skin Changes Sympathomimetics Organophosphates ASA or salicylates Diaphoretic (SOAP) Sympathomimetics Organophosphates ASA or salicylates Phencyclidine (PCP)

Skin Changes Dry Skin Bullous Lesions Antihistamines, Anticholinergics Barbiturates and other sedative- hypnotics Carbon monoxide Tricyclics (personal case series) www.acponline.org/graphics/bioterro/bullous.jpg

Skin Changes Flushed CO (rare) Anticholinergics Boric acid CN (rare)

Skin Changes Cyanosis Phenazopyridine Aniline dyes Nitrates Nitrites Ergotamine Dapsone Any agent hypoxia, hypotension MetHb

Exam - Diagnostic Odors Bitter Almonds Carrots Fruity Garlic Gasoline -Cyanide -Cicutoxin (water hemlock) -DKA, Isopropanol -OP, As, DMSO, selenium, thallium, phosphorus -Petroleum distillates

Diagnostic Odors Mothballs Pears Pungent aromatic Oil of wintergreen Rotten eggs -Naphthlene, camphor -Chloral hydrate -Ethchlorvynol -Methylsalicylate -Sulfur dioxide, hydrogen sulfide Ethchlorvynol is a sedative and hypnotic medication developed by Pfizer in the 1950s.[2] In the United States Abbott Laboratories used to sell it under the tradename Placidyl. During their heyday, they were known on the street as "jelly-bellies". Since Abbott and Banner Pharmacaps, which manufactured the generic version, discontinued production in 1999, ethchlorvynol has no longer been available in the United States

Laboratory Evaluation of the Tox Patient Toxicology Screens Urine Stat Urine vs Serum Acetaminophen level Routine Tests CBC BMP Anion Gap ABGs

Levels - Timing *Clinical Symptoms may dictate treatment, not level.

Suggestive Findings in the Poisoned Patient: Anion Gap A MUD PILE CAT ASA Methanol Uremia DKA Paraldehyde, Phenformin INH, Iron, Ibuprofen Lactic acidosis Ethylene Glycol If you find an elevated anion gap on your lab workup – consider these potential poisonings

Suggestive Findings in the Poisoned Patient: Anion Gap A MUD PILE CAT CO, CN, Caffeine AKA Theophylline, Toluene Others Benzyl alcohol Metaldehyde Formaldehyde H2S

Suggestive Findings in the Poisoned Patient: Anion Gap Decreased Anion Gap Bromide Lithium Hypermagnesemia Hypercalcemia

Osmolar Gap Calculated Significant if >10 2(Na)+[Glu/18] + [BUN/2.8] + EtOH(mg/dL)/4.6 Osm Gap = measured - calculated Significant if >10 Really significant if >19 Remember normal osmolar gap does not rule out toxic alcohol ingestion

Suggestive Findings in the Poisoned Patient: Osmolar Gap Increased Osmolar Gap MAD GAS Mannitol Alcohols (met, EG, Iso, eth) Dyes, Diuretics, DMSO Glycerol Acetone Sorbitol

Toxidromes: Case #1 A 40 year old man collapsed at work while moving his car. He has a hx of depression. He had recently attended his mother’s funeral the day before. He was found slumped over the steering wheel of his car, lethargic and incoherent. A co- worker left the patient and went to call medics. He was intubated and transferred to Regions Hospital.

Toxidromes: Case #1 Examination Labs were unremarkable BP 130/88, P90, R-vent, T 1012 Pupils 6mm unreactive but equal. Skin warm, red, dry Absent bowel sounds Labs were unremarkable ABG:pH 7.50, 32, 140 EKG - QRS 102, occasional PVC

Toxidromes: Case #1 Is there a Toxidrome? A. Opioid B. Anticholinergic C. Delayed Exercise Syndrome D. Cholinergic poisoning Is there an antidote? B. Altered Mental Status, Mydriasis, Hot, Red skin, Dry skin = Anticholinergic Syndrome Antidote - physostigmine

Toxidromes: Case #1 Is there a Toxidrome? A. Opioid B. Anticholinergic Altered Mental Status, Mydriasis, Hot, Red skin, Dry skin = Anticholinergic Syndrome C. Delayed Exercise Syndrome D. Cholinergic poisoning Is there an antidote? Antidote - physostigmine B. Altered Mental Status, Mydriasis, Hot, Red skin, Dry skin = Anticholinergic Syndrome Antidote - physostigmine

The Talkingdromes Anticholinergic (antihistamines, cyclic antidepressants, Jimson weed) Hot as a hare (hyperthermia) Red as a beet (flushed) Dry as a bone (dry skin, urinary retention) Blind as a bat (mydriasis) Mad as a hatter (hallucinations, delirium, myoclonic jerking)

The Talkingdromes Also with anticholinergic How do you treat it? Mydriasis Tachycardia Hypertension Hyperthermia Seizures How do you treat it? Supportive care TCAs – Sodium Bicarb for widened QRS Benzodiazepenes for agitation, seizures Consider physostigmine for pure anticholinergic overdoses (contraindicated in TCA overdose or with dysrhythmias or seizure)

Toxidromes: Case #2 A 19 year old male presents after from a party after his friends noted he was “acting funny.” He was “out of control” and not making sense, so they decided to bring him into the Emergency Room. The patient is agitated on arrival

Toxidromes: Case #2 Examination Labs were unremarkable BP 180/114, P120, R20, T 101 The patient is agitated and appears to be hallucinating Pupils 6mm sluggish but equal. Skin warm, red, very diaphoretic Labs were unremarkable EKG – sinus tachycardia

Toxidromes: Case #2 Is there a Toxidrome? Opioid Anticholinergic Sympathomimetic Cholinergic C - Sympathomimetic

Toxidromes: Case #2 Is there a Toxidrome? Opioid Anticholinergic Sympathomimetic (symptoms can be like anticholinergic except you see diaphoresis) Cholinergic C - Sympathomimetic

Talkingdromes (Toxidromes) Sympathomimetics (cocaine, amphetamines, ephedrine) Mydriasis Tachycardia Hypertension Hyperthermia Seizures Diaphoresis Treatment Supportive care Benzodiazepines as needed

Toxidromes: Case #3 A 40 y/o female is brought by medics. A family member called after a suicide note was found and the patient was found unresponsive. On medic arrival the patient was noted to be very somnolent. She was transported to Regions Hospital.

Toxidromes: Case #3 Examination Labs were unremarkable BP 100/65, P50, R6, T 98.6 The patient is arousable only to sternal rub. Pupils 2mm sluggish but equal. Skin cool, dry Labs were unremarkable EKG – sinus bradycardia

Toxidromes: Case #3 Is there a Toxidrome? Opioid Anticholinergic Sympathomimetic Cholinergic Is there an antidote? A – opioid Treatment - naloxone

Toxidromes: Case #3 Is there a Toxidrome? Opioid (key is respiratory depression with miosis Anticholinergic Sympathomimetic Cholinergic Is there an antidote? Naloxone/Narcan. Can give 0.4mg - 2mg as first dose A – opioid Treatment - naloxone

Talkingdromes (Toxidromes) Narcotic (heroin, methadone, other opioids) Miosis Bradycardia Hypotension Hypoventilation Coma/CNS depression Treatment Naloxone

The Imitators – Opioid-like Clonidine Hypotension usually more profound May require HIGH dose naloxone to see any effect Tetrahydrozaline Periodic apnea in kids Kids should be admitted if symptomatic in ED Tetrahydrozoline, a derivative of imidazoline, is found in over-the-counter eye drops and nasal sprays. Other derivatives include naphazoline, oxymetazoline, and xylometazoline.

Toxidromes: Case #4 A 50 y/o male is brought in after being found in his garage. According to paramedics, there were several containers of liquids in glass jars near the patient. They also noted a large amount of emesis. He was noted to have altered mental status and some respiratory distress prior to arrival. He was intubated prior to arrival and transported to Regions Hospital.

Toxidromes: Case #4 Examination Labs were unremarkable BP 110/65, P50, R - intubated, T 98.6 The patient is obtunded, intubated Pupils 2mm sluggish but equal. There are copious secretions in the patient’s mouth and in the endotracheal tube Incontinent of both urine and stool Skin is cool, diaphretic Labs were unremarkable EKG – sinus bradycardia

Toxidromes: Case #4 Is there a Toxidrome? Serotonin Syndrome Anticholinergic Sympathomimetic Cholinergic Is there an antidote? D - cholinergic Treatment – 2PAM, atropine (lots)

Toxidromes: Case #4 Is there a Toxidrome? Serotonin Syndrome Anticholinergic Sympathomimetic Cholinergic Is there an antidote? Atropine given until secretions are improve (no max dose) 2PAM/ Pralidoxime D - cholinergic Treatment – 2PAM, atropine (lots)

Toxidromes: SLUDGE Treatments: Pralidoxime (2PAM), Atropine Cholinergic (DUMBBELS or SLUG BAM) Salivation Lacrimation Urination GI complaints (nausea, vomiting, diarrhea) Bradycardia, Bronchoconstriction Bronchorrea Abdominal cramping Miosis, Muscle fasciculations Treatments: Pralidoxime (2PAM), Atropine

More Talkingdromes

Talkingdromes (Toxidromes) Salicylates (ASPIRIN)Harris Altered MS (lethargy to coma) Sweating Pulmonary edema Increased ventilation, temp, heart rate Ringing in ears Irritable Nausea and vomiting

Talkingdromes (Toxidromes) Serotonin Syndrome VS: T, HR, BP (unstable) MS: Agitation, coma Pupils: Mydriasis Skin: Diaphoresis Other: LE rigidity, myoclonus, hyperreflexia, seizure Hunter Criteria for diagnosis of Serotonin syndrome CNS: AMS/confusion Autonomic instability: Brady/Tachycardia, HTN, hypotension Muscle involement: Nystagmus, clonus, hyperreflexia

Serotonin Syndrome MAOI and other drug Idiosyncratic reaction Alteration in MS Autonomic instability Neuromuscular abnormality Treatment is supportive Symptoms resolve 24-72 hrs Lactic acidosis, rhabdo, hyperthermia

Serotonin Syndrome Specific drugs SSRIs (i.e., Prozac) Dextromethorphan Demerol Ecstasy (MDMA): hallucinogenic amphetamine Cocaine L-tryptophan

Acetaminophen Toxicity - Metabolism Metabolized in the liver primarily to nontoxic glucoronide and sulfide conjugates, however small amount is converted via cytochrome P450 to potentially toxic NAPQI Normally, NAPQI is conjugated with glutathione to nontoxic metabolites In significant overdose, glutathione stores are depleted NAPQI destroys hepatocytes leading to liver failure

Acetaminophen Toxicity – Clinical Presentation First few hours Non-specific signs and symptoms Nausea, vomiting, pallor, diaphoresis Even severely poisoned patients may remain symptomatic 18 – 24 hours Asymptomatic phase No laboratory evidence of hepatotoxicity After 24 – 36 hours Aminotransferases begin to rise Signs and symptoms of hepatotoxicity N, V, RUQ pain, hepatic enlargement, jaundice 72 – 96 hours Peak hepatotoxicity Although massive liver necrosis can occur, recovery is the rule and usually complete if the patient survives

Acetaminophen Level Levels are important Check levels in all cases of suspected overdose or polydrug overdose Antidotal therapy is most effective if started within 8 – 10 hours Signs and symptoms are delayed for 18 – 36 hours Rumack-Matthew nomogram Used to predict the severity of toicity and need for antidotal therapy 4 hour level Levels above the line require antidotal therapy

Acetaminophen Toxicity - Antidote N-acetylcysteine (NAC) Glutathione precursor and glutathione substitute Increases substrate supply for the non-toxic sulfate conjugation pathway Available as oral and IV form Extremely effective if initiated within 8 hours Standard of care to treat patients up to 24 hours

Summary - Systematic Approach ABCs - Antidotes Decontaminate - Special Treatments? Toxidromes? Investigate - look closely REASSESS, MONITOR, SUPPORT

The End…Questions?