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Back to Basics - Poisoning Department of Emergency Medicine The Ottawa Hospital Outline • Directed toxicology history • Toxidromes • Cases/Treatment Toxicology - Objectives list and interpret critical clinical findings, including collateral history aimed at determining the substance involved and the potential severity of the poisoning; results of a physical examination aimed at determining the stability of the patient and the nature of the toxidrome (e.g., cholinergic crisis, serotonergic syndrome); Toxicology - Objectives •list and interpret critical investigations, including 1.laboratory diagnosis of the substance ingested (e.g., acetaminophen, ASA levels); 2.assessment of the toxic effects on the patient 3.(e.g., arterial blood gases, anion and osmolar gaps); Toxicology - Objectives •construct an effective initial management plan, including 1.supportive care before or at the same time as data gathering and investigation, (e.g., ensuring airway adequacy, hemodynamic stability); 2.appropriate decontamination or prevention of further absorption (e.g., activated charcoal); 3.administration of specific antidotes, if indicated (e.g., naloxone, N-acetylcysteine); 4.further elimination of the poison (e.g., alkalinization, dialysis); 5.contacting Poison Control; 6.referral for psychiatric assessment, if indicated. Directed Tox History • When (most NB) • What • How – How much? – Method? • Whose? – Compliance • Coingestants? – Access – Specifics • Self treatment? – Ipecac – Induced emesis – Ethanol • Intent? • Symptoms Toxidrome What it is: – a clustering of symptoms and/or signs – consistent with a class of drugs/medications What it isn’t: – a way to identify a specific substance – a way to discriminate well among “contradictory agents” until repeated over time Common Toxidromes • • • • • • • • Narcotic (coma resp depression, miosis) Anticholinergic (mad as a hatter …) Cholinergic (DUMBELS) Sedative/Hypnotic (pupillary rxn spared) Stimulant or Sympathomimetic Hallucinogens Extrapyrimidal Serotonergic Anticholinergics • TCA’s, atropine, scopolamine, antihistamines – Mad as a hatter (delerium) – Hot as a hare (fever) – Blind as a bat (mydriasis) – Dry as bone (dry mucous membrane, urinary retention, decreased BS) – Red as beet (flushing) – Bowel and bladder lose tone and heart goes on alone • Difference with adrenergics = – Bowel sounds present – Diaphoresis Cholinergics • Pheostigmine, organophosphtes (insecticides), and nerve gas (DUMBELS) – – – – – – – Diaphoresis, diarrhea, decreased BP Urination frequent Miosis Bronchospasm, bronchorrhea, bradycardia Emesis, excitation of skeletal muscle Lacrimation Salivation / seizures Sympathomimetics • Amphetamine, cocaine – – – – – Resemble paranoid schizophrenic CNS stimulation Seizures Psychosis Increased BP, pulse, Temp Hallucinogens: • • • • • Hallucinations May be oriented to time / place / person Tachy HTN mydriasis Opioids • Coma • Resp depression • Miosis (not with demerol) Sedatives • Barbituarates, ethanol, benzo’s, ethanol, GHB (gamma hydroxybutyric acid) – – – – CNS depression Resp depression Coma Pupil rxn usually spared Extrapyramidal • chlorpromazine, stemetil, halodol, metocloperamide – Dystonia (occulogyric crisis, laryngospasm, torticollis) – Akithesia – Parkinson like sx (tremor, ridgidity, akinesia, postural instability) – Dyskinesia (tic, spasm, chorea, myoclonus) Seratonergic • Mimics NMS (neuroleptic malignant syndrome) of increased BP, increased pulse, increased temp, increased resp rate (onset within 24 hours, hyperactive, clonus, hyperreflexic) • NMS (due to massive dopamine blockade) (FARMERS) – Fever – Autonomic changes (increased bp, pulse, sweating) / acidosis (rare) – Rigidity of muscles / rhabdomyolyis – Mental status changes (eg. Confusion) – Elevated BP, HR, pulse, RR – Rhabdomysolysis – Seizures – Onset days to weeks Case A 78 yo F presents with agitation and confusion. BP 180/105, P 110 RR 16 T 38.2 C. Physical exam reveals an acutely agitated pt, pupils 6 mm, CVS/resp normal except tachycardia. Is a toxidrome present? What are the treatment priorities? What tests do you want to order? Investigations • Serum levels – – – – acetaminophen (4 hour level) ASA Ethanol ingestion specific (eg phenytoin, digoxin level) • Electrolytes, BUN/Cr • EKG • Serum osmolarity What about a “Tox Screen”? • Urine immunoassays – lab determines which tests to include on the “screen” • Often clinically irrelevant – confuse the clinical picture • positive cocaine in a patient with an opioid toxidrome • “toxic” TCA level in a cyclobenzaprine (Flexeril) overdose Treat the patient, not the test! Case A 78 yo F presents with agitation and confusion. BP 180/105, P 110 RR 16 T 38.2 C. Physical exam reveals an acutely agitated pt, pupils 6 mm, CVS/resp normal except tachycardia. Is a toxidrome present? What are the treatment priorities? What tests do you want to order? Supportive treatment of the poisoned patient is the cornerstone of management A 20 yo F comes to the ED saying she just took a whole bottle (1.5 grams) of Elavil (amitriptylline). Her vital signs are normal. She is alert and exam is normal. Treatment considerations? Treatment Elimination: -Activated Charcoal -Whole Bowel Irrigation Removal: -Gastric Lavage Antidotes Treatment Elimination: -Activated Charcoal -Whole Bowel Irrigation Removal: -Gastric Lavage Antidotes Activated Charcoal • Ingestion < 1 hr – upto 2 hrs if delayed emptying, bad toxin • 1 g/kg or 10 g for each gram of OD drug • Ineffective – – – – – – Pesticides Hydrocarbons Alcohols Iron Lithium Alkali’s / acids (contraindicated) Activated Charcoal • CX – Aspiration • Gastric content aspiration worse than charcoal aspiration • But a lot worse if dump charcoal into lungs – Perforation if bowels not moving Cathartics • Sorbitol – available premixed with charcoal • can use for first dose – contraindicated if < 2 years • electrolyte problems – Used with charcoal to counteract its constipating effect To Give or Not to Give... An alert 36 year old M 2 hours post accidental ingestion of antifreeze To Give or Not to Give... An alert 36 year old M 2 hours post accidental ingestion of antifreeze A: Not indicated; 2hrs is too late (esp for liquid) and alcohols bind poorly To Give or Not to Give... A somnolent 45 yo F with ingestion of olanzapine (Zyprexa) and venlafaxine (Effexor) at an undetermined time. To Give or Not to Give... A somnolent 45 yo F with ingestion of olanzapine (Zyprexa) and venlafaxine (Effexor) at an undetermined time. A: Not indicated; undetermined time (likely greater than 1 hr for toxicity to develop from these agents) and risk of aspiration given altered mental status. To Give or Not to Give... An intubated 37 yo F 30 min after collapsed after metoprolol OD. To Give or Not to Give... An intubated 37 yo F 30 min after collapsed after metoprolol OD. A: Indicated; recent ingestion, (very) bad drug and airway is protected. Treatment Elimination: -Activated Charcoal -Whole Bowel Irrigation Removal: -Gastric Lavage Antidotes Decontamination • Gastric Lavage – – – – – – – recent (< 1hr) Life threatening ingestion no antidote not adsorbed by AC sustained release concretions no emesis EasyLav Gastric Lavage • Large hose with blunt end (need this for tablets to pass) • LL decubitus position with pylorus pointing upwards • Has to have airway protected either intubated of fully conscious • Have bucket of warm water and bucket on floor Gastric Lavage • Give warm water through funnel / tube above pt … Percuss stomach … move tube below level of head to drain into bucket … repeat • Prevents drug from getting into small intestine as drain directly from stomach Treatment Elimination: -Activated Charcoal -Whole Bowel Irrigation Removal: -Gastric Lavage -Dialysis Antidotes Whole Bowel Irrigation • Polyethylene glycol (eg. Golytely) – 1-2 L/hr via NGT until clear effluent – Do for 4 to 6 hours until clear effluent via rectal tube • SR preps, Lithium, iron, sustained release drugs • Body packers/stuffers A 20 yo F comes to the ED saying she just took a whole bottle (1.5 grams) of Elavil (amitriptylline). Her vital signs are normal. She is alert and exam is normal. Treatment considerations? Tricyclic Antidepressants - Sx • Block sodium channels • Neuro: – mental status changes – anticholinergic toxicity – seizures • Cardiac: – (lethal) arrhythmias – AV blocks – hypotension • QRS > 120 ms and ‘R” in aVR > 3mm predicts seizures/ arrhythmias Tricyclic Antidepressants - Mgmt • Activated Charcoal (no role for dialysis) • Alkalinization of blood (7.45 – 7.50) with sodium bicarbonate – Abolishes dysrhythmias and improves hypotension – Use if QRS > 100 msec – Administer as 1 – 2 mEq/kg IV push then 20 mEq / hr drip Enhanced Elimination • Diuresis – Alkaline • 3 amps NaHCO3 in 1 L D5W with 40 mmol KCl at 250 mL/hr • goal: urine pH 7.5-8 • E.g Salicylates, Phenobarbital – Neutral • Lithium Tricyclic Antidepressants - Mgmt - Seizure mgmt: - avoid dilantin (increases dysrhythmias) - Diazepam/lorazepam/ phenobarbitol - Hypotension - Crystalloid and alkalinization - Vasopressors if no response - Dysrhythmias unresponsive to bicarb - Lidocaine - Consider pacemaker insertion for blocks A 34 yo M presents 4 hours after ingesting 100 regular ASA pills. He complains of tinnitus, is vomiting and has an ASA level of 6 mmol/L. His vital signs are BP 132/78 P 85 RR 28 T 37.5° C Decontamination? Other treatment considerations? Commonly Dialysable Drugs • • • • • • • • Isopropanol Salicylates Theophylline Uremia Methanol Barbiturates Lithium Ethylene Glycol Salicylates - Symptoms • Causes metabolic acidosis .. Initially resp alkalosis as stimulates resp centre • Mild = ototoxicity (tinnitis, vertigo) • Severe = CNS stimulation followed by depression (confusion, delerium, seizures_ – Cardiac dysrhythmias, noncardiogenic pulmonary edema, renal failure, hemorrhage Salicylates – Treatment • Treatment is not dependant on specific serum level; it is a CLINICAL diagnosis • Done nomogram USELESS • Draw levels to ensure declining Salicylates – Evaluation • Decontamination with Activated charcoal • Consider gastric lavage if < 60 min • Alkaline diuresis with bicarb increases elimination of ASA (goal of urine pH 5 – 8) – See TCA OD for bicarb dosing • Hemodialysis is most effective means – Indications include renal failure, severe cardiac tox, rising ASA levels despite alkalinization, pulm edema, severe acidbase imbalance Case A 42 yo M presents after ingesting 30 grams of acetaminophen. He is asymptomatic. A serum level 4 hours after ingestion is 1625 mol/L. Antidotes Acetaminophen N-acetylcysteine Atropine Carbon monoxide Cyanide Physostigmine oxygen Amyl nitrite + sodium nitrite + sodium thiosulfate Ethanol / fomepizole Ethylene glycol / Methanol Iron Lead Deferoxamine EDTA (calcium disodium edetate) Antidotes Nitrites Methylene Blue Organophosphate Opiods Isoniazid Digoxim Benzodiazepines Atropine Naloxone Pyridoxine Digibind Flumazenil Acetaminophen • Delayed hepatoxicity • Consider activated charcoal • Rumack-Matthew nomogram – predicts toxicity 4 hrs after acute ingestion – No use less than 4 hours before • N-acetylcysteine antidote – Minimum 300 mg/kg IV over 20 hrs • Goal of therapy is administration of NAC within 8 hrs of ingestion Methanol • Found in windshield washing fluid, paint thinners, solvents • Converted by alcohol dehydrogenase to formaldehyde (liver) to formic acid – Formic acid – toxic product – Causes high anion gap and osmole gap – Affects optic nerve fxn causing papillitis and retinal edema – “blind drunk” High Anion Gap • • • • • • • • • • • C (carbon monoxide, cyanide) A (Arsenic) T (toluene) M (methanol, metformin) U (uremia) D (DKA) P (paraldehyde, phenformin) I (INH, iron) L (Lactic acidosis) E (ethylene glycol (antifreeze), everything S (salicylates, strychtnine) Anion and osmole gap – AG = Na – Cl – HCO3 – Osmole Gap = 2Na + BUN + glucose + ETOH( 1.25) • Osmole gap causes: – Ethanol, Isopopanol, Methanol, Ethylene glycol, Acetone, Glycerol, Mannitol, Uremia, Ketocacidosis • Isopropanol causes high osmole but not anion gap • Peraldehyde and isoniazide cause high AG but not high osmole gap Methanol • 8 hour – 30 hour latent period followed by onset of abdo pain, nausea, vomiting, blurred vision, metabolic acidosis – Often dilated pupil with photophobia • High anion gap acidosis – Na – Cl – HCO 3 • Osmole gap may be high but can be normal – 2Na + BUN + glucose + EtOH (1.25) – Normal is 280 – 295 mosm Methanol • Supportive measures • Consider bicarbonate with severe acidosis • ADH inhibitor – Fomepizole – inhibits alcohol dehydrogenase – Ethanol (BEER!) – ethanol infusion as alcohol dehydrogenase preferentially metabolizes ethanol (keep at 22 – 33) • Hemodialysis – If symptomatic or methanol level > 8 mmol / L – Severe acidosis TOXICOLOGY AXIOMS • The most important aspect of the history is the time of ingestion and coingestants • The most critical therapy varies with the time course of the patient’s presentation • No evaluation is complete until repeated over time • Toxidromes can help identify classes of drugs • It is often not important to determine the exact drug taken within a class • Supportive tx is the cornerstone of tx