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Toxicology

Toxicology. National Review Course Dr. Marco Sivilotti Dr. Ian Ball October 17, 2013. Acknowledgements. Dr. Jason Lord, University of Calgary. Objectives. Clinical examination of the overdosed patient General treatment strategies Common poisonings

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Toxicology

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  1. Toxicology National Review Course Dr. Marco Sivilotti Dr. Ian Ball October 17, 2013

  2. Acknowledgements Dr. Jason Lord, University of Calgary

  3. Objectives Clinical examination of the overdosed patient General treatment strategies Common poisonings Toxicological concepts applicable to the ER Examinable / Important Lists

  4. History unreliable? What was ingested? How much and when? What was the patient doing when they became ill? Past medical records or d/c summaries Talk to family, friends, paramedics Search belongings All bottles and containers – pill count Search scene ie/ home or garage Track marks, packer and stuffer Query pharmacy or provincial datasets

  5. Physical Examination Vital Signs including temp and glucose ABC’s (Kussmaul, breath odour, Cspine) D = mental status, seizures, tone E = expose, skin findings Autonomic nervous system TOXIDROME

  6. Odors in Toxicology Almonds – CN Mint – Methyl Salicylate Fruity – Acetone, ETOH, Isopropyl Alcohol Garlic – Organophosphates, Arsenic Glue – Toluene, solvents Rotten Eggs – Hydrogen Sulfide Pears – Paraldehyde, Chloral Hydrate

  7. Know Your Toxidromes Mental Status Vital Signs Pupils Skin Secretions Motor Activity GI/GU

  8. Toxidromes: Cholinergic Muscarinic symptoms – Peripheral: DUMBELS (diarrhea/diaphoresis, urination, miosis, bradycardia/bronchospasm, emesis, lacrimation, salivation) or SLUDGE Central: seizures, dec LOC Nicotinic symptoms – Fasciculations, weakness, respiratory arrest Organophosphates, carbamates, nerve agents

  9. Anticholinergic = AntiMUSCARINIC Mad as a hatter, Blind as a bat, Dry as a bone, Hot as a hare, Red as a beet (Anti-DUMBELS) - hot, flushed and dry skin, tachycardia, hypertension, psychosis, mydriasis Cyclic antidepressants, atropine, benztropine, antihistamines, antiemetics, Jimson weed

  10. Toxidromes: Opioid Decreased LOC Respiratory depression Miosis miosis may be absent with meperidine microdose/titrated naloxone to reverse respiratory depression

  11. Toxidromes: Sedative/Hypnotics CNS depression (respiratory depression late, and only at very high doses) hallmark is spared pupillary reactions and normal VS Barbiturates, Ethanol, Benzos, GHB

  12. Toxidromes: Sympathomimetics Psychosis, diaphoresis, mydriasis, agitated, seizure, tremors, HTN (wide pulse pressure), tachycardic, tachypneic Amphetamines, cocaine

  13. Cocaine:Pharmacokinetics Variable onset (Body packers vs stuffers) Duration of effect short Direct Na channel blocker, interferes with neurotransmitter uptake, vasoconstriction Sensitizes the myocardium to catecholamines and decreases myocardial blood flow Increased platelet adhesion Combines with EtOH to form cocaethylene (more potent, longer acting, inc CV injury)

  14. Cocaine:Clinical Features Sympathomimetic Toxidrome CNS: excitation, psychosis, bleeds, seizure, washed out syndrome CV – ischemia, AMI, HTN, platelet aggregation, dysrhythmias, Ao dissection, sudden death Vasospasm Thrombus Increased O2 demand – ischemia Dissection Cardiomyopathy

  15. Cocaine:Clinical Features Resp – Asthma exacerbation, NCPE, PTX, airway burns, pneumomediastinum, pulmonary HTN MSK – Rhabdo and ARF Psych – cocaine bugs, excoriations, crack dancing (choreoathetoid movements)

  16. Cocaine: Treatment AC if stuffer or WBI if packer Aggressively treat agitation with BENZOS Hyperthermia associated with death paralyze with nondepolarizing agents and pack in ice Refractory HTN - Alpha blockade with phentolamine 1-5 mg Q5min PRN or Nitroprusside infusion AVOID Beta blockers (unopposed alpha stimulation), neuroleptics (lower seizure threshold)

  17. What Tests Should You Order? CBC, full lytes (anion gap) If altered mental status: capillary glucose, EtOH If deliberate self-harm: ASA, APAP, pregnancy test If suspect toxic alcohol: volatiles (serum osm if cannot) If sick: ABG or VBG, lactate Specific levels: Dig, Fe, DPH, VAL, CBZ, Li, theo 12-lead ECG

  18. What Test Should You NOT Order? Urine “drug screen” Tests for common drugs of abuse, at threshold appropriate to screen employees for recent use Fun to guess results, but easier/faster to ask the patient Results rarely change ED management

  19. Extra tests to consider CXR Caustics, Aspiration Abdominal XR Body packer CHIPES: Chloral hydrate, Heavy Metals, Iron, Phenothiazines, EC tablets, Solvents Urinalysis FeCl2 (ASA), pH, ketones, myoglobin

  20. When is it Safe to Discharge My Patient? If intentional ingestion for self-harm, 6 hrs of observation recommended, provided: History does not suggest a dangerous substance or toxic time bomb Asymptomatic Routine labs are negative Reliable observer at discharge Psychiatric issues addressed

  21. Toxic Time Bombs Acetaminophen Methadone Anticoagulants MAOIs Antimetabolites Hypoglycemics Body Packers Sotalol Enteric coated products (ASA) SR products Heavy metals Thyroids meds Iron Toxic alcohols Lithium Valproic acid Lomotil Tricyclics

  22. When is it Safe to Discharge My Patient? Now, if accidental and assuredly non-toxic ingestion: Product identified with certainty Single product involved Reliable estimate of maximal possible exposure Asymptomatic Assuredly unintentional/no self-harm intent Reliable patient/parent Poison-proofing advice given

  23. Is the CPS a Useful Resource for the Poisoned Patient? Compendium of Pharmaceuticals and Specialties* 60% contain dangerous or misleading advice Only 21% are adequate to allow clinician to manage overdose Brubacher J, et al. Salty Broth for Salicylate poisoning? CMAJ 165(9). Oct 2002

  24. Where to Turn for Advice? Poisindex (Micromedex) Regional Poison Centre Local Toxicologist Textbooks Internet: UpToDate™ ToxBase™ ToxiNZ™

  25. Whom Should I Decontaminate?* Step 1 – Determine risk of ingestion How much? How toxic? Reliable historian? Step 2 – Decide if substance can be removed Time of ingestion? Likelihood of recovery? Step 3 – Consider risk/benefit Any contraindications to procedure? Step 4 – Determine the most appropriate technique Lavage, Charcoal, WBI?

  26. Decontamination1. Syrup of Ipecac Rarely indicated: no improved mortality/potential for harm complicates care, including other GID contraindicated when potential for seizures or dec LOC, as well as hydrocarbons, caustics should be considered obsolete

  27. Decontamination:2. Gastric Lavage Life threatening ingestion despite maximal supportive care/antidote/elim going forward Drug in stomach (cf < 1 hr since ingestion) 10-30% reduction in absorption ASA, colchicine, TCA 40 Fr Ewald (15-28 in peds) after RSI left lateral decubitus position 200 cc aliquots warm tap water until clear Finish off with AC and remove tube

  28. Decontamination: 3. Activated Charcoal Recent, likely toxic ingestion (“soft hour”) Not useful – alcohols, metals, hydrocarbons C/I = caustics, aspiration, ileus, perforation 1 g/kg plain or with sorbitol OR 10:1 rule (for every ingested 1g toxin, give 10 g charcoal) e.g. ASA, theophylline (10+g ingestions)

  29. Decontamination: 4. Multidose Activated Charcoal Severe ingestions that are well adsorbed EC or SR drugs, toxins that slow GI motility, enterohepatic recirculation, anticonvulsants 0.25 to 0.5 g/kg q2-4h PLAIN AC (no sorbitol) Probably effective: phenobarb, CBZ, quinine, theophylline Possibly effective: digoxin, VAL, sotalol

  30. Decontamination: 5. Whole Bowel Irrigation Life-threatening ingestion in which MD-AC or GL of limited utility Iron, body packers, heavy metals like Pb sustained release CCBs Isotonic PEG solution Not absorbed, no fluid shifts 2L/hr via ng until effluent clear (c. 6 hrs) 500 ml/hr in children

  31. Enhanced Elimination:1. Urinary Alkalinization Promotes ionization of the excreted drug which prevents tubular reabsorption Useful for ingestions of weak acids ASA, phenobarb, chlorpropamide Target urine pH >7 Often difficult to achieve your target pH Replenish Na and K, Foley catheter and hourly pH ASA, lytes q2h Do not use acetazolamide b/c of concomitant metabolic acidosis and inc toxicity Not forced diuresis

  32. HA HA HA HA A- + H+ A- + H+ H+ + A- H+ + A- Blood: lower pH Urine Blood Urine: higher pH Unionized molecules diffuse across renal tubular membranes from blood to renal filtrate but ionized ones cannot cross from one compartment into the other. When urine is alkalinized, weak acids like salicylates will dissociate into ions, become “trapped” and excreted in the urine. Unionized parent molecules then diffuse down their concentration gradient from blood into the urine.

  33. Enhanced Elimination:2. Hemodialysis Small Vd, low protein binding, small size, water soluble, low endogenous clearance methanol, ethylene glycol, ASA, Li, Theophylline Less commonly severe acetaminophen, VAL, atenolol, sotalol

  34. Enhanced Elimination:3. Continuous Renal Replacement NOT generally of benefit for removing toxins peritoneal dialysis also NOT helpful

  35. Case A 24 year female presents to the emergency following a mixed drug ingestion. The paramedics find empty containers of acetaminophen, ASA and diazepam. The ingestion was witnessed approximately 45 min ago. She is now obtunded. What form of GI decontamination, if any, should be performed?

  36. One good answer “Following RSI for airway protection, I will give her 50g of activated charcoal with sorbitol after the position of the ng tube has been confirmed radiographically. The need for subsequent doses of charcoal could be predicated upon the serial serum salicylate concentrations.”

  37. Thou Shalt Know the Big Ones APAP ASA (Toxic) Alcohols CCBs Dig Cocaine Methamphetamine Opioids OP/nerve agents CO Cyanide Iron in a toddler TCAs Caustics Antidotes and maybe a few more

  38. Acetaminophen Antidote:N-acetylcysteine Ideally administer within 8 hrs of ingestion Mechanism of action: GSH precursor GSH substitute Substrate for sulfation Non-specific free radical binder

  39. Acetaminophen:1. Single Ingestion < 8 Hours Toxic dose >150 mg/kg Rumack-Matthew Nomogram at 4+ hrs (use the lower line of 1000 M or 150 g/mL) Pre-4 hour level helpful? If undetectable, excludes APAP overdose

  40. Acetaminophen:2. Single Ingestion Between 8-24 hrs Start NAC if likely toxic/symptomatic Send serum acetaminophen level, AST, INR Continue NAC based on level plotted on nomogram, until Stopping Criteria met Efficacy of NAC decreases with time if administered post 8 hours Only rare fatalities if initiated within 24 hours

  41. Acetaminophen:3. Staggered, Unknown or Ingestion > 24 hrs Empirically start NAC if concerning history and symptomatic Draw serum acetaminophen, AST and INR If any are abnormal (ie detectable APAP, AST > 100, OR INR > 1.5) – treat until Stopping Criteria met If all normal (undetectable APAP, AST < 100, AND INR < 1.5) – D/C NAC Some countries use creatinine as well

  42. Acetaminophen:4. Slow Release Formulations Draw serum acetaminophen at 4 hrs If above toxic threshold on nomogram = NAC Subtoxic level – repeat serum level at 8 hrs, and treat if above threshold

  43. “Patient-tailored Acetylcysteine”

  44. Continue NAC until • Stopping Criteria: • [APAP] undetectable • AST or ALT < 100 IU/L (or have peaked), AND • INR < 1.5 • OR transplant/death

  45. “Patient-tailored Acetylcysteine” • Start NAC unless: • below Rumack-Matthew nomogram • “Stopping Criteria” are met at the outset

  46. N-acetylcysteine IV protocol used in Canada 150 mg/kg over 60 minutes 12.5 mg/kg/hr for 4 hours 6.25 mg/kg/hr until Stopping Criteria met: ? double the 6.25 to 12.5 in high risk pt?? Do not write for finite duration APAP, AST, ALT, INR, lytes q12h

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