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The Poisoned Patient: A Medical Student Review

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1 The Poisoned Patient: A Medical Student Review
William Beaumont Hospital Department of Emergency Medicine

2 Introduction All chemicals, especially medicines, have the potential to be toxic 2006 TESS data 2.7 million exposures 19.8% were treated in a healthcare facility 21.6% of those had more than minor outcomes including death Over half of poisonings occur in children less than 5 years of age

3 The Initial Approach Always consider poisoning in differential dx
IV, O2, monitor Accucheck – in all pts with altered mental status D50 +/-Thiamine or Naloxone as indicated Decontamination, protect yourself Enhanced elimination Antidotal therapy Supportive care

4 History Name, quantity, dose and route of ingestant(s)
Time of ingestion Any co-ingestions Reason for ingestion – accidental, suicidal Other medical history and medications EMS – inquire what they saw at the scene, notes left, smells, unusual materials, pill bottles, etc.

5 Pupils Dilated – anticholinergic or sympathomimetic
Constricted – Cholinergic Pinpoint – Opiods Nystagmus – horizontal – ethanol, phenytoin, ketamine Nystagmus – rotatory or vertical - PCP

6 Skin Hyperpyrexia – anticholinergic, sympathomimetic, salicylates
Hypothermic – Opiods, sedative-hypnotics Dry skin – anticholinergics Moist skin – cholinergics, sympathomimetics Color – cyanosis, pallor, erythema

7 Overall exam Stimulants – everything is UP
 temp, HR, BP, RR, agitated Sympathomimetics, anticholinergics, hallucinogens Depressants – everything is DOWN  temp, HR, BP, RR, lethargy/coma Cholinergics, opioids, sedative-hypnotics Mixed effects: Polysubstance overdose, metabolic poisons (hypoglycemic agents, salicylates, toxic alcohols)

8 Laboratory studies Accucheck Chemistries (BUN, Cr, CO2)
Urinalysis – Calcium oxalate crystals in ehtylene glycol poisoning Drugs of abuse and comprehensive drug screen Acetaminophen, aspirin and ethanol levels Urine HCG if warranted EKG ABG, serum osmolality, Toxic Alcohol screen, LFTS if warranted

9 General Decontamination
Remove all clothing, wash away any external toxic substances If suspect transmittable contaminant, perform in special decontamination area If ocular exposure – flush eyes copiously with at least 2 L NS using lid retractors, until pH 7 – 7.5

10 GI Decontamination Three methods
Gastric emptying Bind the toxin in the gut Enhance elimination Always consider the patient’s mental status, risk of aspiration, airway security and GI motility before attempting any method

11 Orogastric Lavage Indications – life threatening ingestions who present one hour within ingestion With the patient in the left lateral decub position, a 36 fr tube is passed oral - gastric to evacuate gastric contents and lavage with room temperature water until effluent is clear Studies show little benefit (may remove as little as 35% of the substance), the need of a secure airway and relatively high complication rate

12 Activated Charcoal Adsorbs toxin within the gut making it unavailable for absorption 1 g/kg PO or via NGT Contraindications: bowel obstruction or perforation, unprotected airway, caustics and most hydrocarbons, anticipated endoscopy Not effective for alcohols, metals (iron, lead), elements (magnesium, sodium, lithium)

13 Multi-dose Activated Charcoal
MDAC Large doses of toxin Slow release toxins Enterohepatic or enterenteric circulation Toxins that form bezoars “gastrointestinal dialysis” Phenobarbital, theophylline, carbamazepine, dapsone, quinine

14 Cathartics 70% Sorbitol 1g/kg, administered with charcoal
Decreased transit time of both toxin and charcoal through the GI tract Typically only used with the first dose if MDAC Do not use in children under 5, caustic ingestions, or possible bowel obstruction

15 Whole Bowel Irrigation (WBI)
Go-Lytely via PO or NGT at a rate of 2L/hr (500 ml/hr in peds) Typically used for those substances not bound by Activated Charcoal Do not use in patients with potential bowel obstruction

16 Hemodialysis Useful for Salicylates, Methanol, Ethylene Glycol, Lithium, Amanita mushrooms, Isopropyl alcohol, Chloral hydrate Patients must be hemodynamically stable and without bleeding disturbances Charcoal hemoperfusion – essentially HD with a charcoal filter in the circuit Barbituates, Carbamazepine, Phenytoin, Methotrexate, Theophylline and Amanita poisonings

17 Toxin Antidotes Acetaminophen Anticholinergic agent Benzodiazepines
Beta blockers or calcium channel blockers Carbon monoxide Cardiac glycosides Cyanide N-Acetylcysteine Physostigmine Flumazenil Glucagon, calcium Oxygen Digoxin-specific Fab fragments Amyl nitrate, sodium nitrate, sodium thiosulfate, hydroxycobalamin

18 Toxin Antidote Ethylene glycol Heparin Hydrofluoric acid Iron
Isoniazid Lead Mercury, arsenic, gold Methanol Nitrites (Methemoglobin) 4-Methylpyrazole, ethanol Protamine sulfate Calcium gluconate Desferoxamine Pyridoxime (Vit B6) BAL or DMSA, Calcium disodium EDTA BAL Methylene blue

19 Toxins Antidote Opiates, propoxyphene, lomotil Organophosphates
Sulfonylureas Tricyclic antidepressants Naloxone (Narcan) Atropine, pralidoxime Glucose, octreotide Sodium bicarbonate, benzodiazepines

20 Case One 56 y/o male found unconscious in a basement. He has snoring respirations, frothing at the mouth, and rales on pulmonary exam. His pupils are pinpoint. He wakes up swearing and swinging at staff after a little narcan. What could it be?

21 The Toxidromes - Opioid
Heroin, Morphine, fentanyl CNS depression, lethargy, confusion, coma, respiratory depression, miosis Vital signs:  temp, HR, RR, +/- BP Pulmonary edema, aspiration, resp arrest Check for track marks, rhabdomyolysis, compartment syndrome Tx: Naloxone mg iv/im/sc slowly May result in severe agitation Monitor closely and re-dose if necessary

22 The Toxidromes - Sympathomimetic
Cocaine, amphetamines (speed, dex, ritalin), Phencyclidine (PCP), methamphetamines (crank, meth, ice), MDMA (Ecstasy, X, E) Stimulant: Meth > amphetamines > MDMA Hallucinogen: MDMA > Meth > amphetamines Agitation,  temp, HR, BP, mydriasis Seizures, paranoia, rhabdomyolysis, MI, arrythmias

23 Toxidromes - Sympathomimetics
Management - primarily supportive - Benzo’s, IV hydration, cooling if hyperthermic Treat HTN with benzodiazepines, nitrates, phentolamine MI – avoid beta blockers Bodystuffers (small amount, poorly contained) Asymptomatic - AC, monitor for toxicity Symptomatic - AC, WBI, treat symptoms Bodypackers (lg amount, well contained) Asymptomatic - WBI followed by imaging Symptomatic - Immediate surgical consultation

24 The Toxidromes - Cholinergic
Organophosphates Insecticides, nerve gas (Sarin, Tabun, VX) Irreversible binding to ACHe – “aging” Carbamates Insecticides (Sevin) Reversible binding to ACHe – short duration Physostigmine, Edrophonium, Nicotine All increase Ach at CNS, autonomic nervous system and neuromuscular jx

25 The Toxidromes - Cholinergic
Common Clinical Findings SLUDGE Syndrome Parasympathetic hyperstimulation Salivation, Lacrimation, Urinary Incontinence, Defecation, GI pain, Emesis Killer B’s Bradycardia, Bronchorrhea, Bronchospasm Bronchorrhea and respiratory failure is often the cause of death Miosis, garlic odor, CNS ( MS, seizures, muscle fasciculations and weakness, resp depression, coma

26 The Toxidromes - Cholinergic
Diagnose – RBC or plasma cholinesterase level Management Decontamination – protect yourself Supportive therapy Atropine - competitive inhibition of ACH Large doses required mg q 5 minutes End point is the drying of secretions Pralidoxime (2-PAM) - breaks OP-ACHe bond Start with 1-2 g IV over 30 minutes, give before “aging” Adjust dose based on response, ACHe level

27 Case 2 22 y/o F presents with decreased urine output. She is febrile, confused, flushed and has dilated pupils on exam. You also notice a linear, vesicular rash on her lower legs. What do you want to know?

28 Case 2 Meds She has been using oral benadryl and topical caladryl lotion for the poison ivy What is her toxidrome?

29 The Toxidromes - Anticholinergic
Agents Antihistamines: diphenhydramine, loratadine, meclizine, prochlorperazine Antipsychotics: chlorpromazine (Thorazine), Thiroidazine (Mellaril), Belladonna Alkaloids: Jimsonweed, deadly nightshade, mandrake, atropine, scopolamine Cyclic Antidepressants: amitriptyline (Elevil), nortriptyline (Pamelor), fluoxetine (Prozac) OTC’s: Excedrin PM, Actifed, Dristan, Sominex Muscle Relaxants: Orphenadrine (Norflex), cyclobenzaprine (Flexeril) Amanita mushrooms The Toxidromes - Anticholinergic

30 The Toxidromes - Anticholinergic
Common Clinical Findings Dry as a bone - lack of sweating, dry skin and mucous membranes Red as a beet - flushed, vasodilated Hot as Hades - hyperthermia, may be agitation induced Blind as a bat - mydriasis Mad as a hatter - anticholinergic delirium, hallucinations Stuffed as a pipe - hypoactive bowel sounds, ileus, decreased GI motility, urinary retention VS:  temp, HR, BP

31 The Toxidromes - Anticholinergic
R/O psychiatric disorders, DTs, sympathomimetic toxicity Dry skin and absent bowel sounds indicate likely anticholinergic toxicity Management Sedation with high dose benzodiazepines AC (esp if  BS), temp control Treat widened QRS and dysrhythmias with bicarb Physostigmine far more effective but use only in clear cut cases 0.5 to 2.0 mg IVP, every minutes Monitor for excess cholinergic response - SLUDGE

32 The Toxidromes - Salicylate
Aspirin, oil of wintergreen, OTC remedies Altered mentation, tinnitus, diaphoresis, nausea and vomiting, tachycardia Metabolic acidosis and respiratory alkalosis Dx: + anion gap, salicylate level > 30mg/dl Treatment Multidose AC Alkalinize urine HD if levels > 100 mg/dl, altered MS, renal failure, pulmonary edema, severe acidosis or hypotension

33 The Toxidromes - Serotonin Syndrome (SS)
SSRI’s: fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), citalopram (Celexa), escitalopram (Lexapro) MAOI’s, meperidine, tricyclics, trazadone, mertazapine, dextromethorphan, LSD, lithium, buproprion, tramadol SS may be caused by any of the above, but usually occurs with a combination of agents, even if in therapeutic doses

34 The Toxidromes - Serotonin Syndrome (SS)
altered MS, mydriasis, myoclonus, hyperreflexia, tremor, rigidity (especially lower extremities), seizures, hyperthermia, tachycardia, hypo or hypertension Citalopram and escitalopram - prolonged QT and QRS No confirmatory tests – diagnosis is based on clinical suspicion

35 The Toxidromes - Serotonin Syndrome Treatment
Supportive care Single dose AC (ensure airway control) Benzodiazepines to treat discomfort, muscle contractions or seizures) and cooling measures Treat prolonged QT with magnesium Treat widened QRS with Bicarb Cyproheptadine (antiserotonin agent) - 4 to 8 mg PO. Dose may be repeated in 2 hrs. If positive response, give 4 mg PO q 6 hrs for 48 hrs.

36 Acetaminophen Poisoning
Common Clinical Findings Stage I 0-24 hrs, nausea, vomiting, anorexia Stage II hrs, RUQ pain, elevation of AST and ALT, also elevation of bilirubin and PT if severe poisoning Stage III hrs, peak of AST, ALT, bilirubin and PT, possible renal failure and pancreatitis Stage IV > 5 days, resolution of hepatotoxicity or progression to multisystem organ failure

37 Acetaminophen Poisoning
Rummack-Mathew nomogram acetaminophen levels vs time Plot 4 hr level Useful for single acute ingestion only

38 Acetaminophen Poisoning
Management AC assume polypharmacy OD NAC - N-acetylcysteine (NAC) indicated if patient ingested over 140 mg/kg OR toxic level on nomogram IV dose: 150mg/kg IV load, 50 mg/kg over 4 hrs, then 100mg/kg over 16 hrs PO dose: 140 mg/kg load, then 70 mg/kg q 4 hrs x 17 Draw baseline LFTs and PT

39 CASE: UNKNOWN LIQUID 17 y/o M brought in by family for acting “drunk.” He is lethargic, confused, disoriented. Vitals: 130, 90/60, 16, 37 C. Labs: Etoh 0, CO2 12 What else do you want to know?

40 CASE UNKNOWN LIQUID Accucheck: 102 Serum Osmolality 330
Na 140, K 4.0, Cl 100, CO2 12, glucose 90 BUN 28, Cr 2.0 UDS, APAP, ASA are all negative U/A has calcium oxalate crystals What are we hinting at? Osmolal gap = 35

41 Toxic Alcohols Typical Agents All toxic alcohols cause an osmolar gap
Ethanol Isopropanol Methanol Ethylene glycol (EG) All toxic alcohols cause an osmolar gap Methanol and EG cause an anion gap acidosis

42 Useful Equations Anion Gap (mEq/L) Calculated Osmolarity (mosm/L)
Na - (Cl + HCO3) Calculated Osmolarity (mosm/L) 2Na + BUN/2.8 + Glu/18 + ETOH/4.6

43 Toxic Alcohols - Isopropanol
Rubbing alcohol > solvents, antifreeze, disinfectants It is the second most commonly ingested alcohol Isopropyl alcohol has twice the CNS depressing potency and up to 4 times the duration as ethanol Toxic dose of 70% isopropanol is 1ml/kg Lethal dose is as little as 2ml/kg

44 Toxic Alcohols - Isopropanol
Metabolized by alcohol dehydrogenase to acetone Fruity breath, ketonuria, + osmolar gap, no acidosis Clinically may appear similar to ethanol intoxication with greater CNS depression Hypotension, respiratory depression, coma Nausea, vomiting, abdominal pain and upper GI bleeding secondary to hemorrhagic gastritis

45 Toxic Alcohols - Methanol
Typical agent is wood alcohol, used in solvents, paint removers, antifreeze and windshield washer fluid. Also may be found in bootleg liquor. Is rapidly metabolized to toxic formaldehyde and formic acid Can cause permanent retinal injury and blindness as well as parkinsonian syndrome if not treated promptly May have a long latent period (12 to 18 hours), especially if co-ingested with ethanol

46 Methanol diagnosis Common Clinical Findings
Lethargy, nausea, vomiting, abd pain Visual symptoms seen in 50% - blurring, tunnel vision, color blindness  HR, RR, BP (poor prognosis if present) CNS - head ache, seizures or coma Wide anion-gap metabolic acidosis with osmolar gap Toxic alcohol screen to confirm

47 Toxic Alcohols - Ethylene Glycol
Typical agent is antifreeze Often seen in alcoholics, suicide attempts and children Colorless, odorless and sweet Metabolism and treatment similar to methanol Is rapidly absorbed and converted to toxic acids responsible for clinical signs and symptoms Lethal dose is as low as 2 ml/kg

48 Toxic Alcohols - Ethylene Glycol
Common Clinical Findings Three phases 1-12 hours - CNS Depression: inebriation, vomiting, seizures, coma, tetany (hypocalcemia) 12-24 hours - Cardiopulmonary Phase: hypotension, tachydysrhythmias, tachypnea and ARDS 24-72 hours - Nephrotoxic Phase: Oliguric renal failure, ATN, flank pain, calcium oxylate crystalluria

49 Toxic Alcohols - Ethylene Glycol
Additional findings Hypocalcemia secondary to precipitation with oxylate, excreted as urinary calcium oxylate crystals Urine may also fluoresce secondary to fluorescence dye in antifreeze EKG: QT prolongation (hypocalcemia) and peaked T’s (hyperkalemia) Myalgias, secondary to acidosis and elevated CPK

50 Diagnose Ethylene Glycol (EG)
Always consider EG in an inebriated patient without alcohol breath, an anion-gap metabolic acidosis, osmolar gap and calcium oxylate crystalluria

51 Treatment of EG and Methanol
Supportive, especially airway Correct acidosis with IV bicarb, 1meq/kg IV Benzo’s if seizures develop Folic acid 50mg IV q 4 hrs for both Pyridoxine 100 mg IV q 6 hrs, Thiamine 100mg IV q 6 hrs, Magnesium for EG Ca gluconate 10 ml of 10% IV – to correct hypocalcemia – EG only Folinic acid

52 Treatment of EG and Methanol
Block production of toxic metabolites Ethanol infusion or oral administration Load 10% in D5W at 10 ml/kg over 30 min Infuse 10% in D5W at 1.5 ml/kg to maintain ETOH level at > 100 mg/dl Fomepizole - preferred method 15 mg/kg over 30 minutes, then 10 mg/kg q 12 hrs x 4 Has 8000 times the affinity for ADH as ETOH without CNS depression and hypoglycemia Or 4-MP (4-methylpyrazole)

53 Treatment of EG and Methanol
Hemodialysis indicated if Serum level > 50 mg/dl Signs of nephrotoxicity (EC) or CNS or visual disturbances (Methanol) Severe metabolic acidosis

54 Tricyclics Agents Amitriptyline (Elevil), desipramine (Norpramin), imipramine (Tofranil) and nortriptyline (Pamelor) Narrow therapeutic index Have returned to popularity with non-depression indications such as chronic pain, migraines, ADHD and OCD

55 Tricyclics Common Clinical Findings CNS - decreased LOC
Confusion, hallucinations, delirium, seizures Cardiovascular - arrhythmias and hypotension QRS > 100 msec, conduction delays Arrhythmias such as V-tach & Torsades may develop as QRS widens and QT prolongs Anticholinergic Toxidrome Tachycardia, mydriasis, hyperthermia, anhydrosis, urinary retention, decreased bowel sounds

56 Tricyclics EKG during TCA toxicity and after treatment with bicarb. Note wide QRS, prolonged QT and terminal R’s > 3mm in AVR

57 Treatment of tricyclic overdose
AC Na Bicarb – to treat QRS prolongation > 100 msec and hypotension refractory to IV fluids Benzo’s to treat seizures and hyperthermia (avoid physostigmine) Magnesium and Lidocaine for Ventricular arrythmias refractory to Bicarb Magnesium for QT prolongation or Torsades

58 CO Sources Fossil fuel combustion (car exhaust), smoke, kerosene or coal heaters, steel foundries Methylene chloride vapor Found in bubble Christmas tree lights and in paint strippers CO binds to hemoglobin with 230 times the affinity to oxygen, decreasing it’s ability to transport oxygen

59 CO Common Clinical Findings
Organs with high O2 demand become dysfunctional Nausea, malaise, headache, decreased mental status, dizziness, paresthesias, weakness, syncope May progress to vomiting, lethargy, coma, seizures, CVA , MI or respiratory arrest Need a high index of suspicion – multiple family members with flu like symptoms without fever, winter months

60 CO COHb level may not represent the severity of the poisoning
Pulse oximetry also may be misleading Half-life of COHb 4 hours on room air 60 minutes breathing 100% normobaric O2 (NBO) 15 to 23 minutes breathing 100% hyperbaric O2 (HBO) at 2.5 atmospheres

61 CO treatment 100% O2 via NRB for 4 hrs minimum if mild symptoms (nausea, heachache, malaise)

62 CO 100% O2 and transfer to a hyperbaric center if any of the following
Altered mental status or coma History of LOC or near syncope History of seizure Hypotension during or after exposure MI Pregnant with COHb > 15% Arrythmias +/- COHb > 25-40% Only absolute contraindication to hyperbaric chamber is pneumothorax

63 References Tintinalli, J., Kelen, G.D., Stapczynski, J.S., Emergency Medicine, A Comprehensive Study Guide, Sixth Edition 2004, McGraw-Hill, New York, pp Flomenbaum, N., Goldfrank, L., et al., Goldfrank’s Toxicologic Emergencies, Eighth Edition 2006, McGraw-Hill, New York, pp , , , , , Ziad, N.K., Roberge, R.J., A Toxicology Handbook, American Academy of Emergency Medicine

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