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R. Arbeau S. Anderson October 21/ 2010 Case 1 ID: 3 y/o F CC: Ingestion HPI: Was at grandmothers house. Grandmother was gardening and thinks patient ingested something Pmhx: Healthy Rx: Nil All: NKDA Case 1 cont.... O/E BP: 98/64 HR: 106 RR: 22 02: 100% on R/A T: 37.1 Glucose: 4.5 Case 1 cont... Exam: GCS 15. Acting appropriately. CV: N heart sounds Resp: N GI: N CNS: N Case 1 cont... B/W CBC, lytes, BUN, Cr N Tox screen? EKG NSR Case 2 ID: 17 month old CC: ? Ingestion HPI: Was at grandmothers house and became fatigued. Taking lots of naps since 15:00. Presented at 21:00 Pmhx: similar presentation 3 weeks ago Rx: nil All: NKDA Case 2 cont.... O/E: BP: 98/70 HR: 73 RR: 22 02: 100% on R/A T: 37.4 Glucose: 5.1 Case 2 cont... O/E: Fatigued but easily rousable CV: heart sounds normal Resp: N GI: N CNS: No focal abnormalities Case 2 cont... B/W CBC, lytes, BUN, Cr N EKG Sinus bradycardia No QTC/QRS changes Approach to Toxicology ABC’s IV O2 Monitor Approach Cont... History Collateral history VERY important ○ DPV ○ Paramedic reports ○ Witnesses Physical Track marks Pill fragments Look in pockets Approach cont.... Supportive measures Antidotes Call Poison Control What is a poison? Kitchen/Laundry Area Bathroom Garage/Basement/Storage Ammonia Air Fresheners Antifreeze* Bleach After-Shave Lotions Insect Killers* Carpet/Upholstery cleaners Colognes/Perfumes Fertilizers Dishwasher Detergents False Fingernail Removers* Gasoline Disinfectants Hair Remover Glues Drain Cleaners* Hair Styling Products Lotions/Creams/Oils Kerosene Fabric Softeners Floor Cleaners Furniture Polishes Insect Killers* Hand Sanitizer* Makeup Medications* Mothballs Lighter Fluids Lime* Lye* Paints Laundry Detergents Mouthwash* Paint Thinners Metal Cleaners Nail-Polish Removers Pool Supplies Oven Cleaners* Rust Removers Scouring Powders Rubing Alcohol* Shampoos Shaving Creams Rodent Killers Turpentines Weed Killers* Spot Removers Soaps/Deodorants Windshield Wiper Fluids* Spray Starches Toilet Bowel Cleaners* Ingestions The dose is dependent upon * The environmental concentration * The properties of the toxin * The frequency of exposure * The length of exposure * The exposure pathway Toxicological Principles Decrease absorption Enhance elimination Antidotes Considerations Change from normal state could be on the molecular, cellular, organ, or organism level--the symptoms Local vs. Systemic Reversible vs. Irreversible Immediate vs. Delayed Further Consideration Routes and Sites of Exposure Ingestion (Gastrointestinal Tract) Inhalation (Lungs) Dermal/Topical (Skin) Injection ○ intravenous, intramuscular, intraperitoneal Why is pediatrics different? Higher mg/kg dosing based on bodyweight Exploratory behaviour Everything goes into their mouths Pediatric Toxicology One pill killers TCA’s Antimalarials Typical antipsychotics Antidysrythmics Ca2+ channel blockers Beta blockers Opiates (especially long acting) Sulfonyureas (ie./ glyburide) Theophylline Lomotil (immodium) Clonidine One sip killers Ethylene glycol Methanol Camphor Anything containing methylsalicylate Oil of wintergreen (100% methylsalicylate) Ben gay ○ 1 ml of 98% methylsalicylate contains 1.4 g of salicylate ○ One teaspoon (5ml is potentially fatal in 2 year old) Bradycardia in pediatric tox Calcium channel blockers Beta blockers Digoxin Cholinergic compounds (Increased vagal tone) Opiates (related to sedative effect) Clonidine Includes visine (eye drops) and nasal spray (afferin) Back to cases Case 1: 3 y/o asymptomatic Took one of grandmothers 100 mg atenolol Cases Case 2: 17 month old Bradycardic Fatigued Took 0.1 mg of grandmothers clonidine Beta blockers Uses: HTN, dysrhythmias, migraines etc... Preparations: Oral immediate and sustained release, IV, opthalmic Selective (B1 – heart, eye, kidney) or non-selective (B1 and B2 {smooth/skeletal muscle, liver, heart}) Selectivity is lost in overdose situations Beta blockers cont... Pharmacokinetics May be hepatic (propanolol) or renal elimination (atenolol, nadalol) Onset is variable and may be delayed if extended release formula Beta Blockers cont... Clinical Manifestations Safer ingestion in younger people (those not dependant on adrenergic tone) Hypotension, bradycardia, CHF Conduction disturbances (SA and AV nodal blockade, QRS prolongation and QTC prolongation-sotalol) Respiratory depression Delirium, coma or seizures (often in context of hypotension) More worrisome if underlying disease or coingestions Beta Blockers cont... Hypoglycemia may occur Sympathetic stimulation is blocked Gluconeogenesis is impaired so glucose may be low Bronchospasm Underlying lung disease Hyperkalemia may occur Cause K+ efflux as beta agonists cause K+ influx Beta Blocker Management ABC/IV/O2/Monitor Activated charcoal 0.5-1 g/kg Most effective if given within one hour of ingestion (no evidence) Multiple doses have been recommended but no specific evidence Beta Blocker Management cont... Glucagon Inotropic and chronotropic effects Counteracts any hypoglycemia that may occur 5 to 10 mg IV bolus Infusion may be needed Atropine Symptomatic bradycardia 0.5 mg for adults 0.02 mg/kg for children (minimum 0.1 mg) Beta Blocker management cont…. Calcium Pressors Pacing Beta Blocker Management cont... If asymptomatic for 6 hours after an oral overdose of normal release preparations patients may be cleared medically Sustained release preparations should be admitted to a monitored bed, but are unlikely to develop toxicity if asymptomatic for 24 hours (ie./ carvedilol, sotalol) Any hypotension, dysrhythmias should be admitted to ICU/CCU bed Calcium Channel Blockers Pathophysiology: Inhibit L-type Ca2+ channels ○ Decreases calcium influx into myocardial and smooth muscle cells ○ Myocardium: Decreased contractility and conduction ○ Peripheral: Relaxation and vasodilation of vasculature CCB’s pathophysiology cont.. Different affinities ○ Verapamil: greatest effects at SA and AV nodes ○ Nifedipine: Greater effects peripherally than on myocardium ○ Diltiazem: Moderate affinity for both myocardial and peripheral cells Ca2+ channel blockers cont... Clinical Manifestations Hypotension Bradycardia AV conduction delays and complete heart block Cardiogenic shock Hyperglycemia ○ L-type calcium channels are blocked in pancreatic islet cells leading to decreased insulin release CNS ○ Related to hypoperfusion ○ Noted to not have as much CNS effects as other bradycardic medications (unsure of mechanism) Ca2+ channel blockers cont... Management ABC/IV/O2/Monitor Activated charcoal ○ 0.5-1 g/kg ○ Most effective if given within one hour of ingestion ○ Multiple doses have been recommended especially for extended release preparations Ca2+ channel blockers cont... Atropine Symptomatic bradycardia ○ May not work well b/c AV nodal blocking effects Calcium Increases extracellular calcium creating a concentration gradient promoting influx of Ca2+ into cells Contraindicated with digoxin co-ingestion Dosing 1g CaCl- or Ca gluconate ○ Initially 1-2 ampules ○ CaCl- provides three times as much calcium (more sclerosis of vessels – better suited for central venous administration) Ca2+ channel blockers cont... Glucagon Activates adenyl cyclase through glucagon receptor Unlikely to be helpful but consider with refractory hypotension Pressors NE has theoretical advantage ○ B1 adrenergic activity reverses myocardial depressant effects ○ Alpha1 effects increase peripheral vascular effects Ca2+ channel blockers cont... Insulin/glucose Insulin may increase cardiac inotropy and chronotropy ○ Has pressor effects that increases BP and HR Pacing CCB management NEJM, Vol 344, No. 22, May, 2001 Case report of calcium channel blocker OD’s being treated with insulin infusion L-type channels are blocked (including islet cells) resulting in hypoinsulinemia In an unstressed state myocytes oxidize FFA’s for energy, but in a stressed state the hypoinsulinemia may prevent glucose uptake by myocytes causing a loss of inotropy, PVR and shock CCB management NEJM, Vol 344, No. 22, May, 2001 These patients were started on insulin infusions which improved inotropy and peripheral vascular resistance Also thought to improve acidosis by improving uptake of carbohydrates by myocytes and smooth muscle cells Ca2+ channel blockers cont... Disposition If asympomatic for 6 hours then may be medically cleared Any hypotension or dysrythmias should be admitted Digoxin Cardioactive steroid Uses: CHF, controlling ventricular response in a-fib/a-flutter Mechanism of action Increases vagal tone (bradycardia and impaired AV node conduction) Inhibits sodium potassium exchange pump Digoxin Naturally occurring sources Foxglove Lily of the valley Bufo toads Oleander/yellow oleander Dogbane Digoxin The Na/K+ exchange is blocked, thereby decreasing Na+/Ca2+ exchange In OD there is ++ intracellular Ca2+ Increases intracellular resting membrane potential and increases dysrhythmias Digoxin Clinical manifestations GI: nausea, vomiting usually first symptom CNS: lethargy, confusion and weakness. Halos, yellow vision in chronic overdose situations Metabolic: Hyperkalemia is a marker for severe poisoning in acute overdose this is due to blockage of Na/K ATPase, release of K+ from tissues and inhibition of K+ uptake into skeletal muscle Digoxin Cardiac manifestations Increased automaticity with a high degree AV block Any dysrhythmia is possible except a rapidly conducted supraventricular rhythm with a rapid ventricular rate (unless patient has a congenital accessory pathway) Most common disturbance is PVC’s Bidirectional V-tach is rare, but pathognomonic Digoxin EKG Digoxin – Bidirectional V-tach Digoxin Treatment Supportive Charcoal Atropine if indicated Avoid internal electrical pacing ○ May trigger fatal dysrhythmia Potassium/Magnesium if low ○ Magnesium contraindicated in bradycardia/AV block Digoxin Definitive Treatment: Digibind ○ Digoxin specific antibody fragments ○ Binds digoxin in serum, diffuses into interstitial sites and creates a concentration gradient to help digoxin dissociate from the heart Digoxin: Digibind Indications: Adults Ventricular dysrhythmia Hemodynamically significant bradydysrhythmias not responsive to atropine Serum potassium > 5.0 Rapidly progressive rhythm disturbances and rising potassium Co-ingestion of other cardiotoxic drugs Ingestion of plant known to contain cardiac glycosides Acute ingestion of greater than 10 mg Indications: Children Ingestion of greater than 0.1-0.3 mg/kg plus rapidly progressive symptoms or potentially life-threatening dysrhythmias or conduction blocks Co-ingestions of other cardiotoxic drugs Ingestion of plant known to contain cardiac glycosides Digoxin Digibind dosing -If dose ingested known {amount ingested (mg) * 0.8}/ 0.5 (amount digoxin bound/vial) -If serum concentration known {serum concentration * weight in kg} / 100 -Empiric dosing with unknown concentration 10 vials (adult or child) Digoxin Treatment Amiodarone if ventricular dysrhythmias ACLS management ○ Electricity may worsen rhythm, but is obviously treatment of choice in arrest situation ○ Digibind should also be considered if not given already Digoxin Disposition: All patients who are symptomatic require at least 12 hours of monitoring If digibind is required then an ICU/CCU admission is required Clonidine Central alpha agonist ○ Decreases NE release in brain, which decreases sympathetic outflow causing decreased HR, BP and cardiac output Peripheral alpha agonist ○ In overdose ○ Post-synaptic alpha2 adrenergic agonist on peripheral vessels. This increases NE release causing peripheral vasoconstriction which may cause early transient hypertension Clonidine Clinical Manifestations CV: early transient hypertension followed by hypotension and bradycardia from central effects CNS: Lethargy, pinpoint pupils Respiratory: Hypoventilation, hypoxia, periodic apnea, Cheyne Stokes respiration Clonidine Treatment ABC/IV/O2/Monitor Supportive Charcoal Naloxone: may reverse some or all of the sedation associated (mechanism unclear). May need large doses (ie./ 200 mg in 24 hours) For hypotension: ○ IV fluids initially ○ Atropine ○ Consider pressors in refractory hypotension Clonidine Admission if any symptoms for monitoring Monitored for 6-8 hours if asymptomatic Cholinergic Syndrome Bradycardia may caused by action on muscarinic receptors Should be easily recognized and differentiated from other exposures Bradycardia Comparison Drug Temp BP Pupil s CNS K+ Skin Bowe Urine l Glu. EKG CCB N/E Dec N/E +/- +/- N/E N/E N/E Inc Brady AV blocks Bblock N/E Dec N/E Dec Inc N/E N/E N/E Dec Brady, AV blocks Dig N/E +/- Halo Dec vision, yellow haze Acute Inc. N/E N/E N/E N/E PVC’s, Scooped ST’s, bi directional VT Chron ic Dec Cholin N/E ergic +/- miosis Dec +/- Wet Inc Urinat N/E ion Brady Clonid N/E ine Dec pinpoi Dec nt +/- N/E N/E N/E Brady N/E Back to cases Case 1: 3y/o F Took grandmothers atenolol Poison control contacted Given charcoal Remained asymptomatic Transferred to Peds ER for observation Discharged home after 6 hours of observation Cases Case 2: 17 month old Ingested 0.1 mg clonidine Fatigued, bradycardia Given charcoal Narcan was advised, but not given Atropine was given with minimal effect Admitted to PCCU and monitored for 36 hours HR increased with no further intervention required References Rosens Boyer & Shannon. Treatment of Calcium channel blocker intoxication with insulin infusion. NEJM. Vol. 344, No. 22, 2001 New York City Poison Control Handbook Questions?