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pediatric toxicology

Epidemiology. 64 Poison Centers serving 295 million people2.4 million exposures last year39% are children younger than 3 years52% in children younger than 6 years106 deaths in age <19 for 20032003 Annual report of the American Association of Poison Control Centers Toxic Exporure Surveillance System

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pediatric toxicology

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    1. PEDIATRIC TOXICOLOGY Nga B. Pham, M.D.

    3. Epidemiology Most commonly fatal classes of poisoning Analgesics (375) 62 Tylenol only, 52 Tylenol + 1 other, 100 Tylenol combination products (Lortab, etc.) 23 ASA more than half did not have ASA levels >100mg/dl early and more aggressive dialysis recommended Street drugs (124) Antidepressants (112) Amitriptyline

    4. Epidemiology Most common Pediatric Exposure Cosmetics and personal care products (13%) Cleaning substances (10%) Analgesics (7.8%) Foreign Bodies (7.4%) Topicals (7.4%) Cold and Cough Preparations (5.5%) Plants (4.6%) Pesticides (4.1%)

    5. Epidemiology Unintentional (1-2 years) Exploratory Boys > girls Unable to discriminate safe from unsafe liquid Intentional (adolescent) Purposeful Girls > boys

    6. Epidemiology Around meal time Grandparents home Kerosene or gasoline in a soda bottle Older sibling can pharmaceutically treat younger sibling

    7. Evaluation of Suspected Poisoning ABCs and routine ICU management Establishing the diagnosis Must consider poisoning, especially in at risk age groups Less than 6 year old with acute decompensation (AMS, arrhythmias, hypotension, metabolic acidosis, etc.)

    8. Evaluation History of poisoning Physical Examination Laboratory studies Gastrointestinal decontamination

    9. History What? When? How much? Reliability

    10. What? Medication Illicit drug Hazardous chemical

    11. What forms? Pill Solid Liquid Gaseous

    12. What route? Ingestion Inhalation Topical Intravenous

    13. When? Elapsed time

    14. How much? Estimate amount Concentration

    15. PICU Admission Tricyclic antidepressants (TCA) Anticonvulsants Digoxin Opiates Hydrocarbon-based household products

    16. Toxic Exposure - Death Analgesics Sedative-hypnotics Alcohols Gases & fumes Cleaning substances

    17. Toxidromes Anticholinergics Atropine, scopolamine, TCAs, phenothiazines, antihistamines, mushrooms, jimson weed Hot as a hare, dry as a bone, red as a beet, mad as a hatter Neuro: agitation, hallucinations, coma, extrapyramidal movements, mydriasis, hyperthermia CV: tachycardia, hypotension, hypertension, arrhythmia GI/GU: decreased bowel sounds, urinary retention

    18. Toxidromes Cholinergics Organophosphates and carbamates

    19. Muscarinic Effects of Organophosphate Poisoning S alivation *D iaphoresis/diarrhea L acrimation *U rination U rination *M iosis D efecation *B radycardia/bronchospasm G I secrestion/upset *E mesis E mesis *L acrimation excess *S alivation excess

    20. Nicotinic Effects of Organophosphate Poisoning Muscle fasciculation Cramping Weakness (extreme is diaphragmatic failure) Autonomic nicotinic effects include hypertension, tachycardia, pupillary dilation, and pallor

    21. CNS Effects ofOrganophosphate Poisoning Anxiety Restlessness Confusion Ataxia Seizures Insomnia Dysarthria Tremors Coma

    22. Toxidromes Opiates: Morphine, Methadone, Dextromethorphan

    23. Toxidromes Opiates Morphine, methadone, dextromethorphan Resp: decreased respiratory rate, pulmonary edema CV: hypotension, bradycardia Neuro: miosis, AMS, coma, hypothermia, seizures

    24. Toxidromes Sedatives/hypnotics Benzodiazepines, barbiturates Resp: slow respirations CV: tachycardia, hypotension Neuro: AMS, coma, seizures, hypothermia

    25. Toxidromes Tricyclic antidepressants Amitryptiline, nortryptiline, etc. See anticholinergic effects CV: arrhythmias, hypotension Neuro: coma, seizures

    26. Toxidromes Salicylates ASA, oil of wintergreen Resp: tachypnea

    27. Laboratory Tests Suggestive ofPoisoning Elevated osmolar gap (>10) Serum osm = (Na x 2) + BUN/2.8 + glucose/18 Volatile alcohols, mannitol Elevated anion gap (>12) MUDPILES Low anion gap Lithium, iodine, bromine, fluoride Hyperkalemia Postassium, lithium, digoxin, fluoride Hypokalemia Theophylline, toluene

    28. Laboratory Tests Suggestive ofPoisoning Hyperglycemia ASA, theophylline, caffeine, iron Hypocalcemia Ethylene glycol, ASA UA Glowing urine ethylene glycol Calcium oxalate crystals ethylene glycol

    29. Laboratory Testing What is in a urine drug screen? Amphetamines, Barbiturates, Cocaine, Benzodiazepine, Opiates, THC, PCP What is in a serum drug screen? Acetaminophen, ETOH, Salicylate, TCA What is in a comprehensive drug screen? Barbiturates, Salicylates, Cannabinoids, PCP, TCA, Sedatives, Benzodiazepines, Stimulants, Opium alkaloid, Synthetic Narcotics, Tranquilizers, Cocaine

    30. Laboratory Testing Grady unfortunately doesnt do HPLC anymore Options for more comprehensive screen Quest lab if needed in 24 hours or less ARUP 2-4 days turn around SERUM: Acetaminophen, alcohols, barbiturates, benzodiazepines, carbamazepine, carisoprodol, disopyramide, meprobamate, phenytoin, primidone, salicylate, theophylline, tricyclic and other antidepressants URINE: acetaminophen, alcohols, barbiturates, benzodiazepines, carbamazepines, carisoprodol, chlorpheniramine, cocaine & metabolites, diphenhydramine,ethchlorvynol, ibuprefen, lidocaine, meprobamate, narcotics & synthetics, phencyclidine, phenothiazines, phenytoin, primidone & metabolites, pyrilamine, salicylate, sympathomimetic amines, theophylline, tricyclic and other antidepressants, trimethoprim

    31. Laboratory Testing Additional testing is helpful if you have a specific substance that you suspect Usually less helpful as a fishing expedition and wont affect management Am J Emerg Med. 1999 May:17(3):221-4. Belson MG, Simon HK Evaluate the clinical utility and cost-effectiveness of the limited component vs the HPLC component of comprehensive toxicologic screens in children Retrospective from HSCH ED Jan 1994-July 1995 The comprehensive test included a broad-spectrum HPLC component as well as a limited component that examined serum for ethanol, aspirin, and acetaminophen and urine for benzodiazepines, barbiturates, amphetamines, cocaine, phencyclidien, and opiates Comprehensive toxicology screens were performed in 463 cases during the study period; 234 (51%0 were positive for exogenous toxin

    32. Laboratory Testing In 227 of 234 positive screens (97%), toxins were either suspected by history and/or physical, were present on the limited portion of the toxicology screens, or were clinically insignificant The remaining 7 of the 234 positive screens (3%) were clinically significant and detected solely by the broad-spectrum HPLC portion of the comprehensive screen However, in none of these 7 cases was patient management clinically altered as a result of the positive screen The total additional cost of the HPLC component was $16,205 ($35x464), an average distributive charge of $2,315 per patient in whom the HPLC portion provided additional clinical information ($16,205/7) Although adding significant charges to the evaluation of suspected toxic exposures in children, the HPLC component of the comprehensive drug screen was of no additional clinical benefit compared with its limited component alone

    33. Urine Drug Screens THC 1-3 weeks* Cocaine 2-4 days Amphetamine 2 days Barbiturates 1-2 days Opiates 1-2 days PCP 5-7 days LSD 1-2 days Steroids 3 days or longer * Longer if prolonged exposure

    34. Antidotes

    35. Antidotes

    36. Antidotes

    37. Antidotes

    38. Antidotes

    39. Antidotes

    40. Antidotes

    41. Antidotes

    42. Antidotes

    43. Antidotes

    44. Antidotes

    45. Antidotes

    46. Antidotes

    47. Antidotes

    48. Elimination of Poisons Surface decontamination Reduce any additional absorption Ipecac Not routinely recommended anymore Possible useful in an observed, in hospital poisoning Gastric Lavage Most effective 1-2 hours after ingestion Can be effective later in drugs that delay gastric emptying

    49. Elimination of Poisons Activated charcoal Adsorbs many drugs, thus decreasing systemic absorption Doesnt work well for lithium, iron, hydorcarbons, alcohols, solvents, acid/alkali ingestions Role of charcoal in gastrointestinaldialysis Cathartics Not generally used Some charcoal has sorbitol in it Whole bowel irrigation Golytely infusions Initially done with success in iron ingestions Used mostly for drugs that charcoal doesnt work well with

    50. Elimination of Poisons Diuresis +/- alteration of urine pH Obviously, only useful for renally excreted drugs Altering pH example ASA pkA3 At a pH of 3, there is a 1:1 ratio of ionized/unionized At a pH of 7.4, the ratio is 25,000:1 Ionized form cant cross cell membranes so when you dump ASA into the tubule, if the pH is 4.5 you would have about 5,00:1 ratio, if you increase urine pH to 8.0, then essentially all of it is in the ionized form, and cant get reabsorbed

    51. Elimination of Poisons Altering pH Alkalinize the urine ASA, isoniazid, phenobarb Use bicarb in the fluids Dont use acetazolamide (Diamox) in ASA poisoning Metabolic acidosis increases unionized form which can cross into CNS, worsening poisoning Acidify the urine (usually not needed) quinidine, PCP, fenfluramine, amphetamine

    52. Elimination of Poisons Dialysis What makes things dialyzable Low molecular weight Low volume of distribution Low protein binding Charge Methods Intermittent Hemodialysis CVVH/CVVHD/CVVHDF Albumin dialysis

    53. Elimination of Poisons Charcoal hemoperfusion Clear chemicals by direct adsorbtion with charcoal in an extracorporeal circuit Doesnt depend of molecular size, protein binding Can be used for a variety of otherwise difficult to manage poisonings Digoxin, ASA, barbiturates, TCAs, theophylline Not used that much anymore

    54. Elimination of Poisons Plasmapheresis Works very well with highly protein (albumin) bound drugs Not a routine methodology, but has been used to remove theophylline and digoxin/digibind complexes Exchange transfusion Use in smaller infants where vascular access for extracorporeal techniques cant be done

    55. Tylenol Ingestion Clinical manifestations Stage 1 First 12-24 hours Nausea, vomiting, anorexia No CNS involvement of you see it, think of polysubstance ingestion Stage 2 Resolution of GI symptoms 36 hours after ingestion see biochemical evidence of liver dysfunction AST/ALT, bilirubin, PT

    56. Tylenol Ingestion Clinical manifestation Stage 3 Liver dysfunction reaches a peak on day 3-4 Start GI symptoms again High transaminases (>10,000) do not necessarily predict liver failure Fulminant liver failure can occur Stage 4 Recovery stage lasts 7-8 days Chronic hepatitis does not occur LFTs/biopsy return to normal

    57. Tylenol Ingestion Prediction of toxicity Rumack nomogram for single ingestion Rough guide for potential toxicity Children 150 mg/kg Adults 7.5 gm Uncommon 150mg/kg 50% with 250 mg/kg 100% with 350mg/kg

    58. Tylenol Ingestion Therapy N-acetylcysteine (Mucomyst) Oral 140 mg/kg load, followed by 70mg/kg q4 hours for 17 doses Repeat dose if vomits within 1 hour Can mix with carbonated drinks or grapefruit juice Intravenous 150 mg/kg load over 15 minutes, then 50mg/kg over 4 hours, then 100mg/kg over 16 hours

    59. Volatile Alcohols Diagnosis High index of suspision Elevated osmolar gap Volatile alcohol screen + separate test for ethylen glycol Methanol and ethylene glycol no ketones Isopropyl alcohol marked acetone Ethanol acetoacetate and B-hydroxybutyrate

    60. Volatile Alcohols Isopropyl Alcohol Toxic dose is 1 ml/kg of 70% solution More than one swallow in children should be presumed toxic About 20% is broken down by liver ADH to acetone Symptoms are like ethanol ingestion Nystagmus is common More CNS depressant than ETOH, because acetone is a CNS depressant as well Management Supportive (without hypotension essentially 0% mortality) Levels dont mean much prognostically Dialysis will remove it Coma + hypotension 30% mortality Level over 400 (implied severe ingestion)

    61. Volatile Alcohols Methanol No safe dose. 5ml is lethal in toddler age and can cause blindness in adults. 1ml/kg is lethal in adults Metabolism 30% excreted by lungs 5% kidneys Rest to liver to make toxic metabolites

    62. Volatile Alcohols Methanol Clinical symptoms Biphasic Initial CNS depression secondary to direct action of methanol on CNS Delayed Visual disturbances Photophobia, snowflakes, blurred vision CAN HAVE FIXED DILATED PUPILS Metabolic acidosis Laboratory Elevated anion gap is due to formic acid and lactate Retinal damage is due to locally produced formic acid

    63. Volatile Alcohols Methanol Treatment Supportive Ethanol/dialysis Fomepizole +/- dialysis now

    64. Volatile Alcohols Ethylene Glycol Minimum lethal dose is 1.4-1.6 ml/kg Clinical symptoms Severe neurotoxicity, metabolic acidosis, renal failure, cardiovascular collapse 1st phase 30 min 12 hours CNS symptoms, N/V If LP pleocytosis and elevated protein 2nd phase cardiorespiratory failure with pulmonary edema 3rd phase renal failure Metabolism 25% excreted unchanged by kidneys Remainder rapidly metabolized by liver and kidneys to toxic metabolites

    65. Volatile Alcohols Ethylene Glycol Lactic acidosis develops secondary to altered NADH/NAD ratio Oxalic acid chelates calcium Tetany and myocardial dysfunction Renal failure is likely due to glycoaldehyde, glycolic acid, glyoxylic acid Most recover can be prolonged up to 2 months Can see calcium oxalate crystals in urine

    66. Volatile Alcohols Ethylene Glycol Treatment Fomepixole +/- dialysis

    67. Cyanide Poisoning Exposures Mostly from fires in children Acetonitrile in some cosmetics reported lethal Vitamin B17 cyanogenic glycosides sold in health food stores from pits of apricots and bitter almonds Laetrile only when given orally or rectally Nipride use sodium thiosulfate to reduce incidence 1 gram per 100mg of Nipride

    68. Cyanide Poisoning Pathophysiology Reversible binding to a-a3 cytochrome Halts aerobic metabolism and ATP formation Pushes to anaerobic metabolism and resultant lactic acidosis Inability to use oxygen at the cellular level Normal oxygen content and oxygen delivery

    69. Cyanide Poisoning Treatment 100% oxygen always Eli Lilly Cyanide Antidote Kit No M-76 Amyl nitrate pearls inhale for 15-30 secs Produces about 5% methemoglobinemia IV sodium nitrite IV sodium thiosulfate Aiming for methemoglobin of 30%

    70. Hydrocarbon Ingestion Unintentional vs intentional Clinical presentation Respiratory distress Hydrocarbons dissolve the lipid layer in the lung Surfactant inactivation, distal airway closure, hypoxemia, V/Q mismatch Can progress to ARDS CNS abnormalities Mostly due to hypoxia GI abnormalities

    71. Hydrocarbons Ingestion Clinical presentation Fever and leukocytosis common in first 24-48 hours Treatment Supportive Treat the hypoxia No induction of vomiting

    72. Iron Intoxication Relatively common ingestion About 5-10% require hospitalization Can be lethal <20 mg/kg elemental Fe insignificant 20-60 mg/kg mild toxicity >60 mg/kg moderate to severe toxicity >200 mg/kg rapidly lethal if not treated

    73. Iron Intoxication Pathophysiology Huge uptake of iron from small bowel Overwhelm transferrins ability to bind and thus get free iron circulating in blood Disruption of CMS, GI, CV systems Major oxidant stress possibly shunts electrons away from cytochromes in the mitochondria Interferes with activation of thrombin and clot formation, leading to coagulopathy Direct gut toxicity with hemorrhagic gastritis and bowel perforation

    74. Iron Intoxication Clinical manifestation 1st phase GI symptoms (N/V/D, hemorrhagic gastritis, GI bleed) direct effect 2nd phase temporary recovery 6-12 hours from ingestion can last several days 3rd phase return of GIU symptoms and MSOF Metabolic acidosis, shock, CNS depression, liver dysfunction, renal failure, coagulopathy, etc. Die or get better 4th phase 4-6 weeks out pyloric, gastric, or intestinal obstruction due to healing of initial damage

    75. Iron Intoxication Prognosis Ingestion size Serum iron levels Peak 2-6 hours after ingestion <100 unlikely toxicity 100-300 minimal 300-500 moderate 500-1,000 severe >1,000 potentially lethal After 6 hours even in large ingestion, level may be normal

    76. Iron Intoxication Therapy Role of gastric lavage Desferoxamine iron chelator Binds iron to form ferrioxamine which can be safely excreted renally Red (vin rose) color to urine Also has a protective effect of increasing intracellular binding of iron, reducing toxicity Not dialysable

    77. Beta Blockers Widely prescribed and available Phamacology Lipophilicity Membrane stabilizing effect Selective vs non-selective agents Propranolol is most common and most dangerous

    78. Beta Blockers Toxic dose 2-3 times therapeutic dose Signs and symptoms Bradyarrhythmia Hypotension Decrease LOC Respiratory depression Seizure Ventricular arrhythmia

    79. Beta Blockers Prehospital management Aggressive airway management PALS protocol Atropine 1mg prn (max 3 mg) Peds 0.02 mg/kg Transcutaneous pacemaker Do not delay in symptomatic bradycardia

    80. Beta Blockers Prehospital management Glucagon 5mg IV bolus Peds 0.2 mg/kg IV bolus Fluid resuscitation peds 20 ml/kg Pressors Dopamine 5-10 mcg/kg/min Epinephrine drips Titrate to response. May need bigger than normal dose

    81. Beta Blockers Other management issues Treat dysrhytmia Pediatric patient Hypoglycemia more common Seizures more likely than adult Consider heroic measures - ECMO

    82. Calcium Channel Blocker Pharmacology Negative inotrope Blocks flow of calcium ions through slow channels Decreased amount of calcium from sarcoplasmic reticulum Negative chronotrope Decrease automaticity in SA node and AV junction Reduction in PVR

    83. Calcium Channel Blocker Agents Verapamil Significant cardiac depressant Vasodilation AV slowing Diltiazem Nifedipine Felodipine Amlodipine

    84. Calcium Channel Blocker Toxicity Hypotension Bradycardia Arrhythmias Respiratory depression Neurologic disorders Seizures etc.

    85. Calcium Channel Blocker Prehospital management Aggressive airway management PALS protocol Atropine 1 mg prn (max 3mg) Peds 0.02 mg/kg Atropine most often not effective Transcutaneous pacemaker Do not delay in symptomatic bradycardia

    86. Calcium Channel Blocker Prehospital management Calcium chloride 250-500 mg IV Peds 20mg/kg Glucagon 5mg IV bolus Peds 0.1 mg/kg IV bolus Fluid resuscitation peds 20 ml/kg

    87. Calcium Channel Blocker Other management issues Pressors prn Dopamine 5 mcg/kg/min Epinephrine drip 2 mcg/kg/min Titrate to response, may need bigger dose than normal Treat dysrhythmias Pediatric patient Small dose can be lethal Seizures are more likely than adult Consider heroic measures - ECMO

    88. Digoxin Toxicity Dysrhythmias PVCs Slow A-fib Bradycardia, V-fib. V-tach Hypotension Hyperkalemia ( Renal insufficiency is a risk factor) CNS Delirium, hallucinations, lethargy, agitation Ocular disturbances

    89. Digoxin Treatment Basic management (ABCs etc.) Electrolyte disturbances Hyperkalemia Atropine/Pacemaker Manage dysrhythmias Digoxin specific antibody

    90. Digoxin Treatment Digibind Indication Life threatening CV toxicity K > 6.5 mEq/L (except in chronic renal failure) Steady state level >10 ng/ml Ingested dose >10mg (adult)

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