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PEDIATRIC TOXICOLOGY. Nga B. Pham, M.D. Epidemiology. 64 Poison Centers serving 295 million people 2.4 million exposures last year 39% are children younger than 3 years 52% in children younger than 6 years 106 deaths in age <19 for 2003
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PEDIATRIC TOXICOLOGY Nga B. Pham, M.D.
Epidemiology • 64 Poison Centers serving 295 million people • 2.4 million exposures last year • 39% are children younger than 3 years • 52% in children younger than 6 years • 106 deaths in age <19 for 2003 2003 Annual report of the American Association of Poison Control Centers Toxic Exporure Surveillance System – Watson et. al
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
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%)
Epidemiology • Unintentional (1-2 years) • Exploratory • Boys > girls • Unable to discriminate safe from unsafe liquid • Intentional (adolescent) • Purposeful • Girls > boys
Epidemiology • Around meal time • Grandparents home • Kerosene or gasoline in a soda bottle • Older sibling can pharmaceutically treat younger sibling
Evaluation of Suspected Poisoning • ABC’s 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.)
Evaluation • History of poisoning • Physical Examination • Laboratory studies • Gastrointestinal decontamination
History • What? • When? • How much? • Reliability…
What? • Medication • Illicit drug • Hazardous chemical
What forms? • Pill • Solid • Liquid • Gaseous
What route? • Ingestion • Inhalation • Topical • Intravenous
When? • Elapsed time
How much? • Estimate amount • Concentration
PICU Admission • Tricyclic antidepressants (TCA) • Anticonvulsants • Digoxin • Opiates • Hydrocarbon-based household products
Toxic Exposure - Death • Analgesics • Sedative-hypnotics • Alcohols • Gases & fumes • Cleaning substances
Toxidromes • Anticholinergics • Atropine, scopolamine, TCA’s, 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
Toxidromes • Cholinergics • Organophosphates and carbamates
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
Nicotinic Effects of Organophosphate Poisoning • Muscle fasciculation • Cramping • Weakness (extreme is diaphragmatic failure) • Autonomic nicotinic effects include hypertension, tachycardia, pupillary dilation, and pallor
CNS Effects ofOrganophosphate Poisoning • Anxiety • Restlessness • Confusion • Ataxia • Seizures • Insomnia • Dysarthria • Tremors • Coma
Toxidromes • Opiates: • Morphine, Methadone, Dextromethorphan
Toxidromes • Opiates • Morphine, methadone, dextromethorphan • Resp: decreased respiratory rate, pulmonary edema • CV: hypotension, bradycardia • Neuro: miosis, AMS, coma, hypothermia, seizures
Toxidromes • Sedatives/hypnotics • Benzodiazepines, barbiturates • Resp: slow respirations • CV: tachycardia, hypotension • Neuro: AMS, coma, seizures, hypothermia
Toxidromes • Tricyclic antidepressants • Amitryptiline, nortryptiline, etc. • See anticholinergic effects • CV: arrhythmias, hypotension • Neuro: coma, seizures
Toxidromes • Salicylates • ASA, oil of wintergreen • Resp: tachypnea
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
Laboratory Tests Suggestive ofPoisoning • Hyperglycemia • ASA, theophylline, caffeine, iron • Hypocalcemia • Ethylene glycol, ASA • UA • Glowing urine – ethylene glycol • Calcium oxalate crystals – ethylene glycol
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
Laboratory Testing • Grady unfortunately doesn’t 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
Laboratory Testing • Additional testing is helpful if you have a specific substance that you suspect • Usually less helpful as a “fishing expedition” and won’t 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
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
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
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
Elimination of Poisons • Activated charcoal • Adsorbs many drugs, thus decreasing systemic absorption • Doesn’t 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 doesn’t work well with
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 can’t 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 can’t get reabsorbed