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Chairman’s Rounds October 16, 2009; 15 year old with an unintentional overdose

Chairman’s Rounds October 16, 2009; 15 year old with an unintentional overdose. David H. Rubin, MD, FAAP Chairman and Program Director Department of Pediatrics St. Barnabas Hospital Professor of Clinical Pediatrics Albert Einstein College of Medicine. OBJECTIVES. Epidemiology

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Chairman’s Rounds October 16, 2009; 15 year old with an unintentional overdose

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  1. Chairman’s Rounds October 16, 2009;15 year old with an unintentional overdose David H. Rubin, MD, FAAP Chairman and Program Director Department of Pediatrics St. Barnabas Hospital Professor of Clinical Pediatrics Albert Einstein College of Medicine

  2. OBJECTIVES • Epidemiology • Resuscitation • Detoxification • Antidotes/Toxidromes • Case report: 15 year old with an unintentional overdose

  3. EPIDEMIOLOGY(Lapus, 2007) • 2004 data from American Association of Poison Control Centers • 2.4 million exposures • 1.9 million secondary to ingestion • 93% occurred in the home • Majority of calls to poison control centers involve children < 6 years of age • 27 fatalities in children < 6 years of age • 20 unintentional • 7 intentional • 2.3% of all fatalities (n=1,183)

  4. EPIDEMIOLOGY(Watson et al, 2005) Children < 6 years of age, 2004: • Cosmetics and personal care products • Cleaning substances • Analgesics • Topicals • Foreign bodies • Cough and cold preparation • Plants • Pesticides • Vitamins • Antihistamines • Antimicrobials • Gastrointestinal preparations • Arts/crafts/office supplies • Electrolytes/mineral • Hormone related preparations

  5. AMERICAN SOCIETY OF POISON CONTROL CENTERS – 2004(Watson et al, 2005)

  6. TOP 10 CAUSES OF DEATH IN CHILDREN < 6 YEARS 1995-1999 (Abbruzzi and Stork, 2002) • Carbon monoxide inhalation • Hydrocarbon aspiration • Opioid ingestion • Caustic (with and without hydrofluoric acid ingestion) • Iron ingestion • Toxic alcohol ingestion • Tricyclic antidepressant ingestion • Calcium channel blocker or beta-agonist sustained release ingestion • Adrenergic ingestion • Salicylate ingestion

  7. NINE COMMON AGENTS THAT KILL AT LOW DOSES(Michael, 2004) • Calcium channel blockers: bradycardia and hypotension; 1 - 10 mg tablet of nifedipine • Camphor: respiratory depression and seizures; 15 mL of Vicks vapo-rub (700 mg of camphor) • Clonidine: severe bradycardia; 0.1 mg • Tricyclic antidepressants: cardiovascular and CNS toxicity; 10-20mg/kg • Opioids: CNS and respiratory depression; 2.5 mg of hydrocodone

  8. NINE COMMON AGENTS THAT KILL AT LOW DOSES(Michael, 2004) • Lomotil: anticholinergic overdose (tachycardia, seizures, coma); ½ tablet • Salicylates: cerebral edema, coma; ½ teaspoon of wintergreen fatal • Sulfonylureas: severe hypoglycemia; 1 tablet • Toxic alcohols: cardiac and CNS depression; 2.9mL of 95% ethylene glycol has been fatal

  9. RESUSCITATION AND DETOXIFICATION

  10. RESUSCITATION/STABILIZATION (Osterhoudt, 2006) • Airway • NOT PATENT?  jaw lift, jaw thrust, oropharyngeal airway, nasaopharyngeal airway, endotracheal tube • Breathing • NONE DETECTABLE?  mouth/resuscitator to mask or tracheal tube, rescue breathing • Circulation • NONE DETECTABLE?  external compression/ventilation, volume therapy, blood studies, secure intravenous line and assess perfusion

  11. RESUSCITATION/STABILIZATION (Osterhoudt, 2006) • Disability: level of consciousness (AVPU or GCS), pupillary size, reactivity • Drugs • Oxygen • Dextrose 0.25-1 g/kg (10 or 25% solution) • Naloxone (IV, IM, SC): birth-20 kg: 0.1 mg/kg/dose; > 20 kg: 2 mg/kg/dose; ETT dose is 2-10 times IV dose diluted in 3-5 mL saline followed by positive pressure

  12. DECONTAMINATION(Osterhoudt, 2006) • Ocular  saline lavage • Skin  water, then soap and water • Gastrointestinal • Notrecommended: • Ipecac – may delay administration of charcoal, complications (aspiration, diaphragmatic rupture) • Gastric lavage – size of tube often smaller than pills • Cathartics – electrolyte problems, no benefit in RCT

  13. ACTIVATED CHARCOAL(Lapus, 2007) • 1500 BC: use of charcoal in medicine in Egypt; used to absorb odor from rotting wounds • 450 BC: charcoal filters used to purify drinking water • 1773: absorptive powers of charcoal demonstrated • 1963: Holt published study showing benefit in specific ingestions

  14. ACTIVATED CHARCOAL • Used in water filters, medicines that selectively remove toxins, and chemical purification processes • How does it work? • Carbon treated with oxygen resulting in porous charcoal • Surface area of 300-2000 m2/g allows liquids or gases to pass through and bind with the carbon • Interaction with carbon required for absorption • Large organic molecules absorbed better than smaller

  15. ACTIVATED CHARCOAL NOT RECOMMENDED (Lapus, 2007) • P – Pesticides, petroleum distillates, unprotected airway • H – Hydrocarbons, heavy metals, > 1h delay in administration • A – Acids, alkali, alcohol, altered level of consciousness, aspiration risk • I – Iron, ileus, intestinal obstruction • L – Lithium, lack of gag reflex • S – Solvents, seizures

  16. BEZOAR CAUSING SMALL BOWEL OBSTRUCTION AFTER REPEATED ACTIVATED CHARCOAL ADMINISTRATION

  17. ACTIVATED CHARCOAL(Osterhoudt, 2006) • Single dose activated charcoal • 0.5-1 gm/kg, adolescents 50-100 grams PO; maximum dose 100 grams • More benefit if administered within 1 hour of ingestion, but still good for poison which slows gastric motility (anticholinergic, opiates, salicylates) • Strongly consider for acetaminophen overdose > 4 hours • Not recommended for: lithium, iron, alcohols, cyanide, acid/alkali, hydrocarbons

  18. ACTIVATED CHARCOAL(Osterhoudt, 2006) • Multidose activated charcoal • 1 gram/kg q4-6 hours • After absorption, drugs will re-enter the gut by passive diffusion if the concentration there is lower than blood • MDAC maintains a concentration gradient drawing the drug into the gut for absorption • Recommended for:theophylline, phenobarbital, digoxin, salicylate, tricyclic antidepressants, carbamazepine, phenytoin

  19. ACTIVATED CHARCOAL(Lapus, 2007) • If vomiting, carefully consider NG tube • Contraindications • Unprotected airway and  level of consciousness IF not intubated • Increased risk of aspiration – eg hydrocarbons (especially low viscosity kerosene, lighter fluid, lamp oil) • Potential risk of seizures: clonidine, TCA’s • Complications: • Most common: emesis • Most serious: aspiration

  20. WHOLE BOWEL IRRIGATION(Erickson, 2005) • Nonabsorbable, isotonic polyethylene glycol • Toxins “pushed” through GI tract; prevents absorption • Concentration gradient created - allowing absorbed toxin to diffuse back into GI tract • Use where toxins NOT absorbed by charcoal

  21. WHOLE BOWEL IRRIGATION(Erickson, 2005) • Recommended for: • Iron tablets • Lead paint chips • Theophylline • Crack vials/packets • Button batteries • Sustained release calcium channel blockers

  22. WHOLE BOWEL IRRIGATION(Am Acad Clin Tox, 2004) • Use nasogastric tube • No dose-response studies upon which to base dosing. However, recommended dosing schedule is: • Children 9 months to 6 years: 500 mL/h • Children 6-12 years: 1000 mL/h • Adolescents and adults: 1500-2000 mL/h • Continue until rectal effluent clear • Treatment extended based on corroborative evidence of continued presence of toxins in gastrointestinal tract (e.g., radiographs or ongoing elimination of toxins)

  23. WHOLE BOWEL IRRIGATION - CONTRAINDICATIONS(Am Acad Clin Tox, 2004) • Bowel perforation • Bowel obstruction • Clinically significant gastrointestinal hemorrhage • Ileus • Unprotected or compromised airway • Hemodynamic instability • Uncontrollable intractable vomiting

  24. WHOLE BOWEL IRRIGATION - COMPLICATIONS(Am Acad Clin Tox, 2004) • Nausea, vomiting, abdominal cramps, and bloating when WBI used to prepare for colonoscopy and barium enema • Insufficient clinical data for incidence of complications associated with use of WBI • Nausea and vomiting may complicate use of WBI •  vomiting if patient treated with ipecac or ingested agent that produces vomiting • If compromised and unprotected airway, high risk for pulmonary aspiration

  25. ENHANCED EXCRETION • Urinary alkalinization • Salicylate, phenobarbital • Hemodialysis • Lithium, ethylene glycol, methanol, salicylate • Charcoal hemoperfusion • Theophylline, phenobarbital, carbamazepine, procainamide • Plasmapheresis • Phenytoin

  26. ANTIDOTESTOXIDROMESLABORATORY

  27. ANTIDOTES I • Acetaminophen n-Acetylcysteine (NAC) • Anticholinergic Physostigmine • Anticholinesterase Atropine • Organophosphates Atropine/pralidoxime • Carbamate Atropine/pralidoxime • Benzodiazepine Flumazenil • Beta adrenergic blocker Glucagon • Calcium channel blocker Calcium chloride/calcium gluconate • Botulism Botulin antitoxin trivalent (A,B,E) • Carbon monoxide Oxygen • Cyanide Amyl nitrate • Digitalis Fab. antibodies • Ethylene glycol Fomepizole (4-Methylpyrazole) • Fluoride Calcium gluconate • Heavy Metals BAL • Arsenic BAL • Mercury BAL, DMSA

  28. ANTIDOTES II • Iron Deferoxamine • Isoniazid Pyridoxine • Lead BAL, EDTA, penicillamine. DMSA • Methanol Fomepizole (4-Methylpyrazole) • Methemoglobin Methylene blue • Neuroleptic syndrome Dantrolene • Opioids Naloxone • Phenothiazine (dystonic) Diphenhydramine • Sulfonylurea Octreotide • Tricyclic antidepressants Sodium bicarbonate • Warfarin Vitamin K • Snakes, spiders: • Black widow Antivenin, Black widow spider • Coral Antivenin, coral • Crotaline Antivenin, crotaline • Elapid Antivenin, elapid

  29. DIAGNOSIS • History • Substance, how much, where, when • Regular/sustained release • Past illnesses/hospitalizations • Allergies • Physical examination • Vital signs • Neurologic exam

  30. LABORATORY • Electrolytes, BUN, creatinine • Anion Gap = (Na+K)-(CL+HCO3) • 8-14 is normal • Elevated seen in “MUDPILES” • Methanol, uremia, DKA, paraldehyde, iron/isoniazid, lactic acidosis (cyanide), ethanol/ethylene glycol, salicylate • [(Calculated osmolality) – (Serum osmolality)] = -9 to +5 (normal range) • Calculated osmolality=2Na + glucose/18 + BUN/2.8+ ethanol/4.6 • Elevated with ethanol, isopropanol, methanol, ethylene glycol intoxication

  31. LABORATORY • ECG • Arterial blood gas • Pregnancy test • Toxicology • Quantitative: acetaminophen, carbamazepine, carboxyhemoglobin, digoxin, ethanol, ethylene glycol, iron, lead, lithium, methanol, methemoglobin, phenobarbital, phenytoin, salicylate, theophylline, valproic acid

  32. LABORATORY • Common urine substance abuse screens • Amphetamine • Barbiturates • Benzodiazepine • Cannabinoids • Cocaine • Opioids • Phencyclidine

  33. ACETAMINOPHEN (APAP) TOXICITY(Amer Assoc Poison Cntl Center, 2001) • Total reported exposures: 57,516 • Reported exposures, < 19 years: 40,774 • Unintentional overdoses: 35,705 • Intentional overdoses: 20,002 • Total treated for the exposure: 24,934 • Impact on health from the incident: none, 15,029; minor, 6,223; moderate, 3,138; major, 829; fatal: 120

  34. ACETAMINOPHEN OVERDOSE IN THE CALGARY HEALTH REGION BY AGE AND SUICIDAL INTENT (1997–2002)

  35. ACETAMINOPHEN (APAP) TOXICITY • Most common drug overdose at any age • Target organ: liver • Principle metabolism (>90%) by sulfation and glucoronidation - with renal excretion • 5% metabolized by cytochrome P-450 to toxic n-acteyl-p-benzoquinoneimine (NAPQI) • Toxicity produced by saturation of metabolic pathway with excess toxic metabolite (NAPQI) • Normally glutathione detoxifies the metabolite; with overdose, glutathione is depleted causing severe hepatic injury (centrilobular necrosis)

  36. APAP TOXICITY - CLINICAL FINDINGS • Stage I “Gastrointestinal” (24 hours): anorexia, nausea, vomiting, lethargy, diaphoresis, anion gap metabolic acidosis • Stage II “Latent” (24-48 hours): patient may feel better, subclinical increase in hepatic enzymes • Stage III (>48 hours): progressive hepatic encephalopathy, clinical hepatitis, overt coma • Stage IV(4-14 days): recovery

  37. ACETAMINOPHEN (APAP) TOXICITY/LABORATORY EVALUATION • Toxic dose: usually > 150 mg/kg or > 7.5 grams • Try to obtain at 4 hours post ingestion • Plot on nomogram – predictor of liver toxicity • Nomogram • Not accurate for chronic ingestion • Not accurate for multiple doses/overdoses • If level is > potential toxic line, additional workup needed

  38. DIFFERENTIAL DIAGNOSIS • Amanita mushrooms • Hydrocarbon • Heavy metals • Isoniazid • Non steroidal anti-inflammatory • Erythromycin estolate • Vitamin A • Steroids

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