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toxicity; poisoning; overdose

Also see toxidrome. Etiology: 1) common agents associated with death a) carbon monoxide b) most common pharmaceuticals involved in overdose death [24] - opiates, bezodiazepines, stimulants - fentanyl most common cause in 2016 c) calcium channel blockers d) tricyclic antidepressants e) aspirin f) acetaminophen (delayed presentation) g) alcohols 2) others a) arsening poisoning b) cyanide poisoning c) iron overload d) lead poisoning e) organophosphate toxicity f) food poisoning g) laundry detergent pods/packets [12] - ocular burns from laundry detergent pods [13] - intentional ingestion of laundry detergent packets, by teens shared on social media [20] h) recreational drugs Epidemiology: 1) 58% of drug overdoses involve prescription drugs [9] - drug combinations often involved in drug overdose deaths 2) analgesics 57% - opiates play a role in 75% of drug overdose deaths [9] - opiates responsible for 2/3 of overdose deaths in 2016 [21] 3) sedative/hypnotic 32% - benzodiazepines play a role in 29% of drug overdose deaths [9] 4) antidepressants 28% 5) anti-parkinson agents play a role in 29% of drug overdose deaths [9] 6) stimulants/street drugs 22% 7) serious complications 5% 8) in-hospital mortality < 0.5% 9) > 63,600 drug overdose deaths in U.S. in 2016 - average increase of 3%/year from 2006-2014 & 18%/year from 2014-2016 [18] - rates higher for males than females [18] - mortality rate per 100,000 from drug overdoses in teenagers 15-19 years of age 1.6 in 1999, 4.2 in 2007, 3.1 in 2014, 3.7 in 2015 [14] - ~80% of overdose deaths in 2015 were unintentional - mortality rate per 100,000 from drug overdoses in adults 2015 = 16 (urban) & 17 (rural) [15] - 16.3 per 100,000 in 2015 & 19.7 per 100,000 in 2016 [16] 10) opioids, including heroin, with highest death rate by far 11) cocaine major cause of overdose deaths in black men (7.6 per 100,000 person-years); opioids major cause of overdose deaths in white men (7.9 per 100,000 person-years) [17] 12) 72,000 drug overdose deaths in U.S. 2017 [23] 13) overdose deaths in cities exceed those in rural areas [25] Clinical manifestations: (presentations) also see toxidrome 1) altered consciousness 2) cardiac arrhythmias 3) acute organ dysfunction 4) trauma 5) bizarre or puzzling clinical presentation Laboratory: 1) electrolytes & anion gap 2) osmolal gap (measured - calculated osmolality) 3) random comprehensive urine drug screens are seldom useful 4) arterial blood gas 5) liver function tests 6) pregnancy test 7) urinalysis 8) quantitative drug levels when suspecting: a) acetaminophen b) salicylates c) methanol d) ethanol e) isopropyl alcohol f) ethylene glycol g) anticonvulsants h) digoxin i) theophylline j) iron k) lithium Special laboratory: 1) electrocardiogram a) arrhythmias b) conduction delays c) especially important in the case of tricyclic antidepressant (TCA) overdose Complications: 1) anoxic brain injury 2) cardiovascular collapse 3) hepatic failure 4) death 5) coingestion of multiple agents often complicated presentation & management of recreational & therapeutic drug toxicities [10] Management: 1) supportive care a) stabilization of cardiopulmonary status b) empiric therapy for altered mental status - endotracheal intubation for comatose patients - withholding intubation associated with better outcomes [27] - oxygen administration - thiamine 100 mg IV - one ampule of 50% dextrose - naloxone 2-10 mg IV c) removal of contaminated clothing 2) skin & eye decontamination [5] - copious eye irrigation - repeated cleansing of skin with soap & water - calcium for hydroflouric acid burns - polyethylene glycol for phenol burns 3) gastric decontamination a) ipecac - most efficacious when given within 30-45 minutes of ingestion - contraindications: - ingestion of caustic agents, hydrocarbons, drugs known to cause abrupt loss of consciousness or seizures, foreign bodies, non-toxic substances - unconscious patients, patients with seizures, patients with potential for inability to protect airway, patients with intentional ingestion - gut not working (antimuscarinic toxidrome) b) gastric lavage - performed prior to administration of charcoal - 34-40 French orogastric tube (adults) - 150-200 mL aliquots of warm water or normal saline - 5-10 liters total c) activated charcoal - with & without sorbitol - useful for salicylates, theophylline, benzodiazepines, carbamazepine & phenytoin overdoses d) gastric decontamination CONTRAINDICATED ingestion of caustic agents 4) caustic agents - supportive care for stable patients with mild symptoms - ceftriaxone, ranitidine & methylprednisolone for severe cases with deep ulcerations - if evidence of perforation or necrosis, CT scan & surgical consultation [26] - endotracheal intubation for airway compromise [26] 5) whole bowel irrigation a) polyethylene glycol-electrolyte lavage solution to facilitate removal of ingested substances b) indications - late presentation following ingestion - ingestion of sustained release pharmaceuticals - ingestion of toxic substances not removed by activated charcoal - foreign bodies c) most commonly used for: - iron, lithium, cocaine packets, sustained release Ca+2 channel blockers d) dosage: - 2 liters/hour for 5 hours (adults) - 500 mL/hr (children) 6) specific antidotes a) specific antidote available for very few toxins & is not always needed b) duration of antidote may be shorter than duration of toxin activity c) antidote therapy does not replace gastric decontamination d) opiates - antidote: naloxone - start with 2 mg - nasal naloxone kits & training for their use by non-healthcare professionals saves lives [8] e) methanol or ethylene glycol - antidote: ethanol 10% solution - loading dose: 10 mL/kg - maintenance dose: 1.5 mL/kg - titrate to blood alcohol level of 22 mmol/L (100 mg/dL) f) anticholinergics - antidote: physostigmine - 1-2 mg IV over 5 minutes - use only for severe delirium - may be useful for treating seizures or tachydysrhythmias but evidence lacking g) organophosphate poisoning or carbamate insecticides - antidote: atropine & pralidoxime - atropine test dose: 2 mg IV - repeat in larger increments until drying of pulmonary secretions occurs h) isoniazid - antidote: pyridoxine - give in gram per gram equivalent of what was ingested - start with 5 gm IV if amount ingested unknown i) beta-blockers - antidote: glucagon - starting dose 5-10 mg IV - titrate to response (normalization of BP & HR) - maintenance dose of 2-10 mg/hr j) tricyclic antidepressants (TCA) - antidote: bicarbonate - 1-2 mmol/kg for cardiac conduction delays or ventricular arrhythmias - titrate to response & pH 7.45-7.50 k) digitalis glycosides (digoxin) - antidote: digoxin-specific antibodies - equimolar to ingestion - the number of mg of digoxin ingested / 0.6 is the number of vials required - if the amount of ingested digoxin is unknown & the patient has life-threatening arrhythmias, give 10-20 vials IV - if steady state serum digoxin concentration is known # of vials = [digoxin (ng/mL) x 5.6 x weight in kg / 600 l) benzodiazepines - antidote: flumazenil (Romazicon) - 0.2 mg over 30 seconds - repeat q30 seconds up to 3 mg - contraindications - coingestion of tricyclic antidepressants (TCA) - patients taking benzodiazepines for control of seizures m) calcium channel blockers - antidote: calcium chloride - 1 gm CaCl2 given IV over 5 minutes with continuous cardiac monitoring - may be repeated in life-threatening situations - serum calcium should be monitored after 3rd dose - data supporting this treatment lacking n) acetaminophen - antidote: N-acetylcysteine - loading dose: 140 mg/kg PO - 70 mg/kg PO every 4 hours for a total of 17 doses - if 4 hour serum acetaminophen level is in the toxic range, all 17 doses of N-acetylcysteine must be given - thiamine 7) hemodialysis may be useful for specific agents 8) urine alkalinization - aspirin - phenobarbital 9) consultation with regional poison control center 10) National poison hotline (800) 222-1222 [1,2]

Related

toxin (hazardous material, poison)

Specific

acetaminophen poisoning alcohol toxicity aluminum toxicity anticholinergic toxicity anticholinesterase toxicity (muscarinic toxidrome) benzodiazepine toxicity beta-adrenergic receptor antagonist (beta blocker) overdose cadmium toxicity calcium channel blocker toxicity carbon monoxide poisoning cardiotoxicity chloracne chromium toxicity cyanide poisoning cytotoxicity digitalis toxicity eosinophilia-myalgia syndrome (EMS) fluoride toxicity folic acid antagonist toxicity food poisoning (foodborne disease) heavy metal toxicity hepatotoxicity hyperheparinemia (heparin overdose, heparin toxicity) hypervitaminosis A inhalation poisoning intoxication iodine toxicity iron overload (iron poisoning) muscarine toxicity (muscarine poisoning) nephrotoxicity (renal toxicity) neurotoxicity Opioid Overdose organophosphate toxicity ototoxicity plant toxicity propylene glycol intoxication pyridoxine neuropathy; megavitamin-B6 syndrome retinoid toxicity salicylate toxicity tacrolimus toxicity thallium poisoning toxic oil syndrome toxidrome (toxic syndrome) veisalgia zinc toxicity

General

disease

References

  1. Prescriber's Letter 9(3):13 2002
  2. Prescriber's Letter 10(12):67 2003
  3. National poison hotline (800) 222-1222
  4. Prescriber's Letter 11(8): 2004 Poisonings in Toddlers Detail-Document#: 200807 (subscription needed) http://www.prescribersletter.com
  5. Daubert GP, Emergency Medicine, University of California, Davis
  6. The National Academy of Clinical Biochemistry (NACB) Recommendations for the use of laboratory tests to support poisoned patients who present to the emergency department (Guideline withdrawn from National Guideline Clearinghouse March 2009) http://www.nacb.org/lmpg/emergency/emergency_lmpg.pdf
  7. CDC Grand Rounds: Prescription Drug Overdoses - a U.S. Epidemic MMWR January 13, 2012 / 61(01);10-13 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6101a3.htm
  8. Walley AY et al Opioid overdose rates and implementation of overdose education and nasal naloxone distribution in Massachusetts: interrupted time series analysis. BMJ 2013;346:f174 PMID: 23372174 http://www.bmj.com/content/346/bmj.f174
  9. Jones CM et al Pharmaceutical Overdose Deaths, United States, 2010 JAMA. 2013;309(7):657-659 PMID: 23423407 http://jama.jamanetwork.com/article.aspx?articleid=1653518
  10. Medical Knowledge Self Assessment Program (MKSAP) 16, 17. American College of Physicians, Philadelphia 2012, 2015
  11. Centers for Disease Control and Prevention (CDC) Vital Signs: Overdoses of Prescription Opioid Pain Relievers and Other Drugs Among Women - United States, 1999-2010 MMWR. July 5, 2013 / 62(26);537-542 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6226a3.htm
  12. Orciari Herman. Sofair A Laundry Detergent Pods Remain Serious Risk, Despite Changes to Packaging. Physician's First Watch, May 18, 2015 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org - Davis MG, Casavant MJ, Spiller HA, Chounthirath T, Smith GA. Pediatric Exposures to Laundry and Dishwasher Detergents in the United States: 2013-2014 Pediatrics May 2016 PMID: 27244825
  13. Haring RS, Sheffield ID, Frattaroli S Detergent Pod-Related Eye Injuries Among Preschool-Aged Children. JAMA Ophthalmol. Published online February 2, 2017 PMID: 28152145 http://jamanetwork.com/journals/jamaophthalmology/article-abstract/2599445
  14. Curtin SC, Tejada-Vera B, Warner M. Centers for Disease Control and Prevention (CDC) Drug Overdose Deaths Among Adolescents Aged 15-19 in the United States: 1999-2015. NCHS Data Brief No. 282, August 2017 https://www.cdc.gov/nchs/products/databriefs/db282.htm
  15. Mack KA, Jones CM, Ballesteros MF. Illicit Drug Use, Illicit Drug Use Disorders, and Drug Overdose Deaths in Metropolitan and Nonmetropolitan Areas - United States. MMWR Surveill Summ 2017;66(No. SS-19):1-12 https://www.cdc.gov/mmwr/volumes/66/ss/ss6619a1.htm
  16. Centers for Disease Control & Prevention (CDC) Vital Statistics Rapid Release. Mortality Dashboard. November 3, 2017 https://www.cdc.gov/nchs/nvss/vsrr/mortality-dashboard.htm
  17. Shiels MS, Freedman ND, Thomas D, de Gonzalez AB Trends in U.S. Drug Overdose Deaths in Non-Hispanic Black, Hispanic, and Non-Hispanic White Persons, 2000-2015. Ann Intern Med. 2017. Dec 5. PMID: 29204603 http://annals.org/aim/article-abstract/2665041/trends-u-s-drug-overdose-deaths-non-hispanic-black-hispanic
  18. Hedegaard H, Warner M, Minino AM Drug Overdose Deaths in the United States, 1999-2016 NCHS Data Brief No. 294, December 2017 https://www.cdc.gov/nchs/data/databriefs/db294.pdf
  19. Kraut JA, Mullins ME. Toxic Alcohols. N Engl J Med 2018; 378:270-280. Jan 18 PMID: 29342392 http://www.nejm.org/doi/full/10.1056/NEJMra1615295
  20. American Association of Poison Control Centers (AAPCC) HIGH ALERT: Intentional Exposures Among Teens to Single-Load Laundry Packets Continue to Rise. Press Release. Jan 22, 2018 http://www.aapcc.org/press/84/
  21. Seth P, Scholl L, Rudd RA, Bacon S. Overdose Deaths Involving Opioids, Cocaine, and Psychostimulants - United States, 2015-2016. MMWR Morb Mortal Wkly Rep 2018;67:349-358 https://www.cdc.gov/mmwr/volumes/67/wr/mm6712a1.htm
  22. Erickson TB, Thompson TM, Lu JJ. The approach to the patient with an unknown overdose. Emerg Med Clin North Am 2007 May; 25:249. PMID: 17482020
  23. Centers for Disease Control & Prevention (CDC) National Center for Health Statistics. Provisional Drug Overdose Death Counts. Vital Statistics Rapid Release. Aug. 2018 https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm
  24. Brauser D Top Ten Drugs Tied to Overdose Deaths Medscape Medical News. Dec 12, 2018 https://www.medscape.com/viewarticle/906434 - Hedegaard H, Bastian BA, Trinidad JP et al Drugs Most Frequently Involved in Drug Overdose Deaths: United States, 2011-2016, National Vital Statistics Reports. 67(9): Dec 12, 2018 https://www.cdc.gov/nchs/data/nvsr/nvsr67/nvsr67_09-508.pdf
  25. Hedegaard H, Minino AM, Warner M NCHS Data Brief No. 345, August 2019 Urban - rural Differences in Drug Overdose Death Rates, by Sex, Age, and Type of Drugs Involved, 2017. https://www.cdc.gov/nchs/products/databriefs/db345.htm
  26. NEJM Knowledge+ Gastroenterology
  27. Freund Y et al. Effect of noninvasive airway management of comatose patients with acute poisoning: A randomized clinical trial. JAMA. 2023 Dec 19;330(23):2267-2274. PMID: 38019968 https://jamanetwork.com/journals/jama/fullarticle/2812429
  28. OD Prevention Program Locator Overdose Prevention Alliance http://www.overdosepreventionalliance.org/p/od-prevention-program-locator.html
  29. California Poison Control System (800) 222-1222