toxicity; poisoning; overdose

Introduction

Also see toxidrome.

Etiology

• common agents associated with death
  • carbon monoxide
  • most common pharmaceuticals involved in overdose death
    • opiates, bezodiazepines, stimulants
    • fentanyl most common cause in 2016
  • calcium channel blockers
  • tricyclic antidepressants
  • aspirin
  • acetaminophen (delayed presentation)
  • alcohols
• others
  • arsening poisoning
  • cyanide poisoning
  • iron overload
  • lead poisoning
  • organophosphate toxicity
  • food poisoning
  • laundry detergent pods/packets
    • ocular burns from laundry detergent pods
    • intentional ingestion of laundry detergent packets, by teens shared on social media
  • recreational drugs

Epidemiology

• 58% of drug overdoses involve prescription drugs
  • drug combinations often involved in drug overdose deaths
• analgesics 57%
  • opiates play a role in 75% of drug overdose deaths
  • opiates responsible for 2/3 of overdose deaths in 2016
• sedative/hypnotic 32%
  • benzodiazepines play a role in 29% of drug overdose deaths
• antidepressants 28%
• anti-parkinson agents play a role in 29% of drug overdose deaths
• stimulants/street drugs 22%
• serious complications 5%
• in-hospital mortality < 0.5%
• > 63,600 drug overdose deaths in U.S. in 2016
  • average increase of 3%/year from 2006-2014 & 18%/year from 2014-2016
  • rates higher for males than females
  • 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
  • ~80% of overdose deaths in 2015 were unintentional
  • mortality rate per 100,000 from drug overdoses in adults 2015 = 16 (urban) & 17 (rural)
    • 16.3 per 100,000 in 2015 & 19.7 per 100,000 in 2016
• opioids, including heroin, with highest death rate by far
• 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)
• 72,000 drug overdose deaths in U.S. 2017
• overdose deaths in cities exceed those in rural areas

Clinical manifestations

(presentations) also see toxidrome

• altered consciousness
• cardiac arrhythmias
• acute organ dysfunction
• trauma
• bizarre or puzzling clinical presentation

Laboratory

• electrolytes & anion gap
• osmolal gap (measured - calculated osmolality)
• random comprehensive urine drug screens are seldom useful
• arterial blood gas
• liver function tests
• pregnancy test
• urinalysis
• quantitative drug levels when suspecting:
  • acetaminophen
  • salicylates
  • methanol
  • ethanol
  • isopropyl alcohol
  • ethylene glycol
  • anticonvulsants
  • digoxin
  • theophylline
  • iron
  • lithium

Diagnostic procedures

• electrocardiogram
  • arrhythmias
  • conduction delays
  • especially important in the case of tricyclic antidepressant (TCA) overdose

Complications

• anoxic brain injury
• cardiovascular collapse
• hepatic failure
• death
• coingestion of multiple agents often complicated presentation & management of recreational & therapeutic drug toxicities

Management

• supportive care
  • stabilization of cardiopulmonary status
  • empiric therapy for altered mental status
    • endotracheal intubation for comatose patients
      • withholding intubation associated with better outcomes
    • oxygen administration
    • thiamine 100 mg IV
    • one ampule of 50% dextrose
    • naloxone 2-10 mg IV
  • removal of contaminated clothing
• skin & eye decontamination
  • copious eye irrigation
  • repeated cleansing of skin with soap & water
  • calcium for hydroflouric acid burns
  • polyethylene glycol for phenol burns
• gastric decontamination
  • 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)
  • 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
  • activated charcoal - with & without sorbitol
    • useful for salicylates, theophylline, benzodiazepines, carbamazepine & phenytoin overdoses
  • gastric decontamination CONTRAINDICATED ingestion of caustic agents
• 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
  • endotracheal intubation for airway compromise
• whole bowel irrigation
  • polyethylene glycol-electrolyte lavage solution to facilitate removal of ingested substances
  • indications
    • late presentation following ingestion
    • ingestion of sustained release pharmaceuticals
    • ingestion of toxic substances not removed by activated charcoal
    • foreign bodies
  • most commonly used for:
    • iron, lithium, cocaine packets, sustained release Ca+2 channel blockers
  • dosage:
    • 2 liters/hour for 5 hours (adults)
    • 500 mL/hr (children)
• specific antidotes
  • specific antidote available for very few toxins & is not always needed
  • duration of antidote may be shorter than duration of toxin activity
  • antidote therapy does not replace gastric decontamination
  • opiates
    • antidote: naloxone
    • start with 2 mg
    • nasal naloxone kits & training for their use by non-healthcare professionals saves lives
  • 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)
  • 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
  • organophosphate poisoning or carbamate insecticides
    • antidote: atropine & pralidoxime
    • atropine test dose: 2 mg IV
    • repeat in larger increments until drying of pulmonary secretions occurs
  • isoniazid
    • antidote: pyridoxine
    • give in gram per gram equivalent of what was ingested
    • start with 5 gm IV if amount ingested unknown
  • beta-blockers
    • antidote: glucagon
    • starting dose 5-10 mg IV
    • titrate to response (normalization of BP & HR)
    • maintenance dose of 2-10 mg/hr
  • tricyclic antidepressants (TCA)
    • antidote: bicarbonate
    • 1-2 mmol/kg for cardiac conduction delays or ventricular arrhythmias
    • titrate to response & pH 7.45-7.50
  • 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

• • 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
  • 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
  • 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
• hemodialysis may be useful for specific agents
• urine alkalinization
  • aspirin
  • phenobarbital
• consultation with regional poison control center
• National poison hotline (800) 222-1222

More general terms

• disease

More specific terms

• 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

Additional terms

• toxin (hazardous material, poison)