Anticholinergic Toxicity

Aka: Anticholinergic Toxicity, Anticholinergic Poisoning, Anticholinergic Symptoms, Anticholinergic, Anticholinergic Syndrome, Anticholinergic Reaction, Belladonna Poisoning, Antimuscarinic Poisoning, Antimuscarinic Toxicity

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II. Causes: General

  1. Medications (see below)
    1. See Anticholinergic Medications
    2. Antihistamines
    3. Tricyclic Antidepressants
    4. Phenothiazines
    5. Parasympatholytic medications
      1. Atropine
      2. Scopolamine
      3. Hyoscyamine
  2. Toxins
    1. Incapacitating Agents (e.g. BZ)
    2. Botulism (or infant bolulism)
      1. Foodborne Illness or Wound Infection
    3. Ingested items (Belladonna Poisoning)
      1. Jimsonweed or Thorn-Apple (Datura stramonium)
      2. Amanita muscaria mushrooms
      3. Deadly Nightshade
      4. Devil's Apple (Solanum linnaeanum)

III. Causes: Muscarinic Anticholinergic effects (most Anticholinergic first)

  1. Atropine (100% of maximal Anticholinergic effect)
  2. Scopolamine
  3. Tolterodine
  4. Hyoscyamine
  5. Cholinergic Parkinsonism agents
    1. Trihexyphenidyl
    2. Benztropine
  6. Prednisone (55%)
  7. Diphenhydramine (Benadryl)
    1. DiphenhydramineOverdose is responsible for >3% of U.S. Overdose deaths (within top 15 drugs)
    2. Mild Overdose
      1. Causes sedation and muscarinic Anticholinergic Toxicity (Dry Mouth, Tachycardia, Mydriasis)
    3. Severe Overdose
      1. Causes Agitation, Delirium, Hallucinations, Seizures and coma
      2. Diphenhydramine blocks myocardial Sodium and Potassium channels (Wide QRS, QTc Prolongation)
  8. Amitriptyline (Elavil)
  9. Digoxin
  10. Nifedipine
  11. Phenobarbital
  12. Oxybutynin (20%)
  13. Isosorbide Dinitrate
  14. Hydroxyzine
  15. Warfarin
  16. Dipyridamole
  17. Codeine
  18. Ranitidine (10%)
  19. Dyazide
  20. Furosemide (Lasix)
  21. Nortriptyline (3%)

IV. Symptoms: Mnemonic (antimuscarinic)

  1. Hot as a hare (Hyperthermia)
  2. Dry as a bone (Dry Skin)
  3. Red as a beet (Flushed)
  4. Blind as bat (Mydriasis)
  5. Mad as a hatter (Delirium)

V. Symptoms: Complete List (antimuscarinic)

  1. Altered Level of Consciousness
    1. Speech may be soft spoken, or a mumbling Word Salad
    2. Hallucinations
    3. Delirium
    4. Coma
  2. Seizures
  3. Sinus Tachycardia (may approach 150 bpm in adults)
  4. Hypertension
  5. Hyperthermia (typically low grade fever)
  6. Dry Skin
    1. Examine axilla and groin (where dryness is uncommon)
    2. Contrast with Sympathomimetic Toxicity in which skin is diaphoretic
  7. Dry Mouth
    1. Speech may sound muffled as if cotton balls are in mouth
  8. Mydriasis with Blurred Vision
  9. Decreased bowel sounds
  10. Constipation
  11. Urinary Retention

VI. Differential Diagnosis

  1. Sympathomimetic Toxicity
    1. Diaphoretic instead of Dry Skin
  2. Serotonin Syndrome
  3. Malignant Hyperthermia
  4. Neuroleptic Malignant Syndrome
  5. Agitated Delirium
  6. Encephalitis
  7. Sepsis

VII. Labs

  1. See Unknown Ingestion
  2. See Altered Level of Consciousness
  3. Creatine Kinase (CK)
    1. Monitor for Rhabdomyolysis with serial measurements

VIII. Diagnostics: Electrocardiogram

  1. Observe for EKG abnormalities (Intraventricular Conduction Delay)
    1. Prolonged QTc
    2. Wide QRS interval
  2. Exclude contraindications to Physostigmine (esp. Tricyclic Antidepressant Overdose)
    1. Bradycardia
    2. Intraventricular conduction delay (Wide QRS)
    3. AV Nodal block
    4. Terminal R (wide R Wave >3 mm) in AVR (suggests Sodium channel blockade, seen in TCA Overdose)

IX. Management

  1. Gastric Decontamination
    1. Indicated in specific ingestions (e.g. Diphenhydramine) presenting within 2 hours and no contraindications (e.g. ALOC)
  2. Agitation may require treatment
    1. See Sedation in Excited Delirium
    2. Preferred sedation agents
      1. Benzodiazepines
      2. Dexmedetomidine (Precedex)
      3. Propofol could also be used (short course)
    3. Avoid Physical Restraints
      1. Risk of worsening Rhabdomyolysis
    4. Avoid Antipsychotics (e.g. Haloperidol)
      1. Risk of upsetting Temperature Regulation (with worsening hyperthermia)
  3. Seizures
    1. See Status Epilepticus
    2. Benzodiazepines are preferred for Anticholinergic induced Seizures
      1. Lorazepam 0.1 mg/kg IV OR
      2. Diazepam 0.1 to 0.2 mg/kg IV
  4. Control hyperthermia
    1. Monitor Temperature
      1. Consider Temperature-sensing Foley Catheter
    2. Other measures refractory to Benzodiazepines and other Sedatives
      1. Paralysis could be considered (rare cases)
  5. Intravenous Fluids
  6. Intraventricular Conduction Delay on EKG
    1. Child or Teen with QRS interval > 100 ms, QTc Interval > 460 ms
    2. Administer Sodium Bicarbonate 1 mEq/kg IV and repeat as needed until improved QRS, QTc
      1. Initiate Sodium Bicarbonate infusion if more than 2 doses of Sodium Bicarbonate are needed
  7. Antidote: Physostigmine
    1. See Physostigmine for dosing and contraindications
    2. Repeat dosing may be needed (lasts only 30 minutes)
    3. Consider Physostigmine in cases of Altered Level of Consciousness and signs of Anticholinergic Toxicity
      1. Physostigmine will transiently reverse Anticholinergic effects and aid diagnosis in unclear cases
    4. Review contraindications before administration
      1. Obtain EKG prior to administration
        1. Exclude Bradycardia, intraventricular conduction delay or AV Nodal block
        2. Avoid in Tricyclic Antidepressant Overdose (risk of Asystole)
      2. Contraindicated in uncontrolled Asthma or Wheezing
      3. Contraindicated in Seizure Disorder
      4. Contraindicated in Bowel Obstruction
      5. Contraindicated in polysubstance Overdose
  8. References
    1. Claudius and Levine in Majoewsky (2012) EM:Rap 12(5): 7

X. References

  1. Orman and Hatten in Herbert (2016) EM:Rap 16(4): 6
  2. Swaminathan and Monas in Herbert (2020) EM:Rap 20(5):1
  3. Lacey and Dietrich (2023) Crit Dec Emerg Med 37(3): 18-9

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