Anticholinergic Poisoning

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Anticholinergic Poisoning

• Andrew Dawson, Newcastle Mater Hospital
• Robert Hoffman, New York Poison Centre

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Belladonna
Atropa belladonna (Solanaceae)
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Kinetics

• Rapidly absorbed
• Prolonged absorption in overdose
• Large volume of distribution and rapid
  distribution
• Low hepatic clearance

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Dynamics

• 5 muscarinic subtypes
• Different tissue distributions with some overlap
• M1 receptors CNS
• M2 receptorsCNS and heart
• M3 receptors Salivary glands
• M4 receptors Brain and lungs
• Different affinity at different receptors

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• Central Anticholinergic Syndrome
• Delirium (Hyperactive or Hypoactive)
• Seizures
• Peripheral Anticholinergic Syndrome
• thirst, dry mouth, dilated pupils, tachycardia,
  flushed face, slowed gastric emptying and
  decreased bowel sounds, dry skin, hyperthermia,
  urinary retention.

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Anticholinergic Delirium

• Acute confusional state
• Blockade of cholinergic muscarinic receptors
• Pure anticholinergic drugs
• Many psychiatric drugs
• Plants
• 40-50 admissions per annum
• Delirium doubles mean duration of stay to 56
  hours
• Increased levels of staffing

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Treatment Options

• Reassurance
• Physical Containment
• Sedation - benzodiazepines
• Physostigmine
• Close observation
• Risk of medical complications

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Efik People
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Physostigma venosum
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Efik Law

• Trial by ordeal
• Deadly esere
• Administration of the Calabar bean
• First observed by WF Daniell in 1840
• Later described by Freeman 1846 in a
  Communication to the Ethnological Society of
  Edinburgh

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• A suspected person is given 8 beans ground and
  added to water as a drink. If he is guilty, his
  mouth shakes and mucus comes from his nose. His
  innocence is proved if he lifts his right hand
  and then regurgitates.
• If the poison continues to affect the suspect
  after he has established his innocence, he is
  given a concoction of excrement mixed in water
  which has been used to wash the external
  genitalia of a female.
• Simmons 1952

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Hydrolysis of Acetylcholine
O
C
H
C
H
3
3
C
H
C
O
C
H
C
H
N
C
H
3
2
2
3

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? Anticholinesterases
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First Use As An Antidote

• Kleinwächter 1864
• 4 prisoners drank atropine solution thinking it
  was liquor
• 9AM estimated atropine dose 64 mg total
• One patient was asymptomatic (spat it out)
• Another had dilated pupils, with a normal pulse
  and temperature

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• 3 extreme drunkenness laughing, delirious,
  unable to speak coherently, flushed, dilated
  pupils, temp 38.7 oC, pulse 70/min, ? movement
  disorder.
• 4 Unable to stand, flushed, elevated
  temperature, tachypnea, very dilated pupils, dry
  mouth, coma alternating with agitation.

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• Tried ipecac, coffee, tannic acid and cinnamon
• Unable to give beer with tartar emetic
• Both patients deteriorated
• Gave Calabar extract (about 1 mg physostigmine)
  to 4, keep 3 as a control

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• 230 PM
• 4 was conscious, sitting up, able to answer
  questions. Pupils still dilated
• 3 unchanged
• Next day
• 4 Normal
• 3 Still poisoned

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Comparison of Physo and BZs

• Retrospective review of 52 patients with
  anticholinergic symptoms
• Physostigmine
• Controlled agitation 96
• Reversed delirium 87
• Benzodiazepines
• Controlled agitation 24
• Reversed delirium 9

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• Physostigmine
• Lower incidence of complications
• 7 vs 46
• Shorter recovery time
• 12 vs 24 hours
• No difference in side effects
• Burns et al Ann Emerg Med 200035374-381

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Pal in 1900 Reverses Curare
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Tacrine in anticholinergic delirium

• Unblinded Study
• 26 patients
• 15 Retrospective chart review clinical toxicology
  database
• 11 Prospective pilot study safety dose ranging
• Safety primary outcome
• Efficacy secondary outcome

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Defining Success / Response

• Documented clinical resolution of symptoms
• Patient as being described as being lucid
• Shift in 1 level of care

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Response Duration

• The Mean duration of 1st response