anticholinergic delirium

8/7/2019 Anticholinergic Delirium

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Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

Anticholinergic PoisoningAnticholinergic Poisoning

Andrew Dawson, Newcastle Mater Hospital

Robert Hoffman, New York Poison Centre


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BelladonnaBelladonna

Atropa belladonna

(Solanaceae)


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KineticsKinetics

Rapidly absorbed

Prolonged absorption in overdose

Large volume of distribution and rapid

distribution

Low hepatic clearance


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DynamicsDynamics

5 muscarinic subtypes:

Different tissue distributions with some

overlap

M1 receptors: CNS

M2 receptors:CNS 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 DeliriumAnticholinergic 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 56hours

Increased levels of staffing


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Treatment OptionsTreatment Options

Reassurance

Physical Containment

Sedation - benzodiazepines

Physostigmine

Close observation

Risk of medical complications


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PhysostigmPhysostigm

a venosuma venosum


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Efik LawEfik 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 andadded to water as a drink. If he is guilty, hismouth 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 aconcoction of excrement mixed in water which

has been used to wash the external genitalia of afemale.

Simmons 1952


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Hydrolysis of AcetylcholineHydrolysis of Acetylcholine

CH3 C

O

O CH2 CH2 N CH3

CH3CH3

+

Cholinesterase

Serine

Anionicsite

Esteraticsite

CH3 C

OH

O+

CH2 CH2 N CH3

CH3CH3


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? Anticholinesterases? Anticholinesterases

Name Selectivity Site of action

Tacrine BChase > AChase (x 4) Anionicg

Donepezil

AChase >> BChase (x

188) Anionicgp

Rivastigmine AChase = BChase Anionicg

& Esteraticg

Physostigmine BChase > AChase (x 2) Esteratic

Galantaminea

AChase > BChase (x 9) Esteraticgp


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First Use As An AntidoteFirst Use As An Antidote

Kleinwchter 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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2:30 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 BZsComparison of Physo and BZs Retrospective review of52 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 2000;35:374-381


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Pal in 1900Pal in 1900

Reverses CurareReverses Curare


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Tacrine in anticholinergicTacrine in anticholinergic

deliriumdelirium 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 / ResponseDefining Success / Response

Documented clinical resolution of symptoms

Patient as being described as being lucid

Shift in 1 level of care

Rank escription

0 o delirium

1 elirium no intervention

2 elirium reassurance only

3 elirium requires restraint


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Response DurationResponse Duration

The Mean duration of 1st response

Dose

mg

Duration

(hours)

15 1.48 0.10

30 4.21 0.89

45 3.19 1.45

60 5.58 2.60ny dose >15 4.20 0.74

anticholinergic delirium

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