anticholinergic delirium
TRANSCRIPT
-
8/7/2019 Anticholinergic Delirium
1/25
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
Anticholinergic PoisoningAnticholinergic Poisoning
Andrew Dawson, Newcastle Mater Hospital
Robert Hoffman, New York Poison Centre
-
8/7/2019 Anticholinergic Delirium
2/25
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
BelladonnaBelladonna
Atropa belladonna
(Solanaceae)
-
8/7/2019 Anticholinergic Delirium
3/25
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
KineticsKinetics
Rapidly absorbed
Prolonged absorption in overdose
Large volume of distribution and rapid
distribution
Low hepatic clearance
-
8/7/2019 Anticholinergic Delirium
4/25
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
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
-
8/7/2019 Anticholinergic Delirium
5/25
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
-
8/7/2019 Anticholinergic Delirium
6/25
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
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.
-
8/7/2019 Anticholinergic Delirium
7/25
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
-
8/7/2019 Anticholinergic Delirium
8/25
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
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
-
8/7/2019 Anticholinergic Delirium
9/25
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
Treatment OptionsTreatment Options
Reassurance
Physical Containment
Sedation - benzodiazepines
Physostigmine
Close observation
Risk of medical complications
-
8/7/2019 Anticholinergic Delirium
10/25
-
8/7/2019 Anticholinergic Delirium
11/25
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
PhysostigmPhysostigm
a venosuma venosum
-
8/7/2019 Anticholinergic Delirium
12/25
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
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
-
8/7/2019 Anticholinergic Delirium
13/25
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
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
-
8/7/2019 Anticholinergic Delirium
14/25
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
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
-
8/7/2019 Anticholinergic Delirium
15/25
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
? 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
-
8/7/2019 Anticholinergic Delirium
16/25
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
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
-
8/7/2019 Anticholinergic Delirium
17/25
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
#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.
-
8/7/2019 Anticholinergic Delirium
18/25
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
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
-
8/7/2019 Anticholinergic Delirium
19/25
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
2:30 PM:
#4 was conscious, sitting up, able to answer
questions. Pupils still dilated
#3 unchanged
Next day
#4 Normal
#3 Still poisoned
-
8/7/2019 Anticholinergic Delirium
20/25
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
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%
-
8/7/2019 Anticholinergic Delirium
21/25
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
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
-
8/7/2019 Anticholinergic Delirium
22/25
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
Pal in 1900Pal in 1900
Reverses CurareReverses Curare
-
8/7/2019 Anticholinergic Delirium
23/25
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
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
-
8/7/2019 Anticholinergic Delirium
24/25
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
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
-
8/7/2019 Anticholinergic Delirium
25/25
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
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