Rivastigmine for the management of anticholinergic delirium

Figures & data

Table 1. Clinical characteristics and outcomes of 50 patients with anticholinergic delirium, who were treated by transdermal or oral rivastigmine.

	All patients (n = 50)	Rivastigmine transdermal (n = 22)	Rivastigmine oral (n = 28)	95% confidence interval of the difference between medians (topical vs oral)	(P value)*
Median age (years) [interquartile range]	36 [25–49]	40 [26–51]	35 [22–47]	−4–13	0.218
Male	23 (46%)	11 (50%)	12 (43%)		0.776
Ingested >1 anticholinergic agent	7 (14%)	3 (14%)	4 (14%)		> 0.999
Co-ingested ethanol and/or sedating agent	27 (54%)	13 (59%)	14 (50%)		0.577
Tachycardia (heart rate > 100 beats per minute)	45 (90%)	19 (86%)	26 (93%)		> 0.999
Median maximum heart rate (beats per minute) [interquartile range]	121 [109–131]	120 [110–130]	122 [108–132]	−11–9	> 0.999
Median maximum temperature (°C) [interquartile range]	37.1 [36.9–37.9]	37.6 [36.9–38.2]	37.1 [36.8–37.8]	−0.3–0.7	0.342
Median lowest Glasgow Coma Scale score [interquartile range]	12 [8–13]	11 [8–12]	12 [8–14]	−3–0	0.093
Urinary retention requiring an indwelling catheter	40 (80%)	20 (91%)	20 (71%)		0.154
Mydriasis	23 (46%)	10 (45%)	13 (46%)		> 0.999
Management prior to rivastigmine administration
Number administered parenteral sedation and/or physostigmine	44 (88%)	21 (95%)	23 (82%)		0.211
Number administered parenteral sedation	15 (50%)	8 (36%)	7 (25%)		0.536
Number administered physostigmine	43 (86%)	21 (95%)	22 (79%)		0.536
Median dose of physostigmine (mg) prior to rivastigmine [interquartile range]	2.4 [1.2–4]	3.6 [1.8–6]	1.8 [0.8–2.9]	0.4–2.8	0.009
Number physically restrained	14 (28%)	8 (36%)	6 (21%)		0.344
Rivastigmine administration
Time post-ingestion [interquartile range]	22.5 [12.8–28.7, n = 36]	23.8 [12.2–33.3, n = 17]	16.3 [13.0–29.7, n = 19]	−6.1–10.8	0.655
Time post-admission [interquartile range]	11.2 [3.9–16.9]	12.0 [3.9–20.3, n = 22]	10.1 [3.7–15.4, n = 28]	−3.0–7.4	0.494
Time post physostigmine [interquartile range]	2.0 [0.5–9.9, n = 43]	3.8 [0.8–12.3, n = 21]	0.9 [0.2–9.3, n = 22]	−4.5–0.3	0.108
Management post rivastigmine administration
Number administered parenteral sedation and/or physostigmine	25 (50%)	16 (73%)	9 (32%)		0.010
Number administered parenteral sedation	14 (28%)	10 (45%)	4 (14%)		0.025
Number administered physostigmine	19 (38%)	13 (59%)	6 (21%)		0.009
Median dose (mg) of physostigmine administered post rivastigmine [interquartile range]	2 [1.2–4.4]	3.6 [1.2–5.8]	1.4 [1.0–2.1]	−0.4–4.4	0.121

* Mann–Whitney for continuous data and Fisher’s exact test for categorical data.

Table 2. Anticholinergic agents ingested.

Drug ingested with anticholinergic effect	Number of patients* (n = 50)	Rivastigmine transdermal^^ (n = 22)	Rivastigmine oral^# (n = 28)
Quetiapine	17 (Extended release:11, immediate release:6)	7 (Extended release:4, immediate release:3)	10 (Extended release:7, immediate release:3)
Olanzapine	9	6	3
Promethazine	9	3	6
Benzatropine	6	3	3
Amitriptyline	5	3	2
Oxybutynin	3	1	2
Trihexyphenidyl	1	1
Clozapine	1	1
Dimenhydrinate	1		1
Doxylamine	1		1
Datura	1		1
Hyoscine	1		1

* Seven patients ingested more than one anticholinergic agent, ^{^}three patients ingested more than one anticholinergic agent, ^#four patients ingested more than one anticholinergic agent.

Figure 1. Sedation requirements in 50 patients after transdermal or oral rivastigmine administration for anticholinergic delirium.

Table 3. Pharmacokinetic and pharmacokinetic properties of physostigmine and rivastigmine.

	Physostigmine (IV)	Rivastigmine transdermal	Rivastigmine oral
Time to peak plasma concentration	3–8 min	8.0 h	0.8–1.4h
Half-life	15–40 min	Continuous patch	1.3–1.9 h
Time to peak acetylcholinesterase inhibition	5–30* min	8–16 h (decreases with increasing dose)	2–6 h
Duration of acetylcholinesterase inhibition	40–90* min	Sustained over patch application. Once removed: 3.4 h	Up to 8.5 h

* = animal (rat) data [1,3,16–22]

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