Safety and effectiveness of physostigmine: a 10-year retrospective review^*

Figures & data

Figure 1. Flow diagram of poison center cases identified with mention of physostigmine and demographics of included patients.

Table 1. Presenting signs and symptoms.

Presenting sign/symptom	n	%^a
Anticholinergic delirium^b
Agitation	113	59.1
Altered mental status	99	51.8
Hallucinations	97	50.8
Drowsiness	1	0.5
Obtundation	1	0.5
Tachycardia	163	85.3
Mydriasis	105	55.0
Dry skin	49	25.7
Hyperthermia	31	16.2
Urinary retention	8	4.2
Seizure	13	6.8
QTc prolongation^c	8	4.2
QRS prolongation^d	3	1.6
QRS and QTc prolongation^e	1	0.5

^a Reflects percentage of total included patients (n = 191).

^b All patients (n = 191) presented with at least one symptom of anticholinergic delirium (including agitation, altered mental status, hallucinations, drowsiness, obtundation). Patients may have exhibited more than one symptom.

^c QTc prolongation defined as a QTc >450 ms, or as stated in the text of the CPCS record.

^d QRS prolongation defined as QRS >100 ms or as stated in the text of the CPCS record.

^e Patients with both QRS and QTc prolongation, as defined above.

Table 2. Patients with response to initial dose of physostigmine, defined as an improvement or normalization of mental status with associated odds ratio (or), 95% confidence intervals (95% CI), and p values.

Causative substance category	n (%)^a	Responded to physostigmine n (%)^b	OR (95% CI)	p
Anticholinergic plant^c	67 (35.1)	46 (68.7)	0.70 (0.36–1.35)	.29
Diphenhydramine	56 (29.3)	43 (64.2)	1.30 (0.63–2.68)	.48
Other antihistamine^d	14 (7.3)	14 (100)	–	–
Combination products^e	10 (5.2)	8 (80)	1.48 (0.30–7.24)	.62
Muscle relaxants^f	4 (2.1)	3 (75)	1.09 (0.11–10.77)	.94
Antipsychotics^g	4 (2.1)	4 (100)	–	–
Tricyclic antidepressants^h	3 (1.6)	3 (100)	–	–
Other	16 (8.4)	8 (50)	0.33 (0.12–0.92)	.03
Unknown	17 (8.9)	11 (64.7)	0.64 (0.22–1.83)	.40
Totals	191	140 (73.3)

^a Percentage of all included patients (n = 191).

^b Percentage of patients in each substance category.

^c Plant species included: “Jimson weed”, “Datura”, “Angels trumpet”, “belladonna”, “brugmansia”, “Hells bells”, “Trumpet flower”, “unknown plants”.

^d Drugs included: Dicyclomine, benztropine, chlorpheniramine, cyproheptadine, hydroxyzine, and orphenadrine.

^e Products included: Tylenol PM^®, Excedrin PM^®.

^f Products included: Alprazolam, baclofen, cyclobenzaprine.

^g Products included: Olanzapine, quetiapine.

^h Products included: Amitriptyline.

Table 3. Patients requiring repeat doses of physostigmine.

Causative substance category	n (%)^a	Required repeat dose of physostigmine n (%)^b
Anticholinergic plant^c	67 (35.1)	27 (40.3)
Diphenhydramine	56 (29.3)	20 (35.7)
Other antihistamine^d	14 (7.3)	7 (50)
Combination products^e	10 (5.2)	2 (20)
Muscle relaxants^f	4 (2.1)	1 (25)
Antipsychotics^g	4 (2.1)	3 (75)
Tricyclic antidepressants^h	3 (1.6)	1 (33)
Other	16 (8.4)	3 (18.8)
Unknown	17 (8.9)	5 (29.4)
Totals	191	69 (36.1%)

^a Percentage of all included patients (n = 191).

^b Percentage of patients in each substance category.

^c Plant species included: “Jimson weed”, “Datura”, “Angels trumpet”, “belladonna”, “brugmansia”, “Hells bells”, “Trumpet flower”, “unknown plants”.

^d Drugs included: Dicyclomine, benztropine, chlorpheniramine, cyproheptadine, hydroxyzine, and orphenadrine.

^e Products included: Tylenol PM^®, Excedrin PM^®.

^f Products included: Alprazolam, baclofen, cyclobenzaprine.

^g Products included: Olanzapine, quetiapine.

^h Products included: Amitriptyline.

Table 4. Reasons physostigmine dose was not repeated during hospitalization based upon review of CPCS records.

Reason physostigmine was not repeated during hospitalization	n	%^a
Improved delirium
No additional agents required^b	50	44.2
Additional sedation required	11	9.7
Resolution of delirium	23	20.4
Delirium not improved with physostigmine	13	11.5
Intubation^c	10	8.8
Adverse reaction following physostigmine
Seizure	2	1.8
Emesis	1	0.9
Unknown	3	2.7

^a Percentage of patients who did not receive additional doses of physostigmine (n = 113).

^b Additional agents required for sedation, including benzodiazepines or neuroleptics.

^c Includes patients who were intubated prior to receiving physostigmine or after physostigmine failed to improve delirium.

Figure 2. Odds ratios for response to physostigmine by substance category. Substances with 100% response rates were excluded.

Table 5. Reported adverse events following physostigmine administration.

Adverse events	n	%^a
None	182	95.3
Emesis	4	2.1
QTc prolongation^b	2	1.0
QRS prolongation^c	0	0
Seizure	2	1.0
Death	1	0.5

^a Percentage of all included patients (n = 191).

^b QTc prolongation defined as a QTc >450 ms, or as stated in the text of the CPCS record.

^c QRS prolongation defined as QRS >100 ms or as stated in the text of the CPCS record.

Table 6. Doses of physostigmine, by substance category of primary ingestant.

	Total initial physostigmine dose (mg)
Substance category, n^a	Mean	Median	Range
Anticholinergic plant, 44	1.12	1.0	0.5–2
Diphenhydramine, 33	1.25	1.0	0.5–4
Non-diphenhydramine antihistamine, 12	1.33	1.25	0.25–4
Combination products, 6	1.46	1.38	1.25–2
Muscle relaxants^b, 2	1.0	–	1.0
Tricyclic antidepressants^b, 2	1.75	–	1.5–2
Other, 8	1.03	1.0	0.5–2
Unknown, 12	1.31	1.0	0.5–2

^a Numbers of cases for which dosages are known.

^b Median could not be calculated, only two values were available.