Cognitive impairment following sedative overdose

Figures & data

Figure 1. Comparison of patient age between the sedative and non-sedative groups.

Table 1. Characteristics of the sedative and non-sedative groups.

	Sedative group (n = 111)	Non-sedative group (n = 60)	Significance (P)
Number (%) male	65 (58.6)	22 (36.7)	0.006
Median age (IQR; range)	32.1 (22.8–42.8; 16.5–78.2)	22.2 (17.9–33.5; 16.3–77.3)	0.011
Median (IQR, range) education (years)*	13. (11–15, 7–18)	13 (12–15, 10–18)	0.389
Number (%) with major psychiatric diagnosis	60 (54.1)	36 (60.0)	0.455
Median time from exposure to testing in hours (IQR; range)^+	18.4 (12.0–29.7; 5.2–101.3)	16.8 (13.1–30.8, 4.2–299.8)	0.838
Number (%) with alcohol co-ingestion*	58 (56.3)	28 (54.9)	0.868
Number (%) with intent for suicide or self-harm	57 (51.4)	34 (56.7)	0.506
Number (%) medically sedated	23 (20.7)	12 (20.0)	0.911
Number (%) with known dose ingested	64 (57.5)	34 (56.7)

IQR = Interquartile range. Significant (P < 0.05) difference between groups highlighted in bold.

* Not all patients reported their years of education or alcohol consumption status. ⁺Mann-Whitney U test used to determine significance due to non-parametric distribution.

Figure 2. Scatter plot demonstrating Trail Making Test part A time for patients with sedative versus non-sedative overdose. Horizontal bars represent the median and interquartile range for each group.

Figure 3. Scatter plot demonstrating Trail Making Test part B time for patients with sedative versus non-sedative overdose. Horizontal bars represent the median and interquartile range for each group.

Table 2. Comparison of trail making test parts A and B, and duration of admission, between the sedative and non-sedative groups.

	Sedative				Non-sedative
	n	Median	Interquartile range	Range	n	Median	Interquartile range	Range	P
Trail Making Test part A (seconds)*	111	37.0	29.7 to 50.1	14.2 to 123.2	60	33.1	25.1 to 43.4	12.1 to 75.2	0.017
Trail Making Test part B (seconds)	102	112.4	79.3 to 161.3	31.0 to 300.0	56	81.5	66.3 to 107.9	33.0 to 300.0	0.003
Admission duration (hours)*	111	14.2	8.4 to 21.0	1.5 to 100.2	60	13.4	10.4 to 20.6	2.2-124.9	0.932

* Mann-Whitney U test used to determine significance due to non-parametric distribution. Significant (P < 0.05) difference between groups highlighted in bold.

Table 3. Comparison of Trail Making Test parts A and B between those whose overdose included benzodiazepines or did not, within the sedative group.

	Overdose including benzodiazepines				Overdose not including benzodiazepines
	n	Median	Interquartile range	Range	n	Median	Interquartile range	Range	P
Trail Making Test part A (seconds)	52	43.0	31.0 to 60.3	14.2 to 123.2	59	35.7	28.4 to 47.1	18.0 to 99.0	0.031
Trail Making Test part B (seconds)	50	137.8	85.7 to 175.1	31.0 to 300.0	52	91.0	72.2 to 149.3	37.8 to 300.0	0.025

* Mann-Whitney U test used to determine significance. Significant (P < 0.05) difference between groups highlighted in bold.

Table 4. Final regression models of sedative versus non-sedative overdose for trail Making Test part B time. Model created using multiple linear regression refined by backwards elimination method with missing data treated pairwise.

		Contributing variables												Overall model
Model		Overdose type			Age			Perception of recovery			Any sedative exposure					Model significance P
	n	P	Time estimate	95% confidence interval	P	Time estimate	95% confidence interval	P	Time estimate	95% confidence interval	P	Time estimate	95% confidence interval	Adjusted R^2	F
Causative factors Trail Making Test part B	157	0.032	24.020	2.093-45.948	<0.001	1.626	0.886–2.367	NA	NA	NA	NA	NA	NA	0.143	14.136	<0.001
Predictive factors Trail Making Test part B	111	NA	NA	NA	<0.001	1.716	0.871–2.561	0.006	36.368	10.767–61.969	0.017	32.522	5.995–59.049	0.207	10.659	<0.001

NA = not applicable. Significance (P < 0.05) indicated by bold. Time estimate is in number of seconds between categories or per year of age. Patients who perceived they were recovered, or who had not received sedation, performed better on the Trail Making Test part B. Adjusted R2: the proportion of variance in the model explained by the independent variables and corrected for the number of independent variables entered. F: compares the ratio of explained variance to unexplained variance. It determines whether the examined regression model as a whole, or the intercept-only model, is more strongly associated with the outcome.

Two models were created.

The first comprised factors that could potentially contribute to Trail Making Test times: type of overdose, age, gender, time since the overdose, suicide or self-harm intent, medical sedation administration, years of education, mental health diagnosis, or concurrent alcohol use with the overdose.

The second model reported factors at the time of discharge that accounted for the largest adjusted R² including patient perception of recovery and a variable that included sedative overdose and/or medical sedation administration rather than the two datapoints separately.

Table

Drug name	Category	Defined daily dose	Number	Comments
Alprazolam	Sedative	1mg	17
Amitriptyline	Sedative	75mg	1
Amlodipine	Neither	5mg	1
Amyl Nitrite	Neither	Not applicable	2
Aripiprazole	Sedative	15mg	1	Defined daily dose as an antipsychotic
Aspirin (acetylsalicylic acid)	Neither	3g	1
Benzatropine	Sedative	2mg	1
Bleach (sodium hypochlorite)	Neither	Not applicable	2
Bromazepam	Sedative	10mg	1
Bromhexine	Neither	24mg	1
Buprenorphine	Sedative	1.2-8mg	2
Caffeine	Stimulant	400mg	2
Carbon monoxide	Neither	Not applicable	3
Cefalexin	Neither	2g	1
Citalopram	Neither	20mg	3
Clonazepam	Sedative	8mg	3
Clozapine	Sedative	300mg	2	Defined daily dose as an antipsychotic. Sedation would be expected at much lower doses when drug naïve or during titration.
Cocaine	Stimulant	Not applicable	23
Codeine	Sedative	100mg	1	The defined daily dose for codeine is listed as a cough suppressant and would not be expected to cause sedation at twice this dose. There is no indicated defined daily dose for analgesia, however standard preparations are supplied as 240 mg/day (in combination with paracetamol). Hence 240 mg has been used in place of the defined daily dose.
Desvenlafaxine	Neither	50mg	2
Dexamfetamine	Stimulant	15mg	1
Dextromethorphan	Sedative	90mg	1
Diazepam	Sedative	10mg	25
Diclofenac	Neither	100mg	2
Dimenhydrinate	Sedative	300mg	2
Diphenhydramine	Sedative	200mg	1
Doxylamine	Sedative	25mg	2
Duloxetine	Neither	60mg	3
Epsom salts (magnesium sulfate)	Neither	3g	1
Escitalopram	Neither	10mg	1
Fentanyl	Sedative	0.6-1.2 mg	1
Fluoxetine	Neither	20mg	6
Fluvoxamine	Neither	100mg	3
Gamma hydroxybutyrate (GHB)	Sedative	Not applicable	17
Guaifenesin	Neither	900mg	1
Heroin (diamorphine)	Sedative	Not applicable	5
Hyoscine hydrobromide (scopolamine)	Sedative	0.9 mg	1
Ibuprofen	Neither	1200mg	9
Ketamine	Sedative	Not applicable	2
Lamotrigine	Sedative	300mg	2
Lithium	Neither	24mmol	4
Lorazepam	Sedative	2.5 mg	2
Lysergic acid diethylamide (LSD)	Neither	Not applicable	6
Marijuana	Sedative	Not applicable	7
MDMA (3,4-methylenedioxymetamfetamine)	Stimulant	Not applicable	5
Melatonin	Sedative	2mg	2
Metformin	Neither	2g	1
Methadone	Sedative	25mg	4
Metamfetamine	Stimulant	Not applicable	19
Metoclopramide	Neither	30mg	1
Mirtazapine	Sedative	30mg	2
Naproxen	Neither	500mg	1
Nitrazepam	Sedative	5mg	1
Nortriptyline	Sedative	75mg	1
Novorapid (insulin aspart)	Neither	40 units	1
Estrogens	Neither	N/A	1
Olanzapine	Sedative	10mg	5	Defined daily dose as an antipsychotic
Oxazepam	Sedative	50mg	3
Oxycodone (endone, oxycontin)	Sedative	75mg	1
Paracetamol	Neither	3g	31
Pentoxifylline	Stimulant	1000mg	1
Periciazine	Sedative	50mg	1	Defined daily dose as an antipsychotic
Perindopril	Neither	4mg	1
Phentermine	Stimulant	15mg	1
Pregabalin	Sedative	300mg	4
Prochlorperazine	Sedative	100mg	1	Defined daily dose as an antipsychotic; however it is not licensed in Australia as such and the usual maximum dose is 40 mg daily. Consequently, twice the maximum dose was used as our acceptance cutoff.
Promethazine	Sedative	25mg	6
Psilocybe cubensis	Stimulant	Not applicable	2
Quetiapine	Sedative	400mg	10	Defined daily dose as an antipsychotic
Ramipril	Neither	2.5 mg	1
Sertraline	Neither	50mg	5
Tapentadol	Sedative	400mg	1
Telmisartan	Neither	40mg	1
Temazepam	Sedative	20mg	4
Tramadol	Sedative	300mg	2
Valproic acid (sodium valproate)	Sedative	1.5g	1
Venlafaxine	Neither	100mg	4
Zolpidem	Sedative	10mg	3
Zopiclone	Sedative	7.5 mg	1

Notes: Some patients were poisoned with multiple agents, consequently the sum of patients in each category is greater than the total number of participants. The defined daily dose was extracted from the World Health Organization ATC/DDD Index (2023). World Health Organization Collaborating Centre for Drug Statistics Methodology, Norwegian Institute of Public Health, Oslo, available from https://www.whocc.no/atc_ddd_index/. Comments outline deviations in this study from use of twice the defined daily dose for definition of poisoning.

Data availability statement

The participants of this study did not give written consent for their data to be shared publicly, so due to the sensitive nature of the research supporting data is not available.