a b s t r a c t

Introduction: Treatment for pain and related conditions has been identified as the most common reason for Emer- gency Department (ED) visits. Concerns exist regarding the effects of opioid pain medications on cognition and patient ability to consent for procedures, hospital admission, or to refuse recommended medical interventions. This study was undertaken to identify cognitive skills before and after opioid pain medication in the ED setting. Methods: This was a prospective study comparing performance on the Mini-Mental Status Examination (MMSE) and Montreal Cognitive Assessment (MoCA) before and after administration of opioid pain medications. Eligible participants included ED patients with pain, who received opioid treatment. Participants were randomized to re- ceive either the MMSE before pain medication and the MoCA after medication, or the reverse. MoCA scores were converted to MMSE equivalent scores for comparison.

Results: Among 65 participants, the median age was 36 and median triage pain score was 8. 35% of patients were considered cognitively impaired based on their MMSE score prior to any opioid medication (MMSE b 27). There was a median decrease in pain scores of 1 point following pain medication, p-value b 0.001. There was a median decrease in MMSE scores of 1 point following pain medication, p-value = 0.003. The range of change in scores (post minus pre) on the MMSE-equivalent was -7 to 3. 35 patients (56%) had a decrease in scores, 6 (10%) had no change, and 21 (34%) had an increase. After medication, 31 (48%) were abnormal (MMSE score b 27). No differences in MMSE scores were identified by gender, ethnicity, mode of arrival, insurance, age, triage pain scores, opioid agent given, or ED diagnosis.

Conclusions: There is an association between opioid pain medication and decrease in cognitive performance on the MMSE. Because of the wide range of cognitive performance following opioid pain medication, assessment of individual patients’ Cognitive function is indicated.

(C) 2017

Introduction

Treatment for pain and related conditions has been identified as the most common reason for Emergency Department (ED) visits [1]. Effec- tive pain management results in improved patient satisfaction, reduced anxiety, and improved comfort. However, concern exists regarding the effects of opioid pain medications on cognition and patient ability to consent for procedures, hospital admission, or other recommended medical interventions.

decisional capacity is an essential element of informed consent or refusal of treatment, and refers to the ability to make an authentic choice. Decisional capacity is affected by cognitive and affective

* Corresponding author.

E-mail address: [email protected] (C.A. Marco).

functions, including attention, intellect, memory, judgment, insight, lan- guage, emotion, and calculation. Impaired decisional capacity may re- sult from disruption of any of the essential elements: the ability to receive, process, and understand information, the ability to deliberate, or the ability to communicate a decision. Numerous conditions and cir- cumstances may impair decisional capacity, including dementia [2,3], intoxication, psychiatric conditions, minors [4,5], language impairment, cultural issues, physical communication impairments, severe pain, or- ganic Disease states [6,7], and numerous other conditions [8,9]. Some studies have demonstrated variable effects of opiate and benzodiaze- pine medications on cognition [10-17]. A recent literature search did not identify any published studies demonstrating the effects of pain medications on cognition and decisional capacity among ED patients (Pub Med, key words pain emergency cognition capacity).

A standardized test of cognitive performance is the Mini-Mental State Examination (MMSE) [18-20]. The MMSE tests cognitive functions

https://doi.org/10.1016/j.ajem.2017.11.017

0735-6757/(C) 2017

including orientation, recall, attention, calculation, language and con- structional praxis. The maximum score is 30. Authors have suggested that a score of 24 or less is suggestive of dementia or delirium.

A second standardized test which is also easily administered in emergency medicine is the Montreal Cognitive Assessment (MoCA). This test is considered at least as sensitive as the MMSE in a variety of clinical conditions, and can be converted to MMSE-equivalent scores [21-24].

This study was undertaken to identify cognitive skills before and after opioid pain medication in the ED setting, through standardized as- sessment using the MMSE and MoCA.

Methods

This prospective, before and after observational study was approved by the Wright State University Institutional Review Board (IRB). This study was conducted at Miami Valley Hospital, a Level 1 Trauma Center, in Dayton, Ohio. Consecutive patients were enrolled as a convenience sample, when a research assistant was available. Data were collected from November of 2015 through August of 2017.

Inclusion criteria included all adult ED patients receiving an opioid pain medicine with an initial pain score N 5. Exclusion criteria included:

Results

Fig. 1. Cognitive functioning pre and post pain medication.

age (b 18 years old), patients that were severely distressed or unable to communicate, and patients who chose not to participate. Patients did not receive any compensation to participate, and all participants were ensured anonymity.

Following verbal consent, cognitive assessments were conducted by trained research assistants in patient care rooms before and after receiv- ing treatment for pain. Permission was obtained from MoCA Clinic & In- stitute for the use of MoCA in this study. To avoid the previously described learning effect of multiple administrations of the MMSE [25], the MMSE was administered to each patient once (either pre med- ication or post medication) and the MoCA was administered once (ei- ther pre or post); but both tests were not given to the same patient to avoid a learning-effect. The MMSE and MoCA exams were randomly ad- ministrated so that each patient would receive both exams, either be- fore or after treatment.

Data obtained during the cognitive assessment were collected into a spreadsheet. Data included: demographic information (age, gender, ethnicity), mode of arrival to the ED, current insurance, triage vitals and pain score, ED Diagnosis, type of pain medicine, dosage, and time

Among 69 eligible participants, 65 consented to participate (94% participation rate). Participants were 58% female and 62% White (Table 1). Median triage pain score was 8.

opioid medications administered included morphine, fentanyl and hydromorphone. Before medication, 35% of the patients were consid- ered cognitively impaired based on their MMSE score. Following opioid medication, there was a median decrease in pain scores of 1 point. There was a median decrease in MMSE scores of 1 point. The range of scores (post minus pre) on the MMSE-equivalent was -7 to3 (Table 2). 35 pa- tients (56%) had a decrease in scores, 6 (10%) had no change, and 21 (34%) had an increase (Fig. 2).

Categorically, a MMSE cut-off score of 27 was used to categorize pa- tients as abnormal (b 27) or normal (>= 27). Before medication, 22 (35%) of patients were abnormal. After medication, 31 (48%) were abnormal.

Table 1

Patient characteristics.

of medication and assessments, and MoCA and MMSE scores.		No. patients	%
	Day of week
	Sun	3	5%
2.1. Statistical methods	Mon	14	22%
	Tues	8	12%
Categorical data were described with frequency and percentage. Continuous data were described with median and interquartile range	Wed Thurs Fri	11 14 11	17% 22% 17%
(25th to 75th percentiles). The within-person change in pain was tested	Sat	4	6%

with a Signed Rank two-sided test.

Gender
Male	27	42%
Female	38	58%
Ethnicity

Cognitive functioning was measured with the Mini-Mental State Exam (MMSE) and the Montreal Cognitive Assessment (MoCA). Both

tests are scored between 0 and 30 points. At random, 32 of the patients	African American	23	35%
received the MMSE pre and MoCA post; 33 patients received the MMSE post and MoCA pre. For data analysis, MoCA scores are converted to MMSE scores using a conversion table published by Bergeron et al.	White Multiracial Mode of arrival in ED Walk-in	40 2 51	62% 3% 78%

[26]. Three patients had a MoCA score b 14 and we were unable to ob- tain a converted MMSE score per the conversion table. The change in MMSE pre to post was tested with a Signed Rank two-sided test (Fig. 1). Difference in MMSE scores between subgroups of patients (e.g., Males and females) was tested with Mann Whitney Wilcoxon tests. spearman correlation coefficient was used to explore the relationship between MMSE and age and triage pain. p-Values b 0.05 were used to indicate statistical significance. Data were analyzed with SAS v9.4 (SAS

Ambulance Insurance status	14	22%
Selfpay	5	8%
Private insurance	15	23%
Medicare	3	5%
Medicaid	35	54%
Government insurance	2	3%
Workman’s comp	0	0%
Medicare & Medicaid	1	2%
Other	4	6%

Institute, Cary NC).

Table 2

Change in pain and cognitive performance pre and post medication.

N^a Median (25th-75th pctl) Mean (95% CI) p-Value^b

Pre pain score	64	9 (7 to 10)	8 (8 to 9)
Post pain score	64	7 (5 to 8)	6 (6 to 7)
Within-patient change in pain score (post – pre)	63	-1 (-3 to 0)	-2 (-2 to -1)	b0.001
Pre MMSEb score	63	27 (26 to 28)	27 (26 to 27)
Post MMSE score	64	27 (25 to 28)	26 (25 to 27)
Within-patient change in MMSE score (post – pre)	62	-1 (-2 to 1)	-1 (-2 to 0)	b0.003

^a 3 patients with MoCA score b 15 could not be used for analyses due to no conversion value in MoCA-MMSA tables.

^b Signed Rank two-sided p-value is reported for within-patient change. MoCA scores were converted to predicted MMSE scores.

Fig. 2. Distribution of change in MMSE scores post-pre.

Gender, ethnicity, mode of arrival, insurance, age and triage pain scores were not significantly associated with pre-medication cognitive performance on the MMSE (Table 3).

There were no differences in post MMSE scores by drug adminis- tered (Table 4) (Note small sizes from some of the drugs). There were no significant differences in pre, post, nor change in MMSE between ED diagnoses (Table 5).

Table 3

Factors associated with pre medication cognitive performance.

Discussion

Pain is one of the most common complaints in the ED, and the relief of painful conditions is an important component in emergency care. Pain is defined by The International Association for the Study of Pain as an “un- pleasant sensory or emotional experience associated with actual or po- tential tissue damage, or described in terms of such damage.” [27]. Pain is a complex subjective experience that can have a marked negative im- pact on both the psychological and physical state of an individual. It is also extraordinarily subjective and variable between age, gender, and culture, and is affected by multiple social and behavioral factors [28].

Multiple studies have demonstrated that both acute and chronic

Gender

No. patients Pre MMSE Median (IQR)

p-Value

pain can impair cognitive abilities. Cognition is a broad term and is used to define multiple integrative neuropsychological processes such as perception, problem solving, attention, emotion, affect, speed of in- formation processing, psychomotor ability and executive function. Pain has also been demonstrated to affect a person’s ability to multitask and can have significant deleterious effects on attention [29-31]. Pa- tients who self-report greater cognitive effects of chronic pain indeed demonstrate decreased task-switching abilities.

A significant percentage of patients presenting to the Emergency De- partment receive intravenous or intramuscular opiate pain medications

Table 4

Male	27	27 (25 to 29)	0.79
Female Ethnicity African American	36 22	27 (26 to 28) 28 (25 to 28)	0.93
White (Multiracial not included in analysis)	39	27 (26 to 29)
Mode of arrival in ED Walk-in	50	27 (26 to 28)	0.26
Ambulance Insurance status Selfpay	13 20	26 (24 to 28) 28 (27 to 29)	0.09
Private insurance Medicare	39	27 (25 to 28)
Medicaid Government insurance Workman’s comp

Post medication cognitive performance, by drug.

Pain medications administered in ED

No. patients Post MMSE

Median (IQR)

p-Value

Spearman correlation with Pre MMSE (p-Value)

Age (years) -0.17 (0.19)

Triage pain score 0.08 (0.55)

Morphine 32 27 (24 to 28) 0.90

Fentanyl 16 26 (25 to 28)

Dilaudid 6 26 (25 to 28)

Other 10 28 (25 to 28)

Table 5

Pre and post medication cognitive performance and change in MMSE scores, by ED diagnosis.

ED diagnosis	No. patients	Median (IQR)
		Pre MMSE	Post MMSE	Change
GI	22	27 (26 to 28)	26 (25 to 28)	-1 (-3 to 0)
GU	9	28 (27 to 29)	26 (25 to 28)	-2 (-3 to 1)
Musculoskeletal pain	9	27 (26 to 28)	28 (27 to 28)	1 (1 to 2)
Other	8	28 (25 to 29)	28 (25 to 29)	-1 (-3 to 1)
Procedure	3	26 (24 to 27)	22 (20 to 24)	-3 (-3 to -2)
Sickle cell	3	29 (25 to 29)	26 (22 to 28)	-3 (-3 to -1)
Trauma Kruskal Wallis p-value looking for difference among any of the categories Trauma	11 11	26 (24 to 29) 0.64 26 (24 to 29)	27 (24 to 28) 0.24 27 (24 to 28)	0 (-1 to 1) 0.08 0 (-1 to 1)
Not trauma	54	27 (26 to 28)	26 (25 to 28)	-2 (-3 to 1)
Kruskal Wallis p-value comparing trauma to non-trauma		0.24	0.94	0.28

during their visit. Indeed, recent CMS outpatient core measures (OP 21) require documentation of analgesic administration in a time-dependent manner for documented long bone fractures. There is a paucity of studies detailing the effects of opiate analgesics on the cognitive capa- bilities of patients receiving these medications. Particularly in the ED setting, studies involving opiate analgesia have focused on safety and not decision-making capability. High-dose meperidine was assessed for safety and alertness scale effects during procedural sedation. While a statistically significant difference in the alertness scale was noted, cognitive ability was not assessed [32]. Another study identified minimal impairment of cognitive and psychomotor function after a single dose of morphine [33]. A study evaluating the effects of cogni- tive function following butorphanol and dezocine on elderly postoper- ative patients did employ the MMSE as a measurement tool, and identified statistically significant decreases in MMSE scores 6 hour postoperative when butorphanol alone was administered, compared to butorphanol plus dezocine [34]. Another study of analgesia provid- ed by administration of Intravenous morphine and hydromorphone did not address cognitive effects [35]. As patients may be asked to pro- vide consent or make other medical decisions after these medications have been administered, we sought to quantify the effects of opiate analgesics on cognition using changes in cognition based on perfor- mance on the MMSE and MoCA.

In this study, we found a high incidence (35%) of cognitive impair- ment prior to the administration of opioid medication. This may be due to the effects of pain on cognition; alternatively, this may be due to patient characteristics, medications, or other substances used prior to study participation.

We identified a median decrease in pain scores of 1 point following opioid medication, indicating a modest Therapeutic effect [36]. There was a median decrease in MMSE-equivalent scores of 1 point, with a wide range of -7 to 3. This wide range of effects on cognition demon- strates the importance of individual patient assessment of cognition and ability to participate in medical decision-making.

4.1. Limitations

There may be some inaccuracies in assessment due to the use of 2 different cognitive tests. The conversion table for MoCA to MMSE was chosen because it had better accuracy. The conversion table was based on patients from memory clinics in Canada and may not translate the same into the population of Emergency Department patients seeking care for painful diagnoses. Results from this study may not be generaliz- able to individual patients.

Conclusions

There is an association between opioid pain medication and de- crease in cognitive performance on the MMSE. Because of the wide

range of cognitive performance following opioid pain medication, as- sessment of individual patients’ cognitive function is indicated.

Acknowledgement

The authors wish to thank Nancy Buderer, MS, for her assistance with statistical analysis.

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