Neurology

Delirium, confusion, or altered mental status as a risk for abnormal head computed tomogram findings in older adults in the emergency department: A Geriatric Emergency Department Guidelines 2.0 systematic review and meta-analysis

a b s t r a c t

Background: Altered mental status (including delirium) is a common presentations among older adults to the emergency department (ED). We aimed to report the association between altered mental status in older ED pa- tients and acute abnormal findings on head computed tomogram (CT).

Methods: A systematic review was conducted using Ovid Medline, Embase, Clinicaltrials.gov, Web of Science, and

Cochrane Central from conception to April 8th, 2021. We included citations if they described patients aged 65 years or older who received head imaging at the time of ED assessment, and reported whether patients had delirium, confusion, or altered mental status. Screening, data extraction, and Bias assessment were performed in duplicate. We estimated the odds ratios (OR) for abnormal neuroimaging in patients with altered mental status.

Results: The search strategy identified 3031 unique citations, of which two studies reporting on 909 patients with delirium, confusion or altered mental status were included. No identified study formally assessed for delirium. The OR for abnormal head CT findings in patients with delirium, confusion or altered mental status was 0.35 (95% CI 0.031 to 3.97) compared to patients without delirium, confusion or altered mental status.

Conclusion: We did not find a statistically significant association between delirium, confusion or altered mental status and abnormal head CT findings in older ED patients.

(C) 2023

  1. Introduction

Delirium is a common emergency department (ED) presentation that increases hospital costs and is associated with higher mortality. De- lirium is characterized by brain dysfunction such as confusion, Altered level of consciousness, inattention, and perceptual disturbance [1]. It is

* Corresponding author.

E-mail address: [email protected] (S. Lee).

estimated that 6%-38% of older adults who present to the ED have delir- ium [2-4]. Delirium presents a challenge in patient care as it is associ- ated with higher mortality rates and functional decline. Studies estimated that delirium costs up to $152 billion US dollars each year in the healthcare setting [1,5]. Consequently, many geriatric initiatives, including the multidisciplinary Geriatric EMergency department guide- lines, focus on the screening, prevention, and treatment of delirium [6]. The etiology of delirium is often multifactorial and includes infec- tion, medications, pain, surgery, acute medical illness, drug intoxication,

https://doi.org/10.1016/j.ajem.2023.06.034

0735-6757/(C) 2023

immobilization, metabolic derangement, Sleep deprivation, and acute neurological disease [7-13]. The neurological etiologies for delirium in- clude intracranial hemorrhage, ischemic stroke, and brain tumors. Many of these neurological etiologies can be diagnosed with computed to- mography (CT) or magnetic resonance imaging (MRI) imaging. Head CT is commonly used in the ED to evaluate patients presenting with concern for a neurological emergency [13,14]. However, there is vari- ability in the practice of obtaining a head CT for older adult patients pre- senting with confusion, delirium or altered mental status [15-17]. There is no consensus on whether delirium in older ED patients necessitates neuroimaging in all cases [18,19]. We recently showed an incidence of 15% for abnormal neuroimaging in older ED patients with confusion or altered mental status [20]. In order to evaluate whether delirium in older ED patients increases the odds of finding abnormal pathology on neuroimaging, we undertook a systematic review and meta-analysis comparing older ED patients with delirium to those without delirium. Given that many patients with delirium are not formally diagnosed in the ED (ref) and are likely labeled as “confused” or “altered”, we ex- panded our review to capture the more encompassing description of “altered mental status”, which includes the terms confusion as well as delirium. Accordingly, we use the general term “altered mental status” to mean delirium or confusion, throughout the manuscript except where otherwise specified.

  1. Methods
    1. Overview

This manuscript was written in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [21].

    1. Search strategy and study eligibility

We searched Ovid Medline from 1946, Embase from 1947, Web of Science from 1900, Cochrane Central, PubMed Central, and Clinicaltrials.gov up to April 8, 2021. The search strategies were created in collaboration with a medical librarian and can be viewed in Appendix

A. The search strategies involved using many combinations of common key words and terms, such as (delirium OR confusion OR acute Mental status change) and (computed tomography OR magnetic resonance im- aging AND emergency department OR acute care OR emergency physi- cian), filtered to exclude pediatric studies. The unique citations were stored in Covidence systematic review software, Veritas Health Innova- tion, Melbourne, Australia. Specifically for delirium, in order to maxi- mize the sensitivity of our search parameters, we included the more generic terms to capture any instance of potential delirium by adding the terms “confusion” and “altered mental status”. (Appendix A. Search strategy).

We included original studies reporting on patients aged 65 years older who had received neuroimaging during their ED visit. Included studies had to report on patients with and without delirium. We in- cluded confusion or altered mental status as a proxy measure for delir- ium because there is a overlap between these terms. We included patients diagnosed with delirium superimposed on dementia. We ex- cluded conference abstracts, case reports, and published manuscripts. Studies on hospitalized inpatients or only specific subgroups of Delirious patients (such as trauma patients or patients with cancer), were ex- cluded. Two team members independently screened the title and ab- stract of each citation based on the inclusion and exclusion criteria, and a third team member acted as the tiebreaker if needed. All team members were included in full-text reviews to ensure that each citation was independently reviewed by two team members, with a third acting as a tiebreaker if needed, to determine its final inclusion in this system- atic review.

    1. Data extraction and quality assessment

Data were extracted from each study by three team members using a spreadsheet template designed by the investigators. Disagreements were resolved by discussion. The template included information about the study author, years of conduct, research design, and sample size; population characteristics (age, sex); and abnormal neuroimaging find- ings (number and diagnosis). If the results of a study were reported in a manner that did not allow for accurate or complete data extraction, the authors were contacted to obtain primary data for the purpose of this meta-analysis.

Using the “Quality Assessment of Diagnostic Accuracy Studies-2 (QADAS-2)” [22], two team members independently checked for the risk of bias in each of the studies with a third team member acting as a tiebreaker if needed [23]. The tool assesses the representativeness of the general population, accuracy of the assessment of the outcome, and completeness of the data to categorize studies as having a low, intermediate, or high risk of bias.

    1. Statistical analysis

We performed a meta-analysis of the collected data to calculate the pooled random effects estimated odds ratio (OR) and 95% confidence interval of abnormal neuroimaging in those who had delirium/confu- sion/altered mental status compared to those without delirium/confu- sion/altered mental status. Heterogeneity was appraised using I2. The meta-analysis was completed using MedCalc Statistical Software v20.019 (MedCalc Software Ltd., Ostend, Belgium).

  1. Results
    1. Study characteristics

The employed search strategy resulted in the identification of 3035 studies. After title and abstract screnning, 3031 were excluded because they did not meet the inclusion criteria or were a duplicate. Forty-seven studies underwent a full text review, 45 were excluded and 2 studies in- cluded in the analysis [24,25]. Detail of the Selection process can be found in Fig. 1.

Both included studies were retrospective cohort studies that used Head CT imaging only, not MRI [24,25]. We reported on a subset of the study by Nesselroth et al. who were 65 years and older [24]. The authors described the study patients as “confused” and categorized the abnor- mal CT results into “acute” or “chronic” and defined these terms [24]. In the study by Segard et al., all patients were 75 years or older, and ab- normal CT findings were described using the term “abnormal”, but a specific definition was not included [25]. For the purposes of this analy- sis, we considered those classified as having ‘consciouness disorder with GCS < 14’ and ‘delirium without focal Neurological deficits‘ to be posi- tive for delirium, confusion or altered mental status [25]. The method of delirium diagnosis was not stated. Table 1 shows more detailed char- acteristics of these studies.

    1. Risk of bias

Nesselroth et al. [24] showed low risk of bias for patient selection and reference test domains, high risk for index test, and unclear risk of bias for flow and timing domain. Segard et al. [25] showed high risk of bias for index test and reference test and unclear risk of bias for patient selection and flow and timing domains (Table 2).

    1. Synthesis of results

The pooled odds of patients with delirium having an abnormal neu- roimaging compared to those without delirium was 0.35 (95% CI 0.031 to 3.97) and I2 was 97.25% with a p < 0.0001 indicating substantial

Image of Fig. 1

Fig. 1. Flow chart showing article selection.

heterogeneity. The pooled rate of abnormal neuroimaging was 30.7%. Fig. 2 demonstrates the corresponding forest plot.

  1. Discussion

This systematic review and meta-analysis showed that there is very limited quality research addressing whether delirium in older adults is associated with acute intracranial abnormality on head imaging in the

ED. Even when expanded to include altered mental status and confu- sion, the existing research is insufficient to provide a conclusion. Given this limited quality of research, our meta-analysis could not provide conclusive evidence on whether delirium predicted abnormal acute findings on neuroimaging.

This is the first analysis comparing the risk of intracranial pathology among older ED patients with delirium to those who do not have delir- ium. Our systematic review had important findings. There were only two studies. None of the reviewed studies assessed all included patients for delirium, therefore misclassification bias is likely. Neither study used a validated delirium screening tool. Both studies used surrogate mea- sures for delirium such as Glasgow Coma Scale <14 and confusion. Most importantly, the studies had unclear or high risk of bias, meaning that pooling of the results has little clinical meaning.

We previously showed that the rate of abnormal head CT was about 15% for older ED patients with altered mental status [20]. Similarly, Akhtar et al. conducted a systematic review of the yield of head CT for patients with delirium or altered mental status, and reported that the overall percentage of head CT was 13% (95% CI: 10.2%-15.9%) in the in- patient/ED and 17.4% (95% CI: 10%-26.3%) in the intensive care unit, with considerable heterogeneity [26]. Importantly, Akhtar et al. evalu- ated delirium and altered mental status as a separate entities [26]. We suspect the higher rate of abnormal neuroimaging in our present study might be due to random error. Our present meta-analysis was based on a limited number of patients and studies, likely prone to selec- tion bias. The number of abnormal head neuroimaging in these previous studies was not negligible, but our meta-analysis did not show sufficient evidence to support or refute the need for neuroimaging for the indica- tion of acute altered mental state alone.

    1. Limitations

There are several limitations to this study. First, our study used a broader definition of delirium which included confusion and altered mental status because of the paucity of literature focusing on patients with delirium in the ED. However, the chief complaint of altered mental status is highly specific for delirium [27]. The designation of altered mental status is not very sensitive to the presence of delirium, so we suspect that there were patients with delirium, particularly hypoactive

Table 1

Characteristics of included studies.

Author Country Year

Study Design Definition of

Altered mental status

Study Period Age Sex Included in the meta-analysis N Acute Abnormal Head

CT n (%)

CT abnormality

Nesselroth Israel 2021

Retrospective Confusion Jan 2017-Feb

2017

Not reported

Not reported

Patients >=65 who had head CT in the ED

86 17 (19.8%) Not reported for older adults

Segard France 2013

Retrospective GCS < 14 or

delirium with no focal deficits

Not reported Not

reported

Not reported

Patients >=75 who had head CT in the ED

103 41 (39.8%) ?112 Ischemic stroke

35 ICH

5 Brain mass

52 Other

SD: Standard Deviation, CT: Computed Tomography, IQR: Inter Quartile Ratio, ICH: intracranial hemorrhage.

* some patients had more than one abnormality.

Table 2

Risk of bias and concern for applicability for included study

Study

Patient Selection ROB

Patient

Selection Applicability

Index test ROB

Index test Applicability

Reference test ROB

Reference test Applicability

Flow and timing ROB

Nesselroth

Segard

QUADAS -2 used for risk of bias; Color code: green-low risk, yellow-unclear, red-high risk.

Fig. 2. Forest plot showing a pooled odds ratios for abnormal head CT when altered mental status is present.

delirium, who were classified as not having delirium, confusion, or al- tered mental status in our analysis. Second, our work focused on older adults with delirium, confusion or altered mental status who received a head CT in the ED rather than all older patients in the ED. It is likely that the decision to order the head CT introduced spectrum bias. The true proportion of head CT abnormalities in patients with and without delirium may differ. Third, we found only two retrospective studies with high risk of bias.

  1. Conclusion

This meta-analysis showed that exisiting evidence is too limited to determine whether the presence of delirium, confusion, or altered men- tal status is associated with abnormal neuroimaging findings in the ED.

CRediT authorship contribution statement Sangil Lee: Conceptualization, Data curation, Investigation, Method-

ology, Project administration, Supervision, Validation, Visualization,

Writing – original draft, Writing – review & editing. Faithe R. Cavalier: Data curation, Investigation, Methodology, Software, Validation, Visual- ization, Writing – original draft. Jane M. Hayes: Data curation, Formal analysis, Investigation, Methodology, Project administration, Resources, Visualization, Writing – original draft, Writing – review & editing. Michelle Doering: Data curation, Investigation, Methodology, Resources, Writing – review & editing. Alexander X. Lo: Conceptualiza- tion, Data curation, Formal analysis, Investigation, Methodology, Valida- tion, Writing – original draft, Writing – review & editing. Danya Khoujah: Conceptualization, Data curation, Formal analysis, Investiga- tion, Methodology, Project administration, Validation, Visualization, Writing – original draft, Writing – review & editing. Matthew A. How- ard: Investigation, Validation, Writing – review & editing. Kerstin de Wit: Conceptualization, Data curation, Investigation, Methodology, Project administration, Software, Validation, Visualization, Writing – original draft, Writing – review & editing. Shan W. Liu: Conceptualiza- tion, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing.

Declaration of Competing Interest

None.

Acknowledgement

This work was supported in part by John A. Hartford and West Health.

Appendix A. Supplementary data

Supplementary data to this article can be found online at https://doi. org/10.1016/j.ajem.2023.06.034.

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