Abstract
Background
Altered mental status (AMS) in older adults is a common reason for admission to emergency departments (EDs) and usually results from delirium, stupor, or coma. It is important to proficiently identify underlying factors and anticipate clinical outcomes for those patients.
Aim
The primary objective of this study was to reveal and compare the clinical outcomes and etiologic factors of older patients with delirium, stupor, and coma. The secondary objective was to identify the 30-day mortality risk for those patients.
Method
The study was conducted as prospective and observational research. We included patients aged 65 years and older who presented with new-onset neurological and cognitive symptoms or worsening in baseline mental status. Patients who presented no change in their baseline mental status within 48 h and those who needed urgent interventions were excluded. Selected patients were assessed using RASS and 4AT tools and classified into three groups: stupor/coma, delirium, and no stupor/coma or delirium (no-SCD). Appropriate statistical tests were applied to compare these 3 groups. The 30-day mortality risks were identified by Cox survival analysis and Kaplan-Meier curve.
Results
A total of 236 patients were eligible for the study. Based on their RASS and 4AT test scores: 56 (23.7%), 94 (40.6%), and 86 (36.4%) patients formed the stupor/coma, delirium and no-SCD groups, respectively. There was no statistical difference in the three groups for gender, mean age, and medical comorbidities. Neurological (34.7%), infectious (19.4%), and respiratory (19.0%) diseases were the leading factors for AMS. Post-hoc tests showed that CCI scores of the delirium (6, IQR = 3) and stupor/coma (7, IQR = 3) groups were not significantly different. The 30-day mortality rates of stupor/coma, delirium, and no-SCD groups were 42.%, 15.9%, and 12.8%, respectively ( p < 0.005). The hazard ratio of the stupor/coma group was 2.79 (CI: 95%, 1.36–5.47, p = 0.005).
Conclusion
AMS remains a significant clinical challenge in EDs. Using the RASS and 4AT tests provides benefits and advantages for emergency medicine physicians. Neurological, infectious, and respiratory diseases can lead to life-threatening mental deterioration. Our study revealed that long-term mortality predictor CCI scores were quite similar among patients with delirium, stupor, or coma. However, the short-term mortality was significantly increased in the stupor/coma patients and they had 2.8 times higher 30-day mortality risk than others.
1
Introduction
Altered mental status (AMS) is a common reason for emergency department (ED) visits, hospitalization, and neurology consultation for elderly patients [ ]. Those patients generally require an extensive work-up, including a detailed history from families or caregivers, a comprehensive physical examination, and sequential laboratory and radiologic studies [ ]. The general term of AMS has several synonyms such as acute brain dysfunction, organic brain syndrome, or, briefly, ‘not acting right’. AMS comprises two main elements: the level of consciousness (LOC) and the content of consciousness [ ].
Acute change in mental status is usually a result of delirium, stupor, or coma. Coma and stupor are defined as profoundly decreased LOC and awareness. Those patients have no motor or verbal response to external stimulants and present unusual reflex responses [ ]. Several clinical scoring tools are used to grade the LOC. The Glasgow Coma Scale (GCS) was originally developed to assess the physiologic deterioration in traumatic brain injury. Meanwhile, the AVPU scale offers a simple method for grading LOC by assessing the individual’s level of alertness, responses to verbal and painful stimuli, as well as their potential unresponsiveness [ ]. The Richmond Agitation and Sedation Scale (RASS) may be a more reliable and useful method for evaluating the content and consciousness level. The RASS describes patients’ sedation, cooperation, and aggressiveness by ranking them from −5 (unarousable) to +4 (extreme combativeness). 0 point on the RASS indicates calm and alert patients [ ]. A RASS score other than 0 has very good sensitivity and specificity for AMS in older EDs [ ].
Delirium is a complex and severe cognitive problem that begins in days, hours, or even minutes with a fluctuating course. Older age and dementia are the prominent risk factors for delirium. Older adults with delirium, especially those with the hypoactive subtype, can be recognized late or even missed by ED physicians [ ]. Although the gold-standard diagnostic approach is described comprehensively in the Diagnostic and Statistical Manual of Mental Disorders-5th edition (DSM-5), some rapid detection tools exist to recognize delirium [ , ]. The 4AT test was initially designed as a rapid and straightforward assessment instrument for cognitive functions. [ ]. It evaluates a person’s awareness, cooperation, and attention, while also considering the timing of any fluctuations in cognitive ability. A score of 4 or higher (>4) on this test indicates a significant level of cognitive impairment. It was proven that it has acceptable accuracy for diagnosing delirium in older patients in EDs and intensive care units (ICUs) [ ].
In this prospective study, the mental states of geriatric patients were evaluated using RASS and 4AT tests in the ED. The enrolled patients were divided into three groups: stupor/coma, delirium, and no stupor/coma or delirium (no-SCD) groups, respectively. In these settings, our primary objective was to reveal and compare the clinical severity, associated etiologic factors, and clinical outcomes of older adults with stupor, coma, and delirium. Predicting the probability of mortality and worsening outcomes is vitally important for emergency medicine and critical care doctors. Recent studies have suggested that delirium is a remarkable risk factor for one-year mortality in hospitalized patients [ ]. However, it is unclear whether this finding is generalizable to emergency settings. Therefore, our secondary objective was to determine the 30-day mortality risk of those patients.
2
Method
2.1
Study design and ethical approval
This prospective observational study was conducted in a tertiary referral center in Turkey. >70,000 adults receive emergency healthcare services annually from the ED, which also functions as a research and training facility. Approximately 10–15% of these patients are aged 65 years or older. The GCS is commonly used to assess arousal state and LOC. At the start of the study, there was no delirium screening tool integrated into the patient examination chart. Additionally, there was no reliable institutional data available regarding the prevalence of AMS or delirium. To address this gap, we reviewed previous studies to determine the prevalence of AMS and identify patient risk factors. The study protocol and informed consent forms were designed in accordance with the Helsinki Declaration. In cases where possible, the informed consents were obtained from both the patients and their legal guardians. However, if this was not feasible, only legal guardians approved the informed consent forms. The study was ethically approved by the institutional ethics committee of our university (Approval date and number:12/3/2019-A-42).
2.2
Selection of participants
The study employed consecutive sampling to enroll patients. The research team recruited participants between 8 a.m. and 5 p.m. during the period from January to September 2020. The inclusion criteria for this study were patients aged 65 and over who presented with new onset or worsening neurological and cognitive symptoms on their first arrival in the ED. These symptoms included loss of consciousness, somnolence, drowsiness, memory loss, non-cooperation, disorientation, harmful or dangerous behaviors, inattention, nonsense speaking, headache, vertigo, dizziness, near syncope, and so on. Importantly, these symptoms had to manifest within 48 h before the patient’s arrival. Duration of stay in the ED was not considered for inclusion criteria, only on-admission symptoms and mental status were taken into account.
The study excluded patients who required advanced life support (ALS) or percutaneous coronary intervention (PCI), as well as those for whom their legal guardians refused to provide informed consent. Additionally, dementia patients who did not exhibit an acute deterioration in their baseline mental status were excluded from the study. The cut-off time for the beginning of new symptoms or the worsening of the baseline condition was 48 h before the patient’s arrival. This time limit was set to avoid the inclusion of the chronically mentally impaired patient in the study.
2.3
Grouping
Stupor, coma, delirium, and functional mental status were recorded at the admission point by emergency medicine research assistants and specialists who were blinded to this study’s hypothesis. Research assistants were trained for at least two years in the ED and capable of assessing mental status with RASS and 4AT tests. The enrolled patients were grouped according to RASS and 4AT test scores. The RASS scale describes patients’ alertness, sedation, cooperation, and aggressiveness. A score of 0 on the RASS scale indicates a calm and alert state, while other mental states are ranked from −5 (indicating unarousable) to +4 (indicating extreme combativeness) [ ]. The 4AT test, developed by Belleli et al., measures cognition, awareness, cooperation, and attention in two minutes. A score of 4 or above suggests serious cognitive impairment and delirium. Recent studies have shown that it has excellent specificity (95%) and adequate sensitivity (%76) for detecting delirium in older EDs and ICUs [ ].
Patients who were unarousable and unresponsive got −4 and − 5 points on the RASS scale, and they were categorized into the stupor/coma group. Subsequently, the 4AT test was administered to patients with RASS scores of −3 and above. Patients who were disoriented, non-cooperative, agitated, unfocused, or combative and scored >4 points on the 4AT test were classified into the delirium group.
The no-SCD group comprised patients admitted to the ED with symptoms such as non-specific headaches, migraine attacks, syncope or presyncope, peripheral vertigo, general weakness, fatigue, and similar conditions. Even if those patients experienced new-onset or worsening neurological symptoms, they met the criteria for neither stupor/coma nor delirium. Patients in the no-SCD group were fully alert, maintained cooperation and orientation, and exhibited sustained attention. Consequently, the RASS scores for patients in the no-SCD group were either 0 or + 1.
2.4
Baseline variables and clinical severity measurements
We statistically compared the mean age, gender, presence of polypharmacy (regularly taking >3 different medications daily), and chronic diseases of each group. Body temperature (from the tympanic membrane in Celsius), heart rate (per minute), systolic blood pressure, finger-prick blood glucose level, oxygen saturation from pulse oximetry, emergency severity index (ESI), Charlson comorbidity index (CCI), and modified early warning score (MEWS) were obtained and noted from each patient at the first emergency room visit. The ESI is a five-level triage algorithm that provides clinically relevant stratification of patients into five groups from 1 (most urgent) to 5 (least urgent) on the basis of acuity and resource needs. According to ESI, patients with any neurological symptoms were stratified as 3 (moderately urgent) and above [ ]. The CCI is a bedside tool for predicting long-term mortality by classifying and weighing comorbidities. It has been widely applied by clinicians and researchers to measure the burden of diseases [ ]. The MEWS is another well-known, simple, and rapid tool used for stratifying patients according to disease severity and for predicting the risk of mortality [ ].
2.5
Etiologic factors and patient outcomes
In light of the good clinical practices, essential biochemical and microbiological laboratory tests and appropriate imaging techniques for the brain and other body regions were deployed for enrolled patients. Those patients were referred to relevant specialists, if necessary. We clearly identified the final diagnoses of all enrolled patients in the ED. Multiple diagnoses of each patient were recorded separately for the study. Their clinical courses were monitored from electronic health records until the patient’s discharge or death to clarify the patient outcomes.
The etiologic factors of AMS were determined by analyzing the final diagnoses. We utilized the International Classification of Diseases 11th Revision (ICD-11) to identify the etiologic factors of AMS [ ]. For example, if a patient was diagnosed with an ischemic stroke which is under the ‘08-Diseases of the nervous system’ title in ICD-11, we assumed that a neurological factor was responsible for the AMS. In cases where patients had multiple diagnoses, each diagnosis was recorded separately. This means that if a patient had both hypernatremia (ICD-11, 05-Endocrine, nutritional or metabolic diseases) and ischemic stroke diagnoses in the ED, we considered that both neurological and metabolic factors were responsible for the AMS. However, if a patient had both diabetic ketoacidosis and hypernatremia simultaneously, we recorded that only metabolic reasons were responsible for the AMS, in accordance with ICD-11. In conclusion, we briefly identified the etiologic factors under neurological, respiratory, cardiovascular, metabolic, oncological, psychiatric, and trauma/toxicology titles based on their respective ICD-11 codes.
In this study, we compared the associated etiologic factors, final diagnoses, ICU admission rates, length of hospital stay, and 30-day mortality. The primary endpoint was death within 30 days. Mortality in 30 days, intensive care unit admission, and length of stay in the hospital were recorded to observe the prognosis of the patients.
2.6
Statistical analysis
The sample size was calculated using Cochran’s formula with a 95% confidence level and 5% marginal error [ ]. Previous studies were scanned to determine the study proportion value. Han et al. reported that the prevalence of stupor and coma was 5–9%, and the prevalence of delirium was 8–10% in EDs among geriatric patients. Based on this study, the overall prevalence of AMS among older adults ranges between 13 and 19%. Thus, the sample proportion value was accepted as 0.19 [ ]. As a result of Cohcran’s formula and these values, the sample size was calculated as 236 for this study. Hypothesis tests were performed to compare the variables of stupor/coma, delirium, and no-SCD groups. Categorical variables were shown with frequency and percentage. Kolmogorov-Smirnov test measured the normality of numerical variables. If the numerical variables fit the normal distribution, then they were expressed with mean and standard deviation (SD); otherwise, they were expressed with median value and interquartile range (IQR). Pearson Chi-square test was used to compare categorical variables. The one-way ANOVA test was applied to compare the normally distributed numerical variables. Dunnet or Tuckey tests were selected for post-hoc analysis according to the homogeneity of variances. If the numerical variables did not fit the normal distribution, then the Kruskal-Wallis test was used to compare the three groups. Cox regression analysis was performed on the stupor/coma and delirium groups to indicate their 30-day mortality risk. The no-SCD group was taken as the base point for survival analysis. Hazard ratios were calculated after adjusting the gender, cardiovascular comorbidity, cancer history, oxygen saturation, history of chronic obstructive pulmonary diseases (COPD), CCI and MEWS score, sepsis, tumor-related emergencies, and pneumonia. The outcome of the survival analysis was illustrated with the Kaplan-Meier curve. All statistical tests were applied in a 95% confidence level and p < 0.05 significance level. All data analyses were performed using IBM SPSS Version 26.
3
Results
3.1
Baseline characteristics
422 potential participants with neurological and cognitive symptoms were evaluated for grouping eligibility. After the first examination, we realized that 110 dementia patients had no remarkable change in their baseline mental status. Another 22 patients needed CPR or PCI, and the legal guardians of 20 patients refused to give informed consent. The clinical outcomes of 34 patients could not be monitored. Finally, 186 patients were excluded ( Fig. 1 ).
A total of 236 eligible patients were grouped based on their RASS and 4AT test scores: 56 (23.7%) patients scored −4 and − 5 from the RASS and directly formed the stupor/coma group; 94 (40.6%) patients scored 4 and more from the 4AT test and were assigned to the delirium group. In the delirium group, 63 patients were constantly agitated and combative; thus, they received +2 to +4 points from the RASS. However, 31 patients were in drowsiness or light sedation, and they received −2 and − 1 points. The no-SCD group comprised 86 conscious, calm, or slightly anxious and restless patients (RASS scores 0 and + 1) ( Table 1 ).
| Patient characteristics | Total (n=236) | Stupor/coma (n=56) | Delirium (n=94) | No-SCD (n=86) | p-value |
|---|---|---|---|---|---|
| Age (mean±SD) | 78.41±7.93 | 79.28±8.51 | 78.51±7.90 | 78.51±7.90 | 0.523 α |
| >85 years | 61 (25.8%) | 16 (28.5%) | 24 (25.5%) | 21 (24.4%) | 0.988 β |
| Gender | |||||
| Female | 112 (47.4%) | 29 (51.8%) | 42 (44.6%) | 41 (47.6%) | 0.700 β |
| Male | 124 (52.6%) | 27 (48.2%) | 52 (55.4%) | 45 (52.3%) | |
| RASS | |||||
| Unarousable (-5) | 23 (9.7%) | 23 (41.0%) | – | – | |
| Deep sedation (-4) | 33 (14.0%) | 33 (59.0%) | – | – | |
| Moderate sedation (-3) | – | – | – | – | |
| Light sedation (-2) | 12 (5.1%) | – | 12 (12.7%) | – | |
| Drowsy (-1) | 19(8.0%) | – | 19 (20.2%) | – | |
| Alert and calm (0) | 58 (24.5%) | – | – | 58 (67.4%) | |
| Restless (+1) | 28 (11.9%) | – | – | 28 (32.5%) | |
| Agitated (+2) | 48 (20.3%) | – | 48 (51.0%) | – | |
| Very agitated (+3) | 13 (5.5%) | – | 13 (13.8%) | – | |
| Combative (+4) | 2 (0.8%) | – | 2 (2.1%) | – | |
| Chronic Diseases | |||||
| Cardiovascular | 160 (67.7%) | 45 (80.4%) | 64 (68.4%) | 51 (67.4%) | 0.194 β |
| Diabetes mellitus | 89 (37.7%) | 22 (39.3%) | 37 (39.4%) | 30 (34.9%) | 0.794 β |
| Dementia | 73 (30.9%) | 26 2 (35.6%) | 32 1,3 (43.8%) | 15 2 (20.5%) | 0.047 β |
| Cancer | 53 (22.3%) | 14 (25.0%) | 22 (23.4%) | 17 (19.0%) | 0.736 β |
| Chronic renal disease | 50 (21.2%) | 13 (23.2%) | 24 (25.5%) | 13 (15.1%) | 0.212 β |
| COPD | 50 (21.2%) | 13 (23.2%) | 24 (25.5%) | 13 (15.1%) | 0.212 β |
| Polypharmacy | 192 (81.3%) | 48 (85.7%) | 80 (85.1%9 | 64 (74.4%) | 0.812 β |
| Vital signs | |||||
| Body temperature (mean±SD) | 36.59±0.62 | 36.51±0.70 | 36.70±0.67 | 36.51±0.47 | 0.084 α |
| Heart rate (median, IQR) | 88 (27) | 98 2,3 (34) | 87 1 (22) | 84 1 (19) | <0.001 γ |
| Systolic blood pressure (mean±SD) | 129.97±29.13 | 130.16±29.02 | 123.08±25.47 3 | 137.38±31.37 2 | 0.004 α |
| Oxygen saturation (mean±SD) | 92.73±7.04 | 89.01±9.24 2,3 | 93.62±6.00 1 | 94.18±5.50 1 | <0.001 α |
| Blood sugar (mean±SD) | 154.51±74.05 | 156.01±69.61 | 160.11±87.57 | 147.40±59.56 | 0.829 α |
| Emergency severity index | |||||
| ESI-1 | 62 (26.2%) | 45 2,3 (80.3%) | 15 1,3 (15.9%) | 2 1,2 (0.2%) | <0.001 β |
| ESI-2 | 108 (45.7%) | 10 2,3 (17.8%) | 62 1,3 (65.9%) | 36 1,2 (41.8%) | <0.001 β |
| ESI-3 | 66 (27.9%) | 1 2,3 (0.2%) | 17 1,3 (19.2%) | 48 1,2 (55.8%) | <0.001 β |
| CCI (median, IQR) | 6 (3) | 7 3 (3) | 6 3 (3) | 5 1,2 (3) | 0.001 γ |
| MEWS (median, IQR) | 1 (4) | 7 2,3 (6) | 3 1,3 (2) | 0 1,2 (0) | <0.001 γ |
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Chapter 1 Introduction
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