Abstract
Background
Delirium in elderly patients after hip fracture surgery is believed to be a transient event, although it frequently lasts for more than 4 weeks.
Questions/purposes
We determined the incidence, risk factors, morbidity, and mortality of prolonged delirium in elderly patients after hip fracture surgery.
Patients and Methods
We evaluated 232 elderly patients (older than 65 years) (232 hips) who underwent hip fracture surgery for the development and duration of delirium and categorized them into three groups; nondelirium group, transient (≤ 4 weeks) delirium group, and prolonged (> 4 weeks) delirium group. Patients underwent a global geriatric evaluation, which included postoperative complications, mortality, and functional and mental status evaluations. The three groups were compared with respect to these variables.
Results
Seventy patients (30.2%) had delirium develop, and among these, 14 (20%) had prolonged delirium with a total incidence of 6%. Multivariate analysis showed preinjury dementia was a risk factor of prolonged delirium. At the final followup, five (62.5%) of the eight patients who were ambulatory outdoors in the prolonged delirium group became housebound, whereas only 18 (16.4%) of the 110 patients who were ambulatory outdoors in the nondelirium group became housebound. Survival at 40 months was 81.0% (95% confidence interval, 72.6%–89.3%) in the nondelirium group and 63.6% (95% confidence interval, 35.2%–92.1%) in the prolonged delirium group.
Conclusions
Prolonged delirium was found to be associated with a poor functional outcome and increased mortality.
Level of Evidence
Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.
Introduction
Delirium is a common complication in elderly patients after hip fracture surgery, characterized by a change in mental status with attention and awareness deficits, loss of cognitive and perceptive functions, and alterations in the sleep cycle [15, 29]. Delirium also is associated with adverse outcomes, including greater hospitalization time, greater rate of institutional placement, greater dependence on others, higher costs, delayed recovery, and increased mortality [6, 10, 15].
The incidence of delirium in the elderly is known to be higher after hip fracture (range, 28%–61%) than after admission to a general internal medicine unit or an acute geriatric unit (range, 14%–42%) [6, 10, 12, 17, 25, 39]. In nonorthopaedic fields, a chronic type of delirium, which is called prolonged delirium (defined here as lasting > 4 weeks), is reported to exist and is known to be associated with greater mortality and poor functional recovery [4, 21, 22]. However, the duration of delirium and its consequences have received sparse attention in the orthopaedic field.
Our study was designed to answer to the following questions: (1) What was the incidence of prolonged delirium after surgical treatment of patients with hip fracture? (2) Could any risk factors associated with prolonged delirium be identified? (3) How did the morbidity and mortality compare between patients who experienced delirium and those who did not?
Patients and Methods
We reviewed prospectively collected data on 250 patients aged 65 years and older who underwent surgery for a femoral neck fracture or an intertrochanteric fracture from January 2006 to December 2008 in a tertiary referral center. Of the 250 patients, 18 (7.2%), who refused followup after discharge, were excluded from this study (Fig. 1). Thus, we analyzed 232 patients who were followed for a minimum of 12 months or until their death after the fracture operation. The average age of patients was 79 years (range, 65–97 years); 59 patients were male and 173 patients were female. Development and duration of delirium were evaluated using the Confusion Assessment Method (CAM) (Table 1) [2]. All patients underwent global clinical and geriatric evaluations, including history, physical examination, laboratory tests, and a surgical risk evaluation. The design and protocol of this prospective study were approved by the institutional review board at the authors’ hospital, and all patients provided informed consent.
Fig. 1.
A flowchart shows the flow of patients through the study.
Table 1.
Confusion Assessment Method diagnostic algorithm
| Feature | Description |
|---|---|
| Feature 1: acute onset and fluctuating course | This feature is usually obtained from a family member or nurse and is shown by positive responses to the following questions: Is there evidence of an acute change in mental status from the patient’s baseline? Did the (abnormal) behavior fluctuate during the day, that is, tend to come and go, or increase and decrease in severity? |
| Feature 2: inattention | This feature is shown by a positive response to the following question: Did the patient have difficulty focusing attention, for example, being easily distractible, or having difficulty keeping track of what was being said? |
| Feature 3: disorganized thinking | This feature is shown by a positive response to the following question: Was the patient’s thinking disorganized or incoherent, such as rambling or irrelevant conversation, unclear or illogical flow of ideas, or unpredictable switching from subject to subject? |
| Feature 4: altered level of consciousness | This feature is shown by any answer other than “alert” to the following question: Overall, how would you rate the patient’s level of consciousness? (alert [normal]), vigilant [hyperalert], lethargic [drowsy, easily aroused], stupor [difficult to arouse], or coma [unarousable]) |
The diagnosis of delirium requires the presence of Features 1 and 2 and either Feature 3 or 4; (Reprinted with permission from Inouye SK, van Dyck CH, Alessi CA, Balkin S, Siegal AP, Horwitz RI. Clarifying confusion: the Confusion Assessment Method. A new method for detection of delirium. Ann Intern Med. 1990:113:941–948. The American College of Physicians is not responsible for accuracy of this translation.)
The presence of preoperative cognitive impairment/dementia was determined within 24 hours of admission using the Mini-Mental State Examination (MMSE) and the CAM diagnostic algorithm [8, 9, 15]. One orthopaedic surgeon (BGC) and two nurses (HJO, SN) who had been trained for the evaluation of CAM and mental status collected the data. One psychiatric doctor, who specialized in dementia, participated in the design of this study, and we consulted the psychiatric department for evaluation of the patient’s mental status whenever the patients had abnormal scores for the MMSE and abnormal CAM during the initial hospitalization and postoperative period. Through this consultation, the patients were classified to have dementia or delirium. Normal mental status was defined as a MMSE score of 25 points or more (maximum score is 30). Scores of 19 or less were interpreted as definite dementia and scores of 20 to 24 as suspected dementia [23, 34]. In patients with suspected dementia, a diagnosis of dementia was made with consideration of the age, gender, and education level of the patient [23, 34]. CAM scores are determined using a diagnostic algorithm consisting of four features: (1) acute and fluctuating changes in mental status, (2) inattention, (3) disorganized or incoherent thinking, and (4) an altered level of consciousness. CAM scores are considered to indicate delirium if Features 1 and 2 are present and either Feature 3 or 4 is present.
As previous studies reported most patients with hip surgery who have delirium develop recover within 4 weeks [6, 10, 12, 24, 38], we defined “transient delirium” as delirium lasting for 4 weeks or less postoperatively and “prolonged delirium” as delirium lasting more than 4 weeks. Patients were categorized into three groups: (1) a transient delirium group, (2) a prolonged delirium group, and (3) a nondelirium group.
Postoperative delirium was assessed 2 or 3 days postoperatively. Assessment was not performed on the day of surgery because of the difficulty in differentiating true delirium and the residual effects of anesthesia. A second evaluation was performed 1 week postoperatively.
One hundred eleven patients included in the study experienced a delay to the time of surgery after admission for more than 5 days. The reason for delay included the need to allow reversal of anticoagulation for patients receiving aspirin or warfarin, or the need for preoperative evaluations of comorbidities. Of the 232 patients, 204 underwent cementless bipolar hemiarthroplasty and the remaining 28 underwent internal fixation using a dynamic compression hip screw.
We assessed patient characteristics, including age, gender, body mass index (BMI), medical comorbidity, fracture type, presence of preoperative dementia, presence of preoperative delirium, surgical delay, type of anesthesia, duration of anesthesia, amount of blood loss, type of operation (hip arthroplasty or internal fixation), hospitalization after surgery, and surgical risk on the American Society of Anesthesiologists (ASA) rating scale [35] (Classes I and II or Classes III and IV), to determine whether they contributed to the occurrence and duration of delirium. Medical comorbidities were assessed using the modified Charlson’s Comorbidity Index, which is calculated by summing points awarded for disease conditions as follows: 1 point for myocardial infarction, congestive heart failure, deep vein thrombosis, peripheral vascular disease, dementia, chronic obstructive pulmonary disease, arthritis, ulcers, or diabetes; 2 points for cancer or stroke; and 3 points for cirrhosis. Thus, possible total scores range from 0 to 15, where higher scores indicate a poorer health status [2].
Patients were followed up at 1, 3, 6, and 12 months postoperatively and every 6 months thereafter. At each visit, patients were interviewed using a questionnaire that addressed activity level, and MMSE and CAM scores were determined. Postoperative functional outcomes were evaluated using activity levels [33], which were defined as follows: I, normal; II, essentially independent outdoors but requiring help with some activities; III, independent indoors but always requiring help outdoors; IV, not independent indoors but able to transfer and walk independently; and V, confined to bed or chair and not ambulatory. Patients unable to return for followup were interviewed, using a questionnaire, by telephone and were requested to send radiographs. The followups were made taking care to interview the same caregiver who was interviewed during the patient’s hospitalization. This clinical information was collected by one orthopaedic surgeon (BGC) and two nurses (HJO, SN). Seventy-eight patients completed followups with a telephone interview.
Of the 232 patients, all patients had a face-to-face interview at the outpatient clinic at 3 months. However, 41 patients were interviewed by telephone at 6 months, 53 patients at 12 months, 30 patients at 18 months, 24 patients at 24 months, and 16 patients at 36 to 40 months.
Mortality was identified from hospital records or by interviewing a member of the family of the patient involved.
We analyzed the morbidity in patients, who were still alive until the latest followup, which was performed 12 to 40 months postoperatively. The activity levels of patients were dichotomized into ambulatory outdoors (activity levels of I and II) and housebound (activity levels of III, IV, and V) for the analysis.
We used multiple logistic regression analysis to identify the factors that effectively influenced the development of transient delirium and prolonged delirium. First, demographic and clinical variables between patients with nondelirium and patients with transient and prolonged delirium were compared using the independent t test for continuous variables and the chi square test or Fisher’s exact test for categorical data. For p values less than 0.10 by univariate analysis, multiple logistic regression analysis with stepwise selection was performed. In the multivariate analysis model, age, ASA class, operation type, and preoperative dementia were included for comparison between the nondelirium and the total delirium groups (transient and prolonged delirium groups), and preoperative dementia and BMI were included for comparison between the nondelirium and the prolonged delirium groups. The Kaplan-Meier product-limit method with log-rank significance test was used to estimate survival [19] using mortality as an end point. All reported p values are two sided, and p values less than 0.05 were deemed significant. SPSS® Version 15.0 (SPSS Inc, Chicago, IL, USA) was used for the statistical analyses.
Results
Of the 232 study subjects, 162 patients did not have delirium develop and 70 (30.2%) did, and of these 70, 56 (80%) had transient delirium and 14 (20%) had prolonged delirium, resulting in an incidence of prolonged delirium of 6% (Table 2). In the transient delirium group, 50 patients recovered within 7 days and six patients between 10 and 28 days. In the prolonged delirium group, 12 patients recovered between 40 and 160 days (mean, 98 days) and two patients did not recover by the final followup of 18 and 20 months, respectively (Fig. 1).
Table 2.
Demographic data
| Variable | Value |
|---|---|
| Number of patients | 232 |
| Male:female | 59 (25.4%):173 (74.6%) |
| Age (years)* | 79.0 ± 7.7 (65–97) |
| Body mass index* | 21.5 ± 3.8 (15.5–36.0) |
| Residence before injury | |
| Home | 191 (82.3%) |
| Nursing home | 41 (17.7%) |
| Diagnosis | |
| Femoral neck fracture | 116 (50%) |
| Intertrochanteric fracture | 116 (50%) |
| Medical comorbidities* | 2.1 ± 1.3 (0–8) |
| Surgical risk assessment (ASA score) | |
| I | 17 (7.3%) |
| II | 132 (56.9%) |
| III | 82 (35.3%) |
| IV | 1 (0.4%) |
| Duration of anesthesia (minutes)* | 95.1 ± 35.2 (65–180) |
| Amount of transfusion (mL)* | 311.2 ± 166.7 (0–1200) |
| Delay of operation (days)* | 5.4 ± 5.9 (0–60) |
| Operation method | |
| Arthroplasty | 204 (87.9%) |
| Internal fixation | 28 (12.1%) |
| Preoperative mental change | |
| Delirium | 4 (1.7%) |
| Dementia | 10 (4.3%) |
| Postoperative delirium | 70 (30.2%) |
| Transient | 56 (80.0%) |
| Prolonged | 14 (20.0%) |
* Values are expressed as mean ± SD, with range in parentheses; the remaining values are expressed as number of patients, with percentage in parentheses; ASA = American Society of Anesthesiologists
ASA class (p = 0.003), operation type (p = 0.004), preoperative delirium (p = 0.008), and dementia (p = 0.009) were different between the nondelirium group and the total delirium group (transient and prolonged delirium groups) in univariate analysis (Table 3). However, only dementia (p = 0.011) and operative type (p = 0.029) were associated with the development of delirium in multivariate analysis. Comparing the nondelirium group and the prolonged delirium group, univariate analysis showed differences with respect to dementia (p = 0.007) and BMI (p = 0.048), and multivariate analysis showed preoperative dementia to be associated with development of prolonged delirium (p = 0.003) (Table 4). Comparing the transient and prolonged delirium groups, no differences were found between the two groups.
Table 3.
Comparison of demographic and clinical data of the nondelirium and delirium groups
| Variable | Nondelirium group | Total delirium group* | p Value |
|---|---|---|---|
| (n = 162) | (n = 70) | ||
| Male:female | 38:124 | 21:49 | 0.293 |
| Age (years)† | 78.5 ± 7.7 | 80.3 ± 7.4 | 0.090 |
| Body mass index† | 21.7 ± 3.6 | 21.2 ± 4.0 | 0.371 |
| Diagnosis | 0.567 | ||
| Femoral neck fracture | 79 | 37 | |
| Intertrochanteric fracture | 83 | 33 | |
| Medical comorbidities† | 2.1 ± 1.4 | 2.4 ± 1.4 | 0.305 |
| Surgical risk assessment (ASA score) | 0.003 | ||
| I | 16 | 1 | |
| II | 94 | 38 | |
| III | 52 | 30 | |
| IV | 0 | 1 | |
| Type of anesthesia | 0.127 | ||
| Spinal | 133 | 63 | |
| General | 29 | 7 | |
| Duration of anesthesia (minutes)† | 95.9 ± 35.7 | 95.2 ± 35.1 | 0.623 |
| Amount of transfusion (mL)† | 310.5 ± 164.7 | 311.7 ± 172.4 | 0.959 |
| Delay of surgery (days)† | 5.1 ± 5.1 | 6.0 ± 7.6 | 0.338 |
| Hospitalization after surgery (days) | 13.9 ± 2.2 | 14.5 ± 2.4 | 0.072 |
| Type of surgery | 0.004 | ||
| Arthroplasty | 136 | 68 | |
| Internal fixation | 26 | 2 | |
| Preoperative mental change | |||
| Delirium | 0 | 4 | 0.008 |
| Dementia | 3 | 7 | 0.009 |
* Total delirium group = transient delirium group + prolonged delirium group; †values are expressed as mean ± SD; the remaining values are expressed as number of patients; ASA = American Society of Anesthesiologists.
Table 4.
Comparison of demographic and clinical data of the nondelirium and prolonged delirium groups
| Variable | Nondelirium group (n = 162) | Prolonged delirium group (n = 14) | p Value |
|---|---|---|---|
| Male:female | 38:124 | 1:13 | 0.310 |
| Age (years)* | 78.5 ± 7.7 | 81.9 ± 8.4 | 0.114 |
| Body mass index* | 21.7 ± 3.6 | 19.6 ± 3.3 | 0.048 |
| Diagnosis | 0.671 | ||
| Femoral neck fracture | 79 | 6 | |
| Intertrochanteric fracture | 83 | 8 | |
| Medical comorbidities* | 2.1 ± 1.4 | 2.8 ± 2.0 | 0.122 |
| Surgical risk assessment (ASA score) | 0.401 | ||
| I | 16 | 0 | |
| II | 94 | 8 | |
| III | 52 | 6 | |
| IV | 0 | 0 | |
| Duration of anesthesia (minutes)* | 95.9 ± 35.7 | 96.3 ± 37.1 | 0.101 |
| Amount of transfusion (mL)* | 310.5 ± 164.7 | 351.4 ± 273.2 | 0.403 |
| Delay of surgery (days)* | 5.1 ± 5.1 | 8.9 ± 14.94 | 0.362 |
| Type of surgery | 0.104 | ||
| Arthroplasty | 136 | 14 | |
| Internal fixation | 26 | 0 | |
| Preoperative mental change | |||
| Delirium | 0 | 1 | 0.080 |
| Dementia | 3 | 3 | 0.007 |
* Values are expressed as mean ± SD; the remaining values are expressed as number of patients; ASA = American Society of Anesthesiologists.
Thirty-nine patients (16.8%) died after discharge. Overall mortalities after surgery were 7.3% (17 of 232) at 6 months, 9.5% (22 patients) at 12 months, and 12.5% (29 patients) at 24 months. Mortalities at 24 months in the prolonged delirium and nondelirium groups were 12.3% (20 of 162) and 35.7% (five of 14), respectively (p = 0.032), and mortalities at this time in the transient delirium group (seven of 56) and the prolonged delirium group (five of 14) differed with marginal significance (p = 0.054). Survival rates at 40 months were 81.0% (95% confidence interval, 72.6%–89.3%) in the nondelirium group, 73.5% (95% confidence interval, 51.8%–95.2%) in the transient delirium group, and 63.6% (95% confidence interval, 35.2%–92.1%) in the prolonged delirium group (Fig. 2).
Fig. 2.
Kaplan-Meier survival curves show the survival rates at 40 months were 81.0%, 73.5%, and 63.6% for the nondelirium, transient delirium, and prolonged delirium groups, respectively.
For 193 patients who survived 1 year or longer after the operation, the development of delirium was associated with a higher incidence of reduced activity level at followup. Patients with poorer activity level after surgery at the final followup included 35 of the 136 surviving members in the nondelirium group, 20 of 48 in the transient delirium group, and eight of nine in the prolonged delirium group (p < 0.001) (Table 5). At the final followup, 18 of 110 (16.4%) patients in the nondelirium group and 12 of 38 (31.6%) in the transient delirium group were able to ambulate outdoors. Five of eight (62.5%) patients in the prolonged delirium group who were able to ambulate outdoors were housebound at the final followup (p = 0.003) (Fig. 3).
Table 5.
Changes in activity level in the three groups
| Variable | Nondelirium group (n = 136) | Transient delirium group (n = 48) | Prolonged delirium group (n = 9) | p Value |
|---|---|---|---|---|
| Preinjury activity | 0.566 | |||
| Grade I | 86 | 29 | 6 | |
| Grade II | 24 | 9 | 2 | |
| Grade III | 23 | 7 | 0 | |
| Grade IV | 3 | 3 | 1 | |
| Activity at final followup | 0.017 | |||
| Grade I | 63 | 19 | 0 | |
| Grade II | 29 | 7 | 3 | |
| Grade III | 28 | 7 | 3 | |
| Grade IV | 13 | 9 | 2 | |
| Grade V | 3 | 6 | 1 | |
| Number of patients with decreased activity | 35 | 28 | 8 | < 0.001 |
Fig. 3.
An illustration shows activity changes in the nondelirium, transient delirium, and prolonged delirium groups at final followup. Eighteen of 110 (16.4%) patients in the nondelirium group and 12 of 38 (31.6%) in the transient delirium group were able to ambulate outdoors. Five of eight (62.5%) patients in the prolonged delirium group who were able to ambulate outdoors were housebound at final followup (p = 0.003).
Discussion
Delirium is a common complication in elderly patients after hip fracture surgery [29], which is associated with a greater hospitalization time, greater rates of institutional placement, greater dependence on others, higher costs, delayed recovery, and increased mortality [6, 10, 15, 37]. However, the duration of delirium has received little attention, which is known to be associated with worse outcome in nonorthopaedic fields. In this study, we sought to determine the incidence, risk factor, and clinical outcome of prolonged delirium at a minimum followup of 1 year among elderly patients who underwent surgery for a hip fracture.
This study has several limitations. First, although we used an established and validated method, evaluations were performed at an outpatient clinic, and it occasionally was difficult to differentiate symptoms of dementia and delirium; to determine between dementia and delirium at the admission state, the trained physician and nurse evaluated the patient’s mental status using the MMSE and CAM. If the scores were abnormal, the patient has a consultation with the psychiatric department to evaluate his/her mental status and to minimize possible misdiagnosis of delirium to dementia or vice versa. Second, some patients were interviewed by telephone, which increased the risk of misinterpreting the symptoms. To minimize this possibility, the observers who conducted the interview during hospitalization also conducted the telephone interview. Third, the final evaluations were performed over a wide range of intervals (range, 12–40 months) after the operation, and we could not afford to assess the morbidity and mortality at each year after the operation. Finally, this study was conducted at a single tertiary referral center, and thus, caution should be exercised when making generalizations based on our results.
For decades, dementia has been a major public health problem. The rate of dementia among the elderly (65 years and older) has been reported to be approximately 5% to 6% in Western countries [7, 13, 18, 36] and 2% to 7% in Asian countries [3, 27, 28, 41]. In our patients, the rate of dementia was 4%.
Previous studies reported the efficacy of risperidone for the treatment of delirium [14, 42, 44]. In our study, 21 patients with delirium were treated with risperidone. However, we could not determine whether this medication was effective in terms of reducing the severity and duration of delirium because of the lack of randomization and the small sample size in our study.
As previous studies used different criteria to define prolonged delirium [26, 30, 43], no definite definition of prolonged delirium was available. In our study, we defined prolonged delirium as the presence of delirious symptoms for more than 4 weeks postoperatively, referencing the report by Kiely et al. [21]. They defined prolonged delirium as a delirium existing at the 1-month followup, observing most symptoms of delirium recovered within the first 4 weeks [6, 10, 12, 24, 38].
In our study, the incidence of prolonged delirium was 20% (14 of 70) in patients with postoperative delirium and 6% (14 of 232) in all elderly patients, and patients had a mean recovery time of 47 days. The reported incidence of prolonged delirium among patients who have had delirium develop ranges widely from 0% to 61% at 1 month postoperatively [17, 20–22, 40]. The reasons for this wide variation in incidence may be related to differences in patient population, proportions of patients with dementia, the criteria used to determine the presence of delirium at enrollment, and the criteria used to assess prolonged delirium [4, 16, 32].
Preoperative delirium was a single significant risk factor for prolonged delirium compared with the nondelirium group in our study. Previous studies also have reported the presence of preoperative dementia as the strongest risk factor of prolonged delirium among the elderly [16, 21, 31, 32]. Cole et al. [4] explained the relationship between preoperative dementia and prolonged delirium, stating both had similar symptoms, such as inattention and fluctuation, and had similar pathogenesis, which included reduced metabolic rates and impaired cholinergic function, and similar causative factors, such as excitotoxic neuronal damage and neuron death [1, 5, 11].
In our study, patients with prolonged delirium were found to have worse functional outcome and higher mortality rate than patients who did not have delirium develop. This finding is in concordance with other studies [17, 20, 22]. Kiely et al. [22] reported persistent delirium as a significant independent predictor of 1-year mortality, showing a 2.9 times higher rate of mortality compared with the nondelirium group during the 1-year followup, which diminished after the resolution of delirium.
Prolonged delirium after hip fracture surgery is not rare, shows a higher incidence in patients with preoperative dementia, and is associated with poor functional outcome and higher mortality.
Acknowledgments
We thank Byung-Gun Chang MD, Hyun-Jeong Oh RN, and Sere Noh RN, for their efforts in enrolling and interviewing patients for this study.
Footnotes
Each author certifies that he or she has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article.
Each author certifies that his or her institution approved the human protocol for this investigation, that all investigations were conducted in conformity with ethical principles of research, and that informed consent for participation in the study was obtained.
This work was performed at Chung-Ang University College of Medicine.
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