DELIRIUM is a global disorder of cognition, wakefulness,

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1 Journal of Gerontology: MEDICAL SCIENCES 1993, Vol. 48, No. 4, M162-M166 Copyright 1993 by The Gerontological Society of America The Occurrence and Duration of Symptoms in Elderly Patients With Delirium Kenneth Rockwood Division of Geriatric Medicine, Dalhousie University, Halifax, Nova Scotia. Background. This study attempts to estimate the incidence, prevalence, and average duration of delirium in elderly patients; to assess the sensitivity of DSM-III and DSM-III-R in the diagnosis of delirium; and to compare the estimates of the duration of delirium using DSM-III and DSM-III-R criteria. Methods. A 12-month prospective descriptive study of 168 consecutively admitted patients and 5 additional patients with delirium was conducted in the Geriatric Assessment Unit of a teaching hospital. The duration in days of DSM-III and DSM-III-R symptoms for each delirious patient was assessed by two clinicians. The Barthel Index, Mini-Mental State Examination, and Trezpacz Delirium Symptom Rating Scale scores were also recorded. Results. The prevalence of delirium was 18% and the incidence was 7%. Compared to clinical judgment DSM-III-R showed 100% sensitivity. The mean duration of delirium was 8 ± 9 days (DSM-III-R); the DSM estimate was 7 ± 7 days. Complete symptom recovery was seen in only 52% of surviving patients. Prolonged memory impairment was common. Conclusions. As operationalized in this study, DSM-III-R delirium criteria were more sensitive than DSM-III. Persistent symptoms are common in elderly patients with delirium. DELIRIUM is a global disorder of cognition, wakefulness, and attention. The timing and course of this disorder are central to its definition; delirium is typically said to have an acute onset and a transient course (1-7). The extent to which particular symptoms may be transient, however, has recently been called into question (8-10). The questions thus raised are important, as the diagnostic criteria for delirium, including the most recent revisions, have to date largely been developed in the absence of phenomenologic studies (1,11,12). Similarly, there has been little study of how the revisions to the Third Edition of the Diagnostic and Statistical Manual of the American Psychiatric Association (DSM-III/DSM-III-R) have affected estimates of the epidemiology and duration of delirium (11). We set out to address two primary questions: First, what is the prevalence, incidence, and duration of delirium and its individual symptoms in elderly patients? Second, how does the duration of delirium compare, using DSM-III and DSM- III-R criteria, and what is the sensitivity and specificity of each set of criteria? As the diagnosis of delirium remains clinical, a secondary question was: How common is disagreement in the diagnosis of delirium, and what is the nature of this disagreement? METHODS Setting and design. The study was conducted in a 14- bed teaching Geriatric Assessment Unit (GAU) on a 22-bed general medical ward at Camp Hill Hospital, Halifax, Nova Scotia. The GAU admits predominantly urgent and elective patients, approximately 75% of whom are acutely ill. It is strictly targeted to the frail elderly; typically 50% have dementia, more than 90% are dependent in activities of daily living (ADLs), and all are dependent in instrumental ADLs. The study protocol was approved by the Camp Hill Research and Ethics Committee. The study has two components. Part 1, a prospective descriptive study, was conducted to estimate the prevalence and incidence of delirium in patients admitted to the GAU. To allow additional cases for the estimation of the mean duration of delirium among these patients, in Part 2 of the study only patients with delirium were investigated. This part of the study was conducted from March through May, Measures. On admission, demographic, Barthel Index (BI), Mini-Mental State Examination (MMSE) scores, and the cause of delirium were recorded (13,14). Delirium etiology was determined jointly by the attending physicians and the study physician using two criteria: laboratory and/or radiologic confirmation of the putative cause (e.g., sepsis, electrolyte abnormality, intracranial lesion) and temporal relationship. The latter criterion required onset of delirium with onset of the agent, and diminution or resolution with treatment or withdrawal of the agent. In the case of a medication effect, only a temporal relationship was required. Where two or more etiologies were present, the one in which the temporal course most closely conformed to the course of the delirium was said to be the primary cause, and others were recorded as secondary causes. The Trzepacz Delirium Symptom Rating Scale (DSRS) was completed for each delirious patient (15); in half of the cases, the study physician independently completed a second DSRS. In addition, for patients with delirium, a diagnostic checklist was used to record the presence of all DSM- III and DSM-III-R diagnostic criteria. The checklist was coded as 1 = "present; new or worse," 2 = "present; M162

2 OCCURRENCE AND DURATION OF DELIRIUM M163 unchanged," 3 = "absent." These determinations were made clinically, based on corroborating history. In the checklist DSM-III-R criterion "E" (acute onset and fluctuating course) was separated into its two components, and disorientations to person, place, and time were recorded separately. The diagnostic checklist was completed by the attending geriatrician and the study physician in collaboration. All three attending physicians were specialists in internal medicine and geriatric medicine, with considerable experience in the diagnosis of delirium and dementia. At the time of the study, the author was completing fellowship training in geriatric medicine. The presence of individual symptoms was determined by the attending physician and reviewed by the study physician. All physicians used guidelines determined at the outset as follows. Inattention was operationalized as the inability to maintain attention and shift focus; tests of inattention included the MMSE tests of spelling "world" backwards, or counting backwards from 100 by 7. More than one error was recorded as inattention. In the pilot study these tests proved insensitive to small improvements, and thus counting backwards from 20 to 1 in the presence of a distracting auditory stimulus was added for patients failing the above items. Disorganized thinking was operationalized as rambling or incoherent speech and was elicited by asking the patient to explain to the examiner why he or she was in the hospital. Patients who could not speak were asked to follow simple commands. These data were supplemented by observing all patients in their ability to cooperate with the physical examination and simple aspects of routine care. Clouding of consciousness was said to be present only if both inattention and hypoalertness were present. Other behavioral manifestations were operationalized according to the DSRS and were observed directly or elicited by questions of the staff or family. A symptom was recorded as being present on the day in which it was first observed by either examiner. Clinical disagreement over whether a patient was delirious was resolved by consensus; if consensus could not be achieved, the attending physician's opinion was recorded. The presence of individual symptoms was followed daily until discharge. A symptom was said to have resolved if it was not present for three consecutive days but was recorded as having resolved on the first day in which its absence was noted. Both the attending physician and the study physician participated in these decisions. After discharge the latter reviewed the completed symptom checklist to calculate the number of days during which the patient met DSM-III and DSM-III-R criteria. The attending physicians were blinded to the intent of comparing the DSM-III and DSM-III-R criteria, and the criteria were mixed together in the symptom checklist. At discharge, the BI and MMSE and a final symptom checklist were repeated. The discharge disposition and length of stay were also recorded. RESULTS During Part 1, 169 patients were admitted to the GAU. One patient, who refused to complete the MMSE, was excluded. Of the remaining 168, 31 (18%) presented with delirium, and 12 patients (7%) developed delirium during the course of the hospital stay; this included one patient who had been delirious on admission, but whose delirium had cleared in the interval. In Part 2, another 5 patients with delirium were examined. Table 1 compares demographic characteristics of Part 1 patients with and without delirium. In this sample, there is little difference between the two groups. Table 2 compares clinical characteristics of patients with and without delirium. As expected, patients with delirium have lower scores on both the MMSE and the BI on admission. Though they show greater average change scores than patients without delirium, they still have lower mean BI and MMSE scores at discharge. The mean DSRS score for delirious patients was 17 ± 4 (range 10-27). The DSRS score correlated weakly with the MMSE (r =.45) but not the BI (r =.03). Inter-rater reliability of the DSRS was.86. Of the 48 cases of delirium, the etiology in two cases (4%) could not be diagnosed. In the remainder, the chief primary causes were medications (31%), infection (23%), congestive heart failure (21%), and metabolic abnormalities (19%). Infection was a secondary cause in five patients, secondary metabolic changes occurred in three, and medications were implicated as a secondary cause in two other delirious patients. Figure 1 portrays the occurrence, in patients with delirium, of the several symptoms comprising the DSM-III and DSM-III-R criteria. Of the patients with a clinical diagnosis of delirium, all met DSM-III-R criteria (sensitivity = 100%) compared with 40 patients who met DSM-III criteria (sensitivity compared with DSM-III-R = 83%). Two patients, described below, met DSM-III-R criteria but were not judged to be clinically delirious (specificity = 98%). Compared with DSM-III-R, DSM-III had a specificity of 100%. Table 3 reports characteristics of the eight patients (5%) in whom there was disagreement over the diagnosis; delirium Table 1. Demographic Characteristics of Patients Admittted to the Geriatric Assessment Unit, With and Without Delirium Mean age (yrs) Male (%) Married (%) Admitted from community (%) Discharge to community (%) Mean length of stay (days) No Delirium Delirium All Cases 79 ± ± ± ± ± ± 20 Table 2. Clinical Characteristics of Patients Admittted to the Geriatric Assessment Unit, With and Without Delirium Mean Barthel Index score on admisison Mean Barthel Index score at discharge Mean MMSE score on admission Mean MMSE score at discharge Mortality (%) No Delirium Delirium All Cases 64 ±29 36 ± ± ±24 63 ± ± ± 8 12 ± 8 18 ± 9 21 ± 8 17 ± 8 20 ±

3 M164 ROCKWOOD Table 3. Selected Characteristics of Patients in Whom There Was Disagreement Between Clinicians About the Diagnosis of Delirium Age/Sex 74 F 74 F 77 F 82 F 82 F 85 F 94 M 105 F Prior Cognitive State Parkinson's Disease, multiple systems atrophy *MMSE, Mini-Mental State Examination (15). Present New/worse 1 1 Present /old Absent Figure 1. Occurrence of symptoms in delirium. MMSE* on Admission was ultimately diagnosed in one of these patients. In three cases, the disagreement arose from the attending and study physicians having seen the patient on different days; joint observation resulted in agreement. Data on these patients are included in the nondelirious group. One patient presented with an acute paranoid disorder and did not meet delirium criteria until day 4. Two patients presented with a history of dementia and an acute akinetic rigid syndrome. In both cases, this settled with treatment of an underlying acute problem (UTI and adverse medication reaction, respectively). On these latter three patients, consensus was also easily achieved. In the remaining cases disagreement could not be resolved until the course of the illness was known. One patient presented with acute global cognitive impairment. Her ultimate course was consistent with rapidly progressive dementia, and an autopsy revealed multiple systems atrophy. The final patient, a 94-year-old man with severe dementia, presented with drowsiness; disagreement arose over whether MMSE at Discharge Comments Adverse medication reaction (resolved by admission) Aphasic. Akinetic rigidity (resolved with decreasing sinemet) Rapidly progressive dementia Akinetic rigidity Adverse medication reaction (resolved by admission) Resolving delirium Likely delirium Acute paranoia on admission, frank delirium by day 4 Figure 2. Mean duration of symptoms in delirium. worsening of his cognition could reliably be said to have occurred. His subsequent course of increased alertness and improved function following treatment of a urinary tract infection is consistent with delirium, but neither case is included in the delirium group for this analysis. Using DSM-III-R criteria, the mean duration of delirium was 8 ± 9 days, which was not significantly different from the DSM-III estimate of 7 ± 7 days. Figure 2 reports the duration of symptoms comprising DSM-III and DSM-III-R criteria. Although the chief criteria for each settled within 7-12 days, other symptoms persisted, particularly memory impairment. By discharge, entire symptom resolution had occurred in only 19 patients (40%). DISCUSSION This article has reported the prevalence, incidence, and duration of delirium in elderly patients admitted to a GAU and has compared DSM-III and DSM-III-R delirium criteria. The data have some important limitations, and the

4 OCCURRENCE AND DURATION OF DELIRIUM M165 duration of delirium symptoms was not measured beyond the duration of the hospitalization. Nonetheless, each patient with delirium was followed until one of four outcomes (recovery, dementia, discharge, or death) occurred. A limitation inherent in current studies of delirium is the method of diagnosis. We relied on careful clinical diagnosis of delirium by geriatricians experienced in the syndrome, who used predetermined criteria, and who were directing the patients' care. A single study physician corroborated the presence and interpretation of the syndrome and individual symptoms. Instances of disagreement were planned for and were recorded in detail. The study, however, was implemented before recent attempts to standardize the DSM-III/ III-R criteria were reported (12,16,17), and instead operationalized criteria from the MMSE and the DSRS, with amendments arising from a pilot study. As there is currently no "gold standard" for the diagnosis of delirium, apart from diagnosis by experienced physicians, the methodology from this report offers as high a degree of confidence in the resulting estimates as we could devise. The transient nature of delirium has been emphasized by several authors, and has been incorporated into diagnostic criteria for delirium. In ICD-9, the "acute confusional state" is coded under 293 "transient organic psychotic conditions," and is said to last "hours or days" (3). ICD-9 also recognizes a "subacute confusional state" (293.1) "in which the symptoms, usually less florid, last for several weeks or longer." In the draft ICD-10 delirium diagnostic guidelines, it is stated that the total duration of the condition must be under six months (4). A similar stipulation is made in CAMDEX (delirium criterion B) (5). While stipulating the importance of an acute onset, neither DSM-III nor DSM-III-R specifics a period beyond which delirium symptoms should not persist. Their accompanying manuals note that' 'The duration of an episode of Delirium is usually brief, about one week: it is rare for Delirium to persist for more than a month" (6). Our data suggest, however, that individual symptoms may persist. This is particularly relevant for memory impairment, given its importance in the diagnosis of dementia. Recently, Levkoff elal. have reported from the Harvard Delirium Project, which suggested that complete recovery of delirium was uncommon, occurring in only 4% of patients by the time of discharge (8). In contrast, 40% of the patients in the current study had complete recovery by discharge. Two possibilities suggest themselves. The differences may be due to differences in the settings and samples. The mean length of stay of delirious patients in the current study was longer both for those from the community (37 days vs 31 days) and from institutions (29 days vs 11 days), although their finding of complete resolution in only 13% at 3 months argues against this accounting for more than a small part of the difference. Perhaps more important, the Levkoff et al. study included surgical patients and more emergent admissions, in whom the delirium may have been more severe (2). Methodologic differences are also important. The study by Levkoff et al. used data from the patient's chart and nurse but relied in the main on a standard interview administered by a research assistant (16). As its specificity compared to clinical judgment has been reported as 0.80, some overestimation of prevalence is possible. No data are available which compare the Delirium Symptom Interview to the current protocol, so the extent to which this is important is not known. Despite these differences in degree, both the Harvard project and this one report longer estimates of the persistence of symptoms ihan would be expected from DSM-III/III-R. Other empiric studies report a range of less than 1 week to more than 2 months. Sirois retrospectively analyzed delirium cases referred for psychiatric consultation and found that delirium lasted less than 24 hours in 20%, from 1-3 days in 30%, from 3-5 days in 17%, from 5-10 days in 20% and up to 30 days in 13% (18). Koponen et al. described delirium in elderly persons admitted to a psychiatric hospital. The mean duration of delirium was 20 days (range 381) (9). Koizumi et al., using DSM-III criteria, reported that the mean duration in patients with an unconnected electrolyte imbalance was 26 days, compared with a mean duration of 9 days in those in whom the electrolytes were normalized, and 25 ± 6.6 days in patients who were delirious from a cause other than electrolyte imbalance (10). Thus duration of delirium for more than 1 month does not appear to be rare. In an earlier study, the author found that delirium often lasted for less than 24 hours, and in the 20 patients studied never lasted for more than 7 days (19). (Although individual symptoms persisted, their frequency and duration were not recorded.) By contrast, in the current report, only 19% lasted 1 day, and 47% persisted beyond 7 days. The earlier study examined general medicine patients, of whom a smaller proportion were frail compared with patients admitted to the GAU. In predominantly well patients who become delirious when sick, the duration may be shorter than in patients who are both delirious and frail. We also considered the possibility that delirium was investigated more promptly in the earlier study as a consequence of the heightened vigilance afforded by a one-inthree in-hospital call schedule. Although prompt recognition and treatment would seem likely to shorten the course of delirium (10), we found only mixed support for this in a post-hoc comparison of incident and prevalent cases. The mean duration of delirium in incident cases (which by this argument should be shorter) was 10 ± 8.6 days, compared with 8 ± 8.4 days for prevalent cases. The same proportion of incident and prevalent cases, however, had full recovery of symptoms by discharge, despite the incident cases having had a shorter stay after onset of delirium. The discharge BI of incident cases (79) was higher than prevalent cases (61) by a clinically important amount. Further studies of the impact of prompt treatment on the duration of delirium are needed (1,2). The conclusion that many delirium symptoms may persist has important implications for delirium diagnostic criteria. Although the individual symptoms making up the delirium syndrome are not specific to it, the time course has been said to convey some specificity. Further studies should therefore emphasize acute onset and fluctuation in the delirium time course, as has been proposed by Inouye et al. in the Confusion Assessment Method (20). Comparison of DSM-III and DSM-III-R criteria is of interest in examining reports which have used one or the

5 M166 ROCKWOOD other method of diagnosis. Our data suggest that DSM-III is less sensitive than DSM-III-R in diagnosing delirium. By contrast, another report from the 325 patients studied in the Harvard Delirium Project, by Liptzin et al., found DSM-III- R to be less inclusive than DSM-III, as 125 met DSM-III criteria (38%) compared with 106 who met DSM-III-R criteria (33%) (11). Again, methodologic differences are important. In addition to the differences noted above, we operationalized the chief DSM-III criterion (clouding of consciousness) as inattention and a decreased level of arousal/consciousness. Although some reports have required both (19), others, including Liptzin, have defined clouding of consciousness as inattention (11,12). Disagreement over how best to characterize clouding of consciousness, documented by Lipowski (1), is clearly of practical importance. Secondly, Liptzin et al. only recorded disorganized thinking as present if the patient was able to speak, whereas disorganized thinking in our two aphasic patients was interpreted by asking them to follow simple commands, and by observing their compliance with simple aspects of the nursing routines.or the quality of their interaction with their families. Perhaps the most important methodologic difference between the two studies is in the diagnosis of delirium. As noted, the Harvard project employed a research assistant who visited daily to complete a symptom checklist, from which delirium was diagnosed, while the current project relied on clinical diagnoses. This resulted in a greater number of chances to sample the patients' behavior, through the more frequent contact afforded by the combination of routine patient care, and review by a second observer. In contrast to Liptzin et al., who required that all symptoms be present within the same 24-hour period, we did not specify a period in which all symptoms had to occur in order for the patient to meet delirium criteria. We did, however, precisely record the day on which a symptom was present and also recorded occurrences of clinical disagreement, which usually arose from the attending and study physicians having seen the patients at different times. Although clinical disagreement was not uncommon (8 cases/173; 5%), it was usually resolved within 2-3 days. This pattern is in keeping with the important proposal of Liptzin et al. that a 72-hour window, rather than a 24-hour one, be used in deciding whether the patient meets delirium criteria (11). We observed few demographic differences between patients with and without delirium. We believe that this is due to the high prevalence of frailty in the population under study. In our experience, delirium is, for many patients, best interpreted clinically as a nonspecific presentation of illness in the frail elderly. Other reports of greater ADL impairment and higher rates of dementia as predictors of delirium support this (12,17,21,22), as do recent reports of worse longterm outcomes in patients with delirium (8,22). Comparisons of patients with and without delirium often yield differences that might best be attributed to the difference between patients who are ill and frail, and patients who are predominantly well but transiently sick. Further studies of the relationship between frailty and delirium are required. In addition, it is of some importance that the usual duration of delirium be addressed, as intervention trials will need to assess the impact of treatment on duration. ACKNOWLEDGMENTS In the data analysis and report writing, the author was supported by the Nicholas M. and Hedy J. Munk Award. The author is grateful to his colleagues Drs. J. M. Gray and Glen Ginther for their participation in the data collection, and in particular to Dr. Roy Fox for his advice and assistance. Address correspondence to Dr. Kenneth Rockwood, Division of Geriatric Medicine, Dalhousie University, 1763 Robie Street, Halifax, NS, Canada B3H 3G2. REFERENCES 1. Lipowski ZB. Delirium: acute confusional states. Oxford: Oxford University Press, Lindesay Y, MacDonald A, Starke, I. Delirium in the elderly. Oxford: Oxford University Press, World Health Organization. Manual of the international statistical classification of diseases, injuries, and causes of death, 9th rev. Geneva: World Health Organization, World Health Organization. Manual of the international statistical classification of diseases, injuries, and causes of death, 10th rev. Geneva: World Health Organization, Roth M, Huppert FA, Tym E, Mountjoy CQ. CAMDEX: the Cambridge examination for mental disorders of the elderly. Cambridge: Cambridge University Press, American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 3rd ed. Washington, DC: American Psychiatric Association, American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 3rd ed. rev. Washington, DC: American Psychiatric Association, Levkoff SE, Evans DA, Liptzin B, et al. Delirium: the occurrence and persistence of symptoms among elderly hospitalized patients. Arch Intern Med 1992; 152: Koponen H, Stenbreck U, Mathala E, et al. Delirium in elderly persons admitted to a psychiatric hospital: clinical course during the acute stage and one year follow-up. Acta Psych Scand 1989;79: Koizumi J, Shiraishi H, Suzuki T. Duration of delirium shortened by the correction of electrolyte imbalance. Jpn J Psychiat Neurol 1988;42: Liptzin B, Levkoff SE, Cleary PD, et al. An empirical study of diagnostic criteria for delirium. Am J Psych 1991; 148: Johnson JC, Gottlieb GL, Sullivan E. Using DSM-III criteria to diagnose delirium in elderly general medical patients. J Gerontol 1990;45:M Granger CV, Albrecht GL, Hamilton BB. Outcome of comprehensive medical rehabilitation: measurement by PULSES Profile and the Barthel Index. Arch Phys Med Rehabil 1979;60: Folstein MF, Folstein SE, McHugh PR. Mini-mental state: a practical method for grading the cognitive state of patients for the clinician. J Psychiatric Res 1975; 12: Trzepacz PT, Baker RW, Greenhouse J. A symptom rating scale for delirium. Psych Res 1988;23: Albert MS, Levkoff SE, Reilly C, et al. The Delirium Symptom Interview: an interview for the detection of delirium symptoms in hospitalized patients. J Geriatr Psychiatry Neurol 1992;5: Francis J, Martin D, Kapoor WN. A prospective study of delirium in hospitalized elderly. JAMA 1990;263: SiroisF. Delirium: 100 cases. Can J Psychiatry 1988:33: Rockwood K. Acute confusion in elderly medical patients. J Am Geriatric Soc 1989;37: Inouye SK, van Dyck CH, Alessi CA, Balkin S, Siegal AP, Horwitz RI. Clarifying confusion: the Confusion Assessment Method. Ann Intern Med 1990;l 13: Erkinjurti T, Wikstrom J, Palo J, Autio L. among medical inpatients: evaluation of 2000 consecutive admissions. Arch Intern Med 1986; 146: Francis J, Kapoor WN. Prognosis after hospital discharge of older medical patients with delirium. J Am Geriatr Soc 1992;40: Received September 9, 1992 Accepted December 15, 1992

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