Acute confusion following traumatic brain injury - Taylor & Francis Online

BRAIN INJURY, VOL.

18,

NO.

2 (FEBRUARY 2004), 131–142

Acute confusion following traumatic brain injury R I S A N A K A S E - T H O M P S O N y, M A R K S H E R E R yz, S T U A R T A . Y A B L O N yz, T O D D G . N I C K z a n d P A U L A T . T R Z E P A C Z z} y Methodist Rehabilitation Center, Jackson, Mississippi, USA z University of Mississippi Medical Center, Jackson, Mississippi, USA } Lilly Research Laboratories, Indianapolis, Indiana, USA (Received 6 December 2002; accepted 5 May 2003) Primary objective: To determine the incidence, duration and symptoms associated with acute confusion/ delirium among traumatic brain injury (TBI) neuro-rehabilitation admissions. Research design: Prospective evaluation of neurobehavioural impairments following TBI among inpatient neurorehabilitation admissions. Methods and procedures: Eighty-five consecutive TBI model system patients were evaluated using measures of orientation, cognition, motor restlessness and delirium. Main outcomes and results: Fifty-nine individuals met Diagnostic and Statistical Manual of Mental Disorders—Fourth Edition Delirium Diagnostic Criteria (DDC) on initial evaluation and 42 of these resolved delirium during inpatient rehabilitation. Multivariable logistic regression analyses revealed significant unique associations of the Galveston Orientation and Amnesia Test (GOAT), Delirium Rating Scale, Cognitive Test for Delirium and time elapsed since injury with DDC status. Conclusions: Findings indicate that delirium is common among neuro-rehabilitation admissions with TBI. Use of a single measure (e.g. GOAT) will result in poor characterization of the multi-faceted symptom complex shown by patients with post-traumatic confusion.

Introduction Traumatic brain injury (TBI) is commonly associated with some degree of impaired consciousness [1, 2]. Early publications regarding impaired consciousness described a course of recovery that varied with severity of TBI. Patients with mild TBI may experience brief confusion while patients with injury of greater severity may have prolonged confusion with amnesia or coma [2]. Patients who recover from coma initially manifest some degree of confusion, though a few patients remain non-responsive (vegetative) or minimally conscious [3, 4]. Most patients recover from a confused state, though they may be left with persistent cognitive and behavioural impairments [1]. The duration of impaired consciousness is a commonly used index of injury severity [5].

Correspondence to: Risa Nakase-Thompson, PhD, Department of Neuropsychology, Methodist Rehabilitation Center, 1350 East Woodrow Wilson Drive, Jackson, MS 39216, USA. e-mail: [email protected] Brain Injury ISSN 0269–9052 print/ISSN 1362–301X online # 2004 Taylor & Francis Ltd http://www.tandf.co.uk/journals DOI: 10.1080/0269905031000149542

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Impaired consciousness after TBI manifests in a variety of neurobehavioural impairments. Early reports described impairments of arousal, memory, orientation, attention, language, behaviour, mood and perception [6, 7]. This period is now most commonly called post-traumatic amnesia (PTA), but early reports used a variety of terms including ‘acute traumatic psychosis’, ‘after effects of concussion’, ‘traumatic confusion’ and ‘delirium’. Investigations of PTA or impaired consciousness after TBI have primarily focused on disorientation and memory impairment. Symonds and Russell [8] determined the duration of PTA by retrospectively interviewing patients to determine when they were able to demonstrate ongoing memory for events in their environment. Such patients were described as having recovered ‘continuous memory’. More recent approaches to assessment have included contemporaneous assessment of orientation and the ability to recall information from 1 day to the next [9–12]. Investigations of patients during PTA have focused on the process of recovery of orientation and the nature of memory disturbance observed during this period [13]. High et al. [14] found that orientation after TBI recovers sequentially with initial recovery of orientation to person followed by orientation to place and time. Memory disturbance after TBI is characterized by some loss of ability to recall events immediately preceding injury (retrograde amnesia) as well as a period of inability to encode and later recall new memories (anterograde amnesia) [1]. Memory impairment during post-traumatic confusion is greatest for explicit, episodic memory with some sparing of implicit and procedural memory [15]. Other investigators have studied the phenomenon of motor restlessness (agitation) in confused patients after TBI. These investigations have found an association of restlessness with cognitive impairment. Agitation is common in patients with low levels of cognitive functioning, but is less frequent in patients with higher levels of cognitive function [16]. Patients with intermediate levels of cognitive impairment appear equally likely to be agitated or non-agitated. Patients generally experience cognitive improvement prior to resolution of agitation as opposed to resolution of agitation followed by cognitive recovery [16]. Attentional impairments described during early recovery included difficulties focusing attention on the examiner, sustaining attention, processing information and excessive distractibility [17]. More recently, Stuss et al. [18] studied attentional functions in confused patients. These investigators demonstrated that attentional abilities recover in an orderly manner after TBI. Performance on attentional tasks improved prior to return to orientation, as indicated by Galveston Orientation and Amnesia Test scores (see description below) or ability to recall three words at a 24-hour delay [18]. Stuss et al. argued that attentional disturbance is a key aspect of impaired consciousness after TBI. They noted the similarity of this state of impaired consciousness to delirium where attentional deficits are a hallmark symptom and proposed the term ‘post-traumatic confusional state’ to replace the more commonly used PTA. Delirium is defined as a disorder with rapid onset of fluctuating disturbed consciousness and cognitive impairment due to a general medical condition [19]. Delirium may be comprised of many symptoms including attentional abnormalities, sleep–wake cycle disturbance, cognitive impairments, psychomotor alterations (i.e. hypoactive, hyperactive or mixed), perceptual abnormalities and mood lability [20]. The temporal course of delirium includes acute onset and fluctuating symptom severity that is usually reversible and may last for days or weeks [20].

Acute confusion following TBI

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Delirium occurs in up to 20% of hospitalized patients and may be due to a variety of causes [21, 22]. Non-traumatic causes of delirium include drug intoxication/ withdrawal, polypharmacy, infection, cerebrovascular diseases, cardiovascular disorders, post-operative complications, metabolic disturbances and sleep deprivation [20]. Elderly patients with pre-existing dementia are at particular risk for delirium [23]. Studies have cited a significant rate of mortality and morbidity associated with delirium; however, these studies include subjects with an array of primarily nontraumatic medical disorders accounting for delirium [24–26]. There has been relatively little investigation of mortality and morbidity after delirium primarily due to TBI. Since the course of symptoms and outcomes associated with acute confusion may be expected to differ with aetiology of symptoms, this study prospectively examined the incidence of acute confusion or delirium in a consecutive sample of TBI survivors in an acute neurorehabilitation setting. The purpose of this study is to describe the incidence and course of acute confusion or delirium after TBI and describe cognitive and behavioural characteristics of TBI patients who did and did not meet criteria for delirium during acute inpatient neurorehabilitation.

Method Study population The study population consisted of all TBI patients admitted to a free-standing neurorehabilitation hospital, as part of the National Institute on Disability and Rehabilitation (NIDRR) TBI Model Systems programme from January 1999– October 2001. Criteria for the TBI Model Systems programme include: medically documented TBI; treatment at an affiliated Level I trauma centre within 24 hours of injury; receipt of inpatient rehabilitation within the Model System; admission to inpatient rehabilitation within 72 hours of discharge from acute care; age of at least 16 years at the time of injury; and provision of informed consent by the person with injury or a legal proxy [27]. Patients who were minimally conscious or nonresponsive were excluded from the current investigation [4]. Responsiveness was demonstrated by consistent command following, functional use of objects or object manipulation (e.g. wiping face with washcloth, brushing hair with hairbrush), purposeful movements or communication attempts. Finally, individuals with a pre-morbid neurological disorder were also excluded. Data collection Research assistants collected information regarding injury severity (Glasgow Coma Scale scores (GCS), time to follow commands (TFC), CT scan reports) and medical course from hospital and emergency medical service records. All available neuroimaging reports (CT scans) were obtained from the initial 7 days of hospitalization and subsequently coded independently by a brain injury physiatrist for presence of extra-axial fluid collections, parenchymal contusions, SAH and intra-cranial compression. TFC was coded using the TBI Model System Syllabus definition described by Whyte et al. [28] as ‘‘number of days between injury onset and the second consecutive GCS motor score of 6 within a 24-hour interval’’ [28]. TFC was


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recorded as the number of days from time of injury until subjects met the TBI Model System definition [28]. Demographic information such as date of birth, education and employment were collected in interview with the subjects or family/significant others. Subjects were evaluated with a number of scales during inpatient rehabilitation to describe the neurobehavioural impairments in this population. Orientation, cognitive status, agitation and various symptoms of confusion and delirium were assessed weekly by a neuropsychologist and specially trained research assistants. Participants were also rated weekly by a neuropsychologist to determine whether they met Diagnostic and Statistical Manual of Mental Disorders—Fourth Edition (DSM-IV) diagnostic criteria for delirium [19]. Delirium diagnostic criteria (DDC) include: (a) disturbance of consciousness with attentional impairment, ( b) change in cognition or development of a perceptual disturbance not attributable to dementia, (c) disturbance develops over a short time and fluctuates during the course of the day and (d ) disturbance is caused by a general medical condition. Finally, the time elapsed since injury (TSI; in days) was coded for each weekly observation. Measures Agitated Behaviour Scale (ABS) The ABS is a 14-item measure of agitation and distractibility for individuals with TBI [29]. Scores range from 14–56, with higher scores indicating impaired behaviour and attention. The ABS has been found to have good inter-rater reliability for persons with TBI (r ¼ 0.92) [30]. The ABS has been found to account for 36–62% of the variance among simultaneous, independent observations of agitation and predictive of change in cognitive status [16, 29]. Cognitive Test for Delirium (CTD) The CTD was developed to assess cognitive symptoms of delirium in acutely, medically-ill patients [31]. The test may be completed by patients who are not able to give verbal responses as items may be responded to by pointing, nodding the head or raising the hand. The CTD consists of five sub-tests that assess orientation, attention span, memory, comprehension/conceptual reasoning and vigilance. The raw scores from each sub-test are converted to a common metric of 0–6, with lower scores indicating impaired cognition. These converted scores are summed to give overall scores that range from 0–30. In a study of ICU patients with delirium, outpatients with dementia and general psychiatric inpatients with depression or schizophrenia, Hart et al. [31] found that the CTD successfully discriminated patients with delirium from patients with other conditions. Receiver operating characteristic (ROC) curve analysis showed that total scores less than 19 indicated probable delirium. At this level, sensitivity was 100% and specificity 95.1%. Delirium Rating Scale (DelRS) The DelRS is a 10 item rating scale that assesses the presence and severity of various symptoms of delirium [32]. Individual items assess temporal onset of symptoms, perceptual disturbance, hallucination type, delusions, psychomotor behaviour, cognitive status, physical disorder, sleep–wake cycle, lability of mood and variability of symptoms. Item scores are summed to obtain a total score that may range from 0–32. Scores between 8–12 suggest sub-clinical delirium and scores greater


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than or equal to 13 are consistent with delirium. Trzepacz et al. [32] found that the DelRS successfully discriminated patients with delirium from patients with psychosis or dementia. Galveston Orientation and Amnesia Test (GOAT) The GOAT is a 10-item measure that assesses orientation as well as memory for events preceding and following TBI [9]. Areas of orientation include biographical information, place, time and current circumstances. Error points are assigned for incorrect response to items. Total error scores can range from 0–108, with higher error scores indicating poorer orientation. Error scores are subtracted from 100 to determine a GOAT score. Inter-rater reliability has been found to be excellent (correlation coefficient ¼ 0.99) [9]. The GOAT has been used to determine the duration of PTA in numerous studies of TBI. Duration of PTA as determined by the GOAT scores has been shown to be a reliable predictor of outcome after TBI [33]. Analyses Statistical methods The incidence of subjects meeting or not meeting DDC at inpatient rehabilitation was reported along with frequency of DDC symptoms. Duration of delirium was presented for subjects who no longer met DDC (resolved) by the time of discharge from inpatient rehabilitation. Subjects who were DDCþ on their initial evaluations were compared to subjects who were DDC on initial evaluations on demographic variables and injury characteristics using Mann-Whitney tests. To describe the phenomenology of delirium in rehabilitation inpatients with TBI, relations among demographic (age and education), injury characteristics (TFC and TSI) and scores on GOAT, ABS, CTD, and DelRS were examined. Since observations from the same subject over time were correlated, logistic regression analyses using PROC GENMOD of SAS was used to model the dichotomous DDC outcome (DDCþ vs DDC). The autoregressive (AR) correlation structure was specified to model the correlation of the repeated responses from subjects. This is a common structure when dealing with observations over time and assumes a dropping off of the correlation over time (sequence). For multi-variable analyses, inter-quartile range odds ratios (OR) were presented. An OR is the ratio of the odds of an observation with one set of scores being associated with DDCþ as compared to another observation with a different set of scores. An inter-quartile range OR compared the odds of an observation with scores at 75th percentile of the predictor being associated with DDCþ to the odds of an observation with scores at the 25th percentile being associated with DDCþ. Results Study population During the study period, 94 potential subjects with TBI were admitted for inpatient rehabilitation directly from a Level 1 trauma centre. Eight of these individuals did not emerge from a minimally conscious state and one subject had a pre-morbid


136 Table 1.

Descriptive information for the study sample compared with patients not eligible for study

Sex n (%) Male Female Race n (%) White African-American Years of education Quartilesa Cause of injury n (%) Motor Fall Blunt injury Gun shot wound Pedestrian Marital status Married Single Otherb GCS total ED admitc 3–8 9–12 13–15 Missing Age quartiles Acute LOS quartilesd Rehab LOS quartilese

Study sample (n ¼ 85)

Patients not eligible (n ¼ 9)

65 (77%) 20 (23%)

8 (89%) 1 (11%)

56 (66%) 29 (34%)

4 (44%) 5 (56%)

10/12/13

11/12/13

60 9 9 4 3

(70%) (11%) (11%) (5%) (3%)

5 1 1 2 0

(56%) (11%) (11%) (22%) (0%)

31 (37%) 38 (45%) 16 (18%)

2 (22%) 6 (67%) 1 (11%)

54 (64%) 14 (16%) 16 (19%) 1 (1%) 22 / 33 / 47 14 / 22 / 31 15 / 23 / 38

7 (78%) 0 (0%) 2 (22%) 0 (0%) 19 / 24 / 40 32 / 38 / 59 28 / 67 / 92

a

Quartiles correspond to the 25th / 50th / 75th percentiles. The ‘Other’ category includes widowed, divorced or separated. c ED Admit is at the time of admission to the Level I Trauma Centre Emergency Department. d Acute LOS is length of stay during Level I Trauma Centre acute hospitalization. e Rehab LOS is length of stay during inpatient rehabilitation. b

neurologic condition (i.e. brain tumour) with cognitive impairment and, thus, did not qualify for this study [4]. The remaining 85 subjects were enrolled in the study after informed consent was obtained. Descriptive information for the 85 subjects in the study and the nine excluded subjects is shown in table 1.

Analysis 1: initial observations Fifty-nine (69%) of the 85 subjects in the study sample were DDCþ (met all four delirium criteria) on initial evaluation and, of these, 42 subsequently resolved from meeting DDC during inpatient rehabilitation. On initial evaluation, 62 of the study subjects (73%) met criterion A of DDC (disturbance of consciousness with attention impairment) including three of the 26 DDC- subjects (12%). Also, 81 subjects or 95% of the sample met criterion B (cognitive impairment or perceptual disturbance) including 85% of DDC group. Finally, 74% met criterion C (fluctuating course) including 15% of DDC subjects. Every subject (100%) met criterion D (attributed medical disorder).


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Table 2. Frequency of symptoms among the 85 subjects (DDCþ n ¼ 59; DDC n ¼ 26) with positive symptoms on the DelRS during initial observation by DDC status DDC Items of DelRS

Total n (%)

þ

Item Item Item Item Item Item Item Item Item Item

85 (100%) 17 (20%) 14 (16%) 17 (20%) 47 (55%) 84 (99%) 85 (100%) 65 (76%) 39 (46%) 59 (69%)

59 16 13 15 39 59 59 49 33 51

26 1 1 2 8 25 26 16 6 8

1. Sudden onset 2: Perceptual disturbance 3: Hallucinations 4: Delusions 5: Abnormal motor behaviour 6: Cognitive impairment on BSE* 7: General medical condition 8: Sleep–wake cycle disturbance 9: Lability of mood 10: Variability of symptoms

* BSE is bedside examination.

Table 3.

Descriptive and inferential statistics by DDC status for predictor and other variables for initial observations Median (25th, 75th percentile) of initial observationsa

Variables Predictors ABS GOAT CTD total DelRS TFC (days) Age Education TSI (days) Other variables GCS CTc

DDCþ (n ¼ 59) 19 32 11 16 7 36 12 27

(16, 24) (3, 57) (0, 20) (13, 20) (2, 23) (24, 51) (10, 12) (18, 39)

7 (5, 9.5) 1 (1, 2)

DDC (n ¼ 26) 15 87 28 10 4 24 12 17

p-valueb

(14, 16) (70, 96) (18, 30) (8, 12) (1, 8) (20, 40) (10, 16) (14, 26)

9 (5, 13) 1 (0, 1)

0.001 0.001 0.001 0.001 0.03 0.06 0.11 0.01 0.08 0.05

a

The median (50th percentile) and the lower and upper quartiles (25th, 75th percentile). p-values computed using Mann-Whitney test. c Number of contusions coded from CT neuroimaging studies. b

Table 2 shows the occurrence of confusion-related symptoms as measured by the DelRS at the initial evaluation for DDCþ and DDC subjects. Tracking of subjects meeting DDC through weekly evaluations revealed that the median duration of delirium was 43 days from date of injury (31 and 63 days; 25th and 75th percentile, respectively). Chart review indicated that individuals who were DDCþ on their initial evaluation did not statistically differ in Emergency Department GCS score, age or education compared to the DDC group ( p-values determined using MannWhitney test; see table 3). However, the DDCþ group did have significantly longer TFC (median ¼ 7 days) as compared to the DDC group (4 days) and underwent initial evaluation later post-injury (27 days) relative to the DDC group (17 days). Using Fisher’s Exact Test, the DDCþ and DDC groups were equally likely to


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Table 4. Adjusted results of multivariable logistic regression analysis (357 observations) Predictor

Comparisona

ABS GOAT CTD total DelRS TFC (days) Age Education TSI (days)

14, 32, 9, 8, 2, 22, 10, 26,

20 88 28 16 26 47 13 59

ORb

95% CIc

p-value

1.73 0.35 0.31 10.1 0.46 1.16 0.89 0.45

0.89, 0.17, 0.18, 3.72, 0.85, 0.63, 0.64, 0.21,

0.11 0.01