A Psychiatric Study of 247 Liver Transplantation Candidates

Research Articles A Psychiatric Study of 247 Liver Transplantation Candidates PAULA T. TRZEPACZ. M.D. RICHARD BRENNER. M.D. DAVID

H.

VAN THIEL. M.D.

This study prospectively evaluated 247 consecutive liver transplantation candidates/or the presence o/psychiatric disorders. While one-halfdid not meet DSM-lll criteria/or a psychiatric diagnosis. 18.6% had delirium. 19.8% had an adjustment disorder, 9% had alcohol abuse or dependence, 4.5% had major depression. and 2% had other drug abuse or dependence. Delirious subjects were significantly more likely to have a lower serum albumin. lower Mini-Mental State exam scores. higher Trailmaking Test scores (both A and B). and more dysrhythmia on electroencephalogram (EEG)./n addition. while both delirious and nondelirious subjects were judged to have high levels 0/ overall stress. those with delirium had significantly poorer adaptive functioning and lower occupational,family. and social scale ratings. Thus. while all liver transplant candidates are under substantial psychosocial stress and require psychosocial support. those identified as being delirious require particular attention because o/their numerous cognitive, medical, and psychosocial problems.

L

iver transplantation has become a procedure increasingly recommended for the management of end-stage liver disease. Improvements in the surgical technique and the use ofcyclosporine account for the improved results and the increasing referrals by primary care physicians of their patients for the procedure. Despite this increased application of liver transplantation, there has been little attention given to the psychiatric problems of this unique population. Penn I described the behavior of 23 children and 10 adults studied pre- and post-liver transplant and noted a high prevalence of preoperative confusion, anxiety, and depressive symptoms. House et al. 2 studied 14 children and 20 adults who had survived an earlier liver transplant. Prior to the transplant, one-half of the children and nearly all of the adults had experienced a psychiatric disturbance, including organic brain syndromes, depression, and anxiety. In neither study, however, was a VOLUME 30· NUMBER 2 • SPRING 1989

structured, standardized neuropsychiatric evaluation used; thus the findings remain somewhat anecdotal. In our previously reported pilot study of 40 candidates for liver transplantation, we found Diagnostic and Statistical Manual o/Mental Disorders. Third Edition 3 (DSM-III) diagnoses in one-half of the subjects studied and an association between low serum albumin levels and de-

Received February 2. 1988; revised July 12. 1988; accepted July 29. 1988. From the Allegheny General Hospital and the Medical College of Pennsylvania (Allegheny Campus). Pittsburgh. Pennsylvania; and the Departments of Psychiatry and Neurology. and the Division of Gastroenterology. Univ,ersity of Pittsburgh. School of Medicine. Pittsburgh. Pennsylvania. Address reprint requests to Dr. Trzepacz. Department ofPsychiatry•Allegheny General Hospital. 320 East North Avenue. Pittsburgh. PA 15212. Copyright © 1989 The Academy of Psychosomatic Medicine.

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lirium. 4 Patients who have liver failure are particularly susceptible to becoming delirious. Delirium is an organic mental syndrome that includes global cognitive dysfunction, perceptual disturbances, disorientation, hallucinations, delusions, sleep-wake cycle changes, and affective lability. Delirium is also associated with diffuse slowing of the EEG background rhythm. In this article, we report our findings in 247 individuals who were being evaluated for possible liver transplantation. We assessed these patients with a group of standardized neuropsychiatric tests, including cognitive assessment, EEGs, serum albumin levels, and psychosocial-stressor ratings. METHODS Subjects The psychiatric consultation-liaison service of Presbyterian University Hospital in Pittsburgh evaluated 247 consecutive patients with endstage liver disease who were admitted for consideration for orthotopic liver transplantation. These subjects were admitted to the gastroenterology service over the course of two years. While subjects were referred from national and international regions, nearly all spoke English and were able to cooperate with the psychiatric evaluation. When necessary, a family member served both as an interpreter and as a second informant. All information was gathered during a five- to sevenday hospitalization. Informed consent was obtained from each subject for the transplantation evaluation. Procedures Each subject was assessed by a psychiatrist. This psychiatric evaluation included a semistructured diagnostic interview using a modified Brief Evaluation Form (BEF)5 and DSM-III criteria. The BEF includes descriptions and ratings for five psychosocial stressor scales. These are: overall stressor severity during the preceding 12 months, which is rated on a seven-point scale (l=none to 7=catastrophic) and is Axis IV of DSM-III; highest level of adaptive function at148

tained during a few months of the preceding 12 months, which is rated on a seven-point scale (1 =superior to 7=grossly impaired) and is Axis V of DSM-III; and functioning during the preceding month for occupational, family, and social issues, each of which is rated on a five-point scale (I =superior to 5=markedly impaired). These psychosocial scales were clinician-rated using all available sources of information. The Mini-Mental State (MMS) exam was administered to detect cognitive dysfunction. 6 A total score on the MMS of less than 24 indicates diffuse cognitive dysfunction. The Trailmaking Tests, both Parts A and B/ were used to assess cognitive flexibility and concentration, as well as visual-motor tracking skills, counting ability, and spatial skills. Scores were recorded as the number of seconds required to perform each test. Scores of 34 seconds or less on Part A and of 89 seconds or less on Part B were considered within normal limits for most adults. Previous studies have suggested that the Trailmaking Tests are particularly sensitive in detecting diffuse cognitive dysfunction. 4 ,8 The serum level of albumin was recorded, as it has also been shown to correlate with the presence of identified cognitive deficits, while other liver injury and function parameters do not.4 ,9 The normal range for serum albumin is 3.2 gldl to 5.2 gldl in our laboratory. EEGs were performed on 16- or 17-channel instruments by applying disc electrodes in accordance with the International 10-20 System using both bipolar and referential montages. EEGs were rated according to the Mayo Clinic classification system 10 and coded as normal or dysrhythmia grades I through 3. Dysrhythmia grade I recordings usually demonstrate a slight slowing of the dominant posterior rhythm to below alpha (8-13 Hz) frequency, and/or an increase in the amount of diffuse theta (4-7 Hz) activity. Grade 2 dysrhythmias usually have generalized bursts of slower activity, primarily in the theta and occasionally the delta «4 Hz) frequencies, and/ or further slowing of background rhythms. Dysrhythmia grade 3 recordings are characterized by frequent generalized bursts of delta activity and usually the dominant posterior rhythm does not exceed 6 Hz. PSYCHOSOMATICS

Trzepacz et al.

Data Analysis The data were analyzed on a VAX mainframe computer using the SPSS-X statistical software package. In addition to descriptive statistics, such as means and standard deviations, the independent t-test was used to compare delirious subjects and nondelirious subjects for all test variables except EEG. The EEG results were compared using chi square analysis. Pearson correlations were used to compare age, albumin concentrations, and neuropsychiatric variables with the psychosocial ratings. RESULTS Subjects

Of the 247 subjects, 155 were female and 92 were male. The mean age was 41.3 ± 11.1 years (range of 16 to 68), with no significant difference noted between the men and women studied. The most common liver-disease diagnoses were primary biliary cirrhosis (25.9%), postnecrotic cirrhosis (17.8%), cirrhosis of unknown etiology (17.0%), sclerosing cholangitis (14.6%), and other (24.7%). Neuropsychiatric Evaluations Nearly one-half of the subjects had at least one psychiatric diagnosis (Table I). Delirium and adjustment disorders were the most common di-

agnoses, and each was present in nearly one-fifth of the subjects studied. Mean scores for serum albumin (3.0 ± 0.7 g/dl, n=246) and Trailmaking Tests A (47.3 ± 43.9 sec, n=238) and B (116.1 ± 95.8 sec, n=234) were slightly abnormal, while the mean MMS score (28.1 ± 2.8 points, n=244) was normal. EEGs were normal in 63% of the subjects tested (n=212), and demonstrated grade I dysrythmia in 23%, grade 2 in 9%, and grade 3 in 5%. When subjects were divided into delirious (n=46) and nondelirious (n=201) subgroups, no significant difference in age (Table 2) between the two groups was evident. However, the serum albumin level, MMS, and Trailmaking Test TABLE 1. Psychiatric diagnoses (DSM·DI) in 247 liver transplantation candidates (multi· pie diagnoses possible) Diagnosis

n

Percent

None

51.0

125

Delirium

18.6

46

Adjustrnentdisorders

19.8

49

with depressed mood

12.6

31

with anxious features

4.0

10

with mixed emotions

3.2

8

Alcohol abuse/dependence

8.9

22

Major depression

4.5

11

Other drug abuse/dependence Cyclothymic disorder

2.0 0.8

5 2

Organic affective disorder Dementia

0.8 0.8

2 2

TABLE 2. Neuropsychiatric variables compared between delirious and nondelirious cases Variable

I2elirious X±S.D.

No.!!delirious X±S.D.

age (years)

41.9 ± 11.7

41.1 ± 11.0 n=201 3.1 ±0.6 n=200 28.6 ± 1.6 n=200 38.8± 15.4 n=194 89.3±36.7 n=193

n=46

serum albumin (g/dl) Mini-Mental State (points) Trailmaking A (seconds)

Trailmaking B (seconds)

2.6±0.5 n=46

25.8± 5.0 n=44

87.3±90.1 n=41 242.3 ± 165.1 n=41

.

pValue

NS <.001 <.002 <.002 <.001

'by I-test

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Liver Transplant Candidates

scores for both Parts A and B were each significantly more impaired in the delirious subjects (Table 2). The EEG results were also significantly more abnormal in the delirious subjects


TABLE 3. Psychosocial stressor scale ratings obtained In 247 liver transplant candidates: comparison between delirious and nondellrious groups ~1Ir1um

Scale

_Total XtS.D.

Overall stress

4.7 t 1.0

4.9 t 1.0

4.6t J.I

n=208

n=37

Highest level of adaptive function Occupational function Social function

NOJ!dellrium XtS.D.

XtS.D.

pValue " NS

2.6 t 1.0

3.0 t J.I

n=207

n=37

3.4 t 1.4

4.2 t 1.4

n=171 2.5 to.9 n=J70 3.2 t 1.4

n=188

n=35

n=167

2.3 to.9

2.9 t 1.0

2.2tO.8

n=193

n=34

n=159

<.01 <.001 <.002

"by I-test. comparison between delirious and nondelirious groups

FIGURE I. Overall stressor severity ratings 70 l""r'=======J-----~

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FIGURE 2. Ratings 01 the highest level of adaptive functioning In past year

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PSYCHOSOMATICS

Trzepacz et al.

had grade 2, and 10 had grade 3. Thirty-six nondelirious subjects had grade I dysrythmia, and 8 had grade 2.

FIGURE S. Current social function ratlnp

Psychosocial Stressor Scales All of the subjects who were rated had moderate to severe levels of overall psychosocial stress (Table 3), yet most had achieved a "good" to "very good" rating on the highest level of adaptive functioning during the preceding year. The occupational function obtained during the month preceding the evaluation was "moderately impaired" in many subjects, most of whom were too ill to continue to work. On the other hand, social and family relationships were generally viewed as only "slightly impaired" and often were rated as "normal." When subjects were divided into delirious and nondelirious subgroups, no significant difference was noted in overall stress levels (Table 3 and Figure I). However, there were highly significant differences in occupational (Figure 2), family (Figure 3), and social functioning (Figure 4), with the delirious subjects being more impaired in each category. There was also a significant difference in the highest level ofadaptive function attained during the preceding year, such that delirious subjects attained only "good" levels, while the nondelirious subjects attained "very good" levels (Table 3 and Figure 5). Correlations Age did not correlate with any variable evaluated except in the delirious subjects, in whom it correlated with the Trailmaking Test B score (r=.4O, p=.OO5). The serum albumin level correlated inversely with occupational functioning in delirious subjects (r=-.42,p=.006). Lower MMS scores correlated with poorer family functioning in the delirious subjects (r=-.4O, p=.OO8). The significance of each of these correlations persisted at a p<.05 level even after a Bonferroni correction. The cognitive variables that were assessed and the serum albumin levels did not correlate with any of the psychosocial ratings found in the VOLUME 30· NUMBER 2 • SPRING 1989

nondelirious subjects. DISCUSSION Using a prospective, standardized evaluation we assessed both the neuropsychiatric and psychosocial status of 247 consecutive liver-transplant candidates, and this comprises the largest consecutive sample of liver-transplant candidates studied to date. All of our subjects and their families were under considerable stress and were rated, on average, in the more severely stressed range for overall stress. These stressors include the uncertainty of qualifying for a transplant, II waiting for an available donor organ,12 the uncertainty of surviving the surgery and any postoperative complications, and the anticipated complications of immunosuppressant treatment, especially infections. Most of our subjects were occupationally impaired. Financial problems were consequences of not working, family role changes during preoperative disability and postoperative rehabilitation phases, questions about employability, difficulty when new employers were reluctant to provide affordable medical and disability insurance coverage, and the expense of cyclosporine. Family and social functioning was rated as being slightly impaired. Stresses on family members include living away from home in Pittsburgh (often in a hotel for many days), the need to appear emotionally "strong" for the patient, taking on family responsibilities that were previously handled by the patient, and coping with 151

Liver Transplant Candidates

the fear of losing loved ones. Whether or not these stresses are unique to liver-transplantation patients and their families is unknown. To our knowledge. a comparative study between liver- and heart- or kidney-transplantation candidates has not been published. One could expect a certain prevalence ofdelirium or adjustment disorder in anyone who is ill enough to be a candidate for organ transplantation. l] On the other hand. differences in psychosocial stressors might be anticipated in kidney-transplant candidates who have dialysis as an alternative treatment for organ failure. unlike the options available for heart or liver transplant candidates. Psychological issues in candidates for heart l4 ,IS and kidney l6 transplants have been described elsewhere and seem similar to the issues we have described for liver-transplant candidates. Eleven percent of our subjects had a drug or alcohol disorder. and this has implications for debate regarding the use of organ transplantation in drug-dependent persons. Major depression was surprisingly infrequent in our population. while adjustment disorders were more prevalent. The latter is understandable. given the degree of stress that most candidates and their families were under. The prevalence of delirium in our sample was 18.6%. which is similar to that reported to occur in many other general hospital samples. 17.18 However. most other reports of delirium in general hospital samples are either based on referral samples or estimates. while ours was obtained in a consecutive sample of an at-risk. medically ill population. Earlier reports of liver transplant candidates have noted a 30% to 50% prevalence of delirium or encephalopathy.I.2,4 The difference between the earlier reports and this report can probably be explained as a result of evolving improvements in transplantation medicine which currently allow transplantation in less critically ill patients. Our delirious subjects had significantly lower serum albumin levels and more abnormalities in cognitive functioning and on EEG than did the nondelirious subjects. and this is consistent with our prior study.4 Serum albumin is one IS2

indicator of the severity ofliver failure. However. our pilot study did not find significant differences in psychosocial ratings between delirious and nondelirious subjects. perhaps because of the small sample size.4This study found significantly worse functioning in four psychosocial areas in subjects who became delirious. Delirious subjects had significantly more occupational impairment and their ability to perform in their occupations declined linearly with decreasing serum albumin levels. It is unknown whether or not they had optimal medical control of deliriogenic influences. including dietary compliance. prior to the hospitalization. Delirious subjects all demonstrated more impairment in family functioning. and this dysfunction was statistically related to the degree of impairment identified in their cognitive ability as measured on the MMS. The psychosocial rating scales we used are useful for screening purposes only. Further information on psychosocial function of liver-transplant patients and their families would require more focused psychometric instruments. Many transplant candidates and their families underestimate the stress they are experiencing in order to present themselves as "better" candidates for transplantation.4 or they may use denial as a coping mechanism. 19 We surprisingly found that social and family relationships were rated as only slightly impaired. That one-half of our subjects met criteria for a DSM-III diagnosis underscores the need for psychiatric services in this population. The MMS is an easily administered cognitive screening test and could be used by internists to identify delirious patients with liver disease who might benefit from psychiatric intervention and family therapy. We strongly believe that psychiatric and social worker involvement is essential at an active transplantation center and that it is useful to patients. their families. and surgeons. both before and after transplantation.

The authors thank Robert W. Baker, M.D., and Stuart C. Yudofsky. M.D., for manuscript editing and comments, and Ms. Olga Petruskafor manuscript preparation. PSYCHOSOMATICS

Trzepacz et al.

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performance defects in cirrhotic patients without oven encephalopathy. Arch Intern Med 140:519-521,1980 10. Klass DD, Sharbrough FW: Electroencephalography. in Aronson E, Auger RG. Bastron JA, et aI (eds): Clinical Examinations in Neurology. Mayo Clinic and Mayo Foundation. Fifth Edition. Philadelphia, WB Saunders Co, 1981, pp 278-299 I I. Frierson RL, Lippmann SB: Hean transplant candidates rejected on psychiatric indications. Psychosomatics 28:347-355.1987 12. Levenson IL, Olbrisch ME: Shonage of donor organs and long waits. Psychosomatics 28:399-403, 1987 13. Freeman AM, Watts D, Karp R: Evaluation of cardiac transplant candidates: preliminary observations. Psychosomatics25:197-207.1984 14. Christopherson L: Cardiac transplantation need for patient counseling. Nursing Mirror 143:34-36.1976 15. Christopherson LK. Lunde DT: Selection ofcardiac transplant recipients and their subsequent psychosocial adjustment. Seminars in Psychiatry 3:36-45, 197 I 16. Chambers M: Psychological aspects of renal transplantation.lnt J Psychiatry Med 12:229-236.1982-1983 17. Trzepacz PT, Teague GB. Lipowski ZI: Delirium and organic mental disorders in a general hospital. Gen Hosp Psychiatry 7:101-106, 1985 18. Lipowski ZI: Delirium (acute confusional state), in Frederiks JAM (ed): Handbook of Clinical Neurology. Volume 2. No. 46: Neurobehavioral Disorders. New York, Elsevier Science Publishers, 1985. pp 523-559 19. Mai FM: Graft and donor denial in hean transplant recipients. AmJ Psychiatry 143:1159-1161,1986

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