Anxiety Levels Observed in Candidates for Liver Transplantation

Anxiety Levels Observed in Candidates for Liver Transplantation G.R. Santos, I.F.S.F. Boin, M.I.W. Pereira, T.C.M.P. Bonato, R.C.M.A. Silva, R.S.B. Stucchi, and R.F. da Silva ABSTRACT Introduction. Anxiety can be considered an emotional state that does not present itself at the same intensity in all patients, and can be classified into 3 levels: mild, moderate, and severe. The patient, upon entering the waiting list for transplantation, reflects on the decision taken, which leaves him constantly anxious about the idea of possible death. Objective. This study had the aim of evaluating the degree of anxiety observed in orthotopic liver transplantation (OLT) candidates and whether there was a correlation between anxiety and etiologic diagnosis. Methods. This study was a prospective study where the patients underwent psychological evaluation by Beck Anxiety Inventory (BAI). The anxiety level was minimal, mild, moderate, or severe. The Model for End-Stage Liver Disease (MELD) score and etiology were recorded. Results. The level of anxiety found were as follows: 55% minimal, 27% mild, 12% moderate, and 7% severe. The correlation between level of anxiety and etiologic diagnosis showed that 71% of patients with alcoholic cirrhosis and 60% of those with liver cancer showed a minimal degree of anxiety and 27% of patients with autoimmune cirrhosis had severe anxiety. Conclusion. We found that in patients with autoimmune hepatitis, the degree of anxiety was more pronounced. It is believed that the absence of physical symptoms is an important factor when observing anxiety in OLT candidates. T THE TIME of evaluation for Orthotopic liver transplantation (OLT), patients with liver failure typically have clinical impairment due to severe malnutrition, risk of bleeding esophageal varices, and recurrent encephalopathic states. Thus, it can be observed that, for subjects with organ failure, the treatment period is one of poor physical condition and emotional fragility. The onset of psychiatric and psychological problems appear, such as adjustment reactions, depressive symptoms or anxiety, distortion of body image, developmental delays, and sexual dysfunction.1 Upon entering the waiting list for transplantation, the subject may be called at any time due to the unpredictability of the availability of organs. This may be accompanied by successive reflections on the decision taken with constant anxiety about the idea of possible death mainly when the donated organ arrives.2 The previous experiences of individuals who have had other surgical procedures can also compromise their emotional state, mainly due to the use and duration of general

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anesthesia. For the individual, general anesthesia is the mobilization of his protective mechanisms, becoming completely dependent on others, thus losing control of his body, spatial parameters, and favoring the triggering of reactions such as restlessness and anxiety.3 The patients eligible for OLT face from the moment they are diagnosed a fight against time, waiting for the call, the possibility of rejection, the question of healing, and anxiety of death. They are also worried about personal adjustment and the need for family support during the treatament.4

From the Unit of Liver Transplantation, Service of Psychology, Gastrocenter, Faculty of Medical Sciences, State University of Campinas, SP, Brazil and Liver Transplantation Unit, Hospital de Base in São José do Rio Preto, SP, Brazil. Address reprint requests to Ilka Boin, Rua Aldo Oliveira Barbosa 184, Campinas/SP-Brazil CEP 13086-030. E-mail: ilkaboin@ yahoo.com 0041-1345/10/$–see front matter doi:10.1016/j.transproceed.2010.01.009 513

514

Psychological follow-up is extremely important in the pretransplantation period because during this time most patients will not accept their status, do not believe in the necessity to do the transplantation, which brings on their fears and emotions, and can result in poor adherence to treatment and possible organ rejection.5 In the edition of DSM-IV (Diagnosis and Statistical Manual of Mental Disorders),6 anxiety disorders are divided as follows: Panic Attacks, Agoraphobia, Social Phobia, Specific Phobia, Obsessive-Compulsive Disorder, Posttraumatic Stress Disorder, Acute Stress Disorder, Disorder Generalized Anxiety Disorder, Anxiety Disorder Due to a general medical condition, Disorder Substance-Induced Anxiety, Anxiety Disorder Not Otherwise Specified, and Panic Disorder with or without agoraphobia. For Beck et al7 there are 2 types of anxiety. The first type is transient state, associated with unpleasant feelings consciously perceived and attenuated due to the presentation or removal of some external event. The second type is called anxiety-trait, which is behavior that remains latent, although, activated by certain situations, the individual is likely to feel some degree of anxiety about these situations, which are usually environmental. The anxiety may be normal or pathological. This is a very important distinction because only the normal anxiety disorder leads to a necessary and inherent feeling in human beings. According to Cabrera et al,8 pathological anxiety can trigger a loss in self-esteem, acquired knowledge, socialization, memory, and predisposition to greater vulnerability in terms of physical and psychological losses. In specific cases of chronic liver disease, this disorder may be even higher due to the necessity of a transplantation. We sought in this study to evaluate the degree of anxiety related to the completion of OLT and the possible correlation between anxiety and etiologic diagnosis. METHODS This is a prospective study in which we included patients on the waiting list for OLT who attended an outpatient clinic and those hospitalized at 2 hospitals. We studied 215 patients of both genders, regardless of blood type. The subjects live in Campinas, Sao Paulo (SP), São José do Rio Preto (SP), or in other cities in the state of SP. Patients without indication for OLT, those younger than 18 or older than 75 years of age, and those with hepatic encephalopathy prior to psychometric assessment were excluded. The variables studied were age (between 18 and 72 years), both genders, marital status (single/widowed, married/living together, and separated or divorced), occupation (normal retirement or that due to disability, working or unemployed), education (elementary, high school or further education, complete or incomplete), and etiology of liver disease. We used the (Model for End-Stage Liver Disease (MELD) score): (0.957 ⫻ log e [creatinine (mg/dL)] ⫹ 0.378 ⫻ log e [bilirubin (mg/dL)] ⫹ 1.120 ⫻ log e (INR) ⫹ 0.643) * 10, to characterize the patients.9 Psychometric evaluation was performed in these patients based Beck Anxiety Inventory (BAI).10 After reading and signing the

SANTOS, BOIN, PEREIRA ET AL consent term, subjects responded to the questionnaire in about 15 minutes. The BAI consists of 21 items that are descriptive statements (Symptoms of Anxiety) and should be evaluated by the subject referring to himself, on a scale that reflects the increasing severity of each symptom: 0, Not at all; 1, Slightly: not bothered me much; 2, Moderate: it was very unpleasant, but I could bear it; and 3, Severe: it was very difficult to bear. Symptoms included by Cunha10 are as follows: numbness or tingling, sensation of heat, tremors in the legs, unable to relax, fear that the worst can happen, stunned or dazed, palpitations or racing heart, no balance, terrified, nervous, choking feeling, trembling hands, general trembling, fear of losing control, breathing difficulty, fear of dying, scared, indigestion or discomfort in the abdomen, feeling of fainting, flushed face, and sweating (not due to heat). The total score is the result of the sum of the scores of individual items. Inventory BAI allows for the classification levels of intensity of anxiety. These levels are as follows: minimal (from 0 –7); mild (8 –15); moderate (from 16 –25); and severe (26 – 63). Four points are added to the total sum of scores obtained when the subject is a woman. The presence of anxiety was defined as follows: range of 8 – 63 points ⫽ yes (the presence of anxiety); range of 0 –7 ⫽ no (not anxiety). Descriptive statistics were used for continuous variables and frequency tables for categorical variables using the chi-square test and Fisher exact test. To compare the levels of anxiety with age and MELD we used the nonparametric Mann-Whitney (for comparison of 2 levels) and Kruskal-Wallis (for comparison of 4 levels). The level of significance was 5%. The software used was the SAS System for Windows (Statistical Analysis System), version 9.1.3.11 The data were analyzed by the Statistical Office of the Board of Research of the Faculty of Medical Sciences, Unicamp (Microsoft - State University of Campinas software - 2005). The present study was endorsed by the Ethics Committee on Research at the Faculty of Medical Sciences, Unicamp and São Jose do Rio Preto, Hospital de Base.

RESULTS

This study involved 215 patients; 165 (76.7%) were male and 50 (23.3%) were female. The average age of the patients was 49.5 years and the average MELD score was 16.8 ⫾ 4.5. One hundred fifty-eight (73.5%) were married or living together, 37 (17.2%) were single or widowed, and only 20 (9.3%) were separated. Regarding blood type, 97 (45.1%) had blood type A, 96 (44.6%) had blood type O, 17 (7.9%) had blood type B, and only 5 (2.3%) had blood type AB. The etiology of liver disease most commonly found in patients with chronic liver disease was hepatitis C with a frequency of 37%. Regarding the level of anxiety, we noted that 55% of patients had minimal degree, 27% had mild, 12% had moderate, and only 7% had severe. It was observed that 88 (40.9%) patients were retired and 27 (12.6%) were still working. Patients who were unemployed had a higher anxiety level (18%) than those who were working. There was also no statistically significant difference between marital status, age, and level of anxiety, with patients who were separated having a lower prevalence of severe anxiety level with 20%.

ANXIETY LEVELS

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Of the patients studied, 109 (50.7%) had elementary school education, 66 (30.7%) had high school education, and 40 (18.6%) had further education. Patients with autoimmune hepatitis had a tendency to have higher levels of anxiety than alcoholic patients or patients with hepatocellular carcinoma (HCC), although the correlation was not statistically significant. We observed that there was a tendency for high scores of anxiety related to lower MELD scores (P ⫽ .10; Fisher exact test) and also there was no significant difference between MELD score and etiology (P ⫽ .11; Fisher exact test). Table 1 shows the relationship between MELD, observed symptoms, and presence of anxiety. It was noted that the symptoms “numbness or tingling” (P ⫽ .02) and “fear of losing control” (P ⫽ .04) had a statistically significant relationship with the MELD score. DISCUSSION

Liver cirrhosis has affected more than half of patients undergoing OLT, experiencing a decrease in the quality of life by stress, clinical prognosis of the disease, presence of medical complications, social limitations, and prolonged use of drugs. These factors contribute to a great emotional impact of the individual, causing difficulties in the reorganization of family dynamics, with impoverished psychological structure related to different levels of anxiety, phobia, obsession, and depression.12 In the present study we did not observe significant changes in the level of anxiety of OLT candidates, with only 7% with severe anxiety level. Cerezetti4 described the psychiatric disorders most commonly found in these patients, reporting delirium (13%–18.6%), adjustment disorder (8%–19.8%), and organic disorders of anxiety major depression (5%). According to the literature, the pretransplantation period is characterized primarily by anxiety and

depression, the guilt that the patient feels about the death of the donor, the disturbances adaptation, hepatic encephalopathy, and family maladjustment.4 The literature describes numerous tools to evaluate anxiety and depression, such as the Anxiety Scale, the Hamilton Anxiety Inventories, and the Beck Depression Inventory, BAI–BDI, the latter being the most sought for clinical evaluation. Also available are Inventory STAI I and II and the Hospital Anxiety and Depression Scale (HADS).13,14 An evaluation of anxiety and depression conducted by the Santa Casa de Misericordia de Sao Paulo with 79 patients in the preoperative period resulted in 44.3% cases of anxiety and 26.6% cases of depression using the HADS.15 In this study we used the Anxiety Inventory Beck–BAI because it is a psychometric assessment applied by qualified psychologists to assess the level of anxiety. It is, however, difficult to differentiate disease-related symptoms from symptoms related to emotional state changes of the individual. The use of psychometric tests has some limitations because the Brazilian population is inclined to believe that expressing some socially undesirable behaviors, dissatisfaction with the health service, and disbelief in the future may cause the psychological evaluation to affect the pretransplantation evaluation.16 The prevalence of anxiety and depression in the pretransplantation period was described by Marcolino et al in 26.6% of the patients.15 In our study we studied the presence and level of anxiety and we observed 55% of the patients with a minimum level of anxiety. We also tested correlations between anxiety level, educational level, and marital status with no statistically significant results. The patients with “separated” marital status had more severe anxiety level (20%), most probably due to the lack of a specific caregiver in the postoperative period.

Table 1. Distribution of the MELD Score, Presence of Anxiety, and Symptoms Observed MELD Symptoms

Numbness/tingling Unable to relax Fear (worst happens) Nervous Fear (losing control) Fear of dying Scared Indigestion *P ⬍ .05; Fisher exact test.

Anxiety

ⱕ10

11–18

19–25

⬎25

Total

P

Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No

14 (17.1%) 8 (6.0%) 13 (14.4%) 9 (7.9%) 12 (13.3%) 10 (8%) 10 (9.3%) 12 (11.1%) 13 (17.6%) 9 (6.4%) 8 (11.3%) 14 (9.7%) 9 (14.75%) 13 (8.44%) 9 (13.0%) 13 (8.9%)

40 (48.8%) 82 (61.6%) 47 (52.2%) 75 (60.0%) 47 (52.2%) 75 (60%) 61 (57.0%) 61 (56.5%) 35 (47.3%) 87 (61.7%) 44 (61.9%) 78 (54.2%) 31 (50.8%) 91 (59.1%) 42 (60.8%) 80 (54.8%)

28 (34.1%) 40 (30.1%) 30 (33.3%) 38 (30.4%) 30 (33.3%) 38 (30.4%) 33 (30.8%) 35 (32.4%) 25 (33.8%) 43 (30.5%) 19 (26.7%) 49 (34.0%) 19 (31.1%) 49 (31.8%) 17 (24.6%) 51 (34.9%)

0 (0%) 3 (2.3%) 0 (0%) 3 (2.4%) 1 (1.1%) 2 (1.60) 3 (2.8%) 0 (0%) 1 (1.3%) 2 (1.4%) 0 (0%) 3 (2.1%) 2 (3.3%) 1 (0.6%) 1 (1.4%) 2 (1.4%)

82 133 90 125 90 125 107 108 74 141 71 144 61 154 69 146

.02* .15 .51 .45 .04* .49 .19 .38

516

Martins et al16 pointed out a lower incidence of depression in patients with higher education level on the waiting list for OLT. Infection with hepatitis C is the etiology of major indication for OLT and is also the leading cause of cirrhosis, with a prevalence of 3% in the world population. In Brazil the infected population with this virus varies from 2.5%–10%,17 being the main etiology for OLT in this country. In our study hepatitis C was also the main cause for OLT, being found in 37% of all patients. The results concerning the correlation between anxiety level and etiology showed no statistically significant difference, but it was observed that patients with autoimmune hepatitis had severe anxiety (27%). The alcoholic patients and patients with HCC showed minimal anxiety level in 71% and 60% of the patients, respectively, but when we correlated anxiety level and etiology we found a tendency (P ⫽ .10; Fisher exact test). A survey conducted in Portugal by Telles-Correia et al18 found a high frequency of anxiety symptoms in patients with HCC and depression prevalence in female patients, in alcoholics, and in individuals with viral hepatitis C. Autoimmune hepatitis affects mainly childbearing age women and usually those patients had asymptomatic disease with laboratory abnormalities and low MELD score.19,20 This can be a cause found in our study to explain severe anxiety level. The literature has shown that women are more easily affected by anxiety, social, and cultural issues, in a study made in 1998 by La Rosa,21 using the instruments STAI I and II, in which women had significantly higher scores than men, explaining that this fact is due to the ethical expectations involving female behavior. In addition to the disease, women have to deal with entering the labor market, greater need of personal statement, seeking financial independence, desire to start a family, an exhausting work day, acting as mothers and wives. All of these factors produce a lot of tension for herself and her relatives. In this study we observed a tendency in patients with autoimmune hepatitis to present a severe degree of anxiety. It is believed that the absence of physical symptoms could be an important factor when observing anxiety in OLT candidates. REFERENCES 1. Garcia JRC, Zimmermann PR: Falência e Transplante de Órgãos. In Botega NJP (ed): Prática Psiquiátrica no Hospital Geral, 2nd Ed. Artmed, Porto Alegre; 2006

SANTOS, BOIN, PEREIRA ET AL 2. Tavares E: A vida depois da vida: reabilitação psicológica e social na transplantação de órgãos. Aná Psicológica 22:765, 2004 3. Giuntini PB: Avaliação do Estado de Ansiedade em Pacientes Submetidas a Cirurgias Eletivas Sob Regime Ambulatorial ou Sob Regime de Internação. Tese de Doutorado. Escola de Enfermagem de Ribeirão Preto. Universidade de São Paulo. Ribeirão Preto; 2006 4. Cerezetti CRN: O Paciente de Transplante Hepático: Um Estudo Psicológico Sobre a Força do Resiliente do Hepatopata Grave. Tese de Doutorado da Universidade de São Paulo. SP; 2002 5. Abrunheiro LMM, Perdigoto R, Sendas S: Avaliação e Acompanhamento Psicológico Pré e Pós-Transplante Hepático. Coimbra, Portugal Psicologia, Saúde e Doença 6:139, 2005 6. Manual Diagnóstico e Estatístico de Transtornos Mentais: DSM- IV. Porto Alegre: Artmed; 2000 7. Beck A, Freeman A: Terapia Cognitiva dos Transtomos de Personalidade. Porto Alegre: Artes Médicas; 1993 8. Cabrera CCE, Sponholz A Jr: Ansiedade e Insônia. In Botega NJ (ed): Prática Psiquiátrica no Hospital Geral. Porto Alegre: Artmed; 2001, p 251 9. Freeman RB: Mathematical models and behavior: assessing delta MELD for liver allocation. Am J Transplant 4:1735, 2004 10. Cunha JA: Manual da Versão Em Português das Escalas Beck. SP: Casa do Psicólogo, 2001 11. Fleiss JL: Statistical Methods for Rates and Proportions, 2nd Ed. NY: J Wiley & Sons; 1981; p 321 12. Martins PD, Sankarankutty AK, Silva OC Jr, et al: Distress psicológico em pacientes na lista de espera para transplante de figado. Acta Cir Bras 21(suppl 1):40, 2006 13. Marcolino JAM, Suzuki, FM, Alii LAC, et al: Escala hospitalar de ansiedade e depressão: estudo da validade de critério e da confiabilidade com pacientes no pré-operatório. Rev Bras Anestesiol 57:52, 2007 14. Andrade LHSG, Gorenstein C: Aspectos gerais das escalas de avaliação de ansiedade. Rev Psiq Clin 25:285, 1998 15. Marcolino JAM, Suzuki FM, Alli LAC, et al: Medida da ansiedade e da depressão em pacientes no pré - operatório. Estudo comparativo. Rev Bras Anestesiol 57:157, 2007 16. Martins PD, Sankarankutty AK, Silva O de C, et al: Psychological distress in patients listed for liver transplantation. Acta Cir Bras 21(suppl 1):40, 2006 17. Sousa VV, Cruvinel KPS: Ser Portador de Hepatite C: Sentimentos e Expectativas. Texto Contexto Enferm, Florianópolis 17:689, 2008 18. Telles-Correia D, Barbosa A, Barroso E, et al: Abordagem psiquiátrica no transplante hepático. Artigo de revisão. Acta Med Port 19:165, 2006 19. Porta G: Hepatite auto-imune. J Pediatr (Rio J) 6(suppl 1):181, 2000 20. Ferreira AR, Roquete MLV, Penna FJ, et al: Hepatite auto-imune em crianças e adolescentes: estudo clínico, diagnóstico e resposta terapêutica. J Pediatr (Rio J) 78:309, 2002 21. La Rosa J: Ansiedade, sexo, nivel sócio-econômico e ordem de nascimento. Psicol Reflex Crit 11:59, 1998