Underlying pathologies and their associations with clinical features in terminal delirium of cancer patients.

Delirium is a common complication in terminally ill cancer patients. Identification of underlying pathologies and prediction of clinical features may improve effective symptom alleviation. This study aims to clarify precipitating factors and their associations with clinical features of terminal delirium. Consecutive hospice inpatients who developed delirium were prospectively evaluated following a structured protocol. Among 237 patients followed until death, 245 episodes of delirium were identified in 213 patients. Precipitating factors for delirium were disclosed in 93% of the 153 cases in which investigations were completed. Mean number of etiologies was 1.8 +/- 1.1 per patient, and two or more factors were recognized in 52%. The main pathologies identified were hepatic failure, medications, prerenal azotemia, hyperosmolality, hypoxia, disseminated intravascular coagulation, organic damage to the central nervous system, infection, and hypercalcemia. Occurrence of hyperactive delirium and the requirement for symptomatic sedation significantly correlated with hepatic failure, opioids, and steroids, while dehydration-related pathologies were significantly associated with hypoactive delirium. Complete recovery was frequently achieved in cases with medication- and hypercalcemia-induced delirium, whereas a low remission rate was related to hepatic failure, dehydration, hypoxia, and disseminated intravascular coagulation. In conclusion, standard examinations can confirm factors potentially contributing to delirium and thereby predict the severity of agitation and clinical outcomes.

Improved accuracy of physicians' survival prediction for terminally ill cancer patients using the Palliative Prognostic Index.

The Palliative Prognostic Index (PPI) has recently been developed for survival prediction in terminally ill cancer patients. To clarify whether physicians' clinical prediction of survival (CPS) can be improved using this objective assessment aid, two sequential prospective studies were performed on two independent series of hospice inpatients (n = 150 and 108). In the first study, the CPS was prospectively recorded by primary physicians on the basis of their clinical experiences. In the second study, physicians estimated patient prognoses with a reference to the PPI score. The cases where the differences between actual survival (AS) and CPS were 28 days or longer significantly decreased in the second study compared to the first study (42% vs 23%, P < 0.01). Also, the cases where AS was either twice longer or half shorter than CPS significantly declined (49% vs 37%, P = 0.050). As well, serious errors, defined as the cases where AS was either (a) 28 days and twice longer than CPS or (b) 28 days and half shorter than CPS, significantly decreased from 27% in the first study to 16% in the second study (P = 0.028). In conclusion, the PPI can contribute to improvement in physicians' ability to predict survival of terminally ill cancer patients.

Determinants of the sensation of thirst in terminally ill cancer patients.

While a sensation of thirst causes severe distress for a certain proportion of cancer patients in the terminal stage, the factors contributing to this symptom have not been established. To clarify the association between sensation of thirst and medical factors, especially dehydration, a cross-sectional observational study was performed on terminally ill cancer patients receiving inpatient hospice care. On admission to a palliative care unit, 88 consecutive patients underwent blood sampling and were requested to rate the intensity of thirst on a visual analogue scale (VAS). Physicians prospectively evaluated factors that might potentially be contributing to the symptom. The mean VAS score for thirst was 5.0+/-2.8, and 18% of the patients complained of severe thirst with a VAS score of > or = 8. No significant correlations were observed between the VAS score for thirst and the values of total protein, blood urea nitrogen (BUN), creatinine, sodium, osmolality, hematocrit, atrial natriuretic peptide (ANP), and biochemical dehydration defined by the levels of BUN, creatinine, sodium and osmolality. On the other hand, dehydration defined by ANP level (< or = 15 pg/ml), hyperosmolality (> or = 300 mosmol/kg), gastrointestinal cancer, survival, performance status, oral intake, vomiting, and stomatitis were significantly associated with the severity of thirst. In addition, mouth breathing and opioids were determined to be a potential clinical cause of severe thirst when a retrospective chart review was carried out. In conclusion, sensation of thirst is a frequent symptom in terminally ill cancer patients and is associated with dehydration, hyperosmolality, poor general conditions, stomatitis, oral breathing, and opioids. Careful assessments and treatment of underlying causes is important to alleviate patients' distress.

Communication Capacity Scale and Agitation Distress Scale to measure the severity of delirium in terminally ill cancer patients: a validation study.

Although valid measurement of the severity of terminal delirium is of great importance in palliative care settings, existing instruments have considerable limitations. In order to quantify patients' communication capacity and agitated behaviour, two new operational observer-rating scales, the Communication Capacity Scale (Communication Scale) and Agitation Distress Scale (Agitation Scale), were validated. Thirty terminally ill cancer patients diagnosed with delirium were evaluated simultaneously by two palliative care physicians blinded to each other's coding using the Communication Scale and Agitation Scale. In addition, the Memorial Delirium Assessment Scale (MDAS), Delirium Rating Scale (DRS) and Sedation Scale were rated by one researcher. Both scales achieved high internal consistency and inter-rater reliability with Cronbach's alpha coefficients of 0.91 and 0.96, and Cohen's kappa values on each item of 0.72-1.00. The principal components analysis resulted in the emergence of only one component for each scale. The total score on the Communication Scale was highly associated with that of the MDAS (rho = 0.78), Sedation Scale (rho = 0.86), and cognitive items from the MDAS and DRS (rho = 0.83). The whole score on the Agitation Scale was significantly correlated with that of the DRS (rho = 0.61) and agitation items from the MDAS and DRS (rho = 0.61). In conclusion, the Communication Scale and Agitation Scale have acceptable reliability and validity to quantify patients' communication capacity and agitation symptoms of terminally ill cancer patients with delirium.

Effects of high dose opioids and sedatives on survival in terminally ill cancer patients.

Concerns that high dose opioids and sedatives might shorten patient survival could contribute to insufficient symptom alleviation for terminally ill cancer patients. To examine the effects of opioids and sedatives prescribed in the final 48 hours on patient survival, a re-analysis of the prospectively collected data was performed on 209 hospice inpatients. Patient characteristics and clinical symptoms were prospectively recorded, and information about the use of opioids and sedatives in the last two days was collected by a chart review. Opioids were prescribed in 82% of the patients, with a median dose of 80 mg oral morphine equivalent (OME)/48 hours. Sixty percent received some sedative medications, mainly haloperidol (43% of total sample, 7.5 mg/48 hours), midazolam (23%, 23mg/48 hours), and hydroxyzine (15%, 50 mg/48 hours). There were no significant differences in survival between the patients who received different doses of opioids (<240, 240--599, and > or =600 mg OME/48 hours) and of benzodiazepines (0, 1--59, and > or =60 mg parental midazolam equivalent/48 hours). Also, the survival of patients with haloperidol, hydroxyzine, and other sedative medications did not differ from those without. Furthermore, an addition of use of opioids and sedatives in the final 48 hours into the multiple regression model for survival prediction achieved no significant increase in predictability. In conclusion, opioids and sedatives used for symptom control in the last days are not associated with patient survival. They are safe and useful medications to palliate severe distress in the terminal stage of cancer when administered with a low initial dosage and adequate titration.

An exploratory factor analysis of existential suffering in Japanese terminally ill cancer patients.

To determine an underlying factorial structure of existential distress in Japanese terminally ill cancer patients, a principal components analysis was performed on 162 Japanese hospice inpatients. Existential distress commonly identified was dependency (39%), meaninglessness in present life (37%), hopelessness (37%), burden on others (34%), loss of social role functioning (29%), and feeling emotionally irrelevant (28%). By a factor analysis, three primary components accounted for 66% of the variance. 'Dependency' and 'loss of social role functioning' loaded highly on the first factor, which was interpreted as 'loss of autonomy'. 'Burden on others' and 'feeling emotionally irrelevant' loaded highly on the second component interpreted as 'lowered self-esteem', while 'hopelessness' loaded highly on the third factor. On the other hand, 'meaninglessness in present life' loaded equally on all three components, and was significantly associated with other distress. In conclusion, existential suffering of Japanese terminally ill cancer patients has three principal components: loss of autonomy, lowered self-esteem, and hopelessness. It is also suggested that meaninglessness in present life would be an underlying theme in patients' spirituality.

Risk factors for death rattle in terminally ill cancer patients: a prospective exploratory study.

Death rattle is frequently observed in cancer patients whose death is impending and may contribute to the severe distress of patients and their family members. To identify risk factors for development and persistency of death rattle, a prospective study was performed on 245 hospice inpatients. One-hundred-and-seven patients (44%) developed death rattle, 71% of whom achieved satisfactory symptom palliation until death. A multiple regression analysis identified neoplasms of brain and lung as independent risk factors for development of death rattle, while refractory symptoms were significantly associated with pulmonary neoplasms and infection/oedema. In conclusion, development of death rattle was influenced by both brain and lung malignancies, while its persistency was mainly determined by pulmonary pathology. A clinical classification of death rattle based on these factors would be established by a further confirmatory study.

Successful palliation of hypoactive delirium due to multi-organ failure by oral methylphenidate.

Delirium is frequently observed in terminally ill cancer patients, but complete remission is often difficult to achieve. Therefore, symptom palliation is of great importance to improve patients' quality of life. Although it has been suggested that psychostimulants would be beneficial to patients with hypoactive delirium, there have been very few empirical reports so far. We report on a terminally ill cancer patient with hypoactive delirium caused by multi-organ failure, in whom methylphenidate was effective in improving the ability to maintain communication. This case highlights the efficacy of methylphenidate for hypoactive delirium in terminally ill cancer patients.

Terminal sedation for existential distress.

Although sedation for existential distress has been actively discussed in the palliative care literature, empirical reports are limited. A retrospective cohort study was performed to clarify the physical conditions of terminally ill cancer patients who expressed existential distress and received sedation. Of 248 consecutive hospice inpatients, 20 patients expressed a belief that their lives were meaningless and received sedation. The target symptoms for sedation were dyspnea (n = 10), agitated delirium (n = 8), and pain (n = 1). Only one patient received sedation for psychological distress alone, although physical symptoms were acceptably relieved. The Palliative Performance Scale just before sedation was 10 (n = 7), 20 (n = 11), 30(n = 1), and 40(n = 1). All but one patient could take nourishment orally of only mouthfuls or less. Edema, dyspnea at rest, and delirium were observed in 10, 13, and 14 cases, respectively. The Palliative Prognostic Index was greater than 6.0 in all but one case with a mean of 12 +/- 3.3. In conclusion, in our practice, sedation was principally performed for physical symptoms of cancer patients in very late stages. Further research is encouraged to establish standard therapy for existential distress of the terminally ill.

Contributing factors to physical symptoms in terminally-ill cancer patients.

Prediction of future suffering could improve palliative care. To identify the factors contributing to physical symptoms, a prospective study was performed on two series of hospice inpatients with cancer (n = 150 and n = 200, respectively). Physical symptoms, patients' characteristics, and tumor locations were recorded using a structured protocol on admission and throughout the clinical course. Common symptoms on admission and during the patient's course were pain (65%, 88%), general malaise (58%, 77%), anorexia (57%, 94%), constipation (33%, 71%), dyspnea (33%, 66%), nausea/vomiting (29%, 48%), cough/sputum (29%, 48%), edema (27%, 65%), fever (26%, 70%), abdominal swelling (26%, 42%), and dry mouth (25%, 61%), respectively. The mean number of symptoms was 5.7 +/- 3.0 on admission and 9.6 +/- 3.1 during the course. Factors that contributed to the symptoms were young age (pain, abdominal swelling, dry mouth), performance status (anorexia, general malaise, edema, dyspnea), brain tumor (paralysis), neoplasms of lung/pleura (dyspnea, cough/sputum, death rattle), bone metastasis (pain, paralysis), gastric/pancreas cancer (abdominal swelling), peritoneal metastasis (general malaise, edema, nausea/vomiting, abdominal swelling, dry mouth), opioids (constipation, dry mouth, myoclonus), anticholinergics (dry mouth), and antidopaminergics (myoclonus). Opioid requirement was positively correlated with the presence of bone metastasis, and negatively correlated with age and brain involvement. Additional opioids were frequently used in the final 48 hours in cases with lung/pleura neoplasms. These data suggest that terminal symptoms in cancer patients are determined by local and/or general factors. Clinicians can predict the probability of future symptoms from patients' characteristics, general condition, tumor locations, and medications.

Adult T cell leukemia lymphoma (ATL) localized in the right tibial bone.

A 56-year-old man was admitted complaining of pain in the right tibia. He was diagnosed as having adult T-cell leukemia/lymphoma (ATL/L) in the right knee joint by roentgenographic and histological examination. Monoclonal integration of HTLV-I proviral DNA was demonstrated in the bone tumor cells, although polyclonal integration was observed in the peripheral blood. These results led us to make a diagnosis of ATL with localized growth in the right knee joint. The osteolytic bone change was progressive despite radiation therapy. Complete remission was achieved after amputation of his right lower leg and two courses of chemotherapy. Resection of the localized lesion might be useful in cases of ATL, but further studies are necessary to confirm this conclusion.

Survival prediction of terminally ill cancer patients by clinical symptoms: development of a simple indicator.

BACKGROUND: Although accurate prediction of survival is essential for palliative care, no clinical tools have been established. METHODS: Performance status and clinical symptoms were prospectively assessed on two independent series of terminally ill cancer patients (training set, n = 150; testing set, n = 95). On the training set, the cases were divided into two groups with or without a risk factor for shorter than 3 and 6 weeks survival, according to the way the classification achieved acceptable predictive value. The validity of this classification for survival prediction was examined on the test samples. RESULTS: The cases with performance status 10 or 20, dyspnea at rest or delirium were classified in the group with a predicted survival of shorter than 3 weeks. The cases with performance status 10 or 20, edema, dyspnea at rest or delirium were classified in the group with a predicted survival of shorter than 6 weeks. On the training set, this classification predicted 3 and 6 weeks survival with sensitivity 75 and 76% and specificity 84 and 78%, respectively. On the test populations, whether patients survived for 3 and 6 weeks or not was predicted with sensitivity 85 and 79% and specificity 84 and 72%, respectively. CONCLUSION: Whether or not patients live for 3 and 6 weeks can be acceptably predicted by this simple classification.

The Palliative Prognostic Index: a scoring system for survival prediction of terminally ill cancer patients.

Although accurate prediction of survival is essential for palliative care, few clinical methods of determining how long a patient is likely to live have been established. To develop a validated scoring system for survival prediction, a retrospective cohort study was performed with a training-testing procedure on two independent series of terminally ill cancer patients. Performance status (PS) and clinical symptoms were assessed prospectively. In the training set (355 assessments on 150 patients) the Palliative Prognostic Index (PPI) was defined by PS, oral intake, edema, dyspnea at rest, and delirium. In the testing sample (233 assessments on 95 patients) the predictive values of this scoring system were examined. In the testing set, patients were classified into three groups: group A (PPI< or =2.0), group B (2.04.0). Group B survived significantly longer than group C, and group A survived significantly longer than either of the others. Also, when a PPI of more than 6 was adopted as a cut-off point, 3 weeks' survival was predicted with a sensitivity of 80% and a specificity of 85%. When a PPI of more than 4 was used as a cutoff point, 6 weeks' survival was predicted with a sensitivity of 80% and a specificity of 77%. In conclusion, whether patients live longer than 3 or 6 weeks can be acceptably predicted by PPI.

[Accuracy of clinical prediction of survival for terminally ill cancer patients].

Accurate estimation of survival is vital for effective palliative care. To verify the value of clinical prediction of survival (CPS), a prospective study was performed on 150 terminally ill cancer patients. The CPS was highly correlated with actual survival (AS), but the accuracy was not significantly superior to the prediction by performance status alone. Serious pessimistic error, defined as AS was at least 28 days and twice as long as CPS, was recognized in 13%, while serious optimistic error, defined as AS was less than 28 days and half as long as CPS, in 15%. The frequency of serious error was not significantly different by physicians' experiences, patients' age, sex, primary disease, and metastatic locations, but was significantly higher in cases with better performance status. Also, unexpected changes resulting in death were experienced in 42% of another 186 cases. The main underlying causes were pneumonia, bleeding, heart failure, intestinal perforation, cerebrovascular disease, hepatic/renal failure, hypoglycemia, sepsis and electrolyte imbalance. Clinical prediction was not sufficiently reliable and must be further improved.