Current practice of pharmacological treatment for hyperactive delirium in terminally ill cancer patients: results of a nationwide survey of Japanese palliative care physicians and liaison psychiatrists.

OBJECTIVE: The objective of this survey was to identify areas where doctors have divergent practices in pharmacological treatment for hyperactive delirium in terminally ill patients with cancer. METHODS: We conducted a survey of Japanese palliative care physicians and liaison psychiatrists. Inquiries were made regarding: (i) choice of drug class in the first-line treatment, (ii) administration methods of the first-line antipsychotic treatment, (iii) starting dose of antipsychotics in the first line treatment and maximum dose of antipsychotics in refractory delirium, and (iv) choice of treatment when the first-line haloperidol treatment failed. Respondents used a five-point Likert scale. RESULTS: Regarding choice of drug class in the first-line treatment, more doctors reported that they 'frequently' or 'very frequently' use antipsychotics only than antipsychotics and benzodiazepine (oral: 73.4 vs. 12.2%; injection: 61.3 vs. 11.6%, respectively). Regarding administration methods of the first-line antipsychotic treatment, the percentage of doctors who reported that they used antipsychotics as needed and around the clock were 55.4 and 68.8% (oral), 49.2 and 45.4% (injection), respectively. There were different opinions on the maximum dose of antipsychotics in refractory delirium. Regarding the choice of treatment when the first-line haloperidol treatment failed, the percentage of doctors who reported that they increased the dose of haloperidol, used haloperidol and benzodiazepines, and switched to chlorpromazine were 47.0, 32.1 and 16.4%, respectively. CONCLUSIONS: Doctors have divergent practices in administration methods of the first-line antipsychotic treatment, maximum dose of antipsychotics, and choice of treatment when the first-line haloperidol treatment failed. Further studies are needed to determine the optimal treatment.

Association between experiences of advanced cancer patients at the end of life and depression in their bereaved caregivers.

OBJECTIVE: Research on the association between circumstances of death in advanced cancer patients and depression in their bereaved caregivers is limited. METHODS: A longitudinal study was performed on patients admitted to 21 inpatient hospices/palliative care units (PCUs) in Japan. Patient symptoms were assessed at admission and in the last 3 days of life. Data on distressing events (unexpected death, bleeding) and received treatments (morphine prescriptions, continuous deep sedation, cardiopulmonary resuscitation) were also obtained. Bereaved caregiver depression was assessed 6 months or more after patient death via mail survey using the Patient Health Questionnaire-9 (PHQ-9). A multivariable logistic regression analysis was used to explore variables predicting bereaved caregiver depression. RESULTS: Of 1324 deceased patient-bereaved caregiver dyads, data were finally analyzed for 711 dyads. The proportion of probable depression (PHQ-9 scores ≥10) in bereaved caregivers was 13.6% (91/671; 95% confidence interval: 11.0-16.2). The multivariable logistic regression analysis showed that patient hyperactive delirium at PCU admission was significantly associated with the development of bereaved caregiver depression (odds ratio: 2.2, 95% CI: 1.2-3.8). Bereaved caregiver perceived low social support (OR: 4.7, 95% CI: 2.2-10.0) and low preparedness for death (OR: 4.5, 95% CI: 2.6-7.8) were also significantly associated with the development of depression. Other patient and bereaved caregiver variables had no association with depression. CONCLUSIONS: Hyperactive delirium in terminally ill cancer patients was associated with bereaved caregiver depression. The development of effective strategies to reduce delirium-related agitation and to provide educational interventions for caregivers may be needed.

Effectiveness and safety of opioids for dyspnea in patients with lung cancer: secondary analysis of multicenter prospective observational study.

Background: Patients with lung cancer are more likely to have comorbidities [e.g., interstitial lung disease (ILD)], chronic obstructive pulmonary disease) and metastases that may affect dyspnea and the effectiveness and safety of opioids for dyspnea than other cancer types. Therefore, this study examined the effectiveness and safety of opioids for dyspnea, among the patients with lung cancer. Methods: The present study is a secondary analysis of a multicenter prospective observational study examining the effectiveness and safety of opioids for dyspnea in patients with cancer in Japan. For this secondary analysis, patients with lung cancer with a documented dyspnea Numerical Rating Scale (NRS) at baseline were included. The primary outcome was dyspnea NRS, and Integrated Palliative care Outcome Scale/Support Team Assessment Schedule (IPOS/STAS) scores change between baseline and 24 hours after baseline. As secondary outcomes, we investigated the predictors of opioid effectiveness for dyspnea improvement and adverse events (nausea, somnolence, and delirium). Results: This study analyzed 124 patients with lung cancer with known dyspnea NRS at baseline. The median age was 74, and the Eastern Cooperative Oncology Group performance status of 107 patients were 3-4. Both NRS and IPOS/STAS score of dyspnea significantly improved 24 hours after opioid initiation [-1.64, 95% confidence interval (CI): -2.12 to -1.17, P<0.001; -1.03; 95% CI: -1.21 to -0.85, P<0.001; respectively]. Moreover, the improvement of NRS score was greater than the minimal clinically important difference of 1 point. In the multivariate logistic regression analysis, ILD was significantly associated with a better improvement [(hazard ratio (HR): 3.39, 95% CI: 1.34-11.09, P=0.043]. Somnolence was the most common grade 3-4 adverse event (n=16), followed by delirium (n=9). Conclusions: Opioids were effective and safe for treating dyspnea in patients with lung cancer. Furthermore, lung cancer patients with ILD may benefit more from opioids.

Is the 1-day surprise question a useful screening tool for predicting prognosis in patients with advanced cancer?-a multicenter prospective observational study.

BACKGROUND: For cancer patients nearing death, the prediction of their prognosis by physicians is crucial. This study examined the usefulness of the 1-Day Surprise Question (1DSQ). METHODS: This study was conducted as part of a multicenter prospective observational study. The physicians answered the 1DSQ "Would I be surprised if this patient died in the next 1 day?" when patients have palliative performance scale (PPS) ≤20. We calculated the sensitivity and specificity of the 1DSQ. Moreover, using multivariate analysis, we evaluated the characteristics of patients who died among those whose physicians answered the 1DSQ as "not surprised". RESULTS: Overall, 1,896 patients were enrolled, and 1,411 (74.4%) were analyzed between January and December 2017. Among these, 847 (60.0%) patients were placed in the "not surprised" group. The sensitivity, specificity, and positive and negative predictive values of the 1DSQ were 82.0% [95% confidence interval (CI): 77.5-85.8%], 45.5% (95% CI: 44.4-46.4%), 27.4% (95% CI: 25.9-28.7%), and 91.0% (95% CI: 88.9-92.9%), respectively. Multivariate analysis revealed that urine output over last 12 hours <100 mL, decreased response to visual stimuli, respiration with mandibular movement, pulselessness of radial artery, and saturation of percutaneous oxygen <90% were characteristics of patients who died as predicted by the physicians. CONCLUSIONS: The 1DSQ is a helpful screening tool for identifying cancer patients with impending death.

Association between Bathing and Survival in Patients with Advanced Cancer in Their Last Days of Life: A Prospective Cohort Study.

Background: Although many Japanese patients wish to take a bath in their last days, the safety of bathing for patients with a prognosis of a few days is not known. Objective: To examine whether taking a bath affects the survival of advanced cancer patients with prognoses of a few days. Design: A single-center prospective cohort study. Setting/Subject: Advanced cancer patients in their last days of life in a palliative care unit of a Japanese hospital. We compared patients who took baths with those who did not. The primary endpoint was 24-hour survival rate. Result: Among 110 patients eligible for this prospective study, 89 (72%) met the inclusion criteria. Forty-eight patients (43%, 223 person-days) were eligible for analysis. A total of 28 patient-days were classified into the bathing group, and 192 patient-days were classified into the nonbathing group. After propensity score matching, the 24-hour death rate was 10.7% in the bathing group and 8.0% in the nonbathing group, respectively (mean difference 2.8% with 95% confidence interval of -11.2% to 16.8%, p = 0.65). Conclusion: Taking a bath does not appear to bear a significant association with shortening of life among advanced cancer patients in their last days of life.

Efficacy of Proportional Sedation and Deep Sedation Defined by Sedation Protocols: A Multicenter, Prospective, Observational Comparative Study.

PURPOSE: To investigate the efficacy of two types of palliative sedation: proportional and deep sedation, defined by sedation protocols. METHODS: From a multicenter prospective observational study, we analyzed the data of those patients who received the continuous infusion of midazolam according to the sedation protocol. The primary endpoint was goal achievement at 4 hours: in proportional sedation, symptom relief (Integrated Palliative care Outcome Scale: IPOS ≤ 1) and absence of agitation (modified Richmond Agitation-Sedation Scale: RASS ≤ 0); in deep sedation, the achievement of deep sedation (RASS ≤ -4). Secondary endpoints included deep sedation as a result of proportional sedation, communication capacity (Communication Capacity Scale item 4 ≤ 2), IPOS and RASS scores, and adverse events. RESULTS: A total of 81 patients from 14 palliative care units were analyzed: proportional sedation (n = 64) and deep sedation (n = 17). At 4 hours, the goal was achieved in 77% (n = 49; 95% confidence interval: 66-87) with proportional sedation; and 88% (n = 15; 71-100) with deep sedation. Deep sedation was necessary in 45% of those who received proportional sedation. Communication capacity was maintained in 34% with proportional sedation and 10% with deep sedation. IPOS decreased from 3.5 to 0.9 with proportional sedation, and 3.5 to 0.4 with deep sedation; RASS decreased from +0.3 to -2.6, and +0.4 to -4.2, respectively. Fatal events related to the treatment occurred in 2% (n = 1) with proportional and none with deep sedation. CONCLUSION: Proportional sedation achieved satisfactory symptom relief while maintaining some patients' consciousness, and deep sedation achieved good symptom relief while the majority of patients lost consciousness.

Intermittent percutaneous drainage of ovarian tumour.

INTRODUCTION: Abdominal pain and distention are common in ovarian tumours. When the ovarian tumour grows too large, the tumour can cause these symptoms. Percutaneous drainage from ovarian tumours, which can alleviate symptoms, is traditionally discouraged for its potential risk of peritoneal tumour seeding. CASE: A 73-year-old woman with a multilocular ovarian tumour reporting abdominal fullness and pain was referred to the palliative care outpatient department. The multilocular tumour occupied most of the intra-abdominal space, which was determined to cause her symptoms. To alleviate her symptoms, we performed intermittent percutaneous drainage for 1.5 years. A clinical autopsy revealed the tumour was an ovarian mucinous carcinoma. Despite iterative tumour drainage, we observed no feature of peritoneal dissemination. CONCLUSION: Intermittent percutaneous drainage of ovarian tumours could reduce tumour-related abdominal symptoms without pathological evidence of peritoneal dissemination. This procedure can be a new palliative treatment option for ovarian tumour-related abdominal symptoms.

Optimal Paracentesis Volume for Terminally Ill Cancer Patients With Ascites.

CONTEXT: Patients with malignant ascites often suffer from distressing symptoms, especially in their end-of-life stage. Although paracentesis is the most common treatment modality to alleviate such symptoms, the optimal volume of paracentesis is not known. OBJECTIVES: To explore the efficacy and safety of paracentesis by the drainage volume for terminally ill cancer patients with malignant ascites. METHODS: This was part of a multicenter prospective observational study (EASED study). Consecutive adult patients with advanced cancer admitted to 23 participating palliative care units were eligible. We analyzed patients with malignant ascites who received paracentesis. We compared paracentesis-free survival (PFS) using Cox regression among three groups with different paracentesis volumes: minimum: ≤ 1500 mL, small: 1500-2500 mL, and moderate: > 2500 mL. Trends of the difference in the numerical rating scale of abdominal distension (0-10) and adverse events were compared among the 3 groups. RESULTS: Of the 1926 patients enrolled, 673 developed ascites (symptomatic, n = 374 and asymptomatic, n = 299). Finally, we analyzed 87 patients with paracentesis. Median PFS was 7 days. Compared with a moderate volume, small-volume paracentesis was not a significant risk for shorter PFS (HR: 1.14, 95% CI: 0.69-1.93), while a minimum volume was a significant risk (HR: 2.34). The abdominal distension intensity significantly decreased after paracentesis (median: 7.5 to 4.0), while the difference did not significantly increase as the volume of paracentesis rose (P = 0.61). No severe adverse event was observed. CONCLUSION: Even small-volume paracentesis could alleviate abdominal distension of terminally ill cancer patients with malignant ascites without shortening the paracentesis interval compared with moderate-volume paracentesis. Small-volume paracentesis was a well-balanced treatment for these patients.

Complexity of desire for hastened death in terminally ill cancer patients: A cluster analysis.

OBJECTIVES: The present study aims were (1) to identify the proportion of terminally ill cancer patients with desire for hastened death (DHD) receiving specialized palliative care, (2) to identify the reasons for DHD, and (3) to classify patients with DHD into some interpretable subgroups. METHODS: Advanced cancer patients admitted to 23 inpatients hospices/palliative care units in 2017 were enrolled. Data were prospectively obtained by the primarily responsible physicians. The presence/absence of DHD and reasons for DHD were recorded. A cluster analysis was performed to identify patterns of subgroups in patients with DHD. RESULTS: Data from 971 patients, whose Richmond Agitation-Sedation Scale score at admission was zero and who died in palliative care units, were analyzed. The average age was 72 years, common primary cancer sites were the gastrointestinal tract (31%) and the liver/biliary ducts/pancreas (19%). A total of 174 patients (18%: 95% confidence interval, 16-20) expressed DHD. Common reasons for DHD were dependency (45%), burden to others (28%), meaninglessness (24%), and inability to engage in pleasant activities (24%). We identified five clusters of patients with DHD: cluster 1 (35%, 61/173): "physical distress," cluster 2 (21%, 37/173): "dependent and burdensome," cluster 3 (19%, 33/173): "hopelessness," cluster 4 (17%, 30/173): "profound fatigue," and cluster 5 (7%, 12/173): "extensive existential suffering." CONCLUSIONS: A considerable number of patients expressed DHD and could be categorized into five subgroups. These findings may contribute to the development of therapeutic strategies.

Comparison of the prevalence and associated factors of hyperactive delirium in advanced cancer patients between inpatient palliative care and palliative home care.

BACKGROUND: Hyperactive delirium is known to increase family distress and the burden on health care providers. We compared the prevalence and associated factors of agitated delirium in advanced cancer patients between inpatient palliative care and palliative home care on admission and at 3 days before death. METHODS: This was a post hoc exploratory analysis of two multicenter, prospective cohort studies of advanced cancer patients, which were performed at 23 palliative care units (PCUs) between Jan and Dec 2017, and on 45 palliative home care services between July and Dec 2017. RESULTS: In total, 2998 patients were enrolled and 2829 were analyzed in this study: 1883 patients in PCUs and 947 patients in palliative home care. The prevalence of agitated delirium between PCUs and palliative home care was 5.2% (95% CI: 4.2% - 6.3%) vs. 1.4% (0.7% - 2.3%) on admission (p < 0.001) and 7.6% (6.4% - 8.9%) vs. 5.4% (4.0% - 7.0%) 3 days before death (p < 0.001). However, multivariate logistic regression analysis revealed that the place of care was not significantly associated with the prevalence of agitated delirium at 3 days before death after adjusting for prognostic factors, physical risk factors, and symptoms. CONCLUSIONS: There was no significant difference in the prevalence of agitated delirium at 3 days before death between inpatient palliative care and palliative home care after adjusting for the patient background, prognostic factors, symptoms, and treatment.

"3-Day Surprise Question" to predict prognosis of advanced cancer patients with impending death: Multicenter prospective observational study.

BACKGROUND: The study aimed to clarify the efficacy of the "3-Day Surprise Question (3DSQ)" in predicting the prognosis for advanced cancer patients with impending death. PATIENTS AND METHODS: This study was a part of multicenter prospective observational study which investigated the dying process in advanced cancer patients in Japan. For patients with a Palliative Performance Scale ≤20, the 3DSQ "Would I be surprised if this patient died in the next 3 days?" was answered by their physicians. In addition to the sensitivity and specificity of the 3DSQ, the characteristics of patients who survived longer than expected were examined via multivariate analysis. RESULTS: Among the 1896 patients enrolled, 1411 were evaluated. Among 1179 (83.6%) patients who were classified into the "Not surprised" group, 636 patients died within 3 days. Among 232 (16.4%) patients of "Yes surprised" group, 194 patients lived longer than 3 days. The sensitivity, specificity, positive predictive value, and negative predictive value of the 3DSQ were 94.3% (95% confidence interval [CI]: 92.7% to 95.8%), 26.3% (95% CI: 24.8% to 27.6%), 53.9% (95% CI: 53.0% to 54.7%), and 83.6% (95% CI: 78.7% to 87.7%), respectively. Multivariate analysis showed palpable radial artery, absent respiration with mandibular movement, SpO2 ≥ 90%, opioid administration, and no continuous deep sedation as characteristics of patients who lived longer than expected. CONCLUSIONS: The 3-Day Surprise Question can be a useful screening tool to identify advanced cancer patients with impending death.