Visualizing How to Use Antipsychotics for Agitated Delirium in the Last Days of Life.

CONTEXT: How physicians use antipsychotics for agitated delirium in the last days of life varies markedly, which could hamper the quality of care. OBJECTIVES: To examine adherence to an algorithm-based treatment for terminal agitated delirium, and explore its effectiveness and safety. METHODS: A single-center, prospective, observational study was conducted in a 27-bed palliative care unit in Japan. All adult cancer patients who developed agitated delirium with a modified Richmond Agitation-Sedation Scale (RASS) of +1 or more were included; the palliative care specialists determined that the etiology was irreversible, the estimated survival was three weeks or less, and the Eastern Cooperative Oncology Group (ECOG) performance status was three or four. Patients were treated with an algorithm to visualize how to use antipsychotics, with the treatment goal defined as no agitation (RASS≤0) or acceptable agitation for patients and families. We provided all patients nonpharmacological management to alleviate the symptoms of delirium and administered antipsychotic medications when the nonpharmacological approach was insufficient. We measured the adherence rate, RASS, Nursing Delirium Screening Scale items 2, 3, 4 (Nu-DESC), and Agitation Distress Scale item 2 (ADS) on days 0, 1, 3, 7, 14, 21, and 24 hours before death. RESULTS: A total of 164 patients were enrolled. Adherence rates were 99, 94, and 89%, and treatment goals were achieved in 66, 83, and 93% on days one, three, and seven, respectively. The mean RASS decreased from +1.41 to -0.84 on day three; Nu-DESC decreased from 4.19 to 1.83, and ADS decreased from 1.54 to 0.38. There were seven severe adverse events (Common Terminology Criteria for Adverse Events (CTCAE) of 3), including aspiration (n = 3), apnea (n = 2), tremor (n = 1), and muscle rigidity (n = 1) on day three. CONCLUSION: The algorithm-based treatment could be feasible, effective, and safe. Visualizing how palliative care specialists provide pharmacological management could be beneficial for nonspecialist clinicians, and clinical, educational, and research implications warrant further empirical testing.

Association of the RASS Score with Intensity of Symptoms, Discomfort, and Communication Capacity in Terminally Ill Cancer Patients Receiving Palliative Sedation: Is RASS an Appropriate Outcome Measure?

Background: Palliative sedation is sometimes needed for refractory symptoms, and the Richmond Agitation-Sedation Scale (RASS) is one of the key measures. The primary aim of this study was to explore the association between RASS and degree of distress quantified by other measures: Item "symptom control" of Support Team Assessment Schedule (STAS, item 2), Discomfort Scale for Dementia of Alzheimer Type (Discomfort Scale), and Noncommunicative Patient's Pain Assessment Instrument (NOPPAIN), as well as a communication capacity measured by the Communication Capacity Scale (CCS), item 4. Methods: This was a prospective observational study on terminally ill cancer patients with palliative sedation in a palliative care unit of a designated cancer hospital. Primarily responsible palliative care physicians rated RASS, Discomfort Scale, NOPPAIN, and CCS just before sedation and 1, 4, 24, and 48 hours after, and ward nurses rated STAS at the same time. Since the ward nurses evaluated STAS during palliative sedation, we regarded STAS as a standard of distress measure. Results: A total of 249 assessments were performed for 55 patients. RASS was moderately to highly associated with symptom intensity measured by STAS, discomfort measured by the Discomfort Scale, and pain measured by NOPPAIN (r = 0.63 to 0.73). But communication capacity measured by CCS is not parallel with RASS and demonstrated a valley shape. In 82 assessments with an RASS score of -1 to -3, 11 patients (13%) had physical symptoms of STAS of 2 or more. Conclusions: RASS can roughly estimate physical distress in patients with palliative sedation, but a measure to more precisely quantify the symptom experience is needed.

Physicians' Beliefs and Attitudes Toward Hypoactive Delirium in The Last Days of Life.

CONTEXT: The perspective toward hypoactive delirium in the last days of life could be different among physicians. OBJECTIVES: To clarify the attitudes, beliefs, and opinions of palliative care physicians and liaison psychiatrists toward hypoactive delirium in the last days of life and to explore the association among these factors. METHODS: A nationwide cross-sectional questionnaire survey was conducted among 1667 physicians who were either certified palliative care specialists or liaison psychiatrists. Physicians' agreement with the appropriateness of pharmacological management (e.g., antipsychotics) (one item), their beliefs (11 items), and their opinions (four items) were measured. RESULTS: 787 (47%) physicians responded. 481 (62%) agreed to use of medications for hypoactive delirium in the last days of life, whereas 296 (38.1%) disagreed. More than 95% agreed with "hypoactive delirium at the end of life can be considered as a part of natural dying process." Multivariate analysis identified two belief subscales of "hypoactive delirium at the end of life is a natural dying process" and "antipsychotics are futile and harmful in managing hypoactive delirium" had a significant negative correlation with the use of medications. On the other hand, one belief subscale of "hypoactive delirium can be distressing even if patients' consciousness is impaired" had significant positive correlations with the use of medications. CONCLUSION: Pharmacological management of hypoactive delirium in the last days of life differs depending on physicians' beliefs. Future research is needed to clarify the efficacy and safety of pharmacological management of hypoactive delirium.

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.

Family experience of palliative sedation therapy: proportional vs. continuous deep sedation.

PURPOSE: Some patients experience intense symptoms refractory to intensive palliative care, and palliative sedation is sometimes used. Palliative sedation may be classified into proportional and continuous deep sedation (CDS). The primary aim of this study was to compare family experience between families of patients who received proportional or CDS. METHODS: A multicenter questionnaire survey was conducted involving bereaved families of cancer patients who received proportional or CDS based on a sedation protocol. Overall evaluation of sedation (satisfaction, family-perceived distress, appropriateness of timing, and patient distress) and 13-item family concerns, good death, satisfaction with care, depression, quality of care, unfinished business, and balance between symptom relief and maintaining communication were measured. RESULTS: Among the 2120 patients who died, 222 patients received a continuous infusion of midazolam. A sedation protocol was used in 147 patients, and questionnaires were sent to 124 families. A total of 78 responses were finally returned (proportional, 58 vs. CDS, 20). There were no significant differences in the overall evaluation, family concerns, total score of good death, satisfaction, depression, or balance between symptom relief and maintaining communication. On the other hand, some quality of care items, i.e., relationship with medical staff (P < 0.01), physical care by nurses (P = 0.04), and coordination and consistency (P = 0.04), were significantly better in the CDS group than in the proportional sedation group. Family-reported unfinished business was also better in the CDS group, with marginal significance. CONCLUSIONS: Family experience of CDS was not less favorable than proportional sedation, and actually rated more favorably for some elements of quality of care and unfinished business.

Development of a Scoring System to Determine Proportional Appropriateness of Continuous Deep Sedation: A Concept-of-Proof Study.

Context: Some patients require continuous deep sedation (CDS) for refractory symptoms despite intensive palliative care. The principle of proportionality is proposed on the basis of clinical decisions, but no validated tools to assist such decision making are available. Aim: To develop a scoring system to determine whether CDS is proportionally appropriate. Subjects and Methods: A secondary analysis of a nationwide questionnaire survey of Japanese palliative care specialists was performed. Physicians were asked to rate the degree that they believed CDS to be appropriate in a total of 27 scenarios based on a combination of 3 factors with 3 levels: (1) the estimated survival (days, weeks, and months), (2) the patient's wish (clear and consistent, somewhat unclear and/or inconsistent, and unclear or inconsistent), and (3) confidence in refractoriness of the symptom (definite, probable, and unsure). Based on logistic regression analyses, a scoring system with two formulas (the proportionality score to determine that continuous deep sedation is appropriate [ProScoreCDS-appropriate] and proportionality score to determine that continuous deep sedation is inappropriate [ProScoreCDS-inappropriate]) to predict specialists' decision that CDS is appropriate or inappropriate was developed. The accuracy of the formulas was investigated. Results: Among 695 palliative care specialists, 469 returned the questionnaire (response rate, 69%) and 440 were analyzed. Logistic regression analyses identified that all three factors were significantly associated with physicians' decisions about the appropriateness of performing CDS. Using weighted value, the total score ranged from 3 to 67 for ProScoreCDS-appropriate, and 3 to 27 for ProScoreCDS-inappropriate. The area under the curve (AUC) values of ProScoreCDS-appropriate and ProScoreCDS-inappropriate were 0.88 (95% confidence interval [CI], 0.87-0.89) and 0.81 (95% CI, 0.81-0.82), respectively. Using cutoff points of 41 and 14, sensitivity and specificity were 68.6% and 88.9% for ProScoreCDS-appropriate and 67.7% and 76.0% for ProScoreCDS-inappropriate, respectively. Conclusion: A scoring system to determine whether CDS is proportionally appropriate can be constructed, and a further study to develop a clinical tool is promising.

Effects of parenteral nutrition and hydration on survival in advanced cancer patients with malignant bowel obstruction: secondary analysis of a multicenter prospective cohort study.

PURPOSE: The benefits of parenteral nutrition and hydration (PNH) in patients with advanced cancer remain unknown. Therefore, we conducted a prospective multicenter cohort study to assess the effects of PNH on survival in patients with malignant bowel obstruction (MBO). METHODS: The present study was a secondary analysis. Data on primary nutritional administration routes during the first week of admission to palliative care units, i.e., parenteral nutrition and parenteral hydration, were obtained. Data on the averaged calorie sufficiency rate/total calorie intake (75% ≤ or 750 kcal/day ≤ , 50-75% or 500-750 kcal/day, 25-50% or 250-500 kcal/day, and < 25% or < 250 kcal/day) were also obtained. Participants with MBO were included and divided into two groups: PNH-high (25% ≤ or 250 kcal/day ≤) and PNH-low (< 25% or < 250 kcal/day). We performed time-to-event analyses using the Kaplan-Meier method, log-rank test, and univariate and multivariate Cox regression analyses. RESULTS: Patients were divided into the PNH-high (n = 68) and PNH-low (n = 76) groups. A significant difference was observed in survival rates between the two groups (log-rank P < 0.001). Median survival times were 35.5 (95% CI 27-44) and 17.5 (95% CI 13-21) days, respectively. In the multivariate-adjusted model, a significantly lower risk of mortality was observed in Cox's proportional hazard model in the PNH-high group (HR 0.55 (95% CI 0.36-0.83), P = 0.005) than in the PNH-low group. CONCLUSION: The present results indicated the beneficial effects of PNH for prolonging survival in advanced cancer patients with MBO in palliative care units.

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.

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 between patient-reported and clinician-reported outcomes: Validation of the Japanese version of the Integrated Palliative care Outcome Scale for staff.

OBJECTIVES: The goal of palliative and supportive care is to improve patients' quality of life (QoL). Patient-reported outcome measures (PROMs) are the gold standard for the assessment of QoL and symptoms; however, when self-reporting is complicated, PROMs are often substituted with proxy-reported outcome measures, such as clinician-reported outcome measures. The objective of this study was to assess the validity and reliability of the Japanese version of the Integrated Palliative care Outcome Scale (IPOS) for staff (IPOS-Staff). METHODS: This multicenter, cross-sectional observational study was conducted concurrently with the validation of the IPOS for patients (IPOS-Patient). Japanese adult patients with cancer and their staff were recruited. We assessed the characteristics of the patients and staff members, missing values, prevalence, and total IPOS scores. For the analysis of criterion validity, intra-rater, and inter-rater reliability, we calculated intraclass correlations (ICCs). RESULTS: One hundred and forty-three patients completed the IPOS-Patient, and 79 medical staff members completed the IPOS-Staff. The most common missing values from IPOS-Staff were Family Anxiety (3.5%) and Sharing Feelings (3.5%). Over half of the patients scored themselves moderate or worse for Poor Mobility, Anxiety, and Family Anxiety, while staff members scored patients moderate or worse for Weakness, Anxiety, and Family Anxiety. For criterion validity (patient-staff agreement) as well as intra-rater and inter-rater reliability, ICCs ranged from 0.114 (Sharing Feelings) to 0.826 (Nausea), 0.720 (Anxiety) to 0.933 (Nausea), and -0.038 (Practical Problems) to 0.830 (Nausea), respectively. SIGNIFICANCE OF RESULTS: The IPOS-Staff is easy to respond to; it has fair validity and reliability for physical items but poor for psycho-social items. By defining the context and objectives of its use and interpretation, the IPOS-Staff can be a useful tool for measuring outcomes in adult patients with cancer who cannot complete self-evaluations.

Efficacy of two types of palliative sedation therapy defined using intervention protocols: proportional vs. deep sedation.

PURPOSE: This study investigated the effect of two types of palliative sedation defined using intervention protocols: proportional and deep sedation. METHODS: We retrospectively analyzed prospectively recorded data of consecutive cancer patients who received the continuous infusion of midazolam in a palliative care unit. Attending physicians chose the sedation protocol based on each patient's wish, symptom severity, prognosis, and refractoriness of suffering. The primary endpoint was a treatment goal achievement at 4 h: in proportional sedation, the achievement of symptom relief (Support Team Assessment Schedule (STAS) ≤ 1) and absence of agitation (modified Richmond Agitation-Sedation Scale (RASS) ≤ 0) and in deep sedation, the achievement of deep sedation (RASS ≤ - 4). Secondary endpoints included mean scores of STAS and RASS, deep sedation as a result, and adverse events. RESULTS: Among 398 patients who died during the period, 32 received proportional and 18 received deep sedation. The treatment goal achievement rate was 68.8% (22/32, 95% confidence interval 52.7-84.9) in the proportional sedation group vs. 83.3% (15/18, 66.1-100) in the deep sedation group. STAS decreased from 3.8 to 0.8 with proportional sedation at 4 h vs. 3.7 to 0.3 with deep sedation; RASS decreased from + 1.2 to - 1.7 vs. + 1.4 to - 3.7, respectively. Deep sedation was needed as a result in 31.3% (10/32) of the proportional sedation group. No fatal events that were considered as probably or definitely related to the intervention occurred. CONCLUSION: The two types of intervention protocol well reflected the treatment intention and expected outcomes. Further, large-scale cohort studies are promising.

Screening using the fifth vital sign in the electronic medical recording system.

PURPOSE: To investigate the usefulness of screening for patient symptoms as the fifth vital sign using an electronic medical recording system. PATIENTS AND METHODS: In the electronic medical recording system, all admitted patients received routine nurse-based assessment of discomfort (defined as any physical symptom) at every vital sign check regarding item 2 of the Support Team Assessment Schedule Japanese version (STAS-J). All cancer patients admitted to oncology units were screened at 1-week intervals. Screening-positive was defined when patients had a STAS-J score of 2 or more at least two times in a week. For all screening-positive patients, the palliative care team reviewed each patient's medical records, and provided written recommendations as needed. The primary outcomes were the proportion of screening-positive patient, and the proportion of patients deemed to need additional palliative treatment in the screening-positive patients. RESULTS: Of 2427 patients screened, 223 (9.1%; 95% confidence interval, 8-10%) met the screening-positive criterion. A total of 12 (5.4%; 95% confidence interval, 3-9%) of them were deemed to need additional palliative care, including six patients referred to the PCT within 1 week. In the remaining 211 screening-positive patients, 100 had received adequate palliative care, 68 had already been referred to the palliative care team and 43 had self-limiting transient discomfort. CONCLUSION: This screening system was feasible but the majority of screening-positive patients did not require additional palliative care interventions.

Nationwide Japanese Survey About Deathbed Visions: "My Deceased Mother Took Me to Heaven".

OBJECTIVES: Primary aim was to clarify the prevalence and factors associated with the occurrence of deathbed visions, explore associations among deathbed visions, a good death, and family depression. Additional aim was to explore the emotional reaction, perception, and preferred clinical practice regarding deathbed visions from the view of bereaved family members. METHODS: A nationwide questionnaire survey was conducted involving 3964 family members of cancer patients who died at hospitals, palliative care units, and home. RESULTS: A total of 2827 responses (71%) were obtained, and finally 2221 responses were analyzed. Deathbed visions were reported in 21% (95% CIs, 19-23; n = 463). Deathbed visions were significantly more likely to be observed in older patients, female patients, female family members, family members other than spouses, more religious families, and families who believed that the soul survives the body after death. Good death scores for the patients were not significantly different between the families who reported that the patients had experienced deathbed visions and those who did not, whereas depression was more frequently observed in the former than latter, with marginal significance (20 vs. 16%, respectively, adjusted P = 0.068). Although 35% of the respondents agreed that deathbed visions were hallucinations, 38% agreed that such visions were a natural and transpersonal phenomenon in the dying process; 81% regarded it as necessary or very necessary for clinicians to share the phenomenon neutrally, not automatically labeling them as medically abnormal. CONCLUSIONS: Deathbed vision is not an uncommon phenomenon. Clinicians should not automatically regard such visions as an abnormal phenomenon to be medically treated and rather provide an individualized approach.

Current Status of Distress Screening in Designated Cancer Hospitals: A Cross-Sectional Nationwide Survey in Japan.

BACKGROUND: The purpose of this study was to investigate the current status of distress screening implementation in Japanese designated cancer hospitals. SUBJECTS AND METHODS: This was a cross-sectional observational study. Palliative care team representatives in all designated cancer hospitals in Japan completed an ad hoc questionnaire. Demographic data in 2014 were obtained from the Ministry of Health, Labour and Welfare in Japan. RESULTS: Of 422 institutions, 389 responded (92%) and data were obtained from 379 (90%). Approximately 90% of institutions had implemented a distress screening program at some level, and approximately 60% had just started screening. Among those institutions that screened, 77% provided individualized triage to specialized services within the institutions, whereas 60% did not routinely follow-up with patients who had positive screening results. The estimated median percentage of screened patients referred to palliative care teams was 0.4% in outpatient settings and 6.3% in inpatient settings. Although 68% of respondents perceived that screening was useful overall, they also reported difficulties when conducting screening with patients, reporting "no established effective treatment for problems screened" (66%), "patients complain it is difficult to express their distress using scales" (58%), and that it was "difficult to manage screened problems because of lack of time" (49%). Eight perceived barriers to implementing distress screening programs in hospitals were identified; a lack of human resources ranked highest. CONCLUSIONS: Implementation of distress screening in designated cancer hospitals in Japan has just begun. Policymakers should acknowledge that screening can be beneficial for patients when it is implemented with appropriate resources and established methods.

Death Pronouncements: Recommendations Based on a Survey of Bereaved Family Members.

PURPOSE: To clarify the family-perceived necessity of improvement in death pronouncement and explore the potential association between behaviors of physicians and the family-perceived necessity of improvement. SUBJECTS AND METHODS: A questionnaire survey was conducted involving 226 bereaved family members of patients who had died at home while receiving hospice service. A total of 91 responses were analyzed (response rate, 47%). RESULTS: All pronouncements were performed by physicians. A total of 89% (n = 81, 95% confidence interval, 81%-94%) of family members reported that they felt no necessity of improvement at all or that almost no improvement was needed. Behaviors of physicians significantly positively correlated with the family-perceived necessity of improvement were that physicians acted calmly, and were not rushed. Those negatively associated were that physicians did not verify the time of death clearly, left the patient's clothes disheveled, and touched the family members' backs or shoulders as an expression of empathy. More than 90% of family members recommended that physicians act calmly, have a suitable appearance for the situation, introduce themselves to family members, explain the cause of death explicitly, and conduct a check using a light and stethoscope for death pronouncement. CONCLUSION: Most of the family members who had experienced a patient's death at home were satisfied with the death pronouncement. Several factors were associated with family satisfaction, and further large studies are needed to confirm the results.