Comparison of Pharmacological Treatments for Agitated Delirium in the Last Days of Life.

CONTEXT: Antipsychotics are often used in managing symptoms of terminal delirium, but evidence is limited. OBJECTIVES: To explore the comparative effectiveness of haloperidol with as-needed benzodiazepines (HPD) vs. chlorpromazine (CPZ) vs. levomepromazine (LPZ) for agitated delirium in the last days. METHODS: A prospective observational study was conducted in two palliative care units in Japan. Adult cancer patients who developed agitated delirium with a modified Richmond Agitation-Sedation Scale (RASS-PAL) of one or more were included; palliative care specialist physicians determined that the etiology was irreversible; and estimated survival was 3 weeks or less. Patients treated with HPD, CPZ, or LPZ were analyzed. We measured RASS, NuDESC, Agitation Distress Scale (ADS), and Communication Capacity Scale (CCS) on Days 1 and 3. RESULTS: A total of 277 patients were enrolled, and 214 were analyzed (112 in HPD, 50 in CPZ, and 52 in LPZ). In all groups, the mean RASS-PAL score significantly decreased on Day 3 (1.37 to -1.01, 1.87 to -1.04, 1.79 to -0.62, respectively; P < 0.001); the NuDESC and ADS scores also significantly decreased. The percentages of patients with moderate to severe agitation and those with full communication capacity on Day 3 were not significantly different. The treatments were well-tolerated. While one-fourth of HPD group changed antipsychotics, 88% or more of CPZ and LPZ groups continued the initial antipsychotics. CONCLUSION: Haloperidol with as-needed benzodiazepine, chlorpromazine, or levomepromazine may be effective and safe for terminal agitation. Chlorpromazine and levomepromazine may have an advantage of no need to change medications.

Determinants of Attitude Toward End-of-Life Care Among Junior Physicians: Findings from a Nationwide Survey in Japan.

Background: Physicians' attitudes can be critical in quality end-of-life care. However, the determinants of the attitudes and whether the attitudes can be modified remain unclear. Objectives: To investigate factors correlated with physicians' positive attitudes toward end-of-life care and whether these attitudes are modifiable through acquired factors (e.g., education or mentorship). Design: A nationwide survey was conducted in 300 institutions and selected randomly from 1037 clinical training hospitals in Japan. Participants: From each selected institution, two resident physicians of postgraduate year (PGY) 1 or 2 and two clinical fellows from PGY 3-5 were requested to answer the survey. Measurements: The primary outcome was the Frommelt Attitudes Toward the Care of the Dying (FATCOD) scale score. Factors (e.g., the respondents' age, sex, number of years of clinical experience, training environment, religion, and beliefs around death) were examined for correlation with FATCOD score. Results: In all, 198 physicians and 134 clinical fellows responded to the survey (response rate: 33.0% and 22.3%, respectively). Factors with the strongest correlation with FATCOD scores were mostly unmodifiable factors (e.g., being female and one's beliefs around death). Modifiable factors were also identified-number of patient deaths experienced, level of interest in palliative care, availability of support from senior mentors, and frequency of consultation with nonphysician medical staff. Conclusion: Physicians' attitudes toward end-of-life care correlate more strongly with nonmodifiable factors, but attitudes can be meaningfully improved via mentoring by senior physicians. Future studies are warranted to determine the effective interventions to foster positive attitudes among physicians involved in end-of-life care.

Difficulties Facing Junior Physicians and Solutions Toward Delivering End-of-Life Care for Patients with Cancer: A Nationwide Survey in Japan.

Background: Junior physicians' perceived difficulty in end-of-life care of patients with cancer has not been structurally investigated; therefore, current challenges and solutions in this area remain unknown. Objectives: To identify some difficulties junior physicians face in delivering end-of-life care for patients with cancer and to clarify the support required to reduce these difficulties. Design: A nationwide survey was conducted in over 300 institutions selected randomly from 1037 clinical training hospitals in Japan. Participants: From each of these institutions, two resident physicians of postgraduate year (PGY) 1 or 2, two clinical fellows of PGY 3-5, and an attending physician were requested to respond to the survey. Measurements: The survey investigated issues regarding end-of-life care using the palliative care difficulties scale with two additional domains ("discussion about end-of-life care" and "death pronouncement"). Items related to potential solutions for alleviating the difficulties as well were investigated. Results: A total of 198 resident physicians, 134 clinical fellows, and 96 attending physicians responded to the survey (response rate: 33.0%, 22.3%, and 32.0%). The results revealed that junior physicians face difficulties within specific domains of end-of-life care. The most challenging domain comprised communication and end-of-life discussion with patients and family members, symptom alleviation, and death pronouncement. The most favored supportive measure for alleviating these difficulties was mentorship, rather than educational opportunities or resources regarding end-of-life care. Conclusion: The findings of this study reveal the need for further effort to enrich the mentorship and support systems for junior physicians delivering end-of-life care.

Validity and Reliability of the Japanese Version of the Dyspnea-12 Questionnaire in Patients With Lung Cancer.

CONTEXT: The Dyspnea-12 questionnaire is a simple tool to assess dyspnea using qualitative descriptors that include both physical and emotional domains. However, the reliability and validity of the Japanese version in patients with lung cancer have not been assessed. OBJECTIVE: To determine the reliability and validity of the Japanese version of the Dyspnea-12 questionnaire in patients with lung cancer. METHODS: The assessment was based on the numerical rating scale (NRS), cancer dyspnea scale (CDS), and hospital anxiety and depression scale (HADS). Spearman's correlation assessed the convergent validity of Dyspnea-12 using these three scales. Exploratory factor analysis examined the construct validity. The reliability was verified using Cronbach's alpha. Anxiety, depression, clinical dyspnea, presence of chronic obstructive pulmonary disease (COPD), and patient status were identified by discriminating performance. RESULTS: The analysis included 113 patients with lung cancer. A significant positive correlation was found between Dyspnea-12 and NRS, CDS, and HADS scores. Similar to the original version, factor analysis clearly classified Dyspnea-12 into two components (physical and emotional), thereby confirming its construct validity. Cronbach's alpha values for the total Dyspnea-12 and its physical and emotional components were 0.97, 0.95, and 0.96, respectively. Patients with anxiety, depression, and clinical dyspnea and those in the palliative phase had significantly higher Dyspnea-12 scores than their respective counterparts. The Dyspnea-12 scores of patients with and without COPD were similar. CONCLUSION: The Japanese version of the Dyspnea-12 questionnaire is a useful and reliable tool to assess the multi-dimensional aspects of dyspnea in patients with lung cancer.

Effects of Antibiotics on Respiratory Symptoms in Terminally Ill Cancer Patients With Pneumonia: A Multicenter Cohort Study.

CONTEXT: Patients in the terminal stages of cancer are frequently affected by infection, especially pneumonia; but the effects of antibiotics on respiratory symptoms and factors associated with improvement are still unclear. OBJECTIVES: This study aimed to clarify the effects of antibiotics on respiratory symptoms of terminally ill cancer patients with pneumonia, and to explore factors associated with the improvement. METHODS: This was a prospective cohort study in which we consecutively recruited terminally ill cancer patients diagnosed with pneumonia and treated with antibiotics at one of 23 palliative care units across Japan. At the baseline and Day 3, primarily responsible palliative care specialists recorded patient backgrounds, the results of physical and laboratory examination, and patient symptoms using the Support Team Assessment Schedule. Improvement was defined as improvement of dyspnea, cough, and sputum production on Day 3. RESULTS: Among all 1896 patients admitted during the study periods, 137 patients (7.2%) were enrolled into this study. Improvement was achieved in 65 patients (47.4%; 95% confidence intervals, 39-56). Univariate analyses revealed that the Palliative Prognostic Index (PPI), respiratory rate (RR), and oxygen requirement were significantly associated with the improvement. A multiple logistic regression analysis identified that PPI score of ≤ 6 and RR of <20 were independently associated with the improvement (odds ratios, 4.4 [1.6-12] and 2.5 [1.1-5.5], respectively). CONCLUSION: Antibiotics may relieve respiratory symptoms from pneumonia in approximately half of the terminally ill cancer patients. PPI and respiratory rate are useful to identify the patients who received benefits of antibiotics.

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.