Opioids in patients with COPD and refractory dyspnea: literature review and design of a multicenter double blind study of low dosed morphine and fentanyl (MoreFoRCOPD).

BACKGROUND: Refractory dyspnea or breathlessness is a common symptom in patients with advanced chronic obstructive pulmonary disease (COPD), with a high negative impact on quality of life (QoL). Low dosed opioids have been investigated for refractory dyspnea in COPD and other life-limiting conditions, and some positive effects were demonstrated. However, upon first assessment of the literature, the quality of evidence in COPD seemed low or inconclusive, and focused mainly on morphine which may have more side effects than other opioids such as fentanyl. For the current publication we performed a systematic literature search. We searched for placebo-controlled randomized clinical trials investigating opioids for refractory dyspnea caused by COPD. We included trials reporting on dyspnea, health status and/or QoL. Three of fifteen trials demonstrated a significant positive effect of opioids on dyspnea. Only one of four trials reporting on QoL or health status, demonstrated a significant positive effect. Two-thirds of included trials investigated morphine. We found no placebo-controlled RCT on transdermal fentanyl. Subsequently, we hypothesized that both fentanyl and morphine provide a greater reduction of dyspnea than placebo, and that fentanyl has less side effects than morphine. METHODS: We describe the design of a robust, multi-center, double blind, double-dummy, cross-over, randomized, placebo-controlled clinical trial with three study arms investigating transdermal fentanyl 12 mcg/h and morphine sustained-release 10 mg b.i.d. The primary endpoint is change in daily mean dyspnea sensation measured on a numeric rating scale. Secondary endpoints are change in daily worst dyspnea, QoL, anxiety, sleep quality, hypercapnia, side effects, patient preference, and continued opioid use. Sixty patients with severe stable COPD and refractory dyspnea (FEV1 < 50%, mMRC ≥ 3, on optimal standard therapy) will be included. DISCUSSION: Evidence for opioids for refractory dyspnea in COPD is not as robust as usually appreciated. We designed a study comparing both the more commonly used opioid morphine, and transdermal fentanyl to placebo. The cross-over design will help to get a better impression of patient preferences. We believe our study design to investigate both sustained-release morphine and transdermal fentanyl for refractory dyspnea will provide valuable information for better treatment of refractory dyspnea in COPD. Trial registration NCT03834363 (ClinicalTrials.gov), registred at 7 Feb 2019, https://clinicaltrials.gov/ct2/show/NCT03834363 .

The Impact of Palliative Care Team Consultation on Quality of Life of Patients with Advanced Cancer in Dutch Hospitals: An Observational Study.

INTRODUCTION: Experimental studies have shown that palliative care team (PCT) involvement can improve quality of life (QoL) and symptom burden of patients with advanced cancer. It is unclear to what extent this effect is sustained in daily practice of hospital care. OBJECTIVE: This observational study aims to investigate the effect of PCT consultation on QoL and symptom burden of hospitalized patients with advanced cancer in daily practice. METHODS: After admission to 1 of 9 participating hospitals, patients with advanced cancer for whom the attending physician answered "no" to the Surprise Question were invited to complete a questionnaire, including the EORTC QLQ-C15-PAL, at 6 points in time, until 3 months after admission. Outcomes were compared between patients who received PCT consultation and patients who did not, taking into account differences in baseline characteristics. RESULTS: A total of 164 patients consented to participate, of whom 32 received PCT consultation. Of these patients, 108 were able to complete a questionnaire at day 14, of whom 19 after receiving PCT consultation. After adjusting for baseline differences, EORTC QLQ-C15-PAL scores for pain, appetite, and emotional functioning at day 14 were more favorable for patients who received a PCT consultation. CONCLUSION: PCT consultation decreased patients' symptom burden and tends to have a positive effect on QoL of hospitalized patients with advanced cancer, even if the PCT is consulted late in the patient's disease trajectory.

The association between palliative care team consultation and hospital costs for patients with advanced cancer: An observational study in 12 Dutch hospitals.

BACKGROUND: Early palliative care team consultation has been shown to reduce costs of hospital care. The objective of this study was to investigate the association between palliative care team (PCT) consultation and the content and costs of hospital care in patients with advanced cancer. MATERIAL AND METHODS: A prospective, observational study was conducted in 12 Dutch hospitals. Patients with advanced cancer and an estimated life expectancy of less than 1 year were included. We compared hospital care during 3 months of follow-up for patients with and without PCT involvement. Propensity score matching was used to estimate the effect of PCTs on costs of hospital care. Additionally, gamma regression models were estimated to assess predictors of hospital costs. RESULTS: We included 535 patients of whom 126 received PCT consultation. Patients with PCT had a worse life expectancy (life expectancy <3 months: 62% vs. 31%, p < .01) and performance status (p < .01, e.g., WHO status higher than 2:54% vs. 28%) and more often had no more options for anti-tumour therapy (57% vs. 30%, p < .01). Hospital length of stay, use of most diagnostic procedures, medication and other therapeutic interventions were similar. The total mean hospital costs were €8,393 for patients with and €8,631 for patients without PCT consultation. Analyses using propensity scores to control for observed confounding showed no significant difference in hospital costs. CONCLUSIONS: PCT consultation for patients with cancer in Dutch hospitals often occurs late in the patients' disease trajectories, which might explain why we found no effect of PCT consultation on costs of hospital care. Earlier consultation could be beneficial to patients and reduce costs of care.

The COMPASS study: A descriptive study on the characteristics of palliative care team consultation for cancer patients in hospitals.

OBJECTIVE: To describe the characteristics of palliative care team (PCT) consultation for patients with cancer who are admitted in hospital and to investigate when and why PCTs are consulted. METHODS: In this descriptive study in ten Dutch hospitals, the COMPASS study, we compared characteristics of patients with cancer for whom a PCT was or was not consulted (substudy 1). We also collected information about the process of PCT consultations and the disciplines involved (substudy 2). RESULTS: In substudy 1, we included 476 patients. A life expectancy <3 months, unplanned hospitalisation and lack of options for anti-cancer treatment increased the likelihood of PCT consultation. In substudy 2, 64% of 550 consultations concerned patients with a life expectancy of <3 months. The most frequently mentioned problems that were identified by the PCTS were complex pain problems (56%), issues around the organisation of care (31%), fatigue (27%) and dyspnoea (27%). There was much variance between hospitals in the disciplines that were involved in consultations. CONCLUSION: Palliative care teams in Dutch hospitals are most often consulted for patients with a life expectancy of <3 months who have an unplanned hospital admission because of physical symptoms or problems. We found much variance between hospitals in the composition and activities of PCTs.