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 .

Attitudes toward opioids for refractory dyspnea in COPD among Dutch chest physicians.

Dyspnea is the most frequently reported symptom of outpatients with advanced chronic obstructive pulmonary disease (COPD). Opioids are an effective treatment for dyspnea. Nevertheless, the prescription of opioids to patients with advanced COPD seems limited. The aims of this study are to explore the attitudes of Dutch chest physicians toward prescription of opioids for refractory dyspnea to outpatients with advanced COPD and to investigate the barriers experienced by chest physicians toward opioid prescription in these patients. All chest physicians (n = 492) and residents in respiratory medicine (n = 158) in the Netherlands were invited by e-mail to complete an online survey. A total of 146 physicians (response rate 22.5%) completed the online survey. Fifty percent of the physicians reported to prescribe opioids for refractory dyspnea in 20% or less of their outpatients with advanced COPD and 18.5% reported never to prescribe opioids in these patients. The most frequently reported barriers toward prescription of opioids were resistance of the patient, fear of possible adverse effects, and fear of respiratory depression. To conclude, Dutch chest physicians and residents in respiratory medicine rarely prescribe opioids for refractory dyspnea to outpatients with advanced COPD. This reluctance is caused by perceived resistance of the patient and fear of adverse effects, including respiratory adverse effects.

[Treatment of anxiety in COPD with CBT]. / Angst bij COPD behandelen met CGT.

A major part of COPD patients suffers from anxiety. The presence of an anxiety or stress disorder compromises their quality of life. Anxiety and (posttraumatic) stress disorders may be treated with cognitive behavior therapy (CBT). CBT encompasses different treatment interventions and protocols. Some of these interventions have been investigated to treat anxiety in patients with COPD. Those that have been proven to be effective, should be offered to COPD patients with anxiety. Examples are: education about symptoms in COPD (mostly dyspnea) and the bodily anxiety response; education about the positive and negative anxiety and breathing circle; breathing, posture and relaxation exercises; identification and correction of catastrophic thoughts; setting goals and planning activities (behavior activation) and pacing.