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The longitudinal pattern of response when morphine is used to treat chronic refractory dyspnea.

ABSTRACT: While evidence supports using sustained release morphine for chronic refractory breathlessness, little is known about the longitudinal pattern of breathlessness intensity as people achieve symptomatic benefit. The aim of this study is to describe this pattern.This secondary analysis used breathlessness intensity scores (100?mm visual analogue scale (VAS)) from a prospective, dose increment study of once daily (morning) sustained release morphine for chronic refractory breathlessness. Participants who achieved <10% improvement over their own baseline at one week (10?mg) were titrated to 20?mg and if no response, another week later to 30?mg for one week. Time was standardized at the first day of the week in which participants responded generating twice daily data one week either side of symptomatic benefit. Analysis used random effect mixed modeling.Of the 83 participants, 17/52 responders required >10?mg: 13 participants (20?mg) and 4 (30?mg), contributing 634 VAS observations. In the week leading to a response, average VAS scores worsened by 0.3?mm/day (p=0.16); the average improvement in the first 24 hours of response was 10.9?mm (7.0 to 14.7; p<0.0001), with continued improvement of 2.2?mm/day (p<0.001) for six more days.When treating chronic refractory breathlessness with once daily sustained release morphine, titrate to effect, since inadequate dose may generate no response; and following an initial response, further dose increases should not occur for at least one week. Whether further benefit would be derived beyond day six on the dose to which people respond, and what net effect a further dose increase would have are questions yet to be answered.

SUBMITTER: Currow DC

PROVIDER: S-EPMC3718325 | biostudies-other | 2013 Aug

REPOSITORIES: biostudies-other

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The longitudinal pattern of response when morphine is used to treat chronic refractory dyspnea.

Currow David C DC Quinn Stephen S Greene Aine A Bull Janet J Johnson Miriam J MJ Abernethy Amy P AP

Journal of palliative medicine 20130608 8

<h4>Background</h4>While evidence supports using sustained release morphine for chronic refractory breathlessness, little is known about the longitudinal pattern of breathlessness intensity as people achieve symptomatic benefit. The aim of this study is to describe this pattern.<h4>Methods</h4>This secondary analysis used breathlessness intensity scores (100 mm visual analogue scale (VAS)) from a prospective, dose increment study of once daily (morning) sustained release morphine for chronic ref ...[more]

PMID: 23746231

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Project description:BackgroundDyspnea that is refractory to conventional treatments affects up to 50% of patients with advanced chronic obstructive pulmonary disease (COPD). Although professional societies recommend opioids in this setting, evidence supporting their use over months is limited. We conducted a multicentre mixed-methods study to understand patients' experiences when opioids are added to optimized conventional treatments for advanced COPD.MethodsA total of 44 patients (median age 74, range 51-89 years) agreed to participate in this 6-month study. After baseline assessments, immediate-release morphine sulfate syrup (initially 0.5 mg twice daily) was slowly titrated upward based on weekly assessments of symptoms. We conducted semistructured interviews and collected contemporaneous measures of health-related quality of life, severity of dyspnea, anxiety, depression, global ratings of opioid "helpfulness" and adverse effects before, at 2 months and at 4-6 months after opioids were started.ResultsOf the 44 patients, 32 (73%) completed the trial; 27 (90%) of 30 patients reported the opioid treatment as very (43%) or somewhat (47%) helpful. Three main themes emerged from the patients' overall positive experiences: small gains have big impact; realign hopes with reality; and "try it." Significant improvements were observed in median (interquartile range) scores between baseline and 4-6 months' assessment for health-related quality of life (Chronic Respiratory Questionnaire: 3.5 [2.8-4.0] v. 4.2 [3.6-4.8]; and Chronic Respiratory Questionnaire-Dyspnea domain: 2.8 [2.3-3.6] v. 3.9 [2.8-4.5]) and decreases in severity of dyspnea (numerical rating scale: 7.0 [5.0-8.0] v. 5.0 [4.0-6.0]). Adverse effects were minimal for most patients.InterpretationOpioids were a helpful and acceptable intervention for refractory dyspnea in patients with advanced COPD. Many of the patients experienced sustained benefits over months, which supports recent recommendations to consider opioids in this setting.Trial registrationClinicalTrial.gov, no. NCT00982891.

Project description:BackgroundRefractory 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.MethodsWe 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.DiscussionEvidence 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 .

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The longitudinal pattern of response when morphine is used to treat chronic refractory dyspnea.

Publications

The longitudinal pattern of response when morphine is used to treat chronic refractory dyspnea.

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