Opioids for breathlessness in heart failure

Breathlessness is a common and problematic symptom in heart failure. Opioids have traditionally been considered as analgesics, but a potential role for their use in breathlessness is beginning to emerge. This thesis commences with a review of the existing literature in support of a possible role for opioids in the management of breathless in heart failure. A systematic review of existing human symptom control studies in this thesis suggests that opioid administration may have a small but significant benefit in chronic heart failure. However, only six studies were included in the review and most were either small or of poor methodological quality. This presents a relative gap in the knowledge on this topic. A randomised controlled trial was therefore performed to assess the effect of opioids on breathlessness in chronic heart failure. This crossover trial involved the comparison of two oral opioids with placebo. Thirty-five participants completed the trial, making it the largest trial of its type in this area. Opioid administration was shown to be safe in this patient cohort. No statistically significant differences were demonstrated for breathlessness severity between treatments. Participants were subsequently invited to participate in a three month open label extension. Thirty three participants in total were followed up with thirteen remaining on active therapy. This is the first trial of its type in breathlessness in heart failure and represents the longest participant follow-up in this area. Whilst not as robust as the initial trial, this extension period revealed that opioid continuers rated a statistically significant improvement in breathlessness severity from baseline compared to non-continuers. Finally, a semi-structured interview study in ten participants with heart failure revealed for the first time that opioids are acceptable in this population and they describe troublesome symptoms that might respond to opioid treatment.