On 2016 Oct 05, Cicely Saunders Institute Journal Club commented:

The Cicely Saunders Institute journal club discussed this paper on 5th October 2016.

We thought that this review addressed an important question in relation to the pharmacological management of breathlessness at the end of life, and agreed that an update to the previous Cochrane review in this area was warranted.

We were interested in the selection of papers and the fact that some of the studies in the original Jennings et al review were deemed of insufficient quality to include in the update. We also wondered if more information could have been included about the authors’ definition of “advanced progressive illness”.

There was a lively discussion about the heterogeneity of included studies, which was attributed to variations in individual study design, and in the drug, dose and route used for the intervention. Some argued that focusing solely on studies evaluating morphine sulphate, which has high affinity for the µ opioid receptor (the subtype present in the lung) and also appeared to have the most promising results in sub-group analysis, might have provided a clearer picture of the benefit of opioids. Others pointed out that pooling studies for meta-analysis provides a larger sample, and that focusing on morphine alone would exclude patients with renal impairment.

We noted that when reporting the breathlessness outcomes, it would have been useful to define a minimal clinically important difference in breathlessness as well as an effect size, since it is difficult to tell if the standardised mean differences from the meta-analysis would be clinically relevant. In addition lack of standardisation of outcome measurements limited the potential meta-analysis.

We considered that as presented in this paper, the evidence on opioids in breathlessness is insufficient to guide practice. We agreed with the authors that larger, fully powered studies with adequate wash out periods and standardised dosing schedules are the starting point to improve the evidence base. We thought that focusing future studies on a single opioid (morphine sulphate seems the most promising candidate) might reduce heterogeneity and allow clearer measurement of any benefit.

Comment written by Dr Simon Etkind and Dr Sabrina Bajwah

On 2016 Oct 05, Cicely Saunders Institute Journal Club commented:

The Cicely Saunders Institute journal club discussed this paper on 5th October 2016.

We thought that this review addressed an important question in relation to the pharmacological management of breathlessness at the end of life, and agreed that an update to the previous Cochrane review in this area was warranted.

We were interested in the selection of papers and the fact that some of the studies in the original Jennings et al review were deemed of insufficient quality to include in the update. We also wondered if more information could have been included about the authors’ definition of “advanced progressive illness”.

There was a lively discussion about the heterogeneity of included studies, which was attributed to variations in individual study design, and in the drug, dose and route used for the intervention. Some argued that focusing solely on studies evaluating morphine sulphate, which has high affinity for the µ opioid receptor (the subtype present in the lung) and also appeared to have the most promising results in sub-group analysis, might have provided a clearer picture of the benefit of opioids. Others pointed out that pooling studies for meta-analysis provides a larger sample, and that focusing on morphine alone would exclude patients with renal impairment.

We noted that when reporting the breathlessness outcomes, it would have been useful to define a minimal clinically important difference in breathlessness as well as an effect size, since it is difficult to tell if the standardised mean differences from the meta-analysis would be clinically relevant. In addition lack of standardisation of outcome measurements limited the potential meta-analysis.

We considered that as presented in this paper, the evidence on opioids in breathlessness is insufficient to guide practice. We agreed with the authors that larger, fully powered studies with adequate wash out periods and standardised dosing schedules are the starting point to improve the evidence base. We thought that focusing future studies on a single opioid (morphine sulphate seems the most promising candidate) might reduce heterogeneity and allow clearer measurement of any benefit.

Comment written by Dr Simon Etkind and Dr Sabrina Bajwah