Midazolam Indications and Dosing in Palliative Medicine: Results from a Multinational Survey

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Thank you for the opportunity to review this very well-written paper.

I have only very few comments:

- possibly you could tone down the claim in the introduction regarding the merit of midazolam regarding dyspnea (supported with 2 positive references), as you do later in the discussion: “Furthermore, even though the role of midazolam in dyspnoea is debated"......

- for me the numbers above the bars in the figures are confusing. I would prefer them in or under the bars.

Author Response

Comments 1: "possibly you could tone down the claim in the introduction regarding the merit of midazolam regarding dyspnea (supported with 2 positive references), as you do later in the discussion: “Furthermore, even though the role of midazolam in dyspnoea is debated"......"

Response 1: Thank you for highlighting this, I have added that midazolam's role is debated in the introduction. See page 2 line 64. 

Comments 2:  "for me the numbers above the bars in the figures are confusing. I would prefer them in or under the bars."

Response 2: I can understand that the numbers might be confusing. The reason for choosing to put the numbers above the bars were to distinguish them from what the bars show, which is the percentage of respondents. My goal was to show both the percentage and the actual number of respondents from each country. 

Reviewer 2 Report

Comments and Suggestions for Authors

Dear authors,

Thank you for your interesting manuscript on a important topic.

The main question addressed by the paper is to describe and compare the use of midazolam in different countries. The aim of the study could be presented more clearly to the reader. I recommend to write a sentence starting with The aim of the study was…

As midazolam is a drug that is frequently used in palliative care the topic is interesting both for clinicians and researchers.

The manuscript highlights the different practices of midazolam use in specialized palliative care in Norway, Denmark and the UK. The results will contribute to enhance the discussion about the use of midazolam and probably inspire the formation of guidelines for its use.

The most important improvement for he manuscript should be to state the aim of the study more clearly.

The discussion should include some thoughts about the choice of the participating countries. Two Scandinavian countries plus the UK is probably not representative for Europe or other countries. For the future a European study and probably the inclusion from other countries around the world could strengthen the findings.

The conclusions presented are grounded in the data of the study and are consistent with the arguments presented.

The references used in the manuscript are appropriate.

In summary this manuscript reports an interesting pilot study on the use of midazolam in palliative care and should be published in the journal.

 

I have only one minor comment:

1. The aim of the study should be stated more clearly

The future perspective and need for further research could be described in more detail.

I am looking forward to read the revised manuscript.

Author Response

Comment 1: "The aim of the study should be stated more clearly"

Response 1: I agree that the aim could be stated more clearly in the text. I have revised the formulation, please see page 2 paragraph 5, line 78-82.

Comment 2: "The discussion should include some thoughts about the choice of the participating countries. Two Scandinavian countries plus the UK is probably not representative for Europe or other countries. For the future a European study and probably the inclusion from other countries around the world could strengthen the findings."

Response 2: Thank you for pointing this out. I have added a paragraph on the choice of participating countries under 4.8 Strengths and limitations, see page 11 paragraph 5 line 327-330

Comment 3: "The future perspective and need for further research could be described in more detail."

Response 3: I have added a paragraph detailing future perspectives, see subchapter 4.9 page 11 line 334-338

Reviewer 3 Report

Comments and Suggestions for Authors

the analysis is interesting

please take into consideration the following recomm

1 abstract : when you say there are differences please mention here the most relevant one. There are info in the abstract which are somehow repeated and can be deleted to make space to this one

2 introduction midazolam is widely used in palliative care: please state the most common therapeutic indications and conditions (eg cancer? other diseases?)

3 analysis it would also be useful to see where this midazolam is given : GP?, Hospital, day center ? intensive care? hospice? Per country 

3.3 factors influencing the starting dose: the severity/frequency of symptoms ..which type of symptoms? psychiatric? others?

3.5 modes of administration refers to the route of adm ie subcut perfusion, intravenous etc  also if it is PRN which means when required or continuous infusion. your text speaks of the symptoms please revise 

Author Response

Comment 1: "abstract : when you say there are differences please mention here the most relevant one. There are info in the abstract which are somehow repeated and can be deleted to make space to this one"

Response 1: Thank you for addressing this, I have revised the abstract to amend this

Comment 2: "introduction midazolam is widely used in palliative care: please state the most common therapeutic indications and conditions (eg cancer? other diseases?)"

Response 2: Thank you, I have elaborated on the most common indications for midazolam in the introduction, see page 2 line 58-74

Comment 3: "analysis it would also be useful to see where this midazolam is given : GP?, Hospital, day center ? intensive care? hospice? Per country"

Response 3: I agree that these data would be interesting, unfortunately we did not include this question in our survey. I have highlighted this limitation under 4.8 Strengths and limitations, page 11 lines 331-332

Comment 4: "factors influencing the starting dose: the severity/frequency of symptoms ..which type of symptoms? psychiatric? others?"

Response 4: I agree that we should have stated which type of symptoms we meant by symptom intensity, unfortunately we did not specify which. The aim of the question was to ask if symptom intensity for which the respondents start midazolam for played an important part. Hopefully this answer is sufficient. 

Comment 5: "modes of administration refers to the route of adm ie subcut perfusion, intravenous etc  also if it is PRN which means when required or continuous infusion. your text speaks of the symptoms please revise"

Response 5: Thank you for pointing out this misunderstanding of the terminology! I have revised the manuscript.