Influence of Intraoperative Nociception during Hip or Knee Arthroplasty with Supplementary Regional Anaesthesia on Postoperative Pain and Opioid Consumption

Round 1

Reviewer 1 Report

Thanks to the authors for such an interesting paper to investigate the implementation of a nociception level index aiming to find the effect of regional anaesthesia on patients facing hip or knee arthroplasty.

My comments below:

1.      1) Line 24: I couldn’t see any test throughout to paper comparing hip vs knee arthroplasty groups. If the test was made, then the conclusion is inappropriate. You just could not find any differences. The result of the test does not mean that they do not exist.

2.      2) Line 28: Authors claim to have found no association with intraoperative NOL and postoperative opioid consumption (same conclusion for secondary parameters and postoperative parameter levels), yet no suitable statistical analyses have been presented in the paper to sustain this claim. If the authors are referring to line 158 and figure S1, the presentation of the results needs improvement in term of coefficients, corresponding p-values and confidence intervals.

3.      3) I am having problems to understand the calculation of the sample size (line 122) as it considers mean NOL values, an assumed standard deviation, alpha and power, yet there is no mention of the effect size (for NRS in this case) or the test to be conducted. For an 80% of power, you may need far more subjects. Did the authors calculate a posteriori power analysis?

4.      4) Line 132: Following my previous point 1, the assumption of no pain differences (hip vs knee) is inappropriate, and the tests should have been conducted by differentiating both groups.

5.      5) Line 63: Authors argue to have performed an evaluation among the standard references (heart rate and BIS) and nociception data. However, I could not find such evaluation anywhere in the paper (only Wilcoxon tests are shown in tables 2 and S1 comparing for NRS)

6.      6) Following point 5 above, a Wilcoxon test is meant to be used for comparison between two dependent samples. It seems that authors are having two completely independent groups, rendering performed tests invalid.

7.      7) Line 185: I cannot seem to find the argument for this claim within the stats presented. I invite the authors to argue more.

8.      8) Further, from lines 30, 239 and 243 on concluding remarks, the only “significant” result was a NOL difference for the reaction to knife to skin. It seems too bold arguing a cause-effect relationship between intraoperatively nociception and postoperative outcome, using a simple analysis of differences between groups. Authors need more evidence for such a claim.

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Reviewer 2 Report

I read this manuscript with great interest. However I have several concerns as follow:

I am not sure if this study shows that NOL change after skin incision is clinically significant. Many parameters were compared in this study that was conducted in a very small and nonhomogeneous group. It is not surprising that some are statistically significant, however it does not mean that they are clinically significant. How long did the authors wait after performing a block before the skin incision? Momentary NOL scores may be misleading instead of an average score of 2 minutes. Which values did the authors record?

In addition I have several minor concerns:

Introduction

What are the primary or secondary outcomes of this study? Please explain more clearly. 

Sample size

I could not understand how you found the values of NoL with a standard deviation.

Tables

What do NRS d1 and NRS d2 mean?

Table 2: total number of the patients is 35. But data of 36 patients were analyzed. 

Several corrections should be made. 

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Reviewer 3 Report

The addressed issue is of clinical relevance. It is a well-written paper with a clear explanation of methodology, results, and discussion. The conclusions were well-balanced and appropriate. However, the following issues must be addressed before the article is accepted for publication.

- Detail the effects assessment instrument, especially pain, and who made the measurement

- Was this only primary joint arthroplasty?

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

Thanks to the authors for taking the time to update/modify this manuscript.

 

No further comments.

Reviewer 2 Report

There are no further issues.

 

There are few typographical errors.