Efficacy and Safety Comparison of Ulinastatin Versus Flurbiprofen Axetil for Preemptive Analgesia in Reducing Opioid Burden After Total Knee Arthroplasty - Response to Letter

Sep 29, 2026

Point-by-point correspondence addresses comments on a randomized controlled trial comparing ulinastatin (UTI) and flurbiprofen axetil (FA) for preemptive analgesia after total knee arthroplasty. The letter acknowledges a unit-conversion error in the reported UTI dose (“30 IU” corrected to 300,000 IU) and explains rationale and future dosing refinements. It also discusses baseline imbalance in stroke history after randomization, reporting that delirium incidence is lower with UTI and supplemental post hoc stratification supports the robustness of conclusions.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages3

Reading Time8 min

AccessFree to download

Response to the Letter

Dose Selection and Correction of Ulinastatin Dosage Error

Rationale, Future Refinement, and Supplementary Dosing Plans

Imbalance in Stroke History After Randomization

Supporting Delirium and Stratification Analyses

Conclusion

Journal of Pain Research Open Access Full Text Article RESPONSE TO LETTER Efficacy and Safety Comparison of Ulinastatin versus Flurbiprofen Axetil for Preemptive Analgesia in Reducing Opioid Burden After Total Knee Arthroplasty: A Randomized Controlled Trial [Response to Letter] Di Wang 1 , Yan Li 1 , 2 1College of Anesthesiology, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2Tianjin Jizhou People’s Hospital, Fifth Teaching Hospital of Tianjin University of TCM, Jizhou District, Tianjin, People’s Republic of China Correspondence: Yan Li, School of Anesthesiology, Shanxi Medical University, No. 56 Xinjian South Road, Yingze District, Taiyuan, Shanxi, 030001, People’s Republic of China, Email [drliyan@163.com](drliyan@163.com) Dear Editorial Team Thank you for the opportunity to respond to the Letter to the Editor by Wu M and Ye Y regarding our manuscript titled Efficacy and Safety Comparison of Ulinastatin Versus Flurbiprofen Axetil for Preemptive Analgesia in Reducing Opioid Burden After Total Knee Arthroplasty: A Randomized Controlled Trial published in the Journal of Pain Research. We have carefully reviewed the comments and appreciate the thoughtful feedback provided by the readers. Below, we have prepared a point-by-point response to address the concerns raised. Response to the Letter Dose Selection and Correction of Ulinastatin (UTI) Dosage Error We fully acknowledge the comment regarding the reported UTI dosage. The value “30 IU” was indeed an error; the correct dosage is 300,000 IU. This inaccuracy resulted from a unit conversion oversight during manuscript preparation (omission of the term “” [ten-thousand]) . We sincerely apologize for this error and will correct it promptly in the final revised manuscript. ● Rationale for Dose Selection: The single preoperative dose of 300,000 IU was selected based on established clinical practice and pharmacological studies. Multiple references indicate that the commonly used clinical dosage of UTI ranges between 100,000 and 500,000 IU (or 10,000 U/kg) .1–4 Furthermore, preclinical studies using a rat incisional pain model demonstrated that a single preoperative dose within this range effectively reduced postoperative mechanical hypersensitivity.5 Our own pilot data confirmed that this dosage offered an optimal balance between efficacy and safety. ● Future Refinement: We agree with the suggestion to include multiple dosing groups (eg, 100,000 IU, 300,000 IU, 500,000 IU) in future trials to identify the optimal regimen. Additionally, incorporating pharmacokinetic data (eg, plasma concentration-time curves) would further substantiate dose justification. Received: 13 December 2025 Accepted: 19 December 2025 Published: 31 December 2025 Journal of Pain Research 2025:18 7195–7197 7195 © 2025 Wang and Li. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at [https://www.dovepress.com/terms](https://www.dovepress.com/terms). php and incorporate the Creative Commons Attribution – Non Commercial (unported, v4.0) License ([http://creativecommons.org/licenses/by-nc/4.0/](http://creativecommons.org/licenses/by-nc/4.0/)). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ([https://www.dovepress.com/terms.php](https://www.dovepress.com/terms.php)). Imbalance in Stroke History After Randomization We acknowledge the observed imbalance in stroke history between the flurbiprofen axetil (FA) group (20%) and the control group (2%) . Although the trial was double-blinded and randomized, this discrepancy could potentially confound secondary outcomes such as delirium incidence. Below we provide a point-by-point response: ● Stringent

FAQs

What dosage error is corrected regarding ulinastatin in the response?

The reported value “30 IU” was an error; the correct UTI dosage is 300,000 IU. The mistake came from a unit conversion oversight during manuscript preparation.

How is the chosen single preoperative UTI dose justified?

A single 300,000 IU dose is supported by established clinical practice and pharmacological studies showing common UTI ranges of 100,000 to 500,000 IU, as well as preclinical evidence using an incisional pain model.

How does the authors’ response address the imbalance in stroke history after randomization?

The response notes exclusion criteria aimed to minimize confounding stroke-related cognitive sequelae, reports that delirium incidence is significantly lower in the UTI group, and describes post hoc stratification by stroke history (with limited conclusions in the very small stroke-history subgroup).

Sep 29, 2026

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