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]

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 ErrorWe 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). 1-4Furthermore, preclinical studies using a rat incisional pain model demonstrated that a single preoperative dose within this range effectively reduced postoperative mechanical hypersensitivity. 5Our 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.