Regarding - impact of opioid-free anaesthesia on the overall benefit of analgesia score after laparoscopic cholecystectomy

Sep 30, 2026

Letter to the editor responding to a multicentre randomized controlled trial protocol evaluating opioid-free anaesthesia (OFA) after laparoscopic cholecystectomy. The correspondence highlights strengths in the dexmedetomidine- and esketamine-based OFA regimen and the Overall Benefit of Analgesia Score (OBAS), then requests clarification to improve validity. Key concerns include the definition of chronic postsurgical pain at 90 days, the assumed OBAS standard deviation for sample size, and the largely unidimensional pain assessment relying on single time-point NRS intensity.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages2

Reading Time5 min

AccessFree to download

Letter to the editor

Strengths and study design

Methodological clarification requests

Chronic postsurgical pain definition and sample size assumptions

CPSP assessment approach

Summary and implications

AnnAls of Medicine 2026, Vol. 58, no. 1, 2608513 [https://doi.org/10.1080/07853890.2025.2608513](https://doi.org/10.1080/07853890.2025.2608513) LETTER TO THE EDITOR Regarding: ‘impact of opioid-free anaesthesia on the overall benefit of analgesia score after laparoscopic cholecystectomy: protocol and statistical analysis plan for a multicentre, randomized, controlled trial’ To the editor We read with great interest the multicentre randomized controlled trial protocol by Zhao Hanxue et al. investigating the impact of opioid-free anaesthesia (OFA) on the Overall Benefit of Analgesia Score (OBAS) following laparoscopic cholecystectomy [1] . The study employs a dexmedetomidine- and esketamine-based OFA regimen and utilizes OBAS – a composite endpoint that integrates analgesic efficacy with adverse effects – demonstrating a methodologically sound and clinically meaningful design. However, several methodological aspects require further clarification to strengthen the validity and interpretability of the findings. First, the definition of chronic postsurgical pain (CPSP) and its role in sample size estimation warrant careful examination. The authors define CPSP at 90 days as any pain in the surgical area with a Numerical Rating Scale (NRS) score ≥1 . While this threshold enhances sensitivity, it may include subclinical or trivial pain that lacks clinical significance, potentially inflating the estimated incidence of meaningful CPSP [2] . We recommend that the authors explicitly justify this cutoff, ideally by referencing established consensus guidelines, or alternatively conduct sensitivity analyses using a more stringent threshold (e.g. NRS ≥ 3) . Additionally, the sample size calculation assumes an OBAS standard deviation (SD) of 3.0, whereas previous studies report SDs ranging from 2.3 to 3.5 [3,4] . To ensure adequate statistical power, a more robust rationale for the assumed SD should be provided – such as pooled estimates from similar trials or pilot data – or sensitivity analyses should be performed to evaluate the effect of varying SD values on power. Second, the assessment of CPSP is currently unidimensional, relying solely on NRS pain intensity measured at a single time point. A comprehensive evaluation should also consider pain quality (e.g. using the McGill Pain Questionnaire to identify neuropathic or visceral components) and functional impact (e.g. via the Brief Pain Inventory to assess interference with sleep, mood and daily activities) [5] . Sole reliance on pain intensity may fail to capture patients experiencing low-intensity but high-burden symptoms – such as dysesthesia disrupting sleep or discomfort limiting mobility – which could lead to misclassification and bias in outcome interpretation and subgroup analyses. For example, an NRS score of 2–3 associated with burning pain and reduced physical function may represent clinically significant CPSP despite moderate intensity. Future research would benefit from incorporating multidimensional pain assessments to enhance the precision and clinical relevance of CPSP evaluation within OFA protocols. In summary, Zhao Hanxue et al. have designed a methodologically rigorous trial to evaluate OFA in laparoscopic cholecystectomy. Addressing the above aspects regarding CPSP definition and assessment, along with sample size justification, would further strengthen the interpretability and clinical applicability of the trial outcomes. Acknowledgments Chenhui Lv: Conceptualization, Writing – original draft. Qijia Xuan: Writing – review & editing, Investigation. all authors have read and approved the final version of the manuscript. Authors contributions CRediT: Chenhui Lv: Conceptualization, Writing – original draft; Qijia Xuan: Investigation, Writing – review & editing. Disclosure statement No potential conflict of interest was reported by the authors. Funding The author(s) reported there is no funding associated with the work featured in this

FAQs

What trial does the letter address?

It addresses a multicentre randomized controlled trial protocol investigating the impact of opioid-free anaesthesia (OFA) on the Overall Benefit of Analgesia Score (OBAS) after laparoscopic cholecystectomy.

Why does the letter question the CPSP definition used for sample size?

It notes that defining CPSP at 90 days with NRS ≥ 1 may capture trivial or subclinical pain, potentially inflating the incidence of meaningful CPSP and affecting estimated sample size.

What additional measures does the letter suggest for assessing CPSP?

It recommends multidimensional assessment beyond single time-point NRS intensity, including pain quality and functional impact (e.g., tools to evaluate neuropathic/visceral components and interference with sleep, mood, and daily activities).

Sep 30, 2026

Uploaded by Well Done