We read with great interest the study by Shi et al,1 published in Drug Design, Development and Therapy, comparing desflurane-based inhalational anesthesia with propofol-based total intravenous anesthesia (TIVA) in elderly patients undergoing spinal surgery. The authors found that desflurane provided non-inferior postoperative Quality of Recovery-15 (QoR-15) scores, with faster emergence and lower phenylephrine requirements. While acknowledging the clinical relevance of this randomized trial, several methodological and interpretative issues warrant further discussion.

First, regarding the analysis population and post-randomization exclusion. Although the abstract reports 109 randomized patients, the Results section and flowchart indicate that 110 patients were randomized, with one patient in the propofol group subsequently withdrawn because of an unplanned postoperative intensive care unit admission.1 As this clinically important exclusion occurred after randomization, the missing outcome is potentially informative and could be related to prognosis, which may introduce bias in a per-protocol or available-case analysis. The updated Consolidated Standards of Reporting Trials (CONSORT) 2025 guidance emphasizes transparent reporting of which randomized participants are included in each analysis and how missing outcome data are handled.2 It would therefore be helpful to clarify whether the primary analysis was conducted according to the intention-to-treat principle, and to provide a sensitivity analysis that incorporates this patient’s data, perhaps through multiple imputation or a best-worst case scenario.

Second, regarding the non-inferiority margin and the interpretation of “interchangeability”. While we acknowledge that the 6-point margin was based on the minimal clinically important difference, recent methodological guidance emphasizes that non-inferiority margins require explicit empirical and clinical justification and should represent the largest clinically acceptable loss.3 The observed mean difference was −1.4, with the lower limit of the 95% confidence interval at −5.6, which lies only 0.4 points above the margin.1 Furthermore, a non-inferiority design does not establish bidirectional equivalence. Consequently, describing desflurane and propofol as “interchangeable” might be a stronger claim than the study design directly supports. Reporting sensitivity analyses using alternative clinically justified margins, as well as discussing the implications for other outcomes such as cost and adverse-effect profiles, would help further validate the robustness of this conclusion.

Third, regarding the interpretation of vasopressor requirements. Phenylephrine consumption was lower with desflurane (220 [0–400] versus 365 [0–746.5] μg; P=0.049), despite no significant between-group differences in mean arterial pressure or heart rate.1 The anesthesiologist was unblinded, and hypotension could be treated with either ephedrine or phenylephrine without a reported standardized selection algorithm. Vasopressor use may therefore partly reflect clinician-dependent decisions rather than physiological stability. In addition, multiplicity correction was applied only to the five QoR-15 dimensions, making the borderline P value of 0.049 among numerous secondary comparisons worthy of cautious interpretation. Reporting hypotension duration or a time-weighted measure of hypotension, together with a protocolized vasopressor strategy, would provide a more objective comparison.

Fourth, regarding the clinical significance of faster emergence. Desflurane shortened median extubation time from 9 to 6 minutes and orientation recovery from 12 to 8 minutes, but did not shorten post-anesthesia care unit stay, time to ambulation, or postoperative hospital stay.1 A recent meta-analysis of 22 studies involving 1504 participants similarly found that desflurane accelerated early recovery compared with propofol, whereas most intermediate and late recovery outcomes were comparable and in-hospital postoperative nausea and vomiting (PONV) was more frequent.4 In the present study, PONV occurred in 9.1% versus 1.9% of patients, although the difference was not statistically significant.1 Whether several minutes of faster emergence translate into meaningful efficiency or enhanced recovery therefore remains uncertain.

Fifth, regarding intraoperative neurophysiological monitoring (IONM). The study did not report whether somatosensory or motor evoked potentials were monitored.1 Current spine-surgery guidance recommends IONM for patients at high risk of intraoperative spinal cord injury,5 while updated neurophysiological recommendations recognize that propofol-based TIVA generally suppresses evoked potentials less than volatile anesthesia.6 The desflurane group received 0.7–1.0 minimum alveolar concentration, which may influence evoked-potential signals and require anesthetic adjustment. Reporting the proportion of patients receiving IONM, desflurane concentrations during monitoring, and protocol modifications would clarify generalizability to neurologically high-risk spinal surgery.

Sixth, regarding postoperative delirium assessment. Delirium was assessed only on postoperative days 1 and 2, with one event in the desflurane group and none in the propofol group.1 The updated European Society of Anaesthesiology and Intensive Care Medicine guideline specifies validated delirium assessment at least once daily for at least three days, beginning in the recovery area or no later than postoperative day 1.7 The present surveillance window may therefore have missed early, fluctuating, or later-onset delirium. Given the extremely small number of events, absence of statistical significance should not be interpreted as evidence of comparable neurocognitive safety.

In summary, Shi et al provide valuable randomized evidence regarding desflurane and propofol anesthesia in elderly spinal surgery. Further clarification of the analysis population, sensitivity testing of the non-inferiority margin, standardized hemodynamic management, assessment of the clinical value of faster emergence, IONM-specific reporting, and extended delirium surveillance would strengthen interpretation of these findings and better define the relative clinical roles of the two anesthetic strategies.

The authors report no conflicts of interest in this communication.

1. Shi D, Liang X, Xi C, Pei C, Wang G. Effects of desflurane and propofol general anesthesia on postoperative recovery quality in elderly patients undergoing spinal surgery: a randomized non-inferiority trial. Drug Des Devel Ther. 2026;20:601299. doi:10.2147/DDDT.S601299

2. Hopewell S, Chan AW, Collins GS, et al. CONSORT 2025 statement: updated guideline for reporting randomised trials. BMJ. 2025;389:e081123. doi:10.1136/bmj-2024-081123

3. Axelsson E. Equivalence and non-inferiority trials in the evaluation of non-pharmacological interventions: rationale, challenges and recommendations. BMJ Open. 2025;15(8):e102996. doi:10.1136/bmjopen-2025-102996

4. Hu W, Zhuang J, Liu X, Zhang P. Desflurane versus propofol for ambulatory surgery: a systematic review and meta-analysis. J Clin Anesth. 2026;110:112140. doi:10.1016/j.jclinane.2026.112140

5. Fehlings MG, Alvi MA, Evaniew N, et al. A clinical practice guideline for prevention, diagnosis and management of intraoperative spinal cord injury: recommendations for use of intraoperative neuromonitoring and for the use of preoperative and intraoperative protocols for patients undergoing spine surgery. Global Spine J. 2024;14(3 Suppl):212S–3. doi:10.1177/21925682231202343

6. Toleikis JR, Pace C, Jahangiri FR, Hemmer LB, Toleikis SC. Intraoperative somatosensory evoked potential (SEP) monitoring: an updated position statement by the American Society of Neurophysiological Monitoring. J Clin Monit Comput. 2024;38(5):1003–1042. doi:10.1007/s10877-024-01201-x

7. Aldecoa C, Bettelli G, Bilotta F, et al. Update of the European Society of Anaesthesiology and Intensive Care Medicine evidence-based and consensus-based guideline on postoperative delirium in adult patients. Eur J Anaesthesiol. 2024;41(2):81–108. doi:10.1097/EJA.0000000000001876