Thank you for thoroughly examining our study and for giving us the opportunity to discuss the points you raised regarding our research published in Anesthesia & Analgesia. These issues were extensively discussed during the peer review process, which included robust dialogue with the reviewers and the assigned statistical reviewer. This invitation to respond allows us to further elucidate the scientific rigor and validity underpinning our work.
SAMPLE SIZE AND STATISTICAL RIGOR
Based on previous studies, our initial sample size calculation aimed to detect a clinically meaningful difference in total remifentanil dose was initially set at 200 µg. As the study progressed, we adapted the metric to µg/kg/min to better account for patient body weight and procedural duration. Despite these changes, the original sample size retained sufficient power for robust analysis. On consultation during peer review, we applied Bonferroni correction, adjusting our alpha to 0.025 for each primary outcome. This rigorous adjustment ensured a conservative approach to significance testing, enhancing the reliability of our findings.
ANESTHETIC DOSE MANAGEMENT
The reduction in anesthetic doses correlates with improved hemodynamic stability, demonstrating that Autonomic Neural Blockade (ANB) effectively modulates surgical stress responses. This is reflected in the significant reduction in opioid consumption, which, although quantitatively small at 0.04 µg/kg/min, carries substantial clinical importance within the context of the opioid crisis and opioid-sparing initiatives in perioperative care. The total mean difference observed was 182.9 µg, reinforcing its clinical relevance.
PROTOCOL ADHERENCE AND CLINICAL AUTONOMY
While an independent investigator monitored protocol adherence in our study, treating anesthesiologists retained clinical autonomy to adjust anesthesia based on real-time patient needs. Variations in anesthetic administration, such as one anesthesiologist’s increased use of sevoflurane over remifentanil, were based on clinical judgments aimed at optimizing patient care and safety, not a protocol failure. Deviations were documented and analyzed to ensure transparency in how clinical decisions influenced study outcomes, adhering to safety and ethical standards within operational research constraints.
HEMODYNAMIC IMPACT AND CLINICAL STABILITY
In our study, changes in mean arterial pressure (MAP) and heart rate (HR) were not only statistically significant but also clinically meaningful. The group that exhibited improved hemodynamic stability—with a decrease in MAP of 8.2 mm Hg vs 0.6 mm Hg and a reduction in HR of 3.3 beats/min versus an increase of 4.8 beats/min—also received fewer anesthetics due to the early application of ANB. This correlation strongly suggests that ANB reduces the need for anesthetics and enhances physiological stability during surgery. All hemodynamic measurements were taken at 3 critical surgical moments, with careful control for confounding factors like hypertension, age, BMI, and chronic analgesic use across both groups, as detailed in Table 1. This meticulous approach confirms that the observed hemodynamic benefits are directly attributable to ANB, enhancing both patient safety and surgical efficiency.
FOCUS ON ANESTHETIC AGENTS
Our study primarily highlighted remifentanil due to its profound implications for opioid management. Although the less emphasized difference in sevoflurane consumption did not reach statistical significance, it remains an integral part of our comprehensive evaluation of anesthetic agent use. This choice underscores our focus on outcomes significantly affecting patient recovery and safety.
BLINDING AND RANDOMIZATION INTEGRITY
Blinding was meticulously maintained for patients and data collectors, with only the surgical and anesthesiology teams unblinded to ensure the safe management of interventions. Our randomization effectively balanced all significant demographic and clinical variables, as confirmed by the absence of significant differences in baseline characteristics (Table 1).
ADDRESSING POTENTIAL BETA-BLOCKER COMPARISONS
The changes in hemodynamic parameters like mean arterial pressure and heart rate were statistically significant and clinically relevant. The improvement in these parameters demonstrates the efficacy of ANB when applied early in surgery. Unlike beta-blockers, which primarily modulate cardiovascular responses, ANB provides a comprehensive sensory blockade that reduces physiological stress responses, offering a broader range of perioperative benefits than beta-blockers alone.
We hope this response addresses your concerns and clarifies our study’s methodologies and outcomes. We remain committed to advancing surgical anesthesia practices through rigorous research and innovative approaches like ANB.