Effective dosing of anaesthetic agents is essential to achieve adequate analgesia and hemodynamic stability during surgery (1). Surgical stimuli activate nociceptive pathways, which, although suppressed by anaesthetics, can still provoke autonomic responses—even in unconscious patients—leading to fluctuations in heart rate, blood pressure, and circulating stress hormone levels (2).

Heart rate variability (HRV) has long been recognized as a noninvasive marker of autonomic nervous system activity and nociceptive balance. It reflects the dynamic interaction between sympathetic and parasympathetic inputs, which is modulated during anaesthesia in response to both surgical stimulation and analgesic administration (3). However, HRV alone may not fully capture the complexity of intraoperative nociception, especially in patients with altered autonomic tone due to anxiety, comorbidities, or pharmacological influences (4).

To address these limitations, the Analgesia Nociception Index (ANI) was developed as a more refined and dynamic tool for evaluating nociceptive status during general anaesthesia. The ANI is derived from respiratory-modulated R‒R interval variability and provides a real-time numerical index of parasympathetic activity (5). Unlike traditional hemodynamic parameters, ANI offers continuous feedback on nociception–antinociception balance, allowing anesthesiologists to titrate opioids with greater precision. ANI monitoring systems are now widely integrated into clinical practice and have become increasingly accessible (6).

Recent studies suggest that ANI-guided analgesia may reduce intraoperative opioid consumption, improve postoperative pain control, and decrease the incidence of opioid-related adverse effects such as nausea and vomiting (7). These potential benefits are especially relevant in spine surgery, where high-dose remifentanil use is common and associated with postoperative hyperalgesia and an increased risk of PONV(8). This study aimed to assess the clinical utility of ANI monitoring by evaluating intraoperative remifentanil consumption, postoperative pain scores, and patient satisfaction.

Patients were randomly assigned in a 1:1 ratio to either the ANI-guided group or the standard-care group using a computer-generated sequence (Randomizer.org). Allocation concealment was maintained using sealed, opaque envelopes prepared by an independent researcher. The anesthesiologist responsible for intraoperative management was aware of the group assignment, whereas the patients, postoperative assessors, and recovery room staff remained blinded throughout the study.

Owing to the limited availability of prior data on ANI-guided analgesia in spine surgery, a priori sample size calculation was not feasible. Nevertheless, a post hoc power analysis based on the primary outcome (total remifentanil consumption) demonstrated a statistical power of 92% to detect a clinically significant difference between groups at α = 0.05, supporting the adequacy of the sample size.

Standard monitoring included electrocardiography, pulse oximetry, noninvasive blood pressure, capnography, and bispectral index (BIS; target range: 40–60). In the ANI group, additional monitoring was performed using the PhysioDoloris device (Mdoloris Medical Systems, Lille, France), with ANI values maintained between 50 and 70. Anesthesia induction consisted of intravenous propofol 2 mg/kg, fentanyl 2 µg/kg, and rocuronium 0.6 mg/kg for tracheal intubation. Maintenance was achieved with sevoflurane in a 50% oxygen–air mixture, titrated to maintain BIS within the target range. Remifentanil was administered via target-controlled infusion (TCI) using the Minto pharmacokinetic model. In the ANI group, infusion rates were adjusted to maintain ANI values between 50–70; in the control group, dosing was guided by conventional clinical signs (heart rate, blood pressure, lacrimation, sweating). Additional rocuronium boluses (0.15 mg/kg) were administered as needed. Neuromuscular blockade was reversed at the end of surgery with sugammadex 2 mg/kg.

The primary outcome was total intraoperative remifentanil consumption.

Secondary outcomes included:

Adverse events and harms were monitored throughout the trial; however, no formal grading system or predefined criteria were applied for systematic assessment.

A total of 58 patients were enrolled and randomized equally into two groups: the ANI-guided group (n = 29) and the control group (n = 29). Four patients were excluded from the final analysis because of incomplete ANI data (n = 3) or unplanned ICU admission without postoperative awakening (n = 1). Data from 54 patients were analysed (ANI group: n = 26; control group: n = 28). A CONSORT diagram is provided in Fig. 1.

Baseline characteristics

The demographic variables, including age, sex, ASA classification, and surgery duration, were statistically comparable between the groups (Table 1). The mean age was 45.2 ± 9.8 years in the ANI group and 46.0 ± 10.1 years in the control group (p = 0.74). There were no significant differences in sex distribution (p = 0.58) or mean surgical duration (ANI: 112.4 ± 15.6 min vs. control: 115.1 ± 14.9 min; p = 0.42).

Legend: Baseline characteristics and intraoperative hemodynamics were similar between the groups. The ASA class was identical (I-II), and no statistical test was applied.

Hemodynamic parameters

Heart rate and mean arterial pressure (MAP) were recorded at 10, 20, 30, 60, 90, and 120 minutes after the initiation of surgery and upon admission to recovery. No statistically significant differences were observed between the groups at any time point (all p > 0.05), although both groups showed a gradual intraoperative decline followed by a rise upon recovery (Table 2).

Legend: ANI-guided anaesthesia reduces pain scores, opioid use, and postoperative nausea and vomiting.

Intraoperative analgesic consumption

Total remifentanil consumption was significantly lower in the ANI group (636.89 ± 90.32 µg) than in the control group (993.10 ± 146.21 µg; p < 0.001, unpaired t test). The calculated effect size (Cohen’s d) for the difference in remifentanil consumption between the ANI-guided group and the control group was 1.96, indicating a large effect according to conventional thresholds.

The number of intraoperative rescue fentanyl doses was also significantly lower in the ANI group (1.28 ± 0.45 vs. 2.17 ± 0.60; p < 0.001, Mann–Whitney U test).

Postoperative Outcomes

The incidence of postoperative nausea and vomiting (PONV) was significantly lower in the ANI group (6.9%) than in the control group (27.6%; p = 0.037, chi-square test). The absolute risk reduction for PONV was 20.7% (95% CI: 4.1–37.3%), and the relative risk was 0.25 (95% CI: 0.07 to 0.91), indicating a clinically meaningful reduction.

There were no significant differences between the groups in terms of postoperative shivering (p = 0.47) or respiratory complications (p = 0.56).

The mean recovery time was also similar between the groups (ANI: 28.3 ± 4.9 min vs. control: 29.1 ± 5.2 min; p = 0.304). A summary of the clinical outcomes is provided in Tables 3 and 4.

Legend: Hemodynamic parameters remained stable in the ANI group, with a significantly lower heart rate and blood pressure than those in the control group.

Legend: Patient satisfaction was significantly greater in the ANI group. No differences were observed in terms of oxygen saturation or recovery time.

This assessor-blinded randomized controlled trial demonstrated that intraoperative analgesia guided by the Analgesia Nociception Index (ANI) significantly optimizes opioid administration during lumbar spine surgery. Compared with standard practice, ANI-guided remifentanil dosing is associated with reduced total opioid consumption, lower postoperative pain intensity, a decreased incidence of postoperative nausea and vomiting (PONV), and greater patient satisfaction(9). These findings corroborate prior evidence supporting ANI monitoring in individualized intraoperative analgesia (10). Upton et al. (2017) reported improved postoperative recovery in spinal surgery patients who received ANI-directed fentanyl administration (8). Our findings reinforce the notion that real-time assessment of autonomic tone enables more precise nociceptive control and may help mitigate opioid overuse (11). Importantly, the duration of surgery was similar between groups, ruling out operative time as a confounding variable. Although intraoperative heart rate and mean arterial pressure did not differ significantly, the ANI group exhibited consistently lower pain scores and required fewer rescue opioid doses postoperatively, suggesting superior nociception management (12). These observations highlight that traditional hemodynamic markers alone may not reliably reflect nociceptive balance under anesthesia (13).

The significantly lower incidence of PONV in the ANI group is clinically meaningful, given the well-established opioid-PONV relationship (14). Precise titration of remifentanil via ANI monitoring may enhance recovery quality by reducing such adverse effects. Higher patient satisfaction in the ANI group likely reflects better analgesic control and fewer opioid-related complications—key elements of patient-centered care (15).

This study has limitations. It was conducted at a single academic center with a modest sample size, potentially limiting generalizability (16). ANI accuracy may be influenced by ventilation settings, anesthetic depth, individual autonomic variation, and patient movement (17). The predictive value of dynamic ANI changes (ΔANI) was not assessed, although prior evidence suggests it may enhance sensitivity (18). Furthermore, anesthesiologists were not blinded due to the nature of the intervention, but outcome assessments were blinded to minimize bias.

Despite these limitations, the results support the clinical utility of ANI-guided analgesia. Future multicenter randomized trials with larger sample sizes and longer follow-up are warranted to explore the role of ANI integration into multimodal analgesia protocols, especially regarding chronic pain prevention, opioid-sparing strategies, and cost-effectiveness (19).

ANI-guided remifentanil administration during lumbar spine surgery under general anaesthesia resulted in significantly lower intraoperative opioid use, reduced early postoperative pain and nausea, and improved patient satisfaction. These findings suggest that ANI monitoring can facilitate more individualized and effective analgesia by continuously assessing autonomic responses to nociceptive stimuli.

The incorporation of ANI into routine anaesthetic practice may enhance patient outcomes and reduce opioid-related side effects. Nevertheless, further multicenter studies are needed to validate these benefits across broader surgical populations and to investigate long-term outcomes, including chronic pain, opioid dependence, and perioperative recovery trajectories.