Conventional general anesthesia during cardiopulmonary bypass (CPB)-assisted open-heart surgery presents notable limitations. First, pharmacologically induced cardiovascular depression often precipitates hemodynamic instability characterized by hypotension and arrhythmias (1, 2). Second, suboptimal myocardial protective effects may exacerbate ischemia-reperfusion injury, correlating with impaired postoperative ventricular function (3, 4). Third, the systemic inflammatory response caused by this approach increases the incidence of lung-related issues, including acute respiratory distress syndrome (ARDS) (5). Therefore, anesthesia management during CPB requires precise drug adjustment and monitoring to balance the anesthetic depth and hemodynamic stability.

Combining regional anesthesia (RA) with general anesthesia (GA) in open heart surgery provides several significant advantages (6), such as reducing oxidative stress, improving pulmonary complications and postoperative pain, and decreasing the reliance on opioids (7). The transversus thoracis plane block, a form of peripheral thoracic nerve block, proficiently shuts down the anterior divisions of the T2 through T6 intercostal nerves, thereby delivering pain relief for surgeries on the anterior chest wall (8, 9). This approach has been suggested for cardiac procedures in certain studies, demonstrating both effectiveness and safety (10). Long-acting local anesthetics, like ropivacaine and bupivacaine, can certainly enhance pain relief post-surgery (11, 12). Nonetheless, the sensory numbness they provide is still too short to eliminate the need for opioids entirely after an operation, and their overall effectiveness is questionable (13). Consequently, increasing the longevity of nerve blocks to manage postoperative discomfort is a crucial challenge in the field of regional anesthesia.

Dexmedetomidine, a potent and selective α2-adrenergic receptor agonist, is known for its multifaceted pharmacological properties, including sedation, pain relief, anti-inflammatory action, and suppression of sympathetic activity (14). It has been recognized as a safe and effective adjunct in various anesthetic applications and analgesic techniques (15). Its incorporation with local anesthetics has been shown to extend regional anesthesia, speed up the onset of numbness, improve postoperative pain relief, and reduce the need for additional pain medications (16, 17). In this study, we combined dexmedetomidine (DEX) and ropivacaine in bilateral TTP block regimens to observe the effects on stress response of open-heart surgery under CPB, and our findings preliminarily confirmed these clinical benefits.

This prospective randomized controlled trial, conducted exclusively at The First Affiliated Hospital of Fujian Medical University in Longyan, received ethical clearance from the institutional review board after securing written consent from every participant. Prior to commencement, the research protocol was officially registered with the Chinese Clinical Trial Registry under the identifier ChiCTR2400085899.

Between October 2022 and July 2024, 65 consecutive patients were screened for eligibility. Five participants were excluded (two declined participation, two required re-operative cardiac procedures, one developed decompensated heart failure), resulting in 60 patients (20 per group) completing the study protocol and included in the final analysis cohort (Figure 1). Baseline demographic and perioperative data (age, sex, BMI, ASA status, LVEF, intraoperative time, CPB time) are presented in Table 1, demonstrating comparable characteristics across groups (p > 0.05).

As depicted in Figure 2, 24 h post-surgery, both the R and RD groups exhibited significantly reduced serum cortisol levels and blood glucose concentrations compared to the control group, accompanied by a significant elevation in CRP levels (p < 0.05). However, no significant differences were observed between the R and RD groups themselves. Postoperative pain assessment demonstrated superior analgesic efficacy in the intervention groups, with R and RD cohorts showing significantly lower NRS scores vs. controls at extubation (0 h), 6 h, and 12 h post-extubation (all p < 0.05). By 24 h, RD maintained analgesic superiority over both control and R groups, while R group scores converged with controls. All intergroup NRS differences resolved by 48 h postextubation (p > 0.05), as detailed in Figure 2.

The RD group demonstrated significantly shorter postoperative mechanical ventilation duration and ICU length of stay compared to controls (p < 0.05). Postextubation analgesic requirements were markedly reduced in both intervention groups, with R and RD cohorts showing 48-h cumulative sufentanil consumption lower than controls, and the RD group also used significantly less sufentanil than the R group. Moreover, the demand frequency of PCA followed similar patterns, with intervention groups exhibiting fewer effective bolus requests vs. controls as illustrated in Figure 3.

Other postoperative outcomes contained the incidence of postoperative nausea, vomiting, pulmonary complications, and postoperative rescue rate, which were shown in Table 2. No intergroup differences emerged in PONV (15%–40% overall, p = 0.155) or pulmonary complication rates (25%–30% incidence, p = 0.921). However, the RD group demonstrated superior analgesic sustainability, requiring 55% and 15% fewer rescue interventions than controls and R group respectively (p < 0.001).

This randomized controlled trial establishes that dexmedetomidine-enhanced TTP blockade significantly improved postoperative outcomes in cardiac surgery patients undergoing CPB. The intervention demonstrated potential tripartite benefits: (i) superior analgesia extending through 24 h postextubation; (ii) attenuation of surgical stress biomarkers; and (iii) accelerated functional recovery as evidenced by reduced mechanical ventilation duration and ICU stay. These results underscored the significant potential of dexmedetomidine as a valuable adjunct in regional anesthesia for complex surgical procedures, thereby enhancing the overall efficacy and safety of such interventions. Notably, the ropivacaine concentration selection (0.3% for patients <70 kg, 0.5% for ≥70 kg) was based on weight-dependent pharmacokinetics, ensuring adequate blockade while minimizing potential toxicity in smaller patients (20, 21). Although it was expected that the CRP levels in R and RD groups would be lower than control group, the results showed an increase. This might be due to the small sample size. With only about 20 patients per group, there may be insufficient statistical power, increasing the risk of type II errors and masking actual differences. In addition, small samples are more susceptible to random fluctuations, leading to results that deviate from expectations.

The observed reduction in 48-h sufentanil consumption in the RD group, coupled with significant lower rescue analgesia requirements compared to controls, underscored dexmedetomidine's multimodal action. Beyond its recognized α2-adrenergic mediated sympatholytic effects, our biomarker data suggest peripheral modulation of surgical stress pathways. The sustained cortisol suppression at 24 h postoperatively correlated with dexmedetomidine's known inhibition of hypothalamic corticotropin-releasing hormone secretion (22), while attenuated hyperglycemia likely reflects improved insulin sensitivity through reduced catecholamine surge (23).

Clinically, certain important recovery metrics demonstrated the benefit brought from optimized analgesia. The RD group exhibited shorter mechanical ventilation duration and reduced ICU stay, which likely stem from enhanced diaphragmatic function preservation. These outcomes were in line with recent thoracic surgical trials demonstrating that regional anesthesia adjuncts reduce pulmonary complications (23). Besides, NRS were consistently lower in the RD group, particularly during the first 24 h following extubation, demonstrating the ability of dexmedetomidine to prolong sensory blockade when combined with local anesthetics (24). Notably, the opioid-sparing effect persisted even when compared to the R group, indicating dexmedetomidine as an independent role in pain management. These findings hold substantial clinical significance, as opioid-related adverse effects, including respiratory depression, ileus, and delirium, continue to be primary concerns for patients undergoing cardiac surgery (25). Based on TTP block, the combination of dexmedetomidine has solved the problem of relatively limited sustainable duration of analgesia (26). Dexmedetomidine has been proven to prolong the duration of peripheral nerve block by inhibiting the hyperpolarization-activated cation current and enhancing the binding of local anesthetics to sodium channels. Similar results have also been reported in other local techniques, such as interscalene block and femoral nerve block (27). Although the plasma half-life of dexmedetomidine is approximately 2 h, this study found that its analgesic effect lasts more than 24 h. This might be due to its high lipophilicity, which enables it to form tissue reservoir and continuous release, as well as its direct effect on the peripheral α2-adrenergic receptors of the dorsal horn, thereby enhancing and prolonging the effect of local anesthetics (28, 29).

The observed decrease in stress biomarkers (cortisol, glucose) aligns with findings from trials assessing dexmedetomidine in major abdominal surgeries (30). Importantly, the drug's anti-sympathetic effects may also help stabilize CPB-induced hemodynamic fluctuations, possibly diminishing the need for vasopressors or inotropes (31). Nevertheless, this study did not specifically evaluate catecholamine levels or the requirements for vasoactive drugs, thus highlighting a need for further research. Notably, the absence of significant differences in pulmonary complications or PONV across groups was surprising. The universal ondansetron administration may have masked dexmedetomidine's antiemetic properties, potentially underestimating its PONV reduction potential.

This study has several limitations. Firstly, the lack of a pre-trial power calculation and the modest sample size may limit the reliability of subgroup comparisons and time-based interaction analyses. Future studies should consider adaptive or sequential designs to enhance statistical efficiency. Secondly, potential performance bias may have arisen from the unblinding of anesthesiologists performing the TTP blocks, which could have influenced intraoperative management and dosing decisions. The exclusion of high-risk or re-operative patients also restricts the generalizability of our findings. Thirdly, other clinically relevant outcomes were not assessed. We acknowledge that this trial did not evaluate long-term endpoints, such as chronic postoperative pain, persistent opioid use, or late complications. Future studies should include extended follow-up and broader outcome measures. Fourthly, lack of serial plasma catecholamine assays limits the mechanistic interpretation of dexmedetomidine's α2-mediated effects during CPB. Lastly, the use of different ropivacaine concentrations stratified by body weight may have introduced unmeasured pharmacokinetic differences linked to body composition.

In summary, this randomized controlled trial suggests that adding dexmedetomidine to ropivacaine for the TTP block may help attenuate the stress response, optimise analgesia, and improve early postoperative recovery parameters in cardiac surgery with cardiopulmonary bypass. These advantages are consistent with ERAS goals and highlight the potential of adjunctive α2-agonists in regional anesthesia. Although limitations exist, the results provide a strong basis for integrating dexmedetomidine-enhanced TTP blocks into cardiac surgical practice, potentially transforming perioperative care paradigms. Further multi-center trials with larger sample sizes are necessary to confirm these findings and investigate subgroup analyses, such as in elderly patients or those with diabetes.