Effects of driving pressure-guided lung-protective ventilation strategy on respiratory mechanics, oxygenation, and postoperative pulmonary complications in patients undergoing minimally invasive esophagectomy: a randomized clinical trial

Introduction

Despite a gradual decline in the age-standardized incidence and mortality rates of esophageal cancer, it persists as a prominent public health concern in East Asia (1). Minimally invasive Ivor Lewis esophagectomy (MIE) serves as a curative surgical approach for cancers of the middle and lower esophageal segments. This method combines thoracoscopic and laparoscopic techniques, aiming to minimize surgical trauma and expedite hospital discharge (2-5). However, it should be noted that the artificial pneumoperitoneum and one-lung ventilation (OLV) required by MIE significantly alter respiratory mechanics. These alterations manifest as increased driving pressure (DP), decreased lung compliance, and reduced functional residual capacity, leading to hypoxemia and even elevating the risk of postoperative pulmonary complications (PPCs) (6-9). Therefore, optimizing intraoperative mechanical ventilation strategies may assist in protecting lung function and improving pulmonary outcomes in patients undergoing minimally invasive esophagectomy.

Mechanical protective ventilation strategy constitutes a critical component of enhanced recovery after surgery, with individualized positive end-expiratory pressure (PEEP) titration being its cornerstone. However, the optimal method for individualized PEEP titration and its lung-protective efficacy require further investigation. Recent studies indicate that DP is a key mediator of ventilation-induced lung injury. Studies have shown that lower DP improves intraoperative oxygenation and postoperative pulmonary clinical outcomes, exhibiting notable lung-protective benefits (10-12). Furthermore, multiple randomized clinical trials have found that ventilation strategies targeting low DP improve respiratory mechanics, intraoperative oxygenation, and reduce the incidence of PPCs in patients undergoing thoracic and abdominal surgery (13-15). Nevertheless, considering the heterogeneity in patient populations and surgical procedures, the general applicability of the lung-protective effects associated with DP-guided individualized PEEP titration remains unclear. Specifically, its lung-protective efficacy in patients undergoing MIE is yet to be validated.

Therefore, we conducted a clinical randomized controlled trial to evaluate the effects of DP-guided lung-protective ventilation strategy under volume-controlled ventilation mode on intraoperative oxygenation, respiratory mechanics, and PPCs in patients undergoing combined thoracoscopic-laparoscopic radical esophagectomy. We hypothesized that, compared to conventional lung-protective ventilation, this strategy would enhance intraoperative oxygenation and respiratory mechanics, and potentially reduce the risk of PPCs in patients undergoing MIE. We present this article in accordance with the CONSORT reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1588/rc).

Methods

This study was a single-center, prospective, randomized, controlled clinical trial conducted at Jiangsu Cancer Hospital. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the institutional ethics committee of Jiangsu Cancer Hospital (KY-2024-021-01) and informed consent was obtained from all individual participants.

Population

Patients aged 18 to 75 years, classified as American Society of Anesthesiologists (ASA) physical status II or III, and with a body mass index (BMI) ranging from 18.5 to 28 kg/m² were included. Exclusion criteria included: a prior history of pulmonary surgery; acute respiratory infection within the two weeks preceding surgery; comorbid major pulmonary diseases such as severe chronic obstructive pulmonary disease, pulmonary infection, bronchiectasis, or asthma; contraindications to PEEP application (elevated intracranial pressure, bronchopleural fistula, hypovolemic shock, or right heart failure); preoperative severe cardiovascular or cerebrovascular diseases; preoperative hepatic or renal insufficiency; and patient refusal to participate. Moreover, patients were excluded from the study analysis if any of the following occurred intraoperatively: conversion to open surgery; development of severe hypoxemia; occurrence of severe hypotension (defined as inadequate response to repeated vasoactive agent administration or sustained invasive arterial systolic blood pressure ≤90 mmHg); estimated blood loss exceeding 500 mL; or OLV duration falling outside the 120- to 240-minute range.

Randomizing and blinding

Randomization was performed using a computer-generated random number table. Enrolled subjects were randomly assigned at a 1:1 ratio to either the conventional lung-protective ventilation strategy group (VC group) or the DP-guided lung-protective ventilation strategy group (VD group). The random number assignments were prepared in advance by personnel not involved in anesthesia administration and placed inside opaque, sealed envelopes. The anesthesiologist opened the envelope on the day of surgery. Only the anesthesiologist on duty that day was aware of the patient’s group allocation. The patients and their families, surgeons, postoperative follow-up personnel, and statisticians were kept unaware of group allocation.

Anesthesia protocol

All patients had routine preoperative fasting procedures. Upon entering the operating room, peripheral intravenous access was established in an upper limb. Non-invasive blood pressure, pulse oximetry (SpO₂), and electrocardiogram were initiated. Additionally, the multimodal brain function monitor was connected to monitor the patient state index (PSI). Invasive blood pressure and cardiac output monitoring was obtained via left radial artery under local anesthesia. The quantitative neuromuscular monitoring was applied to confirm the depth of neuromuscular blockade (NMB).

After preoxygenation, general anesthesia was induced with midazolam 0.04 mg/kg, propofol 1.0–1.5 mg/kg, sufentanil 0.3–0.5 µg/kg, and rocuronium 0.6 mg/kg. A single-lumen endotracheal tube (ID 7.5–8.0 mm) was inserted under video laryngoscope guidance when the train-of-four count (TOF_C) was 0, followed by mechanical ventilation. The modes and parameters of mechanical ventilation are described in the following text. Total intravenous anesthesia was administered to maintain general anesthesia. The infusion rate of propofol was adjusted to maintain the PSI target 25 to 50. Remifentanil was constant infusion at a rate of 0.15–0.3 µg/kg/min, sufentanil was added as deemed necessary. Rocuronium was continuously infused to maintain moderate to deep NMB [deep NMB defined as post-tetanic count (PTC) 1–2 while moderate NMB being TOF_C =1–2] (16). Invasive mean arterial pressure (MAP) was maintained within ±20% of baseline values. Hypotension (defined as a >20% decrease in MAP from baseline) was treated with intravenous boluses of phenylephrine (40–100 µg) or ephedrine (6 mg). Bradycardia [defined as a heart rate (HR) <50 beats per minute] was treated with intravenous atropine (0.5 mg). Moreover, active warming was provided using a forced-air warming blanket to maintain intraoperative nasopharyngeal temperature ≥36 ℃. The surgical procedures were performed by the same thoracic surgery team. After completion of the abdominal phase, an endobronchial blocker was inserted through the single-lumen endotracheal tube, and its position was confirmed using fiberoptic bronchoscopy. Before initiating OLV, fiberoptic bronchoscopy was repeated to verify correct blocker placement. The endobronchial blocker was removed, airway secretions were suctioned, and ventilation was restored to both lungs after the chest tube was placed at the end of thoracic surgery.

As standard practice in our department, sufentanil 0.1 µg/kg was administered intravenously and patient-controlled anesthesia (PCA) was connected 15 min before the end of the surgery. The PCA medication included sufentanil 2 µg/kg and tropisetron, amounting to a total volume of 100 mL, the background dose was 2 mL/h, the bolus dose was 1.0 mL and a lockout time was 15 min. All anesthetic agents were discontinued before patients were transferred to either the post-anesthesia care unit (PACU) or the intensive care unit (ICU), and deep or moderate NMB was reversed with sugammadex 4 or 2 mg/kg respectively. Patients were extubated after they reached the following criteria: SpO₂ >96%, spontaneous breathing with a respiratory rate (RR) >8 breaths per minute, TOF ratio >0.9, fully awake, and able to follow simple verbal commands.

Study intervention

Mechanical ventilation of all patients was set in VCV mode during the surgery. Tidal volume (VT) was set at 8 mL/kg predicted body weight (PBW) during total lung ventilation and at 6 mL/kg PBW during OLV, with PBW based on a specific formula (17). The inspiratory oxygen fraction (FiO₂) was 60%, inspiration to expiration ratio (I:E) was 1:2, and the fresh gas flow was 3 L/min. The RR was adjusted based on end-tidal CO₂ partial pressure. As shown in Figure 1, patients in the VD group underwent PEEP titration at three points: 5 min after intubation, at the start of OLV, and again when total lung ventilation (TLV) resumed. Before each PEEP titration, a manual recruitment maneuver was performed. During TLV, the adjustable pressure-limiting valve was set to 30 cmH₂O, and during OLV it was set to 20 cmH₂O, with the manual recruitment maneuver being maintained for 20 to 30 seconds. After the maneuver, ventilation was resumed at 12 breaths per minute, and PEEP was decreased stepwise fashion from 10 to 0 cmH₂O, in 1 cmH₂O increments (with exception of PEEP of 1 and 2 cmH₂O which are not available on our anesthesia ventilators). Each level was maintained for one minute. DP, calculated as plateau pressure minus PEEP, was recorded on the final breath at each level. The PEEP associated with the lowest DP was identified as optimal, and remained the PEEP setting for the remainder of that procedural interval. In contrast, patients in the VC group underwent manual recruitment maneuvers at the same time points but remained on a fixed PEEP of 5 cmH₂O setting without titration.

Figure 1 Stepwise decremental PEEP titration protocol. After performing lung recruitment maneuvers, initiate a stepwise decremental titration of PEEP starting from 10 cmH₂O. The optimal PEEP level should be selected at the point where the driving pressure reaches its lowest value. RM, recruitment maneuver; PEEP, positive end expiratory pressure.

Outcomes

The primary outcome was the intraoperative dynamic lung compliance (Cdyn). The values of Cdyn were recorded in both patient groups at specific time points, namely: 5 min after tracheal intubation (T1), 30 min after pneumoperitoneum establishment (T2), just prior to OLV (T3), 15 min (T4), 30 min (T5), 60 min (T6), and 120 min (T7) after OLV initiation, 15 min after restoration of TLV (T8).

Baseline characteristics, operative duration, and the use of anesthetics and vasoactive agents were recorded for both cohorts. Respiratory mechanics parameters, including peak airway pressure (Ppeak), Pplat, and DP, were recorded at intraoperative timepoints ranging from T1 to T8. Arterial blood gas analysis focusing on PaO₂, PaCO₂, and pH was performed preoperatively (T0) and sequentially at T1 to T8. Hemodynamic monitoring included a range of parameters, such as MAP, HR, cardiac output (CO), stroke volume variation (SVV), and stroke volume (SV), measured consistently from time point T0 to T8. PPCs within the first seven postoperative days were evaluated according to the Esophageal Complications Consensus Group (ECCG), including: (I) pneumonia; (II) pleural effusion requiring additional drainage procedure; (III) pneumothorax requiring treatment; (IV) atelectasis mucous plugging requiring bronchoscopy; (V) respiratory failure requiring reintubation; (VI) acute respiratory distress syndrome (Berlin Definition); (VII) acute aspiration; (VIII) tracheobronchial injury; and (IX) chest tube maintenance for air leak for >10 d postoperatively (18). Additionally, hospitalization duration and total costs incurred were analyzed.

Statistical analysis

The PASS 15.0 (NCSS, LLC.) was utilized to calculate the sample size. In our preliminary experiment, we found that the Cdyn values at 30 min after OLV were 30.6±4.9 and 35.1±5.8 mL/cmH₂O in these groups, respectively. Using a two-sided test with α=0.05 and power (1 − β) =0.8, the minimum sample size required for each group was calculated to be 24 patients. Considering a 20% dropout rate based on the calculated sample size, a total of 60 patients were ultimately enrolled in this study.

Statistical analyses were performed using SPSS 26.0 (IBM Corp.). Normally distributed continuous data are presented as mean ± standard deviation (SD). Intergroup comparisons were made using the independent samples t-test, while intragroup comparisons across different time points were analyzed using repeated-measures analysis of variance. Non-normally distributed continuous data were expressed as median and interquartile range [M (P25, P75)], and compared between groups using the Mann-Whitney U test. Categorical data are presented as number (n) and percentage (%), and compared using the Chi-squared test or Fisher’s exact test, as appropriate. P<0.05 was considered statistically significant.

Results

From October 2024 to April 2025, a total of 102 patients underwent screening for enrollment. Among these, 60 patients were randomized and allocated to either the VC group or the VD group. Due to conversion to open surgery, one patient in the VD group withdrew from the study. Consequently, a total of 59 patients were included in the final analysis: 30 in the VC group and 29 in the VD group. Figure 2 shows the CONSORT flow diagram outlining patient enrollment, allocation, follow-up, and analysis.

Figure 2 Patient enrollment, allocation, follow-up, and analysis. VC group, the conventional lung protective ventilation strategy group; VD group, the driving pressure-guided lung protective ventilation strategy group.

The baseline characteristics of the two patient groups, including age, gender, BMI, ASA classification, comorbidities, tumor location, tumor type, history of neoadjuvant therapy, and preoperative pulmonary function, showed no statistically significant differences (P>0.05) (Table 1). Regarding the comparison of intraoperative conditions between the two groups, the VD group demonstrated a significantly higher intraoperative vasoactive drug usage rate compared to the VC group (93.1% vs. 70.0%; χ²=5.189; P=0.02). In contrast, no statistically significant differences were observed in OLV time, operative time, volume of fluid infusion, or quantity of anesthetic agents administered (P>0.05) (Table 2).

Respiratory mechanics outcomes

As shown in Table 3, PEEP titration results showed that during OLV, the VD group had higher PEEP levels than the VC group, which was maintained at a fixed level of 5 cmH₂O. Specifically, 5 min after intubation, the median PEEP was 5.0 cmH₂O in the VD group [median difference 0.00 cmH₂O, 95% confidence interval (CI): 0.00 to 1.00; P=0.19]. At the start of OLV, the median PEEP was 6.0 cmH₂O in the VD group (median difference 1.00 cmH₂O, 95% CI: 1.00 to 2.00; P=0.001). When TLV was resumed, the median PEEP was 4.0 cmH₂O in the VD group (median difference −1.00 cmH₂O, 95% CI: −1.00 to 0.00; P=0.06). Other intraoperative respiratory mechanics outcomes between the two groups are presented in Figure 3 and Table S1. Given that Cdyn and DP are inversely related, the VD group exhibited significantly higher Cdyn at time points T2 to T8 compared with the VC group (P<0.05). Specifically, at 30 min of OLV, the median Cdyn value in the VD group was 36.0 mL/cmH₂O, significantly higher than the 27.0 mL/cmH₂O observed in the VC group, with a median difference of 9 mL/cmH₂O (95% CI: 4.00 to 10.00; P<0.001). The VD group exhibited significantly lower Ppeak compared to the VC group at time points T2 to T8 (during pneumoperitoneum and OLV) (P<0.05). However, the Pplat in the VD group was significantly lower than that in the VC group only at T2 and T8 (P<0.05).

Figure 3 Intraoperative respiratory mechanics parameters. (A) Driving pressure, (B) dynamic compliance, (C) peak inspiratory pressure, and (D) plateau pressure. Error bars represent the interquartile range. VC group, the conventional lung protective ventilation strategy group; VD group, the driving pressure-guided lung protective ventilation strategy group; T1, 5 min after tracheal intubation; T2, 30 min after implementation of pneumoperitoneum; T3, just prior to OLV; T4, 15 min after OLV; T5, 30 min after OLV; T6, 60 min after OLV; T7, 120 min after OLV; T8, 15 min after restoration of total lung ventilation. *, P<0.05; ***, P<0.001; statistical significance was assessed by the Mann-Whitney U test. OLV, one-lung ventilation.

Intraoperative PaO₂, PaCO₂, and pH outcomes

Intraoperative arterial blood gas analysis results are presented in Table 4. Compared with the VC group, patients in the VD group exhibited significantly higher PaO₂ levels at time points T4 to T7 (P<0.05), with no significant differences observed at the remaining time points (P>0.05). Significantly higher PaCO₂ levels were observed in the VD group compared to the VC group at time points T5 to T8 (P<0.05), while no significant differences were found at other time points (P>0.05). There were no significant differences in pH between the two groups at any time point (P>0.05).

Intraoperative hemodynamics outcomes

There were no significant differences in MAP, HR, CO, SV, or SVV between the two groups of patients at any time point during the operation (P>0.05) (Figure 4).

Figure 4 Perioperative hemodynamics outcomes. (A) Mean blood pressure, (B) heart rate, (C) cardiac output, (D) stroke volume, and (E) stroke volume variation. (A-D) Error bars represent standard deviations. (E) Boxes show the interquartile range, center lines mark medians, whiskers extend to the minimum and maximum values of the dataset and scatter points represent individual data points. VC group, the conventional lung protective ventilation strategy group; VD group, the driving pressure-guided lung protective ventilation strategy group; T0, before anesthesia induction; T1, 5 min after tracheal intubation; T2, 30 min after implementation of pneumoperitoneum; T3, before OLV; T4, 15 min after OLV; T5, 30 min after OLV; T6, 60 min after OLV; T7, 120 min after OLV; T8, 15 min after restoration of two-lung ventilation. CO, cardiac output; HR, heart rate; MAP, mean arterial pressure; OLV, one-lung ventilation; SV, stroke volume; SVV, stroke volume variation.

PPCs and other clinical outcomes

The incidence of PPCs within 7 days occurred in 13 patients (43.3%) in the VC group and 7 patients (24.1%) in the VD group; however, there was no statistically significant difference between the two groups (P>0.05) (Figure 5). Moreover, there were no statistically significant differences in the length of hospital stay or hospital costs between the two groups (P>0.05).

Figure 5 Postoperative pulmonary complications and other clinical outcomes. (A) Incidence of postoperative pulmonary complications within 7 days; (B) total hospital stay; (C) total hospitalization costs. VC group, the conventional lung protective ventilation strategy group; VD group, the driving pressure-guided lung protective ventilation strategy group. PPCs, postoperative pulmonary complications.

Discussion

In this randomized controlled trial enrolling patients undergoing MIE, the DP-guided lung-protective ventilation strategy significantly improved intraoperative Cdyn, reduced Ppeak, and enhanced oxygenation during OLV compared with conventional lung-protective ventilation strategy. Notably, the incidence of PPCs within 7 days was 43.3% in the VC group and 24.1% in the VD group, with no statistically significant difference. Additionally, during the manual recruitment maneuver, both groups experienced declines in blood pressure, but the VD group required more frequent administration of vasoactive agents to maintain hemodynamic stability.

MIE has become a critical radical surgical approach for mid-to-lower esophageal cancer (19). However, the procedure involves both pneumoperitoneum and OLV, which can compromise pulmonary function, leading to impaired intraoperative oxygenation and increased risk of adverse postoperative pulmonary outcomes (20-22). Consequently, developing optimal perioperative mechanical ventilation strategies for patients undergoing MIE remains a significant clinical challenge. Individualized PEEP is a cornerstone of mechanical protective ventilation. By preventing small airway closure and alveolar collapse, it mitigates ventilation-perfusion mismatch and improves oxygenation—thereby addressing some limitations of low-tidal-volume ventilation alone (23). Although several methods exist for determining individualized PEEP, no universally optimal approach has been established, owing to considerable heterogeneity among patient populations and surgical types (24). DP directly reflects lung stress during mechanical ventilation and has been recognized as a central mediator of ventilator-induced lung injury (25). A growing body of evidence from randomized controlled trials and meta-analyses indicates that DP-guided PEEP titration can enhance intraoperative oxygenation and reduce the incidence of PPCs following major abdominal and thoracic surgeries (26-28). Building on this evidence, we adopted a DP-guided PEEP titration strategy for MIE patients in this study. To implement this strategy effectively, we selected a decremental PEEP titration method, as it leverages the physiological principle of pulmonary hysteresis to maintain alveolar recruitment at lower DP levels—directly aligning with our goal of minimizing DP (29). To our knowledge, this represents the first study designed to optimize lung-protective ventilation specifically for MIE, with the aim of preserving postoperative lung function.

Recently, scholars have proposed that dynamically titrating individualized PEEP during the perioperative period better accommodates the physiological effects of surgical procedures and positional changes (30). Similarly, we performed PEEP titration at three specific time points in this study: after tracheal intubation, after the initiation of OLV, and after the restoration of TLV. Consistent with the findings of Xu et al. regarding intraoperative individualized PEEP titration in patients undergoing laparoscopic surgery, the median titrated PEEP value in the VD group after tracheal intubation in our study was also 5 cmH₂O (31). During the laparoscopic phase, although respiratory mechanics parameters were significantly affected in both patient groups, the VD group demonstrated lower DP, Ppeak, and Pplat compared to the VC group. This finding aligns with a systematic review and meta-analysis of 21 randomized controlled trials, which suggested that individualized PEEP in non-obese patients during laparoscopic surgery reduces DP, improves lung compliance, and enhances oxygenation—a conclusion corroborated by our trial (32). In our research, the median titrated PEEP value at the initiation of OLV in the VD group was 6.0 cmH₂O, which is higher than values reported in some previous studies (15,33). We hypothesize that diaphragmatic elevation and increased intrathoracic pressure during the laparoscopic phase may lead to persistent small airway closure and atelectasis, effects that potentially persist into the thoracoscopic phase. Recruiting these collapsed alveoli might consequently require higher DPs and elevated PEEP levels. Our future studies, along with the work of researchers like Zhang et al., will also utilize lung ultrasound for dynamic, bedside monitoring of regional lung aeration to enhance pulmonary outcome assessment (34). Although the titrated PEEP values in the VD group were higher than those in the VC group, the VD group consistently maintained superior respiratory mechanics throughout the OLV period, characterized by lower DP and Ppeak, alongside higher Cdyn. These results indicate that DP-guided PEEP titration is a feasible and effective strategy. It serves the dual purpose of reducing lung tissue stress during mechanical ventilation to mitigate ventilator-induced lung injury, and effectively recruiting alveoli to improve oxygenation (35). Finally, the median titrated PEEP value after the restoration of TLV in the VD group was 4.0 cmH₂O, a finding similar to the results reported by Park et al. (15). Respiratory mechanics data revealed that, compared to the VC group, the VD group exhibited a lower Pplat (14.0 vs. 16.0 cmH₂O) and higher Cdyn (63.0 vs. 47.5 mL/cmH₂O). This suggests that after the return to TLV, a lower PEEP level is sufficient to maintain alveolar stability, thereby proactively avoiding alveolar overdistension.

In this study, although PaO₂ remained above 60 mmHg in both groups throughout mechanical ventilation, the VD group achieved significantly higher levels than the VC group at T2 (during pneumoperitoneum) and from T4 to T7 (during OLV). This indicates that a DP-guided PEEP strategy provides superior intraoperative oxygenation than a fixed PEEP of 5 cmH₂O, aligns with recent randomized evidence (36,37). Additionally, both groups received mechanical ventilation with low tidal volumes and underwent pneumoperitoneum and OLV, resulting in an increasing trend in PaCO₂ levels consistent with mild hypercapnia. This moderate elevation in PaCO₂, known as permissive hypercapnia, is permitted by current lung-protective ventilation strategies (38). Relevant studies indicate that permissive hypercapnia can enhance oxygenation during OLV without increasing the risk of PPCs (39).

The study results showed that the incidence of PPCs within 7 days postoperatively was numerically lower in the VD group (24.1%) than in the VC group (43.3%), though the difference was not statistically significant. This finding is consistent with studies in other surgical types. For example, Ernest et al. in emergency abdominal surgery and Park et al. in video-assisted thoracoscopic lobectomy reported that individualized PEEP guided by DP improved intraoperative respiratory mechanics but did not significantly reduce PPCs (15,40). These findings, including our own, suggest that optimizing PEEP based solely on DP may be insufficient to improve clinical outcomes. Future studies should consider integrating more effective ventilation modes, such as pressure-controlled ventilation with volume guarantee (PCV-VG), to potentially improve pulmonary outcomes in patients (41). However, the potential clinical implication indicated by this numerical difference (an absolute risk reduction of 19.2%) should not be overlooked. It is noteworthy that a previous retrospective study on MIE in the prone position found that a moderate level of PEEP may be the appropriate choice to balance atelectasis and alveolar overdistension (42). Fixed high PEEP could potentially be harmful by causing overdistension in some patients, whereas PEEP titrated individually based on respiratory mechanics might be beneficial. A recent large-scale real-world cohort study found that higher DP, whether calculated using Pplat or Peak, is independently associated with a higher risk of PPCs (12). Specifically, the risk of PPCs significantly increases when DP-Pplat is ≥15 cmH₂O or DP-PIP is ≥18 cmH₂O, with each 1 cmH₂O increase in DP raising the odds ratio (OR) for PPCs by approximately 3–5%. Finally, it must be acknowledged that the relatively small sample size of the present study might have limited its power to detect a statistically significant difference in PPC incidence between the groups.

Hemodynamic monitoring in this study demonstrated no significant differences in CO, SVV, or SV between the two groups, indicating that the DP-guided lung-protective ventilation strategy may not increase hemodynamic burden, as observed by Ernest et al. (40). Interestingly, during our initial trial, we observed that maintaining PEEP levels above 10 cmH₂O routinely elicited severe hypotension, which often required large doses of vasoactive agents to maintain hemodynamic stability and exceeded our predefined safety threshold. This finding is consistent with the interim analysis of another ongoing randomized controlled trial, the ‘DESIGNATION’ study (43). Consequently, we titrated PEEP downward from 10 to 0 cmH₂O in decrements of 1 cmH₂O. Nevertheless, the VD group still demonstrated a significantly higher intraoperative vasoactive drug usage rate compared to the VC group (93.1% vs. 70.0%; P=0.02). This clinical phenomenon may be attributed to the typical profile of esophageal cancer patients, who are predominantly elderly, often have poor preoperative nutritional status, and may experience relative hypovolemia due to preoperative fasting. Thus, lung recruitment maneuvers combined with high PEEP levels can significantly alter hemodynamics in patients with esophageal cancer (44). In line with our institutional practice, fluid infusion can be moderately accelerated or goal-directed fluid therapy guided by parameters MAP, CO, and SVV can be implemented to manage such hemodynamic fluctuations, with appropriate vasoactive agents used as needed.

There are several limitations in this study: Firstly, as a single-center investigation with a modest sample size, its findings await validation through future multi-center studies involving larger cohorts. Secondly, the study did not routinely measure intrinsic positive end-expiratory pressure (iPEEP). Although intraprocedural observations suggested that most patients had an iPEEP of 2 or 3 cmH₂O, this omission might have affected the precise assessment of the true DP value. Thirdly, the anesthesia ventilator used in this study had a minimum PEEP setting of 3 cmH₂O, limiting the ability to titrate to lower PEEP levels and potentially affecting the determination of the optimal PEEP. Fourthly, DP-guided PEEP titration was not conducted after the establishment of pneumoperitoneum, which could be considered in future research with careful attention to perioperative safety. Lastly, the study’s exclusive focus on the MIE technique may restrict the broader applicability of its results to other radical esophagectomy procedures for esophageal carcinoma.

Conclusions

In conclusion, in patients undergoing combined thoracoscopic-laparoscopic Ivor Lewis esophagectomy, a DP-guided lung-protective ventilation strategy significantly improved intraoperative respiratory mechanics and oxygenation parameters while maintaining relatively stable hemodynamics. Although this study did not show differences in clinically relevant outcomes such as PPCs within 7 days due to sample size limitations, it warrants further investigation.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CONSORT reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1588/rc

Trial Protocol: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1588/tp

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1588/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1588/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1588/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the institutional ethics committee of Jiangsu Cancer Hospital (KY-2024-021-01) and informed consent was obtained from all individual participants.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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