Driving pressure guided ventilation with lung ultrasound reduces pulmonary complications after epigastric surgery at high altitude

Abstract

Patients undergoing epigastric surgery at high altitudes are at increased risk of postoperative pulmonary complications (PPCs) due to hypobaric hypoxia and altered respiratory mechanics. This study aimed to determine whether a protective ventilation strategy combining driving pressure (ΔP) guidance and lung ultrasound (LUS) monitoring could reduce PPCs compared with conventional protective ventilation in patients undergoing epigastric surgery on the Tibetan Plateau(> 3500 m). In this randomized controlled trial, 152 adult patients scheduled for elective epigastric surgery were assigned to either conventional protective ventilation (n = 75) or ΔP-guided ventilation (n = 77). The conventional group received a tidal volume of 6 mL/kg predicted body weight, PEEP of 5 cmH2O, and a standard recruitment maneuver. The ΔP-guided group received the same tidal volume with individualized PEEP titration to minimize ΔP, combined with an LUS-guided recruitment maneuver. The primary outcome was the incidence of PPCs within seven days after surgery, assessed using the modified Kroenke severity score. Secondary outcomes included intraoperative ΔP, mechanical power, oxygenation, respiratory compliance, and hospital length of stay (assessed on postoperative days 1, 3, and 7). For each patient, the highest modified Kroenke score observed across the scheduled assessments within 7 days was used for analysis. The incidence of clinically significant PPCs (grade ≥ 2) was significantly lower in the ΔP-guided group than in the conventional group. Compared with conventional ventilation, ΔP-guided ventilation achieved lower driving pressure, higher individualized PEEP, improved oxygenation indices, and fewer cases of atelectasis. Mechanical power was modestly higher in the ΔP-guided group, while remaining within a low range in both groups. Hospital stay was shorter in the ΔP-guided group. ΔP-guided ventilation combined with LUS monitoring significantly reduced PPCs and improved intraoperative respiratory mechanics and oxygenation in patients undergoing epigastric surgery at high altitude. This strategy provides a physiologically informed approach to lung protection under hypobaric hypoxia.

Trial registration: This trial was prospectively registered at the Chinese Clinical Trials Registry (ChiCTR) under the registration number ChiCTR2200057189 (02/03/2022).

Supplementary Information

The online version contains supplementary material available at 10.1038/s41598-026-39549-6.

Introduction

Mechanical ventilation is essential for critically ill patients and those undergoing major surgeries, but it comes with a number of risks, such as lung volutrauma, barotrauma, and injury from repeated alveolar collapse and reopening^1–3. Patients undergoing epigastric surgery have a significantly elevated risk of pulmonary complications^4–6. At high altitudes, the inspired oxygen partial pressure (PIO₂) in the air and number of gas molecules per unit volume differ from those at lower altitudes. As altitude increases, atmospheric pressure and partial pressure of oxygen decrease, leading to reduced alveolar oxygen tension. Consequently, the oxygen content diffusing into the pulmonary capillaries decreases, resulting in lower arterial blood oxygen saturation as altitude increases⁷.

Patients at high altitudes are chronically exposed to hypobaric hypoxia, which reduces inspired oxygen partial pressure and may impair pulmonary reserve^8–10. Compared with those at lower altitudes, high-altitude residents often exhibit decreased lung volumes and reduced pulmonary compliance, which can increase work of breathing and ventilatory load. Together, these factors may increase vulnerability to perioperative pulmonary dysfunction. In a large retrospective cohort of Tibetan patients living at ≥ 3000 m, postoperative pulmonary complications within 7 days occurred in 13.7–18.0%, and intraoperative ventilatory settings (including PEEP level) were associated with PPC risk¹¹.

Compared to sea-level populations, the high-altitude environment of Tibet further exacerbates physiological challenges due to hypobaric hypoxia. Epigastric (upper abdominal) surgery is associated with a substantial risk of PPCs in sea-level populations^3,12. This underscores the importance of adopting individualized ventilation strategies to mitigate pulmonary complications in high-risk surgical settings.

In pediatric populations, Jang et al. reported that regular ultrasound-guided alveolar recruitment markedly reduced the incidence of significant atelectasis before extubation in children ventilated in the prone position (8.1% vs. 47.2%)^13,14. Similarly, in adults undergoing non-cardiac surgery, a systematic review and meta-analysis found that ultrasound-guided lung recruitment was associated with improved lung aeration (lower postoperative LUS) and a reduced incidence of postoperative atelectasis compared with conventional strategies^15–17.

Recent evidence has shown that driving pressure during intraoperative ventilation is independently associated with the development of postoperative pulmonary complications, and may be a more reliable predictor of outcomes than tidal volume or plateau pressure alone^18,19. Recent trials have provided preliminary evidence that actively reducing ΔP during thoracic and open abdominal surgeries may reduce pulmonary complications^6,20,21. However, whether other modes of ventilation or reduced driving pressure ventilation in high-altitude patients might reduce complications requires further investigation. It is important to note that definitive conclusions regarding the efficacy of ΔP reduction for improving outcomes are limited owing to the relatively small scale and scope of available studies, as well as the lack of standardized techniques for achieving driving pressure reduction. Therefore, we hypothesized that individualizing PEEP in combination with lung ultrasonography to minimize driving pressure could decrease the incidence of clinically significant PPCs in high-altitude patients.

Patients and methods

Ethic statement

This prospective, randomized, double-blind, parallel-group study was approved by the Bioethical Committee of Shannan Hospital, Tibet, China (approval no. SMC 2021-12-20-05) and registered with Chinese Clinical Trials Registry (Registration No. ChiCTR2200057189; Date of Registration:02/03/2022). All patients have written the statement regarding informed consent. The study had been conducted in accordance with the CONSORT guidelines. The registration details were subsequently updated to reflect the blinding designation: https://www.chictr.org.cn/bin/project/edit?pid=153161. This study was performed in accordance with the Helsinki Declaration of 1964 and its later amendments.This single-center trial was conducted at Shannan People’s Hospital between March 2022 and December 2022.

Inclusion and exclusion criteria

A total of 187 patients who underwent open epigastric surgery in the plateau were enrolled in the study between February 2022 and December 2022. Of 187 patients assessed, 165 met inclusion criteria and were randomized. Post-randomization exclusions (surgical approach change: n = 6; loss to follow-up: n = 4; severe complications: n = 3) yielded 152 patients for analysis (ΔP: n = 77; Control: n = 75) (Fig. 1 CONSORT Flowchart). Participants were recruited from patients scheduled for open epigastric surgery expected to last at least 2 h under general anesthesia, with an intermediate-to-high risk of PPCs as determined by the Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) score²². Inclusion criteria were being at least 19 years old, having an American Society of Anesthesiologists (ASA) physical status of II or III, and a body mass index (BMI) of < 30 kg/m². Exclusion criteria included a history of upper respiratory tract or pulmonary infection within the preceding four weeks, pleural effusion, known chest diseases, neuromuscular disorders, or severe cardiovascular, pulmonary, renal, or hematopoietic conditions (e.g., renal failure or congenital heart disease). Participants were also excluded if they withdrew consent, were unable to complete the required study protocol, or experienced severe hypotension due to intraoperative hemorrhage or other life-threatening complications, which were considered grounds for dropout.

Fig. 1.

CONSORT Flow Diagram of Patient Enrollment and Follow-up. A total of 182 patients scheduled for esophagectomy were assessed for eligibility. Seventeen patients were excluded, including 9 who did not meet the inclusion criteria and 8 who declined to participate. The remaining 165 patients were randomized into two groups: the driving pressure-guided ventilation group (n=84) and the conventional protective ventilation group (n=81). In the ΔP group, 7 patients were excluded due to surgical procedure changes (n=3) or refusal to follow-up (n=4), resulting in 77 patients included in the final analysis. In the control group, 6 patients were excluded owing to severe surgical complications (n=3) or changes in surgical procedure (n=3), leaving 75 patients for final analysis.

Anesthesia protocol

Before preoxygenation, baseline oxygenation parameters (SpO₂ and PaO₂) were obtained on room air (FiO₂ 0.21). A radial arterial catheter was placed under local anesthesia prior to induction for continuous arterial pressure monitoring and arterial blood sampling, and the pre-induction PaO₂ reported in this study was obtained from an arterial blood gas sample collected via this catheter.

Cisatracurium (0.15 mg/kg) was administered for intubation, and additional boluses were given intraoperatively as needed. Neuromuscular blockade management followed routine institutional practice; quantitative neuromuscular monitoring (e.g., TOFR/PTC) was not mandated in all cases. Before extubation, neuromuscular recovery was assessed using standard clinical criteria and, when available, peripheral nerve stimulation.

Intraoperative fluid management followed a stroke volume variation (SVV)-guided goal-directed therapy protocol. Specifically, a 250 mL colloid bolus was administered over 15–20 min when SVV was ≥ 13%²³. If the stroke volume increased by > 10%, an additional bolus was administered. Vasopressors, including phenylephrine, norepinephrine, or ephedrine, were administered in small doses as needed to maintain a mean arterial pressure above 60 mmHg.

All patients were extubated in the operating room once they were fully awake and had resumed spontaneous breathing. Following extubation, patients were transferred in the supine position while breathing room air to the post-anesthesia care unit (PACU).

Randomization and blinding

A simple randomization process was conducted using a computer-based random number generator with an allocation ratio of 1:1. To ensure concealment, sequentially numbered, sealed, opaque envelopes were used. Once the researchers met the inclusion criteria, they were randomly allocated to one of two groups: ΔP-guided ventilation group or conventional protective ventilation group. The lung complications were monitored by physicians and hospitalists who were not involved in the study during their daily routine assessments.

Ventilation protocol

Common ventilation settings for both groups

Both groups had a fixed tidal volume of 6 mL/kg predicted body weight. The fraction of FiO₂ was maintained at 0.4 throughout the surgery. The respiratory rate (RR) was initially set at 12 breaths/min and adjusted to keep the end-tidal CO₂ (EtCO₂) within the range of 30–40 mmHg. Volume-controlled ventilation with an inspiratory pause time of 0.3 s was used throughout the procedure.The inspiratory: expiratory ratio (I: E) was set as 1:2.

Group-specific interventions

Conventional protective ventilation group (Group C). The PEEP was fixed at 5 cmH₂O. A recruitment maneuver was carried out once, 1 h after the start of the surgery. It involved manual inflation with a peak airway pressure of 40 cmH₂O for 10 s. This RM was standardized without monitoring by lung ultrasound.

ΔP-Guided ventilation group (Group ΔP) (Fig. 2). For PEEP titration to minimize driving pressure, after intubation, the baseline ΔP was recorded at PEEP = 0 cmH₂O. Then, PEEP was incrementally increased in steps (6 → 8 → 10 → 12 → 14 cmH₂O), with 2 min of stabilization at each level to achieve hemodynamic and respiratory equilibrium. The ΔP was measured at each step, and the PEEP level corresponding to the lowest ΔP was selected as the final PEEP, which was individualized for each patient. The LUS-guided RM was performed 1 h after the surgery began and after PEEP titration. An initial 12-zone lung ultrasound assessment was done to detect atelectasis (B-pattern or consolidation). If collapse was identified, a stepwise RM was implemented, gradually increasing the airway pressure to 40 cmH₂O (with limitation to avoid barotrauma) and sustaining it for 10 s, followed by a return to baseline ventilation. This RM was repeated until the LUS showed resolution of the collapse (N-pattern or ≤ 2 B-lines per zone). After the RM, the pre-titrated optimal PEEP was maintained to prevent re-collapse. The maximum airway pressure was limited to 40 cmH₂O, and the tidal volume was restricted to 20 ml/kg per additional maneuver^24,25.

Fig. 2.

ΔP-Guided Ventilation Protocol. The PEEP setting and LUS-guided RM methods for ΔP-Guided Ventilation Group were as follows: After endotracheal intubation, PEEP was increased stepwise (6→8→10→12→14 cmH₂O). Maintained for 2 minutes to ensure hemodynamic and respiratory equilibrium. The PEEP level yielding the lowest ΔP was selected and maintained for the remainder of surgery. Performed 1 hour after surgical incision, collapse was identified by LUS, a stepwise RM was implemented, gradually increasing the airway pressure to 40 cmH₂O (with limitation to avoid barotrauma) and sustaining it for 10 seconds. This RM was repeated until the LUS showed resolution of the collapse (N-pattern or ≤2 B-lines per zone). followed by a return to baseline ventilation.

Lung ultrasonography

Lung ultrasonography was performed by two trained and experienced ultrasonographers using a GE LOGIQ™ ultrasound system equipped with a convex array transducer (2–5 MHz; GE Healthcare, Milwaukee, WI, USA). LUS was performed by a dedicated operator using sterile probe covers. Scans occurred during scheduled surgical pauses without breaching the sterile field. A total of twelve lung quadrants were assessed, as previously described by Mongodi et al.^26,27 The thorax was divided into anterior, lateral, and posterior zones by the anterior and posterior axillary lines, and each zone was further subdivided into upper and lower regions on both the right and left lungs²⁸.

In both groups, lung ultrasound examinations were conducted at four standardized time points: upon arrival in the operating room (T0), 30 min after induction of general anesthesia (T1), one hour after the start of surgery and prior to recruitment maneuvers (T2), and 15 min after arrival in PACU (T3). All ultrasound images were independently reviewed by a blinded observer who was not involved in image acquisition.

Four distinct lung aeration patterns were defined: N (normal aeration): presence of lung sliding with A-lines or fewer than two isolated B-lines: B1 (moderate loss of aeration): multiple, well-defined B-lines; B2 (severe loss of aeration): multiple coalescent B-lines; C (consolidation): presence of dynamic air bronchograms. Each region was scored accordingly: N = 0, B1 = 1, B2 = 2, and C = 3. The total lung ultrasound score (LUS) was calculated by summing the scores from all twelve regions, providing a quantitative measure of overall lung aeration status.

Outcomes

The primary outcome was the incidence of clinically significant postoperative pulmonary complications, defined as grade ≥ 2 on the modified Kroenke scale, occurring within the first seven postoperative days (assessed on postoperative days 1, 3, and 7) (supplementary material).

The secondary outcomes included: Intraoperative driving pressure and mechanical power (measured one hour after surgical incision); Respiratory mechanics; Intraoperative hemodynamic variables; Blood gas parameters (PaO₂, FiO₂, PaCO₂); Perioperative lung ultrasound scores; Hospital length of stay (LOS). All postoperative outcomes were assessed by an anesthesiologist blinded to group allocation and uninvolved in intraoperative management.

Mechanical power was calculated using the simplified Gattinoni equation for volume-controlled ventilation: MP (J/min) = 0.098 × RR × VT(L) × (PEEP + ΔP/2).

Sample size calculation

The sample size was estimated using PASS software (version 11.0, NCSS, LLC, Kaysville, UT, USA). Based on prior literature involving abdominal surgical populations at sea level, we assumed an incidence of postoperative pulmonary complications of approximately 20%. To detect a 20% absolute reduction in the incidence of PPCs with 80% power and a two-sided alpha level of 0.05, a minimum of 70 participants per group was required. Accounting for an anticipated 10% dropout rate due to intraoperative protocol deviations or loss to follow-up, the final enrollment target was adjusted to 154 patients (77 per group).

Notably, the observed PPC incidence in our study (~ 40%) exceeded the original estimate. This discrepancy likely reflects high-altitude-specific physiological challenges-such as hypobaric hypoxia, pulmonary vascular remodeling, and reduced lung compliance-which increase the susceptibility to PPCs. Additionally, all surgeries were performed via an open approach, and the majority of patients had ARISCAT scores > 45, indicative of moderate to high risk. A post hoc power analysis confirmed that the final sample size maintained > 85% power to detect statistically significant differences in the primary outcome.

Statistical analysis

Data distribution was assessed using the Shapiro-Wilk test. Continuous variables with normal or approximately normal distribution were expressed as mean ± standard deviation (SD) and compared using the independent-samples t-test. Non-normally distributed variables (e.g., PEEP) were presented as median with interquartile range (IQR) and analyzed using the Mann–Whitney U test. Categorical variables were reported as counts and percentages, with between-group comparisons performed using the Chi-square test.

Logistic regression analysis was used to evaluate the association between ventilation strategy and the incidence of PPCs, severe hypoxemia, atelectasis, and pleural effusion. For outcomes measured repeatedly over time (e.g., oxygenation index, mechanical power, driving pressure), repeated-measures analysis was employed. Bonferroni correction was applied for post hoc pairwise comparisons to adjust for multiple testing across time points. All statistical analyses were conducted using SPSS version 23.0 (IBM Corp., Armonk, NY, USA). A two-sided p-value < 0.05 was considered statistically significant.

Result

There were no significant differences in demographic or operational data between the groups. Preoperative ARISCAT scores indicated comparable baseline risks of postoperative pulmonary complications between the two groups (Table 1). Baseline static respiratory compliance was comparable between groups (Table 1) and markedly reduced compared to sea-level norms (> 50 mL/cmH₂O), consistent with known high-altitude adaptations^29,30 (thickened alveolar septa, pulmonary vascular remodeling).

Table 1.

Baseline characteristics of patients.

	Group C (n = 75)	Group ΔP (n = 77)	χ²/t	P
Age (yr)	54.00 ± 7.99	54.57 ± 5.71	−0.51	0.614
BMI (kg/m2)	22.61 ± 1.80	22.69 ± 2.70	−0.23	0.819
Living area altitude (m)	3729.33 ± 336.83	3799.48 ± 153.19	−1.65	0.103
ARISCAT scores	42.20 ± 7.14	40.90 ± 5.27	1.28	0.203
Anesthesia time (min)	203.09 ± 8.26	201.58 ± 7.17	1.20	0.231
Fluid intake (mL)	2172.00 ± 197.66	2196.10 ± 151.69	−0.84	0.401
Gender, n (%)			0.03	0.864
Male	40 (53.33)	40 (51.95)
Female	35 (46.67)	37 (48.05)
ASA class, n (%)			0.10	0.753
2	39 (52.00)	42 (54.55)
3	36 (48.00)	35 (45.45)
Smoking history, n (%)			0.94	0.333
No	39 (52.00)	34 (44.16)
Yes	36 (48.00)	43 (55.84)
Intraoperative urine output (mL)	628.00 ± 74.54	655.84 ± 91.04	6.83	0.078
Baseline Crs (mL/cmH2O)	34.03 ± 2.03	34.48 ± 1.81	1.45	0.148

t t-test, χ²: Chi-square test.

Data are expressed as mean ± SD (SD: standard deviation).

Group C Conventional Protective Ventilation group, Group ΔP driving pressure-guided ventilation group, BMI body mass index, ASA American Society of Anesthesiologists, ARISCAT scores the Assess Respiratory Risk in Surgical Patients in Catalonia scores, Crs static respiratory system compliance.

Primary outcomes

The incidence of PPCs (grade ≥ 2) was significantly lower in the ΔP group (22.1%) compared with the control group (54.7%), with an odds ratio (OR) of 0.24 (95% CI: 0.12–0.48; p < 0.001). (Table 2)

Table 2.

Clinical outcomes according to the risk of postoperative pulmonary complications.

	Group C (n = 75)	Group ΔP (n = 77)	OR(95%CI)	P
Primary outcome
Clinically significant PPCs (within 7 d; assessed on postoperative days 1, 3, and 7), n(%)*	41(54.74)	17(22.1)	0.24(0.12,0.48)	< 0.001
Secondary outcomes
Severity score of PPCs (within 7 d)	2(1,2)	1(1,1)		< 0.001
PPCs category, n(%)
Severe hyoxaemia	29(38.7)	21(27.3)	0.60(0.30,1.18)	0.136
Atelectasis	47(62.7)	35(45.5)	0.50(0.26,0.95)	0.034
Pleural effusion	7 (9.33)	3 (3.9)	0.39(0.10,1.58)	0.189

OR Odds Ratio, CI Confidence interval, Group C Conventional Protective Ventilation group, Group ΔP driving pressure-guided ventilation group, PPCs postoperative pulmonary complications; * PPCs were scored with a scale from 0 (no) to 5 (most severe) (see Methods). Clinically significant PPCs: with a score equal or greater than grade 2;Binary logistic regression for PPC incidence; Mann-Whitney U-test for ordinal severity score.

Baseline static compliance (Crs) was recorded immediately after intubation and is reported in Table 1. Intraoperative ventilatory variables (including driving pressure and mechanical power) were recorded one hour after skin incision.Mechanical power was calculated using the simplified Gattinoni equation: MP (J/min) = 0.098 × RR × VT(L) × (PEEP + ΔP/2).

Second outcomes

The severity of PPCs, assessed by the modified Kroenke score, was also reduced in the ΔP group (median [IQR]: 1 [1,1] vs. 2 [1,2]; p < 0.001). The ΔP-guided group showed a significantly lower incidence of atelectasis (45.5% vs. 62.7%, OR = 0.50, 95% CI: 0.26–0.95, p = 0.034), while reductions in severe hypoxemia (27.3% vs. 38.7%, p = 0.136) and pleural effusion (3.9% vs. 9.3%, p = 0.189) did not reach statistical significance (Table 2). A detailed breakdown of PPC type and timing (POD1/3/7) is provided in Supplementary Table S1.

Regarding oxygenation, the alveolar-arterial oxygen gradient (A-a DO₂) during the intraoperative period was significantly lower in the ΔP group, with a pronounced difference observed one hour after extubation (Fig. 3B). While the PaCO₂ levels at T1 and T2 were significantly elevated relative to preoperative values in both groups, no significant difference was found at T3 (Fig. 3A). In the ΔP group, the PaO₂/FiO₂ ratios remained stable from T1 to T2, but by T3 these ratios had declined significantly compared to baseline (Fig. 3C). During the postoperative recovery phase, both the oxygenation index and arterial oxygen saturation improved progressively in each group; however, Group ΔP demonstrated significantly higher values on postoperative days 1, 3, and 7, suggesting a more effective recovery of oxygenation in the early and mid-postoperative stages (Fig. 3E and F).

Fig. 3.

Intraoperative and Postoperative Respiratory Outcomes. A PaCO₂ (mmHg) at three intraoperative time points (T1, T2, T3). The ΔP-guided group demonstrated consistently lower PaCO₂ compared to the conventional group, suggesting improved ventilation efficiency. B A-aDO₂(Alveolar–arterial Oxygen Gradient, mmHg) at T1, T2, and T3. A larger gradient indicates poorer oxygen transfer; note the lower A-aDO₂ in the ΔP-guided group, reflecting better alveolar recruitment. C PaO₂/FiO₂ (mmHg) ratios at T1, T2, and T3. The ΔP-guided strategy maintained significantly higher oxygenation levels intraoperatively than the conventional approach (p < 0.05). D LUS (Lung Ultrasound Score) at T0, T1, T2, and T3. Lower scores represent fewer atelectatic areas; the ΔP-guided group exhibited lower LUS, indicating more effective alveolar recruitment over time. E SaO₂ (%) measured on postoperative days 1, 3, and 7. The ΔP-guided group maintained higher arterial oxygen saturation, suggesting improved postoperative pulmonary function. F PaO₂/FiO₂ (mmHg) on postoperative days 1, 3, and 7. This measure of gas exchange was significantly higher in the ΔP-guided group throughout the postoperative course, consistent with sustained benefits of individualized PEEP titration. Data presented as mean ± SD. *p < 0.05, **p < 0.01 between groups at the same time point. For Panels A–C (arterial blood gas analyses), assessments were performed on arrival in the operative suite, 10 min after induction of general anesthesia, before the first recruitment maneuver, and 30 min after arrival in the PACU. ET–PaCO₂ gap was defined as PaCO₂ − ETCO₂. A–aDO₂ was calculated using the alveolar gas equation as described in Methods. Exact input and derived values for Panels A–C are provided in Supplementary Table S2.

Mean lung ultrasound scores were similar between the groups prior to the induction of general anesthesia (T0) and induction (T1). Following one hour after surgery (T2), LUS were significantly lower in the group ΔP than in Group C before emergence from anesthesia. The intergroup differences remained significant at 30 min after arrival in PACU (T3), although Group C showed notable improvements in lung aeration (Fig. 3D).

The ΔP-guided strategy significantly altered respiratory mechanics while maintaining hemodynamic stability: Driving pressure was 34% lower in Group ΔP versus Group C, PEEP levels were individualized in Group ΔP versus fixed low PEEP in Group C, Mechanical power increased modestly in Group ΔP, reflecting energy expenditure for alveolar recruitment. No clinically relevant differences in heart rate or mean arterial pressure. Stroke volume variation was lower in Group ΔP, suggesting improved fluid responsiveness. Critically, hospital stay was 1.5 days shorter in Group, aligning with reduced postoperative pulmonary complications (Table 3).

Table 3.

Intraoperative hemodynamics and outcomes.

Variables	Group C (n = 75)	Group ΔP(n = 77)	t/Z/χ²	P
MAP(mmHg)	88.33 ± 3.17	85.94 ± 2.01	5.56	< 0.001
HR(per minute)	76.55 ± 3.61	77.68 ± 3.48	−1.96	0.052
SVV(%)	10.29 ± 1.08	9.24 ± 1.13	5.86	< 0.001
TV(ml)	424.39 ± 30.42	438.18 ± 39.94	−2.40	0.018
PEEP(cmH2O)	5.00(5.00, 5.00)	8.00(8.00,9.00)	−10.64	< 0.001
Driving pressure(cmH2O)	9.52 ± 0.78	6.44 ± 0.88	22.82	< 0.001
Intraoperative Crs (mL/cmH2O)	44.85 ± 4.60	69.20 ± 10.81	−18.16	< 0.001
Mechanical power (J/min)	5.09 ± 0.46	5.98 ± 0.40	−12.68	< 0.001
Hospital stay (d)	11.07 ± 1.19	9.57 ± 1.45	6.96	< 0.001
Postoperative ICU admission, n(%)			0.08	0.776
No	71 (94.67)	71 (92.21)
Yes	4 (5.33)	6 (7.79)

t: t-test.

Data are expressed as mean ± SD (SD: standard deviation).

Group C Conventional Protective Ventilation group, Group ΔP driving pressure-guided ventilation group, MAP Mean Arterial Pressure, HR Heart Rate, SVV Stroke Volume Variation, TV Tidal Volume, PEEP Positive End-expiratory Pressure.

Discussion

This trial focused on a specific and clinically challenging setting: long-term Tibetan Plateau residents undergoing open upper abdominal surgery. In this population, a ΔP-guided ventilation strategy-individualized PEEP titration combined with LUS-guided, on-demand recruitment was associated with better respiratory mechanics and oxygenation during surgery, fewer ultrasound signs of atelectasis, and fewer clinically significant PPCs within the first postoperative week. These findings support using real-time physiology to guide ventilation when the “margin for error” in oxygenation is small at high altitude.

A key background issue at high altitude is reduced inspired oxygen partial pressure, which lowers oxygen reserve and can make small losses of lung aeration clinically important. In our cohort, baseline static compliance was relatively low, consistent with chronic hypoxia–related adaptations that may reduce the ability to tolerate anesthesia-related aeration loss. In practical terms, a lung that starts “stiffer” and with less reserve can deteriorate faster when atelectasis develops. This provides a plausible reason why preventing perioperative aeration loss may yield a larger clinical effect than what is often reported in sea-level cohorts.

The first “engine” of our protocol was individualized PEEP titration toward the lowest driving pressure under a fixed low tidal volume³¹. Our titration observations provide a simple pattern: as PEEP increased from 0 to 10 cmH₂O, ΔP decreased and oxygenation improved; once PEEP exceeded 10 cmH₂O, oxygenation gains became small while ΔP started to rise, suggesting the beginning of overdistension. With tidal volume held constant, a lower ΔP reflects improved respiratory system compliance and is generally consistent with better aeration/recruitment; by contrast, a higher ΔP at low PEEP suggests derecruitment/atelectasis, while a higher ΔP at higher PEEP may signal overdistension. This “sweet spot” approach gives a practical way to balance recruitment and overdistension during surgery at high altitude.

The second “engine” was ultrasound guidance. Atelectasis under general anesthesia is common and creates uneven lung expansion, which concentrates stress in some regions. Prior studies show that moderate PEEP reduces atelectasis compared with no/very low PEEP, but the optimal level varies and remains uncertain^32–34. Because no single PEEP is ideal for all patients, multiple guidance methods have been proposed (e.g., oxygenation-guided, EIT-guided, compliance-guided, LUS-guided, transpulmonary pressure–guided)^35,36. In our study, LUS served as a bedside check of whether aeration was being lost and whether recruitment actually reversed it, supporting an “on-demand” rather than routine approach³⁷. Importantly, we did not directly measure EELV or pulmonary perfusion, so we interpret our LUS findings as improved aeration/recruitment rather than quantified increases in EELV.

Our results are consistent with existing concepts linking ΔP to lung stress. ΔP has been described as an important determinant of ventilator-related lung injury and outcomes in ARDS¹⁸, and intraoperative ΔP has been associated with PPC risk³⁸. In our cohort, maintaining a fixed low tidal volume while adjusting PEEP to minimize ΔP likely reduced cyclic derecruitment and excessive strain- mechanisms that can contribute to atelectasis and hypoxemia. This interpretation is supported by the physiological improvements we observed (higher PaO₂/FiO₂ and lower A–a gradient), which align with the expected effects of improved aeration and gas exchange^28,39.

Mechanical power (MP) deserves careful framing because it can appear counterintuitive. MP was statistically higher in the ΔP-guided group, but this difference mainly reflects the higher PEEP component rather than higher cyclic strain. Using the simplified Gattinoni equation (MP = 0.098 × RR × VT(L) × [PEEP + ΔP/2]), the protocol shifts energy away from the dynamic component (ΔP/2, linked to cyclic strain and atelectrauma) and toward the static component (PEEP), while ΔP itself was substantially reduced. In plain terms, we used a little more “holding pressure” to keep the lung open, but reduced the repeated “stretching pressure” that is more directly tied to cyclic injury.

Finally, our findings should be interpreted alongside large sea-level evidence. Several multicenter trials in abdominal surgery have not shown a meaningful PPC reduction with higher PEEP and recruitment compared with low-PEEP approaches, despite improvements in oxygenation or mechanics. In the DESIGNATION trial, ΔP-guided higher PEEP plus recruitment did not reduce PPCs versus standard low PEEP without recruitment and was associated with more hypotension and vasoactive use⁴⁰. A patient-level meta-analysis pooling PROVHILO, iPROVE, and PROBESE similarly found no statistically significant PPC reduction with higher PEEP/open-lung approaches¹². Against this background, the magnitude of the between-group difference in our single-center study should be interpreted cautiously. We speculate (i) that reduced oxygen reserve at high altitude may make perioperative aeration loss more likely to be recognized as hypoxemic PPCs, and^41,42 (ii) that LUS may have improved the precision of recruitment (confirming response and avoiding unnecessary maneuvers). These remain hypotheses and require confirmation in larger multicenter high-altitude studies.

This study has limitations. It was performed at a single tertiary hospital, which may limit generalizability. PEEP was identified using an incremental titration method rather than a decremental approach, which may produce different physiological results. Airway driving pressure was used as a surrogate for transpulmonary driving pressure because esophageal manometry was not feasible. At high altitude, reduced inspired PO₂ increases ventilatory drive⁴³; we did not measure awake resting tidal volume, and we therefore avoid quantitative statements about baseline tidal volume. Postoperative assessments occurred on POD1, POD3, and POD7, so PPC timing reflects the first scheduled assessment day on which an event was detected rather than the exact onset between assessments. Postoperative quality of life was not evaluated⁴⁴. Finally, the modest sample size may limit precision of the effect estimate; external validation in larger multicenter high-altitude cohorts is needed.

Conclusion

This study highlights the clinical relevance of ΔP-guided ventilation in high-altitude settings, where individualized strategies mitigate PPCs by addressing unique pathophysiological challenges, thereby improving postoperative outcomes.This positive effect may be attributed to the significant reduction in atelectasis severity with personalized PEEP and decreased ventilator-induced lung injury associated with lower ΔP.

Supplementary Information

Below is the link to the electronic supplementary material.

Author contributions

Ke Chen: Conceptualization, Methodology, Project administration, Investigation, Writing-review and editing，Funding acquisition.Zihui Xu: Conceptualization, Investigation, Data curation, Visualization, Formal analysis.Chunyan Dou : Methodology, Investigation, Formal analysis, Writing-original draft. Ruixue Chen, Yixi Ouzhu: Investigation, Writing-original draft.Weiwei Zhong: Conceptualization, Investigation, Validation, Project administration, Writing-review and editing.Xikui Cheng: Conceptualization, Resources, Supervision, Validation, Writing review and editing.All authors critically reviewed and approved the final version of the manuscript.

Funding

This study was supported by Natural Science Foundation of Tibet Autonomous Region (No. XZ2022ZR-ZY33(Z)) and Anhui Provincial Teaching Quality and Reform Project (No. 2023jyxm1107).

Data availability

The individual deidentified participant data supporting published results, the study protocol, and the statistical analysis plan are available from the corresponding author upon reasonable request.

Declarations

Competing interests

The authors declare no competing interests.

Ethical approval

This study was approved by the Ethics Committee of Shannan People’s Hospital, Tibet, China (Approval No. 2021-12-20-05, dated December 30, 2021). All participants provided written informed consent before inclusion in the study. The study was conducted in accordance with the Declaration of Helsinki (1964) and its subsequent amendments.