Correlation of postoperative inflammatory markers and clinical outcomes with intraoperative carbon dioxide pneumoperitoneum pressure levels in laparoscopic appendectomy

Abstract

BACKGROUND

Laparoscopic appendectomy (LA) is the preferred surgical approach for acute appendicitis. Carbon dioxide (CO₂) is used to establish a pneumoperitoneum to provide clear surgical visualization and adequate operative space. However, the specific prognostic impacts of various pressure levels remain unclear.

AIM

To investigate the effects of various CO₂ pneumoperitoneum pressures during LA on postoperative inflammatory marker levels and clinical outcomes.

METHODS

Patients were assigned to one of four groups according to the pneumoperitoneum pressure during LA: A [12 mmHg (n = 55)], B [13 mmHg (n = 54), C [14 mmHg (n = 53)], and D [15 mmHg (n = 55)]. Preoperative and postoperative inflammatory markers, including white blood cell (WBC) count and procalcitonin (PCT) level, were compared. Clinical efficacy indicators, including operative duration, pain score (s), basic activities of daily living scores, time to first ambulation and flatus, length of postoperative hospital stay, and complication rates were analyzed.

RESULTS

There were no differences in the preoperative WBC count or PCT levels among the four groups (P > 0.05). On postoperative days 1 and 3, group A exhibited lower WBC counts and PCT levels than groups B, C, and D (P < 0.01). Clinical efficacy analysis revealed no differences in operative duration or intraoperative blood loss (P > 0.05). Patients in group A exhibited significantly lower numerical pain rating scale scores on postoperative days 1 and 3 (P < 0.05) and significantly higher basic activities of daily living scores (P < 0.01) than those in the other groups. Furthermore, patients in group A experienced significantly shorter times to first ambulation and flatus (P < 0.05) and shorter hospital stays (P < 0.05). There were no statistically significant differences in the postoperative complication rates among the four groups (P > 0.05).

CONCLUSION

Maintaining a CO₂ pneumoperitoneum pressure of 12 mmHg during LA reduces postoperative inflammation and alleviates pain more effectively, accelerates recovery, and shortens hospital stay without increasing the risk of complications.

Key Words: Acute appendicitis; Laparoscopic appendectomy; Carbon dioxide pneumoperitoneum pressure; Inflammatory markers; Clinical efficacy; Randomized controlled trial

Core Tip: This prospective randomized controlled trial included 217 patients. We compared the effects of four different intraoperative carbon dioxide pneumoperitoneum pressures (12-15 mmHg) during laparoscopic appendectomy. The results showed that a 12-mmHg pneumoperitoneum pressure significantly reduced postoperative white blood cell and procalcitonin levels, lowered the score on the numeric pain scale, shortened the time to first ambulation and anal gas expulsion, and reduced the length of hospital stay, without increasing the risk of complications (Clavien-Dindo classification ≤ grade II). The above results confirm that 12 mmHg is the ideal pneumoperitoneum pressure that balances surgical field visibility and accelerates recovery.

INTRODUCTION

Acute appendicitis is a common surgical emergency. If not treated promptly, it may lead to appendiceal perforation or diffuse peritonitis[1]. Laparoscopic appendectomy (LA), with the advantages of minimal trauma, mild pain, and quick recovery, has become the preferred surgical method for treating acute appendicitis[2,3]. Acute appendicitis is a common surgical emergency. If not treated promptly, it may lead to appendiceal perforation or diffuse peritonitis[1]. LA, with the advantages of minimal trauma, mild pain, and quick recovery, has become the preferred surgical method for treating acute appendicitis[2,3].

During laparoscopic surgery, carbon dioxide (CO₂) is injected to create an intra-abdominal pneumoperitoneum that provides a clear surgical field and sufficient operating space. The selection of pneumoperitoneum pressure is of crucial importance; too low a pressure will result in poor exposure of the surgical field, whereas too high a pressure may cause abdominal membrane traction, diaphragm irritation, hypercapnia, and aggravate the inflammatory response, thereby delaying the patient’s postoperative recovery[4-6]. The recommended pressure range for CO₂ pneumoperitoneum in clinical practice is 12-15 mmHg. However, high-quality prospective studies comparing the specific effects of different pressures within this range are lacking[7,8].

With the widespread application of the enhanced recovery after surgery (ERAS) concept, optimizing controllable intraoperative factors, such as intra-abdominal pressure, has become a key focus in clinical practice[9,10]. Therefore, we conducted a prospective, evaluator-blinded, randomized controlled trial to compare the postoperative inflammatory indicators and clinical outcomes of patients undergoing laparoscopic surgery under different intra-abdominal pressure levels (12, 13, 14, and 15 mmHg), aiming to provide a reference basis for individualized selection of intra-abdominal pressure in clinical settings.

MATERIALS AND METHODS

Study design

This single center, prospective, assessor-blind, randomized controlled trial enrolled patients diagnosed with acute appendicitis who met the specified inclusion criteria from January 2023 to June 2024. The study was approved by the Medical Ethics Committee of our hospital (approval No.[2022]85).

Study participants

Patients with acute appendicitis admitted to our hospital from January 2023 to June 2024 were enrolled. A total of 217 patients were enrolled and randomly assigned to four groups according to CO₂ pneumoperitoneum pressure: Group A (12 mmHg, n = 55), group B (13 mmHg, n = 54), group C (14 mmHg, n = 53), and group D (15 mmHg, n = 55). The inclusion criteria were as follows: Age, 18-60 years; time from onset to hospital admission ≤ 72 hours; confirmed diagnosis of acute appendicitis based on clinical symptoms, signs, and imaging examinations (ultrasound or computed tomography); American Society of Anesthesiologists (ASA) classification I-II; and adequate communication and comprehension abilities to cooperate throughout the study. The exclusion criteria were as follows: Concurrent severe cardiac, pulmonary, hepatic, renal, coagulation disorders, or immune system diseases; preoperative imaging indicating peri-appendiceal abscess formation; history of abdominal surgery with extensive peritoneal adhesions; pregnancy or lactation; and cognitive dysfunction or psychiatric disorders.

Sample size estimation

Sample size estimation was based on primary outcome measures, namely white blood cell (WBC) count and procalcitonin (PCT) levels on postoperative days 1 and 3. Based on pilot trial data, the power of the test (1-β) was set at 0.8, the significance level (α) at 0.05, and a 20% dropout rate was projected. The most conservative estimate of the primary outcome measures was used to ensure adequate statistical power. Calculations indicated that each group required at least 50 patients; therefore, 217 patients were enrolled in this study. Secondary outcome measures were not used for sample size estimation because the sample size determined by the primary endpoints was considered sufficient for a meaningful analysis of these secondary endpoints.

Randomization and blinding

A computer-generated random number table was used to assign patients fulfilling the inclusion criteria in a 1:1:1:1 ratio into four groups according to the CO₂ pneumoperitoneum pressure applied during LA: Group A (12 mmHg), group B (13 mmHg), group C (14 mmHg), and group D (15 mmHg). The randomization sequence, maintained by researchers who were not involved in the clinical data collection, was placed in a sealed opaque envelope. Owing to the characteristics of the surgical procedure, the surgeon could not be blinded to the pneumoperitoneum pressure. However, the patients, outcome evaluators, and data analysts were unaware of the group assignments (i.e., a single-blind design).

Surgery and postoperative management

All procedures were performed by the same team of experienced surgeons with titles of associate chief physician or higher. A standardized LA technique was used. Patients were positioned supine, and after successful endotracheal intubation and general anesthesia, the surgical field was disinfected. A 1 cm incision was made along the superior edge of the umbilicus and pneumoperitoneum was established by puncturing the abdominal cavity with a pneumoperitoneum needle and injecting CO₂ gas. A 10 mm cannula puncture instrument and laparoscopic lens were inserted. Under laparoscopic guidance, a 10 mm cannula puncture instrument was placed in the left lower quadrant and a 5 mm cannula puncture instrument was inserted 3 cm above the pubic symphysis. Laparoscopic visualization was used to identify the location, condition, and relationship of the appendix with surrounding tissues. The appendiceal mesentery was dissected using an electrohook, the appendiceal artery was coagulated and severed, and the appendiceal mesentery was mobilized to its base. The appendix was ligated twice using a No. 7 silk suture at the root and then cut approximately 0.5 cm distal to the root. The residual appendiceal mucosa was cauterized using an electrohook. The appendiceal specimen was excised completely from the puncture site. The exudate was aspirated and the surgical field was examined for bleeding. The CO₂ pneumoperitoneum was closed, laparoscope withdrawn, and incision sutured to complete the procedure. During surgery, the corresponding CO₂ pneumoperitoneum pressure was maintained according to patient group.

Postoperatively, all patients received a standardized antibiotic regimen of intravenous infusion of 2 g ceftriaxone sodium (Shenzhen Lijian Pharmaceutical Co., Ltd., China, National Drug Approval Number H20058023) once daily until discharge. Postoperative analgesia was administered according to uniform standards, without using self-controlled analgesia pumps. Rescue analgesics were administered when pain affected sleep or limited activity [numerical pain rating scale (NRS) score ≥ 4]. This ensured timely pain control to facilitate early mobilization and recovery.

Observation indicators

Inflammatory markers: Fasting venous blood was collected preoperatively, on postoperative day 1, and on the morning of postoperative day 3 to measure WBC (10⁹/L) and PCT (ng/mL) levels.

Clinical efficacy indicators: Operative duration: This was defined as the time from skin incision to completion of suturing (minute). Intraoperative blood loss (mL) and conversion rate to open surgery were also measured. Pain rating: The NRS (0-10 points) was used for evaluation before surgery and on postoperative days 1 and 3, and scored as follows: No pain (0 points), mild pain (1-3), moderate pain (4-7), and severe pain (8-10)[11]. Barthel Index Assessment Scale (0-100 points): This scale was used to evaluate the patients preoperatively and on postoperative days 1 and 3. Higher scores indicated greater independence and a better quality of life[12]. Postoperative recovery status: This included the time to first ambulation after surgery (hour), time to first flatus (hour), and length of postoperative hospitalization (day).

Safety indicators: Safety was assessed according to the 30-day incidence of postoperative complications. All complications were recorded and classified using the Clavien-Dindo grading system (grade I, any deviation from the normal postoperative course without the need for pharmacological treatment or surgical intervention; grade II, requiring pharmacological treatment; grade III, requiring surgical, endoscopic, or radiological intervention; grade IV, life-threatening complications requiring intensive care; grade V, death). Grade II or higher complications were considered clinically significant. Grading was performed by an independent assessor blinded to group allocation.

Statistical analysis

Data analysis was performed using SPSS software (version 27.0; IBM Corporation, Armonk, NY, United States). The normality of the measurement data was assessed using the Kolmogorov-Smirnov test. Measurement data conforming to a normal distribution are expressed as mean ± SD. Univariate analysis of variance (one-way analysis of variance) was used for intergroup comparisons. When the variances were equal, the F-test was used for intergroup comparisons, and the least significant difference method with Bonferroni correction was applied for multiple comparisons to control type I errors. Welch’s correction was used when the variances were unequal, and Tamhane’s T2 method was used for multiple comparisons. Categorical data are expressed as n (%), and intergroup comparisons were performed using the χ² test or Fisher’s exact probability method. The significance level was set at α = 0.05, with P < 0.05 considered to be statistically significant.

RESULTS

Baseline data comparison

Data from 217 patients were analyzed in this study. As shown in Table 1, there were no statistically significant differences among the four groups in baseline characteristics, including age (group A: 38.2 ± 11.5 years, group B: 39.1 ± 10.9 years, group C: 37.8 ± 12.0 years, group D: 38.5 ± 11.3 years; P = 0.742), sex distribution (male: 50.9%-54.5%, P = 0.821), body mass index, ASA classification, disease duration, preoperative WBC count, and preoperative PCT level (P > 0.05 for all comparisons), indicating good comparability among groups.

Table 1 Baseline characteristics of the four study groups, n (%)/mean ± SD.

Variable	Group A (n = 55)	Group B (n = 54)	Group C (n = 53)	Group D (n = 55)	P value
Age (years)	38.2 ± 11.5	39.1 ± 10.9	37.8 ± 12.0	38.5 ± 11.3	0.742
Sex (male)	28 (50.9)	29 (53.7)	28 (52.8)	30 (54.5)	0.821
BMI (kg/m2)	23.5 ± 2.8	23.8 ± 2.6	23.3 ± 2.9	23.6 ± 2.7	0.689
ASA I/II (n)	30/25	28/26	29/24	31/24	0.953
Disease duration (hour)	14.2 ± 5.3	13.9 ± 5.6	14.5 ± 5.1	14.0 ± 5.4	0.862
Preop WBC (× 109/L)	14.52 ± 1.24	14.78 ± 1.11	14.27 ± 1.13	14.30 ± 1.34	0.103
Preop PCT (ng/mL)	2.32 ± 0.41	2.06 ± 0.48	2.17 ± 0.51	2.19 ± 0.60	0.056

BMI: Body mass index; ASA: American Society of Anesthesiologists; WBC: White blood cell; PCT: Procalcitonin.

Comparison of inflammatory markers

WBC: There were no significant differences in preoperative WBC counts among the four patient groups (P > 0.05). On postoperative day 1, the WBC count in group A was 12.17 ± 0.87 ×10⁹/L, which was significantly lower than that in group B (12.73 ± 1.17, P = 0.005), group C (12.74 ± 1.00, P = 0.004), and group D (12.84 ± 1.19, P = 0.002). On postoperative day 3, group A also showed a significantly lower WBC count (7.20 ± 1.46) compared with group B (7.94 ± 1.18, P = 0.003), group C (7.97 ± 1.28, P = 0.002), and group D (8.03 ± 1.31, P = 0.001). No significant differences were observed among groups B, C, and D at any time point (P > 0.05). Pairwise comparisons among groups B, C, and D revealed no significant differences (P > 0.05) (Table 2).

Table 2 Comparison of white blood cell levels before and after surgery in four patient groups, mean ± SD.

Inflammatory markers	Group A (n = 55)	Group B (n = 54)	Group C (n = 53)	Group D (n = 55)	F value	P value
Preoperative WBC (109/L)	14.52 ± 1.24	14.78 ± 1.11	14.27 ± 1.13	14.30 ± 1.34	2.086	0.103
WBC on postoperative day 1 (109/L)	12.17 ± 0.87	12.73 ± 1.171	12.74 ± 1.001	12.84 ± 1.191	4.461	0.005
WBC on postoperative day 3 (109/L)	7.20 ± 1.46	7.94 ± 1.181	7.97 ± 1.281	8.03 ± 1.311	4.818	0.003

¹Compared with group A at the same time point, P < 0.01 (after Bonferroni correction).

WBC: White blood cell.

PCT: There were no significant differences in the preoperative PCT levels among the four patient groups (P > 0.05). On postoperative days 1 and 3, PCT levels in group A were significantly lower than those in groups B, C, and D (P < 0.01). Pairwise comparisons among groups B, C, and D revealed no significant differences (P > 0.05) (Table 3). A comparison of PCT levels among the patients in groups A, B, C, and D is presented in Table 3.

Table 3 Comparison of inflammatory marker procalcitonin levels among patients in groups A, B, C, and D, mean ± SD.

Inflammatory markers	Group A (n = 55)	Group B (n = 54)	Group C (n = 53)	Group D (n = 55)	F value	P value
Preoperative PCT (ng/mL)	2.32 ± 0.41	2.06 ± 0.48	2.17 ± 0.51	2.19 ± 0.60	2.557	0.056
Postoperative day 1 PCT (ng/mL)	1.60 ± 0.57	1.93 ± 0.601	1.97 ± 0.781	1.98 ± 0.681	4.188	0.007
Postoperative day 3 PCT (ng/mL)	0.34 ± 0.14	0.42 ± 0.131	0.42 ± 0.151	0.45 ± 0.131	6.462	< 0.001

¹Compared with group A at the same time point, P < 0.01 (after Bonferroni correction).

PCT: Procalcitonin.

Comparison of clinical efficacy indicators

Surgical-related indicators: There were no statistically significant differences in operative duration, intraoperative blood loss, or conversion to open surgery among the four patient groups (P > 0.05) (Table 4).

Table 4 Comparison of surgical-related indicators among patients in groups A, B, C, and D, n (%)/mean ± SD.

Surgical-related indicators	Group A (n = 55)	Group B (n = 54)	Group C (n = 53)	Group D (n = 55)	F value	P value
Operating time (minute)	40.80 ± 8.05	42.61 ± 6.98	40.45 ± 6.98	40.33 ± 6.43	1.196	0.312
Intraoperative blood loss (mL)	15.27 ± 5.11	15.8 ± 4.92	14.9 ± 5.34	16.1 ± 5.68	0.478	0.698
Conversion to open surgery	0 (0)	0 (0)	1 (1.9)	0 (0)	-	0.2551

¹Fisher’s exact probability method.

Pain and quality of life score: There were no significant differences in the preoperative NRS and basic activities of daily living scores among the four groups (P > 0.05). On postoperative day 1, the NRS score in group A was 3.89 ± 1.29, significantly lower than that in group B (4.48 ± 1.18, P = 0.011), group C (4.66 ± 1.19, P = 0.002), and group D (4.78 ± 1.52, P = 0.001). On postoperative day 3, group A continued to show a lower NRS score (1.80 ± 0.59) compared with group B (2.11 ± 0.66, P = 0.015), group C (2.15 ± 0.69, P = 0.009), and group D (2.18 ± 0.70, P = 0.006). Further details are summarized in Tables 5 and 6. A comparison of the NRS pain scores among the patients in groups A, B, C, and D is presented in Table 5. A comparison of the basic activities of daily living scores among the four groups is shown in Table 6.

Table 5 Comparison of numerical pain rating scale pain scores among patients in groups A, B, C, and D, mean ± SD.

NRS pain score	Group A (n = 55)	Group B (n = 54)	Group C (n = 53)	Group D (n = 55)	F value	P value
Preoperative (score)	6.09 ± 1.36	6.44 ± 1.33	6.19 ± 1.27	6.04 ± 1.51	0.942	0.421
Day 1 postoperatively (score)	3.89 ± 1.29	4.48 ± 1.181	4.66 ± 1.191	4.78 ± 1.521	5.029	0.002
Day 3 postoperatively (score)	1.80 ± 0.59	2.11 ± 0.661	2.15 ± 0.691	2.18 ± 0.701	3.899	0.010

¹Compared with group A at the same time point, P < 0.01 (after Bonferroni correction).

NRS: Numerical pain rating scale.

Table 6 Comparison of basic activities of daily living scores among four patient groups, mean ± SD.

BADL scale score	Group A (n = 55)	Group B (n = 54)	Group C (n = 53)	Group D (n = 55)	F value	P value
Preoperative (score)	75.18 ± 3.84	74.26 ± 3.69	75.00 ± 3.54	75.45 ± 3.51	1.070	0.363
Day 1 postoperatively (score)	60.91 ± 3.61	56.39 ± 4.491	53.30 ± 4.151	49.55 ± 3.761	78.793	< 0.001
Day 3 postoperatively (score)	80.27 ± 4.13	77.78 ± 4.731	74.91 ± 4.651	71.45 ± 4.881	37.324	< 0.001

¹Compared with group A at the same time point, P < 0.01 (after Bonferroni correction).

BADL: Basic activities of daily living.

Postoperative recovery and complications: Patients in group A had a significantly shorter time to first postoperative ambulation (9.15 ± 0.69 hours) compared with group B (9.48 ± 0.62 hours, P = 0.011), group C (9.53 ± 0.77 hours, P = 0.008), and group D (9.57 ± 0.71 hours, P = 0.003). Similarly, the time to first flatus was significantly shorter in group A (15.73 ± 1.15 hours) than in group B (16.52 ± 1.43 hours, P = 0.002), group C (16.57 ± 1.36 hours, P = 0.002), and group D (16.73 ± 1.48 hours, P = 0.001). The postoperative hospital stay was also significantly shorter in group A (4.47 ± 0.57 days) compared with group B (4.76 ± 0.55 days, P = 0.011), group C (4.79 ± 0.53 days, P = 0.008), and group D (4.82 ± 0.64 days, P = 0.006). There were no significant differences among the four groups in the 30 days incidence of postoperative complications (group A, 3.6%; group B, 3.7%; group C, 5.7%; and group D, 5.5%; P = 0.928, χ² test) (Table 7).

Table 7 Comparison of postoperative recovery and complications among the four patient groups, n (%)/mean ± SD.

Postoperative recovery status	Group A (n = 55)	Group B (n = 54)	Group C (n = 53)	Group D (n = 55)	F value	P value
First postoperative ambulation, duration(hour)	9.15 ± 0.69	9.48 ± 0.621	9.53 ± 0.771	9.57 ± 0.711	4.070	0.008
First postoperative anal defecation, time of gas administration (hour)	15.73 ± 1.15	16.52 ± 1.432	16.57 ± 1.362	16.73 ± 1.482	5.894	0.001
Postoperative hospitalization days (day)	4.47 ± 0.57	4.76 ± 0.551	4.79 ± 0.531	4.82 ± 0.641	4.263	0.006
Complications	2 (3.6)	2 (3.7)	3 (5.7)	3 (5.5)	χ2 = 0.457	0.928

¹Compared with group A, P < 0.05 (after Bonferroni correction).

²Compared with group A, P < 0.01 (after Bonferroni correction).

DISCUSSION

This prospective randomized controlled trial systematically compared the effects of four different CO₂ pneumoperitoneal pressures (12-15 mmHg) during LA. The results demonstrated that compared with pressures of 13-15 mmHg, using 12 mmHg significantly reduced postoperative inflammatory responses (as reflected by WBC count and PCT levels), alleviated postoperative pain, promoted earlier ambulation and gastrointestinal function recovery, shortened hospital stay, and did not increase complication rates. These findings provide high-quality evidence that 12 mmHg is the optimal pneumoperitoneal pressure within the conventional range for LA, and support the implementation of ERAS principles in this procedure[13,14].

Consistent with our expectations, operative duration and intraoperative blood loss did not differ significantly among the four groups[15,16]. All participating surgeons were experienced, and their proficiency allowed them to handle minor variations in pneumoperitoneal pressure within the 12-15 mmHg range without affecting surgical efficiency. Previous studies have suggested that reducing the pressure to < 12 mmHg may compromise the operative field and increase surgical difficulty[7], thus offering no additional benefit. Therefore, 12 mmHg represents the lowest safe pressure that ensures adequate exposure while optimizing postoperative recovery.

The most significant advantage of the 12-mmHg group was better control of postoperative inflammation. Acute appendicitis is an infectious condition, and higher CO₂ pneumoperitoneal pressure may exacerbate systemic inflammation through increased peritoneal traction, reduced splanchnic perfusion, and promoting bacterial translocation[17,18]. Elevated pressure also lowers oxygen tension in the peritoneal tissues, creating a favorable environment for bacterial growth[19]. The lower WBC and PCT levels observed in the 12 -mmHg group suggest that lower pressure mitigates surgical stress and the release of inflammatory mediators, establishing a physiological basis for a more stable recovery[20].

Patients in the 12 -mmHg group also experienced less postoperative pain. Lower pneumoperitoneal pressure reduces mechanical stretching of the peritoneum and diaphragm, as well as excessive stimulation of the phrenic nerve endings, thereby alleviating shoulder tip and abdominal wall pain[21]. Reduced pain directly promotes early ambulation, a core ERAS component that enhances gastrointestinal motility via gravitational effects and mechanical stimulation[22,23]. Moreover, lower pressure improves the intestinal oxygen supply, reduces intraabdominal hypertension, protects intestinal microcirculation, and minimizes ischemia-induced toxin absorption, all of which contribute to a faster return to bowel function[24]. The significant differences in the basic activities of daily living scores further indicate that the low-pressure strategy improves patients’ quality of life early after surgery.

Further studies are needed to determine whether low pneumoperitoneal pressure confers additional benefits through neuroendocrine regulation and immune protection. Higher pressure can activate the sympathetic-adrenal medullary axis, increasing stress hormones such as catecholamines and cortisol, which suppress immune function and delay tissue repair[25]. Lower pressure helps maintain intraoperative hemodynamic stability[26], reduces mechanical compression of abdominal organs, preserves intestinal barrier function, and decreases endotoxin translocation, thereby lowering the risk of systemic inflammatory response syndrome[27].

Notably, in addition to the superior recovery indicators in the 12-mmHg group, there was no significant difference in the incidence of postoperative complications (e.g., incisional infection, intraabdominal abscess) among the four groups. This finding confirms that reducing the pressure within the conventional range (12-15 mmHg) is safe and does not achieve faster recovery at the expense of increased complications. From a health economics perspective, a shorter hospital stay in the low-pressure group suggests more efficient utilization of medical resources, which has practical implications for reducing patient burden and alleviating healthcare system strain.

Limitations

This study has several limitations. First, this was a single-center trial, limiting its generalizability; therefore, multicenter validation is required. Second, the surgeons were not blinded to the pressure, although other personnel were blinded, which introduced a possible performance bias. Third, the sample size was powered for inflammatory markers, not complications; the low complication rate (3.6%-5.7%) limits conclusions regarding safety equivalence. Fourth, we did not stratify the patients by body mass index, appendicitis severity, or peritoneal contamination; obese patients or those with advanced inflammation may require higher pressure. Fifth, we did not record total CO₂ volume or pneumoperitoneum duration, both of which may have affected the outcomes. Sixth, follow up was short term (≤ 30 days); long term outcomes (hernia, chronic pain, quality of life, costs) were not assessed. Seventh, our exclusion criteria (age > 60 years, ASA ≥ III, pregnancy, prior extensive adhesions) restrict applicability to these populations. Finally, despite the use of standardized protocols, unmeasured confounders cannot be excluded. Future studies are required to address these limitations.

CONCLUSION

Maintaining a CO₂ pneumoperitoneal pressure of 12 mmHg during LA, compared with 13-15 mmHg, can more effectively reduce postoperative inflammatory responses, alleviate pain, promote gastrointestinal function recovery, and shorten hospital stay without increasing complication risks, representing a safe and effective optimization strategy. These findings provide new evidence supporting the implementation of the ERAS principles in LA, recommending that an initial pneumoperitoneal pressure of 12 mmHg should be prioritized in clinical practice while ensuring adequate surgical field exposure. However, during actual surgical procedures, appropriate CO₂ pneumoperitoneal pressure should be selected based on a comprehensive consideration of patient-specific factors (e.g., age, body weight, degree of obesity, underlying diseases, intra-abdominal adhesions, and disease severity) to achieve optimal surgical outcomes.