Impact of Pneumoperitoneum Pressure on Post-Cholecystectomy Pain.

Background and Aims: Laparoscopic cholecystectomy (LC) often causes significant postoperative pain. While low-pressure pneumoperitoneum (8 mmHg) may reduce pain, optimal patient selection remains unclear. This trial compared pain outcomes between low-pressure (LPLC) and standard-pressure (SPLC) LC and identified predictors for pressure conversion.

This prospective randomized controlled trial (June 2023 to September 2024) randomized 200 elective LC patients 1:1 to 8 or 12 mmHg groups. Postoperative pain was assessed using a facial visual analog scale at 1–72 hours and analyzed by both intention-to-treat (ITT) and per-protocol (PP) approaches. Intraoperative parameters, recovery outcomes, and biochemical markers were also compared. Risk factors for pressure conversion were analyzed using univariate/multivariate methods.

LPLC significantly reduced: visceral pain at 12 hours (ITT: P = .046, PP: P = .005), incisional pain at 48 hours (ITT: P = .017, PP: P = .003), postoperative aspartate aminotransferase (AST)/alanine aminotransferase (ALT) elevation (P < .05). Preoperative C-reactive protein (CRP) ≥12.70 mg/L predicted intraoperative conversion from 8 to 12 mmHg (odds ratio [OR] 1.053, area under the curve [AUC] = 0.704).

The use of low-pressure pneumoperitoneum (8 mmHg) for LC significantly reduces postoperative pain and decreases the impact on liver function. LPLC demonstrates comparable safety and feasibility to SPLC. To achieve maximum benefit in patients with LC, we recommend that patients with preoperative CRP ≥12.70 mg/L carefully choose LPLC as the initial procedure.

Cholecystectomy, Laparoscopic, Pneumoperitoneum

Laparoscopic cholecystectomy (LC) has emerged as the preferred surgical treatment for benign gallbladder disease and is widely practiced in clinical settings.1 In comparison to open cholecystectomy, LC offers benefits such as smaller incisions, shorter hospital stays, quicker recovery, and reduced postoperative pain.2 For laparoscopic surgery, the use of carbon dioxide gas is necessary to establish a pneumoperitoneum to create an operating space. However, higher pneumoperitoneum pressures may result in a decrease in cardiac output and stroke volume, potentially activating the renin-angiotensin-aldosterone system (RAAS).3,4 This physiological response could subsequently increase heart rate, systemic vascular resistance, and pulmonary vascular resistance.5 Low-pressure pneumoperitoneum techniques have been introduced into clinical practice to minimize the adverse effects of high-pressure or standard-pressure pneumoperitoneum. Previous trials comparing low-pressure pneumoperitoneum LC (LPLC) with standard-pressure pneumoperitoneum LC (SPLC) have shown that performing the procedure under low-pressure (6–10 mmHg) reduced the impact on cardiovascular, pulmonary, and intra-abdominal organ functions compared to standard-pressure.6,7 Meanwhile, the early European Association for Endoscopic Surgery (EAES) guidelines recommend utilizing the lowest pressure that allows for adequate exposure to the surgical field, rather than traditional pressures.8 Higher pneumoperitoneum pressure theoretically causes excessive diaphragmatic strain, hypercapnia, and thus increased postoperative pain.9,10 However, the impact of LPLC on postoperative pain remains a topic of debate.11–13 While low-pressure pneumoperitoneum is feasible in 90–94.6% of laparoscopic procedures.2,14 In clinical practice, it has been observed that using low-pressure pneumoperitoneum may limit the effective field of operation and view, making it unsuitable for all patients with factors such as obesity, difficult anatomy, severe adhesions, and exposure difficulties contributing to the inability to complete the operation under low pressure.6,8,15–17 This prospective randomized controlled trial evaluated the efficacy of low-pressure pneumoperitoneum (8 mmHg) compared to standard-pressure pneumoperitoneum (12 mmHg) in reducing postoperative pain following LC. We also conducted a comprehensive analysis to identify clinical characteristics associated with the unsuitability of low-pressure pneumoperitoneum during LC.

This prospective, randomized, controlled clinical study was conducted from June 2023 to September 2024, at the First Affiliated Hospital of Chengdu Medical College, China. This study was reviewed and approved by the Institutional Review Board and adhered to the CONSORT 2010 Guidelines for Reporting of Randomized Trials. Participants Patients undergoing elective LC for benign gallbladder disease with an ASA score ≤3 who consented to participate were included. No emergent cases were enrolled. Patients were excluded if they presented with any of the following: (1) acute biliary pancreatitis or cholangitis; (2) Nongallbladder-related pain, such as gastroduodenal ulcers, periarthritis of the shoulder, abdominal aortic aneurysm; (3) requirement for common bile duct exploration or any additional surgery; (4) conversion to open cholecystectomy; (5) inability to comprehend the face visual analog scale (F-VAS), language barriers, and hearing or visual impairments. All the surgical procedures were performed under standard general anesthesia given by the same anesthesiology team. All LCs were performed by similarly experienced surgeons in laparoscopic surgery. Cholecystitis was diagnosed according to the Tokyo Guidelines of 2018.18 Gallbladder stones and polypoid lesions were primarily identified through imaging studies, including abdominal ultrasonography and/or contrast-enhanced computed tomography. Preoperative and Postoperative Anesthetic Management All patients were randomly assigned to either the SPLC or the LPLC in a 1:1 ratio before surgery, both groups received identical and standardized preoperative and postoperative care. Surgeons utilized visual aids (e.g., anatomical charts and surgical animations) to explain the procedure, the advantages of LC (including faster recovery and smaller scars), the expected postoperative recovery course, and potential risks. In addition, hospital brochures provided detailed information on preoperative preparations, postoperative activity, dietary advice, and pain management plans. Ward nurses delivered postoperative instructions based on a standardized protocol, emphasizing the importance of early ambulation. Finally, patients were given the opportunity to ask questions and discuss any concerns with the medical team. Upon arrival in the operating room, all patients underwent standard hemodynamic monitoring followed by a standardized balanced anesthetic technique combining intravenous and inhalation agents. Postoperatively, all patients were permitted oral intake after 6 hours. In cases where patients reported moderate to severe pain (F-VAS score ≥ 4 points) in either group, they received 30 mg of ketorolac intramuscularly. If the patients still complained of pain and required more pain reduction, a rescue analgesic (100-mg tramadol intramuscularly). Nausea and vomiting complaints triggered an antiemetic regimen of 10 mg metoclopramide hydrochloride intramuscularly, with administration time and frequency documented. Considering both patients’ limited awareness of potential postoperative complications and primary healthcare centers’ constrained capacity to manage postdischarge risks following LC, our institution maintains a standardized 3-day postoperative hospitalization protocol instead of outpatient procedure. Surgical Intervention Three-port LC has become a common surgical technique for gallbladder diseases maintaining optimal operative exposure and instrument maneuverability.19 In our hospital, 3-port LC is a common surgical technique for gallbladder diseases, utilizing 12-, 5-, and 10-mm trocars positioned at the subxiphoid region, right subcostal margin, and umbilical site, respectively. This modified approach reduces the number of incisions compared to conventional four-port LC while maintaining optimal operative exposure and instrument maneuverability.19 Previous studies have confirmed that LC is feasible and safe at an intra-abdominal pressure of 8 mmHg and minimizes adverse hemodynamic effects.20,21 Therefore, in the SPLC group (control group), the operation was initiated with a pneumoperitoneum pressure of 12 mmHg and maintained throughout. In the LPLC group (test group), the operation started with a pneumoperitoneum pressure of 8 mmHg. Pressure could be switched from 8 to 12 mmHg at any time of the operation if the surgeon found inadequate pressure hindering exposure and operation. Patients with 8 mmHg to 12 mmHg switching were categorized as low-pressure unsuitable patients, and the reasons for the switching were documented for subsequent analysis. Those who completed the operation at 8 mmHg were defined as the LPLC group. At the end of the surgery, all port sites were not using local anesthetics, and abdominal gas was evacuated. The decision to place an abdominal drainage tube was determined by the severity of inflammation. In all cases requiring drainage, a closed-suction drain (e.g., 10 Fr Jackson-Pratt) was positioned adjacent to the gallbladder fossa and exited through the right subcostal margin to facilitate postoperative monitoring. Data Collection Baseline characteristics, ASA classification, Charlson comorbidity index, and laboratory tests should be recorded before surgery. In our center, CRP is routinely examined in all patients preoperatively, this helps us promptly detect whether patients have hidden infections or other inflammatory diseases, thus allowing necessary measures to be taken before surgery and reducing the risk of postoperative complications. During surgery, baseline pneumoperitoneum pressure values, pressure changes, and etiology of pressure changes were documented. Postoperative data collection included operation duration (starting from the incision of the skin to the final suture), drain management, and postoperative patient-controlled intravenous analgesia (PCIA). Additionally, Postoperative pain, including incisional, visceral, and shoulder pain, was patient-assessed using the F-VAS (0–10 points) pain scale. Incisional pain was defined as superficial pain, wound pain, or pain located in the abdominal wall. Visceral pain was defined as pain inside the abdomen, which may be deep, dull, and more difficult to localize, and may resemble biliary colic. Shoulder pain was defined as a sensation of pain in the shoulder.9 Postoperative pain scores should be recorded at standardized intervals: 1, 4, 8, 12, 24, 48, and 72 hours. Finally, all collected data should be compiled and subjected to statistical analysis by researchers. Sample Size Based on the recent report by Goel in 201922 the mean VAS score 12 hours after surgery was 2.14 in the low pneumoperitoneum pressure group and 2.65 in the standard pressure group. Assuming a test power of 90% (1-β), a 2-sided test level of α = 0.05, and a superiority test design, it is determined that 100 cases are needed in each group, totaling 200 cases. Randomization, Allocation Concealment, and Blinding Before surgery, qualified participants were randomly divided into the LPLC group and SPLC group at a 1:1 ratio using opaque envelopes based on a computer-generated random allocation sequence. During the procedure, the researcher opened the envelope and adjusted the machine to the designated pressure setting. This study employed a single-blind design, where patients were unaware of their group allocation. Statistical Analysis Quantitative data were analyzed by first conducting a normality test. If the data met normal distribution, it was presented as Mean ± Standard Deviation; otherwise, it was described using the median and interquartile range (IQR). Independent samples t test of variance was utilized to compare differences in quantitative indices between groups unless the prerequisites were not met, in which case the Mann-Whitney U rank sum test was employed. For qualitative data, the theoretical frequency distribution was observed, and depending on the specific situation, either the χ2 test or Fisher's exact probability test method was used. Hierarchical data was statistically analyzed using the Kruskal-Wallis H rank sum test. Intention-to-treat (ITT) and per-protocol (PP) analyses were performed. Single-multifactorial logistic regression analysis was used to identify independent risk factors for patients with unsuitable LPLC and calculate the area under the curve (AUC) of the receiver operating characteristics (ROC) and Youden's index (sensitivity + specificity − 1), which in turn led to the calculation of the critical value. Statistical significance was defined as P < .05. The collected data were analyzed using the SPSS statistical program (version 21.0).

Characteristics of Patients A total of 238 patients who underwent LC during the study period were included in this study. After exclusion, 200 patients were randomized, of which 100 were assigned to LPLC and 100 to SPLC, as shown in Figure 1. There were no significant differences in baseline characteristics. Baseline characteristics that were not significantly different between the 2 groups included mean age (51.97 ± 13.66 vs 53.00 ± 13.23, P = .589), mean body mass index (BMI) (24.97 ± 3.23 vs 24.87 ± 3.56, P = .840), median charlson comorbidity index (CCI) (2 [IQR 1–3] vs 2 [IQR 1–3], P = .617), right upper abdominal pressure (51% vs 51%, P = 1), Murphy’s sign (8% vs 10% P = .622), ASA classification (P = .276), gender (P = .660), and preoperative blood biochemical tests including liver function, renal function, and hematology (Table 1). No postoperative-related adverse events were observed in either group during the study period. Table 1. | Factor | LPLC (8 mmHg) (n = 100) | SPLC (12 mmHg) (n = 100) | P-Value | |---|---|---|---| | Age, mean (SD) | 51.97 ± 13.66 | 53.00 ± 13.23 | .589 | | Gender, n (%) | .660 | || | Male | 38 (38%) | 35 (35%) | | | Female | 62 (62%) | 65 (65%) | | | Diagnosis | .413 | || | Gallbladder stones without cholecystitis | 1 (1%) | 1 (1%) | | | Gallbladder stones with cholecystitis | 96 (96%) | 98 (98%) | | | Polypoid lesions of the gallbladder (including gallbladder adenomyosis) | 3 (3%) | 1 (1%) | | | BMI, mean (SD) | 24.97 ± 3.23 | 24.87 ± 3.56 | .840 | | ASA | .276 | || | I | 14 (14%) | 12 (12%) | | | II | 75 (75%) | 71 (71%) | | | III | 11 (11%) | 17 (17%) | | | CCI, median (IQR) | 2 (1,3) | 2 (1,3) | .617 | | Right upper abdominal tenderness | 51/49 | 51/49 | 1 | | Murphy’s syndrome | 8/92 | 10/90 | .622 | | History of abdominal surgery | 21/79 | 28/72 | .195 | | History of hypertension | 26/74 | 22/78 | .483 | | Ultrasound gallbladder wall thickness (cm), median (IQR) | 0.4 (0.3, 0.5) | 0.4 (0.3, 0.5) | .956 | | Preoperative assessments | ||| | Temperature (°C), median (IQR) | 36.5 (36.3, 36.5) | 36.5 (36.3, 36.5) | .963 | | Heart rate (bpm), median (IQR) | 80.5 (70.5 ,89) | 78 (72, 86.75) | .370 | | Breathing (breaths/minute), median (IQR) | 20 (20, 20) | 20 (20, 20) | .581 | | Systolic blood pressure (mmHg), mean (SD) | 134.98 ± 19.32 | 135.79 ± 19.67 | .769 | | Diastolic blood pressure (mmHg), mean (SD) | 78.45 ± 12.06 | 80.12 ± 12.59 | .339 | | WBC (109/L), median (IQR) | 6.12 (4.96, 7.18) | 6.14 (4.94, 8.13) | .475 | | PLT (109/L), median (IQR) | 180 (142, 245) | 195 (164.75, 249.25) | .123 | | NE%, median (IQR) | 66.9 (59.8, 72.9) | 65.15 (58.5, 73.98) | .794 | | ALT (U/L), median (IQR) | 28 (17.25, 47.5) | 25 (17, 42.75) | .357 | | AST (U/L), median (IQR) | 23 (18, 29.75) | 21.5 (17, 31) | .235 | | GGT (U/L), median (IQR) | 35 (18, 80.75) | 27 (17, 62) | .250 | | ALP (U/L), median (IQR) | 91.5 (72.75, 116) | 88.5 (68, 117) | .453 | | TP (g/L), median (IQR) | 70.85 (67.25, 73.78) | 70.55 (67.4, 74.28) | .950 | | ALB (g/L), median (IQR) | 43.1 (40.5, 45.48) | 43.1 (41.03, 45.18) | .795 | | TB (µmol/L), median (IQR) | 12.1 (9.13, 17.15) | 13 (8.63, 17.23) | .753 | | DB (µmol/L), median (IQR) | 3.9 (2.73, 5.48) | 3.7 (2.63, 5.2) | .757 | | TBA (µmol/L), median (IQR) | 3 (1.8, 5.03) | 2.85 (2.03, 5.4) | .698 | | UREA (mmol/L), median (IQR) | 4.95 (4.08, 6.18) | 4.88 (4.04, 6.33) | .842 | | CREA (µmol/L), median (IQR) | 64.1 (54.13, 81.4) | 65.7 (55.7, 77.5) | .885 | | URIC (µmol/L), median (IQR) | 331.5 (279, 399.25) | 330 (287, 393) | .947 | | CRP (mg/L), median (IQR) | 1.5 (0.73, 5.4) | 1.2 (0.4, 3.5) | .338 | SPLC, standard pneumoperitoneum pressure laparoscopic cholecystectomy; LPLC, low pneumoperitoneum pressure laparoscopic cholecystectomy; BMI, body mass index; ASA, American Society of Anesthesiologists; CCI, Charlson Comorbidity Index; WBC, white blood cell count; PLT, platelet count; NE%; alt, alanine aminotransferase; AST, aspartate aminotransferase; GGT, glutamyl transpeptidase; ALP, alkaline phosphatase; ALB, albumin; TP, total protein; GLB, globulin; TB, total bilirubin; DB, direct bilirubin; TBA, total bile acids; CHE, cholinesterase; UREA, urea; CREA, creatinine; URIC, uric acid; CRP, C-reactive protein. ITT Outcome Analyses In the ITT analyses, no significant differences were found in postoperative hemodynamic or respiratory fluctuations (Table 2). LPLC group (median 46 minutes, IQR 38–58.75) and SPLC group (median 46.5 minutes, IQR 33.5–59.75) revealed comparable operation duration (P = .700). Postoperative pain assessment revealed statistically significant differences between the 2 groups. At the 12-hour postoperative timepoint, patients undergoing LPLC reported markedly lower visceral pain scores compared to those receiving SPLC (LPLC: 0.25 ± 0.72 vs SPLC: 0.55 ± 1.29, P = .046). At 48-hour postoperative timepoint, ITT analysis demonstrated significantly lower incisional pain scores in the LPLC group relative to SPLC group (LPLC: 1.62 ± 0.77 vs SPLC: 1.90 ± 0.80, P = .017) (Table 3, Figure 3). Significant intergroup differences emerged in postoperative liver function tests, with markedly elevated aspartate aminotransferase (AST) (P = .021) and alanine aminotransferase (ALT) (P = .001) levels in the SPLC group compared to LPLC (Table 4). Table 2. | ITT | PP | ||||| |---|---|---|---|---|---|---| | Factor | LPLC (8 mmHg) (n = 100) | SPLC (12 mmHg) (n = 100) | P-Value | LPLC (8 mmHg) (n = 83) | SPLC (12 mmHg) (n = 117) | P-Value | | At 8 postoperative hours | |||||| | Heart rate fluctuations (%), median (IQR) | 12.27 (5.7, 24.25) | 12.99 (6.43, 22.1) | .943 | 12.5 (5.62, 22.81) | 12.66 (6.1, 22.85) | .829 | | Respiratory fluctuations (%), median (IQR) | 0 (0, 5) | 0 (0, 5) | .305 | 0 (0, 5) | 0 (0, 5) | .479 | | Systolic blood pressure fluctuations (%), median (IQR) | 9.7 (3.6, 16.71) | 10.2 (4.12, 16.69) | .709 | 9.72 (4.17, 16.81) | 10 (4.03, 16.57) | .893 | | Diastolic blood pressure fluctuations (%), median (IQR) | 13.38 (5.25, 20.69) | 13.34 (6.35, 22.56) | .670 | 12.94 (4.82, 21.18) | 13.64 (6.54, 22.03) | .646 | | PADS | 9 (9, 10) | 9.5 (9, 10) | .670 | 9 (9, 10) | 9 (9, 10) | .895 | | At 12 postoperative hours | |||||| | Heart rate fluctuations (%), median (IQR) | 13.25 (5.84, 21) | 13.42 (8.6, 21) | .461 | 12.75 (5.36, 21.28) | 13.51 (8.6, 21.08) | .339 | | Respiratory fluctuations (%), median (IQR) | 0 (0, 5) | 0 (0, 5) | .779 | 5 (0, 5) | 5 (0, 5) | .867 | | Systolic blood pressure fluctuations (%), median (IQR) | 11.36 (4.02, 18) | 12.51 (4.28, 18) | .913 | 12.3 (4.26, 18.01) | 10.92 (3.98, 18.16) | .616 | | Diastolic blood pressure fluctuations (%), median (IQR) | 12.99 (3.97, 21) | 12.33 (5.65, 21) | .476 | 13.33 (3.9, 21.74) | 12.16 (5.52, 20.64) | .951 | | PADS | 9 (9, 10) | 9 (9, 10) | .602 | 9 (9, 10) | 9 (9, 10) | .950 | | Operation duration (minutes), median (IQR) | 46 (38, 58.75) | 46.5 (33.5, 59.75) | .700 | 43 (36, 54) | 48 (36, 61.5) | .313 | | Anesthesia duration (minutes), median (IQR) | 75 (65, 100) | 80 (66.25, 95) | .494 | 75 (64, 90) | 80 (69.5, 100) | .024 | | Pneumoperitoneum duration (minutes), median (IQR) | 35 (26, 51.5) | 38.5 (29, 52.75) | .338 | 32 (25, 45) | 43 (30, 56.5) | .002 | | Intraoperative bleeding (ml), median (IQR) | 5 (5, 5) | 5 (5, 10) | .780 | 5 (5, 5) | 5 (5, 10) | .001 | | CO2 consumption (L), median (IQR) | 89 (43.9, 228.5) | 107.5 (70.15, 244) | .347 | 79.5 (41.25, 207) | 106 (70.2, 262) | .152 | | Hospitalization duration (hours), median (IQR) | 120 (96, 168) | 120 (96, 144) | .655 | 120 (96, 168) | 120 (96, 168) | .715 | | Postoperative gallbladder wall thickness (cm), median (IQR) | 0.3 (0.2, 0.4) | 0.3 (0.2, 0.4) | .286 | 0.2 (0.2, 0.4) | 0.3 (0.2, 0.4) | .008 | Abbreviations: ITT, intention-to-treat analyses; PP, per-protocol analyses; PADS, post-anesthesia discharge score. Table 3. | ITT | PP | ||||| |---|---|---|---|---|---|---| | Factor | LPLC (8 mmHg) (n = 100) | SPLC (12 mmHg) (n = 100) | P-Value | LPLC (8 mmHg) (n = 83) | SPLC (12 mmHg) (n = 117) | P-Value | | Incisional pain scores | |||||| | 1 hour | 1.24 ± 1.65 | 1.14 ± 1.47 | .651 | 1.14 ± 1.58 | 1.22 ± 1.55 | .729 | | 4 hours | 1.67 ± 1.58 | 1.89 ± 1.43 | .302 | 1.57 ± 1.56 | 1.93 ± 1.45 | .091 | | 8 hours | 1.69 ± 1.6 | 1.87 ± 1.64 | .426 | 1.63 ± 1.67 | 1.89 ± 1.58 | .262 | | 12 hours | 0.97 ± 1.22 | 1.21 ± 1.68 | .251 | 0.88 ± 1.17 | 1.24 ± 1.65 | .072 | | 24 hours | 2.12 ± 1.07 | 2.32 ± 1.02 | .178 | 2 ± 1.04 | 2.38 ± 1.03 | .012 | | 48 hours | 1.62 ± 0.77 | 1.9 ± 0.8 | .017 | 1.55 ± 0.73 | 1.91 ± 0.81 | .003 | | 72 hours | 1.48 ± 0.77 | 1.6 ± 0.7 | .672 | 1.44 ± 0.7 | 1.59 ± 0.8 | .575 | | Visceral pain scores | |||||| | 1 hour | 0.45 ± 0.98 | 0.49 ± 1.34 | .809 | 0.48 ± 1.03 | 0.46 ± 1.26 | .904 | | 4 hours | 0.5 ± 0.98 | 0.47 ± 0.96 | .827 | 0.49 ± 0.93 | 0.48 ± 1 | .912 | | 8 hours | 0.41 ± 1.02 | 0.6 ± 1.26 | .255 | 0.39 ± 1.02 | 0.59 ± 1.23 | .193 | | 12 hours | 0.25 ± 0.72 | 0.55 ± 1.29 | .046 | 0.18 ± 0.57 | 0.56 ± 1.27 | .005 | | 24 hours | 0.45 ± 1.07 | 0.51 ± 0.99 | .681 | 0.43 ± 1.04 | 0.51 ± 1.02 | .593 | | 48 hours | 0.1 ± 0.52 | 0.18 ± 0.61 | .315 | 0.12 ± 0.58 | 0.16 ± 0.56 | .705 | | 72 hours | 0.08 ± 0.4 | 0 | .535 | 0.11 ± 0.47 | 0 | .331 | | Shoulder pain scores | |||||| | 1 hour | 0.07 ± 0.36 | 0.05 ± 0.36 | .693 | 0.08 ± 0.39 | 0.04 ± 0.33 | .417 | | 4 hours | 0.11 ± 0.47 | 0.04 ± 0.32 | .217 | 0.13 ± 0.51 | 0.03 ± 0.29 | .118 | | 8 hours | 0.12 ± 0.52 | 0.19 ± 0.92 | .517 | 0.14 ± 0.57 | 0.16 ± 0.85 | .858 | | 12 hours | 0.04 ± 0.28 | 0.08 ± 0.37 | .396 | 0.02 ± 0.22 | 0.09 ± 0.39 | .152 | | 24 hours | 0.54 ± 0.93 | 0.68 ± 1.13 | .338 | 0.51 ± 0.86 | 0.68 ± 1.13 | .209 | | 48 hours | 0.13 ± 0.48 | 0.27 ± 0.73 | .131 | 0.14 ± 0.48 | 0.25 ± 0.7 | .206 | | 72 hours | 0.04 ± 0.2 | 0 | .535 | 0 | 0.06 ± 0.24 | .332 | | Postoperative ketorolac (mg) | .328 | .083 | |||| | 30 mg | 26 (26%) | 20 (20%) | 22 (26%) | 22 (19%) | || | 60 mg | 2 (2%) | 2 (2%) | 4 (5%) | 2 (2%) | || | Postoperative PCIA | 54/46 | 51/49 | .323 | 34/49 | 61/56 | .120 | | Nausea/vomit | 9 (11%) | 8 (8%) | .800 | 9 (11%) | 8 (7%) | .314 | | Drainage, n (%) | 15 (15%) | 16 (16%) | .845 | 6 (7.2%) | 25 (21.4%) | .007 | Abbreviations: ITT, intention-to-treat analyses; PP, per-protocol analyses; PCIA, patient-controlled intravenous analgesia. Table 4. | ITT | PP | ||||| |---|---|---|---|---|---|---| | Factor | LPLC (8 mmHg) (n = 100) | SPLC (12 mmHg) (n = 100) | P-Value | LPLC (8 mmHg) (n = 83) | SPLC (12 mmHg) (n = 117) | P-Value | | Postoperative WBC (109/L), median (IQR) | 7.5 (6.26, 9.05) | 7.69 (6.14, 9.27) | .814 | 7.47 (6.22, 8.85) | 7.73 (6.23, 9.54) | .723 | | Postoperative NE%, median (IQR) | 69.39 ± 10.97 | 69.73 ± 8.26 | .807 | 68.9 (62.7, 75.8) | 69 (65.4, 76.05) | .419 | | Postoperative ALT (U/L), median (IQR) | 40 (26, 63.75) | 50 (36, 69) | .021 | 40 (25, 64) | 49 (36, 69) | .033 | | Postoperative AST (U/L), median (IQR) | 26 (21, 39) | 34.5 (26.25, 47.75) | .001 | 26 (21, 39) | 33 (25.5, 46) | .007 | | Postoperative GGT (U/L), median (IQR) | 35 (17.25, 84.25) | 33.5 (18, 72.25) | .683 | 31 (17, 69) | 36 (18, 82.5) | .498 | | Postoperative ALP (U/L), median (IQR) | 86.5 (69.5, 111.75) | 86 (66.25, 108.25) | .678 | 86 (68, 111) | 87 (68.5, 112) | .542 | | Postoperative ALB (g/L), median (IQR) | 37.55 (35.4, 39.88) | 37.6 (35.7, 40.1) | .870 | 38.1 (36, 39.9) | 37.4 (35.3, 40) | .242 | | Postoperative PLT (109/L), median (IQR) | 178.5 (142, 229) | 184 (148.75, 237.5) | .536 | 185.02 ± 66.44 | 198.19 ± 72.78 | .193 | | Postoperative TB (µmol/L), median (IQR) | 23.76 ± 71.1 | 17.14 ± 10.04 | .357 | 14.2 (10.2, 18.5) | 14.7 (10, 19.5) | .892 | | Postoperative CRP (mg/L), median (IQR) | 24.15 (11.6, 50.15) | 26.2 (8.03, 57.05) | .961 | 21.15 (11.15, 41.28) | 33.4 (9.65, 69.7) | .077 | Abbreviations: ITT, intention-to-treat analyses; PP, per-protocol analyses; SPLC, standard pneumoperitoneum pressure laparoscopic cholecystectomy; LPLC, low pneumoperitoneum pressure laparoscopic cholecystectomy; WBC, white blood cell count; PLT, platelet count; NE%, neutrophil percentage; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, glutamyl transpeptidase; ALP, alkaline phosphatase; ALB, albumin; TB, total bilirubin; CRP, C-reactive protein. PP Outcome Analyses In the PP analyses, no significant difference in surgical duration was found between LPLC group (median 43 minutes, IQR 36–54) and SPLC (median 48 minutes, IQR 36.00–61.50) (P = .313). In patients receiving SPLC, prolonged anesthesia duration, extended pneumoperitoneum time, increased intraoperative blood loss, and greater postoperative gallbladder wall thickness were observed (Table 2). These findings were primarily attributed to the inclusion of patients unsuitable for LPLC. Additionally, postoperative pain assessment revealed statistically significant differences between the 2 groups. The drainage rate was significantly higher in the SPLC group compared to the LPLC group (21.4% vs 7.2%, P = .007). At the 12-hour postoperative assessment, visceral pain scores differed significantly between groups (LPLC: 0.18 ± 0.57 vs SPLC: 0.56 ± 1.27, P = .005). Incision pain scores differed significantly between groups at 24 hours (LPLC: 2.00 ± 1.04 vs SPLC: 2.38 ± 1.03, P = .012) and 48 hours (LPLC: 1.55 ± 0.73 vs SPLC: 1.91 ± 0.81, P = .003) (Table 3, Figure 3). Postoperative liver function test revealed significant differences between-group differences in AST (P = .033) and ALT (P = .007) levels (Table 4). Both PP and ITT analyses demonstrated no statistically significant differences between groups in shoulder pain scores, postoperative analgesic pump utilization, or additional analgesics requirements (all P > .05). Univariate and Multivariate Analyses to Identify Factors Associated with Low-Pressure Unsuitable Patients In most cases, surgeon satisfaction with the view at low pressure was consistent with the standard pressure group. However, 17 patients (17%) in the LPLC group still required intraoperative pressure increase to 12 mmHg for procedural safety. Indications included: severe adhesions (n = 5), hemostasis challenges (n = 6), inadequate surgical exposure (n = 5), and gallbladder edema (n = 1). Consequently, 83 patients underwent surgery at 8 mmHg, while 100 procedures were completed at 12 mmHg. Seventeen cases required intraoperative pressure adjustment (Figure 1). Using both univariate and multivariate analyses, we identified significant factors associated with intraoperative pressure transitioning from 8 to 12 mmHg. Univariate analysis revealed that higher preoperative neutrophil percentage (NE%) and preoperative C-reactive protein (CRP) were associated with pressure transition (Table 5). On multivariate analysis, preoperative CRP (odds ratio [OR] 1.053, 95% confidence interval [CI] 1.007–1.102, P = .023) was identified as the unique independent predictor of intraoperative pressure transition (Table 5). ROC curve analysis demonstrated that preoperative CRP provided moderate predictive value for intraoperative pressure transition (AUC = 0.704, 95% CI 0.548–0.860), exhibiting high specificity (93.1%) but limited sensitivity (43.8%) at the optimal cutoff (Figure 2). The Youden's index-optimized cutoff of 12.70 mg/L represents the threshold maximizing both sensitivity and specificity for predicting 8→12 mmHg transitions (Youden’s index = 0.369) (Table 6). Based on our ROC analysis, we established preoperative CRP ≥12.70 mg/L as a high-risk threshold for intraoperative pressure transitioning from 8 to 12 mmHg. For these high-risk patients LC, we recommend against initial low pneumoperitoneal pressure. Conversely, patients with preoperative CRP <12.70 mg/L classified as low risk, making them appropriate candidates for initial low-pressure pneumoperitoneum. Table 5. | Univariate Analyses | Multivariate Analyses | ||||| |---|---|---|---|---|---|---| | Transit or Not | |||||| | Factor | No | Yes | Χ2/t/z | P | OR (95% CI) | P | | Gender | |||||| | Male | 29 (34.9%) | 9 (52.9%) | 1.941 | .164 | || | Female | 54 (65.1%) | 8 (47.1%) | |||| | History of previous seizures | |||||| | Yes | 52 (62.7%) | 8 (47.1%) | 1.492 | .232 | || | No | 31 (37.3%) | 9 (52.9%) | |||| | Preoperative analgesia | |||||| | Yes | 6 (7.4%) | 3 (17.6%) | 1.766 | .184 | || | No | 75 (92.6%) | 14 (82.4%) | |||| | Preoperative antispasmodic | |||||| | Yes | 6 (7.5%) | 0 (0%) | 1.359 | .244 | || | No | 74 (92.5%) | 17 (100%) | |||| | History of abdominal surgery | |||||| | Yes | 18 (21.7%) | 3 (17.6%) | 0.139 | .709 | || | No | 65 (78.3%) | 14 (82.4%) | |||| | Surgical location | |||||| | Upper abdomen | 3 (16.7%) | 0 (0%) | 0.583 | .445 | || | Lower abdomen | 15 (83.3%) | 3 (100%) | |||| | Number of operations | |||||| | 1 | 14 (77.8%) | 2 (66.7%) | 0.175 | .676 | || | 2 | 4 (22.2%) | 1 (33.3%) | |||| | Surgical procedure | |||||| | Open laparotomy | 10 (55.6%) | 1 (52.4%) | 0.509 | .476 | || | Laparoscopic surgery | 8 (44.4%) | 2 (66.7%) | |||| | Right upper abdominal tenderness | |||||| | Yes | 42 (50.6%) | 9 (52.9%) | 0.031 | .860 | || | No | 41 (49.4%) | 8 (47.1%) | |||| | Murphy's syndrome | |||||| | Yes | 6 (7.2%) | 2 (11.8%) | 0.394 | .530 | || | No | 77 (92.8%) | 15 (88.2%) | |||| | ASA | |||||| | I | 10 (12%) | 4 (23.5%) | 2.886 | .239 | || | II | 65 (78.3%) | 10 (58.8%) | |||| | III | 8 (9.6%) | 3 (17.6%) | |||| | Age, mean (SD) | 51.61 ± 13.57 | 53.71 ± 14.36 | 0.573 | .179 | || | BMI, mean (SD) | 24.87 ± 3.22 | 25.47 ± 3.36 | 0.678 | .638 | || | Number of attacks, median (IQR) | 3 (2, 3) | 2 (1, 3) | 1.470 | .166 | || | Duration of preoperative abdominal pain (day), median (IQR) | 5.5 (2, 9.25) | 5.5 (4.25, 10.75) | 0.905 | .365 | || | ACCI, median (IQR) | 2 (1, 3) | 2 (0.5, 4) | 0.094 | .925 | || | Ultrasound gallbladder wall thickness (cm), median (IQR) | 0.4 (0.3, 0.5) | 0.5 (0.4, 0.55) | 1.619 | .106 | || | Preoperative WBC (109/L), median (IQR) | 6.06 (4.82, 6.81) | 7.4 (5.49, 8.44) | 1.786 | .074 | || | Preoperative PLT (109/L), mean (SD) | 189.98 ± 64.69 | 199.29 ± 72.56 | 0.529 | .598 | || | Preoperative NE%, median (IQR) | 64.95 (59.63, 70.08) | 74.4 (67, 82.2) | 2.793 | .005 | 0.999 (1.007–1.102) | .949 | | Preoperative ALT (U/L), median (IQR) | 28 (17, 49) | 27 (17.5, 40.5) | 0.257 | .797 | || | Preoperative AST (U/L), median (IQR) | 23 (19, 30) | 19 (16.5, 30) | 1.319 | .187 | || | Preoperative GGT (U/L), median (IQR) | 33 (16, 75) | 53 (25, 126.5) | 1.648 | .099 | || | Preoperative ALP (U/L), median (IQR) | 91 (72, 117) | 99 (80, 115) | 0.748 | .454 | || | Preoperative ALB (g/L), median (IQR) | 43.3 (40.6, 45.9) | 41.9 (37.7, 44.35) | 1.478 | .140 | || | Preoperative TB (µmol/L), median (IQR) | 12.2 (9.2, 16.7) | 10 (7.75, 17.9) | 0.606 | .545 | || | Preoperative CRP (mg/L), median (IQR) | 1.35 (0.7, 3.15) | 5 (1.05, 48.50) | 2.544 | .011 | 1.053 (0.980–1.019) | .023 | Abbreviation: SPLC, standard pneumoperitoneum; Pressure, laparoscopic cholecystectomy; LPLC, low pneumoperitoneum pressure laparoscopic cholecystectomy; BMI, body mass Index; ASA, American Society of Anesthesiologists; WBC, white blood cell count; PLT, platelet count; NE%, neutrophil percentage; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, glutamyl transpeptidase; ALP, alkaline phosphatase; ALB, albumin; TB, total bilirubin; CRP, C-reactive Protein. Table 6. | Factor | Truncation Value | AUC | P | Sensitivity (%) | Specificity (%) | |---|---|---|---|---|---| | Preoperative CRP (mg/L) | 12.70 | 0.704 | .011 | 43.8 | 93.1 | Abbreviations: CRP, C-reactive protein; AUC, area under the ROC curve.

Most laparoscopic surgery is performed using pneumoperitoneum, which is created by injecting carbon dioxide into the abdominal cavity using a mechanical insufflator. Maintaining positive intra-abdominal pressure during laparoscopic procedures represents a nonphysiological state that may compromise cardiovascular, pulmonary, and intra-abdominal organ function.3,23 To minimize the adverse effects of pneumoperitoneum, innovative surgical approaches have been developed including gasless techniques for abdominal wall elevation and low-pressure pneumoperitoneum.21,24,25 Emerging clinical evidence indicates that low-pressure pneumoperitoneum could significantly reduce postoperative pain compared to standard pressure pneumoperitoneum, potentially enhancing patients’ quality of life during recovery.14,25–28 While biomechanical theory predicts that low-pressure pneumoperitoneum could reduce postoperative pain by minimizing peritoneal stretch, some studies report conflicting results.12,29 While low-pressure pneumoperitoneum is feasible in 90–94.6% of cases, conversion to standard pressure may be required in patients with poor exposure or hemodynamic instability.2,12 For young surgeons—particularly those with limited experience—insufficient preoperative exposure or intraoperative bleeding could compromise their comprehensive grasp of the surgical procedure and subsequently affect the stability of their subsequent maneuvers during the procedure.17 This study aims to compare clinical outcomes between laparoscopic port approaches (LPLC vs SPLC) and identify predictors of conversion. To our knowledge, this study represents the first analysis of patients requiring intraoperative pneumoperitoneum pressure transition, providing objective criteria to guide preoperative pressure selection and enable individualized pneumoperitoneum management. In this study, we found that 17% (17/100) of patients in the LPLC group required conversion to standard-pressure pneumoperitoneum. The primary reasons for transition included: severe adhesions (n = 5), hemostasis challenges (n = 6), inadequate surgical exposure (n = 5), and gallbladder edema (n = 1). Severe cholecystitis, manifesting as marked gallbladder wall edema and vascular congestion, significantly obscures Calot's triangle anatomy and increases hemorrhage risk during dissection.30 CRP serves as a biomarker of systemic inflammation and has been established as an independent predictor for both conversion to open cholecystectomy and difficult LC.31,32 Another research team at our institution also identified preoperative CRP levels as an independent predictor of prolonged operation (OR 1.018, 95% CI: 1.006–1.029, P = .003).33 Moreover, prior research also identified preoperative CRP levels (>5 mg/dL) as a potential predictor for intraoperative conversion in elective LC.34 In our multivariate analysis of converted cases, elevated preoperative CRP level is significantly associated with intraoperative conversion from low-pressure to standard-pressure pneumoperitoneum (OR 1.053, 95% CI 1.007–1.102, P = .023) (Table 5). ROC curve analysis revealed that preoperative CRP levels provided moderate predictive value for intraoperative conversion from low- to standard-pressure pneumoperitoneum (AUC = 0.704, 95% CI 0.548–0.860). Based on Youden’s index analysis, we propose 12.70 mg/L as the optimal preoperative CRP cutoff for predicting failed low-pressure pneumoperitoneum maintenance (sensitivity: 43.8%, specificity: 93.1%) (Table 6). Postoperative CRP elevation reflects the systemic stress response and correlates with surgical trauma severity.35 Elevated postoperative CRP levels can also predict the severity of postoperative complications including severe postoperative pain.36 Our comparative analysis of systemic stress response, as measured by serum CRP levels, revealed no significant differences between the 2 study groups (ITT: P = .961, PP: P = .077) (Table 4). These findings align with previous reports by Shoar et al35 and Sari and Sevinc.37 Obesity (BMI ≥30 kg/m2) and overweight status (BMI 25–30 kg/m2) are well-established independent risk factors for conversion from laparoscopic to open cholecystectomy.32 This increased risk stems from multiple technical challenges, including: (1) higher pneumoperitoneum requirements; (2) impaired liver retraction due to steatosis stiffness; (3) difficult trocar placement and restricted instrument maneuverability; (4) heavy fat infiltration in the Calot's triangle hindering critical anatomical landmarks.32 However, our analysis did not find significant difference in BMI between the transit and no-transit groups (25.47 ± 3.36 vs 24.87 ± 3.22, P = .638) (Table 5). This suggests that BMI may not be a risk factor for pneumoperitoneum pressure transition, though we cannot exclude the possibility of a type II error given the relatively small sample size of our transit group (n = 17). Postoperative pain, including incisional, visceral, and shoulder pain, could affect patient comfort, recovery, potential for same day discharge and overall satisfaction.38 Previous studies have shown that incisional pain occurs more frequently and with greater intensity than visceral pain, which in turn is more common and severe than shoulder pain. Additionally, pain intensity peaks during the first few postoperative hours and gradually subsides within 2 to 3 days.39 Local anesthetic infiltration at trocar sites could reduce postoperative pain in LC patients, this analgesic effect appears to be transient, typically lasting no more than 6–12 hours postoperatively.40,41 In this study, local anesthetics were not administered at trocar puncture sites. Our results have shown that the LPLC group presented significantly lower incisional pain scores at 48 postoperative hours compared to the SPLC group (ITT: P = .017, PP: P = .003). Fathi et al42 demonstrated that impaired drain function exacerbated pain within 24 postoperative hours. While ITT analysis showed no significant intergroup difference in drainage rate (P = .845), PP analysis showed a significantly higher drainage rate in SPLC group compared to LPLC group (21.4% vs 7.2%, P = .007). This difference was primarily attributed to the included patients who exhibited severe local inflammation and adhesions in the transition group. The higher drainage rate in SPLC group was associated with significantly increased incisional pain scores at 24 postoperative hours (LPLC: 2 ± 1.04 vs SPLC: 2.38 ± 1.03, P = .012) (Table 3). Vijayaraghavan et al administered standardized local anesthetic infiltration at all trocar sites and subsequently concluded that postoperative pain was primarily visceral in origin.43 Meanwhile, Joris et al identified visceral pain as the primary source of early postoperative discomfort in LC patients, noting its rapid decline within 24 hours.44 In our study, while ITT and PP analyses at 12 hours postoperatively demonstrated significant differences in visceral pain between groups (P = .046 and P = .005, respectively), incisional pain scores consistently exceeded visceral pain scores across all time points. These findings suggest that postoperative pain following LC primarily originates from incisional sites. Despite LC being a minimally invasive procedure with small incisions, the postoperative supine position may impair adequate relaxation of the rectus abdominis muscle, potentially exacerbating incisional pain. The pathophysiology of postlaparoscopic shoulder pain is primarily mediated by diaphragmatic irritation and phrenic nerve stimulation secondary to CO2 pneumoperitoneum.45 A prospective randomized controlled study revealed a lower incidence of postlaparoscopic shoulder pain in LPCL group (9 mmHg) compared to SPLC group (13 mmHg) (7.14% vs 28.57%, P = .031). Notably, shoulder pain intensity was lower in the LPCL group, though this difference did not reach statistical significance.46 Similarly, our study did not find significant difference in shoulder pain intensity between the LPLC and SPLC. This finding contrast with studies by Yasir et al47 and Bhattacharjee et al11 which reported significantly lower postoperative shoulder pain scores in low-pressure pneumoperitoneum (8–10 mmHg) compared to standard-pressure pneumoperitoneum (14 mmHg). The higher initial insufflation pressures in their SPLC group (14 mmHg) may explain this discrepancy, as elevated intra-abdominal pressure is known to increase diaphragmatic irritation and phrenic nerve stimulation. And Bhattacharjee et al did not employ abdominal compression maneuvers or active suctioning of residual CO2 prior to trocar removal.11 This methodological difference may explain why they observed a more significant difference in shoulder pain between LPLC (9–10 mmHg) and SPLC (14 mmHg) groups at both 8 and 24 hours postoperatively. Compared to low-pressure pneumoperitoneum, high-pressure pneumoperitoneum easily induces fluctuations in hemodynamic parameters.48 Low-pressure pneumoperitoneum reduces hemodynamic instability without compromising surgical comfort or perioperative safety.49,50 In the PP analyses, operative duration was comparable between groups (P = .313), while intraoperative blood loss was significantly reduced with low-pressure pneumoperitoneum relative to SPLC (P = .001). Regarding liver function, Gupta et al51 have demonstrated that high-pressure pneumoperitoneum could lead to significantly postoperative ALT (68.14 ± 31.46 vs 42.75 ± 17.94, P = .001) and AST (66.08 ± 25.59 vs 42.24 ± 14.73, P = .001) increase at postoperative day 1 compared to low-pressure pneumoperitoneum. Our study revealed significantly delayed recovery of ALT (P = .021) and AST (P = .001) levels postoperatively in SPLC group compared to LPLC group, further suggesting high-pressure pneumoperitoneum may contribute to transient postoperative hepatic dysfunction. Thus, we recommend LPLC as the preferred approach for those patients with underlying liver disease (chronic hepatitis, alcoholic or metabolic dysfunction–associated steatotic liver disease) to minimize perioperative hepatic stress. Further prospective studies focusing on patients with chronic liver disease are needed to validate these clinical implications. The safety and feasibility of early discharge ≤24 hours after LC is now well established due to surgeons' extensive experience in laparoscopic surgery, significant advances in various laparoscopic surgical devices, and new anesthesia and analgesia techniques.52–56 Postoperative pain is one of the reasons for delayed discharge >24 hours in day-case surgery.56–58 Our findings demonstrate that LPLC exhibits comparable operative duration and safety profiles to SPLC as measured by the Post-Anesthetic Discharge Scoring System (PADSS) (ITT: P = .602, PP: P = .950). In Asia, day-case LC adoption has been limited due to concerns about postoperative complications.59 Specifically, issues such as postoperative nausea, vomiting, and persistent pain are significant risk factors that hinder same-day discharge and contribute to unplanned hospital admissions.60 Our results, which demonstrated clinical advantages of LPLC including reduced postoperative pain and lower postoperative hepatic stress, suggested that it could serve as a preferred surgical approach to facilitate safe and effective day-case surgery protocols. A key limitation of this study is the inherent subjectivity of pain assessment, as patient-reported outcomes may be influenced by individual variations in pain tolerance. Also, since we have used relatively fixed pneumoperitoneal pressure values of 8 and 12 mmHg, is it possible in the future to use a flexible pneumoperitoneal pressure device to better regulate the pressure to achieve full exposure of the surgical area, and at the same time reduce the negative effects of high pressure? Future large-scale prospective studies are needed to systematically evaluate risk factors associated with intraoperative pneumoperitoneum pressure transitions.

The use of low-pressure pneumoperitoneum force (8 mmHg) for LC significantly reduces postoperative visceral and incisional pain. While maintaining adequate surgical exposure, LPLC demonstrates less impact on liver function with comparable safety and feasibility to SPLC. We recommend that patients with preoperative CRP ≥12.70 mg/L should carefully choose LPLC as the initial procedure. Footnotes Conflict of interests: none. Disclosure: none. Drs. Lu and Yue contributed equally to this paper. Funding sources: none. Ethical Review Grant Number: 2024CYFYIRB-BA-Mar03. Registration Number of the Chinese Clinical Trial Registry: ChiCTR2400086997.

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