Evaluation of thiol–disulfide homeostasis under low and standard pneumoperitoneum in elderly patients undergoing laparoscopic cholecystectomy: a prospective comparative study

Abstract

Background

This study aimed to evaluate the impact of different intra-abdominal pressure (IAP) levels on oxidative stress, as measured by thiol-disulfide homeostasis parameters, in geriatric patients undergoing laparoscopic cholecystectomy.

Methods

A total of 62 patients aged 65 years and older diagnosed with cholelithiasis were included. Patients were randomly assigned to either the low-pressure group (10 mmHg) or the high-pressure group (15 mmHg). Standard laparoscopic cholecystectomy was performed under general anesthesia by the same surgical team. Preoperative and postoperative blood samples were collected to evaluate oxidative stress parameters (native thiol, total thiol, disulfide), as well as basic biochemical markers (AST, ALT, urea, creatinine) and hematological indices (WBC, hemoglobin, hematocrit, platelet count).

Results

Postoperative AST levels were significantly higher in the high-pressure group compared to the low-pressure group (p = 0.031), while ALT differences were not statistically significant. Although disulfide and oxidized thiol ratios were higher in the high-pressure group preoperatively, no significant differences were observed between the groups postoperatively.

Conclusion

While higher intra-abdominal pressure may be associated with mild hepatic stress, it does not appear to cause significant oxidative imbalance in geriatric patients. Both low and high-pressure pneumoperitoneum levels can be used safely during laparoscopic cholecystectomy in elderly individuals, provided that appropriate perioperative management is ensured.

Introduction

Laparoscopic cholecystectomy is a widely preferred minimally invasive technique for treating gallbladder disease and is typically performed using carbon dioxide insufflation to create pneumoperitoneum. The standard intra-abdominal pressure (IAP) used during this procedure generally ranges from 12 to 16 mmHg. However, elevated IAP has been shown to adversely affect hemodynamics by altering splanchnic, hepatic, and renal perfusion. In response, low-pressure laparoscopy has been proposed as a safer alternative to minimize potential physiological disturbances. Yet, using reduced pressures may compromise the operative field visibility, potentially increasing the risk of intraoperative complications [1].

Particularly in complex cases, surgeons often prefer higher insufflation pressures to improve visualization. Elderly patients undergoing surgery for biliary pathology frequently present with more advanced gallstone disease and higher comorbidity burdens, resulting in increased rates of emergency procedures, open conversions, postoperative complications, and longer hospital stays compared to younger cohorts [2]. Therefore, assessing the safety and feasibility of laparoscopic cholecystectomy under varying pressure conditions in geriatric patients remains an important clinical question [3].

Elevated intra-abdominal pressure (IAP) resulting from pneumoperitoneum leads to significant hemodynamic changes by increasing systemic vascular resistance and reducing venous return, cardiac output, and stroke volume. The degree of these physiological alterations depends on the level and duration of pressure applied. As IAP rises, a decrease in visceral, splanchnic, portal, and renal perfusion may occur [4, 5]. This reduction in organ perfusion, particularly within the abdominal cavity, is known to trigger oxidative stress mechanisms. It enhances the production of reactive lipid and protein oxidation byproducts while simultaneously impairing the activity of antioxidant enzymes and the systemic availability of protective micronutrients such as vitamins [5, 6].

Several techniques have been developed to assess oxidative stress levels during surgical procedures. Among them, thiol-disulfide homeostasis serves as a reliable biochemical marker, reflecting the dynamic balance between oxidants and antioxidants. The method introduced by Erel and Neselioglu enables the quantitative measurement of native thiol, total thiol, and disulfide levels in plasma. A reduction in both native and total thiol concentrations accompanied by an elevation in disulfide levels indicates a shift toward oxidative stress [7].

In our study, we selected intra-abdominal pressures of 10 mmHg and 15 mmHg to represent low- and standard-pressure pneumoperitoneum, respectively. This choice is supported by clinical evidence and consensus in laparoscopic surgery. Current guidelines generally define low-pressure insufflation as values below 10–12 mmHg, while standard-pressure insufflation is typically set at 14–15 mmHg during laparoscopic cholecystectomy [8]. These pressure settings are widely used in routine surgical practice and are known to have different physiological and oxidative stress implications, particularly in elderly patients. During laparoscopic cholecystectomy, the tendency to operate under high intra-abdominal pressure to reduce surgery-related complications is considered risky, particularly in elderly patients, due to increased oxidative stress-related non-surgical complications. In this study, we aimed to determine whether different intra-abdominal pressure applications during laparoscopic cholecystectomy for gallstone disease in elderly patients induce oxidative stress by evaluating their effects on THIOS (Thiol-Disulfide Homeostasis) balance. Thiol–disulfide homeostasis parameters were indeed the primary outcome measures, while liver enzymes and hematological parameters were considered secondary endpoints.

Materials and methods

Study design and patient selection

After obtaining Local Ethical Committee approval (Date: 15.03.2023, No: 2023/08) and written consent, this study was carried out at Gaziantep University Hospital, from April 2023 until December 2024. The principles of the Declaration of Helsinki were obeyed at all stages. Demographic data (age, gender, body mass index), ASA (American Society of Anesthesiologists) physical status of the patients, duration of operation, postoperative complication (intraoperative and first month) and comorbidity were recorded. Patients with alcohol or drug addiction, patients using medicine that might affect the oxidation system, and patients with abnormal preoperative blood levels, chronic renal or hepatic failure, acute cholecystitis and converted to open surgery were excluded from the study.

We included 62 patients diagnosed with gallbladder stone who were scheduled to undergo laparoscopic cholecystectomy under general anesthesia. An a priori power analysis was conducted using G*Power 3.1 software. With an effect size of 0.8, alpha of 0.05, and power of 0.80, the required sample size was calculated to be 52. Therefore, the included sample size of 62 patients was deemed sufficient to detect meaningful differences. The patients were assigned to one of 2 groups. Group A (n:31) was the low-pressure (10 mmHg) group and Group B (n:31) was the high-pressure (15 mmHg) group. Patients were randomly assigned to either the low-pressure or standard-pressure group using a computer-generated sequence to minimize selection bias. Allocation concealment was achieved using sealed opaque envelopes, which were opened immediately before the procedure. Premedication was not administered and upon admission to the operating room 5 cc blood samples were collected to evaluate thiol disulfide homeostasis after intravenous access was established. After the induction of general anesthesia, laparoscopic cholecystectomy was performed on both patient groups using the same technique by the same surgical team, with low and high intra-abdominal pressure applications. Due to the nature of the surgical procedure, blinding of the operating team was not feasible; however, outcome assessors and laboratory staff who performed the biochemical analyses were blinded to group allocations to reduce measurement bias. An anesthesia workstation with an electronic vaporizer (Aisys™, GE-Healthcare, Chalfont St Giles/Buckinghamsire/UK) was used. In addition, a standardized laparoscopic system (Richard Wolf GmbH, Knittlingen, Germany) was employed for all procedures to ensure consistency in intra-abdominal pressure and insufflation delivery. A 5 cc venous blood sample was obtained at the end of surgery.

Collection of materials

Blood samples were collected from volunteers in tubes containing gel serum tubes (Becton Dickinson, UK). Blood samples which were placed in gel serum tubes, allowed to coagulate for about 20 min at room temperature. After coagulation, blood samples were centrifuged for 10 min at 4000 rpm. Serum samples were stored at − 80 °C until the study day.

Serum thiol-disulfide homeostasis parameters measurement/calculation

The thiol-disulfide homeostasis parameters in serum were assessed using a fully automated method. This method is based on the principle of reducing reducible disulfide bonds (–S–S–) to functional thiol (–SH) groups with the aid of sodium borohydride (NaBH₄). Initially, disulfide bonds are reduced by NaBH₄ to form free functional thiol groups. Subsequently, the excess NaBH₄ is completely eliminated from the reaction medium using formaldehyde. Finally, the total thiol content of the sample—including both native and reduced thiol groups—is quantified using a modified Ellman's reagent [7].

The homeostasis parameters included native thiol (NT), total thiol (TT), disulfide levels, and the ratios of disulfide/NT, disulfide/TT, and NT/TT. NT and TT concentrations were measured in µmol/L using a commercial assay kit (Rel Assay Diagnostics, Turkey) on a Beckman Coulter AU480 autoanalyzer. Disulfide levels were calculated using the following formula: Disulfide = (Total Thiol–Native Thiol)/2. This method reflects the amount of oxidized thiol groups and is a validated approach for assessing thiol–disulfide homeostasis. Subsequently, the percentage values of thiol oxidation (NT/disulfide), oxidized thiol (disulfide/TT), and reduced thiol (NT/TT) were determined [9].

Statistical analysis

Descriptive statistics for the data obtained from the study were presented as mean and standard deviation for numerical variables, and as frequency and percentage for categorical variables. The normality of preoperative and postoperative laboratory and oxidative stress parameters was assessed using the Shapiro–Wilk test. Comparisons of these variables between the study groups were conducted using the Mann–Whitney U test. Within-group comparisons of preoperative and postoperative values were analyzed using the Wilcoxon signed-rank test. In addition, group comparisons for demographic characteristics were performed using the Chi-square test for categorical variables and the independent samples t-test (Student’s t-test) for continuous variables. Additionally, delta (Δ) values representing the differences between postoperative and preoperative measurements were calculated for each parameter. All statistical analyses were performed using SPSS version 22.0 (IBM Corp., Armonk, NY, USA). A p-value of less than 0.05 was considered statistically significant.

Results

The analyses of patients’ demographic and clinical characteristics are presented in Table 1. There were no statistically significant differences between the groups in terms of sex, ASA physical status, postoperative complications, comorbidity, medication, or smoking status (p > 0.05) (Table 1). Similarly, no significant differences were observed between the groups regarding age, body weight, and duration of surgery (Table 1).

Table 1.

Demographics and clinical characterics of patients

		Group A: 10 mmHg		Group B: 15 mmHg		p value
		n	% or Mean ± SD	n	% or Mean ± SD
Gender	Female	22	71	24	77.4	0.562
	Male	9	29	7	22.6
ASA Score	1	2	6.5	2	6.5	0.147
	2	13	41.9	6	19.4
	3	16	51.6	23	74.2
Postoperative complication	No	31	100	31	100	–
	Yes	0	0	0	0
Mortality within 30 days	No	31	100	31	100	–
	Yes	0	0	0	0
Morbidity within 30 days	No	31	100	31	100	–
	Yes	0	0	0	0
Comorbidity	No	8	25.8	6	19.4	0.544
	Yes	23	74.2	25	80.6
Medication	No	9	29	8	25.8	0.776
	Yes	22	71	23	74.2
Smoking	No	26	83.9	25	80.6	0.740
	Yes	5	16.1	6	19.4
Age (Years)	–	31	69.13 ± 4.83	31	68.68 ± 4.16	0.695
Weight (kg)	–	31	79.84 ± 15.38	31	84.42 ± 18.35	0.291
Duration of operation (min)	–	31	57.03 ± 17.99	31	63.06 ± 23.62	0.262

(*p < 0.05; Chi-square test for categorical variables, Student’s t-test for continuous variables. ASA American Society of Anaesthesiologists, BMI Body Mass Index, SD Standard Deviation, min minute)

Preoperative and postoperative blood samples were obtained from all patients to evaluate the levels of direct bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, urea, creatinine, white blood cell (WBC) count, neutrophil count, lymphocyte count, hemoglobin, and platelet count. Statistical analyses were performed to compare these parameters both between groups and within each group, as well as to assess the preoperative-to-postoperative differences. Additionally, the differences between preoperative and postoperative values were calculated as delta (Δ) values for each parameter. These delta values were then statistically compared between the groups to evaluate the relative changes attributable to the intervention (Table 2). As shown in Table 2, there were no statistically significant differences in preoperative laboratory parameters between the low- and standard-pressure groups (p > 0.05) (Table 2). Among the postoperative values, only ALT and albumin levels showed statistically significant differences between the two groups (p < 0.05) (Table 2).

Table 2.

Laboratory parameters of patients

		Group A (n = 31) median [25–75%]	Group B (n = 31) median [25–75%]	p value
Direct bilirubin	preoperative	0.12 (0.08–0.18)	0.1 (0.07–0.17)	0.238
	postoperative	0.13 (0.1–0.25)	0.17 (0.12–0.2)	0.587
	p value	0.199	0.001*
	Δ (Post–Pre)	0.03 (− 0.04–0.07)	0.03 (0.01–0.09)	0.201
AST	preoperative	20 (18–23)	20 (16–26)	0.888
	postoperative	45 (27–97)	53 (45–76)	0.107
	p value	0.001*	0.001*
	Δ (Post–Pre)	13 (3–81)	32 (21–54)	0.031*
ALT	preoperative	17 (14–22)	19 (14–26)	0.356
	postoperative	33 (22–75)	52 (41–77)	0.043*
	p value	0.001*	0.001*
	Δ (Post–Pre)	14 (4–51)	31 (17–45)	0.054
Albumin	preoperative	40 (39–43)	41 (39–42)	0.898
	postoperative	37 (35–41)	36 (34–38)	0.042*
	p value	0.001*	0.001*
	Δ (Post–Pre)	3 (1–4)	5 (4–6)	0.001*
Urea	preoperative	33 (25–39)	30 (22–37)	0.554
	postoperative	29 (24–33)	29 (23–35)	0.849
	p value	0.087	0.600
	Δ (Post–Pre)	5 (− 1–8)	− 1 (− 4–6)	0.174
Creatinine	preoperative	0.77 (0.63–0.96)	0.7 (0.6–0.89)	0.307
	postoperative	0.65 (0.55–0.83)	0.62 (0.53–0.96)	0.921
	p value	0.001*	0.036*
	Δ (Post–Pre)	0.13 (− 0.03–0.22)	0.05 (− 0.03–0.14)	0.111
WBC	preoperative	7760 (6610–9140)	7760 (6670–9210)	0.762
	postoperative	10,710 (8010–13250)	11,390 (9060–13950)	0.364
	p value	0.001*	0.001*
	Δ (Post–Pre)	2980 (1270–5210)	3750 (1480–5960)	0.324
Neutrophil	preoperative	4510 (3550–5640)	4560 (3740–5610)	0.578
	postoperative	8390 (6550–10810)	10,370 (7450–12230)	0.215
	p value	0.001*	0.001*
	Δ (Post–Pre)	4060 (2190–6700)	4980 (3010–7370)	0.248
Lymphocyte	preoperative	2450 (1800–3010)	2380 (1790–2700)	0.468
	postoperative	1150 (760–1470)	930 (780–1130)	0.172
	p value	0.001*	0.001*
	Δ (Post–Pre)	1090 (700–1610)	1310 (640–1750)	0.871
Hemoglobin	preoperative	13.9 (12.8–14.7)	13.4 (12.5–14.6)	0.278
	postoperative	12.4 (11.5–13.9)	12.1 (11.3–13.6)	0.468
	p value	0.001*	0.001*
	Δ (Post–Pre)	1 (0.5–1.6)	1.1 (0.3–1.5)	0.921
Platelet	preoperative	274,000 (234,000–371000)	283,000 (246,000–357000)	0.668
	postoperative	227,000 (194,000–305000)	236,000 (204,000–271000)	0.720
	p value	0.001*	0.001*
	Δ (Post–Pre)	53,000 (27,000–79000)	56,000 (44,000–105000)	0.342

(*p < 0.05; Mann–Whitney U test; Wilcoxon test, Δ (Delta) values represent the difference between postoperative and preoperative levels for each parameter, AST aspartate aminotransferase, ALT alanine aminotransferase, WBC White blood cell)

In the statistical analysis of the calculated difference values between preoperative and postoperative measurements in both groups, a statistically significant difference was observed for AST and albumin levels (p < 0.05). No statistically significant differences were found for the remaining parameters in terms of the change (difference) between pre- and postoperative values (p > 0.05).

The measured values of thiol-disulfide homeostasis and their statistical comparisons for both patient groups are presented in Table 3. The parameters assessed included total thiol, native thiol, disulfide levels, and the calculated ratios: reduced thiol, oxidized thiol, and thiol oxidation. Statistical analyses were conducted both between groups and within each group for preoperative and postoperative measurements. To evaluate the dynamic changes in oxidative stress status, delta (Δ) values—representing the difference between postoperative and preoperative measurements—were calculated for each parameter. These delta values were statistically compared between the two groups. The analysis revealed no statistically significant differences between the groups or within groups regarding these parameters (p > 0.05). Effect size analysis using rank-biserial correlation (rrb) revealed small to moderate within-group changes in oxidative stress parameters. In Group A, a moderate effect was observed in disulfide levels (rrb: 0.402), while in Group B, small to moderate effects were noted in oxidized thiol (rrb: 0.342) and disulfide levels (rrb: 0.322). Although these changes did not reach statistical significance, the effect sizes suggest a mild oxidative response to pneumoperitoneum, potentially influenced by intra-abdominal pressure differences.

Table 3.

Preoperative and postoperative total thiol, native thiol, disulfide, reduced thiol, oxidized thiol and thiol oxidation values

		Group A (n = 31) median [25–75%]	Group B (n = 31) median [25–75%]	p value
Total thiol (µmol/L)	preoperative	277.09 (189.98–357.07)	316.64 (216.14–397.81)	0.379
	postoperative	293.45 (240.52–364.51)	310.39 (219.41–391.56)	0.994
	p	0.378	0.389
	rrb	0.182	0.177
	Δ (Post–Pre)	59.76 (− 119.82–207.95)	36.87 (−84.44–157.88)	0.894
Native thiol (µmol/L)	preoperative	170.75 (118.62–213.29)	144.51 (95.01–193.43)	0.240
	postoperative	147.92 (124.06–180.09)	127.62 (102.57–202.02)	0.356
	p	0.814	0.666
	rrb	− 0.048	0.089
	Δ (Post–Pre)	12.6 (− 55.73–49.06)	2.82 (− 57.95–39.87)	0.751
Disulfide (µmol/L)	preoperative	51.58 (28.7–73.37)	73.6 (47.1–119.4)	0.016*
	postoperative	80.3 (51.2–101.4)	77.52 (56.2–100.87)	0.627
	p	0.078	0.399
	rrb	0.363	0.173
	Δ (Post–Pre)	11.51 (− 29.08–63.22)	11.05 (− 53.09–58.87)	0.486
Reduced thiol (N.thiol/T.thiol) %	preoperative	60.34 (49.85–69.56)	48.2 (39.3–55.4)	0.004*
	postoperative	51.4 (46.2–58.6)	48.77 (42.6–54.1)	0.068
	p	0.088	0.544
	rrb	− 0.351	− 0.125
	Δ (Post–Pre)	8.94 (− 9.35–21.56)	3.95 (− 11.85–11.64)	0.257
Oxidized thiol (Disulfide/T.Thiol) %	preoperative	19.83 (15.22–25.07)	25.9 (22.3–30.4)	0.004*
	postoperative	24.3 (20.7–26.9)	25.61 (22.95–28.7)	0.073
	p	0.088	0.544
	rrb	0.351	0.125
	Δ (Post–Pre)	4.47 (− 4.73–10.78)	1.97 (− 5.98–5.82)	0.257
Thiol oxidation (N.thiol/disulfide) %	preoperative	304.26 (198.83–457.07)	186.4 (129.3–248.8)	0.004*
	postoperative	211.8 (172–283.6)	190.42 (148.42–235.73)	0.070
	p	0.048*	0.378
	rrb	− 0.407	− 0.181
	Δ (Post–Pre)	92.86 (− 86.24–305.17)	24.44 (− 83.67–99.03)	0.198

(* p < 0.05, Mann–Whitney U test for independent and Wilcoxon test for dependent measurements, Δ (Delta) values represent the difference between postoperative and preoperative levels for each parameter, r_rb: Rank-Biserial Correlation)

Discussion

Surgeons often face uncertainty regarding the optimal level of intra-abdominal pressure (IAP) to be used during laparoscopic procedures. Although higher insufflation pressures are frequently favored due to the enhanced surgical field visibility and improved maneuverability they offer—ultimately reducing intraoperative complications—the potential systemic risks associated with elevated IAP should not be overlooked. With the increasing number of surgeries now performed laparoscopically, the results of studies investigating the physiological effects of IAP have become even more clinically relevant. It has been demonstrated that IAP levels in the range of 15–20 mmHg may induce splanchnic ischemia independent of cardiac output [10]. During standard laparoscopic procedures, intra-abdominal pressure is typically maintained between 10 and 15 mmHg, which notably exceeds the baseline pressure of the portal venous system, generally ranging from 7 to 10 mmHg under physiological conditions [6]. The increase in intra-abdominal pressure (IAP) exerts compressive force on abdominal vascular structures, triggering the release of vasoactive hormones. Conversely, when the pressure is reduced, splanchnic reperfusion occurs. In this context, laparoscopic procedures can be considered to mimic an ischemia–reperfusion model [6]. Although numerous studies in the literature have investigated the relationship between varying levels of intra-abdominal pressure (IAP) and oxidative stress in laparoscopic surgery [5, 6, 11, 12], data regarding geriatric patient populations remain limited. To the best of our knowledge, this is the first study to examine the association between different IAP levels and thiol/disulfide homeostasis in elderly patients undergoing laparoscopic surgery.

One of the anticipated benefits of using higher intra-abdominal pressure is improved visualization and a broader operative field, which may contribute to shorter operative times. However, contrary to expectations, our study found that the duration of surgery was longer in the high-pressure group compared to the low-pressure group, although this difference was not statistically significant. Similarly, Adenuga et al. reported no significant impact of low versus standard IAP on operative time during laparoscopic appendectomy, and Gin et al. reached comparable conclusions in their study on laparoscopic cholecystectomy [13, 14]. In our study, although both AST and ALT levels increased significantly postoperatively compared to preoperative values in both groups, intergroup analysis of the difference values revealed a statistically significant elevation only in AST levels, with a greater increase observed in Group B. While ALT levels were also higher postoperatively in Group B, this difference did not reach statistical significance. Previous studies investigating the effects of intra-abdominal pressure (IAP) on liver enzymes have similarly reported significant elevations in both AST and ALT associated with increased pressure [6, 15–17]. In another study, Akkurt et al. reported that variations in intra-abdominal pressure (IAP) did not result in significant changes in liver enzyme levels [18]. Previous studies have suggested that elevations in liver enzymes may not be solely attributable to intra-abdominal pressure (IAP), but could also be influenced by surgical dissection techniques and anesthesia protocols [19]. In our study, efforts were made to standardize these variables by applying the same surgical technique and anesthetic procedure in all patients. We believe that the higher AST and ALT levels observed in Group B are primarily attributable to the elevated intra-abdominal pressure applied in this group. Despite the significant elevation in AST levels, the oxidative stress markers measured through thiol-disulfide homeostasis did not exhibit statistically significant changes. This may suggest that the thiol-disulfide system is less sensitive to short-term hepatic perfusion alterations induced by increased intra-abdominal pressure, particularly during brief laparoscopic procedures. It is possible that the duration and intensity of oxidative stress in this setting were insufficient to produce measurable shifts in thiol-disulfide balance.

It is hypothesized that excessive increases in intra-abdominal pressure (IAP) may impair renal function. In our study, we observed a postoperative decrease in urea and creatinine levels compared to preoperative values. This finding is likely attributable to perioperative intravenous hydration. When comparing both groups, no statistically significant difference was found between the 10 mmHg and 15 mmHg pressure groups. Similarly, a systematic review evaluating low versus standard IAP also reported no significant differences in renal function between groups [16].

Despite the difference in intra-abdominal pressure, no early or late postoperative complications or mortality were observed in any patient from either group. Similar findings have been reported in previous studies investigating the association between insufflation pressure and surgical complications or mortality [16].

Although statistically significant differences were found between preoperative and postoperative values for all hematological parameters within each group, no statistically significant differences were detected between the groups. Both WBC and neutrophil counts showed significant postoperative increases in both groups; however, the difference in intra-abdominal pressure did not have a statistically significant effect on these parameters. The increase in WBC and neutrophil counts observed in both groups may be indicative of a nonspecific stress or inflammatory response commonly triggered by surgical intervention and anesthesia, rather than being directly attributable to the applied intra-abdominal pressure. Similar findings have been reported in previous studies investigating the impact of intra-abdominal pressure (IAP) on hematological parameters, particularly noting increases in neutrophil and WBC counts [17, 20]. As observed in similar studies [17], we detected a decrease in hemoglobin and platelet counts; however, the difference in intra-abdominal pressure did not have a statistically significant effect on these parameters. In a recent study involving 122 patients with a similar design to ours, Tian et al. reported no significant differences in cardiopulmonary comorbidities between groups undergoing laparoscopic cholecystectomy with 10 mmHg and 14 mmHg IAP [21]. Although our study did not specify comorbidities in detail, no morbidity was observed during the 30-day follow-up period. In contrast to our findings, a study that investigated the relationship between thiol-disulfide homeostasis and intra-abdominal surgical difficulty during laparoscopic cholecystectomy—while maintaining constant IAP—found a significant correlation, suggesting that thiol-disulfide parameters may serve as predictors for identifying technically challenging intra-abdominal cases [22].

A decrease in total and native thiol levels during surgery indicates that these compounds are being consumed due to oxidative stress induced by the procedure. Monitoring thiol-disulfide homeostasis intraoperatively may serve as a valuable biomarker to identify individuals at risk and to guide optimal management and therapeutic strategies during surgery [23].

In geriatric patients who underwent surgery with 10 mmHg and 15 mmHg intra-abdominal pressures, no statistically significant differences were observed in total thiol, native thiol, and disulfide levels when comparing preoperative values with those measured after desufflation. A similar study conducted in a pediatric patient group also investigated the effects of low and high IAP on thiol-disulfide homeostasis. Consistent with our findings, this study demonstrated that pressure differences did not lead to significant alterations in thiol-disulfide balance [12]. In their study comparing 10 mmHg and 15 mmHg intra-abdominal pressures, Polat et al. evaluated the oxidative impact of pressure differences by measuring lipid peroxidase levels, a distinct oxidative stress marker. Their findings, consistent with the results of our study, demonstrated that variations in insufflation pressure did not induce oxidative stress [11]. In another study, the effects of laparoscopic versus open cholecystectomy on thiol-disulfide homeostasis were investigated, and it was found that intra-abdominal pressure (IAP) during laparoscopy induced oxidative stress, in contrast to open surgical procedures [24]. This discrepancy suggests that the presence of pneumoperitoneum itself—rather than pressure variation within laparoscopic settings—may play a more critical role in oxidative stress generation.

In laparoscopic surgery, not only the level of intra-abdominal pressure (IAP) but also the rate at which the pressure is established may contribute to oxidative stress. To ensure standardization between groups in our study, gas insufflation was performed at an equivalent and low rate. In a study by Eminoğlu et al., where different gas insufflation rates were compared, no significant differences were found between the groups in terms of thiol-disulfide homeostasis parameters [25]. In line with the importance of minimizing procedure-related physiological stress, Bai et al. recently demonstrated that a vagus nerve-guided robotic-assisted splenectomy and azygoportal disconnection technique significantly reduced postoperative gastrointestinal complications and promoted faster recovery compared to conventional approaches. Although their study addressed a different surgical setting, their findings highlight that meticulous surgical techniques aimed at preserving physiological homeostasis may improve postoperative outcomes, supporting our conclusion that maintaining optimal intra-abdominal conditions is critical for reducing surgical stress in elderly patients [26].

Conclusion

In conclusion, our findings indicate that different intra-abdominal pressure levels during laparoscopic cholecystectomy in geriatric patients may be associated with varying degrees of liver enzyme elevation, particularly AST. However, postoperative oxidative stress markers, including thiol-disulfide homeostasis, did not show statistically significant differences between the groups. Importantly, no intraoperative visibility or surgical outcome problems were encountered under low-pressure (10 mmHg) pneumoperitoneum, supporting its feasibility in elderly patients. These results suggest that both low and standard-pressure pneumoperitoneum may be feasible options in elderly patients, provided that adequate perioperative care is ensured. Further large-scale, multicenter, and long-term studies are needed to validate these findings and clarify their implications for surgical practice.

Limitations

This study has several limitations. First, the relatively small sample size may limit the statistical power and generalizability of the results. Second, although the surgical technique and anesthetic management were standardized, individual patient responses to surgical stress could not be fully controlled. Additionally, long-term outcomes such as delayed complications or recovery parameters were not evaluated, which may have provided further insight into the clinical relevance of oxidative stress variations. The lack of subgroup analysis by comorbidities is a limitation, although the similar distribution between groups reduces this potential bias. It should also be noted that the thiol–disulfide assay primarily reflects systemic oxidative balance and may not be sensitive to localized hepatic or splanchnic hypoxia. Finally, the study was conducted in a single center, which may introduce institutional bias.

Abbreviations

IAP

Intra-abdominal pressure

THIOS

Thiol-disulfide homeostasis

ASA

American Society of Anesthesiologists

NT

Native thiol

TT

Total thiol

AST

Aspartate aminotransferase

ALT

Alanine aminotransferase

WBC

White blood cell

Author contributions

AA operated on patients, collected the samples and evaluated clinical findings, discussed the results, performed revisions for important intellectual content, and commented on the manuscript. ES analyzed data, discussed the results, performed revisions for important intellectual content, and commented on the manuscript. HU performed the biochemical analyses, analyzed data, discussed the results. All authors contributed to the design of the present study, read and approved the submitted version.

Funding

This study was supported by Gaziantep University, Scientific Research Projects Governing Unit (Project Number: TF.HZP.23.07).

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Declarations

Ethics approval and consent to participate

The study was approved by the local ethics committee of Gaziantep University, Turkey (No: 2023/08).

Consent for publication

All authors have thoroughly reviewed the full manuscript and agreed to the publication of the final version.

Competing interests

The authors declare no competing interests.