Association between anesthetic fresh gas flow and postoperative inflammatory response in laparoscopic sleeve gastrectomy

Abstract

Perioperative inflammation is associated with adverse postoperative outcomes, and anesthetic management may modulate this response. However, the influence of fresh gas flow strategies during volatile anesthesia on perioperative inflammatory responses has not been adequately characterized. Evidence in obese surgical patients remains particularly limited despite the chronic low-grade inflammatory state and exaggerated responses to surgical stress associated with obesity. In this retrospective cohort study, 155 obese adult patients undergoing laparoscopic sleeve gastrectomy under sevoflurane anesthesia were evaluated. Patients received either low-flow (1 L/min, n = 76) or standard-flow (4 L/min, n = 79) anesthesia. Perioperative changes (Δ = postoperative − preoperative) in red cell distribution width (RDW), C-reactive protein (CRP), and neutrophil-to-lymphocyte ratio (NLR) were assessed using preoperative and 24-hour postoperative values. Between-group changes in these 3 designated primary outcomes were compared, and multivariable linear regression analyses were performed as adjusted supportive analyses. Intraoperative hemodynamic and oxygenation parameters and postoperative hospital length of stay were evaluated as exploratory secondary outcomes. ΔRDW and ΔCRP were greater in the standard-flow group than in the low-flow group (both P < .001) and remained statistically significant after Bonferroni correction (α = 0.0167), whereas no statistically significant between-group difference was observed for ΔNLR (P = .902). After adjustment for the measured covariates and calendar period, standard-flow anesthesia remained associated with greater ΔRDW and ΔCRP. No statistically detectable between-group differences were observed in the longitudinal hemodynamic and oxygenation outcomes or postoperative hospital length of stay. Low-flow sevoflurane anesthesia was associated with smaller postoperative increases in RDW and CRP compared with standard-flow anesthesia in obese patients undergoing laparoscopic sleeve gastrectomy. These findings suggest an association between fresh gas flow strategy and selected postoperative inflammatory marker changes during bariatric surgery.

1. Introduction

Surgical procedures induce a complex systemic response characterized by activation of inflammatory and oxidative pathways.^[1,2] While this response is essential for tissue repair and host defense, excessive or prolonged activation may lead to adverse outcomes, including delayed recovery, impaired wound healing, and organ dysfunction.^[3,4] Consequently, perioperative factors that may influence the magnitude of the inflammatory response have attracted increasing clinical interest.

Anesthesia is now recognized not only as a facilitator of surgical procedures but also as an active modulator of immune and inflammatory pathways.^[5–7] This interaction is particularly relevant in obese patients, who exhibit chronic low-grade systemic inflammation, increased oxidative stress, and altered immune regulation.^[8] In this population, the response to surgical stress is often amplified, leading to a more pronounced postoperative inflammatory profile compared with nonobese individuals.^[9] Bariatric surgery therefore represents a clinically relevant setting in which perioperative inflammatory responses can be evaluated.

Low-flow anesthesia using volatile agents such as sevoflurane is widely used because of its economic and environmental advantages. However, whether fresh gas flow strategies influence perioperative oxidative stress and inflammatory responses remains uncertain. Existing experimental and clinical studies are limited in number and have reported inconsistent findings across different surgical settings, while data specifically addressing obese patients undergoing bariatric surgery remain scarce.^[10–12]

To evaluate perioperative inflammatory alterations, we analyzed C-reactive protein (CRP), a well-established acute-phase marker of systemic inflammation; the neutrophil-to-lymphocyte ratio (NLR), which reflects the balance between innate inflammatory activation and immune regulation; and red cell distribution width (RDW), a hematological parameter increasingly associated with inflammation and oxidative stress.^[13–18] Given the potential relationship between exaggerated postoperative inflammation and adverse clinical outcomes, identifying perioperative factors that may modulate these responses is clinically relevant. Therefore, in this retrospective cohort study, we aimed to compare perioperative changes in CRP, NLR, and RDW between low-flow and standard-flow sevoflurane anesthesia in patients undergoing laparoscopic sleeve gastrectomy.

2. Materials and methods

2.1. Study design and patient selection

This retrospective cohort study evaluated the archived anesthesia records of 167 adult patients who underwent laparoscopic sleeve gastrectomy under general anesthesia at University of Health Sciences Adana City Training and Research Hospital between January 2022 and January 2025. The study was conducted in accordance with the principles of the Declaration of Helsinki. Ethical approval for the study was obtained from the Institutional Review Board (Approval No. 11-376; March 6, 2025). Informed consent was waived by the Ethics Committee due to the retrospective study design. This study was retrospectively registered at ClinicalTrials.gov (NCT07230704).

During the study period, both low-flow (1 L/min) and standard-flow (4 L/min) sevoflurane anesthesia techniques were routinely used in our institution as part of standard clinical practice. There was no institutional protocol mandating a specific fresh gas flow strategy. Allocation to the fresh gas flow strategy was not randomized and reflected the routine preference of the attending anesthesiologist. All included procedures were managed by a single attending anesthesiologist, who used both fresh gas flow strategies throughout the study period. All eligible patients meeting the inclusion criteria during the study period were consecutively included and categorized according to the intraoperative fresh gas flow strategy applied.

2.1.1. Inclusion criteria

• Elective laparoscopic sleeve gastrectomy

• Age between 18 and 60 years

• Body mass index (BMI) > 35 kg/m²

• Availability of complete perioperative records (preoperative, intraoperative, and postoperative data)

2.1.2. Exclusion criteria

• Severe cardiovascular, pulmonary, hepatic, or renal disease; poorly controlled diabetes mellitus with end-organ involvement

• Incomplete anesthesia records

• Intraoperative or postoperative complications related to surgery (e.g., major hemorrhage, anastomotic leak)

A total of 167 patients were initially screened for eligibility. Of these, 8 patients were excluded because of incomplete anesthesia records that precluded reliable extraction of the required perioperative data (3 low-flow and 5 standard-flow), and 4 patients were excluded due to severe comorbidities. No patient was excluded because of intraoperative or postoperative surgical complications. Ultimately, 155 patients met the inclusion criteria and were analyzed. The selection process is illustrated in Figure 1.

Figure 1.

Flow diagram of patient selection.

2.2. Anesthesia protocol

Anesthesia was administered according to the standard protocol routinely applied in our clinic. All patients received premedication with intravenous midazolam (0.02 mg/kg). Anesthesia induction was performed using propofol (2.0–3.0 mg/kg), fentanyl (2 mcg/kg), and rocuronium (0.6 mg/kg). Propofol and fentanyl doses were calculated using actual body weight, while rocuronium was administered based on adjusted body weight to ensure accurate dosing in obese patients. Endotracheal intubation was achieved via direct laryngoscopy using appropriately sized tubes.

For both groups, a fresh gas flow of 4 L/min with 50% oxygen in air was administered during the first 6 to 8 minutes after induction until the anesthesia machine indicated a minimum alveolar concentration (MAC) of 1.0. Following this period, the flow rate was adjusted according to group allocation: in the standard-flow group, the fresh gas flow was maintained at 4 L/min throughout the procedure, whereas in the low-flow group, it was reduced to 1 L/min. In both groups, anesthesia was maintained with sevoflurane at concentrations of 2 to 3%, titrated to achieve a MAC of 0.8 to 1.2 under bispectral index (BIS) monitoring, with BIS values targeted between 40 and 60. Neuromuscular blockade was maintained with intermittent boluses of rocuronium (0.1–0.2 mg/kg) administered approximately every 30 minutes.

Mechanical ventilation was adjusted to maintain an end-tidal CO₂ (ETCO₂) level between 30–40 mm Hg. Tidal volume was set at 6 to 8 mL/kg, and respiratory rate was adjusted to 12 to 16 breaths per minute. At the end of surgery, fresh gas flow was increased to 6 to 8 L/min, and the inhaled anesthetic was discontinued. Patients were manually ventilated with 100% oxygen prior to extubation. Neuromuscular blockade was reversed with intravenous sugammadex (2 mg/kg), and extubation was performed once adequate spontaneous ventilation and protective airway reflexes were present.

2.3. Perioperative monitoring and hemodynamic data collection

Standard intraoperative monitoring included electrocardiography (ECG), heart rate (HR), noninvasive blood pressure (NIBP; systolic and diastolic blood pressure), peripheral oxygen saturation (SpO₂), and end-tidal carbon dioxide (ETCO₂). These parameters were recorded at baseline (T0, prior to induction, in the supine position), at 5, 10, and 15 minutes after intubation (T5, T10, T15), and every 15 minutes thereafter. Since the median operative duration was 70 minutes (IQR 65–75) and the final 5 to 7 minutes involved increased fresh gas flow and extubation, only data collected up to the 60th minute were included in the final analysis.

2.4. Laboratory measurements

Peripheral venous blood samples were obtained from all patients at 2 time points:

• Preoperative sample: within 24 hours before surgery

• Postoperative sample: at the 24th postoperative hour

The following inflammatory and hematological parameters were analyzed:

• Red cell distribution width (RDW)

• C-reactive protein (CRP)

• Neutrophil-to-lymphocyte ratio (NLR)

At our institution, complete blood count (including RDW, neutrophil count, and lymphocyte count) and C-reactive protein (CRP) are routinely obtained as part of the standard preoperative evaluation and 24-hour postoperative laboratory assessment for patients undergoing laparoscopic sleeve gastrectomy. Therefore, no additional blood samples or laboratory tests were requested specifically for this study. All laboratory tests were performed in the hospital’s central biochemistry laboratory using standardized methods. RDW, neutrophil count, and lymphocyte count were measured using a Sysmex XN-1000 hematology analyzer. NLR was calculated as the absolute neutrophil count divided by the absolute lymphocyte count. CRP was measured by an immunoturbidimetric assay using a Beckman Coulter AU5800 analyzer. The reference ranges were 12.4 to 14.9% for RDW and 0 to 5 mg/L for CRP, and the analytical coefficients of variation were < 1.5% for RDW and < 2.0% for CRP.

2.5. Study endpoints

The designated primary outcomes were the perioperative changes in RDW, CRP, and NLR between the low-flow and standard-flow groups. Additional exploratory secondary analyses included intraoperative heart rate, systolic and diastolic blood pressure, and peripheral oxygen saturation measurements obtained during the first 60 minutes of surgery, as well as postoperative hospital length of stay.

2.6. Statistical analysis

Statistical analyses were performed using SPSS version 31.0 (IBM Corp., Armonk, NY, USA). The Shapiro–Wilk test was used to assess data normality. Continuous variables with normal distribution were compared using the independent samples t-test, whereas non-normally distributed variables were analyzed using the Mann–Whitney U test. Categorical variables were compared using the Pearson chi-square test. Perioperative changes (Δ = postoperative − preoperative) in RDW, CRP, and NLR were compared between groups using the Mann-Whitney U test, with unadjusted between-group effect estimates expressed as Hodges-Lehmann location-shift estimates (standard-flow minus low-flow) with bootstrap 95% confidence intervals. The unadjusted between-group comparisons of ΔRDW, ΔCRP, and ΔNLR constituted the primary inferential analyses, whereas the multivariable regression models were considered adjusted supportive analyses. Multivariable linear regression analyses were performed for ΔRDW, ΔCRP, and ΔNLR. Regression models were adjusted for age, sex, body mass index (BMI), ASA physical status, operative duration, baseline preoperative marker values, and calendar period. Regression diagnostics included residual distribution, homoscedasticity, multicollinearity assessed using variance inflation factor (VIF), and influential observations. Given evidence of heteroscedasticity, HC3 heteroscedasticity-robust standard errors were used to obtain confidence intervals and P values. Because ΔRDW, ΔCRP, and ΔNLR were designated as primary outcomes, a Bonferroni-corrected significance threshold of α = 0.05/3 = 0.0167 was applied to these 3 between-group comparisons. Serial intraoperative SBP, DBP, HR, and SpO₂ measurements were analyzed using linear mixed-effects models including fixed effects for group, time, and the group-by-time interaction, with a patient-specific random intercept to account for within-patient repeated measurements. For postoperative hospital length of stay, the between-group effect estimate was expressed as the Hodges-Lehmann location-shift estimate (standard-flow minus low-flow) with a 95% confidence interval. Other exploratory secondary analyses were interpreted using a conventional threshold of P < .05.

3. Results

A total of 155 patients who underwent laparoscopic sleeve gastrectomy were included in the study, comprising 76 patients in the low-flow sevoflurane group and 79 patients in the standard-flow sevoflurane group. The distribution of low-flow vs standard-flow cases across calendar years was 22 vs 26 in 2022, 28 vs 25 in 2023, 24 vs 27 in 2024, and 2 vs 1 in January 2025. No statistically detectable between-group differences were observed in demographic characteristics, baseline inflammatory marker levels, operative duration, ASA physical status, or postoperative hospital length of stay (Table 1). For hospital length of stay, the estimated between-group difference was 0 hours (95% CI − 2 to 1 h; P = .536).

Table 1.

Demographic, perioperative, and baseline laboratory characteristics.

Variable	Low-flow (n = 76)	Standard-flow (n = 79)	P-value
Age, years	35 (28–41)	35 (26–42)	.691
BMI, kg/m2	42 (41–45)	42 (41–44)	.308
Operative duration, min	68.0 (65.0–75.0)	70.0 (65.0–73.5)	.381
Preoperative RDW, %	13.95 (13.50–15.50)	14.20 (13.75–15.20)	.202
Preoperative NLR	2.54 (1.85–3.05)	2.04 (1.67–2.91)	.082
Preoperative CRP, mg/L	7.65 (4.20–10.32)	8.80 (5.90–11.00)	.155
Sex, n (%)			.884
Female	48 (63.2)	49 (62.0)
Male	28 (36.8)	30 (38.0)
ASA physical status, n (%)			.304
II	54 (71.1)	50 (63.3)
III	22 (28.9)	29 (36.7)
Postoperative hospital stay, h	48 (48–52)	48 (46–52)	.536

Data are presented as median (interquartile range) or n (%), as appropriate. Continuous variables were compared using the Mann–Whitney U test and categorical variables using the Pearson chi-square test.

BMI = body mass index, CRP = C-reactive protein, NLR = neutrophil-to-lymphocyte ratio, RDW = red cell distribution width.

3.1. Intraoperative oxygenation and hemodynamics

Serial intraoperative SBP, DBP, HR, and SpO₂ measurements were analyzed using linear mixed-effects models. No statistically detectable group-by-time interactions were observed for any of the 4 parameters. Overall between-group effect estimates were small, with 95% confidence intervals including zero for all parameters (Table S1, Supplemental Digital Content 1). Serial measurements with 95% confidence intervals are presented in Figure 2.

Figure 2.

Time-course of SBP, DBP, HR, and SpO₂ under low-flow and standard-flow sevoflurane anesthesia. Data are presented with 95% confidence intervals.

3.2. Inflammatory and hematological markers

The distributions of ΔRDW, ΔCRP, and ΔNLR and their unadjusted between-group effect estimates are presented in Table 2. ΔRDW and ΔCRP were greater in the standard-flow group than in the low-flow group (both P < .001) and remained statistically significant after Bonferroni correction for the 3 primary comparisons (α = 0.0167). No statistically significant between-group difference was observed for ΔNLR (P = .902) (Fig. 3).

Table 2.

Between-group comparisons of perioperative changes in RDW, CRP, and NLR.

Primary outcome	Low-flow (n = 76) Median (IQR)	Standard-flow (n = 79) Median (IQR)	Unadjusted effect estimate* (95% CI)	P-value
ΔRDW, %	0.00 (−0.03 to 0.10)	0.20 (0.10–0.40)	0.20 (0.10–0.30)	<.001
ΔCRP, mg/L	5.25 (2.80–8.13)	10.00 (5.75–19.00)	5.10 (3.00–7.50)	<.001
ΔNLR	2.56 (0.66–5.11)	1.95 (0.90–5.83)	−0.08 (−1.14 to 1.02)	.902

CI = confidence interval, CRP = C-reactive protein, IQR = interquartile range, NLR = neutrophil-to-lymphocyte ratio, RDW = red cell distribution width.

^*Effect estimate represents the Hodges–Lehmann location-shift estimate for standard-flow minus low-flow, with bootstrap 95% confidence intervals. Δ = postoperative − preoperative. A Bonferroni-corrected significance threshold of α = 0.0167 was applied; ΔRDW and ΔCRP remained statistically significant, whereas ΔNLR did not.

Figure 3.

Perioperative changes (Δ) in RDW, NLR, and CRP under low-flow and standard-flow sevoflurane anesthesia.

In multivariable linear regression analyses adjusting for age, sex, BMI, operative duration, ASA physical status, baseline marker values, and calendar period, standard-flow sevoflurane anesthesia remained associated with greater increases in both ΔRDW (β = 0.40, 95% CI 0.18–0.62, P < .001) and ΔCRP (β = 6.25, 95% CI 3.86–8.64, P < .001). No statistically significant association was observed for ΔNLR (β = 0.25, 95% CI − 1.30 to 1.80, P = .752). The maximum variance inflation factor was 1.43, indicating no evidence of problematic multicollinearity (Table 3). Influence diagnostics identified several observations with elevated Cook’s distance; however, sensitivity analyses excluding these observations did not materially alter the direction or statistical interpretation of the flow-group associations.

Table 3.

Multivariable linear regression analyses for perioperative changes in RDW, CRP, and NLR.

Variable	ΔRDW β (95% CI)	P-value	ΔCRP β (95% CI)	P-value	ΔNLR β (95% CI)	P-value
Flow group (standard vs low)	0.40 (0.18–0.62)	<.001	6.25 (3.86–8.64)	<.001	0.25 (−1.30–1.80)	.752
Age (years)	0.00 (−0.01–0.01)	.657	0.06 (−0.04–0.17)	.226	−0.03 (−0.09–0.04)	.443
Sex (female vs male)	−0.02 (−0.26–0.21)	.842	−0.99 (−3.49–1.50)	.436	1.09 (−0.60–2.79)	.207
BMI (kg/m2)	−0.00 (−0.04–0.03)	.805	0.37 (−0.09–0.84)	.117	0.16 (−0.13–0.45)	.284
Operative duration (min)	−0.00 (−0.01–0.01)	.752	0.20 (−0.03–0.44)	.087	−0.15 (−0.31–0.02)	.087
ASA (III vs II)	0.09 (−0.18–0.36)	.525	2.24 (−0.68–5.16)	.132	0.97 (−0.71–2.65)	.258
Baseline marker value	0.06 (−0.06–0.17)	.322	0.56 (0.09–1.04)	.020	−0.96 (−1.31–−0.62)	<.001
Calendar period: 2023 vs 2022	0.05 (−0.23–0.34)	.712	1.80 (−1.76–5.35)	.323	2.47 (0.57–4.36)	.011
Calendar period: 2024–Jan 2025 vs 2022	0.07 (−0.21–0.35)	.633	−2.50 (−5.40–0.41)	.092	0.67 (−1.05–2.40)	.444
Model n	155		155		155
R2/ adjusted R2	0.106/ 0.051		0.309/ 0.266		0.200/ 0.150

Models were adjusted for age, sex, BMI, operative duration, ASA physical status, baseline marker value, and calendar period. January 2025 cases were combined with the 2024 calendar period because only 3 patients were included in January 2025. HC3 heteroscedasticity-robust standard errors were used. Maximum VIF was 1.43.

ASA = American Society of Anesthesiologists, BMI = body mass index, CI = confidence interval, CRP = C-reactive protein, NLR = neutrophil-to-lymphocyte ratio, RDW = red cell distribution width, β = unstandardized regression coefficient.

4. Discussion

In this retrospective cohort study of obese patients undergoing laparoscopic sleeve gastrectomy under sevoflurane anesthesia, patients receiving low-flow anesthesia demonstrated smaller postoperative increases in RDW and CRP compared with those receiving standard-flow anesthesia, whereas no statistically significant between-group difference was observed for ΔNLR. These associations remained evident after adjustment for the measured covariates in multivariable regression analyses. These findings suggest that fresh gas flow strategy may be associated with differences in perioperative inflammatory response in this patient population.

Previous studies have shown that low-flow sevoflurane anesthesia can be used with appropriate settings and monitoring without adversely affecting intraoperative hemodynamic and oxygenation parameters.^[19] Consistent with these findings, no statistically detectable between-group differences were observed in the longitudinal hemodynamic and oxygenation outcomes in our exploratory secondary analyses. However, these findings should not be interpreted as evidence of equivalence or safety, as the study was not powered for these exploratory secondary outcomes. Maintaining stable hemodynamics and adequate oxygenation remains particularly important in obese patients undergoing bariatric surgery, in whom perioperative respiratory and cardiovascular challenges are common.^[20]

One of the notable findings of this study was the different perioperative pattern of RDW change between groups. Beyond its traditional role as a measure of erythrocyte size variability, RDW has increasingly been associated with systemic inflammation and oxidative stress.^[21,22] Acute inflammatory and oxidative stress states may induce structural and functional alterations in circulating erythrocytes, including membrane lipid peroxidation, impaired deformability, and shortened erythrocyte survival, potentially contributing to greater heterogeneity in erythrocyte volume.^[23,24] In the present cohort, the increase in RDW was greater in the standard-flow group than in the low-flow group. Although the underlying mechanisms cannot be determined from the present study, these findings may suggest a possible relationship between anesthetic flow conditions and perioperative alterations in RDW. However, the absolute magnitude of the observed RDW change was small, and its clinical significance remains uncertain. RDW measurements may also be influenced by analytical variability and perioperative fluid shifts or hemodilution, factors that could not be fully accounted for in this retrospective analysis.

Volatile anesthetics, including sevoflurane, have been associated with reactive oxygen species generation and oxidative stress in both experimental and clinical settings.^[25,26] In this context, Kaşıkara et al^[11] demonstrated lower oxidative stress marker levels during low-flow sevoflurane anesthesia compared with higher fresh gas flow strategies. Experimental findings have similarly suggested that higher fresh gas flow rates may augment oxidative injury, whereas low-flow techniques appear to preserve antioxidant balance and reduce oxidative burden.^[27] Collectively, these observations suggest a plausible biological hypothesis that may warrant further investigation; however, oxidative injury was not directly assessed in the present study.

Consistent with the RDW findings, the postoperative increase in CRP was greater in the standard-flow group than in the low-flow group. As CRP production is largely mediated by interleukin-6 and other pro-inflammatory cytokines,^[28] this finding may reflect differences in perioperative inflammatory responses between the anesthetic flow strategies. One potential explanation may involve better preservation of airway heat and humidity and reduced airway irritation during low-flow anesthesia.^[29] Low-flow techniques are known to maintain airway temperature and humidity more effectively than higher fresh gas flow strategies,^[30] while experimental evidence suggests that adequate airway humidification may attenuate ventilation-induced inflammation by preserving epithelial integrity and reducing local cytokine release.^[31] These mechanisms represent possible hypotheses for the observed association; however, airway temperature, humidity, and related inflammatory pathways were not directly measured in the present study.

Notably, no significant difference was observed between the groups in terms of ΔNLR, despite postoperative increases in both groups. NLR is known to be a reliable marker of surgical stress and innate immune activation.^[32,33] Consistently, Wang et al.^[34] reported that patients with more severe tibial plateau fractures – representing higher degrees of tissue trauma – exhibited significantly elevated NLR values. Accordingly, the absence of a between-group difference in NLR in our cohort suggests that surgical trauma and perioperative stress may be more important contributors to this parameter than fresh gas flow strategy.

Despite the observed differences in postoperative inflammatory marker responses between groups, no statistically detectable between-group difference was observed in postoperative hospital length of stay. This finding may suggest that the magnitude of inflammatory differences observed in the present cohort did not translate into detectable differences in short-term clinical recovery. However, hospital length of stay is influenced by multiple perioperative and institutional factors and may not fully reflect the clinical consequences of perioperative inflammatory activation.

Inflammatory markers were assessed at the 24th postoperative hour to capture the early perioperative inflammatory response. Assessment at a later postoperative stage may have introduced additional variability related to postoperative recovery processes, including differences in mobilization, oral intake, fluid balance, and other postoperative clinical factors that could influence inflammatory marker dynamics independently of intraoperative anesthetic management.^[35]

A growing body of evidence indicates that an exaggerated perioperative inflammatory response is not merely an epiphenomenon of surgery but is closely linked to adverse postoperative outcomes.^[36] Large-scale clinical data demonstrate that higher postoperative systemic inflammation, quantified by elevated CRP levels within the first 3 postoperative days, is independently associated with increased risks of major septic complications, acute kidney injury, unplanned ICU admission, poorer quality of recovery, and persistent disability or death.^[37] In addition, Poredos et al.^[38] demonstrated that perioperative systemic inflammation is a key driver of myocardial injury, major adverse cardiovascular events, and postoperative mortality. Elevated RDW levels in surgical patients have likewise been associated with adverse outcomes across a wide range of clinical settings.^[39–41] From this perspective, reducing unnecessary perioperative inflammatory burden may be clinically relevant.

This study has several limitations that should be acknowledged. First, its retrospective, single-center design introduces the possibility of selection bias and unmeasured confounding. Although all procedures were managed by a single attending anesthesiologist, the fresh gas flow strategy was not randomly assigned; therefore, residual confounding related to unmeasured factors influencing strategy selection cannot be excluded. In addition, no formal a priori sample size or power calculation was performed because this was a retrospective cohort study including all eligible patients during the study period. Second, several potentially important intraoperative variables, including estimated blood loss, intraoperative fluid administration, pneumoperitoneum pressure and duration, and intraoperative core temperature, were not available and, therefore, could not be included as covariates in the regression analyses. Third, inflammatory markers were assessed at a single postoperative time point, which may have limited evaluation of the temporal evolution of perioperative inflammatory responses beyond the early postoperative period. Fourth, inflammatory assessment was based on indirect laboratory markers, including CRP, NLR, and RDW, rather than direct measurements of inflammatory cytokines or oxidative stress biomarkers. Finally, because the study population consisted exclusively of obese patients undergoing laparoscopic sleeve gastrectomy under sevoflurane anesthesia, the generalizability of the findings to other surgical populations or anesthetic techniques may be limited.

5. Conclusions

Low-flow sevoflurane anesthesia was associated with smaller postoperative increases in RDW and CRP compared with standard-flow anesthesia in obese patients undergoing laparoscopic sleeve gastrectomy. These findings suggest an association between fresh gas flow strategy and selected postoperative inflammatory marker changes during bariatric surgery. Further prospective randomized studies incorporating broader inflammatory and oxidative stress biomarkers are needed to confirm these findings and clarify their potential clinical significance.

Author contributions

Conceptualization: Uğur Serkan Çitilcioğlu, Hatice Kaya Özdoğan.

Data curation: Uğur Serkan Çitilcioğlu.

Formal analysis: Uğur Serkan Çitilcioğlu.

Methodology: Uğur Serkan Çitilcioğlu, Hatice Kaya Özdoğan.

Writing – original draft: Uğur Serkan Çitilcioğlu.

Writing – review & editing: Uğur Serkan Çitilcioğlu, Hatice Kaya Özdoğan.

Supervision: Hatice Kaya Özdoğan.