The effect of oxygen reserve index guided oxygen titration on oxidative stress in rhinoplasty surgery: a randomized controlled trial

Abstract

Background

The aim of this study is to evaluate whether the use of Oxygen Reserve Index (ORi) can prevent hyperoxia in patients undergoing rhinoplasty surgery and whether it can reduce oxidative stress caused by hyperoxia.

Methods

A total of 60 patients, who were scheduled for rhinoplasty surgery and had an American Society of Anesthesiologists (ASA) score of I and II, were included in the study. The patients were randomly divided into two groups: the ORi group (Group R) and the control group (Group C). In Group R, oxygen support was titrated to keep the ORi values close to zero. In the control group, oxygen support was provided conventionally. Arterial blood gas samples were taken after intubation, at the 120th minute of the surgery and at the end of the surgery to record partial arterial oxygen pressure (PaO₂) values. During this process, patients’ peripheral oxygen saturation (SpO₂) and ORi values were continuously recorded along with hemodynamic data. Preoperative and postoperative blood samples were collected from both groups, and oxidative stress was assessed by evaluating thiol-disulfide homeostasis and ischemia-modified albumin (IMA), which are current indicators of oxidative stress.

Results

The demographic characteristics and the surgical durations were similar between the groups. PaO₂ values were lower in Group R compared to Group C. ORi values were correlated with PaO₂ values. Preoperative native thiol, total thiol, and disulfide values were similar in both groups. In both groups, postoperative native thiol, total thiol, and disulfide values decreased compared to the preoperative period, while IMA values increased. In Group R, the decrease in native thiol and total thiol values and the increase in IMA values were less than in Group C.

Conclusion

We concluded that ORi guided oxygen titration may reduce the severity of hyperoxia and may decrease oxidative stress in rhinoplasty surgery.

Trial registration

ClinicalTrials.gov Identifier NCT07158073. Registered on 21 August 2025.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12871-025-03424-0.

Introduction

ORi is a continuous, non-invasive parameter provided by new-generation pulse oximeters utilizing multi-wavelength pulse oximetry technology. ORi serves as an important monitoring tool for detecting both hyperoxemia and desaturation in patients with decreased PaO₂ levels. Studies have demonstrated that the ORi provides values within a range of 0 to 1, and an ORi value of 0 corresponds to a PaO₂ level between 80 and 125 mmHg [1, 2].

The aim of our study is to evaluate whether the use of ORi monitoring in patients undergoing rhinoplasty can help prevent hyperoxemia -which cannot be clinically anticipated or diagnosed using conventional pulse oximetry- and to assess whether the associated oxidative stress caused by hyperoxemia can be reduced.

Materials and methods

The present study was conducted between March and August 2021, following the approval of the Ethics Committee of the University of Health Sciences Kartal Dr. Lütfi Kırdar City Hospital (Decision No: 2021/514/196/4, dated February 24, 2021) and the Academic Board of the Faculty of Medicine, University of Health Sciences. The study was carried out according to the Declaration of Helsinki and Good Clinical Practice guidelines. All participants provided informed consent to participate in the study. This study was conducted and reported in accordance with the CONSORT guidelines.

A total of 60 patients scheduled to undergo rhinoplasty surgery, classified as ASA physical status I or II, were included in the study after obtaining written informed consent. Patients were excluded from the study if they met any of the following criteria: under 18 years of age; ASA classification greater than II; Mallampati score of 3 or 4; findings suggestive of difficult intubation during physical examination; any pathological findings on chest X-ray evaluation (e.g., pleural effusion, nodular density increase, emphysema, atelectasis, calcification, mediastinal widening, or infiltration); a history of circulatory disorders; hematocrit or hemoglobin values outside the normal range (Hemoglobin: 12–16 g/dL for males, 11–14 g/dL for females; Hematocrit: 36–48% for males, 33–42% for females); or a known hypersensitivity to any anesthetic agent to be used in the study.

On the day of surgery, patients were randomly assigned into two groups —ORi group (Group R) and control group (Group C)— using the sealed envelope method. Both the clinicians involved in intraoperative patient management and the researchers responsible for data collection were blinded to group assignments. Patients in Group R received ORi monitoring in addition to intraoperative standart monitoring (ECG, pulse oximetry, non-invasive arterial blood pressure). For this purpose, an ORi sensor (RD Rainbow SET sensor, Masimo Corp., Irvine, CA, USA) was placed on the fourth finger of the upper extremity where there was no blood pressure cuff. The sensor was wrapped to prevent exposure to light and connected to an oximeter device (Raical-7^® Pulse CO-Oximater^®, Masimo Corp., Irvine, CA, USA). Patients in Group C received only standard monitoring.

After all patients were positioned on the operating table, electrodes were placed in lead II configuration for electrocardiographic (ECG) monitoring. Non-invasive arterial blood pressure (systolic and diastolic) and peripheral pulse oximetry monitoring were performed, and baseline values were recorded. Radial artery cannulation was performed for arterial blood gas sampling and continuous arterial blood pressure monitoring.

A 5 mL venous blood sample was collected through the established intravenous line before the administration of any medications or intravenous fluids and transferred into a yellow-capped gel-containing vacuum tube. Following this, anesthesia induction was initiated. Preoxygenation was performed with 50% oxygen in Group R and 100% oxygen in Group C for 30 s. In both groups, anesthesia induction was achieved via the intravenous route using 2.5 mg/kg propofol, 1–2 µg/kg fentanyl, and 0.6 mg/kg rocuronium. In Group R, mask ventilation was administered with 50% oxygen, while in Group C, 100% oxygen was used for 90 s. Orotracheal intubation was performed using an appropriately sized endotracheal tube after achieving adequate muscle relaxation. In both groups, anesthesia was maintained with 1–2% sevoflurane and 0.05–1 µg/kg/min remifentanil, titrated to maintain a mean arterial pressure between 55 and 65 mmHg, thereby achieving controlled hypotensive anesthesia. In Group R, FiO₂ was titrated between 30% and 50% under the guidance of ORi and SpO₂ values. Accordingly, if SpO₂ was ≥ 98%, FiO₂ was reduced in 5% increments to a minimum of 30%, aiming to achieve an ORi value of 0 or as close to 0 as possible. In Group C, FiO₂ was maintained at 50% throughout the surgery, provided that SpO₂ remained ≥ 98%. In both groups, if SpO₂ dropped below 98%, FiO₂ was increased by 5%. These adjustments were evaluated at 2-minute intervals according to the target SpO₂ and ORi values, and repeated as necessary. Medical air was used as the second gas. After FiO₂ was adjusted according to group assignments on the anesthesia machine, all patients were placed on volume-controlled mechanical ventilation with the following standardized settings: respiratory rate of 12 breaths per minute, inspiration-to-expiration (I/E) ratio of 1:2, inspiratory time of 1.7 s, tidal volume (TV) of 7 mL/kg, fresh gas flow of 2.5 L/min, and positive end-expiratory pressure (PEEP) of 5 cmH₂O. During the operation, ventilation parameters were adjusted to maintain an end-tidal carbon dioxide (ETCO₂) level between 25 and 35 mmHg.

No changes were made to the original trial protocol after the study commenced.

Data collection

Throughout the anesthesia period, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and SpO₂ were recorded at 15-minute intervals in all patients. In Group R, ORi and FiO₂ values were recorded at the end of mask ventilation, at the 10th minute after intubation, and every 15 min during the procedure. Arterial blood gas samples were obtained from all patients after intubation, at the 2nd hour of surgery, and at the end of the procedure before awakening. pH, partial oxygen pressure (PaO₂), and partial carbon dioxide pressure (PaCO₂) values were recorded together with the corresponding ORi values at the time of blood sampling.

A second venous blood sample was collected at the end of the surgical procedure. The blood samples were centrifuged at 4000 rpm for 10 min, after which the serum was separated and transferred into two individual Eppendorf tubes, then stored at − 80 °C. Once the target number of patients was reached, the frozen samples were transferred under appropriate conditions using insulated dry ice containers to the Biochemistry Laboratory for the measurement of thiol/disulfide homeostasis and ischemia-modified albumin (IMA) levels. The obtained results were recorded.

Statistical analysis

The data were analyzed using the Statistical Package for the Social Sciences (IBM^® SPSS Statistics for Windows, Version 23.0, Armonk, NY, USA). Descriptive statistics were used to summarize the data. Quantitative variables were characterized by their mean, maximum, and minimum values, while percentages were used for qualitative variables. The normality of the data distribution was assessed using the Kolmogorov-Smirnov test. Normally distributed variables were reported as mean values and compared between groups using the Student’s t-test. Non-normally distributed continuous variables were reported as medians and compared using the Mann-Whitney U test. For values reported as medians, the interquartile range (IQR) was also provided. Categorical variables were compared using Pearson’s Chi-square test; however, Fisher’s exact test was used when the sample size was small (n ≤ 5). A p-value of < 0.05 was considered statistically significant.

Spearman correlation analysis was performed to determine whether there was a correlation between PaO₂ and ORi values at the 2nd hour of surgery, and the correlation coefficient (rho) was calculated. A positive rho indicated a direct relationship (e.g., both increasing), whereas a negative rho indicated an inverse relationship (e.g., one increasing while the other decreased). A correlation coefficient of < 0.4 was interpreted as weak, between 0.4 and 0.7 as moderate, and > 0.8 as strong.

Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive ability of ORi for PaO₂ >150 mmHg. The area under the curve (AUC) was calculated, and a 95% confidence interval (CI) was determined for the AUC value.

Post-hoc Power Analysis: A post-hoc power analysis was performed using the observed differences in oxidative stress markers between the groups. For Native Thiol, the effect size (Cohen’s d = 0.77) indicated a power of 83% (α = 0.05, n = 30 per group), confirming that the sample size was sufficient to detect significant changes. However, effect sizes for Disulfide (d = 0.36) and IMA (d = 0.16) were lower, yielding powers of 28% and 9%, respectively, suggesting that these outcomes may require larger samples for adequate statistical power.’’.

Results

The demographic and clinical data of the patients are presented in Table 1. The mean age of the patients was 24.2 years (min = 18 years, max = 45 years, median = 22 years), with the majority being female (n = 38, 63.3%). The number of patients classified as ASA I was 43, while the number of ASA II patients was 17. The median duration of the procedure was 225 min (min = 140 min, max = 340 min).

Table 1.

Demographic characteristics of patients and comparison between groups

Variables	Total	Group R (n = 30)	Group C (n = 30)	p value
Age, years, median (IQR)	22 (9)	21 (9)	22 (11)	0.870
Sex, n (%)
Woman	38 (63.3)	18 (60.0)	20 (66.7)
Male	22 (36.7)	12 (40.0)	10 (33.3)	0.592
ASA, n (%)
I	43 (71.7)	22 (73.3)	21 (70.0)
II	17 (26.7)	8 (26.7)	9 (30.0)	0.774
Weight, kg, median (IQR)	60 (15)	60 (14)	61 (20)	0.431
Height, cm, median (IQR)	168 (11)	169 (10)	167 (12)	0.619
Duration of surgery, min, median (IQR)	225 (69)	212 (90)	232 (34)	0.409

N number, IQR Interquartile range, ASA American Society of Anesthesiologists Physical status score, kg kilogram, cm centimeter, min minute

No statistically significant differences were found between the groups regarding age (p = 0.870), gender (p = 0.592), ASA (p = 0.074), weight (p = 0.431), height (p = 0.619), and surgery duration (p = 0.409).

When comparing the systolic blood pressure measurements of the patients between the groups at each time interval, a statistically significant difference was found only at the 300th minute (p = 0.007). At the 300th minute, the systolic blood pressure in Group R was statistically lower than in Group C (p = 0.007).

No statistically significant differences were observed between the two groups in terms of diastolic blood pressure at any time interval.

When the patients’ heart rates were compared between the groups over time, statistically significant differences were observed only at the 180th minute (p = 0.02), the 240th minute (p = 0.01), and the 300th minute (p = 0.04). At all three time points, heart rate was significantly lower in Group R compared to Group C (p = 0.02, p = 0.01, and p = 0.04, respectively).

When comparing EtCO₂ values between the groups over time, no statistically significant differences were found at any time point. Similarly, when comparing SpO₂ values between the groups over time, no statistically significant differences were observed. The comparison of arterial blood gas results between the groups over time is presented in Table 2.

Table 2.

Comparison of arterial blood gas results of patients between groups according to time periods

Time	Variable	Group R	Group C	p value
After intubation	pH, mean ± SD	7.41 ± 0.03	7.42 ± 0.03	0.580
	PaO ₂, mmHg	173.0 ± 26.7	223.3 ± 38.8	< 0.001
	PaCO₂, mmHg	35.2 ± 3.7	34.6 ± 4.2	0.465
2nd hour	pH, mean ± SD	7.42 ± 0.04	7.41 ± 0.04	0.261
	PaO2, mmHg	159.5 ± 18.1	212.7 ± 29.6	< 0.001
	PaCO2, mmHg	33.3 ± 4.4	33.6 ± 3.7	0.646
End of surgery	pH, mean ± SD	7.41 ± 0.04	7.40 ± 0.04	0.494
	PaO2, mmHg	156.3 ± 17.8	214.9 ± 24.6	< 0.001
	PaCO2, mmHg	33.3 ± 4.6	34.1 ± 5.5	0.308

Bold p values indicate statistical significance

Mean, SD Standard deviation, n number, PaO₂ Partial pressure of oxygen, PaCO₂ Partial pressure of carbon dioxide, mmHg millimeters of mercury

No statistically significant differences were observed between the two groups in terms of pH and PaCO₂ values at any time point, whereas PaO₂ values differed significantly at all time intervals (p < 0.001 for all comparisons). Arterial blood gas analyses obtained after intubation, at the intraoperative 2nd hour, and at the end of surgery showed that PaO₂ levels were significantly lower in Group R compared to Group C (p < 0.001 for all comparisons). The temporal changes in PaO₂ levels for both groups are illustrated in Fig. 1.

Fig. 1.

Temporal changes in PaO₂ levels for both groups

Intraoperative changes in ORi and FiO₂ for patients in Group R are presented in Figs. 2 and 3, respectively. The correlation between ORi values at the 120th minute and PaO₂ values at the 2nd hour is presented in Figure 4

Fig. 2.

Intraoperative changes in ORi values in patients from Group R

Fig. 3.

Intraoperative changes in FiO₂ values in patients from Group R

Fig. 4.

Correlation between ORi values at the 120th minute and PaO₂ values at the 2nd hour

A statistically significant correlation was observed between the ORi values at the 120th minute and PaO₂ values at the 2nd hour (p = 0.003). A positive and moderate correlation was found between these two variables (rho = 0.534). The ORi threshold value for predicting PaO₂ >150 mmHg was determined as 0.16 (> 0.16). For this threshold, sensitivity was calculated as 38.1%, specificity as 100%, positive predictive value as 100%, and negative predictive value as 38.1%.

The comparison of preoperative and postoperative oxidative stress markers (IMA, Native Thiol, Total Thiol, Disulfide, and D/NT*100) in Group R is presented in Table 3.

Table 3.

Comparison of the preoperative and postoperative results of oxidative stress markers in the study group

Variable	Preoperative	Postoperative	P value
Nativ Thiol, µmol/L, mean ± SD	559.0 ± 89.4	467.1 ± 75.3	< 0.001
Total Thiol, µmol/L	595.9 ± 94.2	494.5 ± 78.3	< 0.001
Disulphide, µmol/L	18.4 ± 6.7	13.6 ± 5.5	0.004
D/NT*100,	3.35 ± 1.16	2.96 ± 1.22	0.233
IMA, ABSU	0.61 ± 0.11	0.67 ± 0.09	0.02

Bold p-values indicate statistical significance

Italic p-values indicate a trend toward statistical significance

Mean, SD Standard deviation, μmol/L micromole/liter, ABSU Absorbance unit, D/NT Disulfide/native thiol, IMA ischemia modified albumin

In Group R, statistically significant differences were observed between preoperative and postoperative values in terms of Native Thiol (p < 0.001), Total Thiol (p < 0.001), Disulfide (p = 0.004), and IMA (p = 0.02). Native Thiol, Total Thiol, and Disulfide levels were significantly higher in the preoperative period compared to the postoperative period (p < 0.001, p < 0.001, and p = 0.004, respectively), whereas IMA was significantly lower in the preoperative period than in the postoperative period (p = 0.02).

The comparison of preoperative and postoperative results of oxidative stress markers (Native Thiol, Total Thiol, Disulfide, and Disulfide/Native Thiol*100) in Group C is presented in Table 4.

Table 4.

Comparison of preoperative and postoperative oxidative stress marker levels in the control group

Variable	Preoperative	Postoperative	P değeri
Nativ Thiol, µmol/L, mean ± SD	583.7 ± 63.1	436.8 ± 51.8	< 0.001
Total Thiol, µmol/L	617.1 ± 68.2	464.7 ± 55.8	< 0.001
Disulphide, µmol/L	16.6 ± 4.3	13.9 ± 3.9	0.01
D/NT*100	2.84 ± 0.64	3.18 ± 0.80	0.08
IMA, ABSU	0.58 ± 0.04	0.71 ± 0.06	< 0.001

Bold p-values indicate statistical significance

Italic p-values indicate a trend toward statistical significance

Mean, SD Standard deviation, μmol/L micromole/liter, ABSU absorbance unit, D/NT disulphide/native thiol, IMA ischemia modified albumin

In Group C, a statistically significant difference was observed between preoperative and postoperative values for Native Thiol (p < 0.001), Total Thiol (p < 0.001), Disulphide (p = 0.01), and IMA (p < 0.001). Native Thiol, Total Thiol, and Disulfide levels were statistically higher in the preoperative period compared to the postoperative period, whereas IMA levels were statistically lower in the preoperative period compared to the postoperative period.

The comparison of preoperative and postoperative results of oxidative stress markers between the two groups is presented in Tables 5 and 6.

Table 5.

Comparison of preoperative oxidative stress marker levels between groups

Variable	Group R	Group C	P value
Native Thiol, µmol/L, mean ± SD	559.0 ± 89.4	583.7 ± 63.1	0.222
Total Thiol, µmol/L	595.9 ± 94.2	617.1 ± 68.2	0.324
Disulphide, µmol/L	18.4 ± 6.7	16.6 ± 4.3	0.229
D/NT*100	3.35 ± 1.16	2.84 ± 0.64	0.06
IMA, ABSU	0.61 ± 0.11	0.58 ± 0.04	0.291

Bold p-values indicate statistical significance

Italic p-values indicate a trend toward statistical significance

Mean, SD Standard deviation, μmol/L micromole/liter, ABSU absorbance unit, D/NT disulphide/native thiol, IMA ischemia modified albumin

Table 6.

Comparison of postoperative oxidative stress marker levels between groups

Variable	Group R	Group C	P value
Native Thiol, µmol/L, mean ± SD	467.1 ± 75.3	436.8 ± 51.8	0.03
Total Thiol, µmol/L	494.5 ± 78.3	464.7 ± 55.8	0.09
Disulphide, µmol/L	13.6 ± 5.5	13.9 ± 3.9	0.835
D/NT*100	2.96 ± 1.22	3.18 ± 0.80	0.412
IMA, ABSU	0.67 ± 0.09	0.71 ± 0.06	0.01

Bold p-values indicate statistical significance

Italic p-values indicate a trend toward statistical significance

Mean, SD Standard deviation, μmol/L micromole/liter, ABSU absorbance unit, D/NT disulphide/native thiol, IMA Ischemia modified albumin

No statistically significant difference was observed between the two groups in terms of preoperative oxidative stress markers.However, postoperative Native Thiol (p = 0.03) and IMA (p = 0.01) levels showed a statistically significant difference between the groups.Postoperative Native Thiol levels were significantly higher in Group R compared to Group C (p = 0.03), while postoperative IMA levels were significantly lower in Group R compared to Group C (p = 0.01).

The comparison of the changes in oxidative stress markers from preoperative to postoperative between the groups is presented in Table 7.

Table 7.

Comparison of the changes in oxidative stress markers from preoperative to postoperative between the groups

Variable	Group R	Group C	P value
Native Thiol, µmol/L, mean ± SD	−91.8 ± 73.9	−146.9 ± 69.4	0.004
Total Thiol, µmol/L	−101.4 ± 73.7	−152.3 ± 76.3	0.01
Disulphide, µmol/L	−4.7 ± 8.5	−2.7 ± 6.1	0.295
D/NT*100	−0.36 ± 1.75	0.33 ± 1.10	0.06
IMA, ABSU	0.06 ± 0.08	0.12 ± 0.07	0.002

Bold p-values indicate statistical significance

Italic p-values indicate a trend toward statistical significance

Mean, SD Standard deviation, μmol/L micromole/liter, ABSU Absorbance unit, D/NT Disulphide/native thiol, IMA Ischemia modified albumin

A statistically significant difference was found between the two groups in terms of changes in Native Thiol (p = 0.004), Total Thiol (p = 0.01), and IMA (p = 0.002) levels. The decrease in Native Thiol and Total Thiol from the preoperative to the postoperative period was found to be less in Group R compared to Group C (p = 0.004 and p = 0.01, respectively). The increase in IMA levels in Group R was also found to be lower than that in Group C (p = 0.002).

Discussion

In this study, we aimed to evaluate whether the use of ORi monitoring in patients undergoing rhinoplasty could help prevent hyperoxemia and subsequently reduce the oxidative stress induced by hyperoxemia. The results of our study suggest that FiO₂ can be titrated down under ORi guidance, resulting in lower PaO₂ levels and lower incidences of hyperoxemia, thereby reducing oxidative stress.

In the study conducted by Chen et al. [3] PaO₂ levels were categorized as follows: 0–80 mmHg as hypoxemia, 80–100 mmHg as normoxemia, and >100 mmHg as hyperoxemia. Scheeren et al. [2] further classified hyperoxemia into mild (PaO₂ >100 mmHg) and severe (PaO₂ >200 mmHg) categories. As observed in various studies in the literature, different thresholds of PaO₂ have been used to define hyperoxemia.

In our study, PaO₂ values between 90 and 120 mmHg and SpO₂ levels of 98–100% were considered normoxic. PaO₂ values between 120 and 200 mmHg were classified as mild hyperoxemia, while values between 200 and 300 mmHg were defined as severe hyperoxemia. In the group receiving oxygen conservatively, with FiO₂ titrated and reduced according to ORi guidance, mean PaO₂ values were 173 mmHg after intubation, 159 mmHg at the second intraoperative hour, and 156 mmHg at the end of the surgical procedure. In contrast, in the group receiving conventional oxygen therapy without FiO₂ adjustments, the corresponding mean PaO₂ values were 223 mmHg after intubation, 212 mmHg at the second intraoperative hour, and 214 mmHg at the end of the procedure. While mild hyperoxemia predominated in Group R, severe hyperoxemia was observed in Group C.

In our study, no significant differences were observed between the two groups in terms of SpO₂, EtCO₂, pH, and PaCO₂ values, and all results remained within physiological limits. No adverse events, including hypoxemia episodes, were observed in the ORi group during the study period. This indicates that while hyperoxemia was reduced through ORi-guided oxygen titration, other key respiratory parameters were preserved.

In a study conducted by Yoshida et al. [4] involving 20 patients who were scheduled for surgery under general anesthesia with arterial catheterization, FiO₂ was reduced to as low as 0.33 to achieve near-zero ORi values. Arterial blood gas analyses were performed when ORi values were 0.5, 0.2, and 0, and comparisons were made with PaO₂ levels. The results suggested that ORi values below 0.21 could help avoid hyperoxia. Consistent with our findings, this and similar studies confirm the important role of ORi in preventing excessive hyperoxia during general anesthesia.

Duggan et al. [5] demonstrated that the use of pure oxygen can lead to resorption atelectasis shortly after anesthesia induction, which increases right-to-left shunting and impairs pulmonary gas exchange.

Li et al. [6] compared 100% oxygen with 21% oxygen during anesthesia induction during elective surgeries under general anesthesia and found that the safe apnea times were 469 and 63 s, respectively. They also reported that, in patients without difficult airways, the intubation time did not exceed 40 s when performed by experienced anesthesiologists, and that nearly all patients were successfully intubated on the first attempt.

In our study, we administered 50% FiO₂ during induction in the group monitored with ORi. The mean ORi value at the end of mask ventilation was 0.59, and it decreased to 0.03 at the end of intubation. Alongside SpO₂ monitoring, ORi values provided reassurance regarding the safety of the apnea period. Additionally, all patients included in the study were ASA I or II young individuals without any features suggestive of a difficult airway. No hypoxic adverse events occurred in any patient, and all were intubated successfully on the first attempt. We concluded that using 50% oxygen guided by ORi during induction can be safely applied by experienced anesthesiologists in patients without a difficult airway, potentially avoiding the adverse effects of hyperoxia.

A positive correlation exists between ORi and PaO₂. In a study by Applegate et al. [7], which investigated the relationship between PaO₂ and ORi during elective surgery, PaO₂ values were found to be significantly and positively correlated with ORi values. For PaO₂ ≥ 150 mmHg, 96.6% of ORi values were found to be above 0.55.

Similarly, in our study, a positive correlation between ORi and PaO₂ was observed. To detect PaO₂ ≥150 mmHg, we determined an ORi cutoff value of 0.16. ORi values greater than 0.16 predicted PaO₂ ≥150 mmHg with 100% specificity. While many studies in the literature have been conducted in normotensive anesthesia settings, our study was performed in patients under hypotensive anesthesia. We believe this may have influenced the cutoff value observed in our findings.

In the study conducted by Sarızeybek et al. [8], the correlation between ORi and PaO₂ was investigated in patients undergoing hypotensive anesthesia. The ORi cutoff value determined to detect PaO₂ ≥150 mmHg was reported as 0.

Oxygen is commonly used in clinical practice to prevent or treat hypoxia; however, excessive use may lead to oxidative stress. Oxidative stress is defined as a disruption of the oxidative balance resulting from an increased generation of reactive oxygen species (ROS) during cellular metabolism and an insufficient level of antioxidants to detoxify them. ROS is formed by the reaction of molecular oxygen with H₂O, the most stable form of oxygen. In this reaction, the stepwise addition of electrons to molecular oxygen (O₂) leads to the formation of superoxide anion (O₂ˉ), hydrogen peroxide (H₂O₂), and hydroxyl radical (-OH). Among these, the hydroxyl radical is the most reactive form of oxygen radicals. Although ROS are essential for normal cellular functions such as intracellular signaling and defense against external threats, their excessive production can lead to molecular and cellular dysfunction. Excessive ROS attack nucleotide bases in nucleic acids, amino acid side chains in proteins, and double bonds in unsaturated fatty acids, resulting in oxidative stress that damages DNA, RNA, proteins, and lipids, leading to structural and metabolic changes in cells.

The primary aim of our study was to reduce oxidative stress by preventing hyperoxia. We demonstrated that the severity of hyperoxia was reduced through the use of ORi. To evaluate oxidative stress, we assessed the thiol–disulfide balance and ischemia-modified albumin (IMA) levels.

One of the antioxidants that play a significant role in the body’s defense against ROS is thiols. Upon exposure to oxidative stress, thiols react with free radicals, resulting in the formation of disulfides, which are reversible products. Therefore, a decrease in thiol levels indicates the presence of oxidative stress. The ratio of disulfides to thiols reflects the oxidant–antioxidant balance. Another commonly used parameter for evaluating oxidative stress is ischemia-modified albumin (IMA). The generation of ROS can alter the N-terminal region of albumin, thereby increasing IMA levels [9].

Several studies have shown that thiol/disulfide homeostasis and ischemia-modified albumin (IMA) can serve as biomarkers of oxidative stress in various surgical settings. In a study by Kutluhan et al., which compared inhalational and total intravenous anesthesia in vertebral surgery, it was reported that dynamic thiol/disulfide homeostasis reflects oxidative stress. Furthermore, the study indicated that propofol has a beneficial effect on oxidative stress in elective vertebral surgeries [10].

In our study, to evaluate oxidative stress, preoperative and postoperative levels of native thiol, total thiol, disulfide, and ischemia-modified albumin (IMA) were compared between the ORi group (Group R) and the control group (Group C). While no statistically significant differences were observed between the groups in terms of preoperative oxidative stress markers, significant differences were found in postoperative native thiol (p = 0.03) and IMA levels (p = 0.01). Postoperative native thiol levels were significantly higher in Group R compared to Group C, whereas postoperative IMA levels were significantly lower in Group R. Statistically significant differences were also observed between the groups in the changes from pre- to postoperative levels of native thiol (p = 0.004), total thiol (p = 0.01), and IMA (p = 0.002). The decrease in native thiol and total thiol levels from the preoperative period was found to be less pronounced in Group R than in Group C. Similarly, the increase in IMA levels was less in Group R compared to Group C. These findings suggest that Group R, in which ORi monitoring was used, was exposed to less oxidative stress compared to the control group, as indicated by smaller decreases in native and total thiol levels and a smaller increase in IMA levels.

The effects of high perioperative oxygen concentrations on oxidative stress have been emphasized in numerous studies. Oldman et al. [11] conducted a systematic review investigating the impact of perioperative oxygen concentration on oxidative stress in adult surgical patients. In this study, which included 422 patients, it was reported that higher intraoperative FiO₂ levels may be associated with increased perioperative oxidative stress. Köksal et al. [12] compared the administration of 80% perioperative oxygen concentration to 40% oxygen during abdominal surgery. They found that 80% FiO₂ led to higher lactate levels and greater oxidative stress, and it inhibited the antioxidant response compared to 40% FiO₂.

Reiterer et al. [13] investigated the relationship between perioperative supplemental oxygen and oxidative stress in patients undergoing moderate- to high-risk major abdominal surgery. When comparing the administration of 0.8 FiO₂ versus 0.3 FiO₂ throughout surgery and during the first two postoperative hours, they found no significant difference in terms of oxidative stress. They noted that the inclusion of patients with cardiovascular comorbidities, who may have inherently higher oxidative stress levels, could have influenced the results. Additionally, the use of only a single parameter to assess oxidative stress—namely, static oxidation-reduction potential (sORP) and oxidation-reduction potential capacity (cORP)—was highlighted as a limitation of the study. In our study, by selecting young patients with ASA physical status I–II, we aimed to reduce variability and potential confounding effects that might influence the study results.

In our study, we used 50% oxygen during induction in the ORi group and reduced supplemental oxygen levels to normoxic ranges as much as possible through ORi monitoring. Accordingly, the average FiO₂ level in the ORi group remained around 30% after induction. In the control group, 100% oxygen was administered during induction, followed by 50% oxygen from post-intubation until the end of the surgery.

The duration of hyperoxia exposure plays an important role in the development of oxidative stress. Susta et al. [14] did not observe a significant difference in oxidative stress between the normoxic group and volunteers exposed to hyperoxia episodes lasting approximately 40–50 min. Similarly, in the study by Khaw et al. [15] on patients undergoing elective cesarean section under general anaesthesia, the absence of a significant difference in oxidative stress between varying FiO₂ levels may be attributed to the relatively short duration of the surgical procedure. For our study, we selected rhinoplasty procedures that were relatively longer in duration compared to other surgeries performed in our clinic. To minimize the influence of potential confounding factors such as pain and awakening time, we excluded the emergence phase from anesthesia from our analysis. In our study, the mean duration from induction to the end of surgery was 225 min. We concluded that this duration was sufficient for the development of oxidative stress. Nevertheless, the generalizability of our findings to standard rhinoplasty procedures, which are typically shorter in duration, may be limited.

Limitations

There are several limitations in this study that should be considered when interpreting the results. The other indicators of oxidative stress, such as malondialdehyde (MDA), Total Oxidant Status (TOS), and Total Antioxidant Status (TAS), were not evaluated in our study.

Additionally, although the study was sufficiently powered to detect changes in Native Thiol levels, it may have been underpowered for detecting differences in Disulfide and IMA due to smaller effect sizes. Future studies with larger cohorts are warranted to validate these findings. Cigarette smoking increases oxidative stress [16]. The patients classified as ASA 2 were those who smoked without additional comorbidities. Smoking could not be excluded from our study. However, the lack of a statistical difference between groups regarding the preoperative ASA and oxidative stress markers strengthens the significance of the postoperative results.

The study population was young (median age 22) and mostly ASA I/II. Therefore, the findings may not be directly generalizable to older patients or those with significant comorbidities. Further studies involving broader patient populations are warranted to validate these results.

Conclusion

In our study, patients who used ORi had PaO₂ values closer to normoxic levels compared to those who received conventional oxygen. Additionally, in the ORi group, there was less reduction in native thiol and total thiol levels, and a smaller increase in IMA values, indicating a positive impact on oxidative stress. In conclusion, our study suggests that ORi-guided oxygen titration during rhinoplasty may reduce the severity of hyperoxia and may help decrease oxidative stress.

Abbreviations

ORi

Oxygen Reserve Index

PaO₂

Arterial oxygen pressure peripheral oxygen saturation

SpO₂

Peripheral oxygen saturation

FiO₂

Fraction of Inspired Oxygen

IMA

Ischemia-modified albumin

ASA

American Society of Anesthesiologists

HR

Heart rate

SBP

Systolic blood pressure

DBP

Diastolic blood pressure

TV

Tidal volume

PEEP

Positive end-expiratory pressure

Authors’ contributions

RK, FDG, and KTS jointly contributed to the conceptualization and design of the manuscript. RK collected the data. RK, FDG, BEÇ made significant contributions to the analysis and interpretation of the data. All authors have participated to drafting the manuscript, author RK revised it critically. All authors read and approved the final version of the manuscript.

Funding

This study received no funding.

Data availability

De-identified individual participant data, the data dictionary, and the SPSS statistical code used in this study will not be made publicly available. However, they may be provided by the corresponding author upon reasonable request.

Declarations

Ethics approval and consent to participate

The present study was conducted between March and August 2021, following the approval of the Ethics Committee of the University of Health Sciences Kartal Dr. Lütfi Kırdar City Hospital (Decision No: 2021/514/196/4, dated February 24, 2021) and the Academic Board of the Faculty of Medicine, University of Health Sciences. The study was carried out according to the Declaration of Helsinki and Good Clinical Practice guidelines. All participants provided informed consent to participate in the study.

Written informed consent was obtained from all participants prior to their inclusion in the study.

Consent for publication

Not applicable. Our study complies with CONSORT guidelines.

Competing interests

The authors declare no competing interests.