Introduction
The oxygen reserve index is a non-invasive continuous parameter that ranges between 0 and 1 and provides information about the trends in a patient’s oxygen reserve when the arterial partial pressure of oxygen (PaO2) is between 100 and 200 mmHg [1,2]. In contrast to pulse oximetry (SpO2) that only indicates a maximum value of 100% when PaO2 exceeds 100 mmHg, the ORI offers an estimate of both the degree of oxygen saturation in venous blood and the extent of PaO2 elevation. Monitoring the ORI can mitigate the risk of hypoxia in patients undergoing general anesthesia induction, those requiring rapid sequence induction, or those requiring one-lung ventilation (OLV) before the onset of reductions in SpO2 [3–5].
Additionally, the ORI facilitates the estimation of PaO2 values > 100 mmHg, thereby potentially preventing patient exposure to hyperoxemia [4]. Hyperoxemia is associated with increased systemic vascular resistance, reduced microcirculation, and absorption atelectasis, and is frequently refractory to alveolar recruitment maneuvers. In children, hyperoxemia may contribute to postoperative reductions in lung volume and ventilation heterogeneity [6,7]. Moreover, perioperative hyperoxemia is correlated with adverse postoperative outcomes [8]. Therefore, implementing strategies during mechanical ventilation that prevent hypoxia while avoiding unnecessary exposure to elevated oxygen concentrations is crucial, particularly in patients undergoing lung resection surgery.
In pediatric patients undergoing OLV for thoracic surgery, the risk of hypoxemia is greater than that in adults, leading to the frequent use of approximately 100% oxygen. However, especially in small children, frequent arterial blood gas analysis (ABGA) is not feasible, making it challenging to detect hyperoxemia when the SpO2 is 100%. Therefore, the ORI is considered a useful tool for monitoring hyperoxemia in such situations.
A review of preliminary data from 24 pediatric patients who underwent OLV at our center revealed that approximately 88% (21 patients) experienced significant hyperoxemia with PaO2 levels > 200 mmHg, and more than half (14 patients) had PaO2 levels > 300 mmHg. These findings indicate that children are at a risk of excessive oxygen exposure during OLV.
Therefore, this study aimed to evaluate the incidence of significant hyperoxemia (PaO2 > 200 mmHg) [9] when the fraction of inspired oxygen (FiO2) was adjusted based on the ORI compared with conventional FiO2 adjustment methods in pediatric patients undergoing OLV. We aimed to assess whether ORI monitoring enables more precise oxygen control. Additionally, the frequency of hypoxia and the occurrence of postoperative complications were assessed to determine the efficacy of ORI-guided FiO2 adjustment management during surgery.
Materials and Methods
Ethics
The institutional research ethics committee (Institutional Review Board of Seoul National University Hospital) approved this prospective, randomized, single-center study (No. 2205-156-1329; Chairperson Professor Ok-Joo Kim, date of approval: 20 July 2022), and the study protocol was registered at http://clinicaltrials.gov (NCT05912543) before patient enrollment. Before each surgery, the anesthesiologist met with the child’s parents, explained the study protocol, and obtained written informed consent from the parents. The study was conducted per the ethical standards set by the Declaration of Helsinki (2013) and its later amendments.
Study population
Pediatric patients aged < 7 years with an American Society of Anesthesiologists physical status of 1–2 who underwent video-assisted thoracoscopic lung lobectomy or segmentectomy for congenital cystic adenomatoid malformation between June 2023 and July 2024 were enrolled. Patients with respiratory distress, cyanosis, bronchopulmonary dysplasia, tracheal stenosis, tracheomalacia, or under oxygen supplementation preoperatively were excluded from this study. Patients were also excluded if their ORI value was 0 at the time of mask ventilation with 100% oxygen during anesthesia induction.
Group allocation
The patients were randomly assigned to one of two groups, the conventional group or the ORI group, after a simple randomization procedure (computerized randomization: https://sealedenvelope.com/). The anesthesiology research coordinator, who was not involved in patient care, created and managed the sealed, opaque envelopes containing the group allocation. Upon enrollment of a study participant, the envelope was opened to reveal the assigned group.
Blinding was maintained for the patients, their guardians, the surgeons, the nursing staff, and the outcome assessors. However, due to the nature of FiO2 adjustments, the attending anesthesiologists were necessarily aware of group allocation. To minimize bias, anesthesiologists were instructed to follow the assigned protocol strictly, and a separate investigator who remained blinded to the group assignments conducted postoperative data analysis.
Video-assisted thoracoscopic lung resection surgery
All patients, including the study participants, underwent a standardized surgical protocol assessment for video-assisted thoracoscopic lung resection of congenital cystic adenomatoid malformation. The patients were admitted 1 day before surgery for preoperative tests, including chest radiography and venous blood gas analysis. After lung resection, an air leak test was conducted, and a mini-tube was placed in the thoracic cavity. Daily chest radiography was performed until a pneumothorax, hemothorax, pleural effusion, or other complications were observed. The chest tube was removed once normal radiographic findings were confirmed, and the patient was discharged the following day. Additional antibiotics, such as piperacillin/tazobactam, were administered if a respiratory infection was suspected.
Anesthesia protocol
Anesthesia was initiated using atropine (0.02 mg/kg), thiopental sodium (5 mg/kg), and rocuronium (0.6 mg/kg). Subsequently, it was maintained with sevoflurane (1.5–2.5 vol%), titrated to maintain a Patient State Index (SEDLine®; Masimo Corporation) of 20–50, alongside a continuous infusion of remifentanil at 0.1–0.2 µg/kg/min. An additional dose of rocuronium (0.3 mg/kg) was administered during surgery. Electrocardiography, peripheral oxygen saturation, and invasive arterial blood pressure were monitored during anesthesia. Additionally, the ORI (rainbow Pulse CO-Oximetry sensor, Radical-7 Pulse CO-Oximeter, Masimo) was continuously measured and recorded in all patients, regardless of groups, using a pulse oximeter sensor placed on the patient’s toe. The ORI sensor was connected to a Radical-7 pulse oximeter using a Root Platform (Masimo).
Immediately after endotracheal intubation, the ventilator setting was adjusted to an FiO2 of 40%, tidal volume of 7 ml/kg, and positive end-expiratory pressure (PEEP) of 6 cmH2O. An esophageal stethoscope with a temperature sensor (Top probe; MediTop Corp.) was inserted, and the core temperature was continuously monitored. The 3- or 4-Fr Fogarty catheter (Fogarty® Occlusion Catheter; Edwards Lifesciences) or 5-Fr endobronchial blocker (Arndt blocker; Cook Critical Care) was used according to main bronchus size. The Fogarty catheter and bronchial blocker were introduced under fiberoptic bronchoscopy guidance (Olympus LF-DP; Olympus Corporation). After lateral decubitus positioning and lung separation, the OLV was performed. The initial ventilator settings for OLV included FiO2, tidal volume, and PEEP of 100%, 5 ml/kg, and 6 cmH2O, respectively. Respiratory rate was adjusted to maintain an end-tidal CO2 of approximately 40 mmHg. The inspired oxygen concentration was subsequently adjusted according to the treatment group protocol.
ABGA was performed 10 min after the start of OLV (T1) and 30 min after the start of OLV (T2). Additional arterial blood gas analyses were performed as required based on the anesthesiologist’s judgment (Fig. 1).
Study protocol
Inhaled oxygen concentration in each group during OLV was regulated according to the following protocol: In all the groups, the initial FiO2 was set to 100%.
The conventional group followed the institutional protocol for thoracic surgery. FiO2 was changed to 80% if moderate hyperoxemia (200 ≤ PaO2 < 300 mmHg) [10] was detected at T1 or T2. If severe hyperoxemia (PaO2 ≥ 300 mmHg) [10] was identified, the FiO2 was reduced to 70%. FiO2 was adjusted to 100% again when SpO2 gradually decreased to less than 98%, and when hypoxia (SpO2 < 95%) occurred even with an FiO2 of 100%, rescue interventions, including administration of fluid or inotropic agents to increase cardiac output, alveolar recruitment maneuver, return to two-lung ventilation, or application of continuous positive airway pressure, could be applied at any point during OLV.
In the ORI group, ORI monitoring began immediately at the initiation of OLV and was recorded at five-minute intervals thereafter. The FiO2 was adjusted (increased or decreased) by 5% to maintain a target ORI of 0.15. If the ORI dropped below 0.15 despite FiO2 being set at 100%, rescue interventions were initiated following the same protocol as in the conventional group when SpO2 fell below 95%.
The target ORI value was determined based on the results of a previous study conducted by our research team (brief title: The relationship between ORI and PaO2 [clinicaltrials.gov number: NCT03130023]). In that study, linear regression analysis revealed that PaO2 could be calculated using the following formula: PaO2 = (161.7 × ORI) + 150.1 (r2 = 0.408, P < 0.001). When the ORI was set to 0.15, PaO2 was calculated to be 174 mmHg. This value was considered optimal, as it maintained PaO2 to avoid acute hypoxia while ensuring adequate oxygen delivery.
All hemodynamic and respiratory variables were obtained using the Vital Recorder program (VitalDB; https://vitaldb.net/) [11] that is a free Windows program that automatically collects high-resolution time-synchronized vital signs data generated from various anesthesia equipment for research purposes.
Sample size calculation
A retrospective analysis of arterial blood gas results in pediatric patients who underwent OLV at our center showed that approximately 88% developed moderate hyperoxemia (PaO2 > 200 mmHg). It is estimated that adjusting oxygenation based on the ORI could reduce the incidence of hyperoxemia by up to 50%. Assuming an alpha error of 0.05 and a beta error of 0.05 (power = 0.95), 30 patients per group are required. Considering a 15% dropout rate, the total number of participants needed for the study is 70.
Outcome measurement
The primary outcome was the incidence rate of moderate and severe hyperoxemia (PaO2 ≥ 200 mmHg), as assessed by ABGA at T2. The secondary outcomes included the incidence rate of moderate hyperoxemia at T1, mean PaO2 values at T1 and T2, mean ORI values during OLV, time-weighted average FiO2, the occurrence of hypoxia, the number of rescue interventions, and the incidence rate of postoperative complications. The time-weighted average FiO2 was calculated throughout the entire OLV period. FiO2 values were recorded at one-second intervals using the Vital Recorder Program, and the weighted average was determined by multiplying each FiO2 value by the duration it was maintained, then dividing by the total OLV duration. Hypoxia was defined as a SpO2 of ≤ 95%. Postoperative complications were defined as the occurrence of hypoxia, pleural effusion, and pneumothorax confirmed via chest radiography or laryngospasm necessitating intervention during the post-anesthesia care unit stay and within 3 days postoperatively.
Statistical analyses
All data analyses were performed using IBM SPSS Statistics for Windows, version 23.0 (IBM Corp.). Data normality was assessed using the Kolmogorov–Smirnov test. Categorical variables are expressed as numbers and percentages, and continuous variables are expressed as means ± standard deviations or medians and interquartile ranges. The chi-squared test was used to test the significance of categorical data, and Fisher’s exact test was used when the expected count of more than 20% of cells was less than 5. All P values were two-sided, and statistical significance was set at P < 0.05.
Results
Seventy pediatric patients were enrolled and randomized into two groups from June 2023 to July 2024. Among them, six patients were excluded because their ORI data could not be obtained. Therefore, data from 64 pediatric patients (31 and 33 in the conventional and ORI groups, respectively) were analyzed (Fig. 2). The baseline and operative characteristics were comparable between the two groups (Table 1).
The number of patients with PaO2 ≥ 200 mmHg at 30 min after the start of OLV (T2) did not significantly differ between the conventional and ORI groups (17/31, 54.8% vs. 20/33, 60.6%; relative risk [95% CI], 0.90 [0.59–1.38]; P = 0.801). Additionally, no significant difference was found in the number of patients with PaO2 ≥ 200 mmHg at T1 between the conventional and ORI groups (20/31, 64.5% vs. 24/33, 72.7%; relative risk [95% CI], 0.89 [0.63–1.24]; P = 0.592) (Table 2).
Although the mean PaO2 values at T2 did not differ between the two groups (P = 0.851), the ORI group showed lower PaO2 values than the conventional group (214.6 ± 65.5 mmHg vs. 268.8 ± 92.7 mmHg; mean difference [95% CI], 54.2 [–14.7 to 93.8]; P = 0.014) at T1. Additionally, the ORI group showed lower averaged ORI values during OLV than the conventional group (0.16 ± 0.12 vs. 0.27 ± 0.24; mean difference [95% CI], 0.11 [–0.02 to 0.20]; P = 0.027).
The median number of rescue interventions per patient during OLV was significantly higher in the ORI group than in the conventional group (2 [0–4.5] vs. 0 [0–1], P = 0.001). Consequently, hypoxia (SpO2 < 95%) occurred more frequently in the conventional group than in the ORI group during OLV (8/31, 25.8% vs. 2/33, 6.1%; relative risk [95% CI], 4.26 [0.98–18.52]; P = 0.041). The conventional group had higher time-weighted average FiO2 during OLV than the ORI group (0.87 ± 0.09 vs. 0.79 ± 0.12; mean difference [95% CI], –0.08 [–0.13 to –0.02]; P = 0.004) (Table 2).
No statistically significant differences were found in the hemodynamic variables between the two groups (Table 3). Eight patients in the conventional group (25.5%) and five in the ORI group (15.2%) had postoperative complications, without group difference (relative risk [95% CI], 1.70 [0.62–4.65]; P = 0.454) (Table 4).
Discussion
In this randomized controlled trial, ORI-guided FiO2 adjustment during OLV did not decrease the incidence rate of hyperoxemia in pediatric patients undergoing thoracoscopic lung resection. However, ORI-guided FiO2 adjustment resulted in a lower time-weighted average FiO2 during OLV and led to more interventions aimed at optimizing oxygenation that was supported by the fact that it reduced the incidence of hypoxia during OLV.
Our findings indicate that ORI-guided FiO2 adjustment does not conclusively prevent hyperoxemia. There are several possible explanations for these results. Yang et al. [12] explained the failure of ORI-targeted FiO2 adjustment during OLV to reduce oxygen exposure by suggesting that the presence of an intrapulmonary shunt limits the use of true ORI values. The ORI value cannot entirely replace the PaO2 value [13] and may be partially influenced by venous saturation and oxygen reserve. When intrapulmonary shunts are present, the ORI value may underestimate the true PaO2. Additionally, smaller children have a greater ventilation/perfusion (V/Q) mismatch in the lateral position owing to less gravity-driven perfusion distribution [14], and their oxygenation status may not be stable because the cardiac output or blood pressure is rapidly altered by surgical manipulation. Furthermore, in the ORI group, FiO2 was increased when ORI dropped below 0.15, following the study protocol, leading to a subsequent rise in PaO2 levels. While this proactive approach helped prevent hypoxia by adjusting FiO2 before SpO2 declined, it may have also contributed to maintaining high PaO2 values, thereby limiting any potential reduction in hyperoxemia incidence.
Recent studies by Yoshida et al. [15] and Bang et al. [16] found that ORI thresholds of 0.21 and 0.27, respectively, could distinguish PaO2 ≥ 150 mmHg, with a linear correlation between the two values. According to a study conducted in pediatric patients undergoing laryngeal procedures, the optimal cutoff value for ORI was 0.195 when PaO2 was 150 mmHg [13]. We selected the ORI cutoff value of 0.15 based on a linear regression model derived from the data of a previous study by our research team. When the ORI value was 0.15, the measured PaO2 would be 174 mmHg that was considered optimal during OLV to prevent both hyperoxemia and hypoxia.
The positive effect of ORI-guided FiO2 adjustment in this study was a reduced incidence of hypoxia. Young children have higher oxygen demands and lower pulmonary reserves, making them more vulnerable to desaturation [17,18]. As shown by the increased number of rescue interventions in the ORI group, our findings suggest that ORI monitoring enables earlier FiO2 adjustments, preventing hypoxemia before SpO2 declines. This has important clinical implications, as children desaturate rapidly [18], and frequent ABGA is often impractical. ORI monitoring may provide a more efficient, non-invasive method for optimizing oxygen titration, reducing hypoxia risk while maintaining safe oxygenation levels. Our result is similar to that of a previous study, which concluded that ORI enabled prompt interventions ultimately led to fewer episodes of low oxygen saturation in pediatric patients undergoing airway surgery [18].
Notably, the criteria for initiating rescue interventions differed between the two groups. In the ORI group, FiO2 adjustments were made preemptively to maintain an ORI value of 0.15, whereas in the control group, interventions were only triggered when SpO2 decreased despite FiO2 being set at 100%, following conventional OLV management. This difference in intervention thresholds might have influenced the frequency of rescue interventions and the observed outcomes.
ORI-guided FiO2 adjustment reduced time-weighted average FiO2. This result may be considered relatively conflicting with the following results: no difference was found in the mean PaO2 values 30 min after OLV between the two groups, and more hypoxic events occurred in the conventional group. However, when desaturation occurred in the conventional group, FiO2 was changed to 100%, and in the absence of ABGA, FiO2 was not adjusted accordingly. In contrast, in the ORI group, FiO2 was continuously adjusted during OLV, suggesting that oxygen was administered only when necessary to avoid excessive use.
An inconsistency between ORI and PaO2 was observed at T1 and T2. While our previous study suggested that an ORI of 0.15 corresponds to a PaO2 of 174 mmHg, the measured values in this study showed variability. At T2, the conventional group had a mean PaO2 of 215.87 mmHg with an ORI of 0.28, whereas the ORI group had a similar PaO2 of 216.64 mmHg but a lower ORI of 0.16. The inconsistency between ORI and PaO2 at T1 and T2 may be due to the non-linear relationship between ORI and PaO₂, with reduced correlation at higher PaO2 levels [19]. Additionally, individual variability in perfusion, hemoglobin concentration, and technical factors, including low perfusion states and sensor placement, can affect ORI accuracy. Intrapulmonary shunting and V/Q mismatch during OLV in pediatric patients may further contribute to these discrepancies, emphasizing the need for cautious interpretation and further research.
This study had some limitations. First, we could not compare the usefulness of ORI-guided FiO2 adjustment in preventing hyperoxemia before and after pulmonary artery ligation. According to Yang et al. [12], ORI values increased after pulmonary artery ligation, potentially enabling a reduction in time-weighted average FiO2. Second, we conducted ABGA only up to 30 min after the start of OLV. Additional PaO2 data during OLV would have enabled a more detailed assessment of the effect of the ORI in preventing hyperoxemia, with a more precise adjustment for FiO2 in the conventional group. However, frequent blood sampling in young children raises ethical concerns. Third, we did not control FiO2 based on ORI during two-lung ventilation. If we had applied different protocols between the two groups during two-lung ventilation as well, this would have allowed us to better assess the impact of ORI-guided FiO2 adjustment across both the OLV and two-lung ventilation phases. Additionally, in the conventional group, if a desaturation event occurred at least once after T2, FiO2 was maintained at 100% thereafter without further adjustment. This could have contributed to the lower time-weighted FiO2 observed in the ORI group, as FiO2 in the ORI group was continuously titrated based on ORI values. This limitation should be considered when interpreting the results. Finally, ORI data were not obtained in six patients, likely due to a low perfusion index affecting signal detection. As pediatric patients are prone to hypothermia and hemodynamic fluctuations, reduced peripheral perfusion may impact ORI reliability [20]. This limitation should be considered when interpreting ORI values in clinical practice, and further research is needed to optimize ORI signal acquisition in pediatric populations.
In conclusion, this study demonstrates that ORI-guided FiO2 adjustment in pediatric patients undergoing lung resection surgery does not reduce the incidence rate of hyperoxemia during OLV. However, it reduces the time-weighted average FiO2 and incidence rate of hypoxia that appears to be associated with more rescue interventions than the conventional method. Despite these benefits, no significant impact was observed on other postoperative outcomes. Further studies are needed to refine the clinical application of ORI for oxygen management in pediatric patients, particularly in those undergoing thoracic surgery or other procedures with a high risk of hyperoxemia. Those studies should focus on determining optimal ORI thresholds, standardizing FiO2 adjustment protocols, and assessing the long-term clinical impact of ORI-guided oxygen therapy.
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