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Review Articles: Meta-Analysis

The Effectiveness of High-Flow Nasal Oxygen During the Intraoperative Period: A Systematic Review and Meta-analysis

Spence, Emily A. BM BCh*; Rajaleelan, Wesley MD, DA; Wong, Jean MD, FRCPC; Chung, Frances MBBS, FRCPC; Wong, David T. MD, FRCPC

Author Information
doi: 10.1213/ANE.0000000000005073

Abstract

KEY POINTS

  • Question: Is high-flow nasal oxygen (HFNO) better than conventional oxygenation in reducing hypoxemia in the intraoperative setting?
  • Findings: HFNO versus conventional oxygenation reduces the risk of oxygen (O2) desaturation, increases minimum O2 saturation and safe apnea time.
  • Meaning: HFNO should be considered in the intraoperative setting in patients at higher risk of hypoxemia.

Oxygen desaturation may occur during induction of general anesthesia in patients at higher risk of hypoxemia and in patients with potentially difficult airways. Preoxygenation prolongs safe apnea time, improving the safety margin for induction of general anesthesia, and successful placement of the endotracheal tube.1 Conventionally, preoxygenation is performed before the induction of general anesthesia with a facemask and fraction of inspired oxygen (Fio2) 1.0, followed by bag-mask ventilation after unconsciousness ensues. Preoxygenation and apneic oxygenation are especially important in patients whereby manual ventilation after the induction of general anesthesia is to be avoided and in patients at higher risk of hypoxemia.2–4 Oxygen desaturation may also occur in patients undergoing surgical procedures such as bronchoscopy or colonoscopy under sedation without tracheal intubation.5,6 Various forms of supplemental oxygenation have been studied to reduce hypoxemia in patients undergoing procedural sedation.5,6

High-flow nasal oxygen (HFNO) is a novel technique by which heated humidified oxygen is supplied via nasal prongs at flow rates ranging from 40 to 70 L·minute−1.4 The Fio2 ranges from 0.21 to 1.0.3,7 The advantage of HFNO over conventional facemask or low-flow nasal cannula oxygenation is that the oxygen flow rates are comparable or higher than the patient’s inspiratory flow rate, thereby reducing or eliminating the entrainment of room air during inspiration.3,4,7 HFNO flushes out anatomical dead space and reduces the rate of rise of partial pressure of carbon dioxide (Paco2) during apnea. HFNO also provides positive end-expiratory pressure (PEEP), amounting to approximately 1 cm of H2O for every 10 L·minute−1 flow.3,7,8 Additional benefits of HFNO include increased patient comfort and tolerance and reduced respiratory effort.7,8

The use of HFNO has been extensively analyzed in the intensive care settings.4,7–10 In a recent systematic review, Helviz and Einav7 found a reduction in incidence of tracheal intubation without a difference in mortality in patients treated with HFNO compared to conventional oxygen therapy in critically ill patients. However, the utility of intraoperative use of HFNO in surgical patients is much less studied and its effectiveness compared to conventional oxygenation is unclear.2,3 To our knowledge, there was no previously reported systematic review and meta-analysis on the effects of HFNO in surgical patients intraoperatively. The purpose of this systematic review is to compare O2 desaturation, minimum O2 saturation, safe apnea time, and end-tidal CO2 (Etco2) intraoperatively—at induction with general anesthesia and during surgical procedures under sedation without tracheal intubation—in patients receiving HFNO compared to conventional oxygenation.

METHODS

Study Selection, Inclusion, and Exclusion Criteria

Randomized trials and observational studies, in English language, that evaluated the use of HFNO during the intraoperative period, of adult (>18 years old) patients were included. Studies must include at least 1 of these 4 outcomes: (1) O2 desaturation, (2) minimum O2 saturation, (3) safe apnea time, or (4) Etco2, at induction with general anesthesia or during surgical procedures under sedation without tracheal intubation. Qualifying studies with HFNO and conventional oxygenation (control) subjects using either facemask or low-flow nasal cannula oxygenation were entered into meta-analysis. HNFO studies without any control subjects were included for qualitative assessment only. Obstetrics and pediatric patient studies were excluded.

Search Strategy

With the help of a research librarian, the following databases were searched from inception until March 25, 2019 using the Ovid search interfaces: Medline, Medline In-Process/ePubs, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Ovid Emcare Nursing. The Cumulative Index of Nursing and Allied Health Literature (CINAHL) was searched using the EbscoHost platform. The PubMed database (United States National Library of Medicine [NLM]) was searched with results limited to non-Medline citations. Additional searches were run over the clinical trials databases: ClinicalTrials.Gov, World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), and International Standard Randomised Controlled Trial Number (ISRCTNR). An updated search was performed from January 1, 2018 to February 26, 2020 using the same criteria by a research librarian.

The search strategy concept blocks were built on the topics of (high flow nasal oxygen) AND (surgery or perioperative) AND (studies), limited to human, and adults where possible. The search included the combination of the following MESH key words: “high flow nasal oxygen,” “high flow nasal cannula,” “nasal high flow,” “HFNO,” “HFNC,” “NHF,” “preoxygenation,” “peroxygenation,” “Optiflow,” “THRIVE,” “noninvasive ventilation,” “oxygen inhalation therapy,” “perioperative,” “preoperative,” “intraoperative,” “postoperative,” “postextubation,” “induction,” “Anesthesia,” “surgery,” “facemask,” “facemask ventilation.”

Study Screening and Selection

Titles and abstracts were independently screened by 2 authors (E.A.S., W.R.). Following selection of abstracts, full text of articles identified for possible inclusion were obtained and assessed for inclusion independently by the 2 reviewers (E.A.S., W.R.). Disagreements were resolved by consensus or by consulting the senior authors (D.T.W., J.W.). Studies must include 1 of these 4 outcomes: (a) O2 desaturation, (b) minimum O2 saturation, (c) safe apnea time, and (d) Etco2 at induction with general anesthesia or during surgical procedures under sedation.

Data Extraction and Analyses

Study characteristics were extracted independently by 2 authors (E.A.S., W.R.) using a standard data collection form in an Excel worksheet. The following information were extracted from each study: authors, year of publication, country of study, type of study, type of surgery, number of patients, intervention characteristics, use of HFNO. The 4 outcomes extracted were O2 desaturation, minimum O2 saturation, safe apnea time, and Etco2. Data were extracted independently by the 2 authors (E.A.S., W.R.), which were then reviewed by the senior authors (D.T.W., J.W.). The corresponding authors of studies with missing data were contacted to obtain the missing data.

The risk of bias of the randomized studies was assessed using the Cochrane risk of bias tool which evaluated 5 domains: (1) bias arising from the randomization process; (2) bias due to deviations from intended interventions; (3) bias due to missing outcome data; (4) bias in measurement of the outcome; and (5) bias in selection of the reported result (see Supplemental Digital Content, Appendix, https://links.lww.com/AA/D145). Each domain was rated as low risk, some concern, or high risk.

Meta-analysis was performed using Review Manager (RevMan version 5.3.5, The Nordic Cochrane Centre, Copenhagen, Denmark). Categorical and continuous variable summary data from each individual study were entered into Review Manager. The statistical method used for categorical outcome (O2 desaturation) was Mantel-Haenszel and the effect measure was odds ratio (OR). The statistical method used for continuous outcome (minimum O2 saturation, safe apnea time, Etco2) was inverse variance and the effect measure was mean difference. Fixed effect analysis models were used. Forest plots, OR (95% confidence interval [CI]), mean difference (95% CI), and heterogeneity (χ2 and I2) were generated for the 4 outcomes. For studies that showed results in median and range or interquartile range, the methodology of Wan et al11 was used to convert them into mean and standard deviation.

RESULTS

Figure 1 summarizes our strategy for the literature search. We identified 2474 citations; 1603 studies remained after duplicates were removed. Three hundred forty-eight articles were assessed for eligibility. Full-text articles excluded were studies in obstetric, intensive care patients, studies with abstract only, or missing the 4 defined outcomes. A total of 17 studies using HFNO, with or without control groups, were included for qualitative analyses. For quantitative analyses, 9 studies without controls and 2 studies that the authors contacted failed to provide standard deviations or ranges were excluded resulting in 6 studies. A supplementary search performed in February 2020 resulted in 118 citations; 3 studies were included for qualitative analyses and 2 for meta-analyses. The 8 included studies for quantitative analysis had a total of 2314 patients.

Figure 1.
Figure 1.:
PRISMA diagram showing identification, screening, eligibility, and inclusion of studies. PRISMA indicates Preferred Reporting Items for Systematic Reviews and Meta-analyses.

Eight randomized controlled trials (RCTs; 4 induction, 4 procedural, 2314 patients) where data were available for 1 or more of the 4 outcomes, (1) O2 desaturation, (2) minimum O2 saturation, (3) safe apnea time, and (4) Etco2, were included for meta-analyses. Five studies were used for meta-analysis of more than 1 outcome. For the induction cases with general anesthesia, HFNO cases received flow rate at 40–70 L·minute−1 and Fio2 1.0, while control cases received facemask with Fio2 1.0; for the procedural cases, HFNO cases received flow rate at 30–70 L·minute−1 and Fio2 0.40–1.0, while control cases received low-flow nasal cannula oxygenation at 2–4 L·minute−1 or bite block oxygen insufflation at 10 L·minute−1. The rating for risk of bias was generally low for all RCTs (Supplemental Digital Content, Appendix, https://links.lww.com/AA/D145).

The included studies covered a variety of situations in the intraoperative period including awake fiberoptic intubation and emergency surgery requiring rapid sequence induction. The types of surgeries included laryngeal, thoracic, bariatric, abdominal, orthopedic, renal, ophthalmic, dental, neurosurgery; and procedures included bronchoscopy, endobronchial ultrasound, gastroscopy, and colonoscopy. All studies using HFNO in the intraoperative period, both with and without control, were included in the qualitative analysis. Only controlled studies were included for meta-analyses.

O2 Desaturation

Five RCTs,12–16 2 induction and 3 procedural studies, compared the rate of O2 desaturation between HFNO and control patients (Table 1). Desaturation was defined as O2 saturation <90% in 4 studies and 93% in 1 study. HFNO was administered at flow rates between 30 and 70 L·minute−1 while controls received oxygen via facemask, nasal cannula or bite block.

Table 1. - Effect of High-Flow Nasal Oxygen Versus Control Group on O2 Desaturation
Author (Year) Type of Study Total No. of Patients HFNO Control Definition of O2 Desaturation O2 Desaturation: HFNO (No. of Subjects) O2 Desaturation: Control (No. of Subjects)
Lodenius et al13 (2018) RCT: induction
-general anes
80 40–70 lpm

n = 40
FM
Fio 2 = 1.0

n = 40
<93% 0%a (0/40) 12.5%a (5/40)
Rajan et al12 (2018) RCT: induction
-general anes
10 60 lpm

n = 5
FM
Fio 2 = 1.0

n = 5
<90% 0% (0/5) 80% (4/5)
Douglas et al14 (2018) RCT: procedure EBUS sedation 60 30–70 lpm

n = 30
Bite block 10 lpm

n = 30
<90% 13.3% (4/30) 33.3% (10/30)
Lin et al15 (2019) RCT: procedure gastroscopy sedation 1994 60 lpm

n = 994
NP 2 lpm

n = 1000
75%–90% 0%a (0/994) 8.4%a (84/1000)
Riccio et al16 (2019) RCT: procedure colonoscopy sedation 59 60 lpm

n = 28

Fio 2 = 0.4
NP 4 lpm

n = 31
<90% 39.3% (11/28) 45.2% (14/31)
Control = conventional oxygenation using facemask or low-flow nasal cannula.
Abbreviations: EBUS, endobronchial ultrasound; Fio2, fraction of inspired oxygen; FM, facemask; General anes, general anesthesia; HFNO, high-flow nasal oxygen; lpm, liters per minute; NP, nasal prongs; O2, oxygen; RCT, randomized controlled trial; SD, standard deviation.
aStatistically significant difference between HFNO and control groups.

Meta-analyses showed that the risk of intraoperative O2 desaturation was lower in HFNO versus conventional oxygenation control group; at induction, the OR (95% CI) was 0.06 (0.01–0.59; P = .02; Figure 2A); during procedure, OR (95% CI) was 0.09 (0.05–0.18; P < .001; Figure 2B).

Figure 2.
Figure 2.:
Forest plots comparing O2 desaturation in HFNO versus control groups. A, Forest plot of randomized controlled trials comparing O2 desaturation in HFNO versus control groups, at anesthesia induction. B, Forest plot of randomized controlled trials comparing O2 desaturation in HFNO versus control groups, during surgical procedures. CI indicates confidence interval; df, degrees of freedom; HFNO, high-flow nasal oxygen; M-H, Mantel-Haenszel; O2, oxygen.

The rate of O2 desaturation was also assessed in 6 uncontrolled studies consisting of 373 patients.2,17–21 All 6 studies showed low rates of O2 desaturation (0%–14%) when HFNO was used; notably, no patients desaturated in 2 studies.2,17

Minimum O2 Saturation

Five RCTs,12–14,22,23 3 induction and 2 procedural studies, compared the minimum O2 saturation between HFNO and control patients (Table 2). HFNO was administered at flow rates between 30 and 70 L·minute−1 while controls received oxygen via facemask, nasal cannula or bite block.

Table 2. - Effect of High-Flow Nasal Oxygen Versus Control Group on Minimum O2 Sat
Author Type of Study Total No. of Patients HFNO Control Minimum O2 Sat: HFNO (%) Minimum O2 Sat: Control (%)
Lodenius et al13 RCT: induction-general anes 80 40–70 lpm
n = 40
FM
Fio 2 = 1.0
n = 40
[99 (99–100) (96–100)] → 98.5 (1.1) [99 (97–100) (70–100)] → 92 (8.6)
Wong et al22 RCT: induction-general anes 40 40–60 lpm
n = 20
FM
Fio 2 = 1.0
n = 20
90.9a (3.5) 87.9a (4.7)
Rajan et al12 RCT: induction-general anes 10 60 lpm
n = 5
FM
Fio 2 = 1.0
n = 5
85.8a (9.31) 85.8a (9.31)
Douglas et al14 RCT: procedure EBUS sedation 60 30–70 lpm
n = 30
Bite block 10 lpm
n = 30
[97.5a (94–99) (77–100)] → 93 (6.6) [92a (88–95) (79–98)] → 90.3 (5.5)
Takakuwa et al23 Prospective controlled trial: procedure EBUS. Sedation 31 40 lpm
n = 12
NP 2–4 lpm
n = 19
93a (4) 88a (5)
Control = conventional oxygenation using facemask or low-flow nasal cannula. Mean (SD) or numbers after arrow show converted mean (SD) from (median [interquartile range] [range]).
Abbreviations: EBUS, endobronchial ultrasound; Fio2, fraction of inspired oxygen; FM, facemask; General anes, general anesthesia; HFNO, high-flow nasal oxygen; lpm, liters per minute; NP, nasal prongs; O2, oxygen; RCT, randomized controlled trial; Sat, saturation; SD, standard deviation.
aStatistically significant difference between HFNO and control groups.

Figure 3.
Figure 3.:
Forest plots comparing minimum O2 saturation in HFNO versus control groups. A, Forest plot of randomized controlled trials on minimum O2 saturation in HFNO versus control groups, at anesthesia induction. B, Forest plot of randomized controlled trials on minimum O2 saturation in HFNO versus control groups, during surgical procedures. CI indicates confidence interval; df, degrees of freedom; HFNO, high-flow nasal oxygen; IV, inverse variance; O2, oxygen; SD, standard deviation.

Meta-analyses showed that the minimum O2 saturation was higher in HFNO versus conventional oxygenation; at induction, the mean difference (95% CI) was 5.1% (3.3–6.9; P < .001; Figure 3A); during procedure, the mean difference (95% CI) was 4.0 (1.8–6.2; P < .001; Figure 3B). In 5 uncontrolled studies,2,21,24–26 consisting of 278 patients, the minimum O2 saturation ranged from 96% to 99%.

Safe Apnea Time

Four anesthesia induction RCTs12,13,22,27 compared safe apnea time between HFNO and control patients (Table 3). HFNO was administered at flow rates between 30 and 70 L·minute−1 while controls received oxygen via facemask at between 10 and 15 L·minute−1.

Table 3. - Effect of High-Flow Nasal Oxygen Versus Control Group on Safe Apnea Time
Author Type of Study Total No. of Patients HFNO Control Safe Apnea Time: HFNO (Seconds) Safe Apnea Time: Control (Seconds)
Lodenius et al13 RCT: induction-general anes 80 40–70 lpm
n = 40
FM
Fio 2 = 1.0
n = 40
[109 (86–142) (37–291)] → 135.5 (73.3) [116 (92–146) (63–249)] → 136 (53.7)
Wong et al22 RCT: induction-general anes 40 40–60 lpm
n = 20
FM
Fio 2 = 1.0
n = 20
261.4a (77.7) 185.5a (53)
Mir et al27 RCT: induction-general anes 40 30–70 lpm
n = 20
FM
Fio 2 = 1.0
n = 20
248a (71) 123a (55)
Rajan et al12 RCT: induction-general anes 10 60 lpm
n = 5
FM
Fio 2 = 1.0
n = 5
796a (43.36) 444a (52.56)
Control = conventional oxygenation using facemask or low-flow nasal cannula. Mean (SD) or numbers after arrow show converted mean (SD) from (median [interquartile range] [range]).
Abbreviations: Fio2, fraction of inspired oxygen; FM, facemask; General anes, general anesthesia; HFNO, high-flow nasal oxygen; lpm, liters per minute; NP, nasal prongs; O2, oxygen; RCT, randomized controlled trial; SD, standard deviation.
aStatistically significant difference between HFNO and control groups.

Meta-analysis based on the 4 studies showed a significantly longer safe apnea time in the HFNO group. Due to the high heterogeneity, a sensitivity analysis was performed excluding Rajan et al’s12 study, which had a small sample size of 10 and an apnea time much higher than the other 3 trials. We revised the meta-analysis after excluding Rajan et al’s12 study. From meta-analysis of the 3 studies, safe apnea time was significantly longer with HFNO compared to facemask oxygen by a mean difference (95% CI) of 33.4 (16.8–50.1; P < .001) seconds (Figure 4A).

Figure 4.
Figure 4.:
Forest plots comparing safe apnea time and Etco 2 in HFNO versus control groups. A, Forest plot of randomized controlled trials on safe apnea time (in seconds) for HFNO versus control groups. B, Forest plot of randomized controlled trials on Etco 2 level (in mm Hg) for HFNO versus control groups. CI indicates confidence interval; df, degrees of freedom; Etco 2, end-tidal CO2; HFNO, high-flow nasal oxygen; IV, inverse variance; SD, standard deviation.

Safe apnea time was also assessed in 6 uncontrolled studies consisting of 182 patients.2,18–20,24,25 Five of 6 of these studies were elective surgical cases and they showed long safe apnea times using HFNO, ranging from 14 to 22.5 minutes. One study involving emergency intubation showed a safe apnea time of 2 minutes.18

End-Tidal CO2

Three anesthesia induction RCTs13,22,27 compared the Etco2 between HFNO and control patients. Meta-analysis showed that the Etco2 was similar in HFNO and facemask subjects with a mean difference of −1.0 (−2.4 to 0.4) mm Hg (Figure 4B).

Etco2 was also assessed in 8 uncontrolled studies consisting of 205 patients.2,17,19,20,25,26,28,29 The Etco2 ranged between 36 and 64 mm Hg. Of note, in Patel and Nouraei2 study, after a median of 14 minutes apnea time, the mean Etco2was 58.5 mm Hg; the rate of increase was shown to be 1.1 mm Hg per minute.

DISCUSSION

This systematic review and meta-analysis are the first to compare intraoperative HFNO to conventional oxygenation (control group) in patients undergoing surgery. We found the risk of intraoperative O2 desaturation was lower in patients receiving HFNO versus conventional oxygenation; at induction, the OR was 0.06, while during procedure, the OR was 0.09. The minimum O2 saturation was higher in patients receiving HFNO versus conventional oxygenation; at induction, the mean difference was 5.1%, and during procedure, 4.0%. The safe apnea time was prolonged using HFNO by a mean difference of 33.4 seconds. There was no difference in Etco2 between HFNO and conventional oxygenation patients.

Consistent with previous studies in the intensive care setting with patients with acute respiratory failure, we found that patients receiving HFNO were significantly less likely to desaturate compared to conventional oxygenation.4,30 However, 1 study1 showed contrary results with HFNO being no better than facemask preoxygenation for preventing desaturation during tracheal intubation in severely hypoxemic intensive care unit (ICU) patients. In critically ill patients, major shunting exists due to conditions such as adult respiratory distress syndrome and pulmonary edema, HFNO may be less effective dealing with ventilation-perfusion mismatch.

Our finding showed that minimum O2 saturation was 4%–5.1% higher in the HFNO group compared to the conventional oxygenation. This finding is consistent with the literature on HFNO in intensive care settings.4,7–10 Studies in intensive care settings showed the minimum O2 saturation improved versus controls in peri-intubation31 and acute respiratory failure settings.4

Our finding showed that the safe apnea time was extended by 33.4 seconds in HFNO versus conventional oxygenation at the time of anesthesia induction and apneic period. This finding is consistent with articles assessing safe apnea time in both intensive care and operating room settings.7,31 One study also showed prolonged safe apnea time in HFNO versus noninvasive ventilation in hypoxemic intensive care patients.4

There are concerns that if a patient is apneic during treatment with HFNO, rising Etco2 and acidosis may ensue. In our meta-analysis on HFNO compared to facemask oxygenation patients, there was no significant difference in Etco2. The Etco2 was reported in the range of 38–44 mm Hg without any evidence of significant hypercapnia.

The physiologic effect and action mechanisms of HFNO includes the following: (a) steady high Fio2 due to elimination of room air entrainment, (b) pharyngeal dead space washout, (c) PEEP effect, (d) reduction in work of breathing, and (e) improvement of mucociliary clearance and patient comfort.32 With reduced risk for desaturation and extended safe apneic time, HFNO may be applied to improve safety in patients at higher risk of desaturation intraoperatively. HFNO has a wide range of potential applications in patients for or with the following: morbid obesity,22 respiratory insufficiency,1,4,8–10,32 bronchoscopy,14,23 awake intubation,17,33 rapid sequence intubation,13,18,27 known difficult airway,2 and procedural sedation.14–16,23,34

There are several limitations to our study. First, the number of RCTs suitable for meta-analysis was limited to 8. Second, some studies used median rather than mean to describe the outcome variables. Conversion of medians to means assumes a normal distribution without skewed data. Third, the definitions of O2 desaturation varied among studies from 90% to 93%.12–16 Despite these different definitions, it should have an equal effect on the HFNO and control groups. Fourth, safe apnea time should be interpreted in the correct clinical context. For example, safe apnea time while securing the airway during rapid sequence induction has different clinical implications to the prolonged safe apnea time during tubeless laryngeal surgery. Fifth, although we found safe apnea time was significantly longer with HFNO versus conventional oxygenation, the heterogeneity was high and this finding should be interpreted with caution.

CONCLUSIONS

Our systematic review and meta-analysis show that intraoperatively, in patients receiving HFNO compared to conventional oxygenation, the risk of O2 desaturation was lower, minimum O2 saturation was higher, safe apnea time was extended, and Etco2 level was similar. We suggest that the use of HFNO should be considered for anesthesia induction in patients at risk of hypoxemia or with known or potentially difficult airway, and during surgical procedures under sedation without tracheal intubation. Further studies comparing HFNO and low-flow nasal oxygen on O2 desaturation, safe apnea time, and Etco2 level should be performed in the intraoperative settings.

ACKNOWLEDGMENTS

The authors thank Marina Englesakis, MLIS, University Health Network Librarian, Department of Anesthesia, University of Toronto, Toronto, ON, Canada, for her invaluable assistance in conducting the literature search for this review and meta-analysis.

DISCLOSURES

Name: Emily A. Spence, BM BCh.

Contribution: This author helped with review of literature, data extraction, and manuscript writing.

Name: Wesley Rajaleelan, MD, DA.

Contribution: This author helped with review of literature, data extraction, and manuscript writing.

Name: Jean Wong, MD, FRCPC.

Contribution: This author helped with conception of article, data analysis, and manuscript writing.

Name: Frances Chung, MBBS, FRCPC.

Contribution: This author helped with conception of article and manuscript writing.

Name: David T. Wong, MD, FRCPC.

Contribution: This author helped with conception of article, data analysis, and manuscript writing.

This manuscript was handled by: Narasimhan Jagannathan, MD, MBA.

FOOTNOTES

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