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In this preliminary, crossover investigation the investigators will examine the effect of oxygen supplementation on the recovery of breathing in the immediate post-anesthesia period.
In a pilot randomized-controlled trial (NCT04723433) the investigators found that, compared with standard O2 supplementation, hyperoxia enhanced ventilation, as estimated by the fraction of time at a transcutaneous PCO2 (TcPCO2) > 45 mmHg.
More specifically, patients treated with hyperoxia (O2 titrated to: SpO2 > 96%, N=10; Liberal O2) for 90 minutes post-anesthesia, spent 61.2% of the time at TcPCO2 > 45 mmHg, compared with 80.6% of the time in those receiving standard O2 supplementation (O2 titrated to: SpO2 between 90-94%, N=9; Conservative O2 - between-group difference of 19.4% (95% Confidence Intervals: -18.7% to 57.6%), ANCOVA adjusted P = 0.140]. Results were consistent across the 90-min monitoring period. With an observed effect size of 0.73, it was estimated that 30 participants per group are required, to demonstrate this difference with a power of 80% at a two-sided alpha of 5%.
In a follow-up RCT (IRB-63878, NCT05379673) in 18 patients the investigators found that over a 90-minute window, the average percentage of time spent at TcPCO2 > 45mmHg for patients in the Conservative O2 group (N=9) was 57.8% (52 ± 44 minutes), compared with a 45.6% (41 ± 46 minutes) for those in the Liberal O2 group (N=9), (P=0.6134; two-sided two sample t-test). In addition, during the same period, respiratory disturbance index (RDI; events per hour) was higher in the Conservative O2 [median (range): 23.9 (11.0-78.6)], compared with the Liberal O2 group [19.6 (2.8-40.4), Mann-Whitney test, P=0.1615].
Due to the high variability observed in the evaluated respiratory parameters (i.e., TcPCO2 and upper airway obstruction expressed by Respiratory Disturbance Index), the researchers believe that a crossover, rather than a randomized controlled trial, design would improve the power and efficiency of this investigation and also provide an opportunity to characterize better those patients who respond, and separate them from those who do not respond to hyperoxia treatment.
This preliminary investigation will assess how ventilation during recovery from general anesthesia is affected by conservative (Conservative O2: 90% ≤ SpO2 ≤ 94%), compared with liberal (Liberal O2: SpO2 > 96%) O2 supplementation. Using a crossover study design, the investigators aim to: a) assess the breathing pattern and estimate and compare the number of apnea/hypopnea episodes between the two interventions, and b) estimate and compare the cumulative segment of time during which the transcutaneous partial pressure of carbon dioxide (TcPCO2) will exceed 45 mmHg, between the two interventions.
Hypothesis: Conservative O2 will be associated with more unstable and obstructed breathing and less time spent with TcPCO2 > 45 mmHg, compared with Liberal O2 supplementation, during recovery from anesthesia.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| "Conservative O2" | Active Comparator | During the first treatment session, which will last for 40 minutes, O2 supplementation will be titrated to an SpO2 between 90% and 94%. |
|
| "Liberal O2" | Experimental | During the second treatment session, which will last for 40 minutes, O2 supplementation will be titrated to an SpO2 > 96%. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Oxygen gas | Other | Administration of Oxygen by inhalation |
|
| Measure | Description | Time Frame |
|---|---|---|
| Respiratory disturbance index (RDI) | The number of apnea/hypopnea episodes detected using respiratory inductance plethysmography and nasal flow. | Forty minutes of monitoring for each treatment arm |
| Transcutaneous carbon dioxide pressure (TcPCO2) | The cumulative segment of time during which the transcutaneous partial pressure of carbon dioxide will exceed an upper limit of 45 mmHg (i.e., TcPCO2 > 45 mmHg) | Forty minutes of monitoring for each treatment arm |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Anthony Doufas, MD, PhD | Professor, Department of Anesthesiology, Stanford University Medical School | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford University School of Medicine | Stanford | California | 94305 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41175776 | Derived | Kutscher S, Finnsson E, Tian L, Panousis P, Chung BI, Doufas AG. The effect of hyperoxia on disordered breathing during recovery from general anesthesia: A single-blinded, crossover, non-randomized -controlled, trial. J Clin Anesth. 2026 Jan;108:112057. doi: 10.1016/j.jclinane.2025.112057. Epub 2025 Oct 31. |
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| ID | Term |
|---|---|
| D012131 | Respiratory Insufficiency |
| ID | Term |
|---|---|
| D012120 | Respiration Disorders |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| C041364 | nitrox |
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With the patients' admission to the post-anesthesia care unit and after a 20-minute-long stabilization period, two 40-minute-long treatment sessions will be applied to the study patients. In the first 6 patients Conservative O2 treatment will be applied first, whereas in the rest (patients 7-10) the order of the interventions will be reversed. The order of the interventions will not be revealed to the participants before completing the study. In the Conservative O2 treatment session, O2 supplementation will be titrated to an SpO2 between 90% and 94%, while in the Liberal O2, O2 administration will be titrated to an SpO2 > 96%.
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