Effect of high flow nasal cannula oxygenation on incidence of hypoxia during sedated gastrointestinal endoscopy in patients with obesity: multicentre randomised controlled trial

Dear Editor,
We read with interest the multicentre randomised controlled trial by Wang et al. evaluating the efficacy of high-flow nasal cannula (HFNC) oxygenation in reducing hypoxemia during sedated gastrointestinal endoscopy in patients with obesity. While the study provides valuable insights into HFNC’s benefits, several methodological and terminological issues warrant clarification to strengthen the validity and clinical applicability of the findings.
The study consistently employs the term "hypoxia" to describe events defined as SpO₂ <90%. However, SpO₂ is a noninvasive measure of arterial oxygenated hemoglobin levels, providing an estimate of SaO₂(1). It correlates sigmoidally with PaO₂, which aligns with the definition of hypoxemia. In contrast, "hypoxia" refers to inadequate oxygen delivery to tissues, a downstream consequence that may or may not correlate with hypoxemia(2). This terminological conflation introduces conceptual ambiguity, potentially misleading readers about the underlying mechanisms. For clarity, we recommend using "hypoxemia" when describing SpO₂-related outcomes.
The use of 100% oxygen with HFNC, while effective in reducing hypoxemia, deviates from clinical norms where lower FiO₂ (21–60%) is typically used to mitigate risks such as absorption atelectasis and respiratory drive suppression(3). In obese patients—particularly those with obesity hypoventilation syndrome (OHS) or obstructive sleep apnea (OSA)—prolonged high FiO₂ may blunt hypoxic ventilatory drive, exacerbating hypercapnia(4). Preclinical and clinical studies demonstrate that 100% oxygen can induce atelectasis within minutes, especially in populations with reduced functional residual capacity(5). Despite the procedural brevity (~11 minutes), the absence of CO₂ monitoring (e.g., PaCO₂ or EtCO₂) leaves critical safety questions unanswered and deserved further investigations.
The sample size calculation assumed an 8% absolute risk reduction (20% to 12%). However, the observed reduction was markedly larger (21.2% to 2.0%, difference -19.14%). This discrepancy suggests either an underestimation of HFNC’s efficacy or unmeasured confounding variables. Thus, a post-hoc power analysis is necessary to assess whether the trial was overpowered, and the implications of an inflated effect size—such as reduced generalizability to real-world settings—should be discussed.

References
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2. Wang H, Wang Z, Wu Q, Yang Y, Liu S, Bian J, Bo L. Perioperative oxygen administration for adults undergoing major noncardiac surgery: a narrative review. Med Gas Res. 2025;15(1):73-84.
3. Hernández G, Vaquero C, Colinas L, Cuena R, González P, Canabal A, Sanchez S, Rodriguez ML, Villasclaras A, Fernández R. Effect of Postextubation High-Flow Nasal Cannula vs Noninvasive Ventilation on Reintubation and Postextubation Respiratory Failure in High-Risk Patients: A Randomized Clinical Trial. JAMA. 2016;316(15):1565-1574
4. Mokhlesi B, Masa JF, Brozek JL, Gurubhagavatula I, Murphy PB, Piper AJ, Tulaimat A, Afshar M, Balachandran JS, Dweik RA, Grunstein RR, Hart N, Kaw R, Lorenzi-Filho G, Pamidi S, Patel BK, Patil SP, Pépin JL, Soghier I, Tamae Kakazu M, Teodorescu M. Evaluation and Management of Obesity Hypoventilation Syndrome. An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2019;200(3):e6-e24
5. Singer M, Young PJ, Laffey JG, Asfar P, Taccone FS, Skrifvars MB, Meyhoff CS, Radermacher P. Dangers of hyperoxia. Crit Care. 2021;25(1):440.