https://orcid.org/0000-0001-8625-827X
Figures
Abstract
Background
Rapid sequence induction intubation (RSII) is commonly used in emergency surgeries for patients at high risk of aspiration. However, these patients are more susceptible to hypoxemia during the RSII process. High-flow nasal cannula (HFNC) oxygen therapy has emerged as a potential alternative to traditional face mask (FM) ventilation pre- and apneic oxygenation. This meta-analysis aimed to evaluate the efficacy of HFNC compared to FM during RSII in emergency surgeries.
Methods
We conducted a comprehensive literature search across PubMed-MEDLINE, EMBASE-OVID, Scopus, and Web of Science databases up to July 20, 2024. Randomized controlled trials comparing HFNC with FM during RSII for emergency surgery patients were included. The primary outcomes were post-intubation arterial partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2). Secondary outcomes included post-intubation end-tidal carbon dioxide concentration (EtCO2), incidence of desaturation, apnea time, lowest peripheral oxygen saturation (Lowest SpO2), and occurrence of regurgitant aspiration. We used the GRADE approach to assess the certainty of evidence and the Cochrane Risk of Bias 2 (RoB 2) tool to evaluate risk of bias.
Findings
This meta-analysis encompassed six studies, involving a total of 703 patients. HFNC oxygen therapy demonstrated a significant increase in post-intubation arterial PaO2 compared to FM (mean difference = 63.02 mmHg, 95% CI: 8.99 to 117.05, p = 0.02), while no significant difference was observed in arterial PaCO2. Moreover, HFNC substantially prolonged apnea time (mean difference = 19.25 seconds, 95% CI: 1.69 to 36.82, p = 0.03). No statistically significant differences were found between HFNC and FM regarding EtCO2, incidence of desaturation, Lowest SpO2, or regurgitant aspiration.
Conclusion
This systematic review and meta-analysis indicates that HFNC may be superior to FM for pre-oxygenation and apneic oxygenation during RSII in emergency surgeries, particularly in improving oxygenation. While these findings are promising, further high-quality research is necessary to establish definitive guidelines for HFNC use in this context.
Citation: Tang H, Yang Y, Li H (2025) High-flow nasal cannula for pre- and apneic oxygenation during rapid sequence induction intubation in emergency surgery: A systematic review and meta-analysis. PLoS ONE 20(1): e0316918. https://doi.org/10.1371/journal.pone.0316918
Editor: Luis Felipe Reyes, Universidad de La Sabana, COLOMBIA
Received: September 12, 2024; Accepted: December 18, 2024; Published: January 24, 2025
Copyright: © 2025 Tang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: PubMed-MEDLINE, EMBASE-OVID, Scopus, and Web of Science databases.
Funding: This research was funded by a grant from the Talent Innovation Leading Talent Project of Chongqing (Project No.: CQYC20200303142 to H.L.).
Competing interests: The authors have declared that no competing interests exist.
Introduction
For patients with gastrointestinal obstruction, full stomach, or at high risk of regurgitant aspiration, rapid sequence induction intubation (RSII) is commonly employed to minimize the time interval between the loss of airway protective reflexes and successful tracheal intubation. Studies indicate that emergency surgery patients are not only more susceptible to hypoxemia [1], but also experience a high incidence of hypoxemia during the RSII process itself [1,2]. This dual risk underscores the importance of selecting effective pre- and apneic oxygenation methods for patients undergoing RSII in emergency surgeries.
In recent years, trans-nasal humidified rapid insufflation ventilatory exchange (THRIVE), also known as high-flow nasal cannula (HFNC) oxygen therapy, has gained attention. HFNC consists of an air/oxygen blender, an active humidifier, a single heated circuit, and a nasal cannula, capable of delivering a constant fraction of inspired oxygen (0.21–1.0) at high flow rates (up to 60 L·min-1 or higher) [3]. HFNC is widely used in intensive care unit (ICU) patients for the management of hypoxemic respiratory failure, owing to its straightforward setup, good patient tolerance, and demonstrated efficacy [4]. Studies have demonstrated several physiological advantages of HFNC, including generation of continuous positive airway pressure [5], reduction of anatomical dead space [6], improvement of ventilation-perfusion ratio [7], enhancement of mucociliary clearance [8], and reduction of work of breathing [7,9], among others.
Since its first application for pre- and apneic oxygenation during general anesthesia in 2015, HFNC has shown potential benefits in improving pre-oxygenation levels, enhancing oxygenation, and prolonging safe apnea time [10]. Although numerous clinical anesthesia studies have extensively discussed the perioperative application of HFNC, particularly its effects during anesthetic induction and apneic periods, many research findings remain controversial [11–13]. Currently, there is a lack of systematic reviews and meta-analyses on the effectiveness of HFNC application in RSII. Therefore, this meta-analysis aims to evaluate the efficacy of HFNC compared to traditional face mask (FM) ventilation in reducing the risk of hypoxemia during RSII for emergency surgeries by comprehensively analyzing existing randomized controlled trials (RCTs). We hope to provide more reliable evidence-based guidance for clinical practice and optimize oxygenation strategies during RSII through this study.
Methods
The protocol for this systematic review and meta-analysis was prospectively registered in PROSPERO (International Prospective Register of Systematic Reviews; registration number: CRD42024575204). This study was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement [14] (S1 Fig).
Search strategy
A comprehensive literature search was performed in PubMed, Embase, Scopus, and Web of Science databases from inception through July 20, 2024. The full search strategy is detailed in the Supplementary materials. To ensure comprehensive coverage, a manual examination of the bibliographies of all included studies was conducted to identify any additional relevant articles not captured by the electronic search.
Eligibility criteria
Inclusion criteria were: (1) comparing the effects of HFNC and FM during RSII for patients undergoing emergency surgery requiring general anesthesia;(2) RCTs; (3) participants aged over 16 years; (4) non-pregnant individuals. Literature exclusion criteria:(1) case reports, reviews, and other non-original literature were excluded; (2) studies with inaccessible full-text articles or insufficient data for analysis.
Study selection and data extraction
Two independent reviewers (H.T. and Y.Y.Y.) systematically screened titles and abstracts after removing duplicate records, adhering to predetermined inclusion and exclusion criteria. Full-text articles of potentially eligible studies were subsequently retrieved and independently evaluated by the same reviewers. Any discrepancies arising during the screening process were resolved through consultation with a third reviewer (H.L.). From the final set of included studies, we extracted pertinent data, including the first author, publication year, country, sample size, and interventions in both the HFNC and FM groups. Primary outcomes encompassed post-intubation arterial partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2). Secondary outcomes included post-intubation end-tidal carbon dioxide concentration (EtCO2), incidence of desaturation (defined as oxygen saturation <93%) from anesthesia induction to intubation, apnea time, lowest peripheral oxygen saturation (Lowest SpO2), occurrence of regurgitant aspiration. Apnea time was specifically defined as the period from the start of apnea until a carbon dioxide trace was visible on capnography.
Risk of bias and quality assessment
We applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE) [15] approach to assess the certainty of evidence, and utilized the Cochrane Risk of Bias 2 (RoB 2) [16] tool to evaluate risk of bias in the included studies. These assessments were conducted independently by two reviewers (H.T. and Y.Y.Y.), with any disagreements resolved through discussion or consultation with a third reviewer (H.L.) when necessary.
Statistical analysis.
A meta-analysis was conducted using Review Manager (RevMan version 5.4.1), software developed by the Cochrane Collaboration. For categorical outcomes, the Mantel-Haenszel method was employed, with risk ratio (RR) as the effect measure. For continuous outcomes, the inverse variance method was utilized, with mean difference as the effect measure. Due to potential clinical heterogeneity among the included studies, a random-effects model was chosen for data pooling. Heterogeneity among studies was assessed using the I2 statistic. I2 values of 25%, 50%, and 75% were considered to indicate low, moderate, and high heterogeneity, respectively.
Results
Study selection and characteristics
Our initial literature search yielded 728 potentially relevant articles. After a rigorous screening process, six studies met our inclusion criteria and were selected for the meta-analysis. These studies collectively included 703 patients, with 352 allocated to the HFNC group and 351 to the FM group. The detailed study selection process is illustrated in Fig 1. Detailed information about the included studies is presented in S1 Table.
We conducted a comprehensive assessment of the risk of bias for all included studies and evaluated the quality of evidence for each outcome using the GRADE approach. The risk of bias assessment for individual studies is visually presented in S2 and S3 Figs. These figures provide a clear overview of the methodological quality across the included studies. To synthesize our findings and evaluate the overall quality of evidence, we performed a meta-analysis for each outcome and applied the GRADE methodology. S2 Table presents a comprehensive summary of these results, including effect estimates, confidence intervals, and the GRADE quality assessment for each outcome.
Primary outcomes
Our meta-analysis focused on two primary outcomes: post-intubation PaO2 and PaCO2. For post-intubation PaO2, our analysis encompassed four studies with a total of 275 participants. The pooled effect estimate indicated a statistically significant increase in PaO2 favoring HFNC (MD = 63.02, 95% CI: 8.99 to 117.05, p = 0.02). However, high heterogeneity was detected among the studies (I2 = 79%) (Fig 2). For post-intubation PaCO2, our analysis encompassed four studies with a total of 275 participants. The analysis revealed no statistically significant difference between the HFNC and FM groups (MD = -0.37, 95% CI: -4.93 to 4.18, p = 0.87), with high heterogeneity also observed (I2 = 87%) (Fig 3).
Secondary outcomes
The meta-analysis also evaluated several secondary outcomes. For post-intubation EtCO2, the analysis of three studies with 468 participants found no statistically significant difference between the HFNC and FM groups, although high heterogeneity was observed (MD = -3.41, 95% CI: -9.03 to 2.21, p = 0.23) (Fig 4). Regarding apnea time, the pooled analysis of five studies with 663 participants showed a statistically significant increase in apnea time favoring HFNC (MD = 19.25, 95% CI: 1.69 to 36.82, p = 0.03), again with high heterogeneity (I2 = 91%) (Fig 5). For oxygen saturation desaturation, the analysis of two studies with 428 participants found no significant difference between HFNC and FM (RR, 0.39; 95% CI, 0.04 to 3.57; p = 0.40), with moderate heterogeneity (I2 = 55%) (Fig 6). Similarly, the analysis of three studies with 508 participants revealed no significant difference in the lowest SpO2 between the two groups (MD = 0.30, 95% CI: -0.14 to 0.73, p = 0.18), with low heterogeneity (I2 = 0%) (Fig 7). Finally, the analysis of three studies with 543 participants found no significant difference in the incidence of regurgitant aspiration between HFNC and FM (MD = 2.92, 95% CI:0.12 to 69.74, p = 0.18), though the limited number of events prevented a robust assessment of heterogeneity (Fig 8).
Discussion
Our meta-analysis of 6 studies encompassing 703 patients revealed that HFNC demonstrated superior oxygenation compared to FM during RSII, with significantly higher post-intubation PaO2 and longer apnea time. However, no significant differences were found in other outcomes including PaCO2, EtCO2, desaturation incidence, and regurgitant aspiration.
The primary outcome demonstrated significantly higher post-intubation PaO2 in the HFNC group compared to the FM group, suggesting superior oxygenation maintenance with HFNC. Notably, no significant difference was observed in post-intubation PaCO2 between the two groups, indicating that HFNC improved oxygenation without affecting carbon dioxide clearance. This enhanced oxygenation can be attributed to HFNC’s ability to provide a stable inspired oxygen concentration, generate distal positive airway pressure, increase end-expiratory lung volume and alveolar oxygen partial pressure, reduce intrapulmonary shunt, and decrease dead space ventilation due to its washout effect [5–8]. These physiological mechanisms may explain HFNC’s superior performance in increasing PaO2 compared to FM during pre-oxygenation.
Secondary outcomes showed no significant differences between HFNC and FM in EtCO2, incidence of desaturation, lowest SpO2, and regurgitant aspiration. These findings suggest that HFNC is comparable to traditional FM in maintaining these crucial physiological parameters. Of interest is the significantly prolonged apnea time observed with HFNC. Despite this extended apneic period, the HFNC group maintained higher post-intubation PaO2 levels, strongly indicating superior oxygenation during pre- and apneic oxygenation phases. Importantly, our analysis found no significant difference in the incidence of regurgitant aspiration between the two methods, a critical consideration for emergency surgery patients at higher risk of aspiration. This similar safety profile suggests that HFNC could be a viable alternative to FM without increasing aspiration risk. However, the wide confidence interval indicates considerable uncertainty in this estimate, likely due to the rarity of aspiration events in the included studies.
Our findings align with the meta-analysis by Song et al. [17], which did not restrict its focus to RSII, and with Bright et al. [18] study on obese patients. These consistencies across different patient populations and induction methods underscore HFNC’s potential for superior oxygenation maintenance during anesthesia induction in the operating room.
However, this study has several important limitations that warrant consideration. Firstly, the results are specifically applicable to patients undergoing RSII in emergency surgery, potentially limiting generalizability to other patient populations or clinical scenarios. This specificity is both a strength, as it focuses on a critical clinical context, and a limitation in terms of broader applicability. Secondly, the classical RSII technique emphasizes avoiding positive pressure ventilation before tracheal intubation [19], while modified RSII techniques recommend using pressure-limited positive pressure ventilation [20]. Regardless of the method used, these techniques inherently affect the oxygenation efficacy of the FM group during the induction to intubation phase, potentially biasing the comparison with HFNC. Furthermore, our meta-analysis is limited by high heterogeneity in some outcomes and a relatively small number of included studies. This heterogeneity might be attributed to variations in patient populations, pre-oxygenation times, and HFNC application methods across studies. The diversity in RSII techniques employed across different centers and studies further contributes to this heterogeneity, making direct comparisons challenging.
Future research should prioritize several key areas to advance our understanding and application of HFNC in RSII. Firstly, standardizing HFNC protocols for RSII is crucial to ensure consistency across studies and clinical practice. Secondly, investigating HFNC’s efficacy in specific patient subgroups, such as those with obesity or difficult airways, could provide valuable insights into its targeted applications. Thirdly, conducting larger, multicenter trials is essential to reduce heterogeneity and increase the robustness of findings.
Additionally, cost-effectiveness analyses comparing HFNC to FM would be valuable for informing clinical practice and healthcare resource allocation. These economic evaluations, coupled with clinical efficacy data, would provide a more comprehensive basis for decision-making in adopting HFNC for RSII in various healthcare settings.
Conclusion
This systematic review and meta-analysis suggests that HFNC may offer advantages over FM for pre- and apneic oxygenation during RSII in emergency surgeries, particularly in terms of improved oxygenation. While these findings are promising, further high-quality research is needed to establish definitive guidelines for HFNC use in this setting.
Supporting information
S1 Table. Information about the included studies.
https://doi.org/10.1371/journal.pone.0316918.s004
(DOCX)
S2 File. Detailed content of GRADE quality assessment.
https://doi.org/10.1371/journal.pone.0316918.s007
(XLSX)
S4 File. Data extraction from included studies.
https://doi.org/10.1371/journal.pone.0316918.s009
(XLSX)
References
- 1. Baillard C, Boubaya M, Statescu E, Collet M, Solis A, Guezennec J, et al. Incidence and risk factors of hypoxaemia after preoxygenation at induction of anaesthesia. Br J Anaesth. 2019;122(3):388–394. pmid:30770057
- 2. Gebremedhn EG, Mesele D, Aemero D, Alemu E. The incidence of oxygen desaturation during rapid sequence induction and intubation. World J Emerg Med. 2014;5(4):279–285. pmid:25548602
- 3. Nishimura M. High-flow nasal cannula oxygen therapy in adults. J Intensive Care. 2015;3(1):15–22. pmid:25866645
- 4. Liu Q, Zhu C, Lan C, Chen R. High-flow nasal cannula versus conventional oxygen therapy in patients with dyspnea and hypoxemia before hospitalization. Expert Review of Respiratory Medicine. 2020;14(4):425–433. pmid:31985296
- 5. Riva T, Meyer J, Theiler L, Obrist D, Butikofer L, Greif R, et al. Measurement of airway pressure during high-flow nasal therapy in apnoeic oxygenation: a randomised controlled crossover trial. Anaesthesia. 2021;76(1):27–35. pmid:32776518
- 6. Ibarra-Estrada M, Marín-Rosales M, García-Salcido R, Aguirre-Díaz SA, Vargas-Obieta A, Chávez-Peña Q, et al. Prone positioning in non-intubated patients with COVID-19 associated acute respiratory failure, the PRO-CARF trial: A structured summary of a study protocol for a randomised controlled trial. Trials. 2020;21(1):940–947. pmid:33225990
- 7. Mauri T, Turrini C, Eronia N, Grasselli G, Volta CA, Bellani G, et al. Physiologic Effects of High-Flow Nasal Cannula in Acute Hypoxemic Respiratory Failure. Am J Respir Crit Care Med. 2017;195(9):1207–1215. pmid:27997805
- 8. Vitaliti G, Vitaliti MC, Finocchiaro MC, Di Stefano VA, Pavone P, Matin N, et al. Randomized Comparison of Helmet CPAP Versus High-Flow Nasal Cannula Oxygen in Pediatric Respiratory Distress. Respir Care. 2017;62(8):1036–1042. pmid:28487415
- 9. Corley A, Caruana LR, Barnett AG, Tronstad O, Fraser JF. Oxygen delivery through high-flow nasal cannulae increase end-expiratory lung volume and reduce respiratory rate in post-cardiac surgical patients. Br J Anaesth. 2011;107(6):998–1004. pmid:21908497
- 10. Patel A, Nouraei SAR. Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE): a physiological method of increasing apnoea time in patients with difficult airways. Anaesthesia. 2015;70(3):323–329. pmid:25388828
- 11. Vourc’h M, Asfar P, Volteau C, Bachoumas K, Clavieras N, Egreteau PY, et al. High-flow nasal cannula oxygen during endotracheal intubation in hypoxemic patients: a randomized controlled clinical trial. Intensive Care Med. 2015;41(9):1538–1548. pmid:25869405
- 12. Doyle AJ, Stolady D, Mariyaselvam M, Wijewardena G, Gent E, Blunt M, et al. Preoxygenation and apneic oxygenation using Transnasal Humidified Rapid-Insufflation Ventilatory Exchange for emergency intubation. J Crit Care. 2016; 36:8–12. pmid:27546740
- 13. Frat JP, Ricard JD, Quenot JP, Pichon N, Demoule A, Forel JM, et al. Non-invasive ventilation versus high-flow nasal cannula oxygen therapy with apnoeic oxygenation for preoxygenation before intubation of patients with acute hypoxaemic respiratory failure: a randomised, multicentre, open-label trial. The Lancet Respiratory Medicine. 2019;7(4):303–312. pmid:30898520
- 14. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Rev Esp Cardiol (Engl Ed). 2021;74(9):790–799. pmid:34446261
- 15. Balshem H, Helfand M, Schunemann HJ, Oxman AD, Kunz R, Brozek J, et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. 2011;64(4):401–406. pmid:21208779
- 16. Sterne JAC, Savovic J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019; 366:l4898. pmid:31462531
- 17. Song JL, Sun Y, Shi YB, Liu XY, Su ZB. Comparison of the effectiveness of high-flow nasal oxygen vs. standard facemask oxygenation for pre- and apneic oxygenation during anesthesia induction: a systematic review and meta-analysis. BMC Anesthesiol. 2022;22(1):100–108. pmid:35387583
- 18. Bright MR, Harley WA, Velli G, Zahir SF, Eley V. High-Flow Nasal Cannula for Apneic Oxygenation in Obese Patients for Elective Surgery: A Systematic Review and Meta-Analysis. Anesth Analg. 2023;136(3):483–493. pmid:36469483
- 19. Avery P, Morton S, Raitt J, Lossius HM, Lockey D. Rapid sequence induction: where did the consensus go? Scand J Trauma Resusc Emerg Med. 2021;29(1):64–71. pmid:33985541
- 20. Ehrenfeld JM, Cassedy EA, Forbes VE, Mercaldo ND, Sandberg WS. Modified rapid sequence induction and intubation: a survey of United States current practice. Anesth Analg. 2012;115(1):95–101. pmid:22025487