Effectiveness of trans-nasal humidified rapid insufflation ventilatory exchange compared with standard facemask oxygenation for pre- and apneic oxygenation during anesthesia induction: A meta-analysis based on randomized controlled trials

Delai Zheng; Yi Yao; Chuan Luo; Yanhui Yang; Bogang Chen; Nana Li; Yi Wang

doi:10.1371/journal.pone.0302626

Abstract

Purpose

To further identify the effectiveness of trans-nasal humidified rapid insufflation ventilatory exchange (THRIVE) for pre- and apneic oxygenation during the anesthesia induction by comparison to facemask ventilation (FMV) based on current available evidence.

Methods

Medline, EMBASE, Web of Science, Cochrane Library and CNKI databases were searched from inception to December 22, 2023 for available randomized controlled trials (RCTs). Primary outcomes were PaO₂ and PaCO₂ after intubation and safe apnoea time. Secondary outcomes included the O₂ desaturation, end expiratory carbon dioxide (EtCO₂) and complications. The effect measures for continuous and categorical outcomes were separately the mean difference (MD) and relative risk (RR) with 95% confidence interval.

Results

Twelve RCTs with 403 patients in the THRIVE group and 401 patients in th FMV group were included. Pooled results demonstrated that the PaO₂ after intubation was significantly higher (MD = 82.90mmHg, 95% CI: 12.25~153.54mmHg, P = 0.02) and safe apnoea time (MD = 103.81s, 95% CI: 42.07~165.56s, P = 0.001) was longer in the THRIVE group. Besides, the incidence rate of O₂ desaturation (RR = 0.28, 95% CI: 0.12–0.66, P = 0.004) and gastric insufflation (RR = 0.26, 95% CI: 0.13–0.49, P<0.001) was significantly lower in the THRIVE group.

Conclusion

Based on current evidence, THRIVE manifested better effectiveness representing as improved oxygenation, prolonged safe apnoea time and decreased risk of complications compared to standard FMV in surgical patients. Therefore, THRIVE could be served as a novel and valuable oxygenation technology for patients during anesthesia induction.

Citation: Zheng D, Yao Y, Luo C, Yang Y, Chen B, Li N, et al. (2024) Effectiveness of trans-nasal humidified rapid insufflation ventilatory exchange compared with standard facemask oxygenation for pre- and apneic oxygenation during anesthesia induction: A meta-analysis based on randomized controlled trials. PLoS ONE 19(4): e0302626. https://doi.org/10.1371/journal.pone.0302626

Editor: Mert Tanal, Acibadem Maslak Hospital: Acibadem Maslak Hastanesi, TURKEY

Received: January 24, 2024; Accepted: April 6, 2024; Published: April 30, 2024

Copyright: © 2024 Zheng 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: All data used in this meta-analysis are presented in the manuscript.

Funding: The author(s) received no specific funding for this work.

Competing interests: The authors have declared that no competing interests exist.

Introduction

In clinics, face mask ventilation (FMV) during anesthesia induction is a common airway management method, but it also has some drawbacks and limitations. When applying FMV, improper airway management may lead to the entry of gas into the stomach, increasing gastric volume and thereby elevating the risk of gastric distention and aspiration for the patient [1]. Excessive airway pressure during FMV may cause airway injury, especially in patients who require careful handling, such as children and the elderly [2]. Some patients may have difficulty obtaining an effective seal due to facial abnormalities or other reasons, affecting the effectiveness of FMV. Additionally, accurately controlling tidal volume during FMV can be relatively challenging, potentially resulting in inadequate or excessive tidal volumes [3, 4]. Inserting a nasogastric tube may be relatively difficult when using FMV, which could impact the intraoperative need for gastric emptying. Implementing positive end-expiratory pressure (PEEP) during FMV may also be relatively challenging, and PEEP may be necessary for certain patients, such as those with acute respiratory distress syndrome (ARDS) [5, 6].

Trans-nasal humidified rapid insufflation ventilatory exchange (THRIVE), also known as high-flow nasal cannula (HFNC) oxygen therapy, is a novel oxygen therapy method. It delivers a specific concentration of high-flow air-oxygen mixture directly to the patient through heating and humidification, eliminating the need for a closed nasal catheter [7]. THRIVE provides heated and humidified gas at a maximum flow rate of 70 L/min, maintaining stable FiO₂ for the patient while reducing anatomical dead space in the upper airway and increasing intratracheal oxygen concentration. Studies have shown that continuous THRIVE can alleviate the patient’s respiratory effort and produce a continuous positive end-expiratory pressure (PEEP) effect [8]. The positive pressure effect increases with the rising flow rate, providing 1 cm H₂O PEEP with a closed mouth and 0.5 cm H₂O PEEP with an open mouth for every 10 L/min increase in flow rate [8]. The positive pressure effect opens the patient’s upper airway, reduces intrapulmonary shunts, and further enhances the patient’s oxygen reserve [9]. However, currently, there is no high-quality evidence elucidating the specific effectiveness of THRIVE during anesthesia induction.

Therefore, this meta-analysis aimed to further determine the effectiveness of THRIVE for pre- and apneic oxygenation during the anesthesia induction by comparison with FMV based on available randomized controlled trials (RCTs), which might contribute to the clinical application of THRIVE.

Materials and methods

This meta-analysis was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analyses 2020 [10].

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not needed.

Literature search

In this meta-analysis, Medline, EMBASE, Web of Science, Cochrane Library and CNKI databases were searched from their inception up to December 22, 2023. Following terms were applied during the search: transnasal humidified rapid-insufflation ventilatory exchange, THRIVE, surgery, operation, randomized, randomly and random. The specific literature search strategy was as follows: (transnasal humidified rapid-insufflation ventilatory exchange OR THRIVE) AND (surgery OR operation) AND (randomized OR randomly OR random). MeSH terms and free texts were applied during the search. Besides, references listed in included studies were also reviewed.

Inclusion criteria

Studies met following criteria were included: 1) RCTs comparing the effectiveness of THRIVE and FMV during the anesthesia induction; 2) at least one of following indicators was involved with relevant data: PaO₂ and PaCO₂ after intubation, safe apnoea time, O₂ desaturation, end expiratory carbon dioxide (EtCO₂) and complications such as gastric insufflation, reflux, arrhythmias, nausea and vomiting; 3) adult patients (≥ 18-year-old).

Exclusion criteria

Studies met following criteria were excluded: 1) the intervention for control group was not the FMV, including the bite block or nasal cannula ventilation; 2) full texts were not available; 3) letters, editorials, meeting abstracts, animal trials, meta-analyses or reviews; 4) duplicated or overlapped data.

Data collection

We extracted following data from each included RCTs: the first author, publication year, sample size of each group, country, type of surgery, intervention in THRIVE group and FMV group, endpoints including the PaO₂ and PaCO₂ after intubation, safe apnoea time, O₂ desaturation, EtCO₂ and complications and corresponding data.

For the safe apnoea time, the definitions of included studies differ. Three studies defined apnoea time from the onset of cessation of breathing until the SpO₂ decreased to 95% or the apnoea time reached 5 or 6 min [11–13]. Ding et al. defined apnoea time from the end of intravenous muscle relaxation until the SpO₂ decreased to 94% [14]. In the study by Mir et al., it was defined as from the cessation of spontaneous breathing until the SpO₂ decreased to 90% [15]. While six RCTs explored the impact of THRIVE on deoxysaturation [11, 15–19], only two studies were valid for the analysis [16, 17]. The deoxysaturation was separately defined as SpO₂≤90% [17] and SpO₂≤93% [16] in these two studies.

Methodological quality assessment

The risk of bias in included RCTs was assessed by the Review Manager software with the guidance of the Cochrane Collaboration risk-of-bias tool [20]. Studies were divided into high, low or unclear risk of bias involving the aspects including the selection, performance, detection, attrition, reporting and others.

The literature search, selection, data collection and methodological quality assessment were all performed by two authors independently. Any disagreement was resolved by discussion.

Statistical analysis

In this meta-analysis, all analysis was performed by Review Manager (RevMan version 5.4.1). The statistical method for continuous variables was inverse variance and the effect measure was mean difference (MD). The statistical method for categorical variables was Mantel-Haenszel and the effect measure was relative risk (RR). Heterogeneity between studies was evaluated by the I² statistic and Q test. When significant heterogeneity was observed representing as I² > 50% and/or P < 0.10, the random-effect mode was applied; otherwise, the fixed-effect model was used [21, 22]. For studies providing data in median and range or interquartile range, the method described by Wan et al. was used to convert them into mean and standard deviation (SD) [23].

Results

Literature search process

One hundred and thirty-three records were identified from the five databases. Detailed literature selection process for this meta-analysis was presented in Fig 1. Eventually, 12 RCTs were included in our analysis [11–19, 24–26].

Download:

Fig 1. Prisma flow diagram of this meta-analysis.

https://doi.org/10.1371/journal.pone.0302626.g001

Basic characteristics of included RCTs

A total of 804 cases were enrolled with 403 patients in the THRIVE group and 401 patients in the FMV group. Specific information was presented in Table 1. The methodological quality assessment was shown in Fig 2, which indicated the high-quality of included RCTs.

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Fig 2. Risk of bias assessment.

A. Risk of bias summary. B. Risk of bias graph. The plus sign indicates low risk, the sinus sign indicates high risk, and the question sign mark uncertain risk.

https://doi.org/10.1371/journal.pone.0302626.g002

Download:

Table 1. Basic characteristics of included studies.

https://doi.org/10.1371/journal.pone.0302626.t001

Meta-analysis results of primary outcomes

Seven RCTs explored the effect of THRIVE on the PaO₂ and PaCO₂ after intubation with a total of 367 participants [11, 12, 14, 15, 19, 24, 25]. Pooled results demonstrated that the PaO₂ in the THRIVE group was significantly higher than that in the FMV group (MD = 82.90mmHg, 95% CI: 12.25~153.54mmHg, P = 0.02; I² = 98%, P<0.001) (Fig 3). However, no significant statistical difference of PaCO₂ between the two groups was observed (MD = 2.05mmHg, 95% CI: -0.48~4.58mmHg, P = 0.11; I² = 75%, P<0.001). (Table 2)

Download:

Fig 3. Forest plot for PaO₂ in THRIVE versus FMV after intubation.

THRIVE: trans-nasal humidified rapid insufflation ventilatory exchange; FMV: face mask ventilation.

https://doi.org/10.1371/journal.pone.0302626.g003

Download:

Table 2. Results of meta-analysis.

https://doi.org/10.1371/journal.pone.0302626.t002

Five RCTs involving with 227 patients identified the effect of THRIVE on the safe apnoea time [11–15]. Pooled results indicated that the THRIVE could significantly increase the safe apnoea time compared with FMV during the anesthesia induction (MD = 103.81s, 95% CI: 42.07~165.56s, P = 0.001; I² = 95%, P<0.001) (Fig 4). (Table 2)

Download:

Fig 4. Forest plot for safe apnoea time in THRIVE versus FMV after intubation.

THRIVE: trans-nasal humidified rapid insufflation ventilatory exchange; FMV: face mask ventilation.

https://doi.org/10.1371/journal.pone.0302626.g004

Meta-analysis results of secondary outcomes

Six studies with 315 patients investigated the incidence of O₂ desaturation [11, 15–19]. However, only the data of two studies was estimable [16, 17]. Pooled results manifested that THRIVE significantly decreased the risk of O₂ desaturation (RR = 0.28, 95% 95% CI: 0.12–0.66, P = 0.004; I² = 0%, P = 0.34) (Fig 5).

Download:

Fig 5. Forest plot for O₂ desaturation in THRIVE versus FMV after intubation.

THRIVE: trans-nasal humidified rapid insufflation ventilatory exchange; FMV: face mask ventilation.

https://doi.org/10.1371/journal.pone.0302626.g005

Besides, four studies manifested the effect of THRIVE on the EtCO₂ [12–14, 16]. However, no significant statistical difference was observed between the THRIVE and FMV groups (MD = 3.54mmHg, 95% CI: -0.70~7.78mmHg, P = 0.10; I² = 91%, P<0.001). (Table 2)

As for the complications, the incidence rate of gastric insufflation in the THRIVE group was significantly lower than that in the FMV group (RR = 0.26, 95% 95% CI: 0.13–0.49, P<0.001; I² = 0%, P = 0.67) based on the data from two available RCTs (Fig 6) [14, 26]. The incidence risk for reflux (RR = 0.24, 95% CI: 0.06–1.02, P = 0.05), arrhythmias (RR = 1.50, 95% CI: 0.38–6.00, P = 0.57), nausea and vomiting (RR = 0.22, 95% CI: 0.02–2.14, P = 0.19) was not statistically difference between the two groups (Table 2).

Download:

Fig 6. Forest plot for gastric insufflation in THRIVE versus FMV after intubation.

THRIVE: trans-nasal humidified rapid insufflation ventilatory exchange; FMV: face mask ventilation.

https://doi.org/10.1371/journal.pone.0302626.g006

Discussion

In recent years, THRIVE, as a novel method of "apneic oxygenation," has gradually gained attention and application in clinical practice. "Apneic oxygenation" refers to the administration of high concentrations of oxygen through the airway when the body is not in respiratory motion, promoting the exchange of oxygen in the alveoli [27, 28]. Generally, the maximum flow of dry oxygen that can be inhaled by awake patients is limited to 15 L/min, as excessive flow can lead to discomfort such as dry nasal mucosa and frontal/sinus pain. THRIVE, on the other hand, can increase the maximum flow to 70 mL/min through a heating and humidifying device [29]. In theory, at this flow rate, anesthesia patients’ oxygenation can be maintained, achieving CO₂ clearance and "diffusive oxygenation". Compared to traditional oxygen therapy methods, THRIVE, by setting the gas flow higher than the patient’s inspiratory peak flow, can provide a stable inspired oxygen concentration and low-level positive pressure. This reduces nasopharyngeal dead space, improves airway mucosal clearance function, and to some extent, has the effect of opening alveoli and promoting ventilation [30]. Additionally, THRIVE can establish an O₂ pressure difference gradient between the upper airway and alveoli, as well as between alveoli and pulmonary capillaries, driving O₂ diffusion into the pulmonary capillaries, achieving the "apneic diffusive oxygenation" effect [31]. Currently, THRIVE is primarily used for respiratory support in patients with respiratory dysfunction to improve and treat hypercapnia or mild to moderate hypoxic respiratory failure [32–34]. However, its application in the field of anesthesia remains limited.

According to the results of our meta-analysis, THRIVE technique could extend the safe apnea time during patient anesthesia induction, increase oxygen reserve, reduce the risk of hypoxemia during endotracheal intubation, and also decrease the risk of gastric distention. However, in our analysis, THRIVE did not demonstrate an obvious advantage in improving carbon dioxide retention, and further exploration is needed in future studies.

As thoracic surgeons, we paid particular attention to the research conducted by Shen and colleagues [19]. Their results demonstrated that THRIVE played a role in reducing oxygen pressure decline and improving the safety of endotracheal intubation among patients undergoing lung lobectomy with the need for double-lumen endotracheal intubation [19]. During the insertion of a double-lumen endotracheal tube, ventilation can be maintained through THRIVE to improve patient oxygenation. While adjustments are made with a fiberoptic bronchoscope after the placement of the double-lumen endotracheal tube, ventilation can be connected to the anesthesia machine. However, there is still a risk of hypoxia in case of poor alignment and inadequate ventilation. THRIVE significantly extends the safe apnea time, providing a time buffer for the adjustment of the tube position.

Notably, in this meta-analysis, we identified the significant effect of THRIVE on the decreased risk of gastric insufflation. Although the association of THRIVE with decreased risk of reflux did not reach the statistical difference, a clear trend that THRIVE reduced the incidence of reflux was observed (RR = 0.24, P = 0.05). Therefore, we deem that THRIVE might also decrease the incidence rate of reflux among surgical patients. However, more RCTs are still needed to verify this issue.

THRIVE still has some clinical value after the start of surgery. First, THRIVE can continuously provide oxygen to patients during surgery, ensuring the maintenance of their oxygen levels throughout the procedure. This is particularly crucial for procedures with longer durations. Second, during the surgical process, especially during anesthesia induction and maintenance stages, the use of THRIVE can reduce the risk of patients experiencing hypoxemia, enhancing the safety of anesthesia. Third, by delivering humidified gas, THRIVE helps support airway humidification, reducing dryness of the respiratory mucosa and improving airway conditions. Fourth, for certain specialized surgeries like head and neck procedures, THRIVE can maintain patient oxygenation during surgery, minimizing interference with ventilation. Fifth, the use of THRIVE may contribute to reducing the need for mechanical ventilation during surgery, providing a more natural form of ventilatory support.

There are several limitations in our meta-analysis. First, the overall sample size was relatively small and most RCTs were from China. Second, a number of confounding parameters exist in our analysis such as the type of surgery and intervention. More detailed analysis was needed to further verify our conclusions. Third, obvious heterogeneity was detected during the analysis of some indicators such as the PaO₂ after intubation, safe apnoea time and EtCO_2, we were unable to conduct more analysis to identify the source of heterogeneity due to the limited available data. Four, in most included studies, the basic conditions of patients, including combined lung diseases, were not mentioned. Therefore, further exploration is needed to determine whether THRIVE is practical for all patients.

Conclusion

In overall, THRIVE manifested better effectiveness representing as improved oxygenation, prolonged safe apnoea time and decreased risk of complications compared to standard FMV in surgical patients. Therefore, THRIVE could be served as a novel and valuable oxygenation technology for patients during anesthesia induction. However, more high-quality RCTs with big sample sizes are still needed to further testify above findings.

Supporting information

S1 Checklist. PRISMA 2020 checklist.

https://doi.org/10.1371/journal.pone.0302626.s001

(DOCX)

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Figures

Abstract

Purpose

Methods

Results

Conclusion

Introduction

Materials and methods

Ethical approval

Literature search

Inclusion criteria

Exclusion criteria

Data collection

Methodological quality assessment

Statistical analysis

Results

Literature search process

Basic characteristics of included RCTs

Meta-analysis results of primary outcomes

Meta-analysis results of secondary outcomes

Discussion

Conclusion

Supporting information

S1 Checklist. PRISMA 2020 checklist.

References