STRENGTH AND LIMITATIONS OF THIS STUDY
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This will be the first pragmatic randomised single-centre trial to compare high-flow nasal oxygen therapy and standard oxygen therapy (SOT) with matched FiO2 levels, which will isolate the effects of the oxygen delivery method.
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The inability to precisely control FiO2 in the SOT group will be mitigated by using a pre-established abacus for flow adjustment.
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Practitioner blinding will be infeasible, but blinded delayed assessment of primary outcomes will be implemented to reduce bias.
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MostCare data for non-intubated patients may be influenced by respiratory artefacts, though sedation and within-group comparisons will minimise this limitation.
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Stratification by anaemia status will allow subgroup analysis but may not fully address the confounding influence of bleeding in some coronary artery disease cases.
Introduction
Sedation during gastrointestinal endoscopy improves the quality of examination as well as patient comfort and allows for the performance of complex procedures.1 The recent American Society for Gastrointestinal Endoscopy guidelines suggest that sedation, under the care of anaesthesiologists, should be considered for patients with multiple medical comorbidities, including patients with coronary artery disease (CAD) .2 However, hypoxaemia and hypotension during deep sedation may lead to myocardial ischaemia, arrhythmias and cerebral hypoxia, causing adverse cardiovascular and cerebrovascular events, thereby increasing mortality and hospitalisation time. Therefore, it is necessary to ensure the balance of myocardial oxygen supply and demand to ensure stable haemodynamics and avoid myocardial ischaemia. Several conditions common among patients with CAD can increase the risk of adverse outcomes during gastrointestinal endoscopy under deep sedation. For example, patients with CAD commonly take anticoagulant medications, such as aspirin and clopidogrel, which can lead to gastrointestinal bleeding, consequently increasing the risk of bleeding during gastrointestinal endoscopy. Such bleeding can lead to anaemia, which causes a rightward shift of the oxygen dissociation curve and decreased oxygen affinity. Moreover, due to the presence of underlying heart disease and multiple comorbidities, patients with CAD can have poor tolerance to anaesthesia. The hypoxia and circulatory fluctuations occurring during sedation potentially lead to myocardial ischaemia, which is the most common complication of gastrointestinal endoscopy under deep sedation among patients with CAD. Patients with CAD often have comorbid obesity. Sedation-induced myorelaxation and respiratory depression may cause upper airway obstruction and a decrease in functional residual capacity, thereby exacerbating hypoxaemia. Additionally, CAD patients with concomitant hypertension often have poor vascular elasticity, making them prone to hypotension during sedation, further reducing organ tissue perfusion.
In recent years, an increasing number of studies have begun to focus on optimising the haemodynamics of patients with CAD . Although pulmonary artery catheterisation has been the gold standard for assessing overall cardiac status for nearly 50 years, it is associated with a high incidence of complications and complex procedures. The FloTrac system provides a less invasive method for continuous cardiac output monitoring. However, its accuracy is limited in unstable patients with severe arrhythmias and severe aortic valve regurgitation and in patients with other factors that interfere with the arterial waveform.3 Comparable with pulmonary artery catheterisation and Pulse index Contour Continuous Cardiac Output (PiCCO), MostCare monitoring demonstrates excellent consistency not only in haemodynamically stable patients4 but also in critically ill patients with haemodynamic instability. In paediatric patients undergoing cardiac surgery, MostCare monitoring demonstrates consistency with Fick method measurements5 and transoesophageal Doppler echocardiography6 for assessing overall cardiac function.7 In infants receiving intensive care unit (ICU) treatment after cardiac surgery, the MostCare system was shown to effectively monitor cardiac dysfunction and predict mechanical ventilation duration.8 In adult patients undergoing off-pump coronary artery bypass surgery and those receiving veno-venous extracorporeal membrane oxygenation therapy, the use of MostCare showed good consistency and trends for detecting cardiac output compared with intermittent pulmonary artery thermodilution9 and transthoracic echocardiography,10 respectively. Furthermore, in haemodynamically unstable patients (including those with conditions such as ventricular failure, vasoplegic shock, hypertensive crisis, hypovolaemic shock and aortic valve stenosis), good correlation was observed between MostCare data and results produced by high-fidelity human patient simulators.11 In septic patients, when the arterial waveform is accurate, MostCare and PiCCO transpulmonary thermodilution exhibit good agreement even after norepinephrine reduction and changes in vascular tone or volume expansion.12 Despite some controversy, when MostCare was used for unstable patients reliant on high doses of positive inotropic agents or even receiving intra-aortic balloon pump therapy with sinus rhythm, the resulting monitoring data align with pulmonary artery catheterisation data,13 remaining unaffected by the inflation and deflation of the intra-aortic balloon pump.14 MostCare data also offer good predictability of hypotension during the induction of anaesthesia, identifying patients at risk of anaesthesia-induced hypotension.15 Therefore, the MostCare system can be used to monitor and optimise the haemodynamics of patients with CAD undergoing non-intubated sedation for gastrointestinal endoscopy.
Cardiac cycle efficiency (CCE) data generated by MostCare monitoring provide a comprehensive indicator reflecting the venous system, cardiopulmonary interaction and coupling status between the ventricle and arterial system (V–A coupling), which can effectively indicate whether left ventricular function is optimised. By supporting timely intervention, real-time monitoring of perioperative left ventricular function based on CCE may play a crucial role in maintaining cardiopulmonary function and promoting rapid postoperative recovery in patients. CCE reflects the ratio of cardiac systolic energy consumption to total heartbeat energy consumption from the perspective of pressure waveform energy. An increase of CCE reflects a decrease in the energy required to maintain the same haemodynamic balance within the cardiovascular system, which can be interpreted as an improvement in V–A coupling.16 CCE can effectively assess cardiac circulatory function not only in postcardiac surgery patients receiving mechanical ventilation17 but also in hospitalised patients,18 paediatric ICU patients19 20 and non-intubated patients.21 22 During the first 48 hours after paediatric cardiopulmonary bypass, CCE was found to be the most sensitive indicator for assessing improvements in systemic haemodynamics and myocardial performance.23 A 6-month follow-up study found that the occurrence of adverse events is directly proportional to N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and inversely proportional to CCE, suggesting that CCE can identify high-risk patients after cardiac surgery.24 Furthermore, in non-mechanically ventilated patients, although 5 min of negative pressure ventilation can significantly improve CCE in healthy individuals,16 its impact on extubated patients after cardiac surgery is minimal.21 This highlights the assessment value of CCE in non-intubated sedated patients with CAD. More importantly, CCE can not only assess the overall cardiac function of patients with severe aortic valve stenosis undergoing transcatheter aortic valve implantation (TAVI) surgery under deep sedation and femoral nerve block anaesthesia22 but also determine whether any improvement in cardiac function has occurred after TAVI.25 Therefore, CCE may have indicative significance for the occurrence of myocardial ischaemia in non-intubated sedated patients with CAD undergoing gastrointestinal endoscopy.
To prevent myocardial ischaemia in patients with CAD, both the American Society of Anesthesiologists and the American Society for Gastrointestinal Endoscopy recommend the use of oxygen therapy.2 Standard oxygen therapy (SOT) is a widely used method at present. However, high-flow nasal oxygen therapy (HFNO) can provide higher oxygen flow rates and more precise control of the fraction of inspired oxygen (FiO2),26 potentially offering better assessment of CCE and myocardial protection. With HFNO, the delivered gas is heated, humidified and delivered through large-bore nasal cannulas, enhancing patient comfort and tolerance. The gas flow rate is typically set between 30 and 70 L/min, allowing for the delivery of an accurately known FiO2 ranging from 21% to 100%. High gas flow creates resistance against expiration, maintaining mild positive end-expiratory pressure (PEEP) in the airways, while also generating a dead space washout effect.27 By maintaining good airway patency and respiratory function, HFNO may reduce myocardial workload and decrease cardiac burden. Additionally, the PEEP effect of HFNO helps improve alveolar ventilation and alleviate pulmonary oedema, thereby reducing right ventricular load and promoting coronary artery perfusion.
HFNO has many clinical applications in the ICU and operating room, but its utility for procedural sedation is still underestimated. In neuroanaesthesia practice and electroconvulsive therapy, HFNO was shown to improve arterial oxygenation by providing higher inspiratory oxygen concentration and maintaining higher dynamic positive airway pressure.28 In patients undergoing oral maxillofacial surgery and/or dental treatment, HFNO was found to maintain oxygenation and possibly prevent hypercapnia.29 In elderly patients undergoing endoscopic retrograde cholangiopancreatography, HFNO could provide adequate oxygenation without causing procedural interruption under deep sedation.30 During procedural sedation in paediatric patients with congenital heart disease, HFNO was shown to reduce the incidence of desaturation, the need for airway assisted ventilation and the risk of carbon dioxide retention without causing haemodynamic instability or gastric distension.31 Furthermore, HFNO was shown to reduce the risk of desaturation in adults receiving procedural sedation and analgesia during atrial fibrillation ablation.32 In a study of HFNO use during transfemoral transcatheter aortic valve replacement, the HFNO group exhibited a lower incidence of oxygen desaturation and significantly higher comfort scores, indicating that HFNO may reduce the incidence of hypoxemia in patients with moderate to high hypoxemia risk.33
To date, there have been no studies conducted on the use of HFNO in patients with CAD under deep sedation for either upper or lower gastrointestinal endoscopy. Furthermore, in previous studies, the settings for HFNO, such as gas flow rates, have varied greatly while typically comparing HFNO to SOT with a FiO2 set at 100%. Most importantly, it remains unclear whether HFNO can improve CCE and consequently reduce the incidence of myocardial ischaemia in CAD patients under deep sedation. Hence, we propose to test the hypothesis that HFNO during gastrointestinal endoscopy under sedation may decrease the incidence of myocardial ischaemia in comparison with SOT by decreasing hypoxaemia and circulatory fluctuations and improving CCE. Additionally, changes in cardiac enzyme levels will be monitored to comprehensively evaluate the myocardial protective effects of HFNO.
Methods and analysis
Design
This protocol is for an investigator-initiated, prospective, single-centre, randomised controlled, superiority trial comparing the efficacy of HFNO and SOT in patients with CAD undergoing gastrointestinal endoscopy performed under sedation. Our primary hypothesis is that compared with SOT, HFNO may improve CCE and reduce the incidence of hypotension and hypoxaemia. 90 eligible patients will be randomly assigned in a 1:1 ratio to two parallel groups, with 45 patients in each group.
A computer-generated randomisation will be performed with stratification in a 1:1 ratio, using a web-based management system. After randomisation, the intervention (HFNO or SOT) will be initiated. The randomly assigned groups will be documented in patient medical records and dedicated charts, which will summarise all the patient populations allocated throughout the trial.
Oral and written information will be provided during the anaesthesia consultation several days before endoscopy. Written consent will be obtained on the day of the gastrointestinal endoscopy procedure after eligibility verification. Patients will have the right to withdraw their consent and terminate their participation at any time for any reason. We will use the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) reporting guidelines in our study.34
Patients are expected to be included during a 19-month period starting in August 2024.
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August 2024: Ethical approval for the protocol and development of trial tools (case report forms and randomisation system).
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September 2024 – December 2025: Patient enrolment.
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January and February 2026: Database cleaning and closure; data analysis; manuscript writing; and submission of findings to peer-reviewed journals for publication.
Study setting
The trial is being conducted at Beijing Anzhen Hospital. A senior anaesthesiologist will perform all anaesthesia sedation procedures for this study. At the same time, data recording and collection will be carried out by another anaesthesiologist.
Study objectives
The main research objective is to compare CCE between the groups receiving HFNO and SOT. CCE data will be collected and generated by the MostCare monitoring system, which records values before and after sedation, every 3 min after induction, and after patient awakening.
The following secondary parameters will be compared between groups:
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Incidence of hypotension, where hypotension is defined by a systolic blood pressure (SBP) less than 80 mmHg or 20% lower than the baseline value.
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Occurrence of hypoxemia (defined as SpO2≤92%).
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Postoperative BNP, troponin I (TnI) and lactate levels at 6–12 hours.
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Frequency of patient agitation episodes (defined as touching the oxygen supply device).
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Intraoperative adverse memory recall.
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Need for mask ventilation or any airway intervention.
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Duration of sedation (from induction to patient awakening).
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HFNO-related adverse events (such as xeromycteria/rhinalgia).
The following secondary MostCare haemodynamic parameters collected before and after sedation, every 3 min after induction, and after patient awakening will be compared between the groups:
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Heart rate (HR).
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SBP, diastolic blood pressure and mean arterial pressure.
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Diastolic arterial pressure during the anacrotic phase (Pdic-a).
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Stroke volume index (SVI).
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Systemic vascular resistance index.
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Cardiac index (CI).
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Pulse pressure variation.
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Maximum rate of pressure increases in the left ventricle during systole (dP/dtmax).
Data collection
The data from the MostCare monitor and SpO2 monitoring will be automatically recorded. As in the routine clinical setup, the standard arterial pressure transducer will be connected to the Mindray monitor (Mindray, BeneVision N15 OR) via a dual-output pressure module. For this study, the pressure module will also be directly connected to the MostCare device (Bio-Si International, Italy) to allow continuous transmission of the original signal and sampling at 1000 Hz. MostCare provides averaged beat-to-beat calculated data within 30 s, including pressure, and continuously displays the data on the screen. For each parameter, detailed 2-min measurements at 30-s intervals recorded by MostCare will be downloaded to Excel sheets for offline analysis. Subsequently, the four consecutive measurements will be averaged. During the intervention, SpO2 will be recorded every minute using a Mindray monitor to capture hypoxaemia defined as SpO2≤92%. Outcomes will be recorded on paper case report forms. Data collection will stop when the patient leaves the recovery room. Trends in vital signs (including SpO2) and MostCare haemodynamic records will be printed and placed in an envelope with the paper case report forms.
Investigators not involved in patient care and blinded to the allocated intervention will read and review the recorded data to check for consistency with the events reported by clinicians on the paper case report forms.
Sample size
In a preliminary observational study of 20 CAD patients undergoing gastrointestinal endoscopy with SOT or HFNO, we observed a 0.1 increase in CCE with HFNO. We hypothesise that HFNO may reduce the decrease in CCE from 0.2 to 0.1. Using PASS 21.0 with 1:1 randomisation, a power of 1−β=0.80, a two-sided α level of 5% and assuming a 15% dropout rate, we calculated that 45 patients per group would be required.
Recruitment
The researchers will provide patients with an information letter and explain the study details 1 day before the surgery (see online supplemental file 1). Randomisation will be performed on entry to the operating room, and the researcher will conduct the arterial puncture procedure. Patients who agree to participate will simultaneously sign the written informed consent form (see online supplemental file 2). Figure 1 illustrates the research protocol execution process and figure 2 provides an outline of the schedule of enrolment, interventions and assessments.
Example template for the schedule of enrolment, interventions and assessments. *−t1, enrolment time; t1, before sedation; t2, after sedation; t3, 3 min after sedation; t4, 6 min after sedation; tx, after patient awakening. CCE, cardiac cycle efficiency; HFNO, high-flow nasal oxygen therapy; SOT, standard oxygen therapy.
Flow of participants. HFNO, high-flow nasal oxygen therapy; SOT, standard oxygen therapy
Intervention
In the operating room, prior to commencing procedures, standard anaesthesia monitoring equipment will be used to monitor the vital signs of each patient, such as electrocardiography, invasive blood pressure and pulse oximetry. Additionally, haemodynamic data will be monitored using the MostCare monitor and all data will be recorded. Pulse oximetry will be recorded in ambient air. According to random allocation of interventions, preoxygenation will be administered (low flow 10 L/min FiO2 100% for the HFNO group and 10 L/min for the SOT group) for at least 3 min prior to induction.
In this practical study, the investigators will use sufentanil and propofol for anaesthesia.
During anaesthesia, the researchers will administer oxygen therapy at 60 L/min in the HFNO group and at 8 L/min via nasal cannula in the SOT group. In cases of severe intolerance, HFNO or SOT may be discontinued and replaced by any other oxygen therapy technique. Tracheal intubation is permitted if necessary. In all instances, investigators must record all events in the case report form.
At the end of the gastrointestinal endoscopy, patients will be transferred to the recovery room, marking the end of the intervention period. In the recovery room, HFNO will not be utilised. Instead, all patients will be immediately administered SOT in the recovery room until it is deemed no longer necessary. Intraoperative adverse memory recall will be assessed in the recovery room and will be analysed as a secondary outcome.
As in the study by Lin et al, hypercapnia will not be monitored.35 To limit the risk of hypercapnia in our study, the FiO2 will be set at 40% with a flow of 60 L/min.
Intervention group
HFNO will be administered using the HT-08 Optiflow Nasal High Flow device and a dedicated anaesthesia nasal cannula, equipped with filters (Aeonmed Medical System, China). The preoxygenation settings will include a flow rate of 10 L/min on low-flow mode and 100% FiO2, sustained for at least 3 min. Induction will follow after the preoxygenation period. Once the eyelash reflex disappears, the device will be switched to high-flow mode and the flow rate will be increased to 60 L/min (to achieve a higher PEEP effect), and FiO2 will be adjusted to 40%. The decision to set FiO2 at 40% is aimed at achieving similar FiO2 levels in both groups and reducing the risk of hyperoxia and hypercapnia.
Control group
Oxygen therapy at a flow rate of 10 L/min via nasal cannula will be administered for 3 min preoxygenation and 8 L/min throughout the entire anaesthesia procedure.
Similar FiO2
During the preoxygenation period, the FiO2 levels and flow rates will be identical in both groups. The planned settings for the two groups provide equivalent and effective preoxygenation with both methods. For patients with CAD under sedation with retained spontaneous breathing, pre-oxygenation can enhance tolerance during anaesthesia.
During the procedure, we will maintain a similar initial FiO2 in both groups to avoid disadvantaging the SOT group. Moreover, comparable FiO2 levels will aid in determining whether the PEEP and dead space flushing effects induced by HFNO are beneficial. Similar FiO2 will be obtained by using a conversion table. However, because the actual FiO₂ with conventional nasal cannulas is significantly influenced by breathing patterns, the SOT group would actually receive an FiO2 of 35%–45% via nasal cannula at 8 L/min after the standardised preoxygenation period. To ensure comparable FiO2 levels between groups, we will set the HFNO group to receive 60 L/min at 40% FiO2. Compared with an FiO2 of 100%, setting FiO2 at 40% in the HFNO group will not increase the incidence of hypoxemia.36
Eligibility criteria
Inclusion criteria
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Age of at least 18 years.
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CAD defined by single or multiple coronary artery stenosis >50% as determined by coronary angiography.
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Scheduled for or requiring urgent gastrointestinal endoscopy (upper and/or lower endoscopy), with plans for sedation aimed at maintaining spontaneous respiration (as determined during anaesthesia consultation).
Exclusion criteria
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Need for intubation for the procedure.
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At-home oxygen therapy.
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Tracheostomy.
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High risk of aspiration, inability to fully clear upper respiratory secretions, thick or excessive airway secretions and ineffective cough for sputum clearance.
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Haemodynamically unstable (sustained systolic arterial pressure <80 mmHg).
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Severe heart failure (ejection fraction <45%).
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Severe cardiac arrhythmias (atrial fibrillation, frequent premature ventricular contractions, ventricular tachycardia and second-degree or higher atrioventricular block).
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Unresolved tension pneumothorax or mediastinal emphysema.
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Dysfunction of any other organ system (shock, gastrointestinal perforation/major bleeding, severe cerebral disorder and severe hepatic or renal dysfunction).
Outcome
The primary outcome is the difference in CEE levels between the two groups during sedation. Secondary outcomes include the incidence of hypotension (defined by a SBP less than 80 mmHg or 20% lower than the baseline value); the occurrence of hypoxemia (defined as SpO2≤92%); BNP, TnI and lactate levels at 6–12 hours postoperation; frequency of patient agitation episodes; intraoperative adverse memory recall; need for mask ventilation or any airway intervention; duration of sedation; HFNO-related adverse events and MostCare haemodynamic parameters other than the primary outcome.
Statistical analysis
SPSS statistical software 23 (IBM-SPSS, Chicago, IL, USA) will be used for data processing and analysis. The analysis report will adhere to the requirements of the Consolidated Standards of Reporting Trials statement.37 Raw data will be tested for normality using the Kolmogorov–Smirnov and Bartlett tests.
The primary endpoint and secondary haemodynamic parameters will be compared using distinct mixed linear models in which the patient will be considered as a random effect variable. The variable representing the randomised treatment group will be included as a fixed effect variable. The interaction between randomisation and stratification variables will be tested. The results will be presented in the form of estimated marginal means (and their 95% confidence intervals) for each randomised group. If the interaction is significant, results for each stratum group may also be presented. Secondary categorical endpoints will be compared between the two groups using either a χ2 test adjusted for stratification variables or Student’s t-test.
The duration of sedation between the two groups will be compared using the Mann–Whitney U test, taking into account stratification. The interaction between the group of randomisation and the group of stratification will also be tested.
Subgroup analysis will be planned: if a significant interaction is observed between patient haemoglobin levels and randomised treatment groups, the results will be presented stratified by haemoglobin levels. In the case of missing data, multivariate imputation will be planned. Missing values for the primary endpoint, CEE, will not be imputed or replaced.
Patient and public involvement
Patients will not be directly involved in the development of the research or the design of the study.
Ethics and dissemination
Ethics
This research complies with the Pharmaceutical Clinical Trial Quality Management Regulations, Medical Device Clinical Trial Regulations, World Medical Congress Helsinki Declaration, Ethical Review Measures for Biomedical Research Involving People (Trial) and other ethical guidelines, as well as the WHO guidelines on ethical reviews. This study has been approved by the Ethics Committee of Beijing Anzhen Hospital, Capital Medical University (KS2024066), and the rights and safety of participants will be protected.
Dissemination
Paper medical record forms will be used as the source document. The data will be entered into a secure spreadsheet application (Excel) by a member of the research team. The data will be handled in accordance with Chinese law. Only three members of the team (the first author, statistician and last author) will have access to the final experimental dataset.
The results will be submitted for publication in a peer-reviewed journal. The patient data from this clinical study will be treated as confidential and used only for the purposes of conducting this clinical research.
Informed consent
Written consent (see consent form in online supplemental file 2) will be obtained from all participants on the day of the procedure.
After receiving an appropriate explanation of the potential risks and benefits of the study and having understood these explanations (see consent form in online supplemental file 1), participants will be enrolled. Participants can contact the researchers at any time if they have any questions related to the study. They will be given accurate contact information to allow them to contact the Ethics Committee of Anzhen Hospital at any time if they have any questions related to their own rights/interests. Each participant will be free to withdraw his/her consent to participate at any time.
Discussion
The balance between myocardial oxygen supply and demand is a primary concern for anaesthesiologists during invasive procedures (such as gastrointestinal endoscopy performed under deep sedation) in spontaneous breathing patients with CAD. Assessment of CCE in patients with CAD based on MostCare data allows effective evaluation of the oxygen supply and demand.
Due to the presence of multiple comorbidities in patients with CAD (such as anaemia, hypertension and diabetes), achieving deep sedation while maintaining circulatory stability is crucial. While deep sedation in patients helps prevent a stress reaction, maintaining the balance of myocardial oxygen supply and demand in sedated patients is crucial to ensure the safety of gastrointestinal endoscopy procedures.
CCE reflects the ratio between the haemodynamic work performed by the heart and energy expenditure. An improvement in CCE indicates that the cardiovascular system is able to maintain the same haemodynamic status with reduced energy consumption, which essentially reflects enhanced V–A coupling. Previous research on CCE has primarily focused on its predictive role in patient prognosis and has found that a decline in CCE is associated with adverse early postoperative outcomes.20 Giglioli et al reported that the risk of adverse events at the 6-month follow-up was directly related to low values of CCE.24 The CCE in patients who experienced adverse events decreased by 0.18 (0.15±0.17 vs.−0.03±0.29). However, the difference in CCE between HFNO and SOT has not been studied previously in patients with CAD during gastrointestinal endoscopy under deep sedation. Our preliminary results showed that during sedated gastrointestinal endoscopy, CCE showed a smaller decrease of 0.1 compared with SOT. Consequently, the between-group difference of 0.1 was chosen as the basis for calculation. It can be argued that such CCE improvement should be beneficial in patients with a critical balance of myocardial oxygen supply and demand.
HFNO is widely used in sedation anaesthesia for gastrointestinal endoscopy. It is now gradually being extended to high-risk gastrointestinal endoscopy patients to optimize oxygen delivery during anaesthesia. To date, only limited data have been reported regarding the use of HFNO during gastrointestinal endoscopy in patients with CAD. Due to the low incidence of myocardial ischaemia in the healthy population and the higher cost of HFNO compared to SOT, we will only include patients with CAD in this study.
It is important that the flow rate and oxygen concentration during the pre-oxygenation phase are exactly the same for both study groups. More importantly, the initial FiO2 plans must be equivalent in both groups to avoid placing the control group at a disadvantage. Most studies have compared HFNO with 100% FiO2 to standard oxygen at flow rates of 2–5 L/min, which roughly results in FiO2 between 28%–45%.35 38 In contrast, in our study, a similar initial FiO2 in both groups will allow for the determination of whether the HFNO-induced PEEP and dead space washout effects are beneficial. Additionally, in the HFNO group, the gas flow will be set to a higher value (60 L/min), in contrast with previous studies, and all patients will receive preoxygenation before anaesthesia induction.
In this study, we do not plan to monitor the partial pressure of exhaled carbon dioxide (PETCO2). First, measuring PETCO2 during HFNO oxygen therapy is challenging because the high flow of oxygen disturbs the measurement. Although apnoea episodes can be identified by observing chest rising, this assessment is subjective and unreliable, especially in a single-blinded study. Second, any potential hypercapnia will be clinically tolerable given that the average procedure duration is only 5 minutes. Additionally, permissive hypercapnia improves coronary perfusion. The benefit from a full oxygen supply outweighs the potential harm from hypercapnia. Future studies could incorporate arterial blood gas analysis of COâ‚‚ levels.
The study was launched on 1 September 2024. A rapid inclusion rate is expected to facilitate the acquisition of high-quality data by avoiding investigator and research team fatigue. So far, investigators have not reported any serious adverse events related to the study procedures. Dropouts for any reason are rare. All these factors inspire confidence in the timely completion of the study.
In summary, the described study is a pragmatic randomized controlled trial initiated by investigators, aiming to test the hypothesis that HFNO, compared with SOT at similar FiO2 levels, can enhance CCE in patients with CAD undergoing gastrointestinal endoscopy under deep sedation. The study presents several innovative aspects. First, patients are at risk of myocardial oxygen imbalance. Second, the CCE of patients with CAD will be investigated during upper and/or lower gastrointestinal endoscopy under deep sedation. Finally, the use of similar initial FiO2 levels aims to prevent the SOT group from being disadvantaged. If the results are positive, the use of HFNO could potentially become the standard approach for enhancing the safety of gastrointestinal endoscopy performed under deep sedation for patients with CAD.
Ethics statements
Patient consent for publication
Acknowledgments
The authors would like to thank the clinical staff of the trial site (Beijing Anzhen Hospital).
