Authors: Mickael Vourc’h, Donatien Huard, Fanny Feuillet, Gabrielle Baud, Arthur Guichoux, Marielle Surbled, Melanie Tissot, Anne Chiffoleau, Christophe Guitton, Samir Jaber, Karim Asehnoune
Categories: Anaesthesia, anticipated difficult intubation, apneic oxygenation, fiberoptic intubation, high-flow nasal cannula, video-laryngoscopy, 1506, 1682
Source: BMJ Open
Although preoxygenation and airway management respond to precise algorithms, difficult intubation (DI) remains a daily challenge in intensive care units and in the operating rooms because of its frequent complications, including hypoxaemia. To prevent desaturation during DI, high-flow oxygenation by nasal cannula (HFNC) could prove beneficial. Indeed, contrary to standard preoxygenation device, it can be held in place throughout the intubation trying to perform apnoeic oxygenation during DI. Hence, recent guidelines recommend HFNC during DI, but its relevance has never been evaluated in this setting in a large randomised study until now.
The PREOPTIDAM trial is a prospective, single-centre, randomised, controlled study in Nantes University Hospital. In anticipated DI, we hypothesised that HFNC can decrease the incidence of desaturation ≤94% or face mask ventilation from 16% to 4% compared with standard device. Using a two-sided t-test with a first species risk of 5% and 80% power, a total of 186 patients will be included. Using a computer-generated randomisation, with a 1 allocation ratio, patients will be randomised to HFNC or face mask preoxygenation. Randomisation will be stratified on intubation Rapid sequence intubation or awake fibreoptic intubation. The primary objective is to determine whether HFNC is more efficient than standard oxygenation techniques to prevent desaturation ≤94% or face mask ventilation during DI. Intent-to-treat and per-protocol analysis are planned for the primary outcome.
The study project has been approved by an independent ethics committee. Written informed consent will be obtained before study inclusion. Participant recruitment begins in September 2018. Results will be submitted to international peer-reviewed medical journals.
Keywords: high-flow nasal cannula, anticipated difficult intubation, fiberoptic intubation, video-laryngoscopy, apneic oxygenation
Despite major safety improvement over the last decades, substantial morbidity and mortality remains in anaesthesia.^1^ Hypoxaemia represented 20% of these severe adverse events.^2 3^ Although airway management and preoxygenation sequence respond to precise algorithms, anticipated difficult intubation (DI) remains a daily challenge and a major cause of hypoxaemia during anaesthesia.^4 5^ Preoxygenation, which consists in fulfilling functional residual capacity with pure oxygen, is the cornerstone of patient safety during intubation. Increasing oxygen reserve is the best way to extend safe apnoea duration and therefore to avoid hypoxaemia and its related complications. Current preoxygenation guidelines suggest performing eight vital capacities or 3 min of spontaneous breathing with a standard face mask, at FiO2=100% in order to achieve EtO2 of >90%.^4 5^ To reduce desaturation during anticipated DI, two options for airway management can be rapid sequence intubation (RSI) or awake fibreoptic intubation (FOI).^4^ RSI includes preoxygenation with a standard face mask, the administration of hypnotic and neuromuscular blocker with rapid onsets and immediate intubation after mask removal without manual ventilation. RSI aims at (1) minimising the time from induction to intubation to reduce the risk of oxygen desaturation^5^; (2) ensuring a fast recovery of spontaneous breathing when intubation proves impossible with difficult face mask ventilation. FOI, usually performed under local anaesthesia and sedation, is proposed for anticipated ‘cannot ventilate’ or ‘limited mouth-opening’ patients. It preserves the patient’s spontaneous breathing during intubation to avoid major hypoxaemia in case of difficult airway control. After preoxygenation, a dedicated face mask guarantees continuous oxygenation during the procedure. Whatever the option, and despite well-conducted preoxygenation, DI increases first-attempt failure, long-lasting procedure incidence, and leads to frequent oxygen desaturation.^6^ According to the current guidelines, when the level of pulse oximetry (SpO2) drops below 95%, the operator has to interrupt intubation and focus on oxygenation (ie, face mask ventilation).^7^ Nevertheless, face mask ventilation could be difficult or impossible in patients with anticipated DI, and could give rise to gastric insufflation or active gag reflex and provoke vomiting or aspiration. It also often requires deepening anaesthesia, leading to severe hypotension. As a result, to limit face mask ventilation during DI could also reduce adverse events, driving research effort in this field.
High-flow oxygenation by nasal cannulae (HFNC) has been studied in the intensive care unit (ICU) and in the operating room as a preoxygenation device, with controversial results.^8–10^ Recent observational studies have suggested the ability of HFNC to extend safe apnoea time during DI and to be held during FOI.^11 12^ This device can deliver up to 60 L/min with an inspired fraction of oxygen of up to 100%,^13^ and generate a moderate positive supraglottic end expiratory pressure.^14^ HFNC could prove beneficial for anticipated DI, during both the preoxygenation and the intubation^15^: after preoxygenation for RSI, HFNC makes it possible to hold nasal prongs in place during laryngoscopy, trying to perform apnoeic oxygenation throughout the intubation. During FOI, in a spontaneously breathing patient, the preoxygenation and the oxygenation with standard device require a dedicated operator to apply firmly the mask on the patient’s face so as to ensure airtightness which is often poorly tolerated. Moreover, in toothless patients or with a beard, significant leaks around the mask can alter oxygenation. HFNC allows to insert the fibrescope in the patient’s nostril to perform intubation while continuing the oxygenation and may be better tolerated.
Considering its theoretical advantages and recent recommendations,^5 7^ HFNC must be assessed during preoxygenation and apnoeic oxygenation during anticipated DI. Up to now, no large randomised study has compared HFNC oxygenation with standard of care. Our objective will be to evaluate HFNC preoxygenation for anticipated DI compared with face mask. We hypothesise that HFNC could reduce oxygen desaturation during the intubation and the need of face mask ventilation accordingly.
To compare the effectiveness of HFNC (interventional group) and face mask (standard method) as preoxygenation devices to prevent desaturation during anticipated DI.
To compare the quality of preoxygenation, intubation-related complications and patient’s outcome until postanaesthesia care unit (PACU) discharge between groups.
The PREOPTIDAM trial will be a prospective, single-centre, open-label, randomised controlled study. The randomisation sequence will be computer-generated and stratified on the intubation method (RSI or FOI) according to the attending physician’s decision. This study will adhere to the international recommendations for interventional trials.
The study will take place at the Nantes University Hospital, France.
We hypothesise that compared with face mask preoxygenation, HFNC could reduce the incidence of desaturation ≤94% or the necessity to use face mask ventilation for rescue oxygenation during anticipated DI.
Trial site investigators will identify consecutive eligible patients from the listed criteria. Eligible patients will receive written and oral information. They will be included after investigators have obtained informed written consent.
Anticipated DI criteria derived from international guidelines and recent publications^4 16 17^:
OR
Randomisation will be centralised, web-based and accessible 24 hours a day. The randomisation sequence will be carried out in blocks (1:1 ratio) and stratified according to intubation sequence (RSI or FOI).
The randomisation sequence will be generated by a statistician working at the Clinical Research department of Nantes University Hospital and not involved in patient recruitment. The software used to collect the data in the electronic case report form (eCRFs) will automatically allocate patients, thereby ensuring concealment. The physicians and a clinical research nurse and/or clinical research assistant will screen the patients for eligibility.
Blinding of the attending physician and patients to the type of preoxygenation device is not feasible. However, the primary outcome is assessed on the basis of an objective criterion.
After written informed consent, the patients will be randomly assigned to (see figure 1: study intervention):
Figure 1 Study design. After attending physician decision to perform RSI or FOI, patients will be randomised to receive high-flow nasal cannula (HFNC) or face mask oxygenation. FiO 2, fraction of inspired oxygen.
In both groups, the first operator will be a senior or a junior supervised by a senior. All operators will have assisted a three half-day formation programme so as to be familiar with this three oxygenation devices at the Nantes University Hospital Simulation Centre.
The current guidelines advise to interrupt intubation to focus on oxygenation (ie, face mask ventilation) for oxygen desaturation ≤94%.^7^ Nevertheless, the decision to proceed to face mask ventilation mainly depends on the progression of intubation procedure. Thus, mask ventilation is left at the discretion of the physician as well as the algorithm for rescue oxygenation. However, international recommendation will be presented to all of the investigators before the start of the study.^5^ The attending physician will be free to withdraw the oxygenation device if it disrupts the intubation process or the rescue oxygenation. Clinical data will be collected throughout intubation, surgery and until discharge of the PACU.
The drugs for sedation and general anaesthesia induction as well as intubation devices will be left to the discretion of the attending physician.
Patients will be excluded from the trial if they withdraw their consent after randomisation. However, if the patient does not object, the data already collected until consent withdrawal will be analysed. If the patient refuses, the data will be deleted.
Patients will be followed from the beginning of the preoxygenation until PACU discharge (see table 1).
Patients were not directly involved in the development of the research question or the design of the study. However, the primary and secondary outcomes of the study impact patients’ safety and comfort. A written summary of the results of the study will be sent to requesting participants by mail. Participant satisfaction of the intervention will be assessed before PACU discharge and will analysed as a secondary outcome.
Proportion of patients with desaturation ≤94% or need to use face mask ventilation for oxygen desaturation during intubation in each group.
The patients will be classified in two ‘No event’ or ‘at least one event’.
Arterial oxygen saturation will be evaluated by level of oxygen saturation measured by pulse oximetry (SpO2). The evaluation period of SpO2 will be extended to 2 min following intubation completion owing to possible delayed detection of desaturation with this device. Face mask ventilation will be noted if it occurs after general anaesthesia (RSI) or sedation (FOI) induction.
Preoxygenation
Intubation procedure until the 2 following
Intubation-related adverse events during intubation and the following 1 hour:
Per-operative respiratory
Morbidity in the PACU:
Severe adverse events will be immediately declared and analysed by the vigilance unit of research department of the Nantes University Hospital.
Expected intubation-related adverse events are defined
All of the expected or unexpected adverse events (occurring from the beginning of the preoxygenation to the discharge of the PACU) will be collected in the eCRF. The trial may be temporarily stopped for an individual patient at the discretion of the attending physician if a severe adverse event is suspected to be associated with the allocated device.
The primary outcome is the occurrence (yes or no) of desaturation ≤94% or face mask ventilation during the intubation procedure and the 2 following minutes.
We hypothesise that HFNC can decrease the incidence of desaturation ≤94% or the need of face mask ventilation during intubation from 16% to 4% compared with the standard preoxygenation device. The incidence of desaturation during anticipated DI has not been described specifically in the literature up to now. We hypothesise a 12% reduction in desaturation with HFNC based on our previous study in the ICU (2019, Intensive care medicine, in press). Using a two-sided t-test with a first species risk of 5% and 80% power and considering 5% of consent withdrawal, we planned to include 186 patients. We anticipated approximately 50 patients with FOI indication.
For the primary a logistic model will compare the incidence of desaturation ≤94% or face mask ventilation. Intent-to-treat and per-protocol analysis are planned for the primary outcome. We shall also perform exploratory subgroup analysis for the primary outcome regarding the type of intubation (FOI or RSI). An interim analysis will be performed after inclusion of half of the total number of patients (93 patients) to enable re-estimation of the sample size to maintain power.^23 24^ The overall probability of the event will be estimated from the pooled data of both treatment groups. If necessary, the sample size will be adjusted accordingly and an amendment to the protocol will be made.
The secondary outcomes will be described and compared between the two groups with linear regression models, generalised mix models or survival models (Cox or Fine and Gray) according to the nature of the variable. All of the analyses will be adjusted to intubation sequence (FOI or RSI).
A predefined statistical analysis plan will be followed using SAS software V.9.3 (Cary, North Carolina, USA). The statistical analysis will incorporate all of the elements required by the CONSORT statement for non-pharmacological interventions.
Data will be recorded in a web-based eCRF by the research team. Characteristics at baseline will be age, sex, weight, height, medical history, indication for surgery, predictive criteria of difficult mask ventilation or of DI, description of the intubation procedure (technical aspect, drugs and adverse events). During surgery, respiratory and cardiovascular parameters will be assessed.
Any protocol deviations will be recorded in the eCRF and the medical records. To preserve the confidentiality of personal information, data will be key-coded using alphanumerical numbers. To minimise missing data, to improve the quality of data collection and tracking, an external assessor will collect the variation of SpO2.
Data set will be available on reasonable request to the corresponding author.
Monitoring will follow ‘Good Clinical Practice principles’ and will be performed by the independent promotion department of Nantes University Hospital Research Management Unit.
The following data will be
The eCRF is a secure, interactive, web-response system provided and managed by the data manager team of research department and biometrics unit of the Nantes University Hospital (Nantes, France). The physicians and a clinical research nurse will ensure compliance with the study protocol and collect the study data in the eCRFs.
A total of 186 patients are expected to be included within 19 months.
June protocol approval by the Ethics Committee.
September Start of inclusion.
March End of inclusion.
We will submit the manuscript during the second half of 2020.
The trial will be conducted in compliance with the current version of the Declaration of Helsinki and Good Clinical Practice guidelines. The research project was approved.
The study was registered at http://www.clinicaltrials.gov with trial identification NCT03604120 before the first inclusion.
The study data will be handled as requested by the French Data Protection Authority (Commission Nationale de l’Informatique et des Libertés). All original records will be kept on file at the trial site for 15 years. The electronic trial database file will be anonymised and kept on file for 15 years.
This study was supported by institutional funds and a grant from FPH that is inferior to 20% of the total budget (24 000 Euros). FPH did not participate in the study design and will not participate in data collection, analysis and interpretation, nor in the preparation, review approval and decision to submit the manuscript for publication.
The study will be published in an international medical journal.
Among the intubation-related adverse events, hypoxaemia is a life-threatening issue and this complication is mainly encountered during difficult airway management. HFNC presents several theoretical advantages compared with the standard face mask, including the ability to deliver continuous oxygen flow to perform apnoeic oxygenation. Recent expert guidelines have advised the use of such a device to prevent desaturation during DI.^5 7^ However, its relevance has never been evaluated in a large randomised study. This device could improve patient safety but it must be evaluated before systematic implementation in the airway control algorithm.
We are grateful to the medical staff, nurses and research staff of the Anaesthesia and Critical Care Departments of Nantes University Hospital. We thank Ludivine Perrier for administrative and logistic support, Coralie Ono dit Biot for creating the eCRF, and Dr Anne Chiffoleau, MD for safety monitoring.