Non Invasive Ventilation Combined to High Flow Nasal Cannula Oxygen for Preoxygenation of Hypoxemic ICU Patients

Tracheal intubation is a challenging procedure in Intensive Care Unit (ICU), associated with severe life threatening complications. To decrease these complications, preoxygenation is recommended. Non invasive ventilation (NIV) increase effectiveness of preoxygenation, applying a positive end expiratory pressure (PEEP). High-flow nasal cannula oxygen (HFNC) improves oxygenation by increasing end-expiratory lung volume and has a potential of apneic oxygenation. The association of NIV and HFNC for preoxygenation in hypoxemic ICU patients has never been evaluated. The aim of this study is to determine if HFNC combined to NIV could have therapeutic advantages over NIV alone for preoxygenation in the ICU patients intubated for hypoxemic acute respiratory failure.

Patients admitted in Intensive Care Unit (ICU) often need respiratory support. Endotracheal intubation procedure in ICU is associated with severe life threatening complications. In order to decrease the incidence of complications including hypoxemia during intubation procedure, a preoxygenation is recommended, consisting in the administration of pure oxygen before intubation.

Recent data suggest that NIV use for preoxygenation of patients with acute respiratory failure is associated with less hypoxemia during intubation procedure than classic preoxygenation with facial mask. Indeed, associating Pressure Support (PS) with Positive end expiratory pressure (PEEP) limits the alveolar collapse and atelectasis formation. NIV is now used by a lot of of teams for preoxygenation of patients with acute respiratory failure in ICU.

However, although NIV is effective to reduce hypoxemia during intubation procedure, NIV mask has to be taken off after preoxygenation in order to allow the passage of the oro tracheal tube through the mouth. The hypoxemic patient does not receive oxygen during this period, which participates to the episodes of major hypoxemia during intubation.

In contrast, HFNC, which delivers high flow heated and humidified oxygen and air via nasal prongs at a prescribed fraction of inspired oxygen and a maximum flow of 60 L/min can be pursued during the intubation procedure. Some very recent studies suggest that HNFC could allow apneic oxygenation.

Although use of HFNC combined to NIV may have potential advantages over conventional NIV for preoxygenation before intubation in hypoxemic ICU patients, this technique of preoxygenation has never been assessed and benefit remains to be established.

The OPTINIV study aims to compare the effects of preoxygenation with combination of NIV and HFNC versus NIV alone on lowest oxygen saturation during intubation procedure of ICU patients intubated for acute respiratory failure.

Study design and population The OPTINIV trial is an investigator initiated multicenter randomized controlled two-arm blinded trial.

Local investigators screen consecutive patients intubated in ICU, with an acute respiratory failure (respiratory rate \> 25/min) and hypoxemia. Hypoxemia is defined by the need of a fraction inspirated in oxygen (FiO2)\>50% to maintain a saturation of arterial blood with oxygen as measured by pulse oximetry (SpO2)\>90% and a partial pressure of oxygen in the arterial blood (PaO2)/FiO2 ratio\<300 mmHg under mask oxygen therapy with a flow of 15L/min (measured during the 4 hours before inclusion).

Patients fulfilling one or more of the following criteria will not be included: nonadult patients (age \<18 years), pregnant, protected persons, intubation in case of cardio circulatory arrest, nasopharyngeal obstacle contraindicating the use of HNFC.

Ethics and consent The Institutional Review Board of the University Hospital of Montpellier (France) approved the trial. By May 2015, the study had been approved by a central ethics committee (Committee for the Protection of Persons, Montpellier, France) with the registration number IDRCB 2015-A00708-41.

All patients or their next will asked for signed informed consent, as required by the institutional review board in accordance with the Declaration of Helsinki or emergency procedure allowed inclusion as a part of care in acute situation according the French Law.

Data collection The following data will be collected and registered before intubation: demographic data : age, sex, weight, height, date and hour of intubation, severity scores (Simplified Acute Physiologic Score (SAPS) II at admission, Sequential Organ Failure Assessment (SOFA) score on the day of the procedure), type of admission, reason of admission in ICU, indication of intubation, comorbidities, nature and number of operators, formation, fluid loading before intubation, arterial pressure and lowest saturation, therapeutic by vasopressor drugs or non invasive ventilation, predictive criteria of difficult intubation (including the MACOCHA score).

During the preoxygenation, will be recorded : need to change the method of preoxygenation and the reasons for changing, size of intubation tube, vital parameters : oxygen saturation at the beginning and at the end of the preoxygenation, lowest saturation, lowest and highest arterial pressure and heart rate, length and difficulty of preoxygenation.

During the intubation procedure, the following parameters will be collected : hypnotic and neuromuscular blocker used and dose, oxygen saturation at the beginning and at the end, lowest saturation, total length of intubation procedure, difficult intubation, number of operators, number of attempts, Cormack grade, traction force on the laryngoscope, Sellick manoeuver, occurrence of complications related to intubation.

After the intubation procedure (until one hour after): a thorax X-ray will be done, and arterial blood gases. Complications related to intubation will be collected.

Length of mechanical ventilation, length of stay in ICU, mortality at day 28 will be recorded.

Trial interventions Patients eligible for inclusion are randomly assigned to the interventional group or to the reference group. In the interventional group, a preoxygenation by NIV (PS of 10 cm H2O, PEEP of 5 cm H2O, FiO2 = 100%) combined to HNFC (Flow of 60L/min, FiO2 = 100%) is applied. HFNC will applied along all the intubation procedure including the apnea period. In the reference group, a preoxygenation by NIV only (PS of 10 cm H2O, PEEP of 5 cm H2O, FiO2 = 100%) will be applied.

Outcomes Primary outcome variable is the lowest oxygen saturation collected by pulse oxymetry during the intubation procedure. The intubation procedure lasts from the beginning of the first laryngoscopy to the confirmation of the orotracheal intubation.

Secondary outcome variables are preoxygenation quality, complications related to intubation (severe : severe hypoxemia defined by lowest saturation \< 80 %, severe cardiovascular collapse, defined as systolic blood pressure less than 65 mm Hg recorded at least one time or less than 90 mm Hg that lasted 30 minutes despite 500-1,000 ml of fluid loading (crystalloids or colloids solutions) or requiring introduction of vasoactive support, cardiac arrest, death during intubation; moderate: difficult intubation, arrhythmias, esophageal intubations, agitation, pulmonary aspiration, dental injuries), morbidity in ICU (length of stay, length of mechanical ventilation, mortality at 28 days).

Statistical analysis Quantitative variables will be expressed as means (standard deviation) or medians (interquartiles 25%-75%) and compared using the student t test or the Wilcoxon test as appropriate (Gaussian or non Gaussian variables). Qualitative variables will be compared using the chi 2 test or the Fisher test as appropriate.

A linear regression will be used to adjust the relation of lowest oxygen saturation during intubation procedure and group of inclusion. A multivariate model will be established.

A p-value of ≤ .05 will be considered statistically significant. The statistical analysis will be performed by the medical statistical department of the Montpellier University Hospital with the help of statistical software (SAS, version 9.3; SAS Institute; Cary, NC and R, version 2.14.1).

Eligibility Criteria:
Inclusion Criteria:

* Adult hypoxemic patients
* Patients intubated in the ICU for acute respiratory failure (Hypoxemia is defined by the need of a FiO2\>50% to maintain a SpO2\>90% and a PaO2/FiO2 ratio\<300 mmHg under mask oxygen therapy with a flow of 15L/min (measured during the 4 hours before inclusion)).

Exclusion Criteria:

* non adult patients (age \<18 years)
* pregnant woman
* protected persons
* Patient intubated in case of cardio circulatory arrest
* Patient with nasopharyngeal obstacle contraindicating the use of HNFC