Clinical trial NCT03282552: High Flow Oxygen Therapy Versus Conventional Oxygen Therapy in Cardiac Surgery Patients
Official title: High Flow Oxygen Therapy Versus Conventional Oxygen Therapy in Cardiac Surgery Patients-OPTICAR Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hypoxemic Respiratory Failure
Lead sponsor: National and Kapodistrian University of Athens
Sponsor class: OTHER
First posted: 2017-09-14
Enrollment: 99
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: High flow oxygen therapy has been applied after extubation in cardiac surgery patients with uncertain efficacy. The current authors plan to conduct a prospective, randomized, controlled study of nasal high flow therapy (NHF) application with high (60L/min) or low flow (40L/min) oxygen mixture administration versus standard oxygen treatment (Venturi mask) after extubation of patients undergoing elective or non-elective cardiac surgery.

Detailed description: Over the past decade, nasal high flow (NHF) has been introduced for oxygen therapy in adults. Its indications have been expanded, especially in cases of acute hypoxemic respiratory failure.

The device consists of an air/oxygen blender connected via an active heated humidifier to a nasal cannula, through a single limb, heated inspiratory circuit. It delivers a fraction of inspired oxygen (FiO2) from 21% to 100% with a flow rate up to 60 L/min. FiO2 adjustments are independent of the set flow rate so that the patient is given heated, humidified high-flow oxygen, with a flow that can be adjusted above the patient's maximum inspiratory flow rate, thereby increasing confidence about the actual FiO2 being delivered to the patient. These device characteristics make it more promising in comparison with conventional low- and high-flow oxygen devices (e.g., nasal cannula, non-rebreathing masks, Venturi masks), especially in patients with high inspiratory flow rates, such as patients with acute respiratory failure (ARF).

The benefits arising from application of oxygen with high flow rates via NHF are

1. reduction in the entrainment of room air and thus ensuring higher and more stable FiO2 values,
2. generation of positive airway pressures during expiration as a result of the expiratory resistance imposed to the patient's exhalation against the continuous high flow of incoming oxygen gas,
3. improving mucociliary function and clearance of secretion by continuous heating and humidifying of the administered gas,
4. reducing dead space ventilation and
5. reducing work of breathing. All the aforementioned NHF mechanisms of actions exert various effects on the respiratory system, including improved gas exchange, lower respiratory rate and effort and improved lung mechanics which are correlated with more comfort and less subjective dyspnea.

Respiratory complications after cardiac surgery can affect morbidity and mortality, and increase the healthcare cost. Advanced age, duration of extracorporeal circulation, history of significant underlying cardiac or pulmonary disease and phrenic nerve injury are the main prognostic factors for post cardiac surgery respiratory complications.

Traditionally, low- and high-flow oxygen systems are used to reverse postsurgical respiratory complications with or without addition of continuous (CPAP) or bi-level (NIV) positive airway pressure.

NHF might be superior for the prevention or treatment of those respiratory complications, since it can provide high-flow of heated and hydrated oxygen while the positive airway pressure created by the high gas flow can recruit alveoli and increase the end-expiratory lung volume.

Studies applying NHF immediately after extubation in cardiac surgery patients revealed better oxygenation and less need for advanced methods of respiratory support compared to conventional oxygen devices , and similar results compared to noninvasive ventilation. However, Zochios et al, summarized all the available up to date data of NHF compared to conventional oxygen devices and non-invasive ventilation in patients undergoing cardiothoracic surgery and they did not find any further benefit by NHF use. The aforementioned discrepancy could be explained by the differences in the studied populations and NHF flow settings. The proposed initial flow rate differs among the studies, with some authors suggesting initial lower flows (35-40 L/min) that will be better tolerated by the patients and others suggesting initial maximal flows (60 L/min) to rapidly relieve dyspnea and prevent muscle fatigue.

Aim The primary goal of the study is to evaluate the efficacy of NHF (with initial flows of 60 L/min or 40 L/min) versus conventional oxygen systems on respiratory parameters (respiratory rate, pO2/ FiO2, spO2, use of accessory muscles, dyspnoea, comfort and tolerance by using the visual analogue scale) immediately after the extubation of cardiac surgery patients.

Additional goals of the study are to compare two different initial NHF flows of 60 L/min and 40 L/min, ICU Length of Stay, Hospital Length of Stay, rates of ICU re-admission and re-intubation and any other respiratory / non-respiratory complications and adverse events. Moreover, the rate of failure of the initial treatment will be recorded (as a major measure of treatment efficacy).

Method

This is a prospective, non-blinded, randomized study in post-extubated cardiac surgery patients. The study population will consist of three patient groups:

The first group (Study Group 1) will include patients on NHF with initial settings of FiO2=60% and gas flow=60L/min.

The second group (Study Group 2) will include patients on NHF with initial settings of FiO2=60% and gas flow=40L/min In the third group (control group) all patients will receive oxygen therapy according to the standard practice of our cardiac ICU department, i.e., Venturi mask with FiO2=60% and flow of 15L/min.

Patients in both study groups would be weaned off the NHF as follows; First reducing FiO2 gradually to 50%, and then gradually reducing the gas flow (either from 60l/min or 40/min, depending on the study group) down to 30l/min, aiming at the final wean-off goal of 20l/min, unless the attending physician decides to wean-off patient to Venturi mask directly from a higher gas flow supply (e.g.: 30-25l/min) Treatment failure will be defined as any crossover from one treatment to another due to patient's respiratory distress and discomfort. To be more specific, switch of gas flow from 40L/min to 60L/min, crossover from either NHF group to standard practice (Venturi mask) or need for more advanced respiratory support such as non-invasive ventilation or invasive mechanical ventilation.

Any implemented treatment would also be defined as "failure" when any irreversible (for at least 48 hours) FiO2/gas-mixture flow escalation might be needed, either it is being recorded on Study group 1 \& 2 or Control group.

An initial power analysis was based on a predicted, average failure rate of 15% in the 2 NHF groups and a failure rate of 51% in the control group; this analysis yielded the need for enrollment of a total of 41 NHF patients and 21 controls for alpha = 0.05 and power=0.80. To ensure equal numbers of patients in each one of the 2 NHF groups, the authors decided to actually enroll 42 NHF patients (n=21 for each NHF group) and 21 controls, resulting in a total enrollment of 63 patients. At one year after study initiation, actual, total enrollment amounted to 45 patients. At this time point, the Data Monitoring Committee (after confirming the safe application of the study protocol) recommended the continuation of the study until the enrollment of 99 patients (n=33 for each one of the 3 groups); the rationale for this was to compensate for possible dropouts and/or missing data (especially for the secondary and "other" outcomes). Accordingly, the study was completed with an actual enrollment of 99 patients.

Eligibility criteria: Inclusion Criteria:

* Cardiac ICU adult patients
* \>18 years
* After elective or urgent cardiac surgery
* Successful Spontaneous Breathing Trial (SBT) with T-piece and FiO2=60%.
* pO2/ FiO2 \<200
* Hemodynamically stable (160\>SAP\>90mmHg)

Exclusion Criteria:

* Obstructive Sleep Apnea Syndrome supported by CPAP
* COPD, officially diagnosed, respiratory failure with serum blood ph \<7,35.
* Patients with tracheostomy,
* DNR status,
* Glasgow Coma Scale score \< 13,
* Insufficient knowledge of Greek Language
* Visual or hearing impairment.

Primary outcomes:
measure: Successful weaning (i.e. absence of treatment failure) from Nasal Cannula High Flow Oxygenation post extubation from cardiac surgery within at least 48 hours
timeFrame: Up to at least 48 hours post extubation or until ICU discharge (predicted cardiothoracic ICU stay could occasionally extend up to 7 days)
Secondary outcomes:
measure: Successful maintenance of Respiration rate within normal range (12-20/min) on initial air flow at 60 L/min with Nasal Cannula High Flow Oxygenation
timeFrame: Post extubation period up to 48 hours or ICU discharge (if cardiothoracic ICU stay was <48 hours)
measure: Successful maintenance of Respiration rate within normal range (12-20/min) on initial air flow of 40 L/min with Nasal Cannula High Flow Oxygenation
timeFrame: Post extubation period up to 48 hours or ICU discharge (if cardiothoracic ICU stay was <48 hours)
measure: Successful maintenance of Respiration rate within normal range (12-20/min) with Venturi mask , FiO2: 60%, 15L/min
timeFrame: Post extubation period up to 48 hours or ICU discharge (if cardiothoracic ICU stay was <48 hours)
measure: Recording of pO2/FiO2 ratio with initial air flow at 60 L/min with Nasal Cannula High Flow Oxygenation
timeFrame: Post extubation period up to 48 hours or ICU discharge
measure: Recording of pO2/FiO2 ratio with initial air flow at 40 L/min with Nasal Cannula High Flow Oxygenation
timeFrame: Post extubation period up to 48 hours or ICU discharge (if cardiothoracic ICU stay was <48 hours)
measure: Recording of pO2/FiO2 ratio with Venturi mask FiO2: 60%, 15L/min
timeFrame: Post extubation period up to 48 hours or ICU discharge (if cardiothoracic ICU stay was <48 hours)
measure: Successful maintenance of saturation O2 in Hemoglobulin within normal range with initial air flow at 60 L/min with Nasal Cannula High Flow Oxygenation
timeFrame: Post extubation period up to 48 hours or ICU discharge (if cardiothoracic ICU stay was <48 hours)
measure: Successful maintenance of saturation O2 in Hemoglobulin within normal range with initial air flow at 40 L/min with Nasal Cannula High Flow Oxygenation
timeFrame: Post extubation period up to 48 hours or ICU discharge (if cardiothoracic ICU stay was <48 hours)
measure: Successful maintenance of saturation O2 in Hemoglobulin within normal range with Venturi mask, FiO2: 60%, 15L/min
timeFrame: Post extubation period up to 48 hours or ICU discharge (if cardiothoracic ICU stay was <48 hours)
measure: Mobilization of accessory respiratory muscles with initial air flow at 60 L/min with Nasal Cannula High Flow Oxygenation
timeFrame: Post extubation period up to 48 hours or ICU discharge (if cardiothoracic ICU stay was <48 hours)
measure: Mobilization of accessory respiratory muscles with initial air flow at 40 L/min with Nasal Cannula High Flow Oxygenation
timeFrame: Post extubation period up to 48 hours or ICU discharge (if cardiothoracic ICU stay was <48 hours)
measure: Mobilization of accessory respiratory muscles with Venturi mask, FiO2: 60%, 15L/min To record any use of accessory respiratory muscles with Venturi mask , FiO2: 60%, 15L/min
timeFrame: Post extubation period up to 48 hours or ICU discharge (if cardiothoracic ICU stay was <48 hours)
measure: Comfort and tolerance of treatment with Visual Analogue Scale with initial air flow at 60 L/min with Nasal Cannula High Flow Oxygenation
timeFrame: Post extubation period up to 48 hours or ICU discharge (if cardiothoracic ICU stay was <48 hours)
measure: Comfort and tolerance of treatment with Visual Analogue Scale with initial air flow at 40 L/min with Nasal Cannula High Flow Oxygenation
timeFrame: Post extubation period up to 48 hours or ICU discharge (if cardiothoracic ICU stay was <48 hours)
measure: Comfort and tolerance of treatment with Visual Analogue Scale with Venturi mask , FiO2: 60%, 15L/min
timeFrame: Post extubation period up to 48 hours or ICU discharge (if cardiothoracic ICU stay was <48 hours)
Other outcomes:
measure: Length of Stay in the ICU
timeFrame: Post cardiothoracic ICU admission period up to 48 hours or untiI actual cardiothoracic ICU discharge
measure: Length of Stay in the Hospital
timeFrame: Post ICU admission period up to actual hospital discharge
measure: Number of participants with death in the cardiothoracic ICU post extubation
timeFrame: Post cardiothoracic ICU admission period up to 48 hours or untiI actual cardiothoracic ICU discharge
measure: Number of participants with death in the hospital post ICU discharge
timeFrame: Post ICU discharge period up to actual hospital discharge
measure: Number of participants with Atrial Fibrillation in the ICU post extubation
timeFrame: Post ICU admission period up to 48 hours or actual ICU discharge
measure: Number of participants with any Adverse Events in the ICU
timeFrame: Post cardiothoracic ICU admission period up to 48 hours or untiI actual cardiothoracic ICU discharge
measure: Number of participants with any Adverse Events in the Hospital
timeFrame: Up to 1 month, or until actual hospital discharge
measure: Percentage of participants presenting unsuccessful (failed) implementation of NHFO treatment
timeFrame: Post cardiothoracic ICU admission period up to 48 hours or untiI actual cardiothoracic ICU discharge
measure: Number of participants with re-intubation in the ICU
timeFrame: Post cardiothoracic ICU admission period up to 48 hours or untiI actual cardiothoracic ICU discharge
Locations:
city: Athens
country: Greece
facility: Evangelismos General Hospital of Athens
state: Attiki
Study officials:
affiliation: National and Kapodistrian University of Athens
name: Spiros Zakynthinos, Professor
role: STUDY_CHAIR
affiliation: National and Kapodistrian University of Athens
name: Spiridon Mentzelopoulos, AssProfessor
role: STUDY_DIRECTOR
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