High Flow Nasal Oxygenation in Transcatheter Aortic Valve Replacement Procedures. TAVR-Highflow II

Transcatheter aortic valve replacement (TAVR) has revolutionized the treatment of patients with aortic valve disease. TAVR is a less invasive treatment compared to the conventional surgical approach through median sternotomy. These technological advances have enabled a minimally invasive anesthetic approach that avoids mechanical ventilation, central line insertion, and urinary catheterization in most patients undergoing TAVR.

However, patients selected for this procedure often have a profile associated with multiple comorbidities such as pulmonary disease, ischemic coronary artery disease, and atherosclerosis of the carotid and renal arteries, which predispose them to certain complications.

Acute kidney injury (4%-35%), ischemic stroke (1%-3%), acute heart failure (7%-24%), and hypoxemia with hypercapnia are the most common perioperative complications. The overall 30-day mortality rate is 2.2%.

Because they are considered high-risk (both due to the procedure and the type of patient undergoing this procedure) and due to their duration, TAVI procedures were initially performed under general anesthesia. With improved procedure times and improved anesthetic techniques, the trend is to attempt to perform these procedures under deep sedation. As in many settings, sedation for diagnostic and/or therapeutic procedures can be achieved with a variety of medications, the goal of which is sedation to enable procedural success. The development and advancement of procedures as an alternative to surgery and/or more invasive diagnostic and therapeutic procedures means that the use of less invasive techniques is becoming increasingly common. Depending on the procedure, sedation may be required. However, despite the less invasive nature of these tests, deep sedation is frequently required for these procedures.

Deep sedation techniques have developed alongside technological advances that enable the provision of complex diagnostic and therapeutic procedures, often performed in settings outside the operating room. These settings include procedure rooms, radiology departments, outpatient departments, emergency rooms, surgical facilities, interventional cardiology departments, and so on. Deep sedation is used to support and enable the performance of these procedures. Enthusiasm for providing sedation for these procedures in a non-OR setting was tempered by an increase in mortality in non-OR areas, even leading one author to describe this as the "Wild West" of surgical and anesthetic practice. This required both professionals and regulatory authorities have developed increased oversight to improve the quality of care for out-of-the-operative procedures.

When sedation for these procedures requires deep planes, hypoxia is more likely to occur due to respiratory depression, apnea, or airway obstruction. This is even more common in patients at risk due to obesity, sleep apnea, elevated ASA classification, age \>60 years, and combined cardiorespiratory disease. The reported incidence of hypoxia ranges from 10% to 70%, depending on the definition of hypoxia used. The risk of hypoxia further increases with the duration of the procedure.

The risk of periprocedural hypoxia can be reduced by monitoring respiratory and sedation parameters. However, even the most effective monitoring and standards of care may not be sufficient to reverse the respiratory compromise caused by deep sedation. Deep sedation affects the respiratory system through effects on normal cardiorespiratory physiology. These changes include a drop in respiratory rate, tidal volume, and changes in cardiorespiratory dynamics, and these effects are further affected by patient positioning. Subjects with cardiorespiratory diseases, such as pulmonary hypertension and chronic respiratory diseases, are particularly at risk for a critical decline in function.

The provision of supplemental oxygen through nasal cannulae or face masks can prevent the development of hypoxia. Unfortunately, non-humidified nasal oxygen cannot exceed 2-5 L/min without causing damage to the nasal mucosa, and the percentage of oxygen delivered through variable-flow face masks is unpredictable.

High-flow nasal oxygen therapy (HFNO), which is also unique in that it is humidified, was developed to provide flow rates of up to 70 L/min through specially adapted nasal cannulae and reliably delivers oxygen concentrations between 21% and 100%. Many operators are finding that combining deep planes of sedation with HFNC reduces the risk of periprocedural hypoxia. HFNC reduces the work of breathing, physiological dead space and provides an element of positive end-expiratory airway pressure.

HFNO has the potential to reduce procedural hypoxic events, procedural interruptions, and increase therapeutic success. However, although not all trials have concluded that HFNO improves safety compared to standard nasal oxygen therapy, the experience of most operators is positive.

The additional cost of HFNO may be a limiting factor for its use during procedural sedation, but it may be justified in high-risk procedures and patients with risk factors (already discussed), as it improves safety and quality of care. Deep sedation now allows complex diagnostic and therapeutic procedures to be performed outside the operating room in high-risk patients, but it is not without risk, and tools must be developed to mitigate the possibility of such risk.

For all the reasons stated above, TAVI constitutes a risky procedure, presenting a profile of patients undergoing this procedure that can also be considered high risk. The use of HFNC could be justified in this context and could improve the outcomes and safety of these procedures.

The use of HFNC during sedation for TAVI could increase oxygen content and minimize hypercapnia, which frequently occur. This may have two potential benefits: one in terms of facilitating patient tolerance to anesthetic sedation; and the other in optimizing oxygen delivery to organs such as the brain, kidneys, and myocardium. Currently, the profile of patients typically proposed for TAVI is those with aortic disease and significant morbidity and/or older age, who have been ruled out for conventional surgery. These patients are more likely to develop periprocedural complications, being specially sensitive to them.

In a recent study conducted in the United Kingdom, the use of HFNO with a FiO2 of 30% was associated with an 18% reduction in desaturation episodes; however, a decrease in hypoxemia measured by arterial oxygen levels could not be observed.

In a recent randomized clinical trial conducted at the Hospital Clínic in Barcelona (currently under review), the use of HFNO with a FiO2 of 60% was associated with a 31% reduction in desaturation episodes, higher arterial oxygen levels, and improved postoperative renal function, both analytically (measured by creatinine and glomerular filtration rate) and clinically (a 10% reduction in the incidence of renal failure according to VARC criteria).

However, several questions remain to be determined. First, a potential impact (both clinical and analytical) on preventing damage to other target organs (brain and heart). Second, the identification of patient subgroups at higher risk of desaturation and hypoxemia during deep sedation and who, consequently, may benefit more from HFNC treatment. Finally, there is still no data to assess the clinical impact of HFNC on clinical variables such as mortality, hospital stay, and reduction of postoperative complications (stroke, delirium, heart failure, etc.).

The justification for the study would be the use of HFNC, a therapy already available in healthcare centers but not widely used for these procedures. The risks of its use are comparable to those of conventional nasal oxygen therapy. Potential benefits would include a reduction in respiratory complications, a potential improvement in organ-specific biomarker levels, and a potential reduction in clinical cardiological, neurological, and renal complications, as well as an improvement in hospital stay and periprocedural mortality.

The study population would be all patients \>18 years of age undergoing TAVI procedure and who agree to participate in the study in 8 centers in Barcelona.

• Number of Desaturation episodes [Time frame: From enrollment until end of TAVR procedure]
• Desaturation incidence [Time frame: From enrollment until the end of TAVR procedure]
• PaO2 [Time frame: At enrollment and at 45 minutes after enrollment]
• PaCO2 [Time frame: At enrollment and at 45 minutes after enrollment.]
• Neuronal Specific Enolase [Time frame: At enrollment and at 8 hours after enrollment.]
• Creatinine [Time frame: At enrollment and at 8 hours after enrollment.]
• Troponin [Time frame: At enrollment and at 8 hours after enrollment.]
• NT-proBNP [Time frame: At enrollment and at 8 hours after enrollment.]
• Number of patients presenting with respiratory depression [Time frame: From enrollment until the end of TAVR procedure]
• Vasopressors [Time frame: From enrollment until the end of TAVR procedure.]
• Propofol and remifentanil [Time frame: From enrollment until the end of TAVR procedure]
• Procedural duration [Time frame: Procedure (Time from start of sedation to when sedation drugs are stopped)]