High-flow nasal cannula is a type of non-invasive respiratory support that helps patients breathe more comfortably. Because the flow is high, it can deliver more oxygen to the lungs and make breathing easier by reducing the effort needed to breathe. However, the best strategy to determine the best oxygen flow rate remains uncertain. Reducing flow rates prematurely can increase work of breathing and prolong ICU stay, while unnecessary prolongation can increase costs. Currently, evidence to guide titration is limited.

Heart rate variability is the natural variation in the time between each heartbeat. Heart rate variability reflects the level of autonomic nervous system activity in response to stress. The autonomic nervous system is the part of the nervous system that automatically controls how heart rate speeds up and slows down. When heart rate variability is higher, it indicates that the system is able to adjust to changes in the body, including stress. However, when heart rate variability is low, it indicates that the system is constrained and in a state of stress.

The VARIATION study is designed to characterize how heart rate variability goal of this observational study is to learn whether heart rate variability can serve as a marker of the appropriateness of high flow nasal cannula flow support during flow titration in patients with respiratory failure. The main question it aims to answer is:

Does heart rate variability change before other conventional respiratory signs when there are changes in respiratory function due to inadequate flow rate?

Participants already on high flow nasal cannula as part of their regular medical care will:

1. Undergo a stepwise decrease in high flow nasal cannula flow rate.
2. Be recorded continuously with electrocardiogram and electrical impedance tomography.

Previous work has established that high flow nasal cannula can improve outcomes in patients with respiratory failure. However, the optimal approach to titrating HFNC therapy remains uncertain. As a consequence, some patients may be under-supported with HFNC, leading to excessive respiratory muscle effort, while others may be needlessly over-supported, unnecessarily prolonging ICU admission. Prolonged use of HFNC increases costs, but premature decreases in HFNC support may contribute to deteriorations in lung function and delayed recovery, ultimately leading to prolonged hospital stays. Conventional metrics such as respiratory rate are relatively insensitive to early changes in respiratory drive and may therefore fail to detect early respiratory stress in response to reduced flow rates.

One possible approach to monitor the adequacy of HFNC support would be to monitor heart rate variability (HRV). HRV reflects autonomic nervous system function, where healthy individuals exhibit higher HRV, indicating freedom within a biological system to adapt to conditions. HRV is also influenced by respiration, where fluctuations in heart rate at respiratory frequency reflects vagal modulation of cardiac activity.

In patients in the intensive care unit, reduced heart rate variability is a sign of more severe illness. Because the heart and lungs work closely together, and are linked through the autonomic nervous system, changes in respiratory function may affect heart rate variability before more conventional signs of respiratory distress become apparent. Despite these findings, HRV monitoring during HFNC titration remains unexplored.

In this prospective, physiologic crossover study participants will undergo stepwise decreases (from 60 L/min to 20 L/min) in high flow nasal cannula flow rate, while being continuously monitored with electrocardiogram (ECG) and electrical impedance tomography (EIT). The FiO2 will be adjusted to maintain a target SpO2 > 90%. Tidal volume, respiratory rate, FiO2, and SpO2 will be collected and ROX and VOX indices will be collected at each flow rate. Heart rate variability measures will be analyzed from ECG recordings.

If HRV is more sensitive to the physiological effects of HFNC titration compared to conventional respiratory metrics, it could serve as a valuable marker for optimizing flow rate and preventing respiratory deterioration. The results of this project will address a gap in current practice and investigate a physiological marker of respiratory stress that could be used to optimize HFNC weaning strategies.

Inclusion Criteria:

• Age > 18
• Currently receiving High-Flow Nasal Cannula Therapy

Exclusion Criteria:

• FiO2 ≥ 90%
• Pacemaker rhythm or presence of atrial fibrillation
• Post-cardiac surgery patients
• Contra-indications to electrical impedance tomography (EIT) and/or electrocardiogram (ECG) (active implantable medical device, burns, thoracic wounds limiting electrode placement)
• Non-English-speaking

Patients on high flow nasal cannula for respiratory failure at Toronto General Hospital (UHN)