High-flow Air Via Nasal Cannula Versus Non-invasive Continuous Positive Airway Pressure Ventilation Support for Hypercapnic Respiratory Failure The HIGH-for-HYPER Study

Respiratory failure is a leading cause of morbidity and mortality, and one of the most frequently encountered problems at the emergency department. Hypercapnic or hypercarbic respiratory failure, also dubbed respiratory failure type II, is characterized by failure of the respiratory system in one of its two gas exchange functions: carbon dioxide (CO2) elimination. It is thus usually defined via partial pressure of CO2 in the arterial blood gas (PaCO2), a value greater than 50 mmHg being a commonly used cut-off. Hypercapnic respiratory failure is often associated with severe airway disorders, such as asthma and chronic obstructive pulmonary disease (COPD), but might also be found in other conditions, where respiratory drive is restricted, such as intoxications, neuromuscular diseases or chest wall abnormities. Hypercapnic respiratory failure, i.e. respiratory failure type II, is often associated with hypoxemic respiratory failure, i.e. respiratory failure type I, failure of oxygenation. However, type I failure is also often observed without hypercapnia. Respiratory failure, both type I and II, may be further classified into either acute or chronic. Distinction between both forms is often challenging, and, in addition to arterial blood gas analysis, might require additional tests to identify clinical markers such as polycythemia or pulmonary heart disease. For practical reasons, acute respiratory failure is often defined as a condition, in which respiratory failure develops too fast to allow for renal compensation and an increase in bicarbonate (HCO3-) levels, and thus leading to acidosis (pH less than 7.3). Therapeutic strategies for hypercapnic respiratory failure include non-invasive CPAP ventilation support, intubation and mechanical ventilation (both assisted and controlled forms), and, in very severe cases, extracorporeal methods, such as extracorporeal life support systems.

Non-invasive CPAP ventilation support via either helmets, or different kinds of tight masks, is the current method of choice for the treatment of patients with acute respiratory failure in the intensive care setting. Eligible patients include those with an intact airway, airway-protective reflexes, who are alert enough to follow commands, whereas patients who lack those criteria require immediate endotracheal intubation. Non-invasive CPAP ventilation support improves both oxygenation (by providing an inspired fraction of oxygen (FiO2) of 100%, which is not possible via a simple venturi-mask, and the possibility of positive end-expiratory pressure (PEEP), preventing collapsing of the alveoli), and decarboxylation (by increasing tidal volume). It has been shown to decrease both need for intubation and in-hospital mortality. Non-invasive CPAP ventilation support, however, requires a high grade of skill from providers, and intensive communication with the patient to explain the usefulness of a tight-sitting device in the face in a situation of perceived massive dyspnea. Although severe adverse effects of non-invasive CPAP ventilation support are very rare, pain and pressure marks may occur. Despite all efforts of care providers, there is a relevant proportion of patients who do not tolerate ventilation support via a tight mask at all. About 15% of patients not tolerating the therapy, with an additional 25% of patients presenting with contraindications. These might include general contraindications against non-invasive techniques, such as aforementioned lack of airway-protective reflexes, but also such specific for tight masks, such as anatomical abnormities of the face.

High-flow Air via Nasal Cannula (HFA) therapy is usually applied via a wide-bore nasal cannula. It provides up to 60 litres per minute of a heated and humidified gas mixture (with an adjustable FiO2). This therapy is much less invasive for the patient, and thus often better tolerated. HFA has been increasingly used in the last years to treat hypoxic respiratory failure (i.e. type I failure), and numerous studies have shown its efficiency in this indication both at the intensive care unit and at the emergency. A recent systematic review and meta-analysis has concluded in improved patient comfort and reduced dyspnea scores. Despite this good evidence for HFA in hypoxic respiratory failure, it has only reluctantly been used for hypercapnic respiratory failure. This might be explained in a large part by the fact that patients with chronic hypercapnia are known to diminish their respiratory drive when exposed to hyperoxia. However, evidence has begun to change on this indication in recent time. HFA has been shown to generate PEEP, despite not being a closed system, and to improve CO2 clearance by flushing anatomical dead space. It might also help to reduce inspiratory resistance and facilitate secretion clearance from humidified gas. A study on COPD patients showed an increase in breathing pressure amplitude and mean pressure, as well as tidal volume, with a trend towards reduction of pCO2. Based on these findings, the use of HFA has increased in clinical practice, and a number of case reports and -series indicate successful use. Fraser et al. successfully investigated the use of HFA in patients with chronic COPD changes in arterial blood gases during use of HFA in the ED for both hypercapnic and non-hypercapnic patients were analyzed in previous studies, and found a significant reduction of pCO2.

There is, however, to date no randomized controlled trial investigating the effect of HFA in acute hypercapnic respiratory failure.

The study will be performed as a randomized controlled non-inferiority trial. The study site is the Department of Emergency Medicine (ED) at the Vienna General Hospital, a leading academic research center for emergency medicine at a large, tertiary care hospital. Around 90,000 patients are being treated at the department each year, approximately 150-200 of them suffering from hypercapnic respiratory failure, and requiring non-invasive ventilation support. The department features its own ICU and intermediate-care unit, with 7 positions each, for a total of 14 positions capable of providing CPAP therapy. The HFA-device is also at regular use at the department.