Introduction
Disease burden
Acute respiratory failure (ARF) is a common clinical condition accounting for nearly 116 000 of the UK hospital admissions for respiratory support per year and classified as type 1 or type 2.1 Type 2 respiratory failure is also called acute hypercapnic respiratory failure (AHRF) and characterised by an elevated arterial CO2 (PaCO2) level of >6 kPa due to pump failure.2 The pump failure relates to the imbalance between the respiratory demand and the capacity of the muscle pump to match the demand. Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is the most common cause for AHRF with the rest accounted for by neuromyopathies, chest wall deformities and obesity.3 Chronic obstructive pulmonary disease (COPD) is the most common chronic respiratory disease globally with approximately 328 million sufferers worldwide and expected to become the leading cause of death in the next 15 years.4 5 AECOPD leads to 100 000 admissions in England annually. Approximately 20% of patients with AECOPD will present with or develop hypercapnia, an indicator of increased risk of death.6 7 In-hospital mortality in patients with AECOPD is still high, up to 8%, that increases to up to 15% in the intensive care unit (ICU) patients. The 1-year mortality in these patients is up to 44%.8 Adequate treatment of AHRF is essential to prevent mechanical ventilation in these patients to reduce mortality and the demand on critical care resources.
Current management strategy
Treatment for AHRF includes medical therapy such as bronchodilators, diuretics, antibiotics and controlled oxygen therapy aimed at relieving the underlying pathological process such as fluid overload, bronchospasm and infection.3 Patients will also require ventilatory support that may be non-invasive ventilation (NIV) or invasive mechanical ventilation (IMV). NIV is recommended in patients with modest respiratory acidosis, patients with severe respiratory acidosis as a trial prior to IMV or as a ceiling of therapy.9 In a trial comparing NIV to IMV in patients with AECOPD, there was no survival benefit. However, in those patients in whom NIV was successful, duration of hospital stay was shorter, there were fewer complications, fewer patients required de novo oxygen supplementation and there were fewer readmissions to hospital in the following year.10
Limitations of NIV
The failure rate of NIV is still up to 40% with a significant amount of late failure after initial success. The factors leading to NIV failure is multifactorial including ventilator asynchrony due to mask leak, trigger issues, non-compliance due to claustrophobia, delirium, sputum retention, reduced communication and skin compromise. Mask discomfort is seen in up to 50% of patients and skin compromise is seen in up to 20% of patients.11 There are also relative medical contraindications including emesis, reduced mentation and reduced access to physiotherapy manoeuvres that limit its use. A study by Wood et al has suggested worse outcomes that may be secondary to an inadvertent delay in initiating IMV in patients who were failing NIV.12 13 A similar observation was made in a large cohort study where NIV use was associated with a 29% mortality rate that was 60% higher than patients managed by immediate IMV.13 These highlight the importance of vigilance and rapid escalation to IMV in patients failing NIV.
High-flow nasal cannula therapy—beyond an oxygen delivery device
High-flow nasal therapy (HFNT) is a new oxygen delivery system that uses an oxygen-air blender to deliver flow rates of up to 60 L/min. The gas is delivered humidified and heated to the patient via wide-bore nasal cannula. When compared with conventional oxygen via face mask and NIV, the benefits are considered to be multifactorial. The humidified system causes fewer side effects of nasal and throat dryness and or pain. Patients, therefore, tolerate the device for longer, leading to fewer episodes of interface dislodgement with associated desaturations.14 The delivery of a constant fraction of inspired oxygen and ability to achieve high-flow rates above that possible with conventional oxygen (maximum 15 L/min) allows the delivery flow rate to better match that of the patient in ARF, whose inspiratory flow can reach up to 100 L/min.15 A heating system and humidifier allow delivery of gases at temperatures of between 33°C and 43°C and 95%–100% humidity. During exercise or respiratory distress, flow rates of up to 120 L/min can be reached. This results in increased fluid losses and a higher metabolic oxygen requirement to achieve warmed gases. Flow rates such as this are achievable for only short periods and limited by fatigue. The application of cold, dry gases to patients with an increased oxygen requirement may exacerbate the heat loss and is associated with discomfort and reduced compliance with therapy. When this occurs, gas humidification decreases below 50% of relative humidity which can result in drying secretions, reduced cilial function and poor mucous flow. This could promote mucus plugging and exacerbate airway obstruction and atelectasis.16 HFNT circumvents the above problems by providing rates of flow up to 60 L/min, warmed humidified gas delivery that improves patient comfort and supports mucous clearance.
The upper and lower airways from the nasal cavity to the conductive lower airways that do not take part in gas exchange constitute the anatomical dead space. HFNT clears the upper airways of expired air and reduces rebreathing thereby improving the efficiency of ventilation.17 There is an associated increase in positive end-expiratory pressure (PEEP) that could be a potential benefit in patients with obstructive airways disease by increasing end-expiratory lung volume and offsetting intrinsic PEEP.15 18–20 In a study of healthy human volunteers, HFNT in a dose and time-dependent manner was shown to decrease 81mKr gas clearance half-time.21 There was a reduction in inspired CO2 that correlated with an increase of inspired oxygen. In airway models, CO2 clearance has been demonstrated even in apnoeic settings due to flow vortices created by the high‐flow and cardiogenic oscillations.22 23
Current evidence for high-flow nasal oxygen therapy in hypercapnic respiratory failure
We conducted a systematic review that included randomised controlled trials (RCTs) and cohort studies to synthesise the evidence for the efficacy of HFNT for adult patients with AHRF. The systematic review was published a priori in PROSPERO database (CRD42019148748).
Four articles were eligible for qualitative and quantitative synthesis. Three RCTs and one observational study involved 345 patients with acute-moderate hypercapnic respiratory failure or AECOPD or COPD. The results showed that HFNT significantly improves PaCO2 at 4 hours in comparison to NIV. Furthermore, patients in the HFNT group were more comfortable than the NIV group. Secondary outcomes including, arterial oxygen (PaO2), pH, dyspnoea score, intubation rate, mortality rate and hospital stay showed no significant differences between HFNT and NIV or low-flow nasal oxygen (LFO).
Despite the clinical benefits found in improving PaCO2 at 4 hour and patient comfort by HFNT, the review found that the quality of evidence was low and their certainty was affected by the high risk of bias, non-RCT study design and serious imprecision. Therefore, no recommendation could be made regarding the use of HFNT for AHRF. The review highlighted an important knowledge gap in the evidence for the use of HFNT for AHRF. Despite the increasing evidence for the benefit of HFNT in managing AHRF from mechanistic and physiological studies in airway models, healthy volunteers and patients with COPD, urgent high-quality RCTs are recommended to assess HFNT efficacy for patients with AHRF as an initial management strategy.
Current practice
Current guidelines for the management of patients include medical therapy and controlled oxygen administration in patients with AHRF as the initial management strategy. Twenty per cent of patients are expected to improve with this conservative management strategy with LFO.24 NIV is recommended for patients who do not improve where the pH is 7.25–7.35 secondary to hypercapnia with no contraindications for NIV.