Severe COPD exacerbation ‑ What is the optimal noninvasive ventilation treatment?

• COPD is one of the most common diseases worldwide and COPD exacerbation is a frequent cause of ICU admission.
• While NIV is currently the gold standard for treating acute respiratory failure,  high flow nasal therapy has been shown to have physiological advantages for COPD exacerbation.
• A  single‑center randomized controlled trial compared NIV and HFNT in the treatment of 228 patients with severe COPD exacerbation. 
• NIV was found to be superior to HFNC in terms of treatment failure with no difference between the groups in terms of mortality, ICU length of stay, or hospital length of stay.

COPD affects 10% of the adult population with an estimated 3 million deaths yearly, which leads to a major economic and social burden (Global initiative for chronic obstructive pulmonary disease1​). As such, severe COPD exacerbation is a frequent cause of ICU admission (Peñuelas O, Muriel A, Abraira V, et al. Inter‑country variability over time in the mortality of mechanically ventilated patients. Intensive Care Med. 2020;46(3):444‑453. doi:10.1007/s00134‑019‑05867‑92​). Exacerbations are mainly triggered by respiratory viral infection, although a bacterial infection, ambient air pollution, or excess heat may also initiate or amplify the event. The acute respiratory distress results from an imbalance between the increased respiratory load and the impaired neuromuscular capacity, where the intrinsic PEEP is a major burden.

Management combines pharmacological therapies and physiotherapy to treat the cause with temporary respiratory support to relieve the respiratory distress. Noninvasive ventilation (NIV) is currently the gold standard for treating respiratory failure (Osadnik CR, Tee VS, Carson‑Chahhoud KV, Picot J, Wedzicha JA, Smith BJ. Non‑invasive ventilation for the management of acute hypercapnic respiratory failure due to exacerbation of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2017;7(7):CD004104. Published 2017 Jul 13. doi:10.1002/14651858.CD004104.pub43​). The combination of extrinsic PEEP that counterbalances intrinsic PEEP and pressure support decreases the respiratory rate, work of breathing, and PaCO2, while increasing pH. NIV is able to prevent invasive mechanical ventilation in most cases, with a failure rate of around 15% (Lindenauer PK, Stefan MS, Shieh MS, Pekow PS, Rothberg MB, Hill NS. Outcomes associated with invasive and noninvasive ventilation among patients hospitalized with exacerbations of chronic obstructive pulmonary disease. JAMA Intern Med. 2014;174(12):1982‑1993. doi:10.1001/jamainternmed.2014.54304​, Erratum: A Multicenter Randomized Trial Assessing the Efficacy of Helium/Oxygen in Severe Exacerbations of Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2018;197(6):839‑840. doi:10.1164/rccm.1976Erratum5​).

However, high flow nasal therapy (HFNT) has been shown to have physiological advantages for severe COPD exacerbation that help decrease the inspiratory load . The effects  of a decreased respiratory rate, washout of the nasopharyngeal dead space, PEEP that counterbalances intrinsic PEEP, and humidification concur to decrease PaCO2 (Cortegiani A, Longhini F, Madotto F, et al. High flow nasal therapy versus noninvasive ventilation as initial ventilatory strategy in COPD exacerbation: a multicenter non‑inferiority randomized trial. Crit Care. 2020;24(1):692. Published 2020 Dec 14. doi:10.1186/s13054‑020‑03409‑06​). Therefore, the optimal noninvasive ventilation support is now being questioned.

A recent article reports the results from a Chinese single‑center randomized controlled trial that compared NIV and HFNT in the treatment of severe COPD exacerbation (Tan D, Wang B, Cao P, et al. High flow nasal cannula oxygen therapy versus non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease with acute-moderate hypercapnic respiratory failure: a randomized controlled non-inferiority trial. Crit Care. 2024;28(1):250. Published 2024 Jul 18. doi:10.1186/s13054-024-05040-97​). The study was designed as a non-inferiority trial with treatment failure as a primary endpoint. COPD patients with moderate hypercapnic respiratory acidosis defined as PaCO2 ≥ 50 mm Hg and pH between 7.25 and 7.35 were included. Those patients who required immediate endotracheal intubation, had severe hypoxemia, were in palliative care, or had a contra-indication for NIV or HFNT were excluded. Patients received NIV through a facial mask in sessions, with standard low-flow oxygen between the NIV sessions until the respiratory acidosis was corrected. HFNT was set at 40 l/min and 37°C, and used continuously or intermittently according to the patient’s tolerance. Once PaCO2 was corrected, the flow was gradually decreased if the patient had no respiratory distress, then stopped when the flow reached 15 l/min. Cross-over between treatments was allowed. The criteria for intubation were defined. The primary endpoint was treatment failure defined as invasive ventilation, or a switch in the respiratory treatment modality. 

Out of 415 patients screened, 228 patients were randomized. Most of them were COPD GOLD stage II and III, with a pH of around 7.30 and a PaCO2 at 60‑65 mmHg at inclusion. In the intention‑to‑treat analysis, treatment failure occurred in 26% and 14% for the HFNT and NIV groups, respectively. The difference between the groups was higher than the non‑inferiority threshold. Similar results were reported for the per‑protocol analysis. The endotracheal intubation rate was 14% and 5% in the HFNT and NIV groups, respectively (p = 0.026). NIV was better in reducing PaCO2 at 48 hours, while HFNT was associated with better patient‑reported comfort and a lower number of nursing airway interventions. There was no difference between the groups in mortality, or in ICU or hospital length of stay. 

This study suggests that NIV is superior to HFNT in terms of treatment failure rate. NIV offers the possibility to adjust PEEP and provide extra pressure support, which can increase the patient’s minute volume and decrease their work of breathing more effectively when compared to HFNT. However, because NIV is applied in sessions, using HFNT in between the NIV sessions is associated with a lower respiratory rate, less dyspnea, and improved patient‑reported comfort when compared to low‑flow oxygen (Spoletini G, Mega C, Pisani L, et al. High-flow nasal therapy vs standard oxygen during breaks off noninvasive ventilation for acute respiratory failure: A pilot randomized controlled trial. J Crit Care. 2018;48:418-425. doi:10.1016/j.jcrc.2018.10.0048​).

To conclude, NIV should remain the first‑line ventilation support for severe exacerbation of COPD, while HFNT is useful to support the patient in between NIV sessions.

Hamilton Medical ventilators offer HFNT (Standard or optional feature depending on ventilator modelA​), NIV (Standard or optional feature depending on ventilator modelA​), and invasive ventilation modes. When connected to the HAMILTON‑H900 heated humidifier, the clinician can easily follow a treatment strategy combining NIV and HFNT, and switch to invasive mechanical ventilation in the case of failure.