High Flow Nasal Oxygen Therapy for Acute Type II Respiratory Failure in Acute Settings

Abstract

Introduction:

In acute type 2 respiratory failure (AT2RF), carbon dioxide levels in the blood are abnormally elevated. At present, non-invasive ventilation (NIV) with bi-level positive airway pressure is the standard treatment for AT2RF. High-flow nasal therapy (HFNT), which delivers heated humidified oxygen air to the patient with a flow rate of up to 60 L/min, is proposed for treating AT2RF. HFNT has several benefits, such as washout of carbon dioxide (CO2), reduced work of breathing, comfort and tolerance. Nevertheless, these benefits need to be comprehensively evaluated using high-quality evidence. HFNT, due to its tolerability and physiological rationale, could overcome the limitations of NIV. However, the current evidence and guidelines for its use are limited and uncertain. Therefore, this thesis presented a) Systematic evidence synthesis for CO2 clearance to identify the knowledge gap and guide future study designs, b) an exploration of the current practice through the international survey, c) a single centre randomised controlled trial (RCT) conducted to determine if HFNT reduces the need for NIV and partial pressure of CO2 (PaCO2) when used as an initial oxygen delivery method in comparison to LFO.

Methods:

In this thesis, three main methods were used. First, a systematic review was conducted to assess the existing evidence using a predefined protocol and a systematic approach. The inclusion criteria were randomised or non-randomised controlled trials or cohort studies that recruited participants with AT2RF, tested HFNT versus NIV or low-flow oxygen (LFO), and reported PaCO2 and other clinical and patient-related outcomes. Second, an international online survey was conducted to evaluate the current practice, guidelines and audits of HFNT. Participants included medical and respiratory therapists or physiotherapists in three countries: The United Kingdom (UK), Canada, and the USA (North America, NA). Third, a randomised controlled trial (RCT) was performed that assessed the effectiveness of HFNT versus LFO on adult patients with AT2RF (PaCO2 > 6 Kpa and pH < 7.35) admitted to the emergency department to determine the clinical effects of HFNT on the CO2 clearance and the number of patients requiring NIV escalation after 6 hours of treatment.

Results:

In the systematic review, 727 citations were screened, and five studies met the inclusion criteria. Four studies were RCTs, and one was a cohort study. Four studies compared HFNT with NIV and one RCT compared HFNT with LFO. Of four trials evaluating HFNT versus NIV, one RCT reported a significant reduction (HFNT 6.7, 5.6 –7.7 vs NIV 7.6, 6.3 – 9.3 (Median, interquartile range (IQR)) at four hours and no significant difference at other time-points. In relation to the secondary outcomes, there were no significant differences in other blood gases between HFNT and NIV. In two RCTs, HFNT was rated more comfortable than NIV. HFNT and NIV studies reported no effects on intubation rates, dyspnoea scores, length of stay and mortality. In the RCT comparing HFNT with LFO, there was no significant difference in PaCO2, and in terms of comfort, HFNT was rated as being louder than LFO. Other outcomes relevant to the review were not reported. The international survey was completed by 488 participants in the UK and NA. The majority reported using HFNT for acute type 1 respiratory failure (UK 99%, NA 94%). In the UK, HFNT was mainly used in respiratory wards (82%), while in NA, HFNT was primarily used in emergency departments (87%). In all countries, regular audits were lacking, and respondents considered the need for guidance very important (UK 61%, NA 64%) and urgent (UK 77%, 87%). In the RCT, HFNT significantly reduced the escalation to NIV compared to LFO. No significant differences in blood gas, respiratory parameters and patient centred outcomes between treatment groups at different time-points. In dyspnoea, HFNT showed a significant difference compared to LFO.

Conclusion

A few studies with very low to moderate certainty have assessed the clinical effectiveness of HFNT in AT2RF. The advantages of CO2 reduction by HFNT were limited to clinically irrelevant time points. HFNT was used in clinical conditions with poor quality evidence, the practice was not extensively audited and the guidance was lacking. HFNT showed statistical significance in reducing the need for NIV compared to LFO and was better in reducing dyspnoea at an early time point. Based on the thesis results, HFNT showed potential, but due to the limitations found in the thesis, it cannot be recommended for AT2RF until clinical practice guidelines and higher-quality evidence have been conducted.