BackgroundAcute Type 2 respiratory failure (AT2RF) is defined by hypercapnia (>6kPa) and these patients require ventilatory support in a significant proportion of cases. Non-invasive ventilation (NIV) is effective in preventing escalation to invasive mechanical ventilation (IMV) but has a high failure rate. High flow nasal oxygen (HFNO) is a novel device that integrates humidified air with oxygen at flow rates of up to 60 L/min. Various additional benefits including carbon-di-oxide (CO2) clearance have been attributed to HFNO. This systematic review aims to determine whether the use of HFNO for patients with AT2RF 1) improves arterial CO2 (PaCO2), 2) improves other clinical and patient-centred outcomes and 3) assess any potential harms.MethodSearches for relevant studies will be conducted in MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials, with no language restrictions. In addition, we will search Google Scholar and the references of all articles for any pertinent studies not found in our initial search. With the assistance of a professional librarian, we will develop a systematic search strategy using appropriate keywords and MeSH terms. We will identify trials that examined the efficacy of HFNO in adult AT2RF patients. We will include randomised trials and observational studies that compared two or more modalities of oxygen delivery that includes high flow nasal oxygen as one of the modes with the comparator being low flow oxygen and/or non-invasive ventilation. The primary outcome is change in PaCO2 level while other clinical and patient centred outcomes will be collected. Two reviewers will independently assess studies for eligibility, data extraction and quality appraisal. We will conduct a meta-analysis and/or a narrative summary as appropriate.DiscussionHFNO is utilised extensively in clinical practice with widening indications of use. The effects of HFNO includes CO2 clearance and PEEP benefits that may be beneficial to patients with AT2RF. While current publications indicate a beneficial role, no systematic review has attempted to summarise the evidence for this indication. The results of the proposed systematic review will summarise the current evidence to guide practice, guideline development and the design of future trials.Systematic review registrationPROSPERO CRD42019148748. (https://www.crd.york.ac.uk/prospero/)