| Summary: | Abstract Background Respiratory failure requiring mechanical ventilation is a common manifestation of end-organ damage among patients with sepsis and has a high morbidity and mortality rate, as well as substantial associated treatment costs. Considering the burden of this condition, there is great need to identify novel, pragmatic therapies to improve outcomes in this population. Hypercapnia has shown benefits in several different ex vivo and in vivo models of lung injury. However, it is currently unclear if hypercapnia can confer clinical benefit among patients with sepsis. The objective of this systematic review is to collate the biomedical literature of preclinical and clinical studies testing the effects of higher PaCO2 levels in the setting of sepsis. Methods We will perform a qualitative systematic review of preclinical and clinical studies evaluating the effects of hypercapnia in sepsis. We will search CENTRAL, PubMed, CINAHL, and EMBASE using a comprehensive strategy. We will screen the reference lists of the articles we select for inclusion to identify additional studies for potential inclusion. Two independent reviewers will review all search results. Upon inclusion of articles, we will extract data using a standardized form. We will use tables to describe the study type, population included, exposure and control groups, outcome measures, and effects of exposure on outcome measures compared to controls. Discussion This systematic review aims to synthesize the world’s literature on the effects of hypercapnia in the setting of sepsis. We expect this systematic review will find that majority of the studies will demonstrate a potential benefit of higher PaCO2 levels in sepsis. The results of this systematic review will contribute to the understanding of the effects of hypercapnia in the setting of sepsis and promote future research of PaCO2 management in mechanically ventilated patients with sepsis. Systematic review registration The systematic review is registered in the PROSPERO international prospective register of systematic review (PROSPERO # CRD42018086703).
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