RESUMEN
BACKGROUND: Perform a scoping review of (1) pre-clinical studies testing the physiological effects of higher PaCO2 levels in the setting of sepsis models and (2) clinical investigations testing the effects of hypercapnia on clinical outcomes in mechanically ventilated patients with sepsis. METHODS: We performed a search of CENTRAL, PUBMED, CINAHL, and EMBASE. Study inclusion criteria for pre-clinical studies were: (1) bacterial sepsis model (2) measurement of PaCO2 , and (3) comparison of outcome measure between different PaCO2 levels. Inclusion criteria for clinical studies were: (1) diagnosis of sepsis, (2) receiving invasive mechanical ventilation, (3) measurement of PaCO2 , and (4) comparison of outcomes between different PaCO2 levels. We performed a qualitative analysis to collate and summarize the physiological and clinical effects of hypercapnia according to the recommended methodology from the Cochrane Handbook. RESULTS: Fifteen pre-clinical and nine clinical studies were included. Among pre-clinical studies, the individual studies found higher PaCO2 augments tissue blood flow and oxygenation, and attenuates inflammation and lung injury; however, all pre-clinical studies were found to have some degree of risk of bias. Six of the nine clinical studies were deemed to be good quality. Among clinical studies hypercapnia was associated with increased cerebral perfusion and oxygenation; however, there were conflicting results testing the association between hypercapnia and mortality. CONCLUSION: While individual pre-clinical studies identified potential mechanisms by which changes in PaCO2 levels could affect pathophysiology in sepsis, there is a paucity of clinical data as to the optimal PaCO2 range, demonstrating a need for future research. REGISTRATION: PROSPERO number CRD42018086703.
RESUMEN
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 ).