Perioperative goal-directed therapy:A systematic review without meta-analysis

Background: Perioperative goal-directed therapy aims to optimise haemodynamics by titrating fluids, vasopressors and/or inotropes to predefined haemodynamic targets. Perioperative goal-directed therapy is a complex intervention composed of several independent component interventions. Trials on perioperative goal-directed therapy show conflicting results. We aimed to conduct a systematic review and meta-analysis to investigate the benefits and harms of perioperative goal-directed therapy. Methods: PubMED, EMBASE, Web of Science and Cochrane Library were searched. Trials were included if they had a perioperative goal-directed therapy protocol. The primary outcome was all-cause mortality. The first secondary outcome was serious adverse events excluding mortality. Risk of bias was assessed, and GRADE was used to evaluate quality of evidence. Results: One hundred and twelve randomised trials were included of which one trial (1%) had low risk of bias. Included trials varied in patients: types of surgery which was expected due to inclusion criteria; in intervention and comparison: timing of intervention, monitoring devices, haemodynamic variables, target values, use of fluids, vasopressors and/or inotropes as well as combinations of these within protocols; and in outcome: mortality was reported in 87 trials (78%). Due to substantial clinical heterogeneity also within the various types of surgery a meta-analysis of data, including subgroup analyses, as defined in our protocol was considered inappropriate. Conclusion: Clinical heterogeneity in patients, interventions and outcomes in perioperative goal-directed therapy trials is too large to perform meta-analysis on all trials. Future trials and meta-analyses highly depend on universally agreed definitions on aspects beyond type of surgery of the complex intervention and its evaluation