Hemodynamic goals in sepsis and septic shock resuscitation: An umbrella review of systematic reviews and meta-analyses with trial sequential analysis

Objective: The objective of this study was to verify whether any parameter among those used as the target for haemodynamic optimisation (e.g., mean arterial pressure, central venous oxygen saturation, systolic or diastolic dysfunction, CO2 gap, lactates, right ventricular dysfunction, and PvaCO2/CavO2 ratio) is correlated with mortality in an undifferentiated population with sepsis or septic shock. Methods: An umbrella review, searching MEDLINE, the Cochrane Database of Systematic Reviews, Health Technology Assessment Database, and the JBI Database of Systematic Reviews and Implementation Reports, was performed. We included systematic reviews and meta-analyses enrolling a population of unselected patients with sepsis or septic shock. The main outcome was mortality. Two authors conducted data extraction and risk-of-bias assessments independently. We used a random-effects model to pool binary and continuous data and summarised estimates of effect using equivalent odds ratios (eORs). We used the ROBIS tool to assess risk of bias and the assessment of multiple systematic reviews 2 score to assess global quality. Data synthesis: 17 systematic reviews and meta-analyses (15 828 patients) were included in the quantitative analysis. Diastolic dysfunction (eOR: 1.42; 95% confidence interval [CI]: 1.14–1.76), PvaCO2/CavO2 ratio (eOR: 2.15; 95% CI: 1.37–3.37), and CO2 gap (eOR: 1.86; 95% CI: 1.07–3.25) showed a significant correlation with mortality. Lactates were the parameter with highest inconsistency (I2 = 92%). Central venous oxygen saturation and right ventricle dysfunction showed significant statistical excess test of significance (p-value = 0.009 and 0.005, respectively). None of the considered parameters showed statistically significant publication bias. Conclusions: According to this umbrella review, diastolic dysfunction is the haemodynamic variable that is most closely linked to the prognosis of septic patients. The PvaCO2/CavO2 ratio and the CO2gap are significantly related to the mortality of septic patients, but the poor quality of evidence or the low number of cases, studied so far, limit their clinical applicability. Clinical trial registration: PROSPERO: International prospective register of systematic reviews, 2023, CRD42023432813 (Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023432813).