Predictors of fluid responsiveness in critically ill patients mechanically ventilated at low tidal volumes: systematic review and meta-analysis

Abstract

Introduction: Dynamic predictors of fluid responsiveness have shown good performance in mechanically ventilated patients at tidal volumes (Vt) > 8 mL kg^-1. Nevertheless, most critically ill conditions demand lower Vt. We sought to evaluate the operative performance of several predictors of fluid responsiveness at Vt ≤ 8 mL kg^-1 by using meta-regression and subgroup analyses.

Methods: A sensitive search was conducted in the Embase and MEDLINE databases. We searched for studies prospectively assessing the operative performance of pulse pressure variation (PPV), stroke volume variation (SVV), end-expiratory occlusion test (EEOT), passive leg raising (PLR), inferior vena cava respiratory variability (Δ-IVC), mini-fluid challenge (m-FC), and tidal volume challenge (VtC), to predict fluid responsiveness in adult patients mechanically ventilated at Vt ≤ 8 ml kg^-1, without respiratory effort and arrhythmias, published between 1999 and 2020. Operative performance was assessed using hierarchical and bivariate analyses, while subgroup analysis was used to evaluate variations in their operative performance and sources of heterogeneity. A sensitivity analysis based on the methodological quality of the studies included (QUADAS-2) was also performed.

Results: A total of 33 studies involving 1,352 patients were included for analysis. Areas under the curve (AUC) values for predictors of fluid responsiveness were: for PPV = 0.82, Δ-IVC = 0.86, SVV = 0.90, m-FC = 0.84, PLR = 0.84, EEOT = 0.92, and VtC = 0.92. According to subgroup analyses, variations in methods to measure cardiac output and in turn, to classify patients as responders or non-responders significantly influence the performance of PPV and SVV (p < 0.05). Operative performance of PPV was also significantly affected by the compliance of the respiratory system (p = 0.05), while type of patient (p < 0.01) and thresholds used to determine responsiveness significantly affected the predictability of SVV (p = 0.05). Similarly, volume of fluids infused to determine variation in cardiac output, significantly affected the performance of SVV (p = 0.01) and PLR (p < 0.01). Sensitivity analysis showed no variations in operative performance of PPV (p = 0.39), SVV (p = 0.23) and EEOT (p = 0.15).

Conclusion: Most predictors of fluid responsiveness reliably predict the response of cardiac output to volume expansion in adult patients mechanically ventilated at tidal volumes ≤ 8 ml kg^-1. Nevertheless, technical and clinical variables might clearly influence on their operative performance.

Keywords: Critical care; Critical illness; End-expiratory occlusion test; Fluid responsiveness; Inferior vena cava respiratory variability; Mini-fluid challenge; Passive leg raising; Pulse pressure variation; Stroke volume variation; Tidal volume challenge.

Fig. 1

Study selection

Fig. 2

Summary ROC curve for the first group of predictors of fluid responsiveness. SVV, stroke volume variation; PPV, pulse pressure variation; VtC, tidal volume challenge. Closed curve: 95% confidence region

Fig. 3

Summary ROC curve for the second group of predictors of fluid responsiveness. IVC, inferior vena cava respiratory variability. Closed curve: 95% confidence region

Fig. 4

Summary ROC curve for the third group of predictors of fluid responsiveness. EEOT, end-expiratory occlusion test; m-FC, mini-fluid challenge; PLR, passive leg raising. Closed curve: 95% confidence region

Fig. 5

Bubble plot for meta-regression of pulse pressure variation with lung compliance pulmonary as a continuous covariate. The number of the point is the reference number of each study