Abstract
OBJECTIVE: Contrast-enhanced ultrasound (CEUS) is a promising tool to assess renal microcirculation. However, its reproducibility has never been formally assessed. We aimed to assess the reproducibility and precision of CEUS measurements in critically ill patients. METHODS: We conducted an observational study in 20 critically ill patients in stable cardio-pulmonary condition. In group 1 (n = 10), to assess CEUS reproducibility, we performed three CEUS scans within a one-hour time frame in rigorously similar conditions and settings. In group 2 (n = 10), to assess the influence of ultrasound contrast agent rate, we performed two CEUS scans, one with standard settings and the second with a doubled ultrasound contrast agent rate. CEUS-derived parameters included relative blood volume (RBV), mean transit time (mTT) and perfusion index (PI). We used linear quantile mixed models to assess their reproducibility (stability across different time points), precision (variability of consecutive measurements), and the influence of a change in ultrasound contrast agent (UCA) infusion rate. Finally, we sought to determine patients' related factors associated with signal instability. RESULTS: In Group 1, CEUS derived parameters remained similar across the three study timepoints (3 289 vs. 3 680 vs. 3 590 for RBV, 4.1 vs. 4.2 vs. 4.2 for mTT and 684 vs. 762 vs. 735 for PI, all p values > 0.05), indicating stability of these parameters within individual patients over time. Intra-measure coefficient of variability was 23.2% for RBV, 13.9% for mTT and 33.8% for PI. The median of five CEUS assessments yielded reliable estimates. In Group 2, doubling the UCA rate resulted in a significant increase in RBV (3 207 vs. 1 624, p = 0.01), and in PI (977 vs. 617, p = 0.01), while mTT remained stable (4.6 vs. 3.8, p = 0.08). No patients-related parameter could be significantly associated with CEUS parameters variability. CONCLUSIONS: Under controlled conditions, CEUS derived parameters are reproducible and have a fair precision in critically ill patients in stable hemodynamic condition. mTT might be more reliable under varying infusion conditions. Further studies are required to establish the clinical utility of CEUS in critically ill patients.