Influence of the Anesthetic Technique on Circulating Extracellular Vesicles in Bladder Cancer Patients Undergoing Radical Cystectomy: A Prospective, Randomized Trial.

Anesthetics have been shown to alter tumor progression and seem to influence surgical cancer outcome. Circulating extracellular vesicles as mediators of intercellular communication are involved in cancer progression and may be influenced by anesthetics. In this prospective, randomized study, effects of anesthetics on extracellular vesicles and associated micro-RNAs in bladder cancer patients undergoing radical cystectomy were tested. Extracellular vesicles from 51 patients at four perioperative time points receiving Propofol or Sevoflurane were extracted with polymer-based methods and quantified with a nanoparticle-tracking analysis. Vesicle-associated micro-RNAs were analyzed with a real-time polymerase chain reaction using array cards and single assays for tumor-associated miR-21-5p, miR-15a-5p, miR-17-5p and miR-451a. Plasma extracellular vesicle concentration (suture: fold change (fc) in Propofol at 4.1 ± 3.9 vs. Sevoflurane at 0.8 ± 0.5; p = 0.003) and associated miRNAs increased significantly (+30% post induction, +9% 30 Min surgery) in the Propofol group. Tumor-associated miRNAs increased during surgery in both groups (fc in miR-21-5p: 24.3 ± 10.2, p = 0.029; fc in miR-15a-5p: 9.7 ± 3.8, p = 0.027; fc in miR-17-5p: 5.4 ± 1.7, p = 0.014), whereas antitumor miR-451a increased in the Propofol group only (fc: 2.5 ± 0.6 vs. 1.0 ± 0.2; p = 0.022). Anesthetics influence extracellular vesicles and associated micro-RNAs of bladder cancer patients during surgery. Increased expression of antitumor micro-RNA may be an explanatory approach for decreased tumor cell viability after Propofol.

Hypotension Prediction Index and Incidence of Perioperative Hypotension: A Single-Center Propensity-Score-Matched Analysis.

(1) Background: Intraoperative hypotension is common and is associated with increased morbidity and mortality. The Hypotension Prediction Index (HPI) is an advancement of arterial waveform analysis and allows preventive treatments. We used a propensity-score-matched study design to test whether application of the HPI reduces hypotensive events in non-cardiac surgery patients; (2) Methods: 769 patients were selected for propensity score matching. After matching, both HPI and non-HPI groups together comprised n = 136 patients. A goal-directed treatment protocol was applied in both groups. The primary endpoint was the incidence and duration of hypotensive events defined as MAP < 65 mmHg, evaluated by the time-weighted average (TWA) of hypotension. (3) Results: The median TWA of hypotension below 65 mmHg in the matched cohort was 0.180 mmHg (IQR 0.060, 0.410) in the non-HPI group vs. 0.070 mmHg (IQR 0.020, 0.240) in the HPI group (p < 0.001). TWA was higher in patients with ASA classification III/IV (0.170 mmHg; IQR 0.035, 0.365) than in patients with ASA status II (0.100; IQR 0.020, 0.250; p = 0.02). Stratification by intervention group showed no differences in the HPI group while TWA values in the non-HPI group were more than twice as high in patients with ASA status III/IV (p = 0.01); (4) Conclusions: HPI reduces intraoperative hypotension in a matched cohort seen for TWA below 65 mmHg and relative time in hypotension. In addition, non-HPI patients with ASA status III/IV showed a higher TWA compared with HPI-patients, indicating an advantageous effect of using HPI in patients at higher risk.

Hemodynamic monitoring with Hypotension Prediction Index versus arterial waveform analysis alone and incidence of perioperative hypotension.

BACKGROUND: Intraoperative hypotension is associated with increased morbidity and mortality. The Hypotension Prediction Index (HPI) is an advancement of the arterial waveform analysis to predict intraoperative hypotension minutes before episodes occur enabling preventive treatments. We tested the hypothesis that the HPI combined with a personalized treatment protocol reduces intraoperative hypotension when compared to arterial waveform analysis alone. METHODS: We conducted a retrospective analysis of 100 adult consecutive patients undergoing moderate- or high-risk noncardiac surgery with invasive arterial pressure monitoring using either index guidance (HPI) or arterial waveform analysis (FloTrac) depending on availability (FloTrac, n = 50; HPI, n = 50). A personalized treatment protocol was applied in both groups. The primary endpoint was the incidence and duration of hypotensive events defined as MAP <65 mmHg evaluated by time-weighted average of hypotension. RESULTS: In the FloTrac group, 42 patients (84%) experienced a hypotension while in the HPI group 26 patients (52%) were hypotensive (p = 0.001). The median (IQR) time-weighted average of hypotension in the FloTrac group was 0.27 (0.42) mmHg versus 0.10 (0.19) mmHg in the HPI group (p = 0.001). Finally, the median duration of each hypotensive event (IQR) was 2.75 (2.40) min in the FloTrac group compared to 1.00 (2.06) min in the HPI group (p = 0.002). CONCLUSIONS: The application of the HPI combined with a personalized treatment protocol can reduce incidence and duration of hypotension when compared to arterial waveform analysis alone. This study therefore provides further evidence of the transition from prediction to actual prevention of hypotension using HPI.