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.

Quantification of left ventricular ejection fraction and cardiac output using a novel semi-automated echocardiographic method: a prospective observational study in coronary artery bypass patients.

BACKGROUND: Echocardiographic quantification of ejection fraction (EF) by manual endocardial tracing requires training, is time-consuming and potentially user-dependent, whereas determination of cardiac output by pulmonary artery catheterization (PAC) is invasive and carries a risk of complications. Recently, a novel software for semi-automated EF and CO assessment (AutoEF) using transthoracic echocardiography (TTE) has been introduced. We hypothesized that AutoEF would provide EF values different from those obtained by the modified Simpson's method in transoesophageal echocardiography (TOE) and that AutoEF CO measurements would not agree with those obtained via VTILVOT in TOE and by thermodilution using PAC. METHODS: In 167 patients undergoing coronary artery bypass graft surgery (CABG), TTE cine loops of apical 4- and 2-chamber views were recorded after anaesthesia induction under steady-state conditions. Subsequently, TOE was performed following a standardized protocol, and CO was determined by thermodilution. EF and CO were assessed by TTE AutoEF as well as TOE, using the modified Simpson's method, and Doppler measurements via velocity time integral in the LV outflow tract (VTILVOT). We determined Pearson's correlation coefficients r and carried out Bland-Altman analyses. The primary endpoints were differences in EF and CO. The secondary endpoints were differences in left ventricular volumes at end diastole (LVEDV) and end systole (LVESV). RESULTS: AutoEF and the modified Simpson's method in TOE showed moderate EF correlation (r = 0.38, p < 0.01) with a bias of -12.6% (95% limits of agreement (95%LOA): -36.6 - 11.3%). AutoEF CO correlated poorly both with VTILVOT in TOE (r = 0.19, p < 0.01) and thermodilution (r = 0.28, p < 0.01). The CO bias between AutoEF and VTILVOT was 1.33 l min-1 (95%LOA: -1.72 - 4.38 l min-1) and 1.39 l min-1 (95%LOA -1.34 - 4.12 l min-1) between AutoEF and thermodilution, respectively. AutoEF yielded both significantly lower EF (EFAutoEF: 42.0% (IQR 29.0 - 55.0%) vs. EFTOE Simpson: 55.2% (IQR 40.1 - 70.3%), p < 0.01) and CO values than the reference methods (COAutoEF biplane: 2.30 l min-1 (IQR 1.30 - 3.30 l min-1) vs. COVTI LVOT: 3.64 l min-1 (IQR 2.05 - 5.23 l min-1) and COPAC: 3.90 l min-1 (IQR 2.30 - 5.50 l min-1), p < 0.01)). CONCLUSIONS: AutoEF correlated moderately with TOE EF determined by the modified Simpson's method but poorly both with VTILVOT and thermodilution CO. A systematic bias was detected overestimating LV volumes and underestimating both EF and CO compared to the reference methods. TRIAL REGISTRATION: German Register for Clinical Trials (DRKS-ID DRKS00010666, date of registration: 08/07/2016).