Plasma BNP and NT-proBNP levels increased significantly at the end of SBT in patients with CD, with a high diagnostic accuracy of CD (BNP: ROC 0.93, SE 0.034, 95% CI 0.86–0.99, p<.001, cut-off = 32 ng/L, accuracy 81% NT-proBNP ROC 0.79, SE 0.085, 95% CI 0.62– 0.95, p = 0.004, cut-off = 19.5 ng/L, accuracy 77%).Ĥ322 questionnaires were distributed to 74 out of 84 (88%) Swiss ICUs. Basal NT-proBNP did not differ between groups. Plasma BNP level (ng/L) before SBT was significantly higher in CD failures (CD:1320 ±512, RD:300 ☙6 success: 376 ☖8 P =. Weaning failure causes were cardiac dysfunction (CD) in 10 patients (34.5%) respiratory dysfunction (RD) in 17 (58.6%), and neurological in 2 (6.9%). Patients failing SBT needed more days of mechanical ventilation (19.6 ± 16,5 vs 9.1 ± 9.4 p < 0.001) and longer stay in ICU (25.3 ☒1,4 vs 12.7 ± 9.9 p < 0.001). No differences in age, SAPS II, APACHE II and sex distribution were seen between extubation failure and success groups. There was a significant difference between groups observed at t = 3.Ī total of 85 patients were included 29 (34.1%) failed the SBT and 56 (65.9%) were extubated, although 6 (10,7%) required reintubation within 48 h. Similarly VO2i increased to peak at t = 3 but remained increased for the remaining duration of the experiment. DO2i increased in both groups, with a peak at t = 3 before decreasing to values below baseline at t = 6. A-lactate increased significantly in the Levo group. SmvO2 decreased significantly with time with no differences between groups. LVSWI, RVSWI and SVI decreased to the same extent in all animals without intergroup differences. EVLW increased with time in both groups, with higher values in Levo animals. Preload indices CVP, GEDV and PCWP did not differ between groups. MPAP increased over time to the same extent in both groups. MAP remained constant in the Control group, whereas it decreased with time in the Levo group. The Levo group had higher CI compared to the Control group, which could be partially explained by an increased heart rate. TACE activity also increased with bacitracin (29 ± 2 vs 88 ± 35 FU/min, p < 0.01), an inhibitor of the redox-sensitive enzyme, protein disulphide isomerase (PDI), which catalyses disulphide interchange thereby influencing protein conformation.ĬI increased significantly with time in both groups, peaking at t = 3, consistent with the hyperdynamic phase of septic shock, then decreased to below baseline values. Upregulation of TACE activity following addition of H 2O 2 further supported this hypothesis (26 ± 10 vs 136 ± 52 FU/min, p < 0.05). Superoxide dismutase, a superoxide scavenger, or its cell-permeable mimic MnPyP failed to produce the same effects, implicating H 2O 2/OH- as a likely mediator. Co-incubation with N-acetyl-L-cysteine, a broad-spectrum ROS scavenger, attenuated the LPS-induced upregulation of TACE activity (90 ± 4% attenuation, p < 0.01), as did pre-incubation with diphenyleneiodonium, an NADPH oxidase inhibitor (70 ± 6%, p < 0.05). TACE activity was rapidly (30 min) upregulated by LPS stimulation (42 ± 12 vs 116 ± 31 Fluorescence Units/min for 10 5 monocytes, p < 0.01), and was found to be independent of cell surface TACE expression.