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Background: This study aimed to assess a potential organ protective effect of volatile sedation in a scenario of severe inflammation with an early cytokine storm (in particular IL-6 elevation) in patients suffering from COVID-19-related lung injury with invasive mechanical ventilation and sedation. Methods: This is a small-scale pilot multicenter randomized controlled trial from four tertiary hospitals in Switzerland, conducted between April 2020 and May 2021. 60 patients requiring mechanical ventilation due to severe COVID-19-related lung injury were included and randomized to 48-hour sedation with sevoflurane vs. continuous intravenous sedation (= control) within 24 h after intubation. The primary composite outcome was determined as mortality or persistent organ dysfunction (POD), defined as the need for mechanical ventilation, vasopressors, or renal replacement therapy at day 28. Secondary outcomes were the length of ICU and hospital stay, adverse events, routine laboratory parameters (creatinine, urea), and plasma inflammatory mediators. Results: 28 patients were randomized to sevoflurane, 32 to the control arm. The intention-to-treat analysis revealed no difference in the primary endpoint with 11 (39%) sevoflurane and 13 (41%) control patients (p = 0.916) reaching the primary outcome. Five patients died within 28 days in each group (16% vs. 18%, p = 0.817). Of the 28-day survivors, 6 (26%) and 8 (30%) presented with POD (p = 0.781). There was a significant difference regarding the need for vasopressors (1 (4%) patient in the sevoflurane arm, 7 (26%) in the control one (p = 0.028)). Length of ICU stay, hospital stay, and registered adverse events within 28 days were comparable, except for acute kidney injury (AKI), with 11 (39%) sevoflurane vs. 2 (6%) control patients (p = 0.001). The blood levels of IL-6 in the first few days after the onset of the lung injury were less distinctly elevated than expected. Conclusions: No evident benefits were observed with short sevoflurane sedation on mortality and POD. Unexpectedly low blood levels of IL-6 might indicate a moderate injury with therefore limited improvement options of sevoflurane. Acute renal issues suggest caution in using sevoflurane for sedation in COVID-19. Trial registration: The trial was registered on ClinicalTrials.gov (NCT04355962) on 2020/04/21. [ABSTRACT FROM AUTHOR]

Portal vein ligation (PVL) induces liver growth prior to resection. Associating liver partition and portal vein ligation (PVL plus transection=ALPPS) or the addition of the prolyl-hydroxylase inhibitor dimethyloxalylglycine (DMOG) to PVL both accelerate growth via stabilization of HIF-α subunits. This study aims at clarifying the crosstalk of hepatocytes (HC), hepatic stellate cells (HSC) and liver sinusoidal endothelial cells (LSEC) in accelerated liver growth. In vivo, liver volume, HC proliferation, vascular density and HSC activation were assessed in PVL, ALPPS, PVL+DMOG and DMOG alone. Proliferation of HC, HSC and LSEC was determined under DMOG in vitro. Conditioned media experiments of DMOG-exposed cells were performed. ALPPS and PVL+DMOG accelerated liver growth and HC proliferation in comparison to PVL. DMOG alone did not induce HC proliferation, but led to increased vascular density, which was also observed in ALPPS and PVL+DMOG. Activated HSC were detected in ALPPS, PVL+DMOG and DMOG, again not in PVL. In vitro, DMOG had no proliferative effect on HC, but conditioned supernatant of DMOG-treated HSC induced VEGF-dependent proliferation of LSEC. Transcriptome analysis confirmed activation of proangiogenic factors in hypoxic HSC. Hypoxia signaling in HSC induces VEGF-dependent angiogenesis. HSC play a crucial role in the cellular crosstalk of rapid liver regeneration. [ABSTRACT FROM AUTHOR]

Background: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) offer survival benefits in well-selected patients with peritoneal tumors. The complexity of CRS/HIPEC requires surgical specialization. In contrast, limited data are available regarding the impact of anesthesia management. We assessed the role of standard operating procedures (SOPs) for anesthesia on perioperative patient outcomes after CRS/HIPEC. Methods: Between 2009 and 2015, 112 CRS/HIPEC were performed at the University Hospital of Zurich. Procedures were grouped in an "early or late" group before (n = 57) and after (n = 55) the introduction of SOPs, which defined management of fluids, serum albumin, hemostasis, and body temperature. Results: Introduction of SOPs significantly changed patient management. Patients received in total less colloids (p = 0.03) and less diuretics (p = 0.007). We noticed an increased substitution of albumin (p = 0.001) and coagulation factors (p = 0.008). Body temperatures were higher at the end of the operation (p = 0.005), and more patients were extubated in the operating room (66% vs. 42%, p = 0.02). The rate of major complications (p = 0.003) and reoperations (p = 0.01) was reduced after the introduction of SOPs. On multivariate analysis, two independent prognostic factors were identified. The use of > 2000 mL of colloids [odds ratio (OR) 5.31 (1.06–26.56), p = 0.042] was associated with major morbidity. In contrast, substitution of albumin [OR 0.12 (0.01–0.96), p = 0.046] was associated with better outcomes. Conclusions: SOPs for perioperative anesthesia management have a major impact on outcomes of patients after CRS/HIPEC. Management of colloid administration was an independent prognostic factor for perioperative outcomes. This highlights the role of the anesthesiologist and the need for specialization beyond the surgical team. [ABSTRACT FROM AUTHOR]

To assess the impact of short time hypnosis for retro-bulbar anesthesia on ventilation in patients undergoing ophthalmic surgery of the anterior eye chamber. In all patients, a combined continuous transcutaneous carbon dioxide tension (PtcCO2) and partial oxygen saturation (SpO2) measurement was applied in addition to routine monitoring. To enable unconscious application of retro-bulbar anesthesia, intravenous thiopental was given in one to multiple bolus doses. Transient breathing support included chin lift, Esmarch maneuver and manual hand-bag ventilation via face mask. Main endpoints were apnea time, recovery time according to the Richmond Agitation Sedation Scale, as well as SpO2 and PtcCO2 readings at predefined time points. Fifty-two patients with a mean age of 68 ± 13 years were included. Average thiopental dose was 2.7 ± 0.6 mg/kg. In seven (13.5%) patients repeated doses of thiopental were necessary to a total of 3.3 ± 1.1 mg/kg. Except one patient, no severe, significant or clinical relevant hypercapnia or desaturation periods were observed, and the occurring elevation of PtcCO2 values did not correlate with the application of repeated doses of thiopental or the need for the Esmarch maneuver. Higher PtcCO2 values were associated with the presence of hypertension and smoking. Apnea (p < 0.001) and recovery (p = 0.003) time were significantly prolonged in the patients needing the Esmarch maneuver. Short term anesthesia with thiopental in ophthalmic surgery is associated with a mild but not clinically relevant hypercapnia. [ABSTRACT FROM AUTHOR]

Background: A recently published score predicts the occurrence of acute kidney injury (AKI) after liver resection based on preoperative parameters (chronic renal failure, cardiovascular disease, diabetes, and alanine-aminotransferase levels). By inclusion of additional intraoperative parameters we aimed to develop a new prediction model. Methods: A series of 549 consecutive patients were enrolled. The preoperative score and intraoperative parameters (blood transfusion, hepaticojejunostomy, oliguria, cirrhosis, diuretics, colloids, and catecholamine) were included in a multivariate logistic regression model. We added the strongest predictors that improved prediction of AKI compared to the existing score. An internal validation by fivefold cross validation was performed, followed by a decision curve analysis to evaluate unnecessary special care unit admissions. Results: Blood transfusions, hepaticojejunostomy, and oliguria were the strongest intraoperative predictors of AKI after liver resection. The new score ranges from 0 to 64 points predicting postoperative AKI with a probability of 3.5-95 %. Calibration was good in both models (15 % predicted risk vs. 15 % observed risk). The fivefold cross-validation indicated good accuracy of the new model (AUC 0.79 (95 % CI 0.73-0.84)). Discrimination was substantially higher in the new model (AUC 0.81 (95 % CI 0.76-0.86) versus AUC 0.60 (95 % CI 0.52-0.69), p < 0.001). The new score could reduce up to 84 unnecessary special care unit admissions per 100 patients depending on the decision threshold. Conclusions: By combining three intraoperative parameters with the existing preoperative risk score, a new prediction model was developed that more accurately predicts postoperative AKI. It may reduce unnecessary admissions to the special care unit and support management of patients at higher risk. [ABSTRACT FROM AUTHOR]

Background: Angiopoietin-1 (Ang-1) and 2 (Ang-2), high mobility group box 1 (HMGB1), soluble receptor for advanced glycation endproducts (sRAGE), soluble triggering receptor expressed on myeloid cells 1 (sTREM1), and soluble urokinase-type plasminogen activator receptor (suPAR) have shown promising results for predicting all-cause mortality in critical care patients. The aim of our systematic review and meta-analysis was to assess the prognostic value of these biomarkers for mortality in adult patients with sepsis. Methods: A systematic literature search of the MEDLINE, PubMed, EMBASE, and Cochrane Library databases, for articles in English published from 01.01.1990 onwards, was conducted. The systematic review focused exclusively on observational studies of adult patients with sepsis, any randomized trials were excluded. For the meta-analysis, only studies which provide biomarker concentrations within 24 h of admission in sepsis survivors and nonsurvivors were included. Results are presented as pooled mean differences (MD) between nonsurvivors and survivors with 95% confidence interval for each of the six biomarkers. Studies not included in the quantitative analysis were narratively summarized. The risk of bias was assessed in all included studies using the Quality in Prognosis Studies (QUIPS) tool. Results: The systematic literature search retrieved 2285 articles. In total, we included 44 studies in the qualitative analysis, of which 28 were included in the meta-analysis. The pooled mean differences in biomarker concentration (nonsurvivors − survivors), measured at onset of sepsis, are listed as follows: (1) Ang-1: − 2.9 ng/ml (95% CI − 4.1 to − 1.7, p < 0.01); (2) Ang-2: 4.9 ng/ml (95% CI 2.6 to 7.1, p < 0.01); (3) HMGB1: 1.2 ng/ml (95% CI 0.0 to 2.4, p = 0.05); (4) sRAGE: 1003 pg/ml (95% CI 628 to 1377, p < 0.01); (5) sTREM-1: 87 pg/ml (95% CI 2 to 171, p = 0.04); (6) suPAR: 5.2 ng/ml (95% CI 4.5 to 6.0, p < 0.01). Conclusions: Ang-1, Ang-2, and suPAR provide beneficial prognostic information about mortality in adult patients with sepsis. The further development of standardized assays and the assessment of their performance when included in panels with other biomarkers may be recommended. Trial registration This study was recorded on PROSPERO, prospective register of systematic reviews, under the registration ID: CRD42018081226 [ABSTRACT FROM AUTHOR]